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Sample records for staging neoadjuvant treatment

  1. The newly proposed clinical and post-neoadjuvant treatment staging classifications for gastric adenocarcinoma for the American Joint Committee on Cancer (AJCC) staging.

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    In, Haejin; Ravetch, Ethan; Langdon-Embry, Marisa; Palis, Bryan; Ajani, Jaffer A; Hofstetter, Wayne L; Kelsen, David P; Sano, Takeshi

    2018-01-01

    New stage grouping classifications for clinical (cStage) and post-neoadjuvant treatment (ypStage) stage for gastric adenocarcinoma have been proposed for the eighth edition of the AJCC manual. This article summarizes the analysis for these stages. Gastric adenocarcinoma patients diagnosed in 2004-2009 were identified from the National Cancer Database (NCDB). The cStage cohort included both surgical and nonsurgical cases, and the ypStage cohort included only patients who had chemotherapy or radiation therapy before surgery. Survival differences between the stage groups were determined by the log-rank test and prognostic accuracy was assessed by concordance index. Analysis was performed using SAS 9.4 (SAS, Cary, NC, USA). Five strata for cStage and four strata for ypStage were developed. The 5-year survival rates for cStages were 56.77%, 47.39%, 33.1%, 25.9%, and 5.0% for stages I, IIa, IIb, III, and IV, respectively, and the rates for ypStage were 74.2%, 46.3%, 19.2%, and 11.6% for stages I, II, III, and IV, respectively. The log-rank test showed that survival differences were well stratified and stage groupings were ordered and distinct (p < 0.0001). The proposed cStage and ypStage classification was sensitive and specific and had high prognostic accuracy (cStage: c index = 0.81, 95% CI, 0.79-0.83; ypStage: c index = 0.80, 95% CI, 0.73-0.87). The proposed eighth edition establishes two new staging schemata that provide essential prognostic data for patients before treatment and for patients who have undergone surgery following neoadjuvant therapy. These additions are a significant advance to the AJCC staging manual and will provide critical guidance to clinicians in making informed decisions throughout the treatment course.

  2. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial.

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    van Meurs, Hannah S; Tajik, Parvin; Hof, Michel H P; Vergote, Ignace; Kenter, Gemma G; Mol, Ben Willem J; Buist, Marrije R; Bossuyt, Patrick M

    2013-10-01

    To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule. The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy. Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory

  3. A Dilemma in Staging of Esophageal Cancer: How Should We Stage ypT0 N2 M0 Esophageal Cancer after Neoadjuvant Therapy?

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    Sebahattin Celik

    2015-01-01

    Full Text Available Background. Since neoadjuvant treatment in esophageal cancer began to become popular, a complete pathological response at the primary tumour site has been commonly reported. An issue of conflict is whether complete response in the esophageal lumen means that the esophagus is completely tumour-free. Another important issue is whether lymph nodes that are retrieved from pathologically complete response cases are also tumour-free or not. There is a gap in the esophageal cancer staging system for ypT0 N2 M0 tumours that have received neoadjuvant therapy. Here, we will discuss the problem about staging of esophageal cancer associated with neoadjuvant therapy. Case. A female aged 40 years complaining of dysphagia was diagnosed as having locally advanced thoracic esophageal cancer. Neoadjuvant therapy decision was taken by oncology committee. Six weeks after neoadjuvant therapy, with a curative intention, minimal invasive surgery was performed. The pathology report was as follows. “There were no neoplastic cells in the suspected area of the esophageal mucosa upon examination with all staining. There was no cancer at resection margins. Four metastatic lymph nodes were infiltrated with squamous cell cancer.” Conclusion. Despite the growing use of neoadjuvant treatment in locally advanced esophageal cancer in world, we do not have a protocol for the evaluation of these patients’ pathology reports. We believe that new studies and new ideas are needed to resolve this dilemma associated with neoadjuvant therapy.

  4. Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

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    Sada, Yvonne H; Tran Cao, Hop S; Chang, George J; Artinyan, Avo; Musher, Benjamin L; Smaglo, Brandon G; Massarweh, Nader N

    2018-06-01

    For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment. Published by Elsevier Inc.

  5. Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes.

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    Wang, Tao; Liu, Yang; Zhou, Bin; Wang, Zhi; Liang, Naichao; Zhang, Yundong; Dong, Zhouhuan; Li, Jie

    2016-01-01

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC). Preliminary findings suggested that EGFR-TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC. We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA-IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis. A total of 67 patients with NSCLC were reviewed, and approximately half (38/67) of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2-4 weeks' assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011) were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3%) and dry skin (34.4%), which were tolerable. Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings.

  6. Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes

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    Wang T

    2016-03-01

    Full Text Available Tao Wang,1 Yang Liu,1 Bin Zhou,1 Zhi Wang,1 Naichao Liang,1 Yundong Zhang,1 Zhouhuan Dong,2 Jie Li2 1Department of Thoracic Surgery, 2Department of Pathology, People’s Liberation Army General Hospital, Beijing, People’s Republic of China Purpose: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC. Preliminary findings suggested that EGFR–TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC.Patients and methods: We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA–IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis.Results: A total of 67 patients with NSCLC were reviewed, and approximately half (38/67 of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2–4 weeks’ assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028 and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011 were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3% and dry skin (34.4%, which were tolerable.Conclusion: Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings. Keywords: non-small-cell lung cancer

  7. Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects.

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    Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

    2016-09-20

    To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).

  8. Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

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    Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

    2017-11-24

    To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, panalysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

  9. Neoadjuvant Treatment in Rectal Cancer: Actual Status

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    Garajová, Ingrid; Di Girolamo, Stefania; de Rosa, Francesco; Corbelli, Jody; Agostini, Valentina; Biasco, Guido; Brandi, Giovanni

    2011-01-01

    Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas. PMID:22295206

  10. Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

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    Chien, A Jo; Chambers, Julia; Mcauley, Fiona; Kaplan, Tessa; Letourneau, Joseph; Hwang, Jimmy; Kim, Mi-Ok; Melisko, Michelle E; Rugo, Hope S; Esserman, Laura J; Rosen, Mitchell P

    2017-08-01

    To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

  11. Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

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    Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

    2018-03-01

    To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

  12. Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

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    Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

    2016-11-01

    We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

  13. Can we eliminate neoadjuvant chemoradiotherapy in favor of neoadjuvant multiagent chemotherapy for select stage II/III rectal adenocarcinomas: Analysis of the National Cancer Data base.

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    Cassidy, Richard J; Liu, Yuan; Patel, Kirtesh; Zhong, Jim; Steuer, Conor E; Kooby, David A; Russell, Maria C; Gillespie, Theresa W; Landry, Jerome C

    2017-03-01

    Stage II and III rectal cancers have been effectively treated with neoadjuvant chemoradiotherapy (NCRT) followed by definitive resection. Advancements in surgical technique and systemic therapy have prompted investigation of neoadjuvant multiagent chemotherapy (NMAC) regimens with the elimination of radiation (RT). The objective of the current study was to investigate factors that predict for the use of NCRT versus NMAC and compare outcomes using the National Cancer Data Base (NCDB) for select stage II and III rectal cancers. In the NCDB, 21,707 patients from 2004 through 2012 with clinical T2N1 (cT2N1), cT3N0, or cT3N1 rectal cancers were identified who had received NCRT or NMAC followed by low anterior resection. Kaplan-Meier analyses, log-rank tests, and Cox-proportional hazards regression analyses were conducted along with propensity score matching analysis to reduce treatment selection bias. The 5-year actuarial overall survival (OS) rate was 75% for patients who received NCRT versus 67.2% for those who received NMAC (P elimination of neoadjuvant RT for select patients with stage II and III rectal adenocarcinoma was associated with worse OS and should not be recommended outside of a clinical trial. Cancer 2017;123:783-93. © 2016 American Cancer Society. © 2016 American Cancer Society.

  14. Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer : Results of the Dutch national breast cancer audit

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    Spronk, Pauline E.R.; van Bommel, A.C.M.; Siesling, S.; Wouters, M. W.J.M.; Vrancken Peeters, M.T.F.D.; Smorenburg, Carolien H.

    2017-01-01

    Objectives Neoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care.

  15. ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

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    David Vrana

    2018-03-01

    Full Text Available The prognosis of esophageal cancer (EC is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome.

  16. Effect of Postmastectomy Radiotherapy in Patients <35 Years Old With Stage II-III Breast Cancer Treated With Doxorubicin-Based Neoadjuvant Chemotherapy and Mastectomy

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    Garg, Amit K.; Oh, Julia L.; Oswald, Mary Jane; Huang, Eugene; Strom, Eric A.; Perkins, George H.; Woodward, Wendy A.; Yu, T. Kuan; Tereffe, Welela; Meric-Bernstam, Funda; Hahn, Karin; Buchholz, Thomas A.

    2007-01-01

    Purpose: Postmastectomy radiotherapy (PMRT) improves locoregional control (LRC) in patients with high-risk features after mastectomy. Young age continues to evolve as a potentially important risk factor. The objective of this study was to assess the benefits of PMRT in patients <35 years old treated with doxorubicin-based neoadjuvant chemotherapy for Stage II-III breast cancer. Patients and Methods: We retrospectively analyzed 107 consecutive breast cancer patients <35 years old with Stage IIA-IIIC disease treated at our institution with doxorubicin-based neoadjuvant chemotherapy and mastectomy, with or without PMRT. The treatment groups were compared in terms of LRC and overall survival. Results: Despite more advanced disease stages, the patients who received PMRT (n = 80) had greater rates of LRC (5-year rate, 88% vs. 63%, p = 0.001) and better overall survival (5-year rate, 67% vs. 48%, p = 0.03) than patients who did not receive PMRT (n = 27). Conclusion: Among breast cancer patients <35 years old at diagnosis, the use of PMRT after doxorubicin-based neoadjuvant chemotherapy and mastectomy led to a statistically greater rate of LRC and overall survival compared with patients without PMRT. The benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions after mastectomy

  17. Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

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    Avendano Juan; Buitrago, Giancarlo; Ramos, Pedro; Suescun Oscar

    2010-01-01

    Objective: To describe the experience at the National Cancer Institute (NCI) on the use of neoadjuvant chemotherapy as primary treatment for epithelial ovarian cancer among patients in stages IIIC and IV. Methods: We conducted a descriptive retrospective study (case series type) of patients diagnosed with epithelial ovarian cancer in stages IIIC and IV, treated at the NCI from January 1, 2003 to December 31,2006, who underwent neoadjuvant chemotherapy as primary treatment. Demographic characteristics and clinical outcomes are described. Results: Seventeen patients who fulfilled the above mentioned criteria were selected. Once neoadjuvant chemotherapy ended, 5 patients (29.4%) achieved complete or partial clinical response; 4 (23.8%) remained in stable condition, and 8 (47.6%) showed signs of progressive illness. Interval debulking surgery was performed on objective response patients. Maximum cytoreduction was achieved in 5 patients (100%); first relapse was reported at month 18 of follow-up; 2 disease-free survivors were identified in December, 2007; 8 (49%) reported some degree of non-severe chemotherapy-related toxicity. No mortality was related to chemotherapy, no post surgical complications were observed and no patient required advanced support management. Conclusions: Neoadjuvant chemotherapy, followed by optimal interval debulking surgery among selected patients, can be an alternative treatment for advanced epithelial ovarian cancer among women with irresecability or the critically ill. Further studies with improved design are required to confirm these findings.

  18. Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment: Series report and literature review.

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    Bartel, Ricardo; Gonzalez-Compta, Xavier; Cisa, Enric; Cruellas, Francesc; Torres, Alberto; Rovira, Aleix; Manos, Manel

    2017-10-20

    Olfactory neuroblastoma (ONB) is a rare entity that constitutes less than 5% of nasosinusal malignancies. Mainstream treatment consists in surgical resection+/-adjuvant radiotherapy. By exposing results observed with apparition of new therapeutic options as neoadjuvant chemotherapy, the objective is to evaluate a series and a review of the current literature. A retrospective review was conducted including patients diagnosed and followed-up for ONB from 2008 to 2015 in our institution. 9 patients were included. Mean follow-up of 52.5 months (range 10-107). Kadish stage: A, 1 patient (11.1%) treated with endoscopic surgery; B, 2 patients (22.2%) treated with endoscopic surgery (one of them received adjuvant radiotherapy); C, 6 patients (66.7%), 4 patients presented intracranial extension and were treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. The other 2 patients presented isolated orbital extension, treated with radical surgery (endoscopic or craniofacial resection) plus radiotherapy. The 5-year disease free and overall survival observed was 88.9%. Neoadjuvant chemotherapy could be an effective treatment for tumor reduction, improving surgical resection and reducing its complications. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  19. Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer.

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    Zhu, Jun; Zhang, Hai-Ping; Jiang, Sen; Ni, Jian

    2017-08-01

    We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC). This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected. A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6-19.4], and the median OS was 25.0 months (95% CI: 19.1-30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated. Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

  20. Neoadjuvant targeted therapy in patients with renal cell carcinoma

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    B. Ya. Alekseev

    2015-01-01

    Full Text Available Cytoreductive nephrectomy as an independent option in patients with metastatic renal cell carcinoma (mRCC cannot be considered as the only effective method, with rare exception, of a few patients with solitary metastases. Cytoreductive nephrectomy is now part of a multimodal approach encompassing surgical treatment and systemic drug therapy. Many retrospective and two prospective studies have demonstrated that it is expedient to perform cytoreductive nephrectomy. Immunotherapy should not be used as preoperatively in the era of cytokine therapy for mRCC due to that fact that it has no impact on primary tumor. In the current targeted therapy era, many investigators have concentrated attentionon the role of neoadjuvant targeted therapy for the treatment of patients with both localized and locally advanced mRCC. The potential benefits of neoadjuvant therapy for localized and locally advanced RCC include to make surgery easier and to increase the possibility of organsparing treatment, by decreasing the stage of primary tumor and the size of tumors. The possible potential advantages of neoadjuvant targeted therapy in patients with mRCC include prompt initiation of necessary systemic therapy; identification of patients with primary refractory tumors; and a preoperative reduction in the stage of primary tumor. Numerous retrospective and some prospective phase II studies have shown that neoadjuvant targeted therapy in patients with localized and locally advanced RCC is possible and tolerable and surgical treatment after neoadjuvant targeted therapy is safe and executable with a low incidence of complications. If neoadjuvant therapy is to be performed, it should be done within 2–4 months before surgery. Sorafenib and sunitinib are now most tested and suitable for neoadjuvant targeted therapy. Sorafenib is a more preferred drug due to its shorter half-life and accordingly to the possibility of discontinuing the drug immediately prior to

  1. Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Bonnet, R.; Presselt, N.; Przetak, C.; Junker, K.; Schneider, C.P.; Hoeffken, K.; Wendt, T.G.

    2002-01-01

    Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m 2 ) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m 2 ) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

  2. [Complications of surgical stage of treatment in patients with cancer of cervix uteri stage IIB].

    Science.gov (United States)

    Kryzhanivs'ka, A Ie

    2013-11-01

    The results of treatment of 127 patients, suffering cervix uteri cancer stage IIB in period of 1998 - 2012 yrs, were analyzed. Complications of surgical stage of the combined treatment have had occurred in 40.9% patients, including 40.5% patients, to whom neoadjuvant chemotherapy was conducted and in 41.5%--radiation therapy (RTH). The main postoperative complications--retroperitoneal lymphatic cysts--were revealed in 35.4% patients. The factors, raising the risk of postoperative complications occurrence, are following: the primary tumor spreading, metastatic affection of lymphatic nodes of pelvic cavity, preoperative conduction of RTH or chemotherapy.

  3. Neoadjuvant therapy in rectal cancer

    International Nuclear Information System (INIS)

    Della Valle, A.; Roldán, G.; Suárez, L.; Rodríguez, R.; Quarneti, A.

    2004-01-01

    Introduction: Rectal cancer causes about 500 deaths a year in our country. Radio chemotherapy (RTCT) is part of the treatment of rectal tumors especially in stages II and III. The indication for neoadjuvant aims to preserve the sphincter at low tumors and potentially make initially unresectable tumors resectable. Objective: To analyze the indications, treatment, toxicity and development of adenocarcinoma patients receiving treatment rectum preoperative R T ± Q T. Patients and Methods: Retrospective analysis of 31 records of patients rectal adenocarcinoma treated with neoadjuvant in Oncology Services Hospital and Central Clinical Hospital of the Armed Forces between 1994 and , 2003. Results: Men / Women: 1.3. Median age 64 years. Eight patients (30%) endorectal ultrasound as preoperative staging were performed. patients matched 20 (65%) stage II, 6 (19%) stage III, 5 (16%) stage IV with potentially resectable liver metastases. The median dose of R T was 50 Gy (35.8-63 Gy) with a median duration was 5 weeks (4-12). One patient (3%) received exclusive R T. Plans Q T used: 5-F U in I / C 52%, 5-F U bolus and 42% leucovorin and 5-F U bolus 3%. Surgery was achieved with sphincter preservation in 7/31 cases (23%). The most common toxicity was diarrhea and radiodermatitis were the cause of discontinuation in 4 patients. Control hematologic weekly was 38% during the RTCT. Responses were achieved Full 5% partial 39%, 17% and stabilization lesion progression 39%. Discussion: The lack of information recorded in the medical records hindered the Analysis of this work. 70% of stage II and III patients were incompletely staged (30% endorectal ultrasound) and controls during treatment were suboptimal. Only 23% of patients achieved sphincter preservation, lower than the figures reported in the literature (65-

  4. Role of Postmastectomy Radiation After Neoadjuvant Chemotherapy in Stage II-III Breast Cancer

    International Nuclear Information System (INIS)

    Fowble, Barbara L.; Einck, John P.; Kim, Danny N.; McCloskey, Susan; Mayadev, Jyoti; Yashar, Catheryn; Chen, Steven L.; Hwang, E. Shelley

    2012-01-01

    Purpose: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). Methods and Materials: Seven breast cancer physicians from University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. Results: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having ≤10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. Conclusions: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within University of California Athena Breast Health Network.

  5. Pertuzumab for the Neoadjuvant Treatment of Early-Stage HER2-Positive Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Squires, Hazel; Pandor, Abdullah; Thokala, Praveen; Stevens, John W; Kaltenthaler, Eva; Clowes, Mark; Coleman, Robert; Wyld, Lynda

    2018-01-01

    As part of its single technology appraisal process, the National Institute for Health and Care Excellence invited the manufacturer of pertuzumab (Perjeta ® ; Roche Products Limited) to submit evidence of its clinical and cost- effectiveness for the neoadjuvant treatment of women with high-risk, early-stage, HER2-positive breast cancer when used in combination with trastuzumab and chemotherapy. High-risk women included those with locally advanced (including inflammatory) breast cancer and women with high-risk early-stage breast cancer (classified as T2/3 or N1). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group. This article presents the critical review of the company's submission by the Evidence Review Group and the outcome of the National Institute for Health and Care Excellence guidance. The clinical data were mainly taken from a phase II, randomised, open-label, active controlled study (NeoSphere), which reported a significant advantage in terms of pathological complete response rates of pertuzumab in combination with trastuzumab and chemotherapy, compared with trastuzumab alone with chemotherapy (45.8 vs. 29.0%, p = 0.0141). The company did not make any indirect comparisons. A meta-analysis of 12 neoadjuvant studies investigating the relationship between pathological complete response and event-free survival was used to extrapolate the outcomes reported in the NeoSphere study. A cardiac safety study (TRYPHAENA) demonstrated the safety of pertuzumab. The company undertook a model-based economic evaluation of neoadjuvant pertuzumab plus trastuzumab and docetaxel compared with neoadjuvant trastuzumab and docetaxel over a lifetime horizon from the National Health Service and Personal Social Services perspective. The probabilistic incremental cost-effectiveness ratio was estimated to be £20,104 per quality-adjusted life-year gained for pertuzumab

  6. Comparison of mediastinal lymph node status and relapse pattern in clinical stage IIIA non-small cell lung cancer patients treated with neoadjuvant chemotherapy versus upfront surgery: A single center experience.

    Science.gov (United States)

    Savic, Milan; Kontic, Milica; Ercegovac, Maja; Stojsic, Jelena; Bascarevic, Slavisa; Moskovljevic, Dejan; Kostic, Marko; Vesovic, Radomir; Popevic, Spasoje; Laban, Marija; Markovic, Jelena; Jovanovic, Dragana

    2017-09-01

    In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. The rate of N2 disease was significantly higher in the upfront surgery group ( P   0.05). There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  7. Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy and factors influencing consideration for surgery in stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Melissa A.L. Vyfhuis, MD PhD

    2017-07-01

    Conclusions: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

  8. Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction.

    Science.gov (United States)

    Sunde, B; Ericson, J; Kumagai, K; Lundell, L; Tsai, J A; Lindblad, M; Rouvelas, I; Friesland, S; Wang, N; Nilsson, M

    2016-07-01

    Dysphagia is the main symptom of cancer of the esophagus and gastroesophageal junction and causing nutritional problems and weight loss, often counteracted by insertion of self-expandable metal stents or nutrition via an enteral route. Clinical observations indicate that neoadjuvant therapy may effectively and promptly alleviate dysphagia, making such nutrition supportive interventions redundant before surgical resection. The objective of the current study was to carefully study the effects of induction neoadjuvant therapy on dysphagia and its subsequent course and thereby investigate the actual need for alimentary gateways for nutritional support. Thirty-five consecutive patients scheduled for neoadjuvant therapy were recruited and assessed regarding dysphagia and appetite at baseline, after the first cycle of preoperative treatment with either chemotherapy alone or with chemoradiotherapy and before surgery. Platinum-based therapy in combination with 5-fluorouracil was administered intravenously days 1-5 every 3 weeks and consisted of three treatments. Patients receiving combined chemoradiotherapy started radiotherapy on day one of second chemotherapy cycle. They received fractions of 2 Gy/day each up to a total dose of 40 Gy. Watson and Ogilvie dysphagia scores were used to assess dysphagia, while appetite was assessed by the Edmonton Assessment System Visual analogue scale-appetite questionnaire. Patients were evaluated at regular outpatient clinic visits or by telephone. The histological tumor response in the surgical specimen was assessed using the Chirieac scale. Ten patients scheduled for neoadjuvant chemotherapy and 25 patients scheduled for chemoradiotherapy were included in the analysis. There was a significant improvement in dysphagia in both treatment groups, according to both scales, already from baseline to the completion of the first chemotherapy cycle which remained to the end of the neoadjuvant treatment (P dysphagia and the degree of

  9. Analysis of clinical factors for pathological complete response after preoperative neoadjuvant chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Ayiguli Hare; Palida Apizi; Iskandar Abulimiti; Zhang Jinrong; Tian Hanhan

    2014-01-01

    Objective: To evaluate the clinical factors associated with pathological complete response (pCR) after preoperative neoadjuvant chemoradiotherapy for rectal cancer. Methods: A retrospective analysis was performed on the clinical data of 116 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy followed by radical surgery from January 2009 to December 2012. All patients received pelvic intensity-modulated radiotherapy (50 Gy/25 fractions) with concurrent fluorouracil based chemotherapy and then underwent radical surgery 4-8 weeks later. The clinical factors associated with pCR or non-pCR were analyzed by Logistic regression. Results: Of the 116 patients, 20 (17.2%) achieved a pCR after neoadjuvant chemoradiotherapy. The univariate analysis showed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum carcinoembryonic antigen (CEA) level, T stage, N stage, distance from the anal verge, degree of tumor differentiation, and maximum tumor diameter were associated with pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. The multivariate analysis revealed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum CEA level,and T stage were predictive factors for pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. Conclusions: Non-circumferential tumor (percentage of circumference of the rectal tube invaded by the tumor <75 %), low CEA level, and early T stage before treatment may be associated with pCR after neoadjuvant chemoradiotherapy for rectal cancer. (authors)

  10. Prognostic significance of clinical and pathological stages on locally advanced rectal carcinoma after neoadjuvant chemoradiotherapy

    International Nuclear Information System (INIS)

    Wen, Bixiu; Zhang, Luning; Wang, Chengtao; Huang, Rong; Peng, Haihua; Zhang, Tian; Dong, Jun; Xiao, Weiwei; Zeng, Zhifan; Liu, Mengzhong; Gao, Yuanhong

    2015-01-01

    To investigate prognostic significance of clinical and pathological stages in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision. 210 patients with locally advanced rectal carcinoma (cT3-4 or cN+) treated with neo-CRT followed by total mesorectal excision. Treatment outcomes were compared according to clinical and pathological stage. Overall survival (OS), disease free survival (DFS) among patients with different clinical stage and pathological stage after neo-CRT. The median follow-up time was 47 months (range, 14–98 months). Clinical T stage was associated with 5 year OS (p = 0.042) and 5 year DFS (p = 0.014) while clinical N stage was not associated with 5 year OS (p = 0.440), 5 year DFS (p = 0.711). Pathological T stage was associate with 5 year OS (p = 0.001) and 5 year DFS (p = 0.046); and N stage was associated with 5 year OS (p = 0.001), 5 year DFS (p = 0.002). The pathological stage was further classified into three groups: ypT0–2N0 in 91 patients (43.3 %), ypT3–4N0 in 69 patients (32.9 %) and ypT0–4N+ in 50 patients (23.8 %). While pathological stage (ypT0–2 vs ypT3–4N0 vs ypT0–4N+) was associated with 5 year OS (87.9 %, 75.5 %, 56.7 %, p = 0.000), 5 year DFS (74.5 %, 77.4 %, 50.5 %, p = 0.003). Multivariate analysis showed that ypN stage was an independent prognostic factor for patients 5 year DFS. Pathological stage is strongly associated with treatment outcomes in patients with locally advanced rectal carcinoma treated with neo-CRT followed by total mesorectal excision, which may be used as guidance for further individualized treatment

  11. Phase 2 Neoadjuvant Treatment Intensification Trials in Rectal Cancer

    DEFF Research Database (Denmark)

    Teo, Mark T W; McParland, Lucy; Appelt, Ane L

    2018-01-01

    PURPOSE: Multiple phase 2 trials of neoadjuvant treatment intensification in locally advanced rectal cancer have reported promising efficacy signals, but these have not translated into improved cancer outcomes in phase 3 trials. Improvements in phase 2 trial design are needed to reduce these fals...

  12. Neoadjuvant polychemotherapy in combined treatment for oral cavity mucosa carcinoma patients

    International Nuclear Information System (INIS)

    Protsyk, V.S.; Trembach, A.M.; Korobko, E.V.; Garbar, L.I.

    2007-01-01

    Neoadjuvant polychemotherapy and radiotherapy as a pre surgeon combined treatment was applied to 144 patients with cancer of oral cavity mucosa. That method of treatment permit to obtain maximum destroy of tumoral parenchyma and clinical effect to all patients. (authors)

  13. The Role of Neoadjuvant Trials in Drug Development for Solid Tumors.

    Science.gov (United States)

    Funt, Samuel A; Chapman, Paul B

    2016-05-15

    The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323-8. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Pasello, G; Ceresoli, G L; Favaretto, A

    2013-02-01

    Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease. MPM shows high refractoriety to systemic treatment, single-modality treatment was generally ineffective and did not achieve higher results than supportive care. The incidence of local and distant recurrences after surgery remains high and that was the reason for many centres to perform combined treatments. In the attempt of reducing the incidence of local recurrences, a multimodality approach with surgery followed by adjuvant radiotherapy was explored. Extrapleural pneumonectomy (EPP) allows higher doses of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity and the results of this approach is a significant reduction of loco-regional relapses; although, extrathoracic metastasis represent a major problem in the management of the disease because of the impact on overall survival. The success with surgical resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the impetus for several groups to apply this strategy in MPM aiming at reducing the incidence of distant relapse after surgery. Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3-4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. This review will focus on the main clinical studies and overview the results of different chemotherapy regimens in the neoadjuvant treatment of MPM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    Directory of Open Access Journals (Sweden)

    Gollamudi J

    2016-02-01

    Full Text Available Jahnavi Gollamudi,1,* Jenny G Parvani,2,* William P Schiemann,3 Shaveta Vinayak3,4 1Department of Internal Medicine, 2Department of Biomedical Engineering, 3Case Comprehensive Cancer Center, Case Western Reserve University, 4Department of Hematology and Oncology, University Hospitals Case Medical Center, Cleveland, OH, USA *These authors contributed equally to this work Abstract: Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2, a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+ breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. Keywords: breast cancer

  16. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    International Nuclear Information System (INIS)

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2 + ) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2 + breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2 + breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients

  17. Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?

    Science.gov (United States)

    Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

    2015-06-01

    Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes. © 2015 American Cancer Society.

  18. Neoadjuvant treatments in triple-negative breast cancer patients: where we are now and where we are going

    Directory of Open Access Journals (Sweden)

    Omarini C

    2018-01-01

    Full Text Available Claudia Omarini, Giorgia Guaitoli, Stefania Pipitone, Luca Moscetti, Laura Cortesi, Stefano Cascinu, Federico Piacentini Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy Abstract: Triple-negative breast cancer (TNBC remains the poorest-prognosis breast cancer (BC subtype. Gene expression profiling has identified at least six different triple-negative subtypes with different biology and sensitivity to therapies. The heterogeneous nature of TN tumors may justify the difficulty in treating this BC subtype. Several targeted agents have been investigated in clinical trials without demonstrating a clear survival benefit. Therefore, systemic chemotherapy remains the cornerstone of current clinical practice. Improving the knowledge of tumor biology is mandatory for patient management. In stages II and III, neoadjuvant systemic treatment is an effective option of care. The achievement of a pathological complete response represents an optimal surrogate for survival outcome as well as a test for tumor drug sensitivity. In this review, we provide a brief description of the main predictive biomarkers for tumor response to systemic treatment. Moreover, we review the treatment strategies investigated for TNBCs in neoadjuvant settings focusing on experimental drugs such as immunotherapy and poly [ADP-ribose] polymerase inhibitors that hold promise in the treatment of this aggressive disease. Therefore, the management of TNBC represents an urgent, current, unmet need in daily clinical practice. A key recommendation is to design biology-driven clinical trials wherein TNBC patients may be treated on the basis of tumor molecular profile. Keywords: triple-negative breast cancer, neoadjuvant chemotherapy, BRCA, platinum, immunotherapy, PARP-1 inhibitors

  19. Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment - A pilot study.

    LENUS (Irish Health Repository)

    Tsang, J S

    2014-07-28

    In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment.

  20. Histologic response after neoadjuvant chemoradiotherapy in locally ...

    African Journals Online (AJOL)

    Background: Locally advanced rectal cancer can be down staged by neoadjuvant therapy and the resultant tumor response can be quantified histologically. This study aimed to assess pathological response of neoadjuvant chemoradiation in patients with locally advanced rectal cancers treated in Wad Medani Teaching ...

  1. Ultrasound guided pO2 measurement of breast cancer reoxygenation after neoadjuvant chemotherapy and hyperthermia treatment.

    Science.gov (United States)

    Vujaskovic, Z; Rosen, E L; Blackwell, K L; Jones, E L; Brizel, D M; Prosnitz, L R; Samulski, T V; Dewhirst, M W

    2003-01-01

    The objective of this study was to determine whether neoadjuvant chemotherapy in combination with hyperthermia (HT) would improve oxygenation in locally advanced breast tumours. The study describes a new optimized ultrasound guided technique of pO2 measurement using Eppendorf polarographic oxygen probes in 18 stage IIB-III breast cancer patients. Prior to treatment, tumour hypoxia (median pO2pO2=3.2 mmHg). Seven patients had well oxygenated tumours (median pO2 of 48.3 mmHg). Eight patients with hypoxic tumours prior to treatment had a significant improvement (p=0.0008) in tumour pO2 after treatment (pO2 increased to 19.2 mmHg). In three patients, tumours remained hypoxic (average median pO2=4.5 mmHg). The advantages of the ultrasound guided pO2 probe are in the accuracy of the Eppendorf electrode placement in tumour tissue, the ability to monitor electrode movement through the tumour tissue during the measurement and the ability to avoid electrode placement near or in large blood vessels by using colour Doppler imaging. The results of this preliminary study suggest that the combination of neoadjuvant chemotherapy and hyperthermia improves oxygenation in locally advanced breast tumours that are initially hypoxic.

  2. Neoadjuvant androgen deprivation plus prostatectomy for stage T3 disease: lack of PSA-based benefit even among patients with negative lymphadenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Hyslop, T; Corn, B; Werner-Wasik, M; Gomella, L

    1995-07-01

    Objective: Urologists have attempted to treat stage T3 prostate cancer by neoadjuvant total androgen deprivation (TAD) and prostatectomy. This approach has been disappointing because of the inability of ultrasonography to predict pathological disease status and frequent upstaging due to nodal positivity. Moreover, no reports give PSA-based outcome data among patients treated with TAD and prostatectomy. We therefore instituted a pilot study for T3 disease based on non-invasive staging (endorectal coil MRI), mandatory negative laparoscopic nodal dissections prior to hormonal manipulation, and prostatectomy followed by pathological and PSA-based outcome determinations. Materials and Methods: Twenty-one patients had negative laparoscopic lymphadenectomy followed by 4 months of neoadjuvant hormonal treatment (Lupron, Flutamide) prior to radical prostatectomy. Endorectal coil MRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3 month intervals. Prostatectomy specimens were evaluated by 3 mm whole mount step sections. Results: Median age was 63 (range: 51-68). Karnofsky performance status was 90-100 in all patients. The median number of nodes sampled was 10 (range: 2-60). Prior to prostatectomy, downsizing was observed by MRI in 57% and biochemical response was documented in all patients. However, pathological downstaging to a lower state ({<=}T2c) was achieved in only 48%. The actuarial 3 year freedom from biochemical relapse was only 24%. Conclusion: Neither serum PSA response nor MRI downsizing predicted pathological disease status after pre-operative androgen deprivation. Even in the setting of pathologically negative lymph nodes, TAD decreased the pathological stage of disease in the minority of patients. The present approach appeared to offer no advantage when compared with PSA-based benchmarks achieved with conformal irradiation (Urology 45: 484, 1995) or TAD followed by external beam treatment (IJROBP 27: 246

  3. Neoadjuvant androgen deprivation plus prostatectomy for stage T3 disease: lack of PSA-based benefit even among patients with negative lymphadenectomy

    International Nuclear Information System (INIS)

    Hyslop, T.; Corn, B.; Werner-Wasik, M.; Gomella, L.

    1995-01-01

    Objective: Urologists have attempted to treat stage T3 prostate cancer by neoadjuvant total androgen deprivation (TAD) and prostatectomy. This approach has been disappointing because of the inability of ultrasonography to predict pathological disease status and frequent upstaging due to nodal positivity. Moreover, no reports give PSA-based outcome data among patients treated with TAD and prostatectomy. We therefore instituted a pilot study for T3 disease based on non-invasive staging (endorectal coil MRI), mandatory negative laparoscopic nodal dissections prior to hormonal manipulation, and prostatectomy followed by pathological and PSA-based outcome determinations. Materials and Methods: Twenty-one patients had negative laparoscopic lymphadenectomy followed by 4 months of neoadjuvant hormonal treatment (Lupron, Flutamide) prior to radical prostatectomy. Endorectal coil MRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3 month intervals. Prostatectomy specimens were evaluated by 3 mm whole mount step sections. Results: Median age was 63 (range: 51-68). Karnofsky performance status was 90-100 in all patients. The median number of nodes sampled was 10 (range: 2-60). Prior to prostatectomy, downsizing was observed by MRI in 57% and biochemical response was documented in all patients. However, pathological downstaging to a lower state (≤T2c) was achieved in only 48%. The actuarial 3 year freedom from biochemical relapse was only 24%. Conclusion: Neither serum PSA response nor MRI downsizing predicted pathological disease status after pre-operative androgen deprivation. Even in the setting of pathologically negative lymph nodes, TAD decreased the pathological stage of disease in the minority of patients. The present approach appeared to offer no advantage when compared with PSA-based benchmarks achieved with conformal irradiation (Urology 45: 484, 1995) or TAD followed by external beam treatment (IJROBP 27: 246

  4. Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients : Identification rate and influence on axillary treatment

    NARCIS (Netherlands)

    van der Heiden-van der Loo, M.; de Munck, L.; Sonke, G. S.; van Dalen, T.; van Diest, P. J.; van den Bongard, H. J. G. D.; Peeters, P. H. M.; Rutgers, E. J. T.

    The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The

  5. A phase I/II study of neoadjuvant chemotherapy followed by radiation with boost chemotherapy for advanced T-stage nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Johnson, Faye M.; Garden, Adam S.; Palmer, J. Lynn; Shin, Dong M.; Morrison, William; Papadimitrakopoulou, Vassiliki; Khuri, Fadlo; Clayman, Gary; Goepfert, Helmuth; Ang, K. Kian; Hong, Waun K.; Glisson, Bonnie S.

    2005-01-01

    Purpose: Local recurrence is the most common site of failure for locally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant cisplatin/5-fluorouracil (PF) and definitive radiation at our center. Based on this, we studied the addition of chemotherapy during the boost phase of radiation after neoadjuvant PF for advanced T-stage (T3-T4) NPC. This strategy was based on theoretical radiosensitization with chemotherapy during accelerated repopulation of the tumor with relatively radioresistant clonogens. Methods and Materials: Three cycles of neoadjuvant PF was followed by conventionally fractionated radiation with additional PF during the boost portion of the radiation course. An initial Phase I study was done to establish the maximum tolerated dose of concurrent PF. Results: Forty-four patients were enrolled. Six patients in Phase I defined the MTD for concurrent PF as: cisplatin 10 mg/m 2 /day and PF 320 mg/m 2 /day, on Days 1-5 during Weeks 6 and 7 of radiation therapy based on dose-limiting toxicities of mucositis, neutropenia, and thrombocytopenia. Forty-one patients were treated with concurrent therapy per protocol: complete, partial, and minor responses were seen in 23, 16, and 2 patients, respectively. Progression-free and overall survival rates at 5 years were 55% (95% CI, 41-75%) and 66% (95% CI, 52-85%), respectively. Seven of 11 tumor-related deaths were due to local recurrence. Nine of 10 patients with local recurrence had T4-stage disease at presentation. Local control of T4 disease was achieved in 74% of patients overall, and in 25% (1/4) with World Health Organization (WHO) type 1, 76% (16/21) with WHO type 2, and 90% (9/10) with WHO type 3 histology. Common toxicities included mucositis, dermatitis, fatigue, vomiting, and weight loss. Conclusions: This regimen was feasible and associated with promising overall survival. Local recurrence remains the major reason for treatment failure in advanced T-stage NPC, especially WHO types 1 and 2

  6. [Neoadjuvant therapy for esophageal cancer - indication and efficacy].

    Science.gov (United States)

    Kato, Ken; Hamaguchi, Tetsuya; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro

    2007-10-01

    Some approaches such as adjuvant chemotherapy, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been tried to improve the efficacy of treatment for resectable esophageal cancer patients. The usefullness of neoadjuvant chemotherapy, has remained a matter of controversy. However, there is a report from JCOG9907 in Japan that two courses of neoadjuvant 5-FU/CDDP improved the survival of esophageal squamous cell cancer patients. Neoadjuvant chemoradiotherapy has not had a consistent evaluation because of the varying results of each trial. But from the results of meta-analysis and CALGB9781, the neoadjuvant chemoradiotherapy called "trimodality therapy" has been a standard treatment in the United States. We should evaluate whether there would be similar effectiveness in Japan, where the histology and operative approach are different. Some approaches such as DNA microarray and proteomics, which can predict the treatment effect, are being tried.

  7. Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

    Science.gov (United States)

    Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

    2017-06-01

    Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

  8. Treatment of muscle invasive bladder cancer. Is there a role for neoadjuvant chemotherapy?

    International Nuclear Information System (INIS)

    Kuten, A.; Baz, M.; Rubinov, R.; Dale, J.; Haim, N.; Robinson, E.; Cohen, Y.

    1994-01-01

    We compared the outcome of 3 different but widely accepted treatment protocols for bladder cancer in ordet to find which, if any, was superior, with particular emphasis upon the performance of the newest treatment, neoadjuvant chemotherapy. Data on 224 bladder patients treated at our institution (1975 to 1991) with 1 of the 3 protocols was analyzed. Those protocols were: 1. Radiotherapy >60 Gy (143 patients); 2. low dose radiotherapy followed by cystectomy (25 patients); 3. chemotherapy followed by either definitive radiotherapy or surgery (56 patients). Because the latter group was also a chronologically newer group with a shorter possible follow-up, we compared all treatments on the basis of 2-year survival, using Kaplan-Meier life tables. We briefly reviewed those modalities which are bladder-sparing because of the significance to quality of life of this factor. Two-year survival figures for the patients were: 63% for those wo received only radiotherapy; 72% for those undergoing cystectomy: 68% for the group to whom neoadjuvant chemotherapy was administered. The differences were not statistically significant. However, 23% of those patients treated neoadjuvantly were alive with intact bladders at 2 years. (orig./MG) [de

  9. Neoadjuvant therapy for esophageal cancer. Indication and efficacy

    International Nuclear Information System (INIS)

    Kato, Ken; Hamaguchi, Tetsuya; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro

    2007-01-01

    Some approaches such as adjuvant chemotherapy, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been tried to improve the efficacy of treatment for resectable esophageal cancer patients. The usefullness of neoadjuvant chemotherapy, has remained a matter of controversy. However, there is a report from JCOG9907 in Japan that two courses of neoadjuvant 5-fluorouracil/cisplatin (5-FU/CDDP) improved the survival of esophageal squamous cell cancer patients. Neoadjuvant chemoradiotherapy has not had a consistent evaluation because of the varying results of each trial. But from the results of meta-analysis and CALGB9781, the neoadjuvant chemoradiotherapy called ''trimodality therapy'' has been a standard treatment in the United States. We should evaluate whether there would be similar effectiveness in Japan, where the histology and operative approach are different. Some approaches such as DNA microarray and proteomics, which can predict the treatment effect, are being tried. (author)

  10. CT staging of colon cancer

    International Nuclear Information System (INIS)

    Dighe, S.; Swift, I.; Brown, G.

    2008-01-01

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies

  11. CT staging of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dighe, S. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom); Swift, I. [Department of Surgery, Mayday University Hospital, Croydon CR7 7YE (United Kingdom); Brown, G. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom)], E-mail: gina.brown@rmh.nhs.uk

    2008-12-15

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies.

  12. Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major regional differences

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik

    2012-01-01

    The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval debulking...

  13. Bulky mesonephric adenocarcinoma of the uterine cervix treated with neoadjuvant chemotherapy and radical surgery: report of the first case.

    Science.gov (United States)

    Ditto, Antonino; Martinelli, Fabio; Bogani, Giorgio; Gasparri, Maria L; Donato, Violante Di; Paolini, Biagio; Carcangiu, Maria L; Lorusso, Domenica; Raspagliesi, Francesco

    2016-11-11

    Malignant mesonephric adenocarcinoma of the uterine cervix is a rare occurrence with few cases described in the literature. Although surgery seems to be effective in the treatment of early-stage tumor, no cases describing outcomes of locally advanced stage are available. We report the first case of a patient with International Federation of Obstetrics and Gynecologists stage IIB mesonephric adenocarcinoma undergoing neoadjuvant chemotherapy and radical surgery. Despite the inherent limitation of a single description of a case, our experience supports the utilization of neoadjuvant chemotherapy in patients with malignant mesonephric adenocarcinoma of the uterine cervix. Further prospective multi-institutional studies are needed.

  14. Rapidly Growing Esophageal Carcinosarcoma Reduced by Neoadjuvant Radiotherapy Alone

    Directory of Open Access Journals (Sweden)

    Naotaka Ogasawara

    2014-06-01

    Full Text Available Esophageal carcinosarcoma is a rare malignant neoplasm consisting of both carcinomatous and sarcomatous components. It is generally treated by surgery, radiotherapy and chemotherapy according to the protocols used for other esophageal cancers. However, the treatment of esophageal carcinosarcoma by radiotherapy alone before surgery has not been previously described. We report a patient with a rapidly growing esophageal carcinosarcoma that was efficiently reduced by neoadjuvant radiotherapy alone. A previously healthy 69-year-old man was admitted with dysphagia. Initial esophagogastroduodenoscopy (EGD revealed a small nodular polypoid lesion of about 10 mm in the middle esophagus. A second EGD 1 month later showed that the tumor had expanded into a huge mass. A biopsy specimen revealed that the tumor comprised squamous cell carcinoma with spindle cell components, and the tumor was diagnosed as carcinosarcoma which was diagnosed as stage I (T1bN0M0. Due to renal dysfunction, the patient was treated with neoadjuvant radiotherapy (40 Gy without chemotherapy. A third EGD 1 month later revealed remarkable tumor reduction. He then underwent total esophagectomy with regional lymph node dissection (pStage 0, pT1aN0M0. After surgical operation, the patient was followed up without adjuvant therapy. Whole body computed tomography revealed lung metastasis 14 months after surgery, and the patient died 2 months later. The neoadjuvant radiotherapy for esophageal carcinosarcoma was considered to have contributed to the subsequent surgery and his prolonged survival time. Thus, radiotherapy alone might be a suitable neoadjuvant therapy for esophageal carcinosarcomas.

  15. Early prediction of the response of breast tumors to neoadjuvant chemotherapy using quantitative MRI and machine learning.

    Science.gov (United States)

    Mani, Subramani; Chen, Yukun; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Bhave, Sandeep R; Welch, E Brian; Levy, Mia A; Yankeelov, Thomas E

    2011-01-01

    The ability to predict early in the course of treatment the response of breast tumors to neoadjuvant chemotherapy can stratify patients based on response for patient-specific treatment strategies. Currently response to neoadjuvant chemotherapy is evaluated based on physical exam or breast imaging (mammogram, ultrasound or conventional breast MRI). There is a poor correlation among these measurements and with the actual tumor size when measured by the pathologist during definitive surgery. We tested the feasibility of using quantitative MRI as a tool for early prediction of tumor response. Between 2007 and 2010 twenty consecutive patients diagnosed with Stage II/III breast cancer and receiving neoadjuvant chemotherapy were enrolled on a prospective imaging study. Our study showed that quantitative MRI parameters along with routine clinical measures can predict responders from non-responders to neoadjuvant chemotherapy. The best predictive model had an accuracy of 0.9, a positive predictive value of 0.91 and an AUC of 0.96.

  16. Lymph node metastases near the celiac trunk should be considered separately from other nodal metastases in patients with cancer of the esophagus or gastroesophageal junction after neoadjuvant treatment and surgery.

    Science.gov (United States)

    Lagarde, Sjoerd M; Anderegg, Martinus C J; Gisbertz, Suzanne S; Meijer, Sybren L; Hulshof, Maarten C C M; Bergman, Jacques J G H M; van Laarhoven, Hanneke W M; van Berge Henegouwen, Mark I

    2018-03-01

    The aim of the present study is to identify the incidence and prognostic significance of lymph node metastases near the celiac trunk in patients who underwent neoadjuvant chemo(radio)therapy followed by esophagectomy. Between March 1994 and September 2013 a total of 462 consecutive patients with cancer of the esophagus or gastroesophageal junction (GEJ) who underwent potentially curative esophageal resection after neoadjuvant chemotherapy (N=88; 19.0%) or neoadjuvant chemoradiotherapy (CRT) (N=374; 81.0%) were included. Seventy one (15.4%) patients had truncal node metastases in the resection specimen. Metastases to these nodes occurred more frequently in male patients with adenocarcinoma and in tumors at the gastro-esophageal junction. A lower response to neoadjuvant treatment, higher ypT and ypN stages and a poorer grade of differentiation were significantly related with truncal node metastases. Patients with tumor positive truncal nodes had a worse median overall survival (17 vs. 55 months). In multivariate analysis, truncal node metastases were independently associated with a worse survival. Only 22 (31.0%) of the 71 patients with tumor positive truncal nodes were identified preoperatively with EUS or CT. In contrast, 37 patients had suspicious truncal nodes on EUS or CT, but metastases in the pathology specimen were absent. In the present study, it is demonstrated that positive truncal nodes in the resection specimen after neoadjuvant therapy, are associated with advanced tumor stages and are an independent factor for inferior survival.

  17. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial

    NARCIS (Netherlands)

    van Meurs, Hannah S.; Tajik, Parvin; Hof, Michel H. P.; Vergote, Ignace; Kenter, Gemma G.; Mol, Ben Willem J.; Buist, Marrije R.; Bossuyt, Patrick M.

    2013-01-01

    To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. We used data of the European Organisation for Research and

  18. [Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

    Science.gov (United States)

    Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

    2015-01-01

    To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  19. Neoadjuvant twice daily chemoradiotherapy for esophageal cancer: Treatment-related mortality and long-term outcomes

    Directory of Open Access Journals (Sweden)

    Stuart E. Samuels, MD, PhD

    2017-07-01

    Conclusion: Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.

  20. HIFU as a Neoadjuvant Therapy in Cancer Treatment

    Science.gov (United States)

    Zhong, P.; Xing, F.; Huang, X.; Zhu, H.; Lo, H. W.; Zhong, X.; Pruitt, S.; Robertson, C.

    2011-09-01

    To broaden the application spectrum of HIFU in cancer therapy, we performed a pilot experiment to evaluate the potential of using HIFU as a neoadjuvant therapy prior to surgery. Mice bearing wild-type B16F10 melanoma inoculated subcutaneously were either untreated (control) or treated by HIFU, CPA-7 or HIFU+CPA-7 before surgical resection of the primary tumor two days after HIFU treatment. The animals were then followed for four weeks or up to the humane endpoint to determine local recurrence, distant metastasis, and survival rate. The results demonstrate that animals treated by HIFU+CPA-7 (which is a small molecule that suppresses STAT3 activity) had a significantly lower recurrence rate, and slower growth of the recurrent tumor, with concomitantly higher survival rate, followed by those treated with CPA-7 and HIFU, respectively. Immunological assays revealed that CPA-7 treatment could significantly lower STAT3, and subsequently, Treg activities. In particular, the combination of HIFU and CPA-7 can induce a much stronger anti-tumor immune response than HIFU or surgery alone, as assessed by CTL and IFN-γ secretion. Overall, our results suggest that HIFU in combination with immunotherapy strategies has the potential to be used as a neoadjuvant therapy to prime the host with a strong anti-tumor immune response before surgical resection of the primary tumor. This multimodality, combinational therapy has the potential to greatly broaden the range of HIFU applications in cancer therapy with lower tumor recurrence and improved survival rate.

  1. Sorafenib neoadjuvant therapy in the treatment of high risk renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Yushi Zhang

    Full Text Available To evaluate the clinical efficacy of sorafenib as preoperative neoadjuvant therapy in patients with high risk renal cell carcinoma (RCC.Clinical data of 18 patients with high risk RCC who received surgery done successfully after preoperative neoadjuvant therapy with sorafenib in Peking Union Medical College Hospital (PUMCH from April 2007 to October 2013 have been reviewed and analyzed in this study.Among the 18 patients there were 13 male and 5 female, with a median age of 54.6 years. The objective response rate (ORR of the operation on the selected patients is very high (94.4%, including 4 cases (22.2% of partial response (PR and 13 cases (72.2% of stable disease (SD. After preoperative sorafenib treatment, the average tumor size of the 18 patients decreased from 7.8 cm (ranging from 3.6 to 19.2 cm to 6.2 cm (ranging from 2.4 to 16.8 cm, and the median value of average tumor CT value decreased from 61HU to 52 HU. Among the 5 patients who had IVC tumor thrombi, the grades of tumor thrombi in 2 patients who were grade II before sorafenib treatment became grade I and grade 0 respectively, 2 patients of grade III both became grade II.Preoperative neoadjuvant therapy with sorafenib for high risk RCC patients can significantly decrease primary tumor volume as well as tumor thrombus, which could help the nephron-sparing surgery (NSS or radical nephrectomy to be done successfully.

  2. FDG PET in monitoring response to neoadjuvant chemoradiotherapy in patients with locally advanced non-small lung carcinoma

    International Nuclear Information System (INIS)

    Berlangieri, S. U.; Lee, S. T.; Chan, A. M.; Mitchell, P. L.; Knight, S. R.; Feigen, M. M.; Scott, A. M.

    2009-01-01

    Full text:Aim: The aim of our study was to correlate 18F-FDG PET response to neoadjuvant chemoradiotherapy with histopathology in patients with locally advanced non-small cell lung carcinoma. Methods: All patients with stage III NSCLC planned for surgery following induction chemotherpay and/or radiotherapy who underwent pre- and post-treatment FDG-PET between 2004 and 2007 were retrospectively reviewed. The PET scans were performed according to standard protocol. The clinical FDG-PET TNM stage was correlated with the histopathology of the surgical specimens. Results: There were 9 patients (6 M :3 F ), median age 59.7 years (range 49 to 73 years). Post-treatment FDG-PET correctly predicted mediastinal pathological N stage in 8/9 patients, with one patient having microsopic disease in two nodes. The post-treatment FDG-PET correctly predicted pathological T stage in 7/9 patients, with 2 patients having small volume T4 disease not detected by PET. Post-treatment FDG-PET correctly downstaged 4 patients. Of the 5 patients, incorrectly staged on the post-treatment FDG-PET, one patient had microscopic pN 2 disease, 2 had pN 1 disease, and 2 had pT 4 disease. Conclusion: Post-treatment FDG-PET is predictive of pathological nodal stage within the mediastinum in patients with locally advanced NSCLC treated with neoadjuvant chemoradiotherapy. FDG-PET does not detect microscopic or small volume disease, nor is it able to define the boundaries of mediastinal tissue invasion.

  3. Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States)

    2014-06-01

    Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

  4. Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

    International Nuclear Information System (INIS)

    Sher, David J.; Liptay, Michael J.; Fidler, Mary Jo

    2014-01-01

    Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

  5. Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies

    International Nuclear Information System (INIS)

    Kumar, L.; Grover, R.; Pokharel, Y.H.; Chander, S.; Kumar, S.; Singh, R.; Rath, G.K.; Kochupillai, V.

    1998-01-01

    The results of two studies looking at the place of neo-adjuvant chemotherapy in the treatment of locally advanced cervical cancer being treated with radiotherapy are presented. Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IVA were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT). Three patients died of CT toxicity - two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. The neo-adjuvant chemotherapy prior to radiotherapy demonstrated a high response rate, but this did not translate into improved overall survival compared to those patients receiving radiotherapy alone

  6. Hybrid 18F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Goorts, Briete; Nijnatten, Thiemo J.A. van; Voeoe, Stefan; Wildberger, Joachim E.; Lobbes, Marc B.I.; Kooreman, Loes F.S.; Boer, Maaike de; Keymeulen, Kristien B.M.I.; Aarnoutse, Romy; Smidt, Marjolein L.; Mottaghy, Felix M.

    2017-01-01

    Our purpose in this study was to assess the added clinical value of hybrid 18 F-FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed. A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed. Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients. (orig.)

  7. Current Status of Intensified Neo-Adjuvant Systemic Therapy in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Engels, Benedikt; Gevaert, Thierry; Sermeus, Alexandra; De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, UZ Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

    2012-05-25

    The addition of 5-fluorouracil (5-FU) or its prodrug capecitabine to radiotherapy (RT) is a standard approach in the neo-adjuvant treatment of patients with rectal tumors extending beyond the muscularis propria (stage II) and/or with clinical evidence of regional lymph node metastases (stage III). According to European randomized trials, the combined treatment modality resulted in favorable local control rates as compared with radiotherapy (RT) alone, but no improvement was found regarding the occurrence of distant metastases or overall survival. In an effort to further enhance the response rates and to decrease the high incidence of distant metastases in locally advanced rectal cancer patients, the addition of other chemotherapeutical drugs and biologic agents as radiation sensitizers to neo-adjuvant 5-FU based chemoradiotherapy (CRT) has been recently investigated. The role of those agents is however questionable as first results from phase III data do not show improvement on pathologic complete remission and circumferential resection margin negative resection rates as compared to 5-FU based CRT, nevertheless an increased toxicity.

  8. Neoadjuvant chemotherapy in patients with stages III/IV breast ...

    African Journals Online (AJOL)

    The aim of this study was to determine disease response, recurrence and development of distant metastasis with the use of chemotherapy in the form of neoadjuvant chemotherapy. Patients and methods: This was a prospective study that had enrolled a total of 57 patients with locally advanced breast cancer disease ...

  9. Emphasis on neoadjuvant therapy for “resectable” pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Chang

    2015-05-01

    Full Text Available The treatment concept for pancreatic cancer is being transferred from “surgery first” to MDT model. The postoperative adjuvant treatment of pancreatic cancer can significantly improve the prognosis of patients and has become the standardized diagnostic and treatment practice; the value and significance of neoadjuvant therapy remains unclear. Limited clinical studies of “borderline resectable” pancreatic cancer have shown that neoadjuvant therapy can improve the R0 resection rate and improve the prognosis of patients, and it is recommended for clinical application. But the significance of neoadjuvant therapy in “resectable” pancreatic cancer is still controversial. There is a lack of consensus on indications, cycles, and regimens. It is necessary to carry out a series of prospective control studies to objectively evaluate the value of neoadjuvant therapy in improving the prognosis of “resectable” pancreatic cancer.

  10. Prognosis of patients with stage IIIb-IVa squamous cell carcinoma of the cervix following intra-arterial neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fujiwaki, R.; Maede, Y.; Ohnishi, Y.; Watanabe, Y.; Hata, K.; Miyazaki, K.

    1999-01-01

    The aim was to determine the long-term prognosis in patients with stage IIIb-IVa squamous cell carcinoma of the cervix who were treated with intra-arterial neoadjuvant chemotherapy (NAC), and to analyze factors related to prognostic value. The authors assessed the disease-free survival of 21 patients with FIGO stage IIIb-IVa squamous cell carcinoma of the cervix treated with intra-arterial NAC followed by irradiation therapy. Before chemotherapy, five factors (age, clinical stage, histologic type, parametrial involvement and serum level of SCC) were evaluated for their correlation with disease-free survival. Univariate Cox's proportional hazard model also demonstrated that age was a significant prognostic factor as a continuous variable. Intra-arterial NAC thus appeared to be effective in treating older patients with stage IIIb-IVa squamous cell carcinoma of the cervix

  11. Treatment outcomes of neoadjuvant concurrent chemoradiotherapy followed by esophagectomy for patients with esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Hyub; Song, Sang Yun; Shim, Hyun Jeong; Chung, Woong Ki; Ahn, Sung Ja; Yoon, Mee Sun; Jeong, Jae Uk; Song, Ju Young; Nam, Taek Keun [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2015-03-15

    To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT). We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.

  12. Hybrid {sup 18}F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Goorts, Briete; Nijnatten, Thiemo J.A. van [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); Voeoe, Stefan; Wildberger, Joachim E.; Lobbes, Marc B.I. [Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); Kooreman, Loes F.S. [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Pathology, Maastricht (Netherlands); Boer, Maaike de [Maastricht University Medical Center, Department of Medical Oncology, Maastricht (Netherlands); Keymeulen, Kristien B.M.I. [Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Aarnoutse, Romy; Smidt, Marjolein L. [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Mottaghy, Felix M. [Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany)

    2017-10-15

    Our purpose in this study was to assess the added clinical value of hybrid {sup 18}F-FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed. A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed. Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients. (orig.)

  13. Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial.

    Science.gov (United States)

    Karoui, Mehdi; Rullier, Anne; Luciani, Alain; Bonnetain, Franck; Auriault, Marie-Luce; Sarran, Antony; Monges, Geneviève; Trillaud, Hervé; Le Malicot, Karine; Leroy, Karen; Sobhani, Iradj; Bardier, Armelle; Moreau, Marie; Brindel, Isabelle; Seitz, Jean François; Taieb, Julien

    2015-07-10

    In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22--ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and

  14. Neoadjuvant Treatment With Single-Agent Cetuximab Followed by 5-FU, Cetuximab, and Pelvic Radiotherapy: A Phase II Study in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Bertolini, Federica; Chiara, Silvana; Bengala, Carmelo; Antognoni, Paolo; Dealis, Cristina; Zironi, Sandra; Malavasi, Norma; Scolaro, Tindaro; Depenni, Roberta; Jovic, Gordana; Sonaglio, Claudia; Rossi, Aldo; Luppi, Gabriele; Conte, Pier Franco

    2009-01-01

    Purpose: Preoperative chemoradiotherapy followed by surgery represents the standard of care for locally advanced rectal cancer (LARC). Cetuximab has proved activity in advanced colorectal cancer, and its incorporation in preoperative treatment may increase tumor downstaging. Methods and Materials: After biopsy and staging, uT3/uT4 N0/+ LARC received single-agent cetuximab in three doses, followed by weekly cetuximab plus 5-fluorouracil (5-FU), concomitantly with RT. Sample size was calculated according to Bryant and Day test, a two-stage design with at least 10 pathologic complete remissions observed in 60 patients (pts) able to complete the treatment plan. Results: Forty pts with LARC were entered: male/female = 34/6; median age: 61 (range, 28-77); 12 uT3N0 Ed(30%); 25 uT3N1 (62%); 3 uT4N1 (8%); all Eastern Cooperative Oncology Group = 0. Thirty-five pts completed neoadjuvant treatment; 5 (12%) withdrew therapy after one cetuximab administration: three for hypersensitivity reactions, one for rapid progression, and one for purulent arthritis. They continued 5-FU in continuous infusion in association with RT. Thirty-one pts (77%) presented with acnelike rash; dose reduction/interruption of treatment was necessary in six pts (15%): two for Grade 3 acnelike rash, two for Grade 3 gastrointestinal toxicity, and two for refusal. Thirty-eight pts were evaluable for pathological response (one patient refused surgery, and one was progressed during neoadjuvant treatment). Pathological staging was: pT0N0 three pts (8%), pT1N0 1 pt (3%); pT2N0 13 pts (34%), and pT3 19 pts (50%) (N0:9, N1:5; N2:5); pT4 2 pts (5%). Conclusions: Preoperative treatment with 5-FU, cetuximab, and pelvic RT is feasible with acceptable toxicities; however, the rate of pathologic responses is disappointingly low

  15. Evaluation of response to neoadjuvant chemotherapy in breast cancer

    International Nuclear Information System (INIS)

    Jia Li; Deng Zhiyong

    2013-01-01

    Preoperative neoadjuvant chemotherapy has become the standardized treatment for patients with locally advanced breast cancer. With the wide application of neoadjuvant chemotherapy in clinic, evaluation of response to neoadjuvant chemotherapy seems increasingly important. How to evaluate the curative effect of chemotherapy timely, accurately, effectively and noninvasively has become the focus of clinical research. At present, clinical palpation,radiographic measurement and pathological examination are usually used in clinic, and the study of breast cancer biology factor is also rapidly spread. The application status of different evaluation methods of neoadjuvant chemotherapy were reviewed in this article. (authors)

  16. Utility of the CPS+EG staging system in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with neoadjuvant chemotherapy.

    Science.gov (United States)

    Marmé, Frederik; Lederer, Bianca; Blohmer, Jens-Uwe; Costa, Serban Dan; Denkert, Carsten; Eidtmann, Holger; Gerber, Bernd; Hanusch, Claus; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kümmel, Sherko; Loibl, Sibylle; Paepke, Stefan; Untch, Michael; von Minckwitz, Gunter; Schneeweiss, Andreas

    2016-01-01

    Pathologic complete response after neoadjuvant chemotherapy (NACT) correlates with overall survival (OS) in primary breast cancer. A recently described staging system based on pre-treatment clinical stage (CS), final pathological stage (PS), estrogen receptor (ER) status and nuclear grade (NG) leads to a refined estimation of prognosis in unselected patients. Its performance in luminal type breast cancers has not been determined. This study investigates the clinical utility of this CPS+EG score when restricted to hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients and compares the results to a cohort of unselected patients. The CPS+EG score was calculated for 6637 unselected patients and 2454 patients with HR+/HER2- tumours who received anthracycline/taxane-based NACT within 8 prospective German trials. Five-year disease-free survival (DFS) and OS were 75.6% and 84.1% for the unselected cohort and 80.6% and 87.8% for the HR+/HER2- subgroup, respectively. The CPS+EG system distinguished different prognostic groups with 5-year DFS ranging from 0% to 91%. The CPS+EG system leads to an improved categorisation of patients by outcome compared to CS, PS, ER or NG alone. When applying the CPS+EG score to the HR+/HER2- subgroup, a shift to lower scores was observed compared to the overall population, but 5-year DFS and OS for the individual scores were identical to that observed in the overall population. In HR+/HER2- patients, the CPS+EG staging system retains its ability to facilitate a refined stratification of patients according to outcome. It can help to select candidates for post-neoadjuvant clinical trials in luminal breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Validation of the CPS + EG Staging System for Disease-Specific Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Abdelsattar, Jad M; Al-Hilli, Zahraa; Hoskin, Tanya L; Heins, Courtney N; Boughey, Judy C

    2016-10-01

    CPS + EG staging, which incorporates estrogen receptor (ER) status and tumor grade with pretreatment clinical stage (CS) and post-treatment pathologic stage (PS), has been reported to have better correlation with outcome than classic TNM staging for patients treated with neoadjuvant chemotherapy (NAC). Our goal was to evaluate the performance of CPS + EG staging system in an external cohort treated with NAC. We reviewed patients with stages I-IIIC breast cancer treated with NAC and surgery at our institution between 1988 and 2014. ER status, Nottingham grade, treatment, American Joint Committee on Cancer (AJCC) CS before NAC and PS after NAC, and follow-up data were collected. The discrimination of CPS + EG and pathologic AJCC stage were assessed using area under the curve (AUC) for survival data. A total of 769 patients were analyzed with a median follow-up of 2.6 (range 0.0-19.4) years; 103 patients died of breast cancer. Overall, the 5-year breast cancer cause-specific survival was 81.5 % [95 % confidence interval (CI) 77.6-85.5]. The 5-year, cause-specific survival by CPS + EG score was 93.8 % score 0, 89.9 % score 1, 90.7 % score 2, 84.8 % score 3, 67.7 % score 4, and 43.4 % score 5/6. CPS + EG score was significantly associated with cause-specific survival (p < 0.001) with an AUC of 0.69 (95 % CI 0.62-0.77) at 5 years. This was higher than the AUC of 0.63 (95 % CI 0.56-0.70) for AJCC PS (p = 0.10). This study validates the CPS + EG staging system using Nottingham grade in an external cohort. Addition of tumor biology and treatment response shows promise in improving survival estimates for patients treated with NAC.

  18. Evidence-based guideline recommendations on treatment strategies for localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy.

    Science.gov (United States)

    Werier, Joel; Yao, Xiaomei; Caudrelier, Jean-Michel; di Primio, Gina; Ghert, Michelle; Gupta, Abha A; Kandel, Rita; Verma, Shailendra

    2016-06-01

    (1) To provide recommendations regarding the choice of surgery, radiation therapy (RT), or the combination of surgery plus RT in patients with localized Ewing's sarcoma of bone following neoadjuvant chemotherapy. (2) To determine the appropriate surgical planning imaging (pre-chemotherapy magnetic resonance imaging [MRI] or post-chemotherapy MRI) to identify optimal resection margins in patients with localized Ewing's sarcoma who undergo surgery following neoadjuvant chemotherapy. MEDLINE, EMBASE, the Cochrane Library (1999 to February 2015), main guideline websites, and relevant annual meeting abstracts (2012 to January 2015) were searched. Internal and external reviews were conducted. 1. Recommendation (1) - In patients with localized Ewing's sarcoma of bone following neoadjuvant chemotherapy: (a) Surgery alone or RT alone are two reasonable treatment options; the combination of surgery plus RT is not recommended as an initial treatment option. (b) The local treatment for an individual patient should be decided by a multidisciplinary tumour board together with the patient after consideration of the following: (1) patient characteristics (e.g., age, tumour location, tumour size, response to neoadjuvant chemotherapy, and existing comorbidities), (2) the potential benefit weighed against the potential complications from surgery and/or toxicities associated with RT, and (3) patient preferences. 2. Recommendation (2) - In patients with localized Ewing's sarcoma who will undergo surgery: (a) Both pre-chemotherapy and post-chemotherapy MRI scans should be taken into consideration for surgical planning. In certain anatomic locations with good chemotherapy response, the post-chemotherapy MRI may be the appropriate imaging modality to plan surgical resection margins. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

    Science.gov (United States)

    Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

    2014-06-01

    The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p5 cm (p35 days (p5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

  20. Controversies in breast cancer: adjuvant and neoadjuvant therapy.

    Science.gov (United States)

    Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

    2005-06-01

    Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

  1. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.

    Science.gov (United States)

    Ladoire, Sylvain; Mignot, Grégoire; Dabakuyo, Sandrine; Arnould, Laurent; Apetoh, Lionel; Rébé, Cedric; Coudert, Bruno; Martin, Francois; Bizollon, Marie Hélène; Vanoli, André; Coutant, Charles; Fumoleau, Pierre; Bonnetain, Franck; Ghiringhelli, François

    2011-07-01

    Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial – the PRODIGE 22 - ECKINOXE trial

    International Nuclear Information System (INIS)

    Karoui, Mehdi; Rullier, Anne; Luciani, Alain; Bonnetain, Franck; Auriault, Marie-Luce; Sarran, Antony; Monges, Geneviève; Trillaud, Hervé; Le Malicot, Karine; Leroy, Karen; Sobhani, Iradj; Bardier, Armelle; Moreau, Marie; Brindel, Isabelle; Seitz, Jean François; Taieb, Julien

    2015-01-01

    In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30 % of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22 - ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and

  3. Neoadjuvant Treatment Does Not Influence Perioperative Outcome in Rectal Cancer Surgery

    International Nuclear Information System (INIS)

    Ulrich, Alexis; Weitz, Juergen; Slodczyk, Matthias; Koch, Moritz; Jaeger, Dirk; Muenter, Marc; Buechler, Markus W.

    2009-01-01

    Purpose: To identify the risk factors for perioperative morbidity in patients undergoing resection of primary rectal cancer, with a specific focus on the effect of neoadjuvant therapy. Methods and Materials: This exploratory analysis of prospectively collected data included all patients who underwent anterior resection/low anterior resection or abdominoperineal resection for primary rectal cancer between October 2001 and October 2006. The study endpoints were perioperative surgical and medical morbidity. Univariate and multivariate analyses of potential risk factors were performed. Results: A total of 485 patients were included in this study; 425 patients (88%) underwent a sphincter-saving anterior resection/low anterior resection, 47 (10%) abdominoperineal resection, and 13 (2%) multivisceral resection. Neoadjuvant chemoradiotherapy was performed in 100 patients (21%), and 168 (35%) underwent neoadjuvant short-term radiotherapy (5 x 5 Gy). Patient age and operative time were independently associated with perioperative morbidity, and operative time, body mass index >27 kg/m 2 (overweight), and resection type were associated with surgical morbidity. Age and a history of smoking were confirmed as independent prognostic risk factors for medical complications. Neoadjuvant therapy was not associated with a worse outcome. Conclusion: The results of this prospective study have identified several risk factors associated with an adverse perioperative outcome after rectal cancer surgery. In addition, neoadjuvant therapy was not associated with increased perioperative complications.

  4. Using Flow Characteristics in Three-Dimensional Power Doppler Ultrasound Imaging to Predict Complete Responses in Patients Undergoing Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Shia, Wei-Chung; Huang, Yu-Len; Wu, Hwa-Koon; Chen, Dar-Ren

    2017-05-01

    Strategies are needed for the identification of a poor response to treatment and determination of appropriate chemotherapy strategies for patients in the early stages of neoadjuvant chemotherapy for breast cancer. We hypothesize that power Doppler ultrasound imaging can provide useful information on predicting response to neoadjuvant chemotherapy. The solid directional flow of vessels in breast tumors was used as a marker of pathologic complete responses (pCR) in patients undergoing neoadjuvant chemotherapy. Thirty-one breast cancer patients who received neoadjuvant chemotherapy and had tumors of 2 to 5 cm were recruited. Three-dimensional power Doppler ultrasound with high-definition flow imaging technology was used to acquire the indices of tumor blood flow/volume, and the chemotherapy response prediction was established, followed by support vector machine classification. The accuracy of pCR prediction before the first chemotherapy treatment was 83.87% (area under the ROC curve [AUC] = 0.6957). After the second chemotherapy treatment, the accuracy of was 87.9% (AUC = 0.756). Trend analysis showed that good and poor responders exhibited different trends in vascular flow during chemotherapy. This preliminary study demonstrates the feasibility of using the vascular flow in breast tumors to predict chemotherapeutic efficacy. © 2017 by the American Institute of Ultrasound in Medicine.

  5. The Impact of Skin-Sparing Mastectomy With Immediate Reconstruction in Patients With Stage III Breast Cancer Treated With Neoadjuvant Chemotherapy and Postmastectomy Radiation

    International Nuclear Information System (INIS)

    Prabhu, Roshan; Godette, Karen; Carlson, Grant; Losken, Albert; Gabram, Sheryl; Fasola, Carolina; O’Regan, Ruth; Zelnak, Amelia; Torres, Mylin

    2012-01-01

    Purpose: The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non–SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT). Methods and Materials: Between October 1997 and March 2010, 100 consecutive patients (40 SSM with IR vs. 60 non-SSM) with Stage III breast cancer received anthracycline- and/or taxane-based neoadjuvant chemotherapy, mastectomy, and adjuvant XRT. Clinical stage (SSM with IR vs. for non-SSM) was IIIA (75% vs. 67%), IIIB (8% vs. 18%), and IIIC (8% vs. 8%). Tumors greater than 5 cm were found in 74% vs. 69%; 97% of patients in both groups were clinically node positive; and 8% vs. 18% had T4b disease. Results: The time from initial biopsy to XRT was prolonged for SSM–IR patients (274 vs. 254 days, p = 0.04), and there was a trend toward XRT delay of more than 8 weeks (52% vs. 31%, p = 0.07) after surgery. The rate of complications requiring surgical intervention was higher in the SSM–IR group (37.5% vs. 5%, p < 0.001). The 2-year actuarial locoregional control, breast cancer–specific survival, and overall survival rates for SSM with IR vs. non-SSM were 94.7% vs. 97.4%, 91.5% vs. 86.3%, and 87.4% vs. 84.8%, respectively (p = not significant). Conclusions: In our small study with limited follow-up, SSM with IR prolonged overall cancer treatment time and trended toward delaying XRT but did not impair oncologic outcomes. Complication rates were significantly higher in this group. Longer follow-up is needed.

  6. Dosimetric Feasibility of Hypofractionated Proton Radiotherapy for Neoadjuvant Pancreatic Cancer Treatment

    International Nuclear Information System (INIS)

    Kozak, Kevin R.; Kachnic, Lisa A.; Adams, Judith C; Crowley, Elizabeth M.; Alexander, Brian M.; Mamon, Harvey J.; Fernandez-Del Castillo, Carlos; Ryan, David P.; DeLaney, Thomas F.; Hong, Theodore S.

    2007-01-01

    Purpose: To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. Methods and Materials: The first 9 pancreatic cancer patients treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5 fraction proton regimen. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions (≤20% prescribed dose for both kidneys and ≤60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. Conclusions: A proton radiotherapy schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent target volume coverage, dose homogeneity, and normal tissue sparing. Hypofractionated proton radiotherapy in this setting merits Phase I clinical trial investigation

  7. Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance)

    Science.gov (United States)

    Ellis, Matthew J.; Suman, Vera J.; Hoog, Jeremy; Goncalves, Rodrigo; Sanati, Souzan; Creighton, Chad J.; DeSchryver, Katherine; Crouch, Erika; Brink, Amy; Watson, Mark; Luo, Jingqin; Tao, Yu; Barnes, Michael; Dowsett, Mitchell; Budd, G. Thomas; Winer, Eric; Silverman, Paula; Esserman, Laura; Carey, Lisa; Ma, Cynthia X.; Unzeitig, Gary; Pluard, Timothy; Whitworth, Pat; Babiera, Gildy; Guenther, J. Michael; Dayao, Zoneddy; Ota, David; Leitch, Marilyn; Olson, John A.; Allred, D. Craig; Hunt, Kelly

    2017-01-01

    Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) –positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for

  8. Neoadjuvant chemoradiotherapy for cStage IIIA/IIIB locally advanced gastric cancer

    International Nuclear Information System (INIS)

    Inoue, Tatsushi; Suto, Hiromasa; Kashiwagi, Hirotaka

    2010-01-01

    We evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) with radio-enhancing S-1 for locally advanced gastric cancer. Patients who had a gastric cancer infiltrating into other organs (T4) or with bulky N2 were enrolled in this study. They received oral S-1 (65 mg/m 2 /day) administration and 50 Gy radiotherapy followed by radical surgery. In 12 subjects (male:female ratio, 7:5; mean age, 70.0 years), 10 (83.3%) completed NACRT and 12 (100%) underwent curative resection. Histopathological efficacy (≥Grade 1b) and down staging were observed 6 patients (75.0%) and 5 (62.5%), respectively, in 8 T4 patients. The efficacy was ≥Grade 2 in all 4 patients with bulky N2. No extra-nodal invasion was noted. In this series 1-and 3-year survival rates were 90.9% and 60.6%, respectively, during a mean observation period of 18.6 months. This procedure is applicable even to hemorrhaging patients. Outstanding antineoplastic effects are expected in locally advanced gastric cancer. (author)

  9. Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

    Directory of Open Access Journals (Sweden)

    I.P.C. Buzatto

    Full Text Available The purpose of this study was to retrospectively review the pathologic complete response (pCR rate from patients (n=86 with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012. Stage II patients achieved a higher response rate compared to stage III (P=0.03. The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively. Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03 and death (HR=0.21; P=0.02. In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

  10. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    Science.gov (United States)

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  11. Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.

    Science.gov (United States)

    Samrao, Damanzoopinder; Wang, Dan; Ough, Faith; Lin, Yvonne G; Liu, Song; Menesses, Teodulo; Yessaian, Annie; Turner, Nicole; Pejovic, Tanja; Mhawech-Fauceglia, Paulette

    2012-12-01

    The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen's kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of 20 months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.

  12. CCR 20th Anniversary Commentary: Simpson's Paradox and Neoadjuvant Trials.

    Science.gov (United States)

    Carey, Lisa A

    2015-09-15

    The research article by Carey and colleagues, published in the April 15, 2007, issue of Clinical Cancer Research, described the relationship between response to neoadjuvant chemotherapy and outcome by tumor subtype. Today neoadjuvant clinical trials are often designed to provide correlative data to help identify predictive biomarkers or to focus on poor-risk patients identified by residual disease after neoadjuvant treatment. ©2015 American Association for Cancer Research.

  13. Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study.

    Science.gov (United States)

    Magi-Galluzzi, Cristina; Zhou, Ming; Reuther, Alwyn M; Dreicer, Robert; Klein, Eric A

    2007-09-15

    staining patterns were compared between PBx and RP specimens using the Wilcoxon signed-rank test, only p53 expression (P = .017) and Bcl-2 expression (P = .014) were found to be increased significantly after neoadjuvant docetaxel treatment. However, after performing the Bonferroni adjustment, these differences were no longer significant (P > .005). Ki-67, ApopTag, beta-tubulin I, and beta-tubulin III expression levels also were increased after treatment; however, the differences were not found to be statistically significant. The expression levels of AMACR, p27, p21, and cyclin D1 were comparable in pretreatment and posttreatment specimens. The current results indicated that, although it will require longer follow-up studies and larger numbers of patients to ascertain the value of neoadjuvant treatment, the negative findings of the current study may explain the lack of clinical response in patients who received neoadjuvant docetaxel for PCa. Although the results were subject to interpretation limits based on the study size, the increased expression of p53 and Bcl-2 that was detected after treatment using the Wilcoxon signed-rank test suggested that the apoptotic pathway may be an important target for this drug, and further investigation is warranted. (c) 2007 American Cancer Society.

  14. Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate

    NARCIS (Netherlands)

    van Vliet, Esther I.; van Eijck, Casper H.; de Krijger, Ronald R.; Nieveen van Dijkum, Elisabeth J.; Teunissen, Jaap J.; Kam, Boen L.; de Herder, Wouter W.; Feelders, Richard A.; Bonsing, Bert A.; Brabander, Tessa; Krenning, Eric P.; Kwekkeboom, Dik J.

    2015-01-01

    Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) may be an option. We

  15. Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment.

    Science.gov (United States)

    Chen, Jianghao; Yao, Qing; Wang, Hui; Wang, Bo; Zhang, Juliang; Wang, Ting; Lv, Yonggang; Han, Zenghui; Wang, Ling

    2015-07-01

    Neoadjuvant chemotherapy has been increasingly used to downstage breast cancer prior to surgery recently. However, in some cases, it was observed that despite sufficient regression of primary tumors, the metastatic lymph nodes remained nonresponsive. In this study, we applied lymphatic-targeted strategy to evaluate its efficacy and safety for patients presenting refractory nodes following systemic chemotherapy. A total of 318 breast cancer patients were demonstrated with lymph node metastasis by needle biopsy and given neoadjuvant chemotherapy. Two cycles later, 72 patients were observed with responsive tumors but stable nodes, 42 of which received a subcutaneous injection of lymphatic-targeted pegylated liposomal doxorubicin during the third cycle, while the remaining 30 patients were continued with former neoadjuvant therapeutic pattern and regarded as the control. Lymphatic-targeted treatment substantially increased both clinical and pathological node response rate [62 % (26/42) vs. 13 % (4/30) and 12 % (5/42) vs. 0 (0/30), respectively], and induced a higher apoptosis level of metastatic cells (median, 41 vs. 6 %), compared with the control. Moreover, a higher disease-free survival was observed after a median follow-up of 4 years (69 vs. 56 %). Inflammatory reaction surrounding injection sites was the most common side effect. Lymphatic chemotherapy has reliable efficacy and well-tolerated toxicity for breast cancer patients presenting refractory lymph nodes following neoadjuvant chemotherapy.

  16. A Feasibility Study of Neoadjuvant XELOX Without Radiotherapy for Locally Advanced Lower Rectal Cancer.

    Science.gov (United States)

    Ueki, Takashi; Manabe, Tatsuya; Inoue, Shigetaka; Ienaga, Jun; Yamanaka, Naoki; Egami, Takuya; Ishikawa, Mikimasa; Konomi, Hiroyuki; Ikubo, Akashi; Nagayoshi, Kinuko; Nakamura, Masafumi; Tanaka, Masao

    2016-02-01

    This study was planned to evaluate the efficacy and safety of preoperative capecitabine and oxaliplatin (XELOX) without radiation in patients with locally advanced lower rectal cancer. Patients with clinical stage II/III lower rectal cancer underwent three cycles of XELOX followed by radical surgery. The primary end-point was the R0 resection rate. Thirty-one patients were recruited between February 2012 and August 2014. The completion rate of neoadjuvant chemotherapy was 96.5% among the 29 patients who received it; the remaining two refused chemotherapy and underwent immediate surgery. Grade 3-4 adverse events occurred in nine patients (31%). All 29 patients who received chemotherapy underwent radical resection. The R0 resection rate was 96.5% among these 29 patients. Pathological complete responses were achieved in three patients (10.3%) and downstaging occurred in 13 (44.8%). This pilot study found that neoadjuvant XELOX for locally advanced lower rectal cancer is feasible and safe. This neoadjuvant treatment improved resection margin status. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Intensity-modulated radiotherapy for neoadjuvant treatment of gastric cancer

    International Nuclear Information System (INIS)

    Knab, Brian; Rash, Carla; Farrey, Karl; Jani, Ashesh B.

    2006-01-01

    Radiation therapy plays an integral role in the treatment of gastric cancer in the postsurgery setting, the inoperable/palliative setting, and, as in the case of the current report, in the setting of neoadjuvant therapy prior to surgery. Typically, anterior-posterior/posterior-anterior (AP/PA) or 3-field techniques are used. In this report, we explore the use of intensity-modulated radiotherapy (IMRT) treatment in a patient whose care was transferred to our institution after 3-field radiotherapy (RT) was given to a dose of 30 Gy at an outside institution. If the 3-field plan were continued to 50 Gy, the volume of irradiated liver receiving greater than 30 Gy would have been unacceptably high. To deliver the final 20 Gy, an opposed parallel AP/PA plan and an IMRT plan were compared to the initial 3-field technique for coverage of the target volume as well as dose to the kidneys, liver, small bowel, and spinal cord. Comparison of the 3 treatment techniques to deliver the final 20 Gy revealed reduced median and maximum dose to the whole kidney with the IMRT plan. For this 20-Gy boost, the volume of irradiated liver was lower for both the IMRT plan and the AP/PA plan vs. the 3-field plan. Comparing the IMRT boost plan to the AP/PA boost-dose range ( 10 Gy) in comparison to the AP/PA plan. The IMRT boost plan also irradiated a smaller volume of the small bowel compared to both the 3-field plan and the AP/PA plan, and also delivered lower dose to the spinal cord in comparison to the AP/PA plan. Comparison of the composite plans revealed reduced dose to the whole kidney using IMRT. The V20 for the whole kidney volume for the composite IMRT plan was 30% compared to approximately 60% for the composite AP/PA plan. Overall, the dose to the liver receiving greater than 30 Gy was lower for the composite IMRT plan and was well below acceptable limits. In conclusion, our study suggests a dosimetric benefit of IMRT over conventional planning, and suggests an important role for

  18. Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer

    Science.gov (United States)

    Mellado, B; Font, A; Alcaraz, A; Aparicio, L A; Veiga, F J G; Areal, J; Gallardo, E; Hannaoui, N; Lorenzo, J R M; Sousa, A; Fernandez, P L; Gascon, P

    2009-01-01

    Background: The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment. Methods: Patients with T1c–T2 clinical stage with prostate-specific antigen (PSA) >20 ng ml−1 and/or Gleason score ⩾7 (4+3) and T3 were included. Treatment consisted of three cycles of D 36 mg m−2 on days 1, 8 and 15 every 28 days concomitant with CAB, followed by radical prostatectomy (RP). Results: A total of 57 patients were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and T3, 16 (28%) patients. Gleason score was ⩾7 (4+3) in 44 (77%) patients and PSA >20 ng ml−1 in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%) patients completing neoadjuvant therapy together with RP. The rate of pCR was 6% (three patients). Three (6%) additional patients had microscopic residual tumour (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%) patients presented PSA relapse. Conclusion: Short-term neoadjuvant D and CAB induced a 6% pCR rate, which is close to what would be expected with ADT alone. The combination was generally well tolerated. PMID:19755998

  19. MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

    2017-06-01

    Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    International Nuclear Information System (INIS)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner; Brunner, Thomas B.; Witzigmann, Helmut; Marti, Lukas; Bechstein, Wolf-Otto; Bruns, Christiane; Jungnickel, Henry; Schreiber, Stefan; Grabenbauer, Gerhard G.; Meyer, Thomas; Fietkau, Rainer

    2015-01-01

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [de

  1. Race is associated with completion of neoadjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Knisely, Anne T; Michaels, Alex D; Mehaffey, J Hunter; Hassinger, Taryn E; Krebs, Elizabeth D; Brenin, David R; Schroen, Anneke T; Showalter, Shayna L

    2018-05-03

    Completion of prescribed neoadjuvant chemotherapy for breast cancer is paramount to patients obtaining full benefit from the treatment; however, factors affecting neoadjuvant chemotherapy completion are not known. We hypothesized that race is a predictor of completion of neoadjuvant chemotherapy in patients with breast cancer. All patients with breast cancer treated with neoadjuvant chemotherapy 2009-2016 at a single institution were stratified by completion of neoadjuvant chemotherapy and by race. Univariate analysis and multivariable logistic regression were used to identify patient and tumor characteristics that affected the rate of neoadjuvant chemotherapy completion. A total of 92 (74%) of 124 patients completed their prescribed neoadjuvant chemotherapy. On univariate analysis, white patients were more likely to complete neoadjuvant chemotherapy than non-white patients (76% vs 50%, P = .006). Non-white patients were more likely to have government insurance and larger prechemotherapy tumors (both, P < .05), but these factors were not associated with rates of neoadjuvant chemotherapy completion. After controlling for age, insurance status, tumor size, and estrogen receptor status, whites remained associated with completion of neoadjuvant chemotherapy (OR 3.65, P = .014). At our institution, white patients with breast cancer were more likely than non-white patients to complete neoadjuvant chemotherapy. Further investigation into the underlying factors impacting this disparity is needed. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Neoadjuvant chemotherapy for primary adenocarcinomas of the urinary bladder: a single-site experience.

    Science.gov (United States)

    Yu, Bin; Zhou, Jin; Cai, Hongzhou; Xu, Ting; Xu, Zicheng; Zou, Qing; Gu, Min

    2015-01-28

    Adenocarcinoma of the urinary bladder is a rare malignancy. Radical surgery is suggested as the best available treatment for early-stage disease, but there is currently no consensus on standard chemotherapy regimen for advanced stage. We assessed the feasibility and effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) plus S-1 for patients with locally advanced primary adenocarcinomas of the urinary bladder. Six patients with locally advanced urachal or non-urachal (n = 3, each) primary adenocarcinoma of the bladder were treated from October 2010 to October 2013 at a single center. All the patients were treated with 3 cycles (21d, each) of GC plus S-1 (gemcitabine, 1000 mg/m2, days 1 and 8; cisplatin, 70 mg/m2, day 2; and S-1, 50 mg bid, day 1-14). After neoadjuvant chemotherapy, patients with urachal cancer were treated with en bloc radical cystectomy and umbilectomy; the remaining 3 patients were treated with cystectomy. All patients successfully completed the neoadjuvant chemotherapy without serious side effects. Two patients were assessed as complete response, 2 as partial response, 1 as stable disease and 1 as progressive disease. Despite the limitations of a small study population, the GC plus S-1 regimen for locally advanced primary adenocarcinoma of the urinary bladder was effective, and facilitated the success of surgery to a certain extent. Short follow-up time was also a limitation of our study. More studies are needed to evaluate the results.

  3. Histologic response after neoadjuvant chemoradiotherapy in locally ...

    African Journals Online (AJOL)

    proven advantages of lower acute toxicity7, lower total dose of radiation needed8 and eventual tumor regression and down-staging to enable curative resection and even sphincter preservation8-13. The objective of this study is to assess the pathological response of neoadjuvant chemo radiation in patients with.

  4. Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Diocésio Alves Pinto de [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Zucca-Matthes, Gustavo; Vieira, René Aloísio da Costa [Hospital de Câncer de Barretos, Barretos, SP (Brazil); Andrade, Cristiane Thomaz de Aquino Exel de [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Costa, Allini Mafra da [Hospital de Câncer de Barretos, Barretos, SP (Brazil); Monteiro, Aurélio Julião de Castro [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Lago, Lissandra Dal [Institut Jules Bordet, Brussels (Belgium); Nunes, João Soares [Hospital de Câncer de Barretos, Barretos, SP (Brazil)

    2013-07-01

    To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/ cyclophosphamide regimen followed by paclitaxel. A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m{sup 2} and cyclophosphamide 600mg/m{sup 2} every 21 days; 4 cycles of paclitaxel 175mg/m{sup 2} every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose – duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. Neoadjuvant chemotherapy with doxorubicin/ cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.

  5. Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Songliang ZHANG

    2015-06-01

    Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

  6. MRI in staging of rectal carcinoma

    International Nuclear Information System (INIS)

    Gourtsoyianni, S.

    2012-01-01

    Full text: MRI of the rectum is performed for initial local staging of primary rectal cancer in order to identify locally advanced rectal cancers and for assessment of treatment response after completion of neoadjuvant therapy. Introduction of new generation MRI scanners with optimal phased array body coils, resulting in improved contrast and spatial resolution images due to better signal to noise ratio, have contributed to production of high resolution images in which visualization of anatomical details such as the mesorectal fascia and the bowel wall layers are feasible. Pre-operative MRI of the rectum using mainly high resolution T2 weighted sequences has gained significant accreditation, especially after the introduction of total mesorectal excision (TME) surgery and neoadjuvant therapy in the treatment regimen of rectal cancer. MR Imaging is so far the only method that can preoperatively identify patients most likely to benefit from neoadjuvant therapy as well as demonstrate high risk patients for local recurrence. Regarding N stage besides of mesorectal lymph nodes which are removed during TME, especially in case of low lying rectal cancers, MRI may provide information regarding external/internal iliac lymph node involvement. High resolution MRI images may demonstrate lymph nodes with a diameter down to 2 mm, however these are still characterized based on their morphological features. Patients identified at initial MRI staging as having locally advanced rectal cancer undergo neoadjuvant chemoradiation therapy (CRT) in order for their tumor to be downsized and downstaged, especially in low rectal cancers so that sphincter sparing surgery may be performed. In 15-30% of patients complete pathological response is achieved. Reimaging with MRI at 6 weeks post treatment is of great importance for assessing tumor response. Conventional MRI has a reported moderate accuracy for prediction of mesorectal fascia (MF) involvement after CRT therapy, mainly due to its

  7. Clinicopathologic Comparison of High-Dose-Rate Endorectal Brachytherapy versus Conventional Chemoradiotherapy in the Neoadjuvant Setting for Resectable Stages II and III Low Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Jessica A. Smith

    2012-01-01

    Full Text Available Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT or intensity-modulated radiotherapy (IMRT versus high-dose-rate endorectal brachytherapy (EBT. Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P<0.001. There was a trend towards higher rate of pathologic CR for EBT (P=0.06. Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P=0.025. Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.

  8. Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer.

    Science.gov (United States)

    Tomasello, Gianluca; Ghidini, Michele; Barni, Sandro; Passalacqua, Rodolfo; Petrelli, Fausto

    2017-06-01

    Neoadjuvant chemoradiotherapy (CTRT) is the current standard of care for treatment of locally advanced cancer of the esophagus or gastroesophageal junction. Many efforts have been made over the last years to identify the best chemotherapy and radiotherapy combination regimen, but specific randomized trials addressing this issue are still lacking. Areas covered: A systematic review of the literature was performed searching in PubMed all published studies of combinations CTRT regimens for operable or unresectable esophageal cancer to describe activity and toxicity. Studies considered were prospective series or clinical phase II-III trials including at least 40 patients and published in English language. Expert commentary: Long-term results of CROSS trial have established RT combined with carboplatin plus paclitaxel chemotherapy as the preferred neoadjuvant treatment option for both squamous and adenocarcinoma of the esophagus. More effective multimodal treatment strategies integrating novel biological agents including immunotherapy and based on an extensive molecular tumor characterization are eagerly awaited.

  9. Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of neoadjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Letourneau, Joseph M; Sinha, Nikita; Wald, Kaitlyn; Harris, Eve; Quinn, Molly; Imbar, Tal; Mok-Lin, Evelyn; Chien, A Jo; Rosen, Mitchell

    2017-10-01

    Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast cancer? Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely to delay time to initiation of neoadjuvant chemotherapy start. Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not well-understood. Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consultation prior to starting neoadjuvant chemotherapy for breast cancer. A chart-review was performed. Study inclusion criteria were female sex; age 18-45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evaluation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those who did not using T-tests and linear modeling. A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for those

  10. Postmastectomy radiotherapy reduces locoregional and disease recurrence in patients with stage II–III triple-negative breast cancer treated with neoadjuvant chemotherapy and mastectomy

    Directory of Open Access Journals (Sweden)

    Chen XX

    2018-04-01

    -free survival in the entire cohort as well as in patients with stage IIA disease. Our results may help in tailoring adjuvant treatment decisions for these particular patient populations. Keywords: triple-negative breast carcinoma, neoadjuvant chemotherapy, surgery, adjuvant radiation therapy, locoregional recurrence, disease recurrence

  11. Diagnostic accuracy of computed tomography and magnetic resonance imaging obtained after neoadjuvant chemoradiotherapy in predicting the local tumor stage and circumferential resection margin status of rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Hoon; Kim, Young Hoon; Lee, Yoon Jin; Lee, Kyoung Ho; Kang, Sung Bum; Kim, Duck Woo; Kim, Jae Hyun; Kim, Jae Sung; Lee, Hye Seung [Dept. of Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Lee, Sang Min [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-02-15

    To measure the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) obtained after neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer for a prediction of the local tumor stage and circumferential resection margin (CRM). Two independent radiologists reviewed CT and MRI obtained after neoadjuvant CRT. The accuracy of the local tumor staging and the diagnostic performance for the prediction of CRM involvement were calculated. The agreement between the measurements of the distance to potential CRM on both imaging modalities and the histopathology findings was assessed using Bland-Altman plots. 57 patients (mean age, 59.2 years; 24 females) were included. The accuracy of T and N staging were 43.9% (95% confidence interval, 30.8-57.7%) and 77.2% (64.2-87.3%) on CT and 63.2% (49.4-75.6%) and 77.2% (64.2-87.3%) on MRI for Observer 1. The accuracy of T and N staging were 54.4% (40.7-67.7%) and 77.2% (64.2-87.3%) on CT and 68.4% (54.7-80.1%) and 80.7% (68.1-90.0%) on MRI for Observer 2. Sensitivity and specificity on CRM involvement were 83.3% (43.7-97.0%) and 88.2% (76.6-94.5%) on CT and 100% (61.0-100%) and 90.2% (79.0-95.7%) on MRI for Observer 1. Sensitivity and specificity on CRM involvement were 66.7% (30.0-90.3%) and 88.2% (76.7-94.5%) on CT and 100% (61.0-100%) and 90.2% (79.0-95.7%) on MRI for Observer 2. Bland-Altman plots showed wide discrepancies between measurements of the distance to CRM on each CT and MRI and those on histopathology findings. CT and MRI showed limited performance in predicting the local tumor staging and CRM involvement in patients with neoadjuvant CRT although MRI tended to show a better performance than CT.

  12. Diagnostic accuracy of computed tomography and magnetic resonance imaging obtained after neoadjuvant chemoradiotherapy in predicting the local tumor stage and circumferential resection margin status of rectal cancer

    International Nuclear Information System (INIS)

    Park, Jin Hoon; Kim, Young Hoon; Lee, Yoon Jin; Lee, Kyoung Ho; Kang, Sung Bum; Kim, Duck Woo; Kim, Jae Hyun; Kim, Jae Sung; Lee, Hye Seung; Lee, Sang Min

    2014-01-01

    To measure the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) obtained after neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer for a prediction of the local tumor stage and circumferential resection margin (CRM). Two independent radiologists reviewed CT and MRI obtained after neoadjuvant CRT. The accuracy of the local tumor staging and the diagnostic performance for the prediction of CRM involvement were calculated. The agreement between the measurements of the distance to potential CRM on both imaging modalities and the histopathology findings was assessed using Bland-Altman plots. 57 patients (mean age, 59.2 years; 24 females) were included. The accuracy of T and N staging were 43.9% (95% confidence interval, 30.8-57.7%) and 77.2% (64.2-87.3%) on CT and 63.2% (49.4-75.6%) and 77.2% (64.2-87.3%) on MRI for Observer 1. The accuracy of T and N staging were 54.4% (40.7-67.7%) and 77.2% (64.2-87.3%) on CT and 68.4% (54.7-80.1%) and 80.7% (68.1-90.0%) on MRI for Observer 2. Sensitivity and specificity on CRM involvement were 83.3% (43.7-97.0%) and 88.2% (76.6-94.5%) on CT and 100% (61.0-100%) and 90.2% (79.0-95.7%) on MRI for Observer 1. Sensitivity and specificity on CRM involvement were 66.7% (30.0-90.3%) and 88.2% (76.7-94.5%) on CT and 100% (61.0-100%) and 90.2% (79.0-95.7%) on MRI for Observer 2. Bland-Altman plots showed wide discrepancies between measurements of the distance to CRM on each CT and MRI and those on histopathology findings. CT and MRI showed limited performance in predicting the local tumor staging and CRM involvement in patients with neoadjuvant CRT although MRI tended to show a better performance than CT

  13. Automatic staging of bladder cancer on CT urography

    Science.gov (United States)

    Garapati, Sankeerth S.; Hadjiiski, Lubomir M.; Cha, Kenny H.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Alva, Ajjai; Paramagul, Chintana; Wei, Jun; Zhou, Chuan

    2016-03-01

    Correct staging of bladder cancer is crucial for the decision of neoadjuvant chemotherapy treatment and minimizing the risk of under- or over-treatment. Subjectivity and variability of clinicians in utilizing available diagnostic information may lead to inaccuracy in staging bladder cancer. An objective decision support system that merges the information in a predictive model based on statistical outcomes of previous cases and machine learning may assist clinicians in making more accurate and consistent staging assessments. In this study, we developed a preliminary method to stage bladder cancer. With IRB approval, 42 bladder cancer cases with CTU scans were collected from patient files. The cases were classified into two classes based on pathological stage T2, which is the decision threshold for neoadjuvant chemotherapy treatment (i.e. for stage >=T2) clinically. There were 21 cancers below stage T2 and 21 cancers at stage T2 or above. All 42 lesions were automatically segmented using our auto-initialized cascaded level sets (AI-CALS) method. Morphological features were extracted, which were selected and merged by linear discriminant analysis (LDA) classifier. A leave-one-case-out resampling scheme was used to train and test the classifier using the 42 lesions. The classification accuracy was quantified using the area under the ROC curve (Az). The average training Az was 0.97 and the test Az was 0.85. The classifier consistently selected the lesion volume, a gray level feature and a contrast feature. This predictive model shows promise for assisting in assessing the bladder cancer stage.

  14. Neratinib for the treatment of HER2-positive early stage breast cancer.

    Science.gov (United States)

    Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

    2017-08-01

    Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

  15. Pathologic complete response in patients with neoadjuvant chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Espinola M, Daniela; Espinola M, Daniela; Bellolio R, Felipe; Gellona V, Jose; Bustos C, Mariza; Zuniga D, Alvaro

    2013-01-01

    Background: The standard treatment of locally advanced rectal cancer (RC) of the middle and lower third of the rectum is neoadjuvant chemoradiotherapy (XRQT) follow by oncologic resection. After this treatment in 15-25% of the cases, the pathologist reports complete pathological response (pCR). Aim: To describe demographic, clinical and survival data of patients with pCR undergoing chemoradiotherapy and radical resection for RC. Material and Methods: Historic cohort study. In a prospectively maintained database between 2000 and 2010, we identified patients with RC, who underwent neoadjuvant chemoradiotherapy according to protocol, followed by radical resection. The preoperative staging was obtained by clinical examination, endoscopy, rectal ultrasound, CT scan of chest, abdomen and pelvis and pelvic MRI. Demographic data, tumor location, time between the end of XRTQ and surgery, postoperative staging (according AJCC) and survival, were collected. Results: 119 patients received preoperative XRTQ, 65% male, with a mean age of 58 years. The most frequent tumor site was the lower third (63%). Surgery was performed 8 weeks after the end of XRTQ. Of 119 patients with XRTQ, 15.1% had a pCR. Overall survival was 75%, and cancer-specific survival was 80.4% at 5 years in patients without pCR. For patients with pCR, the 5 year survival estimates for overall and cancer specific survival was 100%. We did not identify factors associated with pCR. Conclusions: In this study, pCR was comparable to other larger series reported elsewhere. No factors associated with pCR were identified

  16. Prognostic implication of serum hepatocyte growth factor in stage II/III breast cancer patients who received neoadjuvant chemotherapy.

    Science.gov (United States)

    Kim, Hyori; Youk, Jeonghwan; Yang, Yaewon; Kim, Tae-Yong; Min, Ahrum; Ham, Hye-Seon; Cho, Seongcheol; Lee, Kyung-Hun; Keam, Bhumsuk; Han, Sae-Won; Oh, Do-Youn; Ryu, Han Suk; Han, Wonshik; Park, In Ae; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

    2016-03-01

    In stage II/III breast cancer, neoadjuvant chemotherapy (NAC) is a standard treatment. Although several biomarkers are used to predict prognosis in breast cancer, there is no reliable predictive biomarker for NAC success. Recently, the hepatocyte growth factor (HGF) and cMet signaling pathway demonstrated to be involved in breast cancer tumor progression, and its potential as a biomarker is under active investigation. In this study, we assessed the potential of serum HGF as a prognostic biomarker for NAC efficacy. Venous blood samples were drawn from patients diagnosed with stage II/III breast cancer and treated with NAC in Seoul National University Hospital from August 2004 to November 2009. Serum HGF level was determined using an ELISA system. We reviewed the medical records of the patients and investigated the association of HGF level with patients' clinicopathologic characteristics. A total of 121 female patients (median age = 45 years old) were included. Median level of HGF was 934 pg/ml (lower quartile: 772, upper quartile: 1145 pg/ml). Patients with higher HGF level than median value were significantly more likely to have clinically detectable regional node metastasis (p = 0.017, Fisher's exact test). Patients with complete and partial response according to the American Joint Committee on Cancer 7th Edition criteria tended to have higher HGF level (p = 0.105 by t test). Patients with an HGF level higher than the upper quartile value had longer relapse-free survival than the other patients (106 vs. 85 months, p = 0.008). High serum HGF levels in breast cancer patients are associated with clinically detectable regional node metastasis and, paradoxically, with longer relapse-free survival in stage II/III breast cancer.

  17. Smoking may modify the association between neoadjuvant chemotherapy and survival from ovarian cancer.

    Science.gov (United States)

    Kelemen, Linda E; Warren, Graham W; Koziak, Jennifer M; Köbel, Martin; Steed, Helen

    2016-01-01

    Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer. Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease. Among patients receiving adjuvant chemotherapy (N=432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50-48.7) and progression-free (PFS; HR, 5.74; 95% CI, 1.05-31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However, among patients receiving neoadjuvant chemotherapy (N=44), current smokers had shorter PFS (HR, 4.32; 95% CI, 1.36-13.8; N=32 progressed/9 censored events) compared to never smokers, but the HRs were not statistically different across smoking categories (P interaction=0.87). Adverse associations were observed between smoking status and OS or PFS among patients with mucinous ovarian cancer receiving adjuvant chemotherapy. No significant effect was found from neoadjuvant chemotherapy on PFS overall; however, smoking may modify this association. Although needing replication, these findings suggest that patients may benefit from smoking cessation interventions prior to treatment with chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Neoadjuvant Therapy in Patients with Pancreatic Cancer: A Disappointing Therapeutic Approach?

    International Nuclear Information System (INIS)

    Zimmermann, Carolin; Folprecht, Gunnar; Zips, Daniel; Pilarsky, Christian; Saeger, Hans Detlev; Grutzmann, Robert

    2011-01-01

    Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed

  19. Neoadjuvant Treatment of High-Risk, Clinically Localized Prostate Cancer Prior to Radical Prostatectomy.

    Science.gov (United States)

    Pietzak, Eugene J; Eastham, James A

    2016-05-01

    Multimodal strategies combining local and systemic therapy offer the greatest chance of cure for many with men with high-risk prostate cancer who may harbor occult metastatic disease. However, no systemic therapy combined with radical prostatectomy has proven beneficial. This was in part due to a lack of effective systemic agents; however, there have been several advancements in the metastatic and castrate-resistant prostate cancer that might prove beneficial if given earlier in the natural history of the disease. For example, novel hormonal agents have recently been approved for castration-resistant prostate cancer with some early phase II neoadjuvant showing promise. Additionally, combination therapy with docetaxel-based chemohormonal has demonstrated a profound survival benefit in metastatic hormone-naïve patients and might have a role in eliminating pre-existing ADT-resistant tumor cells in the neoadjuvant setting. The Cancer and Leukemia Group B (CALGB)/Alliance 90203 trial has finished accrual and should answer the question as to whether neoadjuvant docetaxel-based chemohormonal therapy provides an advantage over prostatectomy alone. There are also several promising targeted agents and immunotherapies under investigation in phase I/II trials with the potential to provide benefit in the neoadjuvant setting.

  20. Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects.

    Science.gov (United States)

    Berstein, Lev; Maximov, Sergei; Gershfeld, Eduard; Meshkova, Irina; Gamajunova, Vera; Tsyrlina, Evgenia; Larionov, Alexei; Kovalevskij, Anatolii; Vasilyev, Dmitry

    2002-11-15

    To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer. Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3H-water release assay) were evaluated before and after treatment. Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.

  1. Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial.

    Science.gov (United States)

    Thomas, Jeremy St John; Provenzano, Elena; Hiller, Louise; Dunn, Janet; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Gounaris, Ioannis; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Stephen; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Caldas, Carlos; Bartlett, John Ms; Cameron, David Allan; Hayward, Richard Laurence; Earl, Helena Margaret

    2017-08-01

    The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation

  2. Neoadjuvant treatment intensification or adjuvant chemotherapy for locally advanced carcinoma rectum: The optimum treatment approach remains unresolved.

    Science.gov (United States)

    Mallick, Supriya; Benson, Rony; Haresh, K P; Rath, G K

    2015-12-01

    Rectal carcinoma [RC] is often managed with preoperative radiotherapy or radio-chemotherapy followed by total mesorectal excision (TME). Efforts are being made to improve outcome by intensifying the preoperative treatment. However, the optimum therapy remains unclear. There is ongoing controversy regarding the optimum radiation dose, chemotherapy regimen and schedule. In addition there exists growing disagreement regarding the role of adjuvant chemotherapy after neoadjuvant radiation or chemoradiation. We reviewed the recent land mark trials to find a road map in the management of locally advanced rectal carcinoma. Preoperative short course radiotherapy has long been proven to improve local disease control. The initial trials with long course chemoradiotherapy, comparing short course radiotherapy have shown to increase local control and pathological complete response rates. Since then treatment intensification of this neoadjuvant schedule has been tried by many researchers. But initial results of these treatment intensification trials, show no significant benefit and are associated with increased toxicity. There is an unmet need to stratify patients depending on risk to assign them to long course chemoradiotherapy or short course radiotherapy. Current evidence does not support the use of adjuvant chemotherapy in patients who were treated with preoperative (chemo)radiotherapy. Preoperative radiotherapy appears to improve disease control with favorable toxicity profile and there is very little to choose between long course chemoradiotherapy and short course radiotherapy. However, long course chemoradiotherapy may be beneficial for patients with high risk features like positive circumferential resection margin [CRM] and extramural spread of >5mm. There is no role for adjuvant chemotherapy in patients who were treated preoperative (chemo)radiotherapy. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  3. Neoadjuvant treatment intensification or adjuvant chemotherapy for locally advanced carcinoma rectum: The optimum treatment approach remains unresolved

    International Nuclear Information System (INIS)

    Mallick, S.; Benson, R.; Haresh, K.P.; Rath, G.K.

    2015-01-01

    Background: Rectal carcinoma [RC] is often managed with preoperative radiotherapy or radio chemotherapy followed by total meso rectal excision (TME). Efforts are being made to improve outcome by intensifying the preoperative treatment. However, the optimum therapy remains unclear. There is ongoing controversy regarding the optimum radiation dose, chemotherapy regimen and schedule. In addition there exists growing disagreement regarding the role of adjuvant chemotherapy after neoadjuvant radiation or chemo radiation. Methodology: We reviewed the recent land mark trials to find a road map in the management of locally advanced rectal carcinoma. Results: Preoperative short course radiotherapy has long been proven to improve local disease con- trol. The initial trials with long course chemoradiotherapy, comparing short course radiotherapy have shown to increase local control and pathological complete response rates. Since then treatment intensification of this neoadjuvant schedule has been tried by many researchers. But initial results of these treatment intensification trials, show no significant benefit and are associated with increased toxicity. There is an unmet need to stratify patients depending on risk to assign them to long course chemoradiotherapy or short course radiotherapy. Current evidence does not support the use of adjuvant chemotherapy in patients who were treated with preoperative (chemo)radiotherapy. Conclusion: Preoperative radiotherapy appears to improve disease control with favorable toxicity profile and there is very little to choose between long course chemoradiotherapy and short course radiotherapy. However, long course chemoradiotherapy may be beneficial for patients with high risk features like positive circumferential resection margin [CRM] and extramural spread of >5 mm. There is no role for adjuvant chemotherapy in patients who were treated preoperative (chemo)radiotherapy

  4. [Effect of neoadjuvant chemotherapy on nutritional status of locally advanced gastric cancer].

    Science.gov (United States)

    Deng, Guopeng; Qu, Jianjun; Zhai, Shengyong; Shi, Yiran; Wang, Xinbo

    2018-03-25

    To study the effect of neoadjuvant chemotherapy on nutritional status in patients with locally advanced gastric cancer. Cases inclusion criteria: (1)18-65 years old; (2) Gastric cancer confirmed by gastroscopic biopsy; (3) Preoperative TNM stage III( according to the AJCC stage 2000 standard; (4) Kamosfsky functional status score> 60 points; (5)Receiving neoadjuvant chemotherapy voluntarily and signing the informed consent form. Case exclusion criteria: (1)Having contraindications of chemotherapy and surgery; (2) Suffering from heart, liver and kidney and other underlying diseases; (3) Concurrent with malignant diseases, wasting disease or other digestive diseases. According to the above criteria, clinical data of 73 patients of stage III( gastric cancer receiving neoadjuvant chemotherapy at Weifang People's Hospital from May 2015 to March 2017 were prospectively collected. The cohort study was adopted. After removing 3 patients who did not complete the chemotherapy, a total of 70 patients who completed the chemotherapy were included in the study. All the patients received SOX chemotherapy without nutritional support during chemotherapy. Changes of body composition and nutritional indicators were analyzed before and after chemotherapy, and according to the tumor regression after chemotherapy, patients were divided into response group (complete or sub-total tumor regression) and non-response group (tumor part, with or without a small amount of retreat) for stratified analysis. Of 70 gastric cancer patients, 40 were male and 30 were female with a age of (53.8±6.4) (28 to 64) years. There were 26 cases (37.1%) of stage III(a, 35 cases (50.0%) of stage III(b and 9 cases (12.9%) of stage III(c. There were 41 cases in response group and 29 cases in non-response group. Three patients (4.3%) were complete remission (CR) and 38 patients (54.3%) were partial remission (PR) in response group, while 23 cases (32.9%) were stable disease (SD) and 6 cases (8.6%) were progressive

  5. Preoperative staging of rectal cancer.

    Science.gov (United States)

    Smith, Neil; Brown, Gina

    2008-01-01

    Detailed preoperative staging using high resolution magnetic resonance imaging (MRI) enables the selection of patients that require preoperative therapy for tumour regression. This information can be used to instigate neoadjuvant therapy in those patients with poor prognostic features prior to disturbing the tumour bed and potentially disseminating disease. The design of trials incorporating MR assessment of prognostic factors prior to therapy has been found to be of value in assessing treatment modalities and outcomes that are targeted to these preoperative prognostic subgroups and in providing a quantifiable assessment of the efficacy of particular chemoradiation treatment protocols by comparing pre-treatment MR staging with post therapy histology assessment. At present, we are focused on achieving clear surgical margins of excision (CRM) to avoid local recurrence. We recommend that all patients with rectal cancer should undergo pre-operative MRI staging. Of these, about half will have good prognosis features (T1-T3b, N0, EMVI negative, CRM clear) and may safely undergo primary total mesorectal excision. Of the remainder, those with threatened or involved margins will certainly benefit from pre-operative chemoradiotherapy with the aim of downstaging to permit safe surgical excision. In the future, our ability to recognise features predicting distant failure, such as extramural vascular invasion (EMVI) may be used to stratify patients for neo-adjuvant systemic chemotherapy in an effort to prevent distant relapse. The optimal pre-operative treatment regimes for these patients (radiotherapy alone, systemic chemotherapy alone or combination chemo-radiotherapy) is the subject of current and future trials.

  6. Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.

    Science.gov (United States)

    Strassburg, Joachim; Junginger, Theo; Trinh, Trong; Püttcher, Olaf; Oberholzer, Katja; Heald, Richard J; Hermanek, Paul

    2008-11-01

    Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning? One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME. With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%). By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

  7. HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

    International Nuclear Information System (INIS)

    Tiezzi, Daniel G; Andrade, Jurandyr M; Ribeiro-Silva, Alfredo; Zola, Fábio E; Marana, Heitor RC; Tiezzi, Marcelo G

    2007-01-01

    Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. Sixty patients received preoperative docetaxel (75 mg/m 2 ) in combination with epirubicin (50 mg/m 2 ) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination

  8. Intravoxel incoherent motion (IVIM histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Gene Y. Cho

    Full Text Available Objective: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM metrics and their ability to predict response to neoadjuvant treatment (NAT. Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. Methods: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions. Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12–14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT, excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. Results: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70% and VTT% values generally decreased (∼20% post-treatment. Conclusion: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT. Keywords: Breast cancer, Diffusion weighted MRI, Intravoxel incoherent motion, Neoadjuvant treatment, Response evaluation criteria in solid tumors

  9. The value of diffusion kurtosis magnetic resonance imaging for assessing treatment response of neoadjuvant chemoradiotherapy in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jing; Xu, Qing; Song, Jia-Cheng; Li, Yan; Dai, Xin; Zhang, Ling; Shi, Hai-Bin [First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing (China); Huang, Dong-Ya [First Affiliated Hospital of Nanjing Medical University, Department of General Surgery, Nanjing (China); Li, Yang [First Affiliated Hospital of Nanjing Medical University, Department of Pathology, Nanjing (China)

    2017-05-15

    To evaluate the feasibility and value of diffusion kurtosis (DK) imaging in assessing treatment response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Forty-one patients were included. All patients underwent pre- and post-CRT DCE-MRI on a 3.0-Tesla MRI scanner. Imaging indices (D{sub app}, K{sub app} and ADC values) were measured. Change value (∇X) and change ratio (r ∇X) were calculated. Pathological tumour regression grade scores (Mandard) were the standard reference (good responders: pTRG 1-2; poor responders: pTRG 3-5). Diagnostic performance was compared using ROC analysis. For the pre-CRT measurements, pre-D{sub app-10th} was significantly lower in the good responder group than that of the poor responder group (p = 0.036). For assessing treatment response to neoadjuvant CRT, pre-D{sub app-10th} resulted in AUCs of 0.753 (p = 0.036) with a sensitivity of 66.67 % and a specificity of 77.78 %. The r ∇D{sub app} had a relatively high AUC (0.859) and high sensitivity (100 %) compared with other image indices. DKI is feasible for selecting good responders for neoadjuvant CRT for LARC. (orig.)

  10. Early increase in circulating carbonic anhydrase IX during neoadjuvant treatment predicts favourable outcome in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Hektoen, Helga Helseth; Flatmark, Kjersti; Andersson, Yvonne; Dueland, Svein; Redalen, Kathrine Røe; Ree, Anne Hansen

    2015-01-01

    Locally advanced rectal cancer (LARC) comprises heterogeneous tumours with predominant hypoxic components. The hypoxia-inducible metabolic shift causes microenvironmental acidification generated by carbonic anhydrase IX (CAIX) and facilitates metastatic progression, the dominant cause of failure in LARC. Using a commercially available immunoassay, circulating CAIX was assessed in prospectively archived serial serum samples collected during combined-modality neoadjuvant treatment of LARC patients and correlated to histologic tumour response and progression-free survival (PFS). Patients who from their individual baseline level displayed serum CAIX increase above a threshold of 224 pg/ml (with 96 % specificity and 39 % sensitivity) after completion of short-course neoadjuvant chemotherapy (NACT) prior to long-course chemoradiotherapy and definitive surgery had significantly better 5-year PFS (94 %) than patients with below-threshold post-NACT versus baseline alteration (PFS rate of 56 %; p < 0.01). This particular CAIX parameter, ΔNACT, was significantly correlated with histologic ypT0–2 and ypN0 outcome (p < 0.01) and remained an independent PFS predictor in multivariate analysis wherein it was entered as continuous variable (p = 0.04). Our results indicate that low ΔNACT, i.e., a weak increase in serum CAIX level following initial neoadjuvant treatment (in this case two cycles of the Nordic FLOX regimen), might be used as risk-adapted stratification to postoperative therapy or other modes of intensification of the combined-modality protocol in LARC. ClinicalTrials.gov: NCT00278694

  11. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer

    OpenAIRE

    Chen, Victor E.; Gillespie, Erin F.; Zakeri, Kaveh; Murphy, James D.; Yashar, Catheryn M.; Lu, Sharon; Einck, John P.

    2017-01-01

    Purpose: Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy. Methods and materials: This was an institutional review board–approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservat...

  12. Outcome analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy

    International Nuclear Information System (INIS)

    Higgins, Geoffrey S.; McLaren, Duncan B.; Kerr, Gillian R.; Elliott, Tony; Howard, Grahame

    2006-01-01

    Purpose: Neoadjuvant androgen deprivation and radical radiotherapy is an established treatment for localized prostate carcinoma. This study sought to analyze the outcomes of patients treated with relatively low-dose hypofractionated radiotherapy. Methods and Materials: Three hundred patients with T1-T3 prostate cancer were treated between 1996 and 2001. Patients were prescribed 3 months of neoadjuvant androgen deprivation before receiving 5250 cGy in 20 fractions. Patients' case notes and the oncology database were used to retrospectively assess outcomes. Median follow-up was 58 months. Results: Patients presented with prostate cancer with poorer prognostic indicators than that reported in other series. At 5 years, the actuarial cause-specific survival rate was 83.2% and the prostate-specific antigen (PSA) relapse rate was 57.3%. Metastatic disease had developed in 23.4% of patients. PSA relapse continued to occur 5 years from treatment in all prognostic groups. Independent prognostic factors for relapse included treatment near the start of the study period, neoadjuvant oral anti-androgen monotherapy rather than neoadjuvant luteinizing hormone releasing hormone therapy, and diagnosis through transurethral resection of the prostate rather than transrectal ultrasound. Conclusion: This is the largest reported series of patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy in the United Kingdom. Neoadjuvant hormonal therapy did not appear to adequately compensate for the relatively low effective radiation dose used

  13. Preoperative staging of rectal cancer; Praeoperatives Staging des Rektumkarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, A.O.; Baumann, T.; Pache, G.; Langer, M. [Abt. Roentgendiagnostik, Radiologische Universitaetsklinik Freiburg, Freiburg im Breisgau (Germany); Wiech, T. [Inst. fuer Pathologie, Universitaetsklinik Freiburg, Freiburg (Germany)

    2007-07-15

    Accurate preoperative staging of rectal cancer is crucial for therapeutic decision making, as local tumor extent, nodal status, and patterns of metastatic spread are directly associated with different treatment strategies. Recently, treatment approaches have been widely standardized according to large studies and consensus guidelines. Introduced by Heald, total mesorectal excision (TME) is widely accepted as the surgical procedure of choice to remove the rectum together with its enveloping tissues and the mesorectal fascia. Neoadjuvant radiochemotherapy also plays a key role in the treatment of locally advanced stages, while the use of new drugs will lead to a further improvement in oncological outcome. Visualization of the circumferential resection margin is the hallmark of any preoperative imaging and a prerequisite for high-quality TME surgery. The aim of this article is to present an overview on current cross-sectional imaging with emphasis on magnetic resonance imaging. Future perspectives in rectal cancer imaging are addressed. (orig.)

  14. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    International Nuclear Information System (INIS)

    Lorenzen, Sylvie; Debus, Jürgen; Jäger, Dirk; Münter, Marc W; Gall, Carl von; Stange, Annika; Haag, Georg M; Weitz, Jürgen; Haberkorn, Uwe; Lordick, Florian; Weichert, Wilko; Abel, Ulrich

    2011-01-01

    18-Fluorodeoxyglucose-PET ( 18 F-FDG-PET) can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG) undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy. The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a < 35% decrease of SUV two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (chemoradiotherapy (45 Gy) before surgery. 18 FDG-PET scans will be performed before (= Baseline) and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1) and at the end of radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference ΔSUV = 100 (SUV Baseline - SUV PET1 )/SUV Baseline

  15. State of the art of neoadjuvant chemotherapy in breast cancer: rationale, results and recent developments

    Directory of Open Access Journals (Sweden)

    Solomayer, Erich-Franz

    2005-09-01

    Full Text Available Aims, results, advantages and possible disadvantages of preoperative chemotherapy (pCHT for breast cancer are discussed in this review. Established chemotherapeutic regimens are described with respect to new drugs that are added to combinations now and in the future. Illustrating the potential of new components, trastuzumab and cytotoxic chemotherapy, were combined in neoadjuvant trials for the first time. This approach yielded impressing and unprecedented high pathological response rates. An overview regarding current neoadjuvant cytostatic and immunotherapy trials is given. Established prognostic factors like axillary lymph-nodal status are altered during pCHT, which causes the need for new prognostic markers. The consequences of these changes for clinical decision making are demonstrated. It seems possible that the advances of gene array and protein expression profile technologies will lead to improved prognostic and predictive statements. Tumor tissue can be analyzed before during and after treatment in this regard recent studies investigating the response to specific, chemotherapeutics in correlation to molecular markers are reviewed. These approaches might enable us to identify chemoresistance of specific tumors. Furthermore pCHT allows testing of chemosensitivity in vivo in an early stage, which might lead to a more individualized cancer therapy. We discuss radiotherapy after neoadjuvant therapy and the risk of local relapse after breast conserving surgery, which was made feasible by pCHT. It is shown how the evaluation of efficacy of new cancer drugs, using the neoadjuvant situation, can be done more rapidly than in the metastatic and adjuvant setting.

  16. Neoadjuvant Therapy for Breast Cancer : Established Concepts and Emerging Strategies

    NARCIS (Netherlands)

    Steenbruggen, Tessa G; van Ramshorst, Mette S.; Kok, Marleen; Linn, Sabine C.; Smorenburg, Carolien H.; Sonke, Gabe S

    2017-01-01

    In the last decade, the systemic treatment approach for patients with early breast cancer has partly shifted from adjuvant treatment to neoadjuvant treatment. Systemic treatment administration started as a ‘one size fits all’ approach but is currently customized according to each breast cancer

  17. Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

    2017-07-01

    Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Clinical efficacy of breast-conserving surgery combined with neoadjuvant chemotherapy for locally advanced breast cancer: a report of 81 cases

    Directory of Open Access Journals (Sweden)

    Zhi-yu CAO

    2015-07-01

    Full Text Available Objective To investigate the clinical efficacy of neoadjuvant chemotherapy combined with breast-conserving surgery for locally advanced breast cancer. Methods Eighty-one patients with locally advanced breast cancer were selected from those who were admitted into 309 Hospital of PLA from January 2009 to October 2013, consisting of 65 patients in stage Ⅲa and 16 in stage Ⅲb, and they were treated with neoadjuvant chemotherapy combined with breast-conserving surgery. The clinical efficacy [complete response (CR, partial response (PR, stable disease (SD and progress disease (PD] was observed during follow-up. Results All the patients were followed-up for 12-60 months with a median of 34 months. There were 12 CR patients (14.8%, including 4 with pathological complete response (4.9%, and 52 PR patients (64.2%, 17 SD patients (21.0%. No PD was observed. The overall response rate(ORR was 79.0%(64/81. After follow-up for 12-60 months (median 34 months, distant metastasis to the lung, liver, meninges and bone occurred in 3 patients (3.7%, 3/81 and 1 of them died. Forty-eight patients received breastconserving surgery. The local recurrence rate was 6.3% (3/48. Assessment of cosmetic result was carried out in 48 patients who received breast-conserving surgery and comprehensive treatment for one year, and excellent results were obtained in 14.6% (7/48, good in 43.8% (21/48, and poor in 41.7% (20/48. Conclusions The therapeutic efficacy of locally advanced breast cancer is satisfactory by neoadjuvant chemotherapy and breast-conserving surgery. Standardization of excision and postoperative radiotherapy, systemic comprehensive treatment is the key to the success of the treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.14

  19. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG: The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    Directory of Open Access Journals (Sweden)

    Weichert Wilko

    2011-06-01

    Full Text Available Abstract Background 18-Fluorodeoxyglucose-PET (18F-FDG-PET can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy. Methods/Design The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a 18FDG-PET scans will be performed before ( = Baseline and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1 and at the end of radiochemotherapy (PET2. Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV. The percentage difference ΔSUV = 100 (SUVBaseline - SUV PET1/SUVBaseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference

  20. Neoadjuvant intra-arterial chemotherapy with a combination of radiotherapy for the treatment of invasive bladder carcinoma

    International Nuclear Information System (INIS)

    Sumiyoshi, Yoshiteru; Uyama, Takeshi.

    1992-01-01

    Fifty patients with invasive bladder carcinoma were treated with neoadjuvant intra-arterial chemotherapy using doxorubicin or pirarubicin, and this was combined with low dose radiotherapy. All of 50 patients were evaluated for clinical and histological efficacy. Twenty-nine of 50 (58%) patients achieved a clinically complete remission (CR) and 17 of 50 (34%) achieved a clinically partial remission (PR). Twenty-eight of 50 (56%) achieved a histological CR and 13 of 50 (26%) achieved a histological PR. The patients who underwent bladder preservation operations after this treatment and were followed up for longer than 3 years were evaluated for long-term results. The 5-year survival for 35 patients in this group was 74.1%. The 5-year survival for patients with a clinical CR was 93.3%, and for patients with a clinical PR it was 45.3%. The survival for patients with a histological CR was 93.3%, and for patients with a histological PR, it was 85.7%. This study suggests that neoadjuvant intra-arterial chemotherapy plus radiotherapy is a useful regimen that could become the treatment of first choice for patients with invasive bladder carcinoma. Patients who achieved a histological CR or PR with this regimen, might be able to retain the function of their bladders. (author)

  1. The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan; Zhang, Lu; Guo, Shan-Shan; Guo, Ling; Mo, Hao-Yuan; Zhao, Chong; Guo, Xiang; Cao, Ka-Jia; Qian, Chao-Nan; Zeng, Mu-Sheng; Bei, Jin-Xin; Hong, Ming-Huang; Shao, Jian-Yong; Sun, Ying; Ma, Jun; Mai, Hai-Qiang

    2015-01-01

    Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.

  2. The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan; Zhang, Lu; Guo, Shan-Shan; Guo, Ling; Mo, Hao-Yuan; Zhao, Chong; Guo, Xiang; Cao, Ka-Jia; Qian, Chao-Nan [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou (China); Zeng, Mu-Sheng; Bei, Jin-Xin [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Hong, Ming-Huang [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Good Clinical Practice Center, Sun Yat-sen University Cancer Center, Guangzhou (China); Shao, Jian-Yong [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou (China); Sun, Ying; Ma, Jun [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Mai, Hai-Qiang, E-mail: maihq@sysucc.org.cn [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou (China)

    2015-11-15

    Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.

  3. Expense and benefit of neoadjuvant treatment in squamous cell carcinoma of the esophagus

    Directory of Open Access Journals (Sweden)

    Hartmann Karl A

    2001-11-01

    Full Text Available Abstract Background The effectiveness of neoadjuvant treatment (NT prior to resection of squamous cell carcinoma of the esophagus (SCCE in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates. Methods From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival. Results Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.. The response to NT was detected in 23 patients (70%. In 11 instances (33%, the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193. The average pretreatment time was 113 ± 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834. Conclusions NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival.

  4. [A Case of Emergency Resection of Esophageal Cancer Which is on the Brink of Perforation after Neoadjuvant Chemotherapy].

    Science.gov (United States)

    Yasuda, Atsushi; Yasuda, Takushi; Kimura, Yutaka; Kato, Hiroaki; Hiraki, Yoko; Iwama, Mitsuru; Shiraishi, Osamu; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko

    2017-11-01

    According to the Guidelines for Diagnosis and Treatment of Carcinoma of the Esophagus in Japan, the standard treatment of esophageal cancer with cStage II / III is preoperative chemotherapy and radical resection. But when the tumor has deep ulcer, the perforation of it is sometimes occurred due of the anti-tumor effect and we are forced to change the standard treatment. In this time, we report a case of emergency resection of esophageal cancer which is on the brink of perforation after neoadjuvant chemotherapy. A 62-year-old woman had locally advanced esophageal cancer(cT4N2M0)and performed neoadjuvant chemotherapy(NAC). After 2 courses of NAC, the patient got into critical condition that the esophageal cancer was on the brink of perforation, thus we immediately performed emergency resection of the tumor. Unfortunately, the tumor was not completely resected because of invasion to the Botallo ligament, but we were able to avoid a critical state such as mediastinitis or penetration to the aorta. In multimodality therapy for locally advanced tumor, immediate response to oncologic emergency is significantly required, impacting on the prognosis and quality of life.

  5. DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

    Science.gov (United States)

    de Rosa, Nicole; Rodriguez-Bigas, Miguel A; Chang, George J; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A; Skibber, John M; Feig, Barry W; Lynch, Patrick M; Vilar, Eduardo; You, Y Nancy

    2016-09-01

    DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. © 2016 by American Society of Clinical Oncology.

  6. Thoraco-laparoscopic esophagectomy: thoracic stage in prone position

    Directory of Open Access Journals (Sweden)

    Carlos Bernardo Cola

    Full Text Available ABSTRACT Objective: to analyze the National Cancer Institute Abdominopelvic Division (INCA / MS/HC I initial experience with thoraco-laparoscopic esophagectomy with thoracic stage in prone position. Methods: we studied 19 consecutive thoraco-laparoscopic esophagectomies from may 2012 to august 2014, including ten patients with squamous cells carcinoma (five of the middle third and five of the lower third and nine cases of gastroesophageal junction adenocarcinoma (six Siewert I and three Siewert II. All procedures were initiated by the prone thoracic stage. Results: There were minimal blood loss, optimal mediastinal visualization, oncological radicality and no conversions. Surgical morbidity was 42 %, most being minor complications (58% Clavien I or II, with few related to the technique. The most common complication was cervical anastomotic leak (37%, with a low anastomotic stricture rate (two stenosis: 10.53%. We had one (5.3% surgical related death, due to a gastric tube`s mediastinal leak, treated by open reoperation and neck diversion. The median Intensive Care Unit stay and hospital stay were two and 12 days, respectively. The mean thoracoscopic stage duration was 77 min. Thirteen patients received neoadjuvant treatment (five squamous cells carcinoma and eight gastroesophageal adenocarcinomas. The average lymph node sample had 16.4 lymph nodes per patient and 22.67 when separately analyzing patients without neoadjuvant treatment. Conclusion: the thoraco-laparoscopic approach was a safe technique in the surgical treatment of esophageal cancer, with a good lymph node sampling.

  7. 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) PET in the clinical decision making of esophageal carcinoma: Initial staging and re-staging, evaluating treatment response and residual disease and detecting relapse

    International Nuclear Information System (INIS)

    Basu, S.; Nair, N.; Joseph, J.K.; Sharma, S.; Kanhere, H.

    2004-01-01

    Full text: Accurate initial staging is essential in the management of esophageal carcinoma. The 5-year survival rate is 3% for patients with metastatic disease at the initial assessment, while the same is 42% for patients with nodal disease. 18F-FDG PET is being actively tested regarding its clinical utility at several centers in this malignancy. We at our center are assessing the role of this investigational modality in staging, evaluating treatment response especially after neo-adjuvant therapy and detecting relapse vis-a-vis the other conventionally used modalities e.g. Endoscopic ultrasound (EUS) and the CT scan. The study population consisted of histologically proven cases of esophageal carcinoma who were mainly referred from the department of thoracic surgery of the neighboring Tata Memorial Hospital with few cases from the outside centers. FDG was produced by an automated nucleophilic method based on the Hamacher procedure. Patients were fasting at least for 6 hours. Sixty minutes after injection of 370 MBq FDG, patients were imaged on the dedicated BGO based GE Advance PET scanner (General Electric Medical systems, Milwaukee, WI). Images were reconstructed using the attenuation weighted Ordered Subsets Expectation Maximization (OSEM) algorithm. Axial, coronal, sagittal and 3D images were visually interpreted and foci of increased tracer uptake were considered as disease involvement. The PET scan was interpreted by two experienced nuclear medicine physicians, who were blinded regarding the results of CT scan and EUS except for the location of the primary. The findings of PET were then compared lesion by lesion with that of CT and EUS regarding staging, treatment response evaluation and residual disease evaluation. Till date, the total number of cases of esophageal carcinoma studied was 12, which consisted of primaries in the proximal third (n=1), middle third (n=4) and distal third (n=7). The number of cases assessed for the initial staging purpose was 7

  8. Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

    2011-01-01

    This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

  9. Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Wang, Chia-Chun; Cheng, Jason Chia-Hsien; Tsai, Chiao-Ling; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Hsieh, Min-Shu; Chang, Yih-Leong; Hsu, Feng-Ming

    2015-01-01

    Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

  10. Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Lindebjerg, Jan

    2017-01-01

    BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy....... MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors...... was 55%, compared to 94% in the group of patients with a high TSR. CONCLUSIONS: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting...

  11. CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and locally advanced pancreatic adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Mathilde; Lucidarme, Oliver [Sorbonne Universites, UPMC, Department of Radiology, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France); Antunes, Celia [Coimbra University Hospital, Department of Radiology, Coimbra (Portugal); Pietrasz, Daniel [Sorbonne Universites, UPMC, Department of Digestive and Hepatobiliary Surgery, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France); Cassinotto, Christophe [Centre Hospitalier Universitaire de Bordeaux, Department of Diagnostic and Interventional Imaging, Hopital Haut Leveque, Bordeaux (France); Zappa, Magaly [Hopitaux Universitaires Paris Nord Val de Seine, Department of Radiology, Hopital Beaujon, Assistance Publique-Hopitaux de Paris, Clichy (France); Sa Cunha, Antonio [Hopitaux Universitaires Paris Sud, Department of Hepatobiliary Surgery, Liver Transplant Center, Hopital Paul Brousse, Villejuif (France); Bachet, Jean-Baptiste [Sorbonnes Universites, UPMC, Department of Gastroenterology and Digestive Oncology, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France)

    2017-07-15

    To assess anatomic changes on computed tomography (CT) after neoadjuvant FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) chemotherapy for secondary resected borderline resectable (BR) and locally advanced (LA) pancreatic adenocarcinoma and their accuracy to predict resectability and pathological response. Thirty-six patients with secondary resected BR/LA pancreatic adenocarcinoma after neoadjuvant FOLFIRINOX chemotherapy (± chemoradiotherapy) were retrospectively included. Two radiologists reviewed baseline and pre-surgical CTs in consensus. NCCN (National Comprehensive Cancer Network) classification, largest axis, product of the three axes (P3A), and arterial/venous involvement were studied and compared to pathological response and resection status and to disease-free survival (DFS). Thirty-one patients had R0 resection, including only six exhibiting a downstaging according to the NCCN classification. After treatment, the largest axis and P3A decreased (P < 0.0001). The pre-surgical largest axis and P3A were smaller in case of R0 resection (P = 0.019/P = 0.021). The largest axis/P3A variations were higher in case of complete pathological response (P = 0.011/P = 0.016). A decrease of the arterial/venous involvement was not able to predict R0 or ypT0N0 (P > 0.05). Progression of the vascular involvement was seen in two (5 %) patients and led to a shorter DFS. In BR/LA pancreatic adenocarcinoma after the neoadjuvant FOLFIRINOX regimen (± chemoradiotherapy), significant tumour size decreases were observed on CT. However, CT staging was not predictive of resectability and pathological response. (orig.)

  12. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    Science.gov (United States)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  13. Neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs

    International Nuclear Information System (INIS)

    Ramos, Pedro; Gonzalez, Manuel; Perry, Fernando; Cardona, Andres Felipe

    2005-01-01

    Background: the use of neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs continues to be an area of controversy; however, the number of clinical studies favoring the use of an anthracycline and iphosphamide-based regimen is increasing steadily. This approach may provide some advantages for facilitating the surgical resection of the tumor and for local disease control. The historical 5-year survival rate of approximately 50% in this high-risk group treated with local therapy alone represents a poor standard of care; thus, there is a need to incorporate systemic therapy early in the management of these patients. Objective: to describe the role of neoadjuvant chemotherapy in the treatment of soft-tissue sarcomas. Materials and methods: the records of 42 patients who attended the national cancer institute of Colombia in search for management of primary soft-tissue sarcomas were retrospectively reviewed. Ten patients with high-grade tumors larger than 8 cm, treated from June 2000 to February 2002 with neoadjuvant chemotherapy based on an anthracycline and iphosphamide regimen, plus vincristin and cisplatinum in selected cases, followed by surgery and adjuvant therapy with chemotherapy combined with local radiotherapy, were included. Evaluations of objective tumor response, survival, and toxicity were carried out. Results: after neoadjuvant therapy, s ix patients underwent conservative and limb-salvage surgery, three required radical interventions, and one refused surgical treatment. Seven experienced an objective response: it was complete in four and partial in three; the disease kept stable in two patients, and the tumor progressed in one case. After an average 46-month follow-up, four patients were permanently free of disease. Hematological and gastrointestinal toxicity was remarkable, and no patient had a long-term morbidity related to the treatment. Conclusions: this limited retrospective review suggests an advantage for the use of

  14. Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

    International Nuclear Information System (INIS)

    Hulshof, M.C.C.M; Crezee, J.; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J.J.B.; Richel, D.J.

    2005-01-01

    Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m 2 ) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea ≤ grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients with

  15. Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, M C.C.M; Crezee, J; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J J.B.; Richel, D J [Academical Medical Center of Amsterdam (Netherlands)

    2005-07-01

    Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m{sup 2}) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea {<=} grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients

  16. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    Directory of Open Access Journals (Sweden)

    Takatori E

    2016-09-01

    Full Text Available Eriko Takatori, Tadahiro Shoji, Anna Takada, Takayuki Nagasawa, Hideo Omi, Masahiro Kagabu, Tatsuya Honda, Fumiharu Miura, Satoshi Takeuchi, Toru Sugiyama Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, Iwate, Japan Objective: In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group with patients who underwent RH without NAC (Ope group. Patients and methods: The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS and overall survival (OS between the groups. Results: There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days in the NAC group and 25 days (21–34 days in the Ope group; the patients in the NAC group were discharged earlier (P=0.032. The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91, and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028. Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24, and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101. Conclusion: NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous

  17. Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

    Science.gov (United States)

    Tanaka, Satoru; Iwamoto, Mitsuhiko; Kimura, Kosei; Matsunami, Nobuki; Morishima, Hirotaka; Yoshidome, Katsuhide; Nomura, Takashi; Morimoto, Takashi; Yamamoto, Daigo; Tsubota, Yu; Kobayashi, Toshihiro; Uchiyama, Kazuhisa

    2015-06-01

    We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with

  18. [Occupational cholangiocarcinoma in a printer that responded to neoadjuvant chemoradiotherapy].

    Science.gov (United States)

    Nakagawa, Kei; Katayose, Yu; Ishida, Kazuyuki; Hayashi, Hiroki; Morikawa, Takanori; Yoshida, Hiroshi; Motoi, Fuyuhiko; Naitoh, Takeshi; Kubo, Shoji; Unno, Michiaki

    2015-07-01

    A 42-year-old man working at a printing company was referred to our hospital for examination and treatment of icterus. We diagnosed resectable hilar cholangiocarcinoma and provided neoadjuvant chemoradiotherapy, extended right hepatectomy, and extrahepatic bile duct resection. A detailed history revealed that he had used 1,2-dichloropropane as part of his work as an offset colour proof-printer, and he has subsequently been recognized as having occupational cholangiocarcinoma. He has survived without recurrence for more than 2 and half years since the liver resection. In the present report, we describe our valuable experience of neoadjuvant chemoradiotherapy for occupational cholangiocarcinoma.

  19. 18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Eschmann, Susanne M.; Reimold, Matthias; Bares, Roland; Friedel, Godehard; Paulsen, Frank; Hehr, Thomas; Budach, Wilfried; Langen, Heinz-Jakob

    2007-01-01

    The aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy (NARCT) of advanced non-small cell lung cancer (NSCLC). Seventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NARCT. Changes in FDG uptake and PET findings after completion of NARCT were compared with (1) the histology of tumour samples obtained at surgery or repeat mediastinoscopy, and (2) treatment results in terms of achieved operability and long-term survival. The mean average FDG uptake of the primary tumours in the patient group decreased significantly during NARCT (p = 0.004). Sensitivity, specificity and overall accuracy of FDG-PET were 94.5%, 80% and 91%, respectively, for the detection of residual viable primary tumour, and 77%, 68% and 73%, respectively, for the presence of lymph node metastases. A negative PET scan or a reduction in the standardised uptake value (SUV) of more than 80% was the best predictive factor for a favourable outcome of further treatment. Progressive disease according to PET (new tumour manifestations or increasing SUV) was significantly correlated with an unfavourable outcome (p = 0.005). In this subgroup, survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery, whereas for the whole patient group, complete tumour resection had a significant influence on outcome. FDG-PET is suitable to assess response to NARCT in patients with stage III NSCLC accurately. It was highly predictive for treatment outcome and patient survival. PET may be helpful in improving restaging after NARCT by allowing reliable assessment of residual tumour viability. (orig.)

  20. Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

    International Nuclear Information System (INIS)

    Gao, Yuan-Hong; Lin, Jun-Zhong; An, Xin; Luo, Jie-Lin; Cai, Mu-Yan; Cai, Pei-Qiang; Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2014-01-01

    Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen

  1. Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuan-Hong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Lin, Jun-Zhong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); An, Xin [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Luo, Jie-Lin [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); Cai, Mu-Yan [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou (China); Cai, Pei-Qiang [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou (China); Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); Ding, Pei-Rong, E-mail: dingpr@mail.sysu.edu.cn [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China)

    2014-12-01

    Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen

  2. Initial Experience of Sorafenib Neoadjuvant Therapy Combined with Retroperitoneoscopy in Treating T2 Large Renal Carcinoma

    Directory of Open Access Journals (Sweden)

    Chun-hua Lin

    2015-01-01

    Full Text Available Objectives. To investigate the safety and feasibility of sorafenib neoadjuvant therapy combined with retroperitoneoscopic radical nephrectomy (RRN in treating T2 large renal cell carcinoma (RCC. Methods. Retrospectively analyzed 5 cases (2 males and 3 females, aged 52–73 years of T2 stage large RCC who receive preoperative sorafenib targeted treatment (400 mg bid for 1–3 months and RRN between March, 2013, and July, 2014. Patient information, therapeutic regimen, drug adverse effect, tumor changes before and after surgery, and perioperative parameters were recorded. Results. During the sorafenib therapy adverse effects included 2 cases of hypertension (Grade I toxicity, 1 case of hand-foot syndrome (Grade I, and 1 case of diarrhea (Grade II, which were all tolerable for patients. CT scan and histopathological tests confirmed significant reduction in the longest dimension (LD and medium density (MD of the tumor after therapy as well as tumor hemorrhage, necrosis, and cystic degeneration. All 5 patients received RRN surgery successfully around 2 weeks after drug discontinuation with only 1 case of perioperative complication. Conclusions. Sorafenib neoadjuvant therapy could significantly reduce the size and aggressiveness of T2 large renal tumors, thus reducing the operative challenge and enabling patients who were previously disqualified for operation to receive surgical treatment.

  3. NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial)

    International Nuclear Information System (INIS)

    Heijl, Mark van; Gaast, Ate van der; Nieuwenhuijzen, Grard AP; Bonenkamp, Han J; Plukker, John ThM; Bilgen, Ernst J Spillenaar; Kate, Fibo JW ten; Boellaard, Ronald; Pruim, Jan; Sloof, Gerrit W; Lanschot, J Jan B van; Omloo, Jikke MT; Berge Henegouwen, Mark I van; Busch, Olivier RC; Tilanus, Hugo W; Bossuyt, Patrick MM; Hoekstra, Otto S; Stoker, Jaap; Hulshof, Maarten CCM

    2008-01-01

    Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score). Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant

  4. NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial)

    Energy Technology Data Exchange (ETDEWEB)

    Heijl, Mark van [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Gaast, Ate van der [Department of Medical Oncology, Erasmus Medical Center, Rotterdam (Netherlands); Nieuwenhuijzen, Grard AP [Department of Surgery, Catharina Hospital Eindhoven, Eindhoven (Netherlands); Bonenkamp, Han J [Department of Surgery, Radboud University Medical Center, Nijmegen (Netherlands); Plukker, John ThM [Department of Surgery, University Medical Center Groningen, Groningen (Netherlands); Bilgen, Ernst J Spillenaar [Department of Surgery, Rijnstate Hospital, Arnhem (Netherlands); Kate, Fibo JW ten [Department of Pathology, Academic Medical Center, Amsterdam (Netherlands); Boellaard, Ronald [Department of Nuclear Medicine and PET research, VU Medical Center, Amsterdam (Netherlands); Pruim, Jan [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Sloof, Gerrit W [Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Lanschot, J Jan B van [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Department of Surgery, Erasmus Medical Center, Rotterdam (Netherlands); Omloo, Jikke MT; Berge Henegouwen, Mark I van; Busch, Olivier RC [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Tilanus, Hugo W [Department of Surgery, Erasmus Medical Center, Rotterdam (Netherlands); Bossuyt, Patrick MM [Department of Clinical Epidiomiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam (Netherlands); Hoekstra, Otto S [Department of Nuclear Medicine, VU Medical Center, Amsterdam (Netherlands); Stoker, Jaap [Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); Hulshof, Maarten CCM [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands)

    2008-07-31

    Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score). Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant

  5. Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

    Science.gov (United States)

    Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

    2016-11-01

    Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response

  6. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Katz, Matthew S.; Minsky, Bruce D.; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-01-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  7. Adaptive radiotherapy for long course neo-adjuvant treatment of rectal cancer

    International Nuclear Information System (INIS)

    Nijkamp, Jasper; Marijnen, Corrie; Herk, Marcel van; Triest, Baukelien van; Sonke, Jan-Jakob

    2012-01-01

    Purpose: To quantify the potential margin reduction with adaptive radiotherapy (ART) during neo-adjuvant treatment of locally-advanced rectal cancer. Methods and materials: Repeat CT scans were acquired for 28 patients treated with 25 × 2 Gy, daily during the first week, and followed by weekly scans. The CTV was delineated on all scans, and shape variation was estimated. Five ART strategies were tested, consisting of an average CTV over the planning CT and one to five repeat CTs. Required PTV margins were calculated for adapted and non-adapted treatment. The strategy with the least PTV volume over the whole treatment was selected and bowel area dose reduction was estimated. Results: Substantial systematic and random shape variation demanded for a PTV margin up to 2.4 cm at the upper-anterior part of the CTV. Plan adaptation after fraction 4 resulted in a maximum 0.7 cm margin reduction and a significant PTV reduction from 1185 to 1023 cc (p < 0.0001). The bowel area volume receiving 15, 45, and 50 Gy was reduced from 436 to 402 cc, 111 to 81 cc, and 49 to 29 cc, respectively (p < 0.0001). Conclusions: With adaptive radiotherapy, maximum required PTV margins can be reduced from 2.4 to 1.7 cm, resulting in significantly less dose to the bowel area.

  8. Preoperative staging of rectal cancer

    International Nuclear Information System (INIS)

    Schaefer, A.O.; Baumann, T.; Pache, G.; Langer, M.; Wiech, T.

    2007-01-01

    Accurate preoperative staging of rectal cancer is crucial for therapeutic decision making, as local tumor extent, nodal status, and patterns of metastatic spread are directly associated with different treatment strategies. Recently, treatment approaches have been widely standardized according to large studies and consensus guidelines. Introduced by Heald, total mesorectal excision (TME) is widely accepted as the surgical procedure of choice to remove the rectum together with its enveloping tissues and the mesorectal fascia. Neoadjuvant radiochemotherapy also plays a key role in the treatment of locally advanced stages, while the use of new drugs will lead to a further improvement in oncological outcome. Visualization of the circumferential resection margin is the hallmark of any preoperative imaging and a prerequisite for high-quality TME surgery. The aim of this article is to present an overview on current cross-sectional imaging with emphasis on magnetic resonance imaging. Future perspectives in rectal cancer imaging are addressed. (orig.)

  9. Role of chemoradiotherapy in oesophageal cancer -- adjuvant and neoadjuvant therapy

    NARCIS (Netherlands)

    Gwynne, S.; Wijnhoven, B. P. L.; Hulshof, M.; Bateman, A.

    2014-01-01

    Despite low postoperative mortality rates, the long-term outcomes from surgical-based treatment for oesophageal cancer remain poor. Chemoradiotherapy (CRT), either given before surgical resection as neoadjuvant therapy or after resection as adjuvant therapy, has been postulated to improve these

  10. ACR Appropriateness Criteria® Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer.

    Science.gov (United States)

    Slanetz, Priscilla J; Moy, Linda; Baron, Paul; diFlorio, Roberta M; Green, Edward D; Heller, Samantha L; Holbrook, Anna I; Lee, Su-Ju; Lewin, Alana A; Lourenco, Ana P; Niell, Bethany; Stuckey, Ashley R; Trikha, Sunita; Vincoff, Nina S; Weinstein, Susan P; Yepes, Monica M; Newell, Mary S

    2017-11-01

    Patients with locally advanced invasive breast cancers are often treated with neoadjuvant chemotherapy prior to definitive surgical intervention. The primary aims of this approach are to: 1) reduce tumor burden thereby permitting breast conservation rather than mastectomy; 2) promptly treat possible metastatic disease, whether or not it is detectable on preoperative staging; and 3) potentially tailor future chemotherapeutic decisions by monitoring in-vivo tumor response. Accurate radiological assessment permits optimal management and planning in this population. However, assessment of tumor size and response to treatment can vary depending on the modality used, the measurement technique (such as single longest diameter, 3-D measurements, or calculated tumor volume), and varied response of different tumor subtypes to neoadjuvant chemotherapy (such as concentric shrinkage or tumor fragmentation). As discussed in further detail, digital mammography, digital breast tomosynthesis, US and MRI represent the key modalities with potential to help guide patient management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  11. Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

    Science.gov (United States)

    Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

    2015-01-01

    The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

  12. Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

    Science.gov (United States)

    Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

    2013-01-01

    Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

  13. The clinical significance of axillary sentinel lymph node biopsy in different clinical stages breast cancer patients after neoadjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Juan Xu; Xinhong Wu; Yaojun Feng; Feng Yuan; Wei Fan

    2013-01-01

    Objective:We aimed to study the success and false negative rate of sentinel lymph node biopsy (SLNB) in dif-ferent clinical stages breast cancer patients being carried out with neoadjuvant chemotherapy (NAC), and the clinical signifi-cance of SLNB, we conducting this trial. Methods:One hunderd and thirty-seven cases were enrol ed in this clinical research from March 2003 to March 2007. Al of the patients’ sentinel lymph nodes were detected with 99mTc-Dx and methylene blue. There were 61 patients with stage T1-2N0M0 carried SLNB without NAC (group A), 76 cases were carried out NAC 3-4 cycles before SLNB, including 39 T2-4N0-1M0 cases (group B) and 27 T2-4N2-3M0 cases (group C). The success and false negative rate of SLNB were analysed with chi-square test. Results:In group A, the successful and false negative rate of SLNB were 92.31%(36/39), 8.57%(3/35), and in group B and C were 92.31%(36/39), 8.57%(3/35) and 74.07%(20/27), 18.52%(5/27), respectively. The successful rate of group C decreased and false negative rate increased significantly compared with group A and B (P0.05). Conclusion:The SLNB can accurately predict lymph node status of axil ary lymph node in N0-1 stage patients with NAC, but in N2-3 stage patients the success rate decreased and false rate increased negative significantly.

  14. Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

    Science.gov (United States)

    Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

    1996-04-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

  15. Evolving strategies in the treatment of childhood rhabdomyosarcoma. Slovenian experience

    International Nuclear Information System (INIS)

    Pohar-Marinsek, Z.; Anzic, J.; Jereb, B.

    2001-01-01

    Background. Neoadjuvant chemotherapy (Cht) has changed the treatment of rhabdomyosarcoma (RMS) in children. The purpose of our study was to review the children treated for RMS between 1974 and 1996. Patients and methods. Fifty-one children, 1-15 years old, were included. Primary sites of tumour were: head and neck 15, orbit 6, genitourinary 12, extremity 9, torso 5 and paratesticular 4. Twelve patients were in stage I, 10 in stage II, 26 in stage III and 3 in stage IV. Of 43 histologically confirmed RMS 25 were embryonal, 13 alveolar, 1 botryoid, 1 spindle cell and 3 sarcoma NOS. In 8 patients, only fine needle aspiration biopsy (FNAB) was available. All patients had Cht, 29 neoadjuvant, 20 had surgery first, 40 had irradiation (RT), 2 stage IV patients had bone marrow transplant (ABMT). Multidrug Cht varied: VCR, AMD, and cyclophosphamide (VAC) were used in the 1970s, with Adriablastine (T2), methotrexat (MTX) and/or other drugs (T6, T11) in the 1980s, and in the 1990s, cyclophosphamide was replaced by ifosfamide (VAIA). The treatment was started with Cht in orbital and head and neck tumours and in the majority of genitourinary tumours, but surgery was first in paratesticular and in the majority of extremity tumours. Results. The 3 patients with stage IV disease died. Of those with localised tumour, 34 (70%) were alive and well 5 years after treatment, 80% stage I, 75% stage II and 61% stage III. One patient died of heart failure, 3 of Cht toxicity and 1 of intercurrent disease. Conclusions. The survival of our patients has improved during the last 2 decades and increased from 57 % to 70 % for patients treated after 1985. It is now comparable to that in other centres. With the introduction of neoadjuvant Cht, surgery and RT have become more conservative and could sometimes even be abandoned, thereby reducing considerably the risk of late sequels. Orbital, genitourinary and paratesticular embryonal RMS of low stages have very good prognosis. Primary tumours of the

  16. Complete pathological response after neoadjuvant therapy in patients with rectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    E.A. Sánchez-Pérez

    2017-10-01

    Full Text Available Background: Colorectal cancer is the fourth most common cancer and the second leading cause of death from cancer in the United States. Preoperative neoadjuvant therapy (chemotherapy and radiotherapy is the gold standard in the management of rectal cancer before surgical resection. The literature includes reports of absence of neoplastic cells after neoadjuvant therapy. There are no reports on complete pathological response to this type of therapy in Mexico. Objectives: Determine the percentage of patients with rectal adenocarcinoma with complete pathological response after neoadjuvant therapy. All patients were treated in a colorectal surgery department of a tertiary care hospital. Materials and methods: A total of 64 patients with rectal adenocarcinoma diagnosed by biopsy were treated from January 2010 to December 2015. Demographic data, tumour localisation, pathological report, TNM stage, neoadjuvant therapy, surgical procedure and postoperative pathological report were collected from patient records. Results: Mean patient age was 52.8 years (range of 26–73; 31 were women and 33 men. Twenty-seven patients (27 were stage II and 27 stage III. The preoperative biopsy results were classified as: well differentiated (10; moderately differentiated (48; and poorly differentiated/undifferentiated adenocarcinoma (6. Twenty patients received neoadjuvant therapy (31.2%. In these, 2 tumours were localised in the upper third of the rectum, 6 in the middle third, and 12 in the lower third. Six patients underwent abdominoperineal resection, 10 total mesorectal excision, and four posterior pelvic exenteration. Six patients undergoing neoadjuvant therapy had a complete pathological response. Conclusions: The percentage of patients with a complete pathological response is similar to that in other literature reports. More evidence is needed to define good prognosis factors in patients who might not require surgery after neoadjuvant therapy. Resumen

  17. Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours

    DEFF Research Database (Denmark)

    Sengeløv, Lisa; von der Maase, Hans; Lundbeck, Finn

    2002-01-01

    This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma...... was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were...... independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19...

  18. Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma

    International Nuclear Information System (INIS)

    Masao, Murakami; Yasumasa, Kuroda; Yosiaki, Okamoto; Koichi, Kono; Eisaku, Yoden; Fusako, Kusumi; Kiyoshi, Hajiro; Satoru, Matsusue; Hiroshi, Takeda

    1997-01-01

    Purpose: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for the esophageal carcinoma. Materials and Methods: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (stage 0 to III: UICC 1987), aged 45 to 78 (mean:64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44Gy in 40 fractions for 4 weeks (2.2Gy/2Fr./day) through 10MVX rays, with one or two courses of cisplatin (80-150mg/body, mean:90mg/m 2 , day 1, bolus injection) and 5-fluorouracil (500-1500mg/body/day, mean:600mg/m 2 , day 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, clinical complete response (CR) was observed in 16 patients, partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR:16, PR:14) entered in CRT group, and 10 non-responding patients (PR:8, NC:2) followed by surgery (CRT-S group). A cumulative median dose of 66Gy for Tis,T1 and 71Gy for T2-T4 tumor with/without high-dose-rate intraluminal brachytherapy, and one to three courses of chemotherapy were delivered in CRT group. Intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added in CRT-S group. Results: Clinical CR rate at the completion of treatment showed 90% in CRT group, and pathological CR rate 10% in CRT-S group. The overall median survival was 45 months, survival at 1, 2, 3 years being 100%, 72%, 56%, respectively. Loco-regional failure was observed in 7 patients (all in CRT group), distant failure in 6 (3 in CRT group, 3 in CRT-S group) and loco-regional with distant failure in 1 (CRT group). Four patients of loco-regional recurrence in CRT group were salvaged by surgery. Overall survival at 2-, 3-years for CRT vs. CRT-S group was 72%, 64% vs. (1(1)); 100

  19. Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Narayan, Vivek; Mamtani, Ronac; Keefe, Stephen; Guzzo, Thomas; Malkowicz, S Bruce; Vaughn, David J

    2016-07-01

    We sought to investigate the safety and efficacy of gemcitabine, cisplatin, and lapatinib (GCL) as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) planned for radical cystectomy. Four cycles of GCL were administered as neoadjuvant therapy for patients with MIBC. Although initially designed as a phase II efficacy study with a primary endpoint of pathologic complete response at the time of radical cystectomy, the dose selected for investigation proved excessively toxic. A total of six patients were enrolled. The initial four patients received gemcitabine 1,000 mg/m(2) intravenously on days 1 and 8 and cisplatin 70 mg/m(2) intravenously on day 1 of each 21-day treatment cycle. Lapatinib was administered as 1,000 mg orally daily starting one week prior to the initiation of cycle 1 of gemcitabine and cisplatin (GC) and continuing until the completion of cycle 4 of GC. These initial doses were poorly tolerated, and the final two enrolled patients received a reduced lapatinib dose of 750 mg orally daily. However, reduction of the lapatinib dose did not result in improved tolerance or drug-delivery, and the trial was terminated early due to excessive toxicity. Grade 3/4 toxicities included diarrhea (33%), nausea/vomiting (33%), and thrombocytopenia (33%). The addition of lapatinib to GC as neoadjuvant therapy for MIBC was limited by excessive treatment-related toxicity. These findings highlight the importance of thorough dose-escalation investigation of combination therapies prior to evaluation in the neoadjuvant setting, as well as the limitations of determination of maximum tolerated dose for novel targeted combination regimens.

  20. Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the German Retinoblastoma Referral Centre.

    Science.gov (United States)

    Künkele, Annette; Wilm, Josephine; Holdt, Markus; Lohmann, Dietmar; Bornfeld, Norbert; Eggert, Angelika; Temming, Petra; Schulte, Johannes H

    2015-07-01

    Retinoblastoma can extend beyond the structures of the eye, where cells can enter the bloodstream and cause metastases. Various types of protocols for adjuvant treatment risk-adapted according to histopathological risk factors are used worldwide. Between 1997 and 2009, 420 children were diagnosed with retinoblastoma at the German Retinoblastoma Referral Centre and risk factors were assessed. Patients with post-laminar optic nerve infiltration or choroid or minor scleral invasion received six courses of adjuvant chemotherapy using vincristine, etoposide, carboplatin and cyclophosphamide (group 1). Patients with microscopic extension beyond the sclera to the resection margin of the optic nerve or potential spread due to vitrectomy received chemotherapy plus orbital radiotherapy (group 2). Neoadjuvant chemotherapy was performed in patients with local extraocular invasion detected on MRI. Following this protocol, 42 of the 420 patients and 21 referred from other centres showed high-risk histopathological factors qualifying for adjuvant therapy (57 in group 1 and 6 in group 2). Seven of the 63 patients received neoadjuvant and adjuvant treatment. During a mean follow-up of 5.8 (range 0.4-15.4) years, one of six patients in group 2 developed metastases and died. No patients died from toxicity. The 5-year overall survival was 100% for group 1 and 80% for group 2. This retrospective single-site study reveals a 10% incidence of high-risk features in children with retinoblastoma diagnosed at the German Retinoblastoma Referral Centre. Overall survival rates of 98.3% underline the safety of this adjuvant chemotherapy protocol and its efficiency in preventing metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

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    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Brunner, Thomas B. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); University Hospital Freiburg, Department of Radiation Oncology, Freiburg (Germany); Witzigmann, Helmut [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Marti, Lukas [Hospital of Kanton St. Gallen, General Surgery, St. Gallen (Switzerland); Bechstein, Wolf-Otto [University Hospital Frankfurt, Department of Surgery, Frankfurt/Main (Germany); Bruns, Christiane [University Hospital Munich, Department of Surgery - Hospital Campus Grosshadern, Munich (Germany); University Hospital Magdeburg, Department of Surgery, Magdeburg (Germany); Jungnickel, Henry [Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Schreiber, Stefan [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Grabenbauer, Gerhard G. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Coburg, Department of Radiation Oncology, Coburg (Germany); Meyer, Thomas [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Hospital Ansbach, General Surgery, Ansbach (Germany); Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

    2014-09-25

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [German] Mehrere nichtrandomisierte Studien zeigten, dass eine neoadjuvante Therapie das Ueberleben bei Patienten mit Pankreaskarzinom verlaengert. Beim lokal fortgeschrittenen Rektumkarzinom gehoert die

  2. Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.

    Science.gov (United States)

    McCaffrey, Rebecca; Bahtiyar, Mert; Kohorn, Ernest I; Chambers, Joseph T; Schwartz, Peter E; Chambers, Setsuko K

    2011-04-01

    The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented. Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied. The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation. Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant

  3. Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2011-02-01

    Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

  4. What is the significance of the circumferential margin in locally advanced rectal cancer after neoadjuvant chemoradiotherapy?

    Science.gov (United States)

    Trakarnsanga, Atthaphorn; Gonen, Mithat; Shia, Jinru; Goodman, Karyn A; Nash, Garrett M; Temple, Larissa K; Guillem, José G; Paty, Philip B; Garcia-Aguilar, Julio; Weiser, Martin R

    2013-04-01

    The circumferential resection margin (CRM) is highly prognostic for local recurrence in rectal cancer surgery without neoadjuvant treatment. However, its significance in the setting of long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined. Review of a single institution's prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6 weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed. The authors noted that 75 % of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39 months after resection, local and distant relapse were noted in 12 (2.1 %) and 98 (17.4 %) patients, respectively. On competing risk analysis, the optimal cutoff point of CRM was 1 mm for local recurrence and 2 mm for distant metastasis. Factors independently associated with local recurrence included CRM ≤1 mm, and high-grade tumor (p = 0.012 and 0.007, respectively). CRM ≤2 mm, as well as pathological, nodal, and overall tumor stage are also significant independent risk factors for distant metastasis (p = 0.025, 0.010, and dataset of locally advanced rectal cancer treated with nCRT followed by TME, CRM ≤1 mm is an independent risk factor for local recurrence and is considered a positive margin. CRM ≤2 mm was associated with distant recurrence, independent of pathological tumor and nodal stage.

  5. Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer in a population with a high HIV prevalence in Johannesburg, South Africa.

    Science.gov (United States)

    Ruff, Paul; Cubasch, Herbert; Joffe, Maureen; Rosenbaum, Evan; Murugan, Nivashni; Tsai, Ming-Chih; Ayeni, Oluwatosin; Crew, Katherine D; Jacobson, Judith S; Neugut, Alfred I

    2018-01-01

    showed age <40 years and disease stage to be independently associated with the receipt of NACT. Most women receiving NACT with available response data showed a clinical benefit. Stage III disease at diagnosis and age <40 years were predictors of neoadjuvant versus adjuvant chemotherapy treatment.

  6. Long-term survival of patients with primary oral squamous cell carcinoma. Comparison of two treatment protocols in a prospective study; 5-Jahres-Ueberlebenswahrscheinlichkeit von Patienten mit primaeren Plattenepithelkarzinomen der Mundhoehle. Vergleich von zwei Behandlungsstrategien in einer prospektiven Studie

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, P.; Bloch-Birkholz, A.; Neukam, F.W. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Mund-, Kiefer-, Gesichtschirurgie; Grabenbauer, G.; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Leher, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizininformatik, Biometrie und Epidemiologie; Vairaktaris, E. [Univ. of Athens Medical School (Greece). Dept. of Maxillofacial Surgery

    2007-04-15

    Background and Purpose: In recent years, different concepts for the treatment of oral squamous cell carcinomas (OSCC) have been developed; these include preoperative simultaneous neoadjuvant radiochemotherapy and one-stage surgery with tumor ablation and reconstruction. When considering long-term survival, there is substantial evidence that multimodality treatment based on a neoadjuvant radiochemotherapy is superior to adjuvant therapy concepts based on a surgical approach with postoperative irradiation. The aim of this study was to discuss the 5-year survival rate in a neoadjuvant and an adjuvant combination treatment in patients with primary OSCC. Patients and Methods: This nonrandomized longitudinal study prospectively evaluates the long-term tumor-free survival in 128 patients with oral cancer. Two groups consisting of 74 neoadjuvantly and 54 primarily surgically treated patients were formed. 99 patients suffered from stage III and IV disease according to the UICC criteria. Long-term survival was estimated according to the Kaplan-Meier assumption. Results: The neoadjuvant treatment increases the prospect of a long-term tumor-free survival. According to Kaplan-Meier assumption the estimation for a 5-year tumor-free survival in OSCC in category T1 is 83.1% in neoadjuvant, and 70.1% in adjuvant treatment, in T2 79.6% and 57.7%, in T3 68.2% and 33.2%, in T4 51.4% and 30.5%, respectively. Significance (p < 0.05) could be proven for T1 (p = 0.002), T2 (p = 0.028), and T4 (p < 0.0001) tumors. The effectiveness of the preoperative radiochemotherapy was demonstrated in the pathohistological result of tumor-free resection specimens in 28 patients of the neoadjuvant treatment group (37.8%). On the other hand, four patients died during the preoperative combination therapy. 64.8% of the patients in the adjuvant and 71.6% in the neoadjuvant treatment group survived the observation period. Conclusion: Neoadjuvant therapy is highly effective and results in a better 5-year

  7. Nomogram for predicting pathologically complete response after neoadjuvant chemoradiotherapy for oesophageal cancer

    International Nuclear Information System (INIS)

    Toxopeus, Eelke Lucie Anne; Nieboer, Daan; Shapiro, Joel; Biermann, Katharina; Gaast, Ate van der; Rij, Carolien M. van; Steyerberg, Ewout Willem; Lanschot, Joseph Jan Baptiste van; Wijnhoven, Bas Peter Louis

    2015-01-01

    Background: A pathologically complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in 30% of the patients with oesophageal cancer. The aim is to identify patient and tumour characteristics associated with a pCR and to develop a nomogram for the prediction of pCR. Patients and methods: Patients who underwent nCRT followed by surgery were identified and response to nCRT was assessed according to a modified Mandard classification in the resection specimen. A model was developed with age, gender, histology and location of the tumour, differentiation grade, alcohol use, smoking, percentage weight loss, Charlson Comorbidity Index (CCI), cT-stage and cN-stage as potential predictors for pCR. Probability of pCR was studied via logistic regression. Performance of the prediction nomogram was quantified using the concordance statistic (c-statistic) and corrected for optimism. Results: A total of 381 patients were included. After surgery, 27.6% of the tumours showed a pCR. Female sex, squamous cell histology, poor differentiation grade, and low cT-stage were predictive for a pCR with a c-statistic of 0.64 (corrected for optimism). Conclusion: A nomogram for the prediction of pathologically complete response after neoadjuvant chemoradiotherapy was developed, with a reasonable predictive power. This nomogram needs external validation before it can be used for individualised clinical decision-making

  8. Incidence and Timing of Thromboembolic Events in Patients With Ovarian Cancer Undergoing Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Greco, Patricia S; Bazzi, Ali A; McLean, Karen; Reynolds, R Kevin; Spencer, Ryan J; Johnston, Carolyn M; Liu, J Rebecca; Uppal, Shitanshu

    2017-06-01

    To identify the incidence and timing of venous thromboembolism as well as any associated risk factors in patients with ovarian, fallopian tube, or primary peritoneal cancer undergoing neoadjuvant chemotherapy. We conducted a retrospective cohort study of patients diagnosed with ovarian, fallopian tube, and primary peritoneal cancer and receiving neoadjuvant chemotherapy from January 2009 to May 2014 at a single academic institution. The timing and number of venous thromboembolic events for the entire cohort were categorized as follows: presenting symptom, during neoadjuvant chemotherapy treatment, after debulking surgery, and during adjuvant chemotherapy. Of the 125 total patients with ovarian cancer undergoing neoadjuvant chemotherapy, 13 of 125 patients (10.4%, 95% confidence interval [CI] 6.1-17.2%) had a venous thromboembolism as a presenting symptom and were excluded from further analysis. Of the 112 total patients at risk, 30 (26.8%, 95% CI 19.3-35.9%) experienced a venous thromboembolism. Based on the phase of care, 13 (11.6%, 95% CI 6.8-19.1%) experienced a venous thromboembolism during neoadjuvant chemotherapy, six (5.4%, 95% CI 2.4-11.5%) developed a postoperative venous thromboembolism, and 11 (9.9%, 95% CI 5.5-17%) developed a venous thromboembolism during adjuvant chemotherapy. Two of the four patients with clear cell histology developed a venous thromboembolism in this cohort. Overall new diagnosis of venous thromboembolism was associated with one fourth of the patients undergoing neoadjuvant chemotherapy for ovarian cancer with nearly half of these diagnosed during chemotherapy cycles before interval debulking surgery. Efforts to reduce venous thromboembolism so far have largely focused on the postoperative period. Additional attention to venous thromboembolic prophylaxis during chemotherapy (neoadjuvant and adjuvant) in this patient population is warranted in an effort to decrease the rates of venous thromboembolism.

  9. Circumferential resection margin (CRM) positivity after MRI assessment and adjuvant treatment in 189 patients undergoing rectal cancer resection.

    Science.gov (United States)

    Simpson, G S; Eardley, N; McNicol, F; Healey, P; Hughes, M; Rooney, P S

    2014-05-01

    The management of rectal cancer relies on accurate MRI staging. Multi-modal treatments can downstage rectal cancer prior to surgery and may have an effect on MRI accuracy. We aim to correlate the findings of MRI staging of rectal cancer with histological analysis, the effect of neoadjuvant therapy on this and the implications of circumferential resection margin (CRM) positivity following neoadjuvant therapy. An analysis of histological data and radiological staging of all cases of rectal cancer in a single centre between 2006 and 2011 were conducted. Two hundred forty-one patients had histologically proved rectal cancer during the study period. One hundred eighty-two patients underwent resection. Median age was 66.6 years, and male to female ratio was 13:5. R1 resection rate was 11.1%. MRI assessments of the circumferential resection margin in patients without neoadjuvant radiotherapy were 93.6 and 88.1% in patients who underwent neoadjuvant radiotherapy. Eighteen patients had predicted positive margins following chemoradiotherapy, of which 38.9% had an involved CRM on histological analysis. MRI assessment of the circumferential resection margin in rectal cancer is associated with high accuracy. Neoadjuvant chemoradiotherapy has a detrimental effect on this accuracy, although accuracy remains high. In the presence of persistently predicted positive margins, complete resection remains achievable but may necessitate a more radical approach to resection.

  10. Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

    Science.gov (United States)

    Power, D G; Ilson, D H

    2009-11-01

    Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

  11. Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

    2016-12-01

    Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  12. Neoadjuvant chemotherapy and radiotherapy in locally advanced hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Kim, Su Zy; Wu, Hong Gyun; Heo, Dae Seog; Park, Cham II

    2000-01-01

    factor affecting overall survival was the response to overall treatment (CR vs. PR, p<0.01). In this study, there were only five patients who achieved CR after neoadjuvant chemotherapy. Therefore the difference of overall survival rates between CR and PR to chemotherapy group was not statistically significant. Only the response to chemo-radiotherapy was the most important prognostic factor. There needs to be more effort to improve CR rate of neoadjuvant chemotherapy and consideration for future use of concurrent chemoradiotherapy

  13. Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

    Science.gov (United States)

    Matsuda, S; Tsubosa, Y; Sato, H; Takebayashi, K; Kawamorita, K; Mori, K; Niihara, M; Tsushima, T; Yokota, T; Onozawa, Y; Yasui, H; Takeuchi, H; Kitagawa, Y

    2017-02-01

    Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5

  14. Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won Tae; Kim, Yong Kan; Lee, Ju Hye; Kim, Dong Hyun; Park, Dahl; Cho, Kyu Sup; Kim, Dong Won [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Ji Ho; Roh, Hwan Jung [Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2013-09-15

    The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m2) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens.

  15. Quality of Life During Neoadjuvant Treatment and After Surgery for Resectable Esophageal Carcinoma

    International Nuclear Information System (INIS)

    Meerten, Esther van; Gaast, Ate van der; Looman, Caspar W.N.; Tilanus, Hugo W.G.; Muller, Karin; Essink-Bot, Marie-Louise

    2008-01-01

    Purpose: Because of the trade-off between the potentially negative quality-of-life (QoL) effects and uncertain favorable survival effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable esophageal cancer, we assessed heath-related QoL (HRQoL) for up to 1 year postoperatively in these patients treated with preoperative CRT with a non-platinum-based outpatient regimen followed by esophagectomy. Methods and Materials: Patients undergoing neoadjuvant paclitaxel and carboplatin therapy concurrent with radiotherapy followed by surgery completed standardized HRQoL questionnaires before and after CRT and at regular times up to 1 year postoperatively. We analyzed differences in generic Qol core questionnaire [QLQ-C30] and condition-specific (esophageal site-specific [OES-18]) HRQoL scores over time by using a linear mixed-effects model. Results: Mean scores of most HRQoL scales deteriorated significantly during neoadjuvant CRT. The largest deterioration was observed for physical and role-functioning scales. All except two symptom scores worsened significantly. Postoperatively, most mean HRQoL scores improved until recovery to baseline level. Speed of improvement varied. Average taste score returned to baseline 3 months postoperatively, whereas it took 1 year for the average role-functioning score to restore. The emotional-functioning score showed a different pattern; it was worst at baseline and increased over time during CRT and postoperatively. Dysphagia and pain scores worsened considerably during CRT, restored to baseline 3 months postoperatively, and were even significantly better 1 year postoperatively. Conclusions: Preoperative CRT with paclitaxel and carboplatin for patients with resectable esophageal cancer had a considerable temporary negative effect on most aspects of HRQoL. Nonetheless, all HRQoL scores were restored or even improved 1 year postoperatively

  16. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

    International Nuclear Information System (INIS)

    Sher, David J.; Fidler, Mary Jo; Seder, Christopher W.; Liptay, Michael J.; Koshy, Matthew

    2015-01-01

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  17. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States); Seder, Christopher W.; Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Koshy, Matthew [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

    2015-06-01

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  18. Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Al-Amro, Abdullah; Al-Rajhi, Nasser; Khafaga, Yasser; Memon, Mohammad; Al-Hebshi, Adnan; El-Enbabi, Ashraf; El-Husseiny, Gamal; Radawi, Amer; Belal, Abdulaziz; Allam, Ayman; El-Sebaie, Medhat

    2005-01-01

    Purpose: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Methods and Materials: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m 2 and epirubicin 70 mg/m 2 on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m 2 for 4 days on Days 42, 63, and 84. Results: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient

  19. A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

    International Nuclear Information System (INIS)

    Garcia-Casado, Zaida; Cervera-Deval, Jose; Campos, Josefina; Albaladejo, Carlos Vazquez; Llombart-Bosch, Antonio; Guillem, Vicente; Lopez-Guerrero, Jose A; Guerrero-Zotano, Angel; Llombart-Cussac, Antonio; Calatrava, Ana; Fernandez-Serra, Antonio; Ruiz-Simon, Amparo; Gavila, Joaquin; Climent, Miguel A; Almenar, Sergio

    2010-01-01

    Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4 th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients

  20. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    International Nuclear Information System (INIS)

    Alexander, Brian M.; Wang Xiaozhe; Niemierko, Andrzej; Weaver, David T.; Mak, Raymond H.; Roof, Kevin S.; Fidias, Panagiotis; Wain, John; Choi, Noah C.

    2012-01-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  1. Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

    Science.gov (United States)

    Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

    2017-10-01

    To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a

  2. Neoadjuvant treatment and adjuvant radiotherapy for patients with high risk prostate cancer and radical prostatectomy

    International Nuclear Information System (INIS)

    Scorticati, Carlos; Aguilar, Jorge A.; Gonzalez Granda, Pablo; Mendez, Fernando; Montiel, Raul; Rege, Eduardo; Alvarez, Patricio; Lopez, Miguel A.; Rizzi, Alfredo; Mazza, Osvaldo

    2009-01-01

    Introduction and Objectives: To analyze the results of the treatment in patients with cancer of prostate of high risk. Material and Method: Retrospective and observational analysis of 130 patients operated by CAP of high risk (criteria of D'Amico) average 41,48 months, divided in form nonrandomized in three groups 1: radical prostatectomy, 2: neoadjuvant hormonoterapy (BAC) + PR, 3: BAC + PR + x-ray (RT). Statistical analysis: multivaried, test of curved Chi2 and p statistical and of Kaplan Meier. Results: Biochemical relapse 68 patients (52.3%), average 23,37 months. Without differences according to therapeutic modality (p: 0.043). In the multivaried analysis of the 3 factors of presurgical, single risk we found a statistically significant relation in the coexistence of the 3 factors with the presence of positive margin in the PR piece. (p: 0,002). The analysis to make or not, neoadjuvant BAC without significant difference (p: 0,403) evaluating in such the rate of M+, actuarial global survival according to curves of Kaplan Meier to 5 and 10 years (P: 0,5257) and survival 5 actuarial specific cancer to and 10a (P: 0,2165). Conclusions: Without significant differences in: RB, clinical progression, pathological relapse, global and specific survival, rate of positive surgical margins. The 3 criteria of D'Amico were predictive of positive surgical margins and RB, the patients with RB in group 2 presented/displayed greater risk of clinical progression, the PR demonstrated a global survival and specify actuarial to 10 years greater to 50%, considering it therapeutic an option been worth. (authors) [es

  3. Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

    Science.gov (United States)

    Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

    2008-09-01

    Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

  4. Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer

    International Nuclear Information System (INIS)

    Lamb, David S.; Denham, James W.; Mameghan, Hedy; Joseph, David; Turner, Sandra; Matthews, John; Franklin, Ian; Atkinson, Chris; North, John; Poulsen, Michael; Kovacev, Olga; Robertson, Randall; Francis, Lynne; Christie, David; Spry, Nigel A.; Tai, K.-H.; Wynne, Chris; Duchesne, Gillian

    2003-01-01

    Purpose: To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer. Methods: Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals. Results: All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible. Conclusion: Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant

  5. Assessing Prediction Performance of Neoadjuvant Chemotherapy Response in Bladder Cancer

    OpenAIRE

    Cremer, Chris

    2016-01-01

    Neoadjuvant chemotherapy is a treatment routinely prescribed to patients diagnosed with muscle-invasive bladder cancer. Unfortunately, not all patients are responsive to this treatment and would greatly benefit from an accurate prediction of their expected response to chemotherapy. In this project, I attempt to develop a model that will predict response using tumour microarray data. I show that using my dataset, every method is insufficient at accurately classifying responders and non-respond...

  6. Early port-site metastasis during neoadjuvant chemotherapy in advanced stage ovarian cancer: report of two cases

    OpenAIRE

    Özmen, Batuhan; Şükür, Yavuz Emre; Atabekoglu, Cem Somer; Heper, Aylin Okçu; Sönmezer, Murat; Güngör, Mete

    2011-01-01

    Port-site metastases in gynecological malignancies subsequent to laparoscopy have been reported with an incidence of 1.1-16%. These metastases tend to be disappearing after primary debulking surgery and subsequent primary chemotherapy. Local resection, chemotherapy and/or radiotherapy have been defined in the management of these metastases with enhanced clinical success. However, in extremely rare cases these metastases were also defined very early during neoadjuvant chemotherapy. Herein, we ...

  7. The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

    Science.gov (United States)

    Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

    2012-04-01

    This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

  8. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...

  9. Early Evaluation of Response Using 18F-FDG PET Influences Management in Gastrointestinal Stromal Tumor Patients Treated with Neoadjuvant Imatinib.

    Science.gov (United States)

    Farag, Sheima; Geus-Oei, Lioe-Fee de; van der Graaf, Winette T; van Coevorden, Frits; Grunhagen, Dirk; Reyners, Anna K L; Boonstra, Pieter A; Desar, Ingrid; Gelderblom, Hans; Steeghs, Neeltje

    2018-02-01

    18 F-FDG PET has previously been proven effective as an early way to evaluate the response of gastrointestinal stromal tumors (GISTs) to imatinib treatment. However, it is unclear whether early evaluation of response affects treatment decisions in GIST patients treated with neoadjuvant intent. Methods: We retrospectively scored changes in management based on early evaluation of response by 18 F-FDG PET in patients in the Dutch GIST registry treated with neoadjuvant imatinib. Results: Seventy 18 F-FDG PET scans were obtained for 63 GIST patients to evaluate for an early response to neoadjuvant imatinib. The scans led to a change in management in 27.1% of the patients. Change in management correlated strongly with lack of metabolic response ( P PET for early evaluation of response often results in a change of management in GIST patients harboring the non- KIT exon 11 mutation and should be considered the standard of care in GIST patients treated with neoadjuvant intent. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  10. Neoadjuvant chemoradiation (modified Eilber protocol) versus adjuvant radiotherapy in the treatment of extremity soft tissue sarcoma

    International Nuclear Information System (INIS)

    Lehane, Chris; Parasyn, Andrew; Ho, Frederick; Thompson, Stephen R.; Smee, Robert; Links, David; Crowe, Phil; Lewis, Craig; Friedlander, Michael; Williams, Janet

    2016-01-01

    Local control for extremity soft tissue sarcomas (STS) requires surgery combined with radiotherapy, usually given pre-operatively or post-operatively. The modified Eilber protocol, a neoadjuvant chemoradiation regimen, has been reported with excellent local control rates. This retrospective single-centre study compared outcomes for patients treated with the modified Eilber protocol with those treated with standard adjuvant radiotherapy. Twenty-nine patients were treated with modified Eilber protocol. Thirty-four patients received adjuvant radiotherapy. Three patients (10%) in the Eilber group and five patients (15%) in the Adjuvant group developed local recurrence (P = 0.87). Major acute wound complications were noted in four patients in each group (P = 0.55). One patient (3.4%) in the Eilber group developed Grade 3 or 4 late toxicities after 1 year compared with nine patients (27%) in the Adjuvant group (P = 0.02). Patients with a diagnosis of extremity STS were retrospectively reviewed from the Prince of Wales Hospital Sarcoma Database from 1995 to 2012. Sixty-three patients underwent curative surgery with either neoadjuvant Eilber chemoradiotherapy (Eilber) or adjuvant radiotherapy (Adjuvant). Neoadjuvant chemoradiation (Eilber protocol) provided similar rates of local control when compared with adjuvant radiotherapy. Acute wound complication rates were similar but there was less severe late toxicity in the Eilber group.

  11. Neoadjuvant radiotherapy followed by mastectomy and immediate breast reconstruction. An alternative treatment option for locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pazos, Montserrat; Corradini, Stefanie; Schoenecker, Stephan; Scheithauer, Heike; Belka, Claus [LMU Munich, Department of Radiation Oncology, Munich (Germany); Dian, Darius [Mednord Munich Clinic, Munich (Germany); Bodungen, Vera von; Ditsch, Nina; Wuerstlein, Rachel; Harbeck, Nadia [LMU Munich, Breast Center, Department of Obstetrics and Gynecology, Munich (Germany)

    2017-04-15

    The optimal sequence of mastectomy with immediate breast reconstruction (IBR) and radiotherapy (RT) for the treatment of locally advanced breast cancer (LABC) is still under debate. Increased rates of postoperative complications are described following postmastectomy RT. Neoadjuvant RT aims to improve the aesthetic results and simplify the reconstructive pathway. A total of 22 patients diagnosed with LABC and treated with neoadjuvant RT followed by mastectomy and IBR between 04/2012 and 03/2015 were retrospectively analyzed. RT consisted of external beam RT to the breast and the regional lymphatics, if indicated. Both implant-based and autologous tissue-transfer reconstruction techniques were used. At the time of RT, 10 patients had no prior surgery and 12 patients had previously undergone breast-conserving surgery (BCS) with positive resection margins without the possibility to perform a second BCS. Additional neoadjuvant chemotherapy was administered in 18 patients prior to RT. A complete pathological response was achieved in 55.0% of patients. The 2-year overall survival rate was 89.3%, the 2-year disease-free-survival 79.8% and the local-recurrence-free survival was 95.2%. The cosmetic result was excellent or good in 66% of the patients treated with upfront mastectomy and 37% of the patients who had previously undergone BCS. Among patients who received implant-based IBR, 4 patients developed serious wound-healing problems with implant loss. The most satisfactory results were achieved with autologous tissue reconstruction. A sequential neoadjuvant chemo-/radiotherapy to allow IBR following mastectomy in selected cases of LABC seems feasible and can be safely attempted. Careful patient selection, close monitoring, and continuous patient support is mandatory to ensure compliance in this treatment strategy. (orig.) [German] Die optimale Therapiesequenz von Mastektomie mit sofortiger Brustrekonstruktion (IBR) und Radiotherapie (RT) beim lokal fortgeschrittenen

  12. Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

    Science.gov (United States)

    Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

    2014-01-17

    Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy

  13. Pretreatment Dysphagia in Esophageal Cancer Patients May Eliminate the Need for Staging by Endoscopic Ultrasonography.

    Science.gov (United States)

    Ripley, R Taylor; Sarkaria, Inderpal S; Grosser, Rachel; Sima, Camelia S; Bains, Manjit S; Jones, David R; Adusumilli, Prasad S; Huang, James; Finley, David J; Rusch, Valerie W; Rizk, Nabil P

    2016-01-01

    Neoadjuvant therapy is commonly administered to patients with localized disease who have T3-4 esophageal disease as staged by endoscopic ultrasound (EUS). Previously, we noted that patients who present with dysphagia have a higher EUS T stage. We hypothesized that the presence of dysphagia is predictive of EUS T3-4 disease and that staging EUS could be forgone for esophageal cancer patients with dysphagia. We performed a prospective, intent-to-treat, single-cohort study in which patients with potentially resectable esophageal cancer completed a standardized four-tier dysphagia score survey. EUS was performed as part of our standard evaluation. To determine whether the presence of dysphagia predicted EUS T3-4 disease, the dysphagia score was compared with EUS T stage. The study enrolled 114 consecutive patients between August 2012 and February 2014: 77% (88 of 114) received neoadjuvant therapy, 18% (20 of 114) did not, and 5% (6 of 114) pursued treatment elsewhere. In total, 70% (80 of 114) underwent esophagectomy; of these, 54% (61 of 114) had dysphagia and 46% (53 of 114) did not. Dysphagia scores were 66% (40 of 61) grade 1, 25% (15 of 61) grade 2, and 10% (6 of 61) grade 3 to 4. Among patients with dysphagia, 89% (54 of 61) had T3-4 disease by EUS; among those without dysphagia, only 53% (28 of 53) had T3-4 disease by EUS (p < 0.001). The presence of dysphagia in patients with esophageal cancer was highly predictive of T3-4 disease by EUS. On the basis of this finding, approximately 50% of patients currently undergoing staging EUS at our institution could potentially forgo EUS before neoadjuvant therapy. Patients without dysphagia, however, should still undergo EUS. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial

    International Nuclear Information System (INIS)

    Gérard, Jean-Pierre; Chamorey, Emmanuel; Gourgou-Bourgade, Sophie; Benezery, Karène; Laroche, Guy de; Mahé, Marc-André; Boige, Valérie; Juzyna, Béata

    2015-01-01

    Background: During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Material and methods: Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine + oxaliplatin + 50 Gy vs Cap 45: capecitabine + 45 Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. Results: The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p = 0.025); tumors <4 cm in diameter (14%; p = 0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p = 0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 “watch and wait”. A complete response was associated with more ypT0 (73%; p < 0.001); ypNO (92%); R0 circumferential margin (100%). Conclusion: These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers

  15. Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial.

    Science.gov (United States)

    Gérard, Jean-Pierre; Chamorey, Emmanuel; Gourgou-Bourgade, Sophie; Benezery, Karène; de Laroche, Guy; Mahé, Marc-André; Boige, Valérie; Juzyna, Béata

    2015-05-01

    During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine+oxaliplatin+50Gy vs Cap 45: capecitabine+45Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p=0.025); tumors <4cm in diameter (14%; p=0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p=0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 "watch and wait". A complete response was associated with more ypT0 (73%; p<0.001); ypNO (92%); R0 circumferential margin (100%). These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. [Oligometastasized colorectal cancer-modern treatment strategies].

    Science.gov (United States)

    Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

    2018-06-05

    The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.

  17. Prognostic impact of {sup 18}F-FDG PET/CT staging and of pathological response to neoadjuvant chemotherapy in triple-negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Groheux, D.; Merlet, P. [Saint-Louis Hospital, Department of Nuclear Medicine, Paris Cedex 10 (France); University of Paris VII, B2T Doctoral School, Institut Universitaire d' Hematologie, Paris (France); Giacchetti, S.; Hamy, A.S.; Espie, M. [Saint-Louis Hospital, Breast Diseases Unit, Department of Medical Oncology, Paris (France); Delord, M. [Institut Universitaire d' Hematologie, Department of Biostatistics and Bioinformatics, Paris (France); Roquancourt, A. de [Saint-Louis Hospital, Department of Pathology, Paris (France); Hindie, E. [University of Bordeaux, Department of Nuclear Medicine, Haut-Leveque Hospital, CHU Bordeaux, Bordeaux (France)

    2014-11-29

    Mortality is high in patients with locally advanced triple-negative breast cancer (TNBC), especially in those with residual tumour after neoadjuvant chemotherapy (NAC). The aim of this study was to determine if pretreatment {sup 18}F-FDG PET/CT staging and pathological findings after NAC could together allow stratification of patients into prognostic groups. Initial staging with {sup 18}F-FDG PET/CT was performed prospectively in 85 consecutive patients with stage II/III TNBC. Correlations between PET findings and disease-specific survival (DSS) were examined. In patients without distant metastases on PET staging, the impact of pathological response to NAC on DSS was examined. Patterns of recurrence were also analysed. {sup 18}F-DG PET/CT revealed distant metastases in 11 of 85 patients (12.9 %). Among 74 M0 patients, 23 (31.1 %) showed a pathological complete response (pCR) at surgery, while 51 had residual invasive disease (no pCR). DSS differed considerably among the three groups of patients (log-rank P <.001): among patients with occult metastases on baseline PET/CT, 2-year DSS was 18.2 %, and among patients without initial metastases on PET/CT, 5-year DSS was 61.3 % in patients without pCR after NAC and 95.2 % in those with pCR. Of the 51 patients who did not achieve pCR, 21 relapsed (17 developed distant metastases). The sites of distant recurrence were: lung/pleura (nine patients), brain (eight patients), liver (six patients), distant lymph nodes (six patients) and bone (five patients). In patients with clinical stage II/III TNBC, {sup 18}F-FDG PET/CT findings at initial staging and pathological response at the end of NAC allow three groups of patients with quite different prognoses to be defined. Extraskeletal recurrences predominated. Specific follow-up strategies in patients with TNBC who do not achieve pCR deserve investigation. (orig.)

  18. The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc-IV high-grade serous ovarian cancer.

    Science.gov (United States)

    Xu, Xia; Deng, Fei; Lv, Mengmeng; Chen, Xiaoxiang

    2017-02-01

    No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1-8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p cycles was shorter than those of patients who underwent cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

  19. Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

    NARCIS (Netherlands)

    Schmitz, Alexander M Th; Teixeira, Suzana C; Pengel, Kenneth E; Loo, Claudette E; Vogel, Wouter V; Wesseling, Jelle; Rutgers, Emiel J Th; Valdés Olmos, Renato A; Sonke, Gabe S; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T F D; Gilhuijs, Kenneth G A

    2017-01-01

    PURPOSE: To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. MATERIALS AND METHODS: In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and

  20. Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

    Science.gov (United States)

    2015-11-01

    the acoustic output power for SHAPE has been developed on the scanner. Briefly, the optimization algorithm steps the ultrasound scanner from 0 to... ultrasound contrast agents to improve the monitoring of breast cancer treatment response to neoadjuvant therapies in women diagnosed with LABC by imaging...estimation (SHAPE). Software for analyzing RF data from a Logiq 9 ultrasound scanner (GE Healthcare, Milwauke, WI) to produce 3D SHAPE pressure

  1. Study comparing sequential (neo-adjuvant) versus concurrent chemo-radiotherapy in patients with squamous cell carcinoma

    International Nuclear Information System (INIS)

    Okawa, Tomohiko; Karasawa, Kumiko; Kaneyasu, Yuko; Tanaka, Makiko; Kita-Okawa, Midori; Ishii, Tetsuo

    1994-01-01

    Radiotherapy combined with chemotherapy is still used for standard treatment in patients with locally advanced unresectable cancer. A study was undertaken to compare a sequential (neo-adjuvant) with a simultaneous (concurrent) chemotherapy and radiotherapy program. Neo-adjuvant chemotherapy with cisplatin (80 mg/m 2 i.v. day 1) and 5FU (600 mg/m 2 continuous i.v. day 1-5) every 3 weeks prior to definitive conventional radiotherapy (60-65 Gy), or cisplatin (20 mg/m 2 i.v. day 1-5) and 5FU (250 mg/m 2 continuous i.v. infusion. day 1-14) were given simultaneously for same radiotherapy. Complete response rate was 45% in the sequential treatment and 43% in the simultaneous arm. Leukopenia and other adverse effects were slightly more frequent in the simultaneous arm, but there were no significant differences. These results suggested that individualization of treatment planning and establishment of optimum treatment were most important for combination of chemotherapy and radiotherapy. (author)

  2. Treatments for esophageal cancer. A review

    International Nuclear Information System (INIS)

    Kato, Hiroyuki; Nakajima, Masanobu

    2013-01-01

    Esophageal cancer is the eighth most common form of cancer worldwide. The treatments for esophageal cancer depend on its etiology. For mucosal cancer, endoscopic mucosal resection and endoscopic submucosal dissection are standard, while for locally advanced cancer, esophagectomy remains the mainstay. The three most common techniques for thoracic esophagectomy are the transhiatal approach, the Ivor Lewis esophagectomy (right thoracotomy and laparotomy), and the McKeown technique (right thoracotomy followed by laparotomy and neck incision with cervical anastomosis). Surgery for carcinoma of the cervical esophagus requires an extensive procedure with laryngectomy in many cases. When the tumor is more advanced, neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is added. The theoretical advantages of adding chemotherapy to the treatment of esophageal cancer are potential tumor down-staging prior to surgery, as well as targeting micrometastases and, thus, decreasing the risk of distant metastasis. Cisplatin- and 5-fluorouracil-based regimes are used worldwide. Chemoradiotherapy is the standard for unresectable esophageal cancer and could also be considered as an option for resectable tumors. For patients who are medically or technically inoperable, concurrent chemoradiotherapy should be the standard of care. Although neoadjuvant chemoradiotherapy followed by surgery or salvage surgery after definitive chemoradiotherapy is a practical treatment; judicious patient selection is crucial. It is important to have a thorough understanding of these therapeutic modalities to assist in this endeavor. (author)

  3. Comparing treatment outcomes of different chemotherapy sequences during intensity modulated radiotherapy for advanced N-stage nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    Sun, Xueming; Zeng, Lei; Chen, Chunyan; Huang, Ying; Han, Fei; Xiao, Weiwei; Liu, Shuai; Lu, Taixiang

    2013-01-01

    N-stage is related to distant metastasis of nasopharyngeal carcinoma (NPC) patients. We performed this study to compare the efficacy of different chemotherapy sequences in advanced N-stage (N2 and N3) NPC patients treated with intensity modulated radiotherapy (IMRT). From 2001 to 2008, 198 advanced N-stage NPC patients were retrospectively analyzed. Thirty-three patients received IMRT alone. Concurrent chemoradiotherapy (CCRT) was delivered to 72 patients, neoadjuvant chemotherapy (NACT) + CCRT to 82 patients and CCRT + adjuvant chemotherapy (AC) to 11 patients. The 5-year overall survival rate, recurrence-free survival rate, distant metastasis-free survival rate and progress-free survival rate were 47.7% and 73.1%(p<0.001), 74.5% and 91.3% (p = 0.004), 49.2% and 68.5% (p = 0.018), 37.5% and 63.8% (p<0.001) in IMRT alone and chemoradiotherapy group. Subgroup analyses indicated that there were no significant differences among the survival curves of CCRT, NACT + CCRT and CCRT + AC groups. The survival benefit mainly came from CCRT. However, there was only an improvement attendency in distant metastasis-free survival rate of CCRT group (p = 0.107) when compared with RT alone group, and NACT + CCRT could significantly improve distant metastasis-free survival (p = 0.017). For advanced N-stage NPC patients, NACT + CCRT might be a reasonable treatment strategy

  4. The updated network meta-analysis of neoadjuvant therapy for HER2-positive breast cancer.

    Science.gov (United States)

    Nakashoji, Ayako; Hayashida, Tetsu; Yokoe, Takamichi; Maeda, Hinako; Toyota, Tomoka; Kikuchi, Masayuki; Watanuki, Rurina; Nagayama, Aiko; Seki, Tomoko; Takahashi, Maiko; Abe, Takayuki; Kitagawa, Yuko

    2018-01-01

    We previously described a systematic assessment of the neoadjuvant therapies for human epidermal growth factor receptor-2 (HER2) positive breast cancer, using network meta-analysis. Accumulation of new clinical data has compelled us to update the analysis. Randomized trials comparing different anti-HER2 regimens in the neoadjuvant setting were included, and odds ratio for pathologic complete response (pCR) in seven treatment arms were assessed by pooling effect sizes. Direct and indirect comparisons using a Bayesian statistical model were performed. All statistical tests were two-sided. A database search identified 993 articles with 13 studies meeting the eligibility criteria, including three new studies with lapatinib (lpnb). In an indirect comparison, dual anti-HER2 agents with CT achieved a better pCR rate than other arms. The credibility intervals of CT + tzmb + lpnb arm were largely reduced compared to our former report, which we added sufficient clinical evidence by this update. Values of surface under the cumulative ranking (SUCRA) suggested that CT + tzmb + pzmb had the highest probability of being the best treatment arm for pCR, widening the difference between the top two dual-HER2 blockade arms compared to our former report. The overall consistency with our first report enhanced the credibility of the results. Network meta-analysis using new clinical data firmly establish that combining two anti-HER2 agents with CT is most effective against HER2-positive breast cancer in the neoadjuvant setting. New pzmb related trials are required to fully determine the best neoadjuvant dual-HER2 blockade regimen. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Yutaka Yonemura

    2012-01-01

    Full Text Available Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m2 of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m2 of Taxotere and 30 mg/m2 of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69% patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8% patients. Stage migration was experienced in 12 patients (14.6%. Complete cytoreduction was achieved in 58 patients (70.7%. By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI≤6, which are supposed to be removed completely by peritonectomy.

  6. Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

    LENUS (Irish Health Repository)

    Mulsow, J

    2012-02-01

    Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

  7. Neoadjuvant radiochemotherapy and radical resection for advanced squamous cell carcinoma of the oral cavity. Outcome of 134 patients

    International Nuclear Information System (INIS)

    Eich, H.T.; Loeschcke, M.; Kocher, M.; Bongartz, R.; Mueller, R.P.; Scheer, M.; Zoeller, J.E.; Wacker, S.

    2008-01-01

    Background and purpose: several multimodal strategies have been developed to treat patients with squamous cell carcinoma of the oral cavity. The advantages of preoperative radiochemotherapy are downstaging of the primary tumor, an increased resectability rate, and the elimination of micrometastases. After successful phase II trials, the following therapy regimen for resectable advanced oral carcinoma was applied. Patients and methods: 134 patients with resectable squamous cell carcinoma of the oral cavity stage II-IV received neoadjuvant radiochemotherapy consisting of 39.6 Gy in daily fractions of 1.8 Gy and concomitant carboplatin (70 mg/m 2 days 1-5). Radical resection and neck dissection were carried out afterwards. Results: after a median follow-up of 73 months, 82 patients (61%) had died. 54 patients (40%) experienced locoregional relapses or distant metastases. The overall survival was 65% ± 4% after 2 years and 45% ± 4% after 5 years. Cox regression survival analysis identified tumor regression, extracapsular lymph node spread and resection state as prognostic factors. Side effects of grade 3-4 were rare. Conclusion: neoadjuvant radiochemotherapy with subsequent radical surgery can be recommended as an effective and safe treatment for primary resectable advanced tumors of the oral cavity. Acute and long-term toxicities appear to be moderate. (orig.)

  8. Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

    NARCIS (Netherlands)

    Schmitz, Alexander M. Th; Teixeira, Suzana C.; Pengel, Kenneth E.; Loo, Claudette E.; Vogel, Wouter V.; Wesseling, Jelle; Rutgers, Emiel J. Th; Valdés Olmos, Renato A.; Sonke, Gabe S.; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T. F. D.; Gilhuijs, Kenneth G. A.

    2017-01-01

    To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and 18F-FDG-PET/CT were acquired

  9. PLANNING PHASE 2 MULTICENTER RANDOMIZED TRIAL OF NEOADJUVANT CHEMO-RADIOTHERAPY FOLLOWED BY D2 GASTRECTOMY AND ADJUVANT CHEMOTHERAPY FOR LOCALLY ADVANCED GASTRIC CANCER

    Directory of Open Access Journals (Sweden)

    V. Yu. Skoropad

    2016-01-01

    Full Text Available Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers: CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo

  10. Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fristachi, Carlos Elias

    2005-01-01

    Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

  11. Use of Proktis-M suppositories in patients undergoing neoadjuvant radiochemotherapy for adenocarcinoma of the rectum.

    Science.gov (United States)

    Montrone, S; Gonnelli, A; Cantarella, M; Sainato, A

    2015-12-01

    Generally speaking, the negative side of radiation treatment of the pelvic district is the toxicity that may compromise the patient's quality of life and lead to temporary suspension of treatment with possible negative effects on its effectiveness. In neoadjuvant radiochemotherapy for locally advanced rectal cancer (LARC), the toxicity that is most frequently observed is proctitis, usually treated with topical corticosteroids or mesalazine. Hyaluronic acid's function is to restore the regular trophism and elasticity of the connective tissues leading to faster repair of the damage, and this could represent a viable option for the control of actinic proctitis. Since March 2012, a neoadjuvant radiochemotherapy protocol has been active at the Pisa Universitary Hospital for patients with LARC; 23 patients have been enrolled up to the present. Treatment involves an induction chemotherapy phase according to the FOLFOXIRI + Bevacizumab regimen for 6 cycles, followed by chemotherapy (capecitabina + Bevacizumab) concomitant with radiotherapy (5040 cGy in 28 fractions). Surgery is scheduled 6-8 weeks after the end of RTCT. During the course of associated treatment (RTCT), 12/23 patients received topical therapy with hyaluronic acid (Proktis-M suppositories) for the prevention of proctitis. All 23 patients enrolled in the study completed the induction chemotherapy phase. In the first 11 enrolled patients who did not receive prior Proktis-M suppositories, intense rectal toxicity was observed. Proctalgia of grade G1-2 and G3-4 presented respectively in 64% and 36% of cases, with consequent interruption of treatment which, in 45% of patients, lasted longer than 10 days. In the remaining 12 patients who underwent prior treatment with Proktis-M suppositories, the percentage of rectal toxicity was lower. In those cases where it did present, onset was later and its intensity and duration lower. 25% of patients did not develop proctalgia, 33% developed proctalgia of grade G1 and 42

  12. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer.

    LENUS (Irish Health Repository)

    Armstrong, John G

    2010-08-24

    PURPOSE: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng\\/mL, Gleason score >\\/=7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. RESULTS: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  13. Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response.

    Science.gov (United States)

    Díaz-Expósito, R; Martí-Bonmatí, L; Burgués, O; Casáns-Tormo, I; Bermejo-de Las Heras, B; Julve-Parreño, A; Caballero-Garate, A

    Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, pcancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  14. Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

    International Nuclear Information System (INIS)

    Fietkau, Rainer; Roedel, Claus; Hohenberger, Werner; Raab, Rudolf; Hess, Clemens; Liersch, Torsten; Becker, Heinz; Wittekind, Christian; Hutter, Matthias; Hager, Eva; Karstens, Johann; Ewald, Hermann; Christen, Norbert; Jagoditsch, Michael; Martus, Peter; Sauer, Rolf

    2007-01-01

    Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% ± 7.8%; inadequate RT, 21.2% ± 5.6%; adequate RT, 6.8% ± 1.4%; p = 0.0001) and DFS (no RT, 55.1% ± 9.1%; inadequate RT, 57.4% ± 6.3%; adequate RT, 69.1% ± 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender

  15. [Neoadjuvant Chemotherapy Using S-1 for Pancreatic Cancer - Mid-Term Results].

    Science.gov (United States)

    Homma, Yuki; Honda, Goro; Sakamoto, Katsunori; Kurata, Masanao; Honjo, Masahiko; Hirata, Yoshihiro; Shinya, Satoshi

    2016-10-01

    Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled. The NACRT comprised radiotherapy( 1.8 Gy×28 days)and full-dose twice-daily oral S-1 given on the same days as the radiotherapy. The results of the NACRT and pancreatectomy and the patients' prognoses were evaluated. Fifty-five patients(69.6%)underwent pancreatectomy, with no case of mortality. The curative resection rate was 94.5%. Postoperative adjuvant chemotherapy was administered in 46 patients(83.6%). The 3-year survival rates of all 79 patients and 55 pancreatectomy patients were 40.1% and 50.4%, respectively. NACRT using S-1 was found to be feasible, and good mid-term outcomes were obtained. However, analysis of the long-term outcomes and comparisons with other novel anti-cancer drugs are still required.

  16. Effect of neoadjuvant chemotherapy in hepatic steatosis.

    Science.gov (United States)

    Jiménez, Raúl; Hijona, Elizabeth; Emparanza, José; Alústiza, Jose M; Hijona, Lander; Macarulla, Maria T; Portillo, Maria P; Herreros-Villanueva, Marta; Beguiristain, Adolfo; Arenas, Juan; Bujanda, Luis

    2012-01-01

    Chemotherapy drugs often produce side effects in the liver. In recent years, there has been speculation about the ability to produce hepatic steatosis in patients treated with 5-fluorouracil and oxaliplatin. This prospective study examines whether these drugs can produce steatosis in patients with neoadjuvant treatment who were operated on for liver tumors. Our objective was to assess the effect of neoadjuvant chemotherapy (NAC) on the development of hepatic steatosis in the healthy liver. This was a prospective study based on 32 patients divided into two groups. The presence of steatosis was assessed using a histological score (Kleiner classification) and a biochemical method (Folch method) for patients from both groups. A total of 14 patients (44%) had hepatic steatosis and half of these were in each group. The steatosis was moderate to severe (grades 2-3) in 4 patients (13%), 2 in each group. The mean levels of triglycerides in the liver were 33.38 and 29.94 mg/g in group I and group II, respectively, with the difference not being statistically significant. Almost half of the patients treated with NAC for liver neoplasia developed steatosis. Nevertheless, NAC does not seem to increase the risk of hepatic steatosis. Copyright © 2012 S. Karger AG, Basel.

  17. A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Xun He

    2015-01-01

    Conclusion: Neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve the 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in the patients with locally advanced nasopharyngeal carcinoma.

  18. Treatment of carcinoma of uterine cervix stage III by adriamycin, bleomycin and cisplatinum, neoadjuvant, modified radical hysterectomy and adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Valle, J.C. do; Ribeiro, C.W.; Rezende, Magda C.; Figueiredo, E.; Chu, C.

    1987-01-01

    Forty-eight patients with untreated carcinoma of the cervix stage III A and IIIB, were submitted to 3 to 5 cycles of a combination of adriamycin (ADR), bleomycin (BLEO) and cisplatinum (CDDP), followed by modified radical hysterectomy and adjuvant chemotherapy, 6 cycles, of the same association. The surgical aspect is emphasized and the operative sequence is described. A comparative evaluation between the treatment presented and the radiotherapy is done. The survical rate is studied. (M.A.C.) [pt

  19. Exploring patient experiences of neo-adjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Beaver, Kinta; Williamson, Susan; Briggs, Jean

    2016-02-01

    Neo-adjuvant chemotherapy is recommended for 'inoperable' locally advanced and inflammatory breast cancers. For operable breast cancers, trials indicate no survival differences between chemotherapy given pre or post-surgery. Communicating evidence based information to patients is complex and studies examining patient experiences of neo-adjuvant chemotherapy are lacking. This study aims to explore the experiences of women who received neo-adjuvant chemotherapy for breast cancer. A qualitative approach using in-depth interviews with 20 women who had completed neo-adjuvant chemotherapy for breast cancer. Interview data were analysed using thematic analysis. The sample included a relatively young group of women, with caring responsibilities. Five main themes emerged: coping with the rapid transition from 'well' to 'ill', information needs and decision making, needing support and empathy, impact on family, and creating a new 'normal'. More support was needed towards the end of chemotherapy, when side effects were at their most toxic, and decisions about forthcoming surgery were being made. Some women were referred to psychological services, but usually when a crisis point had been reached. Information and support would have been beneficial at key time points. This information is vital in developing services and interventions to meet the complex needs of these patients and potentially prevent late referral to psychological services. Specialist oncology nurses are able to develop empathetic relationships with patients and have the experience, knowledge and skills to inform and support women experiencing neo-adjuvant chemotherapy. Targeting key time points and maintaining relationship throughout neo-adjuvant chemotherapy would be highly beneficial. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes.

    Science.gov (United States)

    Pareja, Rene; Rendón, Gabriel J; Vasquez, Monica; Echeverri, Lina; Sanz-Lomana, Carlos Millán; Ramirez, Pedro T

    2015-06-01

    Radical trachelectomy is the treatment of choice in women with early-stage cervical cancer wishing to preserve fertility. Radical trachelectomy can be performed with a vaginal, abdominal, or laparoscopic/robotic approach. Vaginal radical trachelectomy (VRT) is generally not offered to patients with tumors 2cm or larger because of a high recurrence rate. There are no conclusive recommendations regarding the safety of abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) in such patients. Several investigators have used neoadjuvant chemotherapy in patients with tumors 2 to 4cm to reduce tumor size so that fertility preservation may be offered. However, to our knowledge, no published study has compared outcomes between patients with cervical tumors 2cm or larger who underwent immediate radical trachelectomy and those who underwent neoadjuvant chemotherapy followed by radical trachelectomy. We conducted a literature review to compare outcomes with these 2 approaches. Our main endpoints for evaluation were oncological and obstetrical outcomes. The fertility preservation rate was 82.7%, 85.1%, 89%; and 91.1% for ART (tumors larger than >2cm), ART (all sizes), NACT followed by surgery and VRT (all sizes); respectively. The global pregnancy rate was 16.2%, 24% and 30.7% for ART, VRT, and NACT followed by surgery; respectively. The recurrence rate was 3.8%, 4.2%, 6%, 7.6% and 17% for ART (all sizes), VRT (all sizes), ART (tumors>2cm), NACT followed by surgery, and VRT (tumors>2cm). These outcomes must be considered when offering a fertility sparing technique to patients with a tumor larger than 2cm. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

    BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...... 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005). CONCLUSION: Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted....

  2. Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer in a population with a high HIV prevalence in Johannesburg, South Africa

    Directory of Open Access Journals (Sweden)

    Ruff P

    2018-02-01

    . Results: Of 554 women with nonmetastatic breast cancer, the median age at diagnosis was 52 years (range: 28–88 years. Only 5.8% of patients were diagnosed with stage I disease; 49.3% and 44.9% were diagnosed with stages II and III, respectively. Most patients had hormone-responsive tumors: luminal A, 38.1%; luminal B1 (human epidermal growth factor receptor 2 [HER2]-negative and high grade, 12.5%, and luminal B2 (HER2-positive any grade, 11.6%; 11.6% had a HER2-enriched tumor and 20.6% a triple-negative tumor. Eighty (14.4% patients were HIV-positive. In total, 195 patients (35.2% received NACT, 264 (47.7% patients received adjuvant chemotherapy, and 95 patients (17.1% received no chemotherapy, including 62 (11.2% patients who received only hormonal therapy. Of patients receiving NACT, 125 (64.1% were evaluable for clinical response. Eighty (64.0% patients had a clinically significant response; 19 (15.2% patients had a stable disease, and 26 (20.8% patients had a progressive disease. Multivariate analysis showed age <40 years and disease stage to be independently associated with the receipt of NACT. Conclusion: Most women receiving NACT with available response data showed a clinical benefit. Stage III disease at diagnosis and age <40 years were predictors of neoadjuvant versus adjuvant chemotherapy treatment. Keywords: breast cancer, chemotherapy, neoadjuvant, South Africa, HIV, LMICs

  3. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review...

  4. Four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (NSABP-B27 with concomitant trastuzumab as neoadjuvant therapy for high-risk, early-stage, HER2-positive breast cancer patients

    Directory of Open Access Journals (Sweden)

    Abdel-Razeq H

    2018-04-01

    Full Text Available Hikmat Abdel-Razeq,1,2 Salwa S Saadeh,1 Mahmoud Abu-Nasser,1 Hazem Abdulelah,1 Lina Marie,1 Murad Salam,1 Basel Al-Haj Ali,1 Mohammad Ibrahim,1 Dalia Rimawi3 1Department of Internal Medicine, Section of Hematology and Medical Oncology, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, University of Jordan, Amman, Jordan; 3Office of Scientific Affairs and Research, King Hussein Cancer Center, Amman, Jordan Background: The majority of breast cancer patients in Jordan are diagnosed at a young age and present with metastatic or locally advanced disease. The National Surgical Adjuvant Breast and Bowel Project Protocol B27 (NSABP-B27 (four cycles of adriamycin and cyclophosphamide [AC] followed by four cycles of docetaxel is a standard neoadjuvant regimen in our institution. In this study, we report the efficacy of adding trastuzumab to docetaxel in this regimen for high-risk human epidermal growth factor receptor 2 (HER2-positive early-stage disease. Patients and methods: Consecutive HER2-positive breast cancer patients treated with this regimen were included. Treatment was given at standard doses and schedules as reported in NSABP-B27. Trastuzumab was given with docetaxel and then continued for 1 year. Results: A total of 121 patients (mean age 45.4 years were included. The majority had high-risk features including large tumor size, positive axillary lymph nodes, and grade III disease. Three patients did not complete the planned cycles of AC due to a lack of response. Eight (6.6% patients missed at least one cycle of docetaxel. Following neoadjuvant therapy, 119 patients underwent surgery, of whom 59 (49.6% patients achieved pathological complete response. The response was higher in node-negative patients (64.0 vs 45.7%; P=0.03 and in hormone receptor-negative disease patients (69.7 vs 41.9%; P=0.018. Breast-conserving surgery was performed in 21.5% of the patients. The median disease-free survival (DFS for the whole group was not

  5. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwang Zoo [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-09-15

    To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary.

  6. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwang Zoo

    2016-01-01

    To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary

  7. [Evaluation of breast cancer treatment at a tertiary-level institution with Popular Health Insurance in Mexico].

    Science.gov (United States)

    Arce-Salinas, Claudia; Lara-Medina, Fernando Ulises; Alvarado-Miranda, Alberto; Castañeda-Soto, Noel; Bargalló-Rocha, Enrique; Ramírez-Ugalde, María Teresa; Pérez-Sánchez, Víctor; Rivera, Lesbia; Gambo-Vignole, Carlos; Santamaría-Galicia, Julieta; Nieves-Casas, Rosa Isela; Morán-Muñoz, Héctor; Mohar-Betancourt, Alejandro

    2012-01-01

    In our country breast cancer represents a major health problem. Only 45% of all population has access to health services, the consequence is delay in diagnosis and treatment. In Mexico, 66% of all new cases of breast cancer are diagnosed in locally advanced stages. From May 2007 the Health System Protection Against Catastrophic Expenses, called Seguro Popular (SP), breast cancer was included in covering the treatment of this neoplasm in any patient without access to social security. To evaluate the results and impact of SP in the adjuvant and neoadjuvant treatment of a group of patients diagnosed with breast cancer at an institution of national reference. We analyzed a group of 259 patients in stages (I-IIIC). The clinical stages I and II (55 patients) were treated with adjuvant chemotherapy FAC -T (fluorouracil 500 mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2 (FAC) followed by 12 weeks of paclitaxel 80 mg/m2 +/- trastuzumab loading dose of 4 mg/kg followed by 2 mg/kg); 204 patients in locally advanced stages (IIB-IIIC) received FAC-T +/- trastuzumab followed by surgery. Adjuvant treatment consisted of endocrine therapy for hormone-sensitive patients and radiotherapy 50 cGy according to international standards. The age at diagnosis was 47 years (range 23-68). 80% of them were locally advanced stages (IIB-IIIC) and were treated in a neoadjuvant setting, 20% was in early stages, treated with surgery and adjuvant chemotherapy The disease-free survival and overall survival at 30 months was 85.7 and 90% respectively. Overall pathologic complete response was obtained in 15% of cases. In the subgroup analysis showed that 41% of patients HER2 (+), 29% of triple-negative patients and 9% of hormone-sensitive tumors achieved complete pathological response (p = 0.0001). This is the first analysis of efficacy of adjuvant and neoadjuvant treatment in breast cancer since the introduction of popular secure non-entitled population. It is clear that treatment efficacy

  8. Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG)

    DEFF Research Database (Denmark)

    Skriver, Signe Korsgaard; Laenkholm, Anne-Vibeke; Rasmussen, Birgitte Bruun

    2018-01-01

    response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment......INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here......, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive...

  9. Problems in neoadjuvant chemoradiotherapy preceding surgery for advanced squamous cell carcinoma of the thoracic esophagus

    International Nuclear Information System (INIS)

    Ishida, Kaoru; Koeda, Keisuke; Sato, Nobuhiro

    1999-01-01

    The adverse effect of neoadjuvant chemoradiotherapy on the postoperative course in esophageal cancer was studied in 9 patients undergoing neoadjuvant chemoradiotherapy preceding surgery for thoracic esophageal carcinoma possibly involving adjacent organs (neoadjuvant group), and 13 patients undergoing surgery without neoadjuvant therapy for same disease (control group). The two groups were compared for volume of intraoperative hemorrhage, surgical duration, frequency of postoperative morbidity, and for postoperative changes in blood platelet counts, and serum thrombopoietin and interleukin-6 levels. Mean intraoperative blood loss was 1121 g (580-1,662 g) in the neoadjuvant group and 546.5 g (274.7-778.3 g) in controls group (Student's T test: p<0.01). No significant difference was seen found between the two groups in the degree of postoperative deterioration in cardiopulmonary function or in interleukin-6 levels. Blood platelet counts decreased in both groups until postoperative day 7, but recovery on postoperative day 14 was significantly depressed in the neoadjuvant group compared to controls. Serum thrombopoietin levels were higher in the neoadjuvant group than in controls (Mann-Whitney U-test: p<0.05). We found that neoadjuvant chemoradiotherapy induces latent postoperative myelosuppression and may lead to intractable infection. (author)

  10. Breast conserving treatment of breast carcinoma T2 ({<=} 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis; Tratamento conservador do cancer de mama T2 ({<=} 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante: analise de controle local e sobrevida global

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Celia Regina; Miziara Filho, Miguel Abrao; Fogaroli, Ricardo Cesar; Baraldi, Helena Espindola; Pellizzon, Antonio Cassio Assis; Pelosi, Edilson Lopes [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia], e-mail: celiarsoares@terra.com.br; Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia; Paes, Roberto Pinto [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil)

    2008-12-15

    Objective: to assess the treatment of breast cancer T2 ({<=} 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. Material and method: this clinical prospective descriptive study was based on the evaluation of 88 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on anthracyclines. Overall survival and local control were assessed according to Kaplan-Meier methodology. Results: Local control and overall survival in five years were 90% and 73.5%, respectively. Conclusion: local control and overall survival were comparable to other forms of treatment. (author)

  11. Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus

    International Nuclear Information System (INIS)

    Minsky, Bruce D.; Neuberg, Donna; Kelsen, David P.; Pisansky, Thomas M.; Ginsberg, Robert J.; Pajak, Thomas; Salter, Merle; Benson, Al

    1999-01-01

    Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (100 mg/m 2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (75 mg/m 2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123

  12. Bladder cancer staging in CT urography: effect of stage labels on statistical modeling of a decision support system

    Science.gov (United States)

    Gandikota, Dhanuj; Hadjiiski, Lubomir; Cha, Kenny H.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Alva, Ajjai; Paramagul, Chintana; Wei, Jun; Zhou, Chuan

    2018-02-01

    In bladder cancer, stage T2 is an important threshold in the decision of administering neoadjuvant chemotherapy. Our long-term goal is to develop a quantitative computerized decision support system (CDSS-S) to aid clinicians in accurate staging. In this study, we examined the effect of stage labels of the training samples on modeling such a system. We used a data set of 84 bladder cancers imaged with CT Urography (CTU). At clinical staging prior to treatment, 43 lesions were staged as below stage T2 and 41 were stage T2 or above. After cystectomy and pathological staging that is considered the gold standard, 10 of the lesions were upstaged to stage T2 or above. After correcting the stage labels, 33 lesions were below stage T2, and 51 were stage T2 or above. For the CDSS-S, the lesions were segmented using our AI-CALS method and radiomic features were extracted. We trained a linear discriminant analysis (LDA) classifier with leave-one-case-out cross validation to distinguish between bladder lesions of stage T2 or above and those below stage T2. The CDSS-S was trained and tested with the corrected post-cystectomy labels, and as a comparison, CDSS-S was also trained with understaged pre-treatment labels and tested on lesions with corrected labels. The test AUC for the CDSS-S trained with corrected labels was 0.89 +/- 0.04. For the CDSS-S trained with understaged pre-treatment labels and tested on the lesions with corrected labels, the test AUC was 0.86 +/- 0.04. The likelihood of stage T2 or above for 9 out of the 10 understaged lesions was correctly increased for the CDSS-S trained with corrected labels. The CDSS-S is sensitive to the accuracy of stage labeling. The CDSS-S trained with correct labels shows promise in prediction of the bladder cancer stage.

  13. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Qiuyun Li

    Full Text Available BACKGROUND: Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. METHODS: The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. RESULTS: Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87-1.40, p = 0.43, pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83-1.18, p = 0.90, overall response rate (ORR; RR = 1.00, 95% CI 0.94-1.07, p = 0.93, or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93-1.04, p = 0.49. CONCLUSIONS: Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.

  14. Rectal and colon cancer : Not just a different anatomic site

    NARCIS (Netherlands)

    Tamas, K.; Walenkamp, A. M. E.; de Vries, E. G. E.; van Vugt, M. A. T. M.; Beets-Tan, R. G.; van Etten, B.; de Groot, D. J. A.; Hospers, G. A. P.

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total

  15. Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

    International Nuclear Information System (INIS)

    Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S.

    2011-01-01

    Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.

  16. Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

    Science.gov (United States)

    Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

    2003-10-01

    The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced

  17. When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer.

    Science.gov (United States)

    Papadia, Andrea; Bellati, Filippo; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Lorusso, Domenica; Donfrancesco, Cristina; Gasparri, Maria Luisa; Raspagliesi, Francesco

    2015-12-01

    The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.

  18. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial.

    Science.gov (United States)

    Blackwell, Kimberly; Donskih, Roman; Jones, C Michael; Nixon, Allen; Vidal, Maria J; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

    2016-07-01

    Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2)) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count prevention of neutropenia in patients with early-stage breast cancer receiving TAC. The granulocyte colony-stimulating factor pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. Biosimilars are biologics with similar quality, safety, and efficacy to a reference product that may increase the affordability of treatment compared with their reference compounds. There are currently no approved biosimilars of pegfilgrastim in highly regulated markets. No previous phase III studies have been performed with LA-EP2006. PROTECT-2 was conducted to confirm the similarity of the proposed biosimilar LA-EP2006 to pegfilgrastim. Biosimilar pegfilgrastim (LA-EP2006) may benefit oncology patients by offering increased access to biological treatments that may improve clinical outcomes. This means that patients could potentially be treated prophylactically with biologics rather than only after complications have occurred. ©AlphaMed Press.

  19. The role of preoperative systemic treatment in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Sylwia Dębska-Szmich

    2016-06-01

    Full Text Available The goal of preoperative pharmacotherapy in patients with breast cancer is to enable breast conserving surgery in stage T3N0-1M0 or radical mastectomy in patients with primary inoperative tumors (T1-4N0-3M0. The choice of optimal treatment should be based not only on risk factors resulting from the stage but also on predicted cancer responsiveness to the treatment. The breast cancer subtypes defined by immunohistochemical profile (expression of ER, PR, HER2 and Ki67 are characterized by different responsiveness to therapy. Complete response confirmed by histopathological evaluation after neoadjuvant chemotherapy is a positive prognostic factor in some breast cancer subtypes. This marker is not of value in postmenopausal patients with ER/PR+ HER2– tumors, who are candidates for neoadjuvant hormone therapy. These patients have a good prognosis if in a histopathological report after surgery there are features such as pT1, pN0, Ki67 < 3%, and ER Allred score ≥ 3. The goal of the paper is to present current knowledge about preoperative pharmacotherapy of breast cancer.

  20. Clinical Outcome of Patients with Complete Pathological Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancers: The Indian Scenario

    Directory of Open Access Journals (Sweden)

    Snita Sinukumar

    2014-01-01

    Full Text Available Introduction. Neoadjuvant chemoradiotherapy and total mesorectal excision are considered the standard treatment for locally advanced rectal cancer. Various studies have reported pathological downstaging and a complete pathological response rate of 15%–27% following neoadjuvant chemoradiotherapy which has translated into improved survival. We endeavour to determine the clinical outcome of patients attaining a complete pathological tumor response following neoadjuvant chemoradiotherapy in the Indian setting where most of our patient population is younger and presents with aggressive tumor biology. Materials and Methods. Clinicopathological and treatment details were recorded for 64 patients achieving pathological complete response from 2010 to 2013. Disease-free survival (DFS, overall survival (OS, and locoregional and systemic recurrence rates were evaluated for these patients. Results. After a median follow-up of 30.5 months (range 11–59 months, the 3-year overall survival (OS was 94.6% and the 3-year disease-free survival (DFS was 88.5%. The locoregional and systemic recurrence rates were 4.7% and 3.1%, respectively. Conclusion. In the Indian subcontinent, despite younger patients with aggressive tumor biology, outcome in complete responders is good.

  1. Endoscopic ultrasonography and computed tomography scanning for preoperative staging of colonic cancer

    DEFF Research Database (Denmark)

    Malmstrøm, M L; Gögenur, I; Riis, L B

    2017-01-01

    PURPOSE: With an increasing demand for more accurate preoperative staging methods for colon cancer, we aimed to compare preoperative tumour (T)- and nodal (N)-stage in patients with left-sided colon cancer by endoscopic ultrasonography (EUS) and computed tomography (CT) with post......-operative histology as gold standard. METHODS: A total of 44 patients were prospectively recruited at Herlev and Roskilde University Hospitals during November 2014-January 2016. Thirty-five patients were included in the final analysis and underwent EUS, CT and surgery within 2 weeks. Diagnostic values were evaluated...... difficult to evaluate due to small patient numbers. EUS could be considered as a supplement to CT scans in selecting patients for neoadjuvant therapies, or local transmural treatment, in the future. TRIAL REGISTRATION: NCT02324023....

  2. Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades.

    Science.gov (United States)

    Fischer, Joern; Joern, Fischer; Hellmich, Gunter; Gunter, Hellmich; Jackisch, Thomas; Thomas, Jackisch; Puffer, Erik; Erik, Puffer; Zimmer, Jörg; Jörg, Zimmer; Bleyl, Dorothea; Dorothea, Bleyl; Kittner, Thomas; Thomas, Kittner; Witzigmann, Helmut; Helmut, Witzigmann; Stelzner, Sigmar; Sigmar, Stelzner

    2015-06-01

    This study aimed to investigate the outcome for stage II and III rectal cancer patients compared to stage II and III colonic cancer patients with regard to 5-year cause-specific survival (CSS), overall survival, and local and combined recurrence rates over time. This prospective cohort study identified 3,355 consecutive patients with adenocarcinoma of the colon or rectum and treated in our colorectal unit between 1981 and 2011, for investigation. The study was restricted to International Union Against Cancer (UICC) stages II and III. Postoperative mortality and histological incomplete resection were excluded, which left 995 patients with colonic cancer and 726 patients with rectal cancer for further analysis. Five-year CSS rates improved for colonic cancer from 65.0% for patients treated between 1981 and 1986 to 88.1% for patients treated between 2007 and 2011. For rectal cancer patients, the respective 5-year CSS rates improved from 53.4% in the first observation period to 89.8% in the second one. The local recurrence rate for rectal cancer dropped from 34.2% in the years 1981-1986 to 2.1% in the years 2007-2011. In the last decade of observation, prognosis for rectal cancer was equal to that for colon cancer (CSS 88.6 vs. 86.7%, p = 0.409). Survival of patients with colon and rectal cancer has continued to improve over the last three decades. After major changes in treatment strategy including introduction of total mesorectal excision and neoadjuvant (radio)chemotherapy, prognosis for stage II and III rectal cancer is at least as good as for stage II and III colonic cancer.

  3. Surgery and Multimodal treatments in pancreatic cancer. A review on the basis of future multimodal treatment concepts

    International Nuclear Information System (INIS)

    Link, K.H.; Leder, G; Formentini, A.; Fortnagel, G.; Kornmann, M.; Schatz, M.; Beger, H.G.

    1999-01-01

    The literature on the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. A special view was concentrated on the biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities, to characterize the disease for an optimally targeted treatment in conjunction with surgical removal of the tumor. The results of systemic and regional chemotherapy and radiotherapy either alone or in combination, before, during, and after surgery, were critically analyzed with respect to the oncological possibilities and pitfalls of each treatment method. In two randomized trials, one testing postoperative radio chemotherapy (GITSG), and one postoperative chemotherapy (Bakkevold), the adjuvant treatment, achieved a significant prolongation of the median survival time. The 5- and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radio chemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy, the survival times were improved vs. surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radio chemotherapy has several advantages, and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to down stage primarily nonresectable pancreatic cancers. (K.H.). 111 refs

  4. A Patient with a Large Gastric Tumor and Protein-Losing Gastroenteropathy Successfully Treated with Neoadjuvant TS-1 Combined with CDDP Therapy

    Directory of Open Access Journals (Sweden)

    Tatsuya Hashimoto

    2014-11-01

    Full Text Available Gastric cancer with protein-losing gastroenteropathy is relatively rare worldwide. The most important problem for the treatment of these patients is their low nutritional status and protein level, which can cause severe postoperative complications. We report a 49-year-old Japanese female with a large gastric tumor and protein-losing gastroenteropathy successfully treated with neoadjuvant TS-1 combined with CDDP therapy. She had a type 5 tumor with partially cauliflower-like appearance. Her blood chemistry revealed low serum total protein (3.3 g/dl and low albumin (1.7 g/dl. She was additionally diagnosed with protein-losing gastroenteropathy based on 99mTc-human serum albumin scintigraphy. Initial neoadjuvant chemotherapy decreased the size of the tumor and led to a marked improvement in her serum protein levels. She then underwent a total gastrectomy and lymph node dissection (D2 with a combined resection of the spleen and gallbladder. Therefore, neoadjuvant chemotherapy may provide a safe treatment before definitive surgery for gastric cancer with protein-losing gastroenteropathy.

  5. Prognostic and Predictive Value of Baseline and Posttreatment Molecular Marker Expression in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy

    International Nuclear Information System (INIS)

    Bertolini, Federica; Bengala, Carmelo; Losi, Luisa; Pagano, Maria; Iachetta, Francesco; Dealis, Cristina; Jovic, Gordana; Depenni, Roberta; Zironi, Sandra; Falchi, Anna Maria; Luppi, Gabriele; Conte, Pier Franco

    2007-01-01

    Purpose: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. Methods and Materials: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. Results: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. Conclusions: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer

  6. Sixteen years follow-up results of a randomized phase II trial of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast cancer: GOCS experience.

    Science.gov (United States)

    Leone, José Pablo; Leone, Julieta; Vallejo, Carlos Teodoro; Pérez, Juan Eduardo; Romero, Alberto Omar; Machiavelli, Mario Raul; Romero Acuña, Luis; Domínguez, María Ester; Langui, Mario; Fasce, Hebe Margot; Leone, Bernardo Amadeo; Ortiz, Eduardo; Iturbe, Julián; Zwenger, Ariel Osvaldo

    2014-01-01

    Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival.

  7. Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

    Science.gov (United States)

    Goodman, Karyn A; Patton, Caroline E; Fisher, George A; Hoffe, Sarah E; Haddock, Michael G; Parikh, Parag J; Kim, John; Baxter, Nancy N; Czito, Brian G; Hong, Theodore S; Herman, Joseph M; Crane, Christopher H; Hoffman, Karen E

    2016-01-01

    To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings

  8. How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

    Science.gov (United States)

    Martinelli, F; Bogani, G; Ditto, A; Carcangiu, M; Papadia, A; Lecce, F; Chiappa, V; Lorusso, D; Raspagliesi, F

    2015-08-01

    Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.

    Science.gov (United States)

    Lacava, J A; Leone, B A; Machiavelli, M; Romero, A O; Perez, J E; Elem, Y L; Ferreyra, R; Focaccia, G; Suttora, G; Salvadori, M A; Cuevas, M A; Acuña, L R; Acuña, J R; Langhi, M; Amato, S; Castaldi, J; Arroyo, A; Vallejo, C T

    1997-02-01

    To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. VNB is an active drug against ACC with moderate

  10. Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy.

    Science.gov (United States)

    Huang, Xuan-Zhang; Gao, Peng; Song, Yong-Xi; Sun, Jing-Xu; Chen, Xiao-Wan; Zhao, Jun-Hua; Ma, Bin; Wang, Jun; Wang, Zhen-Ning

    2016-04-12

    Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992-2009. We enrolled patients with yp stages I-III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan-Meier survival analysis with propensity score-matching and Cox proportional hazards models. Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN- patients.

  11. Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

    International Nuclear Information System (INIS)

    Petry, V.; Gagliato, D.M.; Leal, A.I.C.; Arai, R.J.; Longo, E.; Andrade, F.; Ricci, M.D.; Piato, J.R.; Barroso-Sousa, R.; Hoff, P.M.; Mano, M.S.

    2015-01-01

    Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m 2 during 8 weeks followed by weekly doxorubicin at 24 mg/m 2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment

  12. Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Petry, V.; Gagliato, D.M.; Leal, A.I.C.; Arai, R.J.; Longo, E. [Divisão de Oncologia Médica, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Andrade, F. [Núcleo de Mastologia, Hospital Sírio Libanês, São Paulo, SP (Brazil); Ricci, M.D.; Piato, J.R.; Barroso-Sousa, R.; Hoff, P.M.; Mano, M.S. [Divisão de Oncologia Médica, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-03-06

    Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m{sup 2} during 8 weeks followed by weekly doxorubicin at 24 mg/m{sup 2} for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

  13. Variability of inter-observer agreement on feasibility of partial nephrectomy before and after neoadjuvant axitinib for locally advanced renal cell carcinoma (RCC): independent analysis from a phase II trial.

    Science.gov (United States)

    Karam, Jose A; Devine, Catherine E; Fellman, Bryan M; Urbauer, Diana L; Abel, E Jason; Allaf, Mohamad E; Bex, Axel; Lane, Brian R; Thompson, R Houston; Wood, Christopher G

    2016-04-01

    To evaluate how many patients could have undergone partial nephrectomy (PN) rather than radical nephrectomy (RN) before and after neoadjuvant axitinib therapy, as assessed by five independent urological oncologists, and to study the variability of inter-observer agreement. Pre- and post-systemic treatment computed tomography scans from 22 patients with clear cell renal cell carcinoma in a phase II neoadjuvant axitinib trial were reviewed by five independent urological oncologists. R.E.N.A.L. nephrometry score and κ statistics were calculated. The median R.E.N.A.L. nephrometry score changed from 11 before treatment to 10 after treatment (P = 0.002). Five tumours with moderate complexity before axitinib treatment remained moderate complexity after treatment. Of 17 tumours with high complexity before axitinib treatment, three became moderate complexity after treatment. The overall κ statistic was 0.611. Moderate-complexity κ was 0.611 vs a high-complexity κ of 0.428. Before axitinib treatment the κ was 0.550 vs 0.609 after treatment. After treatment with axitinib, all five reviewers agreed that only five patients required RN (instead of eight before treatment) and that 10 patients could now undergo PN (instead of three before treatment). The odds of PN feasibility were 22.8-times higher after treatment with axitinib. There is considerable variability in inter-observer agreement on the feasibility of PN in patients treated with neoadjuvant targeted therapy. Although more patients were candidates for PN after neoadjuvant axitinib therapy, it remains difficult to identify these patients a priori. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  14. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    International Nuclear Information System (INIS)

    Kuremsky, Jeffrey G.; Tepper, Joel E.; McLeod, Howard L. Phar

    2009-01-01

    Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.

  15. Expression of Transketolase like gene 1 (TKTL1 predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Hofmann Wolf-Karsten

    2011-08-01

    Full Text Available Abstract Background For patients with locally advanced rectal cancer (LARC neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor (VEGF-R and Transketolase-like-1 (TKTL1 are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of VEGFR-1, VEGFR-2 and TKTL1 in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab. Methods Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy were analysed by quantitative PCR. Results Significantly higher expression of VEGFR-1/2 was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High TKTL1 expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers. Conclusion High TKTL-1 expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.

  16. Evaluation of resistance training to improve muscular strength and body composition in cancer patients undergoing neoadjuvant and adjuvant therapy: a meta-analysis.

    Science.gov (United States)

    Padilha, Camila S; Marinello, Poliana Camila; Galvão, Daniel A; Newton, Robert U; Borges, Fernando H; Frajacomo, Fernando; Deminice, Rafael

    2017-06-01

    Muscle atrophy and strength decline are two of the most prominent characteristics in cancer patients undergoing cancer therapy, leading to decreased functional ability and reduced quality of life. Therefore, the aim is to systematically review research evidence of the effects of resistance exercise (RE) on lower-limb muscular strength, lean body mass (LBM), and body fat (BF) in cancer patients undertaking neoadjuvant or adjuvant therapy. This research was conducted using the following online database: Clinical Trial Register, Cochrane Trial Register, PubMed, SPORT Discus, and SciELO, from September 2014 until May 2015. We used the following keywords in various combinations with a systematic search: "Cancer therapy," "Wasting muscle," "Muscle loss," "Muscle function," "Neoadjuvant therapy," "Adjuvant thera-py," "Resistance Training," "Weight training," and "Exercise." After selection of 272 full-text articles, 14 publications were included in this meta-analysis. Resistance exercise (RE) during neoadjuvant or adjuvant therapy increased lower-limb muscular strength (mean: 26.22 kg, 95% CI [16.01, 36.43], heterogeneity: P = body mass (LBM) increased (mean 0.8 kg, 95% CI [0.7, 0.9], heterogeneity: P = 0.99, I 2  = 0%, P body fat (BF) (mean: -1.3 kg, 95% CI [-1.5, 1.1], heterogeneity: P = 0.93, I 2  = 0%, P cancer patients undergoing neoadjuvant and adjuvant therapy regardless of the kind of treatment. RE increases muscle strength, maintains LBM, and reduces BF in cancer patients undergoing adjuvant and neoadjuvant therapies. Cancer patients and survivors should consider undertaking RE as an effective countermeasure for treatment-related adverse effects to the musculoskeletal system.

  17. Feasibility of Breast Conservation after Neoadjuvant Chemotherapy in 58 Patients with Locally Advanced Breast Cancer Using p53 and MDRI Genes as Predictors of Response

    International Nuclear Information System (INIS)

    Elsawy, W.H.; Abdel Kader, M.; Abdulla, M.H.

    2002-01-01

    The aim of this prospective trial was to evaluate the feasibility and outcome of breast conservation therapy for patients with locally advanced breast cancer after neoadjuvant chemotherapy. We studied also the value of p53 and MDR1 as predictors to neoadjuvant chemotherapy. Patients and methods: Bet ween August 1997 and May 2000, 58 patients with locally advanced breast carcinoma (stages IlIA and lllB) completed treatment consisting of 5 fluorouracil 600 mg/m 2 , epirubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 (FEC) administered intravenously, at intervals of 3 weeks. The number of cycles of chemotherapy given depended on the clinical tumor response. Surgery (local excision if sufficiently down staged, or mastectomy if not, both with axillary dissection) was performed. Surgery was followed by radiation therapy and 4 more cycles of FEC chemotherapy as an adjuvant therapy. P53 and MDR1 were assessed in the initial tissue biopsy by means of reverse transcriptase-mediated polymerase chain reaction (RT-PCR). p53 and MDR1 findings were correlated with treatment response and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Results: The overall response (CR+PR) was 87.9%, with a clinical complete response rate of 29.3%. Six patients had a pathological complete response and 10 patients had only minimal residual disease. Median followup from the start of chemotherapy was 24 months (range 6 to 40). Twenty two patients (43%) underwent BCS with actuarial 3-year disease-free and overall survival of 58% and 75% respectively. Cosmetic results were good to excellent in 77.2% of the patients. Modified radical mastectomy was done in 29/51 (56.9%) patients with actuarial 3 year disease-free and overall survival of 60% and 78% respectively.In 13 out of 58 patients (22.4%), p53 mutations could be identified, including eight point mutations, three minor deletions and two complex deletions

  18. International preoperative rectal cancer management: staging, neoadjuvant treatment, and impact of multidisciplinary teams.

    LENUS (Irish Health Repository)

    Augestad, Knut M

    2010-11-01

    Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates.

  19. Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    J. Iglesias García

    Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

  20. Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    J. Iglesias García

    2009-09-01

    Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

  1. Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy.

    Science.gov (United States)

    Sun, Zhipeng; Zhang, Nengwei

    2014-12-29

    In the clinical practice of neoadjuvant chemotherapy, response markers are very important. We aimed o investigate whether tumor markers CEA(carcino-embryonic antigen), CA19-9(carbohydrate antigen 19-9), CA72-4(carbohydrate antigen 72-4), and CA125(carbohydrate antigen 125) can be used to evaluate the response to neoadjuvant chemotherapy, and to evaluate the diagnosis and prognosis value of four tumor markers in the patients of gastric cancer. A retrospective review was performed of 184 gastric cancer patients who underwent a 5-Fu, leucovorin, and oxaliplatin (FOLFOX) neoadjuvant chemotherapy regimen, followed by surgical treatment. Blood samples for CEA, CA19-9, CA72-4, and CA125 levels were taken from patients upon admission to the hospital and after neoadjuvant chemotherapy. Statistical analysis was performed to identify the clinical value of these tumor markers in predicting the survival and the response to neoadjuvant chemotherapy. Median overall survival times of pretreatment CA19-9-positive and CA72-4-positive patients (14.0 +/-2.8 months and 14.8 +/-4.0 months, respectively) were significantly less than negative patients (32.5 +/-8.9 months and 34.0 +/-10.1 months, respectively) (P = 0.000 and P = 0.002, respectively). Pretreatment status of CA19-9 and CA72-4 were independent prognostic factors in gastric cancer patients (P = 0.029 and P = 0.008, respectively). Pretreatment CEA >50 ng/ml had a positive prediction value for clinical disease progression after neoadjuvant chemotherapy according to the ROC curve (AUC: 0.694, 95% CI: 0.517 to 0.871, P = 0.017). The decrease of tumor markers CEA, CA72-4, and CA125 was significant after neoadjuvant chemotherapy (P = 0.030, P = 0.010, and P = 0.009, respectively), especially in patients with disease control (including complete, partial clinical response, and stable disease) (P = 0.012, P = 0.020, and P = 0.025, respectively). A decrease in CA72-4 by more than 70% had

  2. Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki [Shimane Medical Univ., Izumo (Japan)

    1998-03-01

    Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

  3. Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

    International Nuclear Information System (INIS)

    Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki

    1998-01-01

    Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

  4. Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

    Science.gov (United States)

    Mowery, Yvonne M; Salama, Joseph K; Zafar, S Yousuf; Moore, Harvey G; Willett, Christopher G; Czito, Brian G; Hopkins, M Benjamin; Palta, Manisha

    2017-04-15

    Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer. The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice. Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT. US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased

  5. Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

    Science.gov (United States)

    Gaß, Paul; Fasching, Peter A.; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W.; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M.; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y.; Beckmann, Matthias W.; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R.

    2016-01-01

    Background Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. PMID:27920623

  6. Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized Phase III study

    International Nuclear Information System (INIS)

    Lewin, Freddi; Damber, Lena; Jonsson, Haakan; Andersson, Torsten; Berthelsen, Anne; Bioerklund, Anders; Blomqvist, Erik; Evensen, Jan F.; Hansen, Hanne S.; Hansen, Olfred; Jetlund, Olav; Mercke, Claes; Modig, Hans; Overgaard, Marie; Rosengren, Bengt; Tausjoe, Johan; Ringborg, Ulrik

    1997-01-01

    Background and purpose: In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. Methods. Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m 2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m 2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. Results: Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. Conclusions: No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment

  7. Neoadjuvant radiation therapy prior to total mesorectal excision for rectal cancer is not associated with postoperative complications using current techniques.

    Science.gov (United States)

    Milgrom, Sarah A; Goodman, Karyn A; Nash, Garrett M; Paty, Philip B; Guillem, José G; Temple, Larissa K; Weiser, Martin R; Garcia-Aguilar, Julio

    2014-07-01

    Neoadjuvant radiation therapy (RT) downstages rectal cancer but may increase postoperative morbidity. This study aims to quantify 30-day complication rates after total mesorectal excision (TME) using current techniques and to assess for an association of these complications with neoadjuvant RT. Stage I-III rectal cancer patients who underwent TME from 2005 to 2010 were identified. Complications occurring within 30 days after TME were retrieved from a prospectively maintained institutional database of postoperative adverse events. The cohort consisted of 461 patients. Median age was 59 years (range 18-90), and 274 patients (59 %) were male. Comorbid conditions included obesity (n = 147; 32 %), coronary artery disease (n = 83; 18 %), diabetes (n = 65; 14 %), and inflammatory bowel disease (n = 19; 4 %). A low anterior resection (LAR) was performed in 383 cases (83 %), an abdominoperineal resection (APR) was performed in 72 cases (16 %), and a Hartmann's procedure was performed in 6 cases (1 %). Preoperative RT was delivered to 310 patients (67 %; median dose of 50.4 Gy, range 27-55.8 Gy). The 30-day incidence of postoperative mortality was 0.4 % (n = 2), any complication 25 % (n = 117), grade 3 or more complication 5 % (n = 24), intra-abdominal infection 3 % (n = 12), abdominal wound complication 9 % (n = 42), perineal wound complication after APR 11 % (n = 8/72), and anastomotic leak after LAR 2 % (n = 6/383). These events were not associated with neoadjuvant RT. In a cohort undergoing TME using current techniques, neoadjuvant RT was not associated with 30-day postoperative morbidity or mortality.

  8. Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

    OpenAIRE

    Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas; Hatschek, Thomas

    2017-01-01

    Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advance...

  9. Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

    International Nuclear Information System (INIS)

    Kim, Jisun; Kim, Lee Su; Han, Sehwan; Nam, Seok Jin; Kang, Han-Sung; Kim, Seung Il; Yoo, Young Bum; Jeong, Joon; Kim, Tae Hyun; Kang, Taewoo; Kim, Sung-Won; Lim, Woosung; Jung, Yongsik; Lee, Jeong Eon; Kim, Ku Sang; Yu, Jong-Han; Chae, Byung Joo; Jung, So-Youn; Kang, Eunyoung; Choi, Su Yun; Moon, Hyeong-Gon; Noh, Dong-Young; Kim, Eun-Kyu; Han, Wonshik; Kim, Min-Kyoon; Paik, Nam-Sun; Jeong, Sang-Seol; Yoon, Jung-han; Park, Chan Heun; Ahn, Sei Hyun

    2014-01-01

    Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. ClinicalTrials.gov Identifier http://clinicaltrial.gov/ct2/show/NCT01589367?term

  10. The role of neoadjuvant chemotherapy in the management of locally advanced cervix cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Mohammed Osman

    2014-09-01

    Full Text Available Cervical cancer is the second most common cancer in women. Neoadjuvant chemotherapy for patients with locally advanced cervix cancer has comparable benefits to concurrent chemoradiotherapy (CCRT, but with fewer side effects. This systematic review aims to provide a comprehensive summary of the benefits of neoadjuvant chemotherapy for the management of locally advanced cervix cancer from stage IB2 (tumor >4.0 cm to IIIB (tumor extending to the pelvic wall and/or hydronephrosis. Our primary objective was to assess benefits in terms of survival. The data source included the USA national library of medicine, Medline search, and the National Cancer Institute PDQ Clinical Protocols. Inclusion criteria for consideration in the current systematic review included studies published between January 1997 and December 2012. In terms of histology, they had to be focused on squamous cell carcinoma, adenosquamous carcinoma, and/or adenocarcinoma. Patients should be either chemotherapy naïve or cervix cancer chemotherapy naïve, and have a performance status ≤2. The search in the above-mentioned scientific websites led to identify 49 publications, 19 of which were excluded, as they did not meet the inclusion criteria of this systematic review. Therefore only 30 studies were deemed eligible. Data was collected from 1760 patients enrolled in the current systematic review study. The mean age was 45.2 years. The mean tumor size was 4.7 cm. The most commonly used chemotherapies were cisplatin doublets. Paclitaxel was the most commonly used chemotherapeutic agent in the doublets. The mean chemotherapy cycles were 2.7. After chemotherapy, patients underwent surgery after a mean time of 2.5 weeks. The standard operation was radical hysterectomy with pelvic lymphadenectomy. Chemotherapy achieved an objective response rate of 84%. The 5-year progression-free survival and overall survival were 61.9% and 72.8% respectively. The treatment protocol was associated

  11. Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive Intracranial Immature Teratoma.

    Science.gov (United States)

    Kitahara, Takahiro; Tsuji, Yoshihito; Shirase, Tomoyuki; Yukawa, Hiroyuki; Takeichi, Yasuhiro; Yamazoe, Naohiro

    2016-04-01

    Immature teratoma (IMT) is the most frequent histological subtype of infantile intracranial teratoma, the most common congenital brain tumor. IMT contains incompletely differentiated components resembling fetal tissues. Infantile intracranial IMT has a dismal prognosis, because it is often inoperable due to its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to be effective in decreasing tumor volume and vascularity to facilitate surgical resection in other types of infantile brain tumors. However, only one recent case report described the effectiveness of neoadjuvant chemotherapy for infantile intracranial IMT in the literature, even though it is common entity with a poor prognosis in infants. Here, we describe the case of a 2-month-old male infant with a very large intracranial IMT. Maximal surgical resection was first attempted but was unsuccessful because of severe intraoperative hemorrhage. Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered with the aim of shrinking and devascularizing the tumor. After neoadjuvant chemotherapy, tumor size did not decrease, but intraoperative blood loss significantly decreased and near-total resection was achieved by the second and third surgery. The patient underwent adjuvant CARE chemotherapy and has been alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant chemotherapy does not decrease tumor volume of infantile intracranial IMT, surgical resection should be tried because chemotherapy can facilitate surgical resection and improve clinical outcome by reducing tumor vascularity.

  12. Neoadjuvant Down-Sizing of Hilar Cholangiocarcinoma with Photodynamic Therapy—Long-Term Outcome of a Phase II Pilot Study

    Directory of Open Access Journals (Sweden)

    Andrej Wagner

    2015-11-01

    Full Text Available Hilar cholangiocarcinoma (CC is non-resectable in the majority of patients often due to intrahepatic extension along bile duct branches/segments, and even after complete resection (R0 recurrence can be as high as 70%. Photodynamic therapy (PDT is an established palliative local tumor ablative treatment for non-resectable hilar CC. We report the long-term outcome of curative resection (R0 performed after neoadjuvant PDT for downsizing of tumor margins in seven patients (median age 59 years with initially non-resectable hilar CC. Photofrin® was injected intravenously 24–48 h before laser light irradiation of the tumor stenoses and the adjacent bile duct segments. Major resective surgery was done with curative intention six weeks after PDT. All seven patients had been curatively (R0 resected and there were no undue early or late complications for the neoadjuvant PDT and surgery. Six of seven patients died from tumor recurrence at a median of 3.2 years after resection, the five-year survival rate was 43%. These results are comparable with published data for patients resected R0 without pre-treatment, indicating that neoadjuvant PDT is feasible and could improve overall survival of patients considered non-curatively resectable because of initial tumor extension in bile duct branches/segments—however, this concept needs to be validated in a larger trial.

  13. Screening vs. non-screening detected colorectal cancer: Differences in pre-therapeutic work up and treatment.

    Science.gov (United States)

    Saraste, D; Martling, A; Nilsson, P J; Blom, J; Törnberg, S; Janson, M

    2017-06-01

    Objectives To compare preoperative staging, multidisciplinary team-assessment, and treatment in patients with screening detected and non-screening detected colorectal cancer. Methods Data on patient and tumour characteristics, staging, multidisciplinary team-assessment and treatment in patients with screening and non-screening detected colorectal cancer from 2008 to 2012 were collected from the Stockholm-Gotland screening register and the Swedish Colorectal Cancer Registry. Results The screening group had a higher proportion of stage I disease (41 vs. 15%; p team-assessed than the non-screening group ( p team-assessed than patients with surgically resected cancers ( p team assessed more extensively than patients with non-screening detected cancers. Staging and multidisciplinary team assessment prior to endoscopic resection was less complete compared with surgical resection. Extensive surgical and (neo)adjuvant treatment was given in stage I disease. Participation in screening reduced the risk of emergency surgery for colorectal cancer.

  14. Optimization of multi-stage dynamic treatment regimes utilizing accumulated data.

    Science.gov (United States)

    Huang, Xuelin; Choi, Sangbum; Wang, Lu; Thall, Peter F

    2015-11-20

    In medical therapies involving multiple stages, a physician's choice of a subject's treatment at each stage depends on the subject's history of previous treatments and outcomes. The sequence of decisions is known as a dynamic treatment regime or treatment policy. We consider dynamic treatment regimes in settings where each subject's final outcome can be defined as the sum of longitudinally observed values, each corresponding to a stage of the regime. Q-learning, which is a backward induction method, is used to first optimize the last stage treatment then sequentially optimize each previous stage treatment until the first stage treatment is optimized. During this process, model-based expectations of outcomes of late stages are used in the optimization of earlier stages. When the outcome models are misspecified, bias can accumulate from stage to stage and become severe, especially when the number of treatment stages is large. We demonstrate that a modification of standard Q-learning can help reduce the accumulated bias. We provide a computational algorithm, estimators, and closed-form variance formulas. Simulation studies show that the modified Q-learning method has a higher probability of identifying the optimal treatment regime even in settings with misspecified models for outcomes. It is applied to identify optimal treatment regimes in a study for advanced prostate cancer and to estimate and compare the final mean rewards of all the possible discrete two-stage treatment sequences. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Benefits and Disadvantages of Neoadjuvant Radiochemotherapy (RCT) in the Multimodal Therapy of Squamous Esophageal Cancer (ESC).

    Science.gov (United States)

    Hanna, Adrian; Birla, Rodica; Iosif, Cristina; Boeriu, Marius; Constantinoiu, Silviu

    2016-01-01

    The purpose of this paper is to present the advantages and disadvantages of neoadjuvant RCT in multimodal therapyof ESC. Between 1998-2014 221 patients were treated with ESC, 85 of whom received neoadjuvant RCT. For these we have made imaging and pathologic assessment of response using RECIST and MANDARD criteria and statistical data were interpreted in terms of the factors that influence the response. Also, they were evaluated statistical correlations between RCT and resectability, postoperative morbidity, mortality and long-term survival. 45 patients were imagistic responders and 34 underwent surgery, 40 non-responders of which 14 underwent surgery. Of the 48 surgical patients with preoperative RCT, histopathological evaluation showed that 32 were pathological responders and 16 non responders. There were performed statistical analyzes of correlations between RCT and resectability, stage, location of ESC, morbidity, mortality and survival. RCT increase resectability, improves survival and maximum duration of survival, more in responders than in nonresponders and does not affect postoperative complications and postoperative mortality, nor among the responders or nonresponders. Imaging evaluation result of the response to RCT overestimate responders. Celsius.

  16. Abordaje multidisciplinar en el tratamiento del cáncer de recto: eficacia del tratamiento neoadyuvante Multidisciplinary approach to the treatment of rectal cancer: the benefits of neoadjuvant therapy

    Directory of Open Access Journals (Sweden)

    P. Priego

    2008-07-01

    ínico parece ofrecer al paciente mejores oportunidades de curación.Objective: the aim of this study was to assess the impact of neoadjuvant treatment on rectal cancer following involvement of a multidisciplinary team (MDT. Materials and methods: between January 2000 and December 2005, 90 patients with rectal adenocarcinoma were evaluated by a MDT and operated on after receiving neoadjuvant treatment with radiochemotherapy (RTCT -67% were men and 33% were women, with a mean age of 65.04 years (21-83 years. Surgery was low anterior resection in 50% and abdominoperineal amputation in 42.2%. Results: the rate of complications associated with neoadjuvant treatment was 54.4%, with gastrointestinal complications being most frequent. However, this toxicity was tolerated by most patients. It was severe in two cases (2.2%, leading to chemotherapy discontinuation. A histological analysis of specimens showed a complete pathologic response in 10 cases (11.1% and a partial response (downstaging of T in 32 cases (35.6%, hence overall response to neoadjuvant treatment was 46.6%. Postoperative complications included anastomotic leakage in 8.3%, perineal wound complications in 34.2%, and urinary disease in 12.2%. The surgical mortality rate was 0%. Local recurrence occurred in 4.4%, and distant metastases were found in 22.2%. Both overall and disease-free survivals were 80 and 64%, respectively. Conclusions: neoadjuvant treatment results in low local recurrence rates and optimal survival rates, with no increase in morbidity or mortality. A systematic evaluation by a MDT in the context of a clinical protocol offers better cure rates.

  17. Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Drisis, Stylianos; Stathopoulos, Konstantinos; Chao, Shih-Li; Lemort, Marc [Institute Jules Bordet, Radiology Department, Brussels (Belgium); Metens, Thierry [Erasme University Hospital, Radiology Department, Brussels (Belgium); Ignatiadis, Michael [Institute Jules Bordet, Oncology Department, Brussels (Belgium)

    2016-05-15

    To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups. Eighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2-, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model. At EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER-. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCR Quantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group. (orig.)

  18. Accuracy of magnetic resonance imaging in the pre-operative staging of rectal adenocarcinoma: Experience from a regional Australian cancer center.

    Science.gov (United States)

    White, Rohen; Ung, Kim Ann; Mathlum, Maitham

    2013-12-01

    Selection of the optimal treatment pathway in patients with rectal adenocarcinoma relies on accurate locoregional staging. This study aims to assess the accuracy of staging with magnetic resonance imaging (MRI) and in particular, its accuracy in differentiating patients with early stage disease from those with more advanced disease who benefit from a different treatment approach. Patients who were staged with MRI and received surgery as the first line of treatment for biopsy-proven adenocarcinoma of the rectum were identified. Comparison was made between the clinical stage on MRI and the pathological stage of the surgical specimen. The sensitivity, specificity and overall accuracy of MRI was assessed. In all, 58 eligible patients were identified. In 31% of patients, the extent of disease was underrepresented on preoperative MRI. Sensitivity, specificity and overall accuracy of anorectal MRI in detecting stage II/III disease status in this cohort was 59, 71 and 62%, respectively. MRI underestimated the pathological stage in many patients in this series who may have benefited from the addition of neoadjuvant radiotherapy to their management. This study supports further refinement of preoperative staging and demonstrates that impressive results from highly controlled settings may be difficult to reproduce in community practice. © 2012 Wiley Publishing Asia Pty Ltd.

  19. Prospective and comparative assessment of toxicity of adjuvant concomitant chemo-radiotherapy after neo-adjuvant chemotherapy in breast cancer; evaluation prospective et comparative de la toxicite de la chimioradiotherapie concomitante adjuvante apres chimiotherapie neoadjuvante dans le cancer du sein

    Energy Technology Data Exchange (ETDEWEB)

    Marchand, V.; Angelergues, A.; Gobaux, V.; Kirova, Y.M.; Campana, F.; Dendale, R.; Reyal, F.; Pierga, J.Y.; Fourquet, A.; Bollet, M.A. [Institut Curie, Paris (France)

    2011-10-15

    The authors report a prospective assessment of toxicity a treatment comprising an adjuvant chemo-radiotherapy after neo-adjuvant chemotherapy and a comparison with a treatment comprising only radiotherapy. Two sets of patients have been treated for a breast cancer between 1997 and 2002 by association of neo-adjuvant chemotherapy, surgery and radiotherapy with or without concomitant chemotherapy. Late toxicity has been assessed prospectively according to Common Terminology Criteria for Adverse Events. Acute toxicity has been noticed in medical files. The analysis of 142 treatments reveals that the concomitant administration of chemotherapy to radiotherapy after neo-adjuvant chemotherapy and surgery is associated with an increase of acute toxicity without increase of long term toxicity. Short communication

  20. Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity

    International Nuclear Information System (INIS)

    Howard, G.C.W.; Cornbleet, M.A.; Whillis, D.; Hargreave, T.B.; Chisholm, G.D.

    1991-01-01

    A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate and cisplatin prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy. (author)

  1. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  2. Prospective prediction of resistance to neoadjuvant therapy in patients with locoregional esophageal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Rosen DG

    2015-02-01

    negative predictive value of 83% was reported by both laboratories. Interobserver concordance was 97%. Discussion: We report the second validation of a multianalyte algorithmic IHC-based predictive test that accurately identifies EC patient response to fluorouracil-based neoadjuvant chemoradiotherapy regimens under College of American Pathologists-accredited Clinical Laboratory Improvement Amendment-certified laboratory protocols. The validated assay provides the opportunity to identify patients with EC who have extreme resistance to neoadjuvant chemoradiotherapy who are resistant to fluorouracil-based neoadjuvant chemoradiotherapy, allowing for more effective treatment planning by clinicians and less toxicity for patients. Keywords: neoadjuvant chemoradiation, immunohistochemistry, predictive test, validation

  3. MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

    International Nuclear Information System (INIS)

    Svoboda, Marek; Sana, Jiri; Fabian, Pavel; Kocakova, Ilona; Gombosova, Jana; Nekvindova, Jana; Radova, Lenka; Vyzula, Rostislav; Slaby, Ondrej

    2012-01-01

    Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients. We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling. Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified. Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established

  4. Effects on quality of life, anti-cancer responses, breast conserving surgery and survival with neoadjuvant docetaxel: a randomised study of sequential weekly versus three-weekly docetaxel following neoadjuvant doxorubicin and cyclophosphamide in women with primary breast cancer

    Directory of Open Access Journals (Sweden)

    Wiseman Janice

    2011-05-01

    Full Text Available Abstract Background Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS, Disease Free Survival (DFS and Overall Survival (OS. Methods Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m2 or four cycles of 3-weekly docetaxel (100 mg/m2. The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed. Results At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%, pathological complete response (20% vs. 27%, and breast-conserving surgery (BCS rates (49% vs. 42%. Disease-free survival and overall survival were similar between treatment groups. Conclusions Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS or survival outcomes in the neoadjuvant setting. Trial registration ISRCTN: ISRCTN09184069

  5. Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zschaeck, Sebastian [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Hofheinz, Frank [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). PET Center, Inst. of Radiopharmaceutical Cancer Research; Zoephel, Klaus; Kotzerke, Joerg [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Carl Gustav Carus, Dresden (Germany). Dept. of Nuclear Medicine; National Center for Tumor Diseases (NCT), Dresden (Germany); Buetof, Rebecca; Schmollack, Julia [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Jentsch, Christina [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Loeck, Steffen; Baumann, Michael; Krause, Mechthild [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Baretton, Gustavo [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Pathology; Weitz, Juergen [German Cancer Consortium (DKTK), Dresden (DE); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Visceral, Thoracic and Vascular Surgery

    2017-10-15

    Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of {sup 18}F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis. This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUV{sub max}, SUV{sub mean}) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis. Increased FDG uptake, measured in terms of SUV{sub mean} in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUV{sub max} and SUV{sub mean} in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUV{sub max} and SUV{sub mean} in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011). FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization. (orig.)

  6. Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

    Science.gov (United States)

    Vetterlein, Malte W; Wankowicz, Stephanie A M; Seisen, Thomas; Lander, Richard; Löppenberg, Björn; Chun, Felix K-H; Menon, Mani; Sun, Maxine; Barletta, Justine A; Choueiri, Toni K; Bellmunt, Joaquim; Trinh, Quoc-Dien; Preston, Mark A

    2017-11-15

    Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [Pchemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society. © 2017 American Cancer Society.

  7. Correlation between Tumor-Infiltrating Lymphocytes and Pathological Response in Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy in H. Adam Malik General Hospital

    Directory of Open Access Journals (Sweden)

    Kamal Basri Siregar

    2017-08-01

    Full Text Available Background: Tumor-infiltrating lymphocytes (TILs are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value, particularly in triple-negative and human epidermal growth factor receptor-2-positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy, and there is a strong correlation with pathologically complete response. In this study, we analyzed whether changes in TILs take place after neoadjuvant therapy and if they correlate with pathological response to treatment. Patients and Methods: We retrospectively analyzed the specimen slides from the Department of Anatomic Pathology of H. Adam Malik General Hospital during 2011–2015. We identified 51 patients fulfilling the inclusion criteria of this study. The histological sections had already been evaluated by hematoxylin and eosin slides. They were reassessed by our pathologist for the percentage of intratumoral and stromal TILs. The correlation with pathological response of the tumor after neoadjuvant therapy was also studied in these patients. Each case was also defined as high- or low-TIL breast cancer adopting previously validated cutoffs. Results: The mean age of the 51 patients was 49.22 years. The most frequent type of breast cancer histology was invasive ductal breast carcinoma in 49 (96% patients, and there were 2 (4% patients with lobular carcinoma. The histopathological grading for high TILs was grade 1 in 5 patients, grade 2 in 15 patients, and grade 3 in 3 patients. High TILs that had a pathologically complete response were found in 47.8% of patients, and low TILs were found in 28.8%. There was no significant correlation between TILs and pathological response in patients with neoadjuvant chemotherapy (p = 0.157. Conclusions: This research has not been able to demonstrate a significant correlation between TILs and

  8. Restaging oesophageal cancer after neoadjuvant therapy with {sup 18}F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery

    Energy Technology Data Exchange (ETDEWEB)

    Findlay, John M. [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Churchill Hospital, NIHR Oxford Biomedical Research Centre, Oxford (United Kingdom); Gillies, Richard S.; Maynard, Nicholas D. [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Franklin, James M.; Teoh, Eugene J.; Gleeson, Fergus V.; Bradley, Kevin M. [Churchill Hospital, Department of Nuclear Medicine, Oxford (United Kingdom); Jones, Greg E. [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Royal Berkshire Hospital, Reading (United Kingdom); Di Carlo, Sara [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Queen' s Medical Centre, Nottingham (United Kingdom); Middleton, Mark R. [Churchill Hospital, NIHR Oxford Biomedical Research Centre, Oxford (United Kingdom)

    2016-10-15

    It is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk. This was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by {sup 18}F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014). Three hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91 %) and PET-CT in 17 (6.07 %). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1 %). PET-CT was more sensitive than CT (p = 0.005, McNemar's test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0 %; both risk factors), medium (22.4 %; either), and low risk (3.87 %; neither) groups (p < 0.001). Decision theory supported restaging PET-CT. PET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply. (orig.)

  9. Restaging oesophageal cancer after neoadjuvant therapy with "1"8F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery

    International Nuclear Information System (INIS)

    Findlay, John M.; Gillies, Richard S.; Maynard, Nicholas D.; Franklin, James M.; Teoh, Eugene J.; Gleeson, Fergus V.; Bradley, Kevin M.; Jones, Greg E.; Di Carlo, Sara; Middleton, Mark R.

    2016-01-01

    It is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk. This was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by "1"8F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014). Three hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91 %) and PET-CT in 17 (6.07 %). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1 %). PET-CT was more sensitive than CT (p = 0.005, McNemar's test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0 %; both risk factors), medium (22.4 %; either), and low risk (3.87 %; neither) groups (p < 0.001). Decision theory supported restaging PET-CT. PET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply. (orig.)

  10. Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection

    NARCIS (Netherlands)

    van Rijk, Maartje C.; Nieweg, Omgo E.; Rutgers, Emiel J. T.; Oldenburg, Hester S. A.; Valdés Olmos, Renato; Hoefnagel, Cornelis A.; Kroon, Bin B. R.

    2006-01-01

    BACKGROUND: Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy,

  11. Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features.

    Directory of Open Access Journals (Sweden)

    Lakshmanan Sannachi

    Full Text Available Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS, textural analysis and molecular features in patients with locally advanced breast cancer.The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR, partial responders (PR, and non-responders (NR. Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times.Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the

  12. Predictive value of PET-CT for pathological response in stages II and III breast cancer patients following neoadjuvant chemotherapy with docetaxel.

    Science.gov (United States)

    García García-Esquinas, Marta A; Arrazola García, Juan; García-Sáenz, José A; Furió-Bacete, V; Fuentes Ferrer, Manuel E; Ortega Candil, Aída; Cabrera Martín, María N; Carreras Delgado, José L

    2014-01-01

    To prospectively study the value of PET-CT with fluorine-18 fluorodeoxyglucose (FDG) to predict neoadjuvant chemotherapy (NAC) response of locoregional disease of stages II and III breast cancer patients. A written informed consent and approval were obtained from the Ethics Committee. PET-CT accuracy in the prediction of pathologic complete response (pCR) after NAC was studied in primary tumors and lymph node metastasis in 43 women (mean age: 50 years: range: 27-71 years) with histologically proven breast cancer between December 2009 and January 2011. PET-CT was performed at baseline and after NAC. SUV(max) percentage changes (ΔSUV(max)) were compared with pathology findings at surgery. Receiver-operator characteristic (ROC) analysis was used to discriminate between locoregional pCR and non-pCR. In patients not achieving pCR, it was investigated if ΔSUV(max) could accurately identify the residual cancer burden (RCB) classes: RCB-I (minimal residual disease (MRD)), RCB-II (moderate RD), and RCB-III (extensive RD). pCR was obtained in 11 patients (25.6%). Residual disease was found in 32 patients (74.4%): 16 (37.2%) RCB-I, 15 (35.6%) RCB-II and 2 (4.7%) RCB-III. Sensitivity, specificity, and accuracy to predict pCR were 90.9%, 90.6%, and 90.7%, respectively. Specificity was 94.1% in the identification of a subset of patients who had either pCR or MRD. Accuracy of ΔSUV(max) in the locoregional disease of stages II and III breast cancer patients after NAC is high for the identification of pCR cases. Its specificity is potentially sufficient to identify a subgroup of patients who could be managed with conservative surgery. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  13. A systematic review of optimal treatment strategies for localized Ewing's sarcoma of bone after neo-adjuvant chemotherapy.

    Science.gov (United States)

    Werier, Joel; Yao, Xiaomei; Caudrelier, Jean-Michel; Di Primio, Gina; Ghert, Michelle; Gupta, Abha A; Kandel, Rita; Verma, Shailendra

    2016-03-01

    To perform a systematic review to investigate the optimal treatment strategy among the options of surgery alone, radiotherapy (RT) alone, and the combination of RT plus surgery in the management of localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy. MEDLINE and EMBASE (1999 to February 2015), the Cochrane Library, and relevant conferences were searched. Two systematic reviews and eight full texts met the pre-planned study selection criteria. When RT was compared with surgery, a meta-analysis combining two papers showed that surgery resulted in a higher event-free survival (EFS) than RT in any location (HR = 1.50, 95% CI 1.12-2.00; p = 0.007). However another paper did not find a statistically significant difference in patients with pelvic disease, and no papers identified a significant difference in overall survival. When surgery plus RT was compared with surgery alone, a meta-analysis did not demonstrate a statistically significant difference for EFS between the two groups (HR = 1.21, 95% CI 0.90-1.63). Both surgical morbidities and radiation toxicities were reported. The existing evidence is based on very low aggregate quality as assessed by the GRADE approach. In patients with localized Ewing's sarcoma, either surgery alone (if complete surgical excision with clear margin can be achieved) or RT alone may be a reasonable treatment option. The optimal local treatment for an individual patient should be decided through consideration of patient characteristics, the potential benefit and harm of the treatment options, and patient preference. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. FIGO Stage IIIB squamous cell carcinoma of the uterine cervix: natural history, treatment results, and prognostic factors

    International Nuclear Information System (INIS)

    Eifel, Patricia J.; Logsdon, Mark D.

    1996-01-01

    Purpose: To define patient, tumor, and treatment factors that influence the outcome of patients with FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix. Materials and Methods: The hospital and radiotherapy records of 1007 consecutive patients treated between 1960 and 1989 for FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix were reviewed retrospectively. All patients were treated with radiation therapy (RT) either with curative intent (903 patients) or to palliate symptoms (104 patients). Patients who were selected for palliative treatment usually had a combination of adverse characteristics including massive tumor with bilateral pelvic wall fixation, hydronephrosis, bulky adenopathy, pathologic evidence of extrapelvic disease, and poor performance status. 64 (7%) of 903 patients failed to complete planned curative RT either because of progressive disease, complications, or poor compliance. Of 903 patients treated with curative intent, 319 (35%) were treated with external beam radiotherapy (EBRT) alone and 586 (65%) were treated with a combination of EBRT and intracavitary irradiation (ICRT). EBRT was usually delivered using 18-25 MV photons and ICRT was administered with Fletcher-Suit-Delclos applicators. Treatment philosophies evolved during the study period with greater emphasis placed on EBRT between 1966 and 1979 (52% treated with EBRT alone) compared with the other study years (15% treated with EBRT alone). 206 patients received investigational treatments including neutrons (69 pts), hyperbaric oxygen (66 pts), concurrent chemotherapy (29 pts), or neoadjuvant chemotherapy (42 pts). 875 patients have been followed until death. Median follow up for surviving patients is 171 months with only 9 surviving patients followed for 10%, or hgb < 10 gm% before treatment or at any time during radiotherapy. DSS was significantly better for patients whose treatment included ICRT (43% vs 21%; P< 0.0001). Also, patients who received

  15. Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype.

    Science.gov (United States)

    Williamson, Jeremy Stuart; Jones, Huw Geraint; Williams, Namor; Griffiths, Anthony Paul; Jenkins, Gareth; Beynon, John; Harris, Dean Anthony

    2017-05-15

    To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer. Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed. There were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival ( P CIMP status was significantly associated with KRAS mutation ( P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant ( P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced "T" stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence. We report a novel

  16. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

    Science.gov (United States)

    Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

    1998-01-01

    The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

  17. Predictive value of BRCA1/2 mRNA expression for response to neoadjuvant chemotherapy in BRCA-negative breast cancers.

    Science.gov (United States)

    Xu, Ye; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2018-01-01

    It is well known that BRCA1 and BRCA2 play a central role in DNA repair, but the relationship between BRCA1 and BRCA2 mRNA expression and response to neoadjuvant chemotherapy in sporadic breast cancer patients has not been well established. Here, we investigate the association between BRCA1 or BRCA2 mRNA expression levels and pathological response in 674 BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant chemotherapy. BRCA1 and BRCA2 mRNA expression were assessed using quantitative real-time polymerase chain reaction in core biopsy breast cancer tissue obtained prior to the initiation of neoadjuvant chemotherapy. A total 129 patients (19.1%) achieved pathological complete response (pCR) after neoadjuvant chemotherapy. Among patients treated with anthracycline-based chemotherapy (n = 531), BRCA1 mRNA low expression patients had a significantly higher pCR rate than intermediate or high BRCA1 mRNA expression groups (24.6% vs 16.8% or 14.0%, P = .031) and retained borderline significance (OR = 1.54, 95% CI = 0.93-2.56, P = .094) in multivariate analysis. Among the 129 patients who received a taxane-based regimen, pCR rate showed no differences in BRCA1 low, intermediate, and high mRNA level subgroups (19.6%, 26.8% and 21.4%, respectively; P = .71). BRCA2 mRNA level was not associated with pCR rate in the anthracyline-based treated subgroup (P = .60) or the taxane-based regimen subgroup (P = .82). Taken together, our findings suggested that BRCA1 mRNA expression could be used as a predictive marker in BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant anthracycline-based treatment. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Zinser-Sierra Juan

    2009-07-01

    Full Text Available Abstract Background Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC, 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh after neoadjuvant chemotherapy (NCT in patients with LABC. Methods One hundred twelve patients with LABC (stage IIB-IIIB were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC, or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC IV in four 21-day courses followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg, and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR in the breast was 42% (95% CI, 33.2–50.5% and, 29.5% (95% CI, 21.4–37.5% if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016. The 5-year disease-free survival (DFS was 76.9% (95% CI, 68.2–84.7%. No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04. Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%. The toxicity profile was acceptable. Conclusion This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

  19. Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

    International Nuclear Information System (INIS)

    Oberholzer, Katja; Menig, Matthias; Kreft, Andreas; Schneider, Astrid; Junginger, Theodor; Heintz, Achim; Kreitner, Karl-Friedrich; Hötker, Andreas M.; Hansen, Torsten; Düber, Christoph; Schmidberger, Heinz

    2012-01-01

    Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p ≤ 0.001). Positive resection margins (ypCRM ≤ 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p ≤ 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

  20. Staging and treatment of ovarian carcinoma

    International Nuclear Information System (INIS)

    De Palo, G.; Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan

    1989-01-01

    The staging and treatment of ovarian cancer is reviewed with special attention to developments during the last decade. Pathways of spread, presurgical and surgical staging are described and discussed, as are the biologic characters of the different histologic subtypes. Principles of surgery, endoperitoneal and external radiotherapy, single-drug and multiple-drug systemic chemotherapy (therapeutic and adjuvant), intraperitoneal chemotherapy, second-line chemotherapy, hormone therapy and the use of biologic response modifiers are reported and discussed with background of recent clinical trials. It is concluded that considerable progress has been made concerning diagnosis, staging and treatment of ovarian cancer. The proportion of cases in advanced stages has thus decreased and the survival rate increased. However, it is also obvious that the long-term prognosis for patients with advanced disease has not significantly improved over the last 10 years, despite introduction of multiple-drug regimens with high initial response rates. Ovarian cancer remains the most important gynecologic cause of death in the Western countries. (orig.)

  1. Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study.

    Directory of Open Access Journals (Sweden)

    Wolfgang Hilbe

    Full Text Available Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles.Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2 and docetaxel (75 mg/m2 d1 q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly. The primary endpoint was radiological response according to RECIST.40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95% underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months.Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected.EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.

  2. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial

    NARCIS (Netherlands)

    Verleye, Leen; Ottevanger, Petronella B.; Kristensen, Gunnar B.; Ehlen, Tom; Johnson, Nick; van der Burg, Maria E. L.; Reed, Nick S.; Verheijen, René H. M.; Gaarenstroom, Katja N.; Mosgaard, Berit; Seoane, Jose M.; van der Velden, Jacobus; Lotocki, Robert; van der Graaf, Winette; Penninckx, Björn; Coens, Corneel; Stuart, Gavin; Vergote, Ignace

    2011-01-01

    To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant

  3. Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score

    International Nuclear Information System (INIS)

    Huang, Eugene H.; Strom, Eric A.; Perkins, George H.; Oh, Julia L.; Chen, Allen M.; Meric-Bernstam, Funda; Hunt, Kelly K.; Sahin, Aysegul A.; Hortobagyi, Gabriel N.; Buchholz, Thomas A.

    2006-01-01

    Purpose: We previously developed a prognostic index that stratified patients treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy into groups with different risks for local-regional recurrence (LRR). The purpose of this study was to compare the rates of LRR as a function of prognostic index score for patients treated with BCT or mastectomy plus radiation after neoadjuvant chemotherapy. Methods and Materials: We retrospectively analyzed 815 patients treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were assigned an index score from 0 to 4 and given 1 point for the presence of each factor: clinical N2 to N3 disease, lymphovascular invasion, pathologic size >2 cm, and multifocal residual disease. Results: The 10-year LRR rates were very low and similar between the mastectomy and BCT groups for patients with an index score of 0 or 1. For patients with a score of 2, LRR trended lower for those treated with mastectomy vs. BCT (12% vs. 28%, p = 0.28). For patients with a score of 3 to 4, LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs. 61%, p = 0.009). Conclusions: This analysis suggests that BCT can provide excellent local-regional treatment for the vast majority of patients after neoadjuvant chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT and was <20% with mastectomy. If these findings are confirmed in larger randomized studies, the prognostic index may be useful in helping to select the type of surgical treatment for patients treated with neoadjuvant chemotherapy, surgery, and radiation

  4. Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction – a prospective cohort pilot study within a randomized clinical trial

    International Nuclear Information System (INIS)

    Lund, Mikael; Alexandersson von Döbeln, Gabriella; Nilsson, Magnus; Winter, Reidar; Lundell, Lars; Tsai, Jon A; Kalman, Sigridur

    2015-01-01

    Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. 40 patients participated (chemoradiotherapy, n = 17; chemotherapy, n = 23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p = 0.02, p = 0.01, and p = 0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p = 0.09 and p = 0.09). NT-proBNP increased following chemoradiotherapy (p = 0.05) but not after chemotherapy (p > 0.99), and there was a trend towards an interaction effect (p = 0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p = 0.03) and was more pronounced after

  5. Systemic therapy for HER2-positive early-stage breast cancer.

    Science.gov (United States)

    Mathew, Aju; Romond, Edward H

    The advent of the targeted monoclonal antbody trastuzumab for treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer marked a revolution in the understanding and management of mammary carcinoma and, in practice, separated this subtype from other kinds of primary breast malignancy. Long term follow-up from the initial large adjuvant trials continue to show remarkably positive results. Currently, at least four additional agents targeting this receptor, using different and complementary mechanisms of action compared with trastuzumab, have been incorporated into clinical trials. The small molecule tyrosine kinase inhibitors lapatinib and neratinib, in addition to the antibody pertuzumab and the antibody-drug conjugate trastuzumab-ematansine, have shown efficacy in metastatic breast cancer and are being evaluated both in neoadjuvant and adjuvant trials for early stage disease. The cytotoxic chemotherapy regimens used in combination with these agents also are evolving and different therapeutic approaches are emerging for patients depending on their relative level of risk from their cancers, thus moving clinical management toward individualized therapy. Much has been learned about managing the toxicities of treatment and pre-operative approaches have provided a means of assessing the sensitivity of individual patients' cancers to specific treatment regimens. This review traces the development of these studies and focuses on improvements in adjuvant and neoadjuvant therapy for patients with HER2-positive disease whose prognosis has changed in the last decade from dire to favorable. A path forward has been set by which the goal of cure is attainable for almost all patients faced with this aggressive form of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Preoperative axillary lymph node staging by ultrasound-guided cytology using a four-level sonographic score

    International Nuclear Information System (INIS)

    De Coninck, Caroline; Noël, Jean-Christophe; Boutemy, Rachel; Simon, Philippe

    2016-01-01

    The staging of axillary lymph nodes is critical to the management and prognosis of breast cancer, the most frequent cancer in females. Neoadjuvant therapy and lymph node dissection are recommended when malignant cells invade the lymph nodes. Therefore the pre-operative examination of these lymph nodes is crucial to treatment. In this study, we examined the effectiveness of cytology through ultrasound-guided fine needle aspiration (USG-FNA) and ultrasound (US) imaging using an established classification system in correctly identifying lymph node status compared to the final histological results after surgery. Cytology by USG-FNA and US classification were found to be promising methods of axillary lymph node staging. US and CB offer minimally invasive techniques to pre-operatively examine these lymph nodes in patients with primary breast cancer

  7. [Utilization of multimodal therapy concepts in stomach carcinoma in Germany].

    Science.gov (United States)

    Bösing, N M; Heise, J W; Röher, H D

    2000-01-01

    In view of disappointing results after surgery alone multimodal therapeutic regimes are used to improve long-term prognosis in locally advanced gastric carcinomas. In presence of many reports about encouraging results ("down staging", improved R0-resection rates) but simultaneously missing evidence of efficiency of neoadjuvant therapies in respect to long-term survival (large randomized multicenter trials do not exist until today) and the herewith related uncertainties, we started an inquiry among many surgical units with the intention to evaluate the clinical practice of multimodal treatment for gastric cancer patients in Germany today. In a questionnaire (3/99) we asked among 97 surgical units (41 university hospitals, 56 big community hospitals) in Germany for the management of gastric cancer patients with special interest to practice and state of adjuvant and neoadjuvant therapeutic strategies. Further we analyzed all resected gastric cancer patients (1986-1995) without neoadjuvant treatment in advanced stage of disease (pT3/4NxMx; stage III/IV (UICC'92) in respect to R0-resection rate and long-term prognosis (Kaplan-Meier). Overall feedback amounted to 78% (76/97) and was higher in university hospitals (90%) than in big community hospitals (70%). Today, neoadjuvant therapies are of more interest than adjuvant therapeutic regimes. But also neoadjuvant therapy is only used in 32% as a rule (in 16% with, in 16% without study conditions). 25% of all surgical units do not employ any neoadjuvant therapy in locally advanced gastric cancer until today. In all other surgical units neoadjuvant treatment is performed more individually and sporadically (43%) only in some patients. Neoadjuvant therapies are practiced by haematooncologists in 50%, gastroenterologists in 32% and surgeons in 27%. The predominant neoadjuvant therapeutic strategy is chemotherapy alone (84%). Many surgical units in Germany are interested to participate in a multicenter trial with more interest

  8. Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Pickles, Martin D.; Manton, David J.; Lowry, Martin; Turnbull, Lindsay W.

    2009-01-01

    The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

  9. Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Pickles, Martin D. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.pickles@hull.ac.uk; Manton, David J. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: d.j.manton@hull.ac.uk; Lowry, Martin [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.lowry@hull.ac.uk; Turnbull, Lindsay W. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: l.w.turnbull@hull.ac.uk

    2009-09-15

    The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

  10. Evaluation of tolerability and efficacy of incorporating carboplatin in neoadjuvant anthracycline and taxane based therapy in a BRCA1 enriched triple-negative breast cancer cohort.

    Science.gov (United States)

    Sella, Tal; Gal Yam, Einav Nili; Levanon, Keren; Rotenberg, Tal Shapira; Gadot, Moran; Kuchuk, Iryna; Molho, Rinat Bernstein; Itai, Amit; Modiano, Tami Mekel; Gold, Raya; Kaufman, Bella; Shimon, Shani Paluch

    2018-05-22

    The addition of carboplatin (Cb) to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) has been demonstrated to improve pathologic complete response (pCR) at the expense of increased toxicity. We aimed to evaluate the effectiveness and tolerability of dose-dense anthracycline & cyclophosphamide (ddAC) followed by weekly paclitaxel (wT) in combination with weekly Cb. Retrospective data was collected on patients with clinical stage I-III TNBC treated with neoadjuvant ddAC-wTCb (four cycles of ddA 60 mg/m 2 and ddC 600 mg/m 2 every 2 weeks followed by 12 cycles of wT 80 mg/m 2 with Cb AUC 1.5). Indices of tolerability and pCR were evaluated and compared to a historical cohort (n = 76) treated with ddAC-T. A secondary objective was to evaluate the rates of pCR by BRCA status. For 43 eligible patients, mean age was 41.5 years, 51% had clinical stage II disease, 81.4% were clinically node positive and 32.6% carried a deleterious BRCA1 mutation. Only 35% completed all scheduled doses of chemotherapy. Grade 3/4 neutropenia was observed in 42.5% of patients. Overall pCR was 51.2%; 44.8% in BRCA wild-type compared to 64.3% in BRCA-associated TNBC (p = 0.232). pCR rates with ddAC-wTCb were similar to historic institutional rates with ddAC-T (51.2% vs. 51.3%, p = 0.987) and were comparable when stratified by BRCA status. In pooled multivariate analysis, only BRCA status (HR 4.00, 95%CI 1.65-9.75, p = 0.002) was significantly associated with pCR. Neoadjuvant ddAC-wTCb is less tolerable in clinical practice compared to most clinical trials, with a pCR comparable to historic rates using non-platinum regimen. The role of Cb in neoadjuvant chemotherapy for BRCA mutated TNBC remains uncertain. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Chen L

    2017-05-01

    chemotherapy was not an independent prognostic factor for DFS and OS. However, median DFS and median OS were worse for high neutrophil values than for low neutrophil values (median DFS: 21.03 and 26.87 months, respectively, P=0.396; median OS: 24.43 and 29.37 months, respectively, P=0.534; for low lymphocyte values than for high lymphocyte values before neoadjuvant chemotherapy (median DFS: 22.33 and 26.87 months, respectively, P=0.624; median OS: 26.37 and 27.93 months, respectively, P=0.584. Nevertheless, patients with low NLR had better 1-year, 3-year, and 5-year DFS and OS rates.Conclusion: NLR may serve as a cheap and convenient prognostic indicator in gastric carcinoma patients receiving SOX or XELOX neoadjuvant chemotherapy. Low NLR may help the doctors to take efficient treatment measures for gastric cancer. Keywords: advanced gastric cancer, neoadjuvant chemotherapy, disease-free survival, overall survival, neutrophil-to-lymphocyte ratio

  12. Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer. Comparison of two different definitions of PSA failure

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Sasaki, Yoshihide; Mizowaki, Takashi

    2006-01-01

    We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the ''nadir plus 2'' definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial. (author)

  13. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial.

    Science.gov (United States)

    Bear, Harry D; Tang, Gong; Rastogi, Priya; Geyer, Charles E; Liu, Qing; Robidoux, André; Baez-Diaz, Luis; Brufsky, Adam M; Mehta, Rita S; Fehrenbacher, Louis; Young, James A; Senecal, Francis M; Gaur, Rakesh; Margolese, Richard G; Adams, Paul T; Gross, Howard M; Costantino, Joseph P; Paik, Soonmyung; Swain, Sandra M; Mamounas, Eleftherios P; Wolmark, Norman

    2015-09-01

    NSABP B-40 was a 3 × 2 factorial trial testing whether adding capecitabine or gemcitabine to docetaxel followed by doxorubicin plus cyclophosphamide neoadjuvant chemotherapy would improve outcomes in women with operable, HER2-negative breast cancer and whether adding neoadjuvant plus adjuvant bevacizumab to neoadjuvant chemotherapy regimens would also improve outcomes. As reported previously, addition of neoadjuvant bevacizumab increased the proportion of patients achieving a pathological complete response, which was the primary endpoint. We present secondary patient outcomes, including disease-free survival, a specified endpoint by protocol, and data for distant recurrence-free interval, and overall survival, which were not prespecified endpoints but were collected prospectively. In this randomised controlled trial (NSABP B-40), we enrolled women aged 18 years or older, with operable, HER2-non-amplified invasive adenocarcinoma of the breast, 2 cm or greater in diameter by palpation, clinical stage T1c-3, cN0, cN1, or cN2a, without metastatic disease and diagnosed by core needle biopsy. Patients received one of three docetaxel-based neoadjuvant regimens for four cycles: docetaxel alone (100 mg/m(2)) with addition of capecitabine (825 mg/m(2) oral twice daily days 1-14, 75 mg/m(2) docetaxel) or with addition of gemcitabine (1000 mg/m(2) days 1 and 8 intravenously, 75 mg/m(2) docetaxel), all followed by neoadjuvant doxorubicin and cyclophosphamide (60 mg/m(2) and 600 mg/m(2) intravenously) every 3 weeks for four cycles. Those randomly assigned to bevacizumab groups were to receive bevacizumab (15 mg/kg, every 3 weeks for six cycles) with neoadjuvant chemotherapy and postoperatively for ten doses. Randomisation was done (1:1:1:1:1:1) via a biased-coin minimisation procedure to balance the characteristics with respect to clinical nodal status, clinical tumour size, hormone receptor status, and age. Intent-to-treat analyses were done for disease-free survival and

  14. Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy.

    Science.gov (United States)

    Bouzón, Alberto; Acea, Benigno; García, Alejandra; Iglesias, Ángela; Mosquera, Joaquín; Santiago, Paz; Seoane, Teresa

    2016-01-01

    Breast conservative surgery after neoadjuvant chemotherapy intends to remove any residual tumor with negative margins. The purpose of this study was to analyze the preoperative clinical-pathological factors influencing the margin status after conservative surgery in breast cancer patients receiving neoadjuvant chemotherapy. A retrospective study of 91 breast cancer patients undergoing neoadjuvant chemotherapy (92 breast lesions) during the period 2006 to 2013. A Cox regression analysis to identify baseline tumor characteristics associated with positive margins after breast conservative surgery was performed. Of all cases, 71 tumors were initially treated with conservative surgery after neoadjuvant chemotherapy. Pathologic exam revealed positive margins in 16 of the 71 cases (22.5%). The incidence of positive margins was significantly higher in cancers with initial size >5cm (P=.021), in cancers with low tumor grade (P=.031), and in patients with hormone receptor-positive cancer (P=.006). After a median follow-up of 45.2 months, 7 patients of the 71 treated with conservative surgery had disease recurrence (9.8%). There was no significant difference in terms of disease-free survival according to the margin status (P=.596). A baseline tumor size >5cm, low tumor grade and hormone receptor-positive status increase the risk for surgical margin involvement in breast conservative surgery after neoadjuvant chemotherapy. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer.

    Science.gov (United States)

    Lee, Hee Yeon; Jung, Ji-Han; Cho, Hyun-Min; Kim, Sung Hwan; Lee, Kang-Moon; Kim, Hyung-Jin; Lee, Jong Hoon; Shim, Byoung Yong

    2015-10-01

    We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045). GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT.

  16. Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy

    International Nuclear Information System (INIS)

    Krainick-Strobel, Ute E; Lichtenegger, Werner; Wallwiener, Diethelm; Tulusan, Augustinus H; Jänicke, Fritz; Bastert, Gunther; Kiesel, Ludwig; Wackwitz, Birgit; Paepke, Stefan

    2008-01-01

    In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established. This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed. Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates

  17. The Prognostic Value of {sup 18}F-FDG PET/CT for Early Recurrence in Operable Breast Cancer: Comparison with TNM Stage

    Energy Technology Data Exchange (ETDEWEB)

    O, Joo Hyun; Choi, Woo Hee; Han, Eun Ji; Choi, Eunkyoung; Chae, Byung Joo; Park, Yonggyu; Kim, Sung Hoon [The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    2013-12-15

    We evaluated whether the maximum standardized uptake values (SUV{sub max}) of primary tumor from the initial staging by {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) of patients with breast cancer could identify patients at risk for early recurrence within 2 years, particularly in comparison to the American Joint Committee on Cancer (AJCC) stage. We reviewed the staging {sup 18}F-FDG PET/CT images of patients with primary breast cancer and their medical records. The SUV{sub max} of the primary tumor was measured. The presence or absence of FDG uptake in the axillary lymph node (ALN) was also assessed. The patient's pathologic primary tumor stage (pT), pathologic regional lymph node stage (pN), stage grouping, age, estrogen receptor (ER) and progesterone receptor (PR) status, and neoadjuvant chemotherapy history were evaluated with the FDG uptake parameters for recurrence within 2 years following the end of first-line therapy. Recurrence within 2 years was present in 9.1%(n =40) out of the 441 patients assessed. The FDG uptake in ALN, pT, pN, stage grouping and neoadjuvant chemotherapy history were prognostic for early recurrence, while primary tumor SUV{sub max}, age, and ER or PR status were not significant on logistic regression. On multivariate analysis, only the stage grouping (odds ratio 2.79; 95 % CI 1.73, 4.48; p <0.0001) and neoadjuvant chemotherapy history (odds ratio 2.70; 95 % CI 1.22, 5.98; p =0.0141) could identify patients at increased risk for recurrence within 2 years. Primary tumor FDG uptake measured by SUV{sub max}, and visual assessment of FDG uptake in the ALN in the initial staging PET/CT of patients with breast cancer may not have additional prognostic value compared with the AJCC stage grouping for early recurrence.

  18. Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment F-18-FDG PET/CT Imaging

    NARCIS (Netherlands)

    Beukinga, Roelof J.; Hulshoff, Jan B.; van Dijk, Lisanne V.; Muijs, Christina T.; Burgerhof, Johannes G. M.; Kats-Ugurlu, Gursah; Slart, Riemer H. J. A.; Slump, Cornelis H.; Mul, Veronique E. M.; Plukker, John Th. M.

    Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUVmax in F-18-FDG PET/ CT imaging. To improve the prediction of

  19. Pathological response for neoadjuvant chemotherapy in locally ...

    African Journals Online (AJOL)

    Background: Breast cancer is the leading cancer in Sudanese females. Objectives: This study was done to evaluate the clinical response to neoadjuvant chemotherapy for patients treated at National Cancer Institute (NCI) and to compare it with the published literature. Methods: This is a retrospective study conducted in ...

  20. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Narang, Amol K. [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Department of Hematology Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Reese, Jennifer B. [Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Gearhart, Susan L. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Azad, Nolifer S. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chan, June; Olsen, Leah [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Efron, Jonathan E. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Lawrence, Theodore S.; Ben-Josef, Edgar [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  1. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (−9.50, P=.0024) but returned to baseline 1 month after the end of treatment (−0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are

  2. Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Icro Meattini

    2014-01-01

    Full Text Available Neoadjuvant chemotherapy (NAC is widely used in locally advanced breast cancer (BC treatment. The role of postmastectomy radiotherapy (PMRT after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6% underwent PMRT and 72 cases (42.4% did not receive radiation. At a median follow-up period of 7.7 years (range 2–16 for the whole cohort, median time to locoregional recurrence (LRR was 3.3 years (range 0.7–12.4. The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P=0.035, extracapsular extension (HR 2.18, 1.37–3.46; P=0.009, and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P=0.003. Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P=0.015. Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy.

  3. Local staging of sigmoid colon cancer using MRI

    DEFF Research Database (Denmark)

    Dam, Claus; Lindebjerg, Jan; Jakobsen, Anders

    2017-01-01

    BACKGROUND: An accurate radiological staging of colon cancer is crucial to select patients who may benefit from neoadjuvant chemotherapy. PURPOSE: To evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) in identifying locally advanced sigmoid colon cancer, poor...... prognostic factors, and the inter-observer variation of the tumor apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). MATERIAL AND METHODS: Using 1.5 T MRI with high resolution T2-weighted (T2W) imaging, DWI, and no contrast enhancement, 35 patients with sigmoid colon cancer were...... the measured mean ADC values were below 1.0 × 10(-3) mm(2)/s with an intra-class correlation coefficient in T3cd-T4 tumors of 0.85. CONCLUSION: Preoperative MRI can identify locally advanced sigmoid colon cancer and has potential as the imaging of choice to select patients for neoadjuvant chemotherapy. Initial...

  4. Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations

    Energy Technology Data Exchange (ETDEWEB)

    Bedair, Reem; Manavaki, Roido; Gill, Andrew B.; Abeyakoon, Oshaani; Gilbert, Fiona J. [University of Cambridge, Department of Radiology, School of Clinical Medicine, Cambridge (United Kingdom); Priest, Andrew N.; Patterson, Andrew J. [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); McLean, Mary A. [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); University of Cambridge, Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Graves, Martin J. [University of Cambridge, Department of Radiology, School of Clinical Medicine, Cambridge (United Kingdom); Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); Griffiths, John R. [University of Cambridge, Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Cambridge (United Kingdom)

    2017-07-15

    To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm{sup 2}). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D{sub t}), vascular fraction (Florin), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. (orig.)

  5. Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations

    International Nuclear Information System (INIS)

    Bedair, Reem; Manavaki, Roido; Gill, Andrew B.; Abeyakoon, Oshaani; Gilbert, Fiona J.; Priest, Andrew N.; Patterson, Andrew J.; McLean, Mary A.; Graves, Martin J.; Griffiths, John R.

    2017-01-01

    To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm"2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D_t), vascular fraction (Florin), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. (orig.)

  6. Non-randomized clinical study comparing chemotherapy plus radiotherapy with radiotherapy alone in neoadjuvant therapy for oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kayahara, Hiroaki; Okuda, Mamiko; Terakado, Nagaaki; Shintani, Satoru; Hamakawa, Hiroyuki [Ehime Univ., Shigenobu (Japan). School of Medicine

    2002-06-01

    Neoadjuvant therapy plays an important role for organ preservation and survival rate in the treatment of oral cancer. We clinically compared the effect of neoadjuvant radiotherapy and chemoradiotherapy in patients with oral cancer. We retrospectively examined 47 patients diagnosed with oral squamous cell carcinoma who underwent neoadjuvant therapy followed by curative surgery in the oral and maxillofacial surgery department of Ehime University Hospital. We divided them into two groups: radiotherapy alone (24 cases) and chemoradiotherapy (23 cases). The patients in the radiotherapy group underwent irradiation of 32.6{+-}5.0 Gy (mean {+-}SD). The patients in the chemoradiotherapy group received a low-dose fraction of cisplatin (8 mg/mm{sup 2}/day, 5 days a week; total dose: 139.4{+-}67.1 mg) and 5-fluorouracil (300 mg/mm{sup 2}/day, 5 days a week; total dose: 5,900{+-}1,839.8 mg) combined with simultaneous irradiation of 31.0{+-}3.2 Gy. None of the 24 patients had a complete response to radiotherapy alone and 12 (50%) had a partial response. Six (26%) of the 23 patients had a complete response to chemoradiotherapy and 12 (52%) had a partial response. The primary control rate (82.6%) to chemoradiotherapy was higher than that (67.5%) to radiotherapy alone although no significant difference was found. The 5-year survival rate was 64.3% in the radiotherapy group and 62.8% in the chemoradiotherapy group. The findings of the present study suggest that while the combination of radiation and cisplatin/5-fluorouracil in neoadjuvant therapy for oral cancer may not bring a significant benefit to improve survival rate, the primary local control rate is improved in comparison with radiotherapy alone. (author)

  7. Cross-sectional imaging to evaluate the extent of regional nodal disease in breast cancer patients undergoing neoadjuvant systemic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Tara L., E-mail: anderson.tara@mayo.edu [Mayo Clinic, Department of Radiology, 200 First Street SW, Rochester, MN, 55905 (United States); Glazebrook, Katrina N., E-mail: glazebrook.katrina@mayo.edu [Mayo Clinic, Department of Radiology, 200 First Street SW, Rochester, MN, 55905 (United States); Murphy, Brittany L., E-mail: murphy.brittany@mayo.edu [Mayo Clinic, Department of Surgery, 200 First Street SW, Rochester, MN, 55905 (United States); Viers, Lyndsay D., E-mail: viers.lyndsay@mayo.edu [Mayo Clinic, Department of Radiology, 200 First Street SW, Rochester, MN, 55905 (United States); Hieken, Tina J, E-mail: hieken.tina@mayo.edu [Mayo Clinic, Department of Surgery, 200 First Street SW, Rochester, MN, 55905 (United States)

    2017-04-15

    Purpose: Cross-sectional imaging often is performed in breast cancer patients undergoing neoadjuvant systemic therapy (NST) and may identify level III axillary and extra-axillary nodal disease. Our aim was to investigate associations of radiologic nodal staging with pathological N (pN) stage at operation and to explore how this might aid surgical and radiotherapy treatment planning. Materials and methods: With IRB approval, we reviewed pre-treatment breast MRI, PET/CT, and CT imaging and clinicopathologic data on 348 breast cancer patients with imaging available for review undergoing NST followed by operation at our institution 1/2008-9/2013. We defined abnormal lymph node findings on MRI, CT, and PET/CT to include cortical thickening, FDG-avidity and loss of fatty hilum. Patients were assigned a radiologic nodal (rN) stage based on imaging findings. Statistical analysis was performed using JMP 10.1 software Results: Pre-NST imaging included axillary ultrasound in 338 patients (97%), breast MRI in 305 (88%) and PET/CT or CT in 215 (62%). 213 patients (61%) were biopsy-proven axillary lymph node-positive (LN+) pre-treatment. cT stage was T1 in 9%, T2 in 49%, T3 in 29%, T4 in 12%; median tumor size was 4 cm. Pre-treatment rN stage across all the patients was rN0 in 86 (25%), rN1 in 173 (50%), and rN3 in 89 (26%). rN3 disease included level III axillary, supraclavicular and suspicious internal mammary lymph nodes in 47 (53%), 32 (37%) and 45 (52%), respectively. Of patients LN+ at diagnosis, 78 (37%) were rN3. After NST, 162 patients (47%) were node-positive at operation with a median (mean) of 3 (5.9 ± 0.4) positive lymph nodes including 128 of 213 (60%) LN+ at diagnosis. Pre-NST rN stage correlated with the likelihood and extent of axillary disease at operation, p = 0.002. Fifty four of 89 rN3 patients (61%) were node-positive at operation with a median (mean) of 5 (8 ± 1) positive nodes. rN3 patients had larger nodal metastases (median 9 vs 6 mm) and more

  8. Cross-sectional imaging to evaluate the extent of regional nodal disease in breast cancer patients undergoing neoadjuvant systemic therapy

    International Nuclear Information System (INIS)

    Anderson, Tara L.; Glazebrook, Katrina N.; Murphy, Brittany L.; Viers, Lyndsay D.; Hieken, Tina J

    2017-01-01

    Purpose: Cross-sectional imaging often is performed in breast cancer patients undergoing neoadjuvant systemic therapy (NST) and may identify level III axillary and extra-axillary nodal disease. Our aim was to investigate associations of radiologic nodal staging with pathological N (pN) stage at operation and to explore how this might aid surgical and radiotherapy treatment planning. Materials and methods: With IRB approval, we reviewed pre-treatment breast MRI, PET/CT, and CT imaging and clinicopathologic data on 348 breast cancer patients with imaging available for review undergoing NST followed by operation at our institution 1/2008-9/2013. We defined abnormal lymph node findings on MRI, CT, and PET/CT to include cortical thickening, FDG-avidity and loss of fatty hilum. Patients were assigned a radiologic nodal (rN) stage based on imaging findings. Statistical analysis was performed using JMP 10.1 software Results: Pre-NST imaging included axillary ultrasound in 338 patients (97%), breast MRI in 305 (88%) and PET/CT or CT in 215 (62%). 213 patients (61%) were biopsy-proven axillary lymph node-positive (LN+) pre-treatment. cT stage was T1 in 9%, T2 in 49%, T3 in 29%, T4 in 12%; median tumor size was 4 cm. Pre-treatment rN stage across all the patients was rN0 in 86 (25%), rN1 in 173 (50%), and rN3 in 89 (26%). rN3 disease included level III axillary, supraclavicular and suspicious internal mammary lymph nodes in 47 (53%), 32 (37%) and 45 (52%), respectively. Of patients LN+ at diagnosis, 78 (37%) were rN3. After NST, 162 patients (47%) were node-positive at operation with a median (mean) of 3 (5.9 ± 0.4) positive lymph nodes including 128 of 213 (60%) LN+ at diagnosis. Pre-NST rN stage correlated with the likelihood and extent of axillary disease at operation, p = 0.002. Fifty four of 89 rN3 patients (61%) were node-positive at operation with a median (mean) of 5 (8 ± 1) positive nodes. rN3 patients had larger nodal metastases (median 9 vs 6 mm) and more

  9. Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

    Science.gov (United States)

    van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

    2006-04-01

    Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

  10. Rectal Tumour Staging with Endorectal Ultrasound: Is There Any Difference between Western and Eastern European Countries?

    Science.gov (United States)

    Fábián, Anna; Bor, Renáta; Farkas, Klaudia; Bálint, Anita; Milassin, Ágnes; Rutka, Mariann; Tiszlavicz, László; Wittmann, Tibor; Nagy, Ferenc; Molnár, Tamás; Szepes, Zoltán

    2016-01-01

    Background. Rectal tumour management depends highly on locoregional extension. Rectal endoscopic ultrasound (ERUS) is a good alternative to computed tomography and magnetic resonance imaging. However, in Hungary only a small amount of rectal tumours is examined with ERUS. Methods. Our retrospective study (2006-2012) evaluates the diagnostic accuracy of ERUS and compares the results, the first data from Central Europe, with those from Western Europe. The effect of neoadjuvant therapy, rectal probe type, and investigator's experience were also assessed. Results. 311 of the 647 ERUS assessed locoregional extension. Histological comparison was available in 177 cases: 67 patients underwent surgery alone; 110 received neoadjuvant chemoradiotherapy (CRT); ERUS preceded CRT in 77 and followed it in 33 patients. T-staging was accurate in 72% of primarily operated patients. N-staging was less accurate (62%). CRT impaired staging accuracy (64% and 59% for T- and N-staging). Rigid probes were more accurate (79%). At least 30 examinations are needed to master the technique. Conclusions. The sensitivity of ERUS complies with the literature. ERUS is easy to learn and more accurate in early stages but unnecessary for restaging after CRT. Staging accuracy is similar in Western and Central Europe, although the number of examinations should be increased.

  11. Percentage of pathological complete response in patients with rectal cancer that received neoadjuvant therapy with chemotherapy and radiotherapy at the Servicio de Radioterapia from Hospital Mexico, in the period from January 2009 to December 2013

    International Nuclear Information System (INIS)

    Lopez Mena, Stephanie

    2015-01-01

    Percentage of pathologic complete response is determined in patients with rectal cancer, treated with neoadjuvant chemotherapy and radiotherapy, in the Servicio de Radioterapia from Hospital Mexico, in the period between January 2009 and December 2013. Tumor histology is determined. The distance of the tumor is identified with respect to the anal margin. The correlation between the TNM staging and the response received in this type of neoadjuvant therapy is described. Radiotherapy dose used in each case is described. Different schemes of chemotherapy used are characterized. The acute side effects most common are determined in the study population [es

  12. Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

    Science.gov (United States)

    Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

    2017-06-01

    We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

  13. Gastric cancer : staging, treatment, and surgical quality assurance

    NARCIS (Netherlands)

    Dikken, Johannes Leen

    2012-01-01

    Research described in this thesis focuses on several aspects of gastric cancer care: staging and prognostication, multimodality treatment, and surgical quality assurance. PART I - STAGING AND PROGNOSTICATION Cancer staging is one of the fundamental activities in oncology.6,7 For over 50 years, the

  14. Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Rivera Franco, Monica M; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

    2016-01-01

    PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR ( P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens ( P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

  15. Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Monica M. Rivera Franco

    2016-01-01

    Full Text Available PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR. Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5% and overexpression (≥5%. Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2. However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02. Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B overexpression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

  16. Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study.

    Science.gov (United States)

    Noordman, Bo Jan; Spaander, Manon C W; Valkema, Roelf; Wijnhoven, Bas P L; van Berge Henegouwen, Mark I; Shapiro, Joël; Biermann, Katharina; van der Gaast, Ate; van Hillegersberg, Richard; Hulshof, Maarten C C M; Krishnadath, Kausilia K; Lagarde, Sjoerd M; Nieuwenhuijzen, Grard A P; Oostenbrug, Liekele E; Siersema, Peter D; Schoon, Erik J; Sosef, Meindert N; Steyerberg, Ewout W; van Lanschot, J Jan B

    2018-05-31

    After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m 2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during

  17. Pretreatment Diffusion-Weighted MRI Can Predict the Response to Neoadjuvant Chemotherapy in Patients with Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Guo-Yi Zhang

    2015-01-01

    Full Text Available Purpose. To explore the potential of diffusion-weighted (DW magnetic resonance imaging (MRI using apparent diffusion coefficient (ADC for predicting the response to neoadjuvant chemotherapy in nasopharyngeal carcinoma (NPC. Methods and Materials. Ninety-two consecutive patients with NPC who underwent three cycles of neoadjuvant chemotherapy were retrospectively analyzed. DW and anatomical MRI were performed before and after neoadjuvant chemotherapy prior to radiotherapy. Pretreatment ADCs and percentage increases in ADC after chemotherapy were calculated for the primary lesions and metastatic adenopathies. Receiver operating characteristic curve analysis was used to select optimal pretreatment ADCs. Results. Pretreatment mean ADCs were significantly lower for responders than for nonresponders (primary lesions, P=0.012; metastatic adenopathies, P=0.013. Mean percentage increases in ADC were higher for responders than for nonresponders (primary lesions, P=0.008; metastatic adenopathies, P<0.001. The optimal pretreatment primary lesion and metastatic adenopathy ADCs for differentiating responders from nonresponders were 0.897 × 10−3 mm2/sec and 1.031 × 10−3 mm2/sec, respectively. Conclusions. NPC patients with low pretreatment ADCs tend to respond better to neoadjuvant chemotherapy. Pretreatment ADCs could be used as a new pretreatment imaging biomarker of response to neoadjuvant chemotherapy.

  18. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study

    International Nuclear Information System (INIS)

    Velenik, Vaneja; Omejc, Mirko; Ocvirk, Janja; Music, Maja; Bracko, Matej; Anderluh, Franc; Oblak, Irena; Edhemovic, Ibrahim; Brecelj, Erik; Kropivnik, Mateja

    2011-01-01

    Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m 2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower

  19. Topoisomerase II alpha and TLE3 as predictive markers of response to anthracycline and taxane-containing regimens for neoadjuvant chemotherapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Susini T

    2014-11-01

    -positive. Conclusion: TOP2A and TLE3 showed a correlation with response to neoadjuvant chemotherapy. While TOP2A is a well-known marker of response to anthracyclines-based chemotherapy, TLE3 is a new putative predictor of response to taxanes. Data from the current study suggest that TOP2A and TLE3 warrant further investigation in a larger series as predictors of response to neoadjuvant chemotherapy for locally advanced breast carcinoma. Keywords: breast carcinoma, advanced stage disease, immunohistochemical markers

  20. Depression related to (neo)adjuvant hormonal therapy for prostate cancer

    International Nuclear Information System (INIS)

    Tol-Geerdink, Julia J. van; Leer, Jan Willem; Lin, Emile N.J.T. van; Schimmel, Erik C.; Stalmeier, Peep F.M.

    2011-01-01

    Background: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. Methods: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. Results: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small. Conclusions: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

  1. Retrospective case-control study of surgical treatment of stage IB-IIA cervical carcinomas after neoadjuvant radiotherapy

    International Nuclear Information System (INIS)

    Cigriejiene, V. M.; Kajenas, S.; Balnys, M.; Mikuckaite, L.

    2004-01-01

    To evaluate if preoperative radiotherapy influences course of operation (radical hysterectomy and lymphadenectomy) and postoperative period in series of stage IB-IIA cervical carcinomas. Retrospective comparative study was performed. During the study we analyzed 101 case histories of patients who underwent radical type II hysterectomy with lymphadenectomy in Kaunas University of Medicine Hospital and Kaunas Hospital of Oncology between 1995 and 2002. Mean operation time was shorter, hemoglobin and hematocrit values after operation were better, stay in hospital was longer, demand for narcotic analgetics was bigger, function of ovaries was maintained more rarely (p 0.05). In our study, preoperative radiotherapy did not seem to complicate course of radical hysterectomy. (author)

  2. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  3. Mucinous Adenocarcinoma Arising in Chronic Perianal Fistula: Good Results with Neoadjuvant Chemoradiotherapy Followed by Surgery

    Directory of Open Access Journals (Sweden)

    Marisa D. Santos

    2014-01-01

    Full Text Available Chronic perianal fistulas are a common clinical condition. However, their evolution to adenocarcinoma is rare. We report the case of a 48-year-old man with perianal chronic fistulas, who developed two perianal ulcerated lesions near the external orifices of the fistulas, which extended proximally as a pararectal tumor. No intestinal lesion was seen at endoscopic examination. Histopathological biopsy indicated mucinous adenocarcinoma. Staging was performed by pelvic magnetic resonance imaging (MRI and thoracoabdominal CT scan. The patient underwent a laparoscopic colostomy followed by neoadjuvant chemoradiotherapy and then laparoscopic abdominoperineal resection followed by adjuvant therapy. We have seen a favorable outcome with no recurrence at 3 years of follow-up.

  4. Staging laparoscopy improves treatment decision-making for advanced gastric cancer.

    Science.gov (United States)

    Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

    2016-02-07

    To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ(2) test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P advanced GC and decrease unnecessary exploratory laparotomy.

  5. Effects of an immuno-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy.

    Science.gov (United States)

    Aiko, S; Kumano, I; Yamanaka, N; Tsujimoto, H; Takahata, R; Maehara, T

    2012-02-01

    -adsorbent test values were significantly higher in group 2 patients. Oxidative index was significantly suppressed in group 1 compared to group 3. No significant intergroup differences were observed with regard to morbidity after surgery. Although the baseline levels of immunological function might have been different because of less-advanced cancer stages in group 3, neoadjuvant therapy significantly affected several immunological parameters. Preoperative administration of an immuno-enhanced diet did not significantly prevent neoadjuvant therapy-induced immunological deterioration prior to esophageal cancer surgery. Patients with esophageal cancer had elevated levels of oxidant and antioxidant activities before surgery, which were transiently decreased early after surgery. Although the underlying mechanisms for these perioperative changes are unclear, this study showed that an immuno-enhanced diet containing several antioxidants may reduce oxidative stress following esophageal cancer surgery. After these mechanisms are studied further, oxidative stress control may become another tool for perioperative management to reduce morbidity after esophageal cancer surgery. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  6. Could semiquantitative FDG analysis add information to the prognosis in patients with stage II/III breast cancer undergoing neoadjuvant treatment?

    Energy Technology Data Exchange (ETDEWEB)

    Evangelista, Laura; Cervino, Anna Rita [Veneto Institute of Oncology IOV - IRCCS, Radiotherapy and Nuclear Medicine Unit, Padua (Italy); Ghiotto, Cristina; Guarneri, Valentina; Conte, Pierfranco [Veneto Institute of Oncology IOV - IRCCS, Medical Oncology 2 Unit, Padua (Italy); Saibene, Tania; Michieletto, Silvia; Fernando, Bozza [Veneto Institute of Oncology IOV - IRCCS, Breast Unit, Padua (Italy); Orvieto, Enrico [University Hospital of Padua, Department of Pathology, Padua (Italy)

    2015-10-15

    We investigated whether maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and whole-body (WB) SUVmax, WB MTV and WB TLG measured by {sup 18}F-FDG PET/CT could improve prognostic stratification in patients with stage II/III breast cancer (BC). We prospectively enrolled 99 consecutive women (median age 50 years, range 27 - 77 years) with pathologically proven stage II/III BC who underwent pretreatment FDG PET/CT. WB SUVmax, WB MTV and WB TLG were measured in all malignant lesions. Survival was analysed using the Kaplan-Meier method. Cox proportional hazards models were constructed to test for relationships among WB SUVmax, WB MTV, WB TLG, and overall survival (OS) and disease-free survival (DFS), after adjustment for age, and histopathological and immunohistochemical features (oestrogen/progesterone and HER2 expression, proliferation index and grade). The median values of WB SUVmax, WB MTV and WB TLG were 16.2 (range 1.5 - 33.1), 14 cm{sup 3} (range 0.03 - 708.6 cm{sup 3}) and 62.5 (0.06 - 3869.4), respectively. All WB semiquantitative values were higher in patients with higher TNM stage, although not significantly (all p > 0.05). The median follow-up for surviving patients was 30 months, with a range of 13 - 45 months. Both PFS and OS of patients with low WB SUVmax, WB MTV and WB TLG were longer than that of patients with high WB values for progression, although not statistically significant. However, stratifying the patients in accordance with the stage of disease, both PFS and OS were significantly lower in patients with high WB TLG and stage III than in patients with stage II (p < 0.05). In multivariate analyses, WB MTV and WB TLG were independent prognostic factors for PFS (hazard ratio 1.004, 95 % confidence interval 1.002 - 1.006, p < 0.001, and hazard ratio 1.001, 95 % confidence interval 1.000 - 1.001, p = 0.011, respectively). The addition of WB TLG to clinical data may provide a more detailed

  7. Multimodal imaging evaluation in staging of rectal cancer

    Science.gov (United States)

    Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Yong Yeon; Kang, Heoung-Keun

    2014-01-01

    Rectal cancer is a common cancer and a major cause of mortality in Western countries. Accurate staging is essential for determining the optimal treatment strategies and planning appropriate surgical procedures to control rectal cancer. Endorectal ultrasonography (EUS) is suitable for assessing the extent of tumor invasion, particularly in early-stage or superficial rectal cancer cases. In advanced cases with distant metastases, computed tomography (CT) is the primary approach used to evaluate the disease. Magnetic resonance imaging (MRI) is often used to assess preoperative staging and the circumferential resection margin involvement, which assists in evaluating a patient’s risk of recurrence and their optimal therapeutic strategy. Positron emission tomography (PET)-CT may be useful in detecting occult synchronous tumors or metastases at the time of initial presentation. Restaging after neoadjuvant chemoradiotherapy (CRT) remains a challenge with all modalities because it is difficult to reliably differentiate between the tumor mass and other radiation-induced changes in the images. EUS does not appear to have a useful role in post-therapeutic response assessments. Although CT is most commonly used to evaluate treatment responses, its utility for identifying and following-up metastatic lesions is limited. Preoperative high-resolution MRI in combination with diffusion-weighted imaging, and/or PET-CT could provide valuable prognostic information for rectal cancer patients with locally advanced disease receiving preoperative CRT. Based on these results, we conclude that a combination of multimodal imaging methods should be used to precisely assess the restaging of rectal cancer following CRT. PMID:24764662

  8. Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Zong, Yu; Wu, Jiayi; Shen, Kunwei

    2017-03-07

    The value of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in neoadjuvant systemic therapy for breast cancer remains uncertain. Both electronic databases and proceedings of oncologic meetings were included in systematic literature search. Pooled rates of pathological complete response (pCR), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model to determine the effect of neoadjuvant nab-paclitaxel. Twenty-one studies with 2357 patients were included, 3 of which were randomized clinical trials. The aggregate pCR(ypT0/is ypN0) rate was 32% (95% CI 25-38%) in unselected breast cancer patients and variated in different subtypes. Within randomized clinical trials, the probability of achieving pCR was significantly higher in the nab-paclitaxel group than in the conventional taxanes group (OR = 1.383, 95%CI 1.141-1.676, p = 0.001). For non-hematological toxic effect, any grade and grade 3-4 peripheral sensory neuropathy occurred more frequently with nab-paclitaxel compared to paclitaxel (any grade, OR = 2.090, 95%CI 1.016-4.302, p = 0.045; grade3-4, OR = 3.766, 95%CI 2.324-6.100, p < 0.001). Hypersensitivity was more common with paclitaxel than nab-paclitaxel at any grade and grade 3-4. nab-paclitaxel is an effective cytotoxic drug in neoadjuvant treatment of breast cancer, especially for aggressive tumors in terms of pCR. Exchange of nab-paclitaxel for conventional taxanes could significantly improve pCR rate with reasonable toxicities.

  9. Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study.

    Science.gov (United States)

    Tan, A R; Johannes, H; Rastogi, P; Jacobs, S A; Robidoux, A; Flynn, P J; Thirlwell, M P; Fehrenbacher, L; Stella, P J; Goel, R; Julian, T B; Provencher, L; Bury, M J; Bhatt, K; Geyer, C E; Swain, S M; Mamounas, E P; Wolmark, N

    2015-01-01

    This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA-C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.

  10. Three-stage treatment protocol for recalcitrant distal femoral nonunion.

    Science.gov (United States)

    Ma, Ching-Hou; Chiu, Yen-Chun; Tu, Yuan-Kun; Yen, Cheng-Yo; Wu, Chin-Hsien

    2017-04-01

    In this study, we proposed a three-stage treatment protocol for recalcitrant distal femoral nonunion and aimed to analyze the clinical results. We retrospective reviewed 12 consecutive patients with recalcitrant distal femoral nonunion undergoing our three-stage treatment protocol from January 2010 to December 2014 in our institute. The three-stage treatment protocol comprised debridement of the nonunion site, lengthening to eliminate leg length discrepancy, deformity correction, stabilization with a locked plate, filling of the defect with cement spacer for inducing membrane formation, and bone reconstruction using a cancellous bone autograft (Masquelet technique) or free vascularized fibular bone graft. The bone union time, wound complication, lower limbs alignment, amount of lengthening, knee range of motion, and functional outcomes were evaluated. Osseous union with angular deformity lengthening was 5.88 cm (range 3.5-12 cm). Excellent or good outcomes were obtained in 9 patients. Although the current study involved only a small number of patients and the intervention comprised three stages, we believe that such a protocol may be a valuable alternative for the treatment of recalcitrant distal femoral nonunion.

  11. The assessment of breast cancer response to neoadjuvant chemotherapy: comparison of magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Park, Jeong Seon; Moon, Woo Kyung; Lyou, Chae Yeon; Cho, Nariya; Kang, Keon Wook; Chung, June-Key

    2011-01-01

    Background: Neoadjuvant chemotherapy for locally advanced breast cancer is a widely accepted treatment. For assessment of the tumor response after chemotherapy, both magnetic resonance imaging (MRI) and 18 F-fluorodeoxyglucose positron emission tomography (PET) are promising methods. Purpose: To retrospectively compare MRI and PET in the assessment of tumor response to neoadjuvant chemotherapy for primary breast cancer with the pathologic response as the reference standard. Material and Methods: Between August 2006 and May 2008, 32 women with breast cancer underwent concurrent MRI and PET before and after neoadjuvant chemotherapy. For response assessment, we calculated the changes in the maximum diameters of the tumor (ΔDmax) on MRI, and the changes in the standard uptake values (ΔSUV) on PET. The correlation between the ΔDmax and ΔSUV was analyzed using Pearson's correlation coefficient. The correspondence rates between each imaging modality and pathologic assessment were calculated. For prediction of the pathologic complete response (pCR), the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analyzed using the McNemar test. Results: The pathologic assessment of tumor response to neoadjuvant chemotherapy identified eight complete responses (25.0%), 10 partial responses (31.2%), and 14 non-responses (43.8%). The change in size on MRI was moderately correlated with the change in SUV on PET (r = 0.574, p = 0.001). The correspondence rate of response assessment was 75.0% (24/32) between MRI and pathologic response and 53.1% (17/32) between PET and pathologic response. For the pCR, specificity (95.8% vs. 62.5%) and PPV (83.3% vs. 47.1%) were statistically higher on MRI than PET (p < 0.05), while sensitivity (100.0% vs. 62.5%) and NPV (100.0% vs. 88.5%) on PET tended to be higher than MRI. Conclusion: Before and after neoadjuvant chemotherapy for breast cancer, the ΔDmax of MRI correlated moderately with the

  12. Two-stage thermal/nonthermal waste treatment process

    International Nuclear Information System (INIS)

    Rosocha, L.A.; Anderson, G.K.; Coogan, J.J.; Kang, M.; Tennant, R.A.; Wantuck, P.J.

    1993-01-01

    An innovative waste treatment technology is being developed in Los Alamos to address the destruction of hazardous organic wastes. The technology described in this report uses two stages: a packed bed reactor (PBR) in the first stage to volatilize and/or combust liquid organics and a silent discharge plasma (SDP) reactor to remove entrained hazardous compounds in the off-gas to even lower levels. We have constructed pre-pilot-scale PBR-SDP apparatus and tested the two stages separately and in combined modes. These tests are described in the report

  13. Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR.

    Science.gov (United States)

    Generali, Daniele; Corona, Silvia Paola; Pusztai, Lajos; Rouzier, Roman; Allevi, Giovanni; Aguggini, Sergio; Milani, Manuela; Strina, Carla; Frati, Albane

    2018-03-01

    Neoadjuvant hormonal therapy is generally considered a valid option for hormone receptor positive breast cancer (BC) patients who are unfit for chemotherapy or surgery. Whilst numerous studies analyzed efficacy of neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor positive patients, there is a lack of research looking at the usefulness of a preoperative combinatorial approach of CT and HT in this patient subgroup. Using a predictive model previously described in the literature, developed to analyze the probability of benefit from preoperative chemotherapy, we were able to compare pathological complete response (pCR) rates expected with the use of CT alone with the pCR rates reported in a population of 192 patients treated with the combination of tamoxifen plus anthracycline-based CT at Cremona Hospital between 2003 and 2006. Even with a relatively small patient population, this approach provided insightful information for the selection of hormone receptor positive BC patients most likely to benefit from the use of preoperative HT and CT in combination. Whilst no statistically significant benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy in the entire population, or in any of the molecular stratification subgroups, the analysis of the calibration curve showed that a combinatorial approach may improve pCR in patients with luminal B tumors. More specific trials should be designed to confirm our initial results. To the best of our knowledge, this is the first report investigating the efficacy of the combination of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.

  14. Inclusion of PET-CT into planning of primary or neoadjuvant chemoradiotherapy of esophageal cancer improves prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Metzger, Jan-Christopher; Vaupel, Peter; Schmidberger, Heinz; Mayer, Arnulf [University Medical Center, Department of Radiation Oncology and Radiotherapy, Mainz (Germany); Wollschlaeger, Daniel [University Medical Center, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Mainz (Germany); Miederer, Matthias [University Medical Center, Department of Nuclear Medicine, Mainz (Germany); Moehler, Markus [University Medical Center, Department of Internal Medicine I, Mainz (Germany)

    2017-10-15

    PET-CT is widely used for both the staging and planning of primary or neoadjuvant chemoradiotherapy for esophageal cancer. Inclusion of PET-CT information into radiotherapy planning often leads to substantial modifications of the target volume. In the case of detection of distant metastases, it may also result in a switch to a palliative treatment approach. This spares patients from therapy-related toxicities that provide no clinical benefit. However, due to a lack of studies, it is currently unclear whether the advantages of PET-CT also translate into a measurable improvement in patient survival. A retrospective analysis assessed the survival data of 145 patients with esophageal carcinoma stages I (eight patients; 5%), II (45; 31%), III (79; 55%), IV (8; 5%) and unknown (5; 4%). Patients were treated between 1999 and 2014 either with primary chemoradiation (n = 101) or neoadjuvant chemoradiation at the Department of Radiation Oncology, University Medical Center Mainz, followed by transabdominal or transthoracic tumor resection (n = 44). Of the 145 patients, 64 (44%) had undergone PET-CT. Univariate analysis showed the use of PET-CT to be associated with significantly longer local recurrence-free survival (p = 0.006) and tended to translate into a measurable improvement of overall survival (p = 0.071). Since more patients underwent surgery in the group planned using PET-CT (20% vs. 44%; p = 0.002), we carried out a multivariate Cox regression analysis to adjust for this possible confounding factor. Surgery (p = 0.042; HR 0.55; 95% confidence interval: 0.31-0.98) as well as the use of PET-CT (p = 0.048; HR 0.60; 95% confidence interval: 0.36-0.99) nearly halved the risk of local recurrence. It was only in the group of patients with PET-CT that a trend towards a shorter overall survival was evident in lymph node-positive patients (p = 0.16), whereas nodal stage did not impact on survival in patients staged without PET-CT (p = 0.97). To the best of our knowledge these

  15. Noninvasive assessment of response to neoadjuvant chemotherapy in osteosarcoma of long bones with diffusion-weighted imaging: an initial in vivo study.

    Directory of Open Access Journals (Sweden)

    Cheng-Sheng Wang

    Full Text Available OBJECTIVES: The purpose of our study is to investigate whether diffusion-weighted imaging (DWI is useful for monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of long bones. MATERIALS AND METHODS: Conventional magnetic resonance imaging (MRI and DWI were obtained from 35 patients with histologically proven osteosarcomas. MR examinations were performed in all patients before and after 4 courses of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC were measured. The degree of tumor necrosis was assessed macroscopically and histologically by two experienced pathologists after operation. Student's t test was performed for testing changes in ADC value. Pearson's correlation coefficient was used to estimate the correlation between necrosis rate and post- neoadjuvant chemotherapy ADC values. P<0.05 was considered to denote a significant difference. RESULTS: The difference of the whole osteosarcoma between pre- neoadjuvant chemotherapy ADC value (1.24±0.17×10(-3 mm(2/s and post- (1.93±0.39×10(-3 mm(2/s was significant difference (P<0.01. Regarding in patients with good response, the post- neoadjuvant chemotherapy values were significantly higher than the pre- neoadjuvant chemotherapy values (P<0.01. The post- neoadjuvant chemotherapy ADC value in patients with good response was higher than that of poor response (t = 8.995, P<0.01. The differences in post- neoadjuvant chemotherapy ADC between viable (1.03±0.17×10(-3 mm(2/s and necrotic (2.38±0.25×10(-3 mm(2/s tumor was highly significant (t = 23.905, P<0.01. A positive correlation between necrosis rates and the whole tumor ADC values (r = 0.769, P<0.01 was noted, but necrosis rates were not correlated with the ADC values of necrotic (r = -0.191, P = 0.272 and viable tumor areas (r = 0.292, P = 0.089. CONCLUSIONS: DWI can identify residual viable tumor tissues and tumor necrosis induced by neoadjuvant

  16. Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5.

    Science.gov (United States)

    Smith, John W; Buyse, Marc E; Rastogi, Priya; Geyer, Charles E; Jacobs, Samuel A; Patocskai, Erica J; Robidoux, André; Conlin, Alison K; Ansari, Bilal; Keogh, George P; Stella, Philip J; Gross, Howard M; Lord, Raymond S; Polikoff, Jonathan A; Mauquoi, Celine; Mamounas, Eleftherios P; Swain, Sandra M; Wolmark, Norman

    2017-02-01

    The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m 2 ) followed by 4 cycles of docetaxel (100 mg/m 2 ). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Yoon, Sam S.; Duda, Dan G.; Karl, Daniel L.; Kim, Tae-Min; Kambadakone, Avinash R.; Chen, Yen-Lin; Rothrock, Courtney; Rosenberg, Andrew E.; Nielsen, G. Petur; Kirsch, David G.; Choy, Edwin; Harmon, David C.; Hornicek, Francis J.; Dreyfuss, Jonathan; Ancukiewicz, Marek

    2011-01-01

    Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with ≥5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ≥80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62–72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants

  18. Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

    Science.gov (United States)

    Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas

    2017-01-01

    Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative [28% (95% CI 14.8–45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6–16.3); (OR = 3.9 [CI = 1.5–10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS [HR = 0.62 (CI = 0.3–1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials. PMID:28940389

  19. Two stage treatment of dairy effluent using immobilized Chlorella pyrenoidosa

    Science.gov (United States)

    2013-01-01

    Background Dairy effluents contains high organic load and unscrupulous discharge of these effluents into aquatic bodies is a matter of serious concern besides deteriorating their water quality. Whilst physico-chemical treatment is the common mode of treatment, immobilized microalgae can be potentially employed to treat high organic content which offer numerous benefits along with waste water treatment. Methods A novel low cost two stage treatment was employed for the complete treatment of dairy effluent. The first stage consists of treating the diary effluent in a photobioreactor (1 L) using immobilized Chlorella pyrenoidosa while the second stage involves a two column sand bed filtration technique. Results Whilst NH4+-N was completely removed, a 98% removal of PO43--P was achieved within 96 h of two stage purification processes. The filtrate was tested for toxicity and no mortality was observed in the zebra fish which was used as a model at the end of 96 h bioassay. Moreover, a significant decrease in biological oxygen demand and chemical oxygen demand was achieved by this novel method. Also the biomass separated was tested as a biofertilizer to the rice seeds and a 30% increase in terms of length of root and shoot was observed after the addition of biomass to the rice plants. Conclusions We conclude that the two stage treatment of dairy effluent is highly effective in removal of BOD and COD besides nutrients like nitrates and phosphates. The treatment also helps in discharging treated waste water safely into the receiving water bodies since it is non toxic for aquatic life. Further, the algal biomass separated after first stage of treatment was highly capable of increasing the growth of rice plants because of nitrogen fixation ability of the green alga and offers a great potential as a biofertilizer. PMID:24355316

  20. Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis.

    Science.gov (United States)

    Passot, Guillaume; Vaudoyer, Delphine; Cotte, Eddy; You, Benoit; Isaac, Sylvie; Noël Gilly, François; Mohamed, Faheez; Glehen, Olivier

    2012-07-01

    The objective of this retrospective study was to evaluate the influence of neoadjuvant systemic chemotherapy on patients with colorectal carcinomatosis before a curative procedure. Peritoneal carcinomatosis (PC) from colorectal cancer may be treated with a curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The role of perioperative systemic chemotherapy for this particular metastatic disease remains unclear. One hundred twenty patients with PC from colorectal cancer were consecutively treated by 131 procedures combining CRS with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on data from previous explorative surgery and/or radiological imaging. Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom 32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19 (21%) developed diseases progression. Response could not be evaluated in 20 patients (22%). On univariate analysis, the use of neoadjuvant systemic chemotherapy had a significant positive prognostic influence (P = 0.042). On multivariate analysis, the completeness of CRS and the use of adjuvant systemic chemotherapy were the only significant prognostic factors (P systemic chemotherapy had no significant prognostic impact with median survival of 31.4 months in patients showing disease progression. In patients with PC from colorectal cancer without extraperitoneal metastases, failure of neoadjuvant systemic chemotherapy should not constitute an absolute contraindication to a curative procedure combining CRS and HIPEC.

  1. Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01)

    NARCIS (Netherlands)

    Charehbili, A.; Hamdy, N. A. T.; Smit, V. T. H. B. M.; Kessels, L.; van Bochove, A.; van Laarhoven, H. W.; Putter, H.; Meershoek-Klein Kranenbarg, E.; van Leeuwen-Stok, A. E.; van der Hoeven, J. J. M.; van de Velde, C. J. H.; Nortier, J. W. R.; Kroep, J. R.

    2016-01-01

    Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the

  2. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

    Science.gov (United States)

    Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

    2017-04-01

    The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

  3. Self-Expanding Metal Stents Improve Swallowing and Maintain Nutrition During Neoadjuvant Therapy for Esophageal Cancer.

    Science.gov (United States)

    Smith, Zachary L; Gonzaga, Jason E; Haasler, George B; Gore, Elizabeth M; Dua, Kulwinder S

    2017-06-01

    Patients with locally advanced esophageal cancer can have significant dysphagia. Nutritional support during neoadjuvant therapy is often delivered via nasoenteric or percutaneous feeding tubes. These approaches do not allow for per-oral feeding. Evaluate the safety and efficacy of fully covered self-expanding metal esophageal stents for nutritional support during neoadjuvant therapy. This was a pilot, prospective study at a single tertiary center. From March 2012 to May 2013, consecutive patients with esophageal cancer eligible for neoadjuvant therapy were enrolled. Metal stents were placed prior to starting neoadjuvant therapy. Data were collected at baseline and predetermined intervals until an endpoint (surgery or disease progression). Outcomes included dysphagia grade, satisfaction of swallowing score, nutritional status (weight, serum albumin), impact on surgery, and adverse events. Fourteen stents were placed in 12 patients (59.1 ± 9.5 years, 11 men, 1 woman). Dysphagia grade (pre 3.4 ± 0.5 vs post 0.2 ± 0.4, p esophageal cancer, self-expanding metal stents are safe and effective in relieving dysphagia and maintaining nutrition. They allow patients to eat orally, thereby improving patient satisfaction. The presence of an in situ stent did not interfere with surgery.

  4. Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

    Science.gov (United States)

    Wang, Jifei; Sun, Meili; Liu, Dawei; Hu, Xiaoshu; Pui, Margaret H; Meng, Quanfei; Gao, Zhenhua

    2017-08-01

    Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10 -3  mm 2 /s) was significantly ( P  0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.

  5. NeoPalAna: Neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor positive breast cancer

    Science.gov (United States)

    Ma, Cynthia X.; Gao, Feng; Luo, Jingqin; Northfelt, Donald W.; Goetz, Matthew; Forero, Andres; Hoog, Jeremy; Naughton, Michael; Ademuyiwa, Foluso; Suresh, Rama; Anderson, Karen S.; Margenthaler, Julie; Aft, Rebecca; Hobday, Timothy; Moynihan, Timothy; Gillanders, William; Cyr, Amy; Eberlein, Timothy J.; Hieken, Tina; Krontiras, Helen; Guo, Zhanfang; Lee, Michelle V.; Spies, Nicholas C.; Skidmore, Zachary L.; Griffith, Obi L.; Griffith, Malachi; Thomas, Shana; Bumb, Caroline; Vij, Kiran; Bartlett, Cynthia Huang; Koehler, Maria; Al-Kateb, Hussam; Sanati, Souzan; Ellis, Matthew J.

    2017-01-01

    Purpose Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response. Anastrozole was continued until surgery, which occurred 3-5 weeks post palbociclib exposure. Later patients received additional 10-12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression and mutation profiles. The primary endpoint was Complete Cell Cycle Arrest (CCCA: central Ki67<2.7%). Results Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs C1D1 26%, p<0.001). Palbociclib enhanced cell cycle control over anastrozole monotherapy regardless of luminal subtype (A vs B) and PIK3CA status with activity observed across a broad range of clinicopathological and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with non-luminal subtypes and persistent E2F-target gene expression. Conclusions Palbociclib is an active anti-proliferative agent for early-stage breast cancer resistant to anastrozole, however, prolonged administration may be necessary to maintain its effect. PMID:28270497

  6. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer – the RAPIDO trial

    International Nuclear Information System (INIS)

    Nilsson, Per J; Marijnen, Corrie AM; Nagtegaal, Iris D; Wiggers, Theo; Glimelius, Bengt; Etten, Boudewijn van; Hospers, Geke AP; Påhlman, Lars; Velde, Cornelis JH van de; Beets-Tan, Regina GH; Blomqvist, Lennart; Beukema, Jannet C; Kapiteijn, Ellen

    2013-01-01

    Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative

  7. TU-G-BRA-06: PET-Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dalah, E; Tai, A; Oshima, K; Hall, W; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2015-06-15

    Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3) for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment

  8. Clinical efficacy of local targeted chemotherapy for triple-negative breast cancer

    International Nuclear Information System (INIS)

    He, Jinsong; Wang, Xianming; Guan, Hong; Chen, Weicai; Wang, Ming; Wu, Huisheng; Wang, Zun; Zhou, Ruming; Qiu, Shuibo

    2011-01-01

    The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m 2 ]; E: epirubicin [90 mg/m 2 ]; F: 5-fluorouracil [600 mg/m 2 ]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses

  9. Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Arezzo, Alberto, E-mail: alberto.arezzo@unito.it [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy); Arolfo, Simone; Allaix, Marco Ettore [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy); Munoz, Fernando [Radiation Oncology, Department of Oncology, University of Torino, Torino (Italy); Cassoni, Paola [Pathology Unit, Department of Medical Sciences, University of Torino, Torino (Italy); Monagheddu, Chiara [Clinical Epidemiology Unit, Piedmont Reference Centre for Epidemiology and Cancer Prevention, City of Health and Science Hospital of Torino, Torino (Italy); Ricardi, Umberto [Radiation Oncology, Department of Oncology, University of Torino, Torino (Italy); Ciccone, Giovannino [Clinical Epidemiology Unit, Piedmont Reference Centre for Epidemiology and Cancer Prevention, City of Health and Science Hospital of Torino, Torino (Italy); Morino, Mario [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy)

    2015-06-01

    Purpose: This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials: We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. Results: The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. Conclusions: SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous

  10. A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

    Science.gov (United States)

    Alsina, Maria; Rivera, Fernando; Ramos, Francisco Javier; Galán, Maica; López, Rafael; García-Alfonso, Pilar; Alés-Martinez, José Enrique; Queralt, Bernardo; Antón, Antonio; Carrato, Alfredo; Grávalos, Cristina; Méndez-Vidal, Maria José; López, Carlos; de Mena, Inmaculada Ruiz; Tabernero, Josep; Giralt, Jordi; Aranda, Enrique

    2018-02-01

    Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

  11. A complete response to S-1 plus cis-diamminedichloroplatinum in advanced-stage esophageal and gastric adenocarcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Matsuno Yoritaka

    2012-07-01

    Full Text Available Abstract Background Complete remission from advanced-stage synchronous double primary (SDP esophageal and gastric adenocarcinoma by chemotherapy alone is rare. We report a case of advanced-stage SDP esophageal and gastric adenocarcinoma in which a complete response to treatment was obtained with S-1 and cis-diamminedichloroplatinum (CDDP. Case presentation The patient was a 74-year-old man referred to our hospital complaining of dysphagia. Gastrointestinal endoscopy was performed and advanced-stage SDP esophageal and gastric adenocarcinoma diagnosed. Computed tomography revealed multiple regional lymph node metastases in the mediastinum. Neoadjuvant chemotherapy with S-1 and CDDP for advanced esophageal and gastric cancer was planned. An endoscopy following two courses of chemotherapy revealed that the esophageal cancer had been replaced with a normal mucosal lesion and the gastric tumor with a scar lesion; the results of biopsies of both were negative for cancer. Computed tomography revealed that the multiple lymph node metastases had disappeared. We diagnosed a complete response to S-1 and CDDP in advanced-stage SDP esophageal and gastric cancer. The patient is still alive with no signs of recurrence 22 months after the disappearance of the original tumor and metastatic lesions without surgical treatment. Conclusion These results suggest that complete remission from advanced-stage esophageal and gastric cancer can be obtained with chemotherapy with S-1 plus CDDP.

  12. The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery.

    Science.gov (United States)

    Saunders, John H; Bowman, Christopher R; Reece-Smith, Alex M; Pang, Vincent; Dorrington, Matthew S; Mumtaz, Errum; Soomro, Irshad; Kaye, Philip; Madhusudan, Srinivasan; Parsons, Simon L

    2017-06-01

    For patients with operable esophagogastric cancer, peri-operative chemotherapy confers a significant overall survival benefit compared to surgery alone, however only 30-40% of patients demonstrate histopathological response. It is unclear whether those with no neoadjuvant chemotherapy response should go onto receive adjuvant chemotherapy, as no further benefit may be conferred. Esophagogastric cancers were prospectively captured with associated histopathological tumor regression grades following neoadjuvant chemotherapy. This cohort was then interrogated for clinico-pathological and survival outcomes. Following neoadjuvant chemotherapy and surgery, patients with chemotherapy responsive cancers, who were administered adjuvant chemotherapy gained a significant overall survival benefit. Multivariate Cox analysis, demonstrated a final adjusted hazard ratio for adjuvant therapy of 0.509; (95%CI 0.28-0.93); P = 0.028. In contrast, patients with non-responsive tumors, who underwent adjuvant chemotherapy, did not show any survival benefit. Chemotherapy toxicity was prevalent and contributed to only half of patients receiving adjuvant chemotherapy. These results suggest the benefit of the adjuvant portion of chemotherapy is limited to those who demonstrate a histopathological response to neoadjuvant chemotherapy. The administration of the adjuvant portion of chemotherapy to patients without a response to neoadjuvant chemotherapy may not provide any survival benefit, while potentially causing increased morbidity. © 2017 Wiley Periodicals, Inc.

  13. Simulation of Casing Treatments of a Transonic Compressor Stage

    Directory of Open Access Journals (Sweden)

    M. Hembera

    2008-01-01

    Full Text Available This article presents the study of casing treatments on an axial compressor stage for improving stability and enhancing stall margin. So far, many simulations of casing treatments on single rotor or rotor-stator configurations were performed. But as the application of casing treatments in engines will be in a multistage compressor, in this study, the axial slots are applied to a typical transonic first stage of a high-pressure 4.5-stage compressor including an upstream IGV, rotor, and stator. The unsteady simulations are performed with a three-dimensional time accurate Favre-averaged Navier-stokes flow solver. In order to resolve all important flow mechanisms appearing through the use of casing treatments, a computational multiblock grid consisting of approximately 2.4 million nodes was used for the simulations. The configurations include axial slots in 4 different variations with an axial extension ranging into the blade passage of the IGV. Their shape is semicircular with no inclination in circumferential direction. The simulations proved the effectiveness of casing treatments with an upstream stator. However, the results also showed that the slots have to be carefully positioned relative to the stator location.

  14. Neoadjuvant radiation in primary extremity liposarcoma: correlation of MRI features with histopathology

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    Wortman, Jeremy R. [Harvard Medical School, Department of Radiology, Brigham and Women' s Hospital, Boston, MA (United States); Tirumani, Sree Harsha; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H. [Harvard Medical School, Department of Radiology, Brigham and Women' s Hospital, Boston, MA (United States); Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Boston, MA (United States); Tirumani, Harika [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Boston, MA (United States); University of Arkansas Medical Sciences, Department of Radiology, Little Rock, AR (United States); Hornick, Jason L. [Harvard Medical School, Department of Pathology, Brigham and Women' s Hospital, Boston, MA (United States)

    2016-05-15

    To evaluate MRI features of response of primary extremity liposarcoma (LPS) to neoadjuvant radiation therapy (RT) with histopathologic correlation. In this IRB-approved study including 125 patients with extremity LPS treated with neoadjuvant RT from 2000 to 2013, MRI of the primary tumour in 18 patients (5 pleomorphic LPS, 13 myxoid LPS) before and after RT were reviewed by two radiologists by consensus. Histopathology of the surgical specimens was reviewed by a pathologist with expertise in sarcomas. In the pleomorphic LPS cohort, 3/5 tumours increased in size; 3/5 decreased in enhancing component; and 3/5 increased in peritumoral oedema, intratumoral haemorrhage, and necrosis. In the myxoid LPS cohort, 12/13 tumours decreased in size, 8/13 decreased in enhancing component, and 5/13 increased in internal fat following RT. Histopathology showed ≥50 % residual tumour in 1/5 pleomorphic LPS and 2/13 myxoid LPS. Hyalinization/necrosis of ≥75 % was noted in 4/5 pleomorphic LPS and 11/13 myxoid LPS. Cytodifferentiation was noted in 1/5 pleomorphic and 9/13 myxoid LPS. While pleomorphic LPS showed an increase in size, peritumoral oedema, intratumoral haemorrhage, and necrosis on MRI following neoadjuvant RT, myxoid LPS showed a decrease in size and enhancement with an increase in internal fat. (orig.)

  15. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma.

    Science.gov (United States)

    Schmitt, Thomas; Lehner, Burkhard; Kasper, Bernd; Bischof, Marc; Roeder, Falk; Dietrich, Sascha; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G; Mechtersheimer, Gunhild; Wuchter, Patrick; Ho, Anthony D; Egerer, Gerlinde

    2011-12-07

    The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m(2) iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m(2) day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published

  16. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Schmitt Thomas

    2011-12-01

    Full Text Available Abstract Background The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Method Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC] were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m2 iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m2 day 1, pegfilgrastim 6 mg sc day 5, definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Result Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%, 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3, 24% PR (n = 12, 62% SD (n = 31 and 8% PD (n = 4. Local recurrence occurred in 3 subjects (6%. Distant metastasis was observed in 12 patients (24%. Overall survival (OS and disease-free survival (DFS at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50, cardiac toxicity (2/50, and CNS toxicity (4/50 leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. Conclusion The current protocol is feasible for achieving local control rates, as well as OS

  17. Can quantitative contrast-enhanced ultrasonography predict cervical tumor response to neoadjuvant chemotherapy?

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    Peng, Chuan; Liu, Long-Zhong; Zheng, Wei [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China); Xie, Yan-Jun [Department of Gynecology and Obstetrics, Zhongcun Town hospital, 140 Renmin Road, Zhongcun Town, Panyu District, Guangzhou, 511400 (China); Xiong, Yong-Hong; Li, An-Hua [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China); Pei, Xiao-Qing, E-mail: peixq@sysucc.org.cn [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China)

    2016-11-15

    Highlights: • We assessed the clinical value of quantitative CEUS for prediction of cervical tumor perfusion response to NACT. • IMAX, RT, and TTP changed significantly after one NACT cycle. • Pre-treatment IMAX positively correlated with the absolute and percentage changes in all cervical tumor IMAX after NACT. • Pre-treatment IMAX may be predictive of NACT perfusion response in cervical tumor. - Abstract: Objective: To evaluate the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for predicting and assessing cervical tumor response to neoadjuvant chemotherapy (NACT). Methods: Thirty-eight cases with stage IB2 or IIA cervical cancer were studied using CEUS before and after one cycle of NACT. The quantitative CEUS parameters maximum intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (MTT) were compared between cervical tumors and myometrium (reference zone) using Sonoliver software. Absolute and relative changes in quantitative CEUS parameters were also compared among complete response, partial response, and non-responsive groups. Correlations between pre-treatment IMAX and changes in quantitative parameters were assessed after one cycle of NACT. Results: There were significant changes in cervical tumor IMAX (P < 0.001), RT (P < 0.05), and TTP (P < 0.05) after one cycle of NACT. According to the Response Evaluation Criteria In Solid Tumors guidelines, the enrollments were divided into complete response, partial response, stable disease and progressive disease groups. There were no significant differences in quantitative CEUS parameters among complete response, partial response, and non-responsive groups (P > 0.05). In the stable disease group (n = 17), cervical tumor IMAX, RT, and TTP decreased significantly after NACT (P < 0.001). The absolute and percentage changes in IMAX were positively correlated with pre-treatment IMAX in all 38 patients (r = 0.576, P < 0.001 and r = 0.429, P < 0.001). Conclusion

  18. Treatments Results and Prognostic Factors in Locally Advanced Hypopharyngeal Cancer

    International Nuclear Information System (INIS)

    Yoon, Mee-Sun; Chung, Woong-Ki; Ahn, Sung-Ja; Nam, Taek-Keun; Song, Ju-Young; Nah, Byung-Sik; Lim, Sang Cheol; Lee, Joon Kyoo

    2007-01-01

    The purpose of this study is to present the treatment results and to identify possible prognostic indicators in patients with locally advanced hypopharyngeal carcinoma. Materials and Methods: Between October 1985 to December 2000, 90 patients who had locally advanced stage IV hypopharyngeal carcinoma were studied retrospectively. Twelve patients were treated with radiotherapy alone, 65 patients were treated with a combination of chemotherapy and radiotherapy, and 13 patients were treated with surgery and postoperative radiotherapy with or without neoadjuvant chemotherapy. Total radiation dose ranged from 59.0 to 88.2 Gy (median 70 Gy) for radiotherapy alone. Most patients had ciplatin and 5-fluorouracil, and others had cisplatin and peplomycin or vincristin. Median follow-up period was 15 months. Kaplan-Meier method was used for survival rate and Cox proportional hazard model for multivariate analysis of prognostic factors. Results: Overall 3- and 5-year survival rates were 27% and 17%, respectively. The 2-year locoregional control rates were 33% for radiotherapy alone, 32% for combined chemotherapy and radiotherapy, and 81% for combined surgery and radiotherapy (p=0.006). The prognostic factors affecting overall survival were T stage, concurrent chemo radiation and treatment response. Overall 3- and 5-year laryngeal preservation rates in combined chemotherapy and radiotherapy were 26% and 22%, respectively. Of these, the 5-year laryngeal preservation rates were 52% for concurrent chemo radiation group (n=11), and 16% for neoadjuvant chemotherapy and radiotherapy (n=54, p=0.012). Conclusion: Surgery and postoperative radiotherapy showed better results than radiotherapy alone or with chemotherapy. Radiotherapy combined with concurrent chemotherapy is an effective modality to achieve organ preservation in locally advanced hypopharyngeal cancer. Further prospective randomized studies will be required

  19. A retrospective comparative exploratory study on two Methylentetrahydrofolate Reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients

    International Nuclear Information System (INIS)

    Blank, Susanne; Kumar, Rajiv; Ott, Katja; Rachakonda, Sivaramakrishna; Keller, Gisela; Weichert, Wilko; Lordick, Florian; Langer, Rupert; Springfeld, Christoph; Bruckner, Thomas; Becker, Karen

    2014-01-01

    Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p = 0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6 th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7 th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact. The MTHFR A1298C polymorphisms was an independent prognostic factor in patients

  20. Treatment selection for stage IIIA Hodgkin's disease patients

    International Nuclear Information System (INIS)

    Prosnitz, L.R.; Cooper, D.; Cox, E.B.; Kapp, D.S.; Farber, L.R.

    1985-01-01

    Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969-1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III 2 , received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach. Complications from the treatments are discussed

  1. Breast carcinoma conservative treatment. Stages I and II

    International Nuclear Information System (INIS)

    Monti, C.R.

    1990-01-01

    From 1981 to 1988, 265 patients with breast cancer stages I and II (UICC-1987), were evaluated after conservative treatment with quadrantectomy plus axillectomy, radiotherapy and chemotherapy. After surgical treatment, the patients were submitted to radiation therapy in the breast. One hundred and fifty six (58,8%) patients were submitted to adjuvant chemotherapy. The median clinical follow-up period was 42.8 months with a minimum of 24 and a maximum of 99 months. Six (2,3%) patients presented local recurrence and 48 (18,1%) presented distant metastasis. After five years the total survival rate was 89,7% and the disease free survival rate was 75% in the same period. The study did not show significant differences among the clinical stages classified after surgery and the use of adjuvant chemotherapy did not influence the results of the many stages. (author). 194 refs, 33 figs, 6 tabs

  2. Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

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    Serrano, Pablo E. [Department of Surgery, University Health Network, University of Toronto, Toronto, ON (Canada); Herman, Joseph M. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Griffith, Kent A.; Zalupski, Mark M. [Center for Cancer Biostatistics, Biostatistics Unit, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Kim, Edward J. [Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Bekaii-Saab, Tanios S. [Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio (United States); Ben-Josef, Edgar [Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Dawson, Laura A. [Princess Margaret Cancer Center, University Health Network, Toronto, ON (Canada); Ringash, Jolie [Princess Margaret Cancer Center, University Health Network, Toronto, ON (Canada); Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON (Canada); Wei, Alice C., E-mail: alice.wei@uhn.ca [Department of Surgery, University Health Network, University of Toronto, Toronto, ON (Canada); Princess Margaret Cancer Center, University Health Network, Toronto, ON (Canada); Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON (Canada)

    2014-10-01

    Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical

  3. Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

    International Nuclear Information System (INIS)

    Serrano, Pablo E.; Herman, Joseph M.; Griffith, Kent A.; Zalupski, Mark M.; Kim, Edward J.; Bekaii-Saab, Tanios S.; Ben-Josef, Edgar; Dawson, Laura A.; Ringash, Jolie; Wei, Alice C.

    2014-01-01

    Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical

  4. Successful neoadjuvant peptide receptor radionuclide therapy for an inoperable pancreatic neuroendocrine tumour

    Directory of Open Access Journals (Sweden)

    Tiago Nunes da Silva

    2018-04-01

    Full Text Available Non-functional pancreatic neuroendocrine tumours (NETs can present with advanced local or distant (metastatic disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET.

  5. Progress in Rectal Cancer Treatment

    Science.gov (United States)

    Ceelen, Wim P.

    2012-01-01

    The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a “wait and see” approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer. PMID:22970381

  6. Treatment for stage 4A retinopathy of prematurity: laser and/or ranibizumab.

    Science.gov (United States)

    Sukgen, Emine Alyamaç; Koçluk, Yusuf

    2017-02-01

    Stage 4A retinopathy of prematurity (ROP) is a critical phase where retinal detachment develops, but fovea is preserved. The present study aims to evaluate the effect of the first treatment choice (laser photocoagulation (LPC) or intravitreal ranibizumab (IVR)) applied in this critical phase on the prognosis of the disease. Records of patients diagnosed with stage 4A ROP and whose first treatment was applied in our clinic were evaluated retrospectively. All patients were referred to our clinic for the treatment of advanced ROP . While group 1 was composed of the patients who were administered LPC as first treatment, group 2 included patients where IVR was applied as first treatment. The patients in both groups were referred to surgical treatment in the presence of progression. The present study included a total of 31 eyes in 16 patients with stage 4A ROP. Eighteen eyes of nine patients in group 1 were first applied LPC, and 13 eyes of seven patients in group 2 were first applied intravitreal ranibizumab. While anatomic outcomes of ten eyes in both groups were favorable, eight eyes in group 1 and three eyes in group 2 displayed progression and were referred to vitreoretinal surgery. Laser and/or IVR treatment may be effective as a non-surgical treatment for stage 4A ROP. Especially stage 4A ROP until 6 clock hours can regress without surgical treatment. However, in stage 4A with involvement wider than 6 clock hours, non-surgical regression is difficult. Prospective controlled large series studies are necessary.

  7. Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Petruolo, Oriana A; Pilewskie, Melissa; Patil, Sujata; Barrio, Andrea V; Stempel, Michelle; Wen, Hannah Y; Morrow, Monica

    2017-09-01

    The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR). The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC. Patients with stage I-III ER+, HER2- breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP). From 2007 to 2016, 402 ER+/HER2- cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II-III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p benefit from NAC are those with PR- and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.

  8. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

    Directory of Open Access Journals (Sweden)

    Petros-Pavlos Ypsilantis

    Full Text Available Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

  9. Response to neoadjuvant chemotherapy in locally advanced breast cancer according to tumor subtypes

    International Nuclear Information System (INIS)

    Tabassum, S.; Zahid, N.

    2017-01-01

    To compare the pathological response to neoadjuvant chemotherapy in different molecular subtypes of breast cancer Study Design: Prospective cohort study. Place and Duration of Study: Department of Oncology Liaquat National Hospital Karachi from Jan 2013 to Dec 2014. Material and Methods: A total of 119 patients received neo-adjuvant chemotherapy for locally advanced breast cancer followed by definitive surgery. Demographic, clinical and pathological data of 101 patients were available for analysis. Tumors were divided into different molecular subtypes, luminal A, luminal B human epidermal growth factor receptor 2 (HER 2) was negative, luminal B (HER 2 positive), HER 2 over expressed and triple negative. Neoadjuvant chemotherapy was given for total of eight cycles. Primary end point was pathological response [pathological complete response (PCR) versus no PCR] after surgery. Results: A total of 101 patients data were analyzed. Seventeen (16.8%) were luminal A, thirty eight (37.6%) were luminal B, out of 38 luminal B patients, twenty one (55.2%) were HER 2 + and seventeen (44.7%) were HER 2 -ve. Sixteen (15.8%) patients were HER 2 over expressed and thirty (29.7%) were triple negative. Out of 101 patients, twenty eight (27.72%) achieved PCR. A total of 5.9% achieved PCR in luminal A, 4.8% had PCR in luminal B (HER 2 -ve type), 23.5% had in luminal B (HER 2 +ve type), 50% achieved PCR in HER-2 over expressed type and 46.7% had PCR in triple negative subtype, (p=0.001). There was no significant association of PCR with age, tumor size, lymph node status, histology or grade. Conclusion: Molecular subtypes of breat cancer were found to be statistically significant predictor of PCR after neoadjuvant chemotherapy. (author)

  10. Prevalence of Clostridium Difficile Infection in Patients After Radical Cystectomy and Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Cotter, Katherine J; Fan, Yunhua; Sieger, Gretchen K; Weight, Christopher J; Konety, Badrinath R

    2017-10-27

    Clostridium Difficile is the most common cause of nosocomial infectious diarrhea. This study evaluates the prevalence and predictors of Clostridium Difficile infections in patients undergoing radical cystectomy with or without neoadjuvant chemotherapy. Retrospective chart review was performed of all patients undergoing cystectomy and urinary diversion at a single institution from 2011-2017. Infection was documented in all cases with testing for Clostridium Difficile polymerase chain reaction toxin B. Patient and disease related factors were compared for those who received neoadjuvant chemotherapy vs. those who did not in order to identify potential risk factors associated with C. Difficile infections. Chi squared test and logistic regression analysis were used to determine statistical significance. Of 350 patients who underwent cystectomy, 41 (11.7%) developed Clostridium Difficile in the 30 day post-operative period. The prevalence of C. Difficile infection was higher amongst the patients undergoing cystectomy compared to the non-cystectomy admissions at our hospital (11.7 vs. 2.9%). Incidence was not significantly different among those who underwent cystectomy for bladder cancer versus those who underwent the procedure for other reasons. Median time to diagnosis was 6 days (range 3-28 days). The prevalence of C. Diff infections was not significantly different among those who received neoadjuvant chemotherapy vs. those who did not (11% vs. 10.4% p  = 0.72). A significant association between C. Difficile infection was not seen with proton pump inhibitor use ( p  = 0.48), patient BMI ( p  = 0.67), chemotherapeutic regimen ( p  = 0.94), individual surgeon ( p  = 0.54), type of urinary diversion (0.41), or peri-operative antibiotic redosing ( p  = 0.26). Clostridium Difficile infection has a higher prevalence in patients undergoing cystectomy. No significant association between prevalence and exposure to neoadjuvant chemotherapy was seen.

  11. Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer.

    Science.gov (United States)

    Glaser, Rebecca L; Dimitrakakis, Constantine

    2014-06-01

    Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting. To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later. By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone. This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.

  12. MRI in local staging of rectal cancer: an update

    Science.gov (United States)

    Tapan, Ümit; Özbayrak, Mustafa; Tatlı, Servet

    2014-01-01

    Preoperative imaging for staging of rectal cancer has become an important aspect of current approach to rectal cancer management, because it helps to select suitable patients for neoadjuvant chemoradiotherapy and determine the appropriate surgical technique. Imaging modalities such as endoscopic ultrasonography, computed tomography, and magnetic resonance imaging (MRI) play an important role in assessing the depth of tumor penetration, lymph node involvement, mesorectal fascia and anal sphincter invasion, and presence of distant metastatic diseases. Currently, there is no consensus on a preferred imaging technique for preoperative staging of rectal cancer. However, high-resolution phased-array MRI is recommended as a standard imaging modality for preoperative local staging of rectal cancer, with excellent soft tissue contrast, multiplanar capability, and absence of ionizing radiation. This review will mainly focus on the role of MRI in preoperative local staging of rectal cancer and discuss recent advancements in MRI technique such as diffusion-weighted imaging and dynamic contrast-enhanced MRI. PMID:25010367

  13. Clinical trial of neoadjuvant chemotherapy combined with radiotherapy for primary intracranial germinomas

    International Nuclear Information System (INIS)

    Kitamura, Kei; Suzuki, Keishiro; Shirato, Hiroki; Kagei, Kenji; Aoyama, Hidefumi; Sawamura, Yutaka; Ikeda, Jun; Miyasaka, Kazuo

    1997-01-01

    Purpose/Objective: Since 1992, we have been using neoadjuvant chemotherapy to reduce the radiation dose and irradiated volume in the treatment of intracranial germinomas. This study evaluates the initial response and complications of the treatment and also the IQ score and pituitary function of patients before radiotherapy. Materials and methods: Fifteen patients with histologically confirmed intracranial germinomas were treated between 1992 and 1997. Six patients with solitary pure germinoma received 3 to 4 courses of etoposide and cisplatin (EP regimen) followed by localized irradiation of 24Gy (in 12 fractions within 3 weeks). Three patients with germinoma with syncytiotrophoblastic giant cells (STGC) and 4 patients with multifocal pure germinoma received 3 to 5 courses of ifosfamide, cisplatin and etoposide (ICE regimen), followed by localized irradiation of 24 Gy. Two patients with disseminated pure germinoma received 2 to 4 courses of ICE regimen followed by craniospinal irradiation of 24 Gy. In the planning of localized irradiation, the treatment field was determined so as to cover the tumor with a margin of 2cm. The IQ score and pituitary function before radiotherapy were also examined. MRI was performed in all patients one month after the completion of treatment and every 6 months in the follow-up study. The treatment data of our institute before 1991, as historical control, was analyzed and compared to that of the present study. Results: Complete remission (CR) was obtained in all patients after the treatment. One patient with germinoma with STGC experienced recurrence out of the field at 39 months after surgery. He was re-treated with salvage therapy including the ICE regimen and obtained a second complete remission. All patients are alive without disease with a median follow-up period of 29 months. The examination of IQ score and pituitary function before radiotherapy revealed mental retardation in 2 patients (22%) and hypopituitarism in 13 patients (86

  14. 18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making.

    Directory of Open Access Journals (Sweden)

    Maarten C J Anderegg

    Full Text Available Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT. Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery.From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy.156 patients underwent a PET-CT after nCRT. In 31 patients (19.9% PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%. Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490.In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery.

  15. 18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making

    Science.gov (United States)

    Anderegg, Maarten C. J.; de Groof, Elisabeth J.; Gisbertz, Suzanne S.; Bennink, Roel J.; Lagarde, Sjoerd M.; Klinkenbijl, Jean H. G.; Dijkgraaf, Marcel G. W.; Bergman, Jacques J. G. H. M.; Hulshof, Maarten C. C. M.; van Laarhoven, Hanneke W. M.; van Berge Henegouwen, Mark I.

    2015-01-01

    Background Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery. Methods From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy. Results 156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490). Conclusion In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery. PMID:26529313

  16. Efficacy of Anti-HER2 Agents in Combination With Adjuvant or Neoadjuvant Chemotherapy for Early and Locally Advanced HER2-Positive Breast Cancer Patients: A Network Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Márcio Debiasi

    2018-05-01

    Full Text Available BackgroundSeveral (neoadjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy.MethodsPhase II/III randomized clinical trials comparing two or more different (neoadjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS and disease-free survival (DFS.Results17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients; and DFS network (17 trials: 40,992 patients. Two studies—the ExteNET and the NeoSphere trials—were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT plus trastuzumab (T and lapatinib (L and CT + T + Pertuzumab (P are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N was the best treatment option with 50.55%, followed by CT + T + P (26.59% and CT + T + L (20.62%.ConclusionThis network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neoadjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.

  17. Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity.

    Science.gov (United States)

    Chowdhary, Mudit; Sen, Neilayan; Jeans, Elizabeth B; Miller, Luke; Batus, Marta; Gitelis, Steven; Wang, Dian; Abrams, Ross A

    2018-05-18

    Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy with mesna, doxorubicin, ifosfamide, and dacarbazine followed by surgery and 3 cycles of adjuvant mesna, doxorubicin, ifosfamide, and dacarbazine, demonstrated high rates of disease control at the cost of significant toxicity (83% grade 4, 5% grade 5). As such, this regimen has not been widely adopted. Herein, we report our institutional outcomes utilizing a modified interdigitated chemoradiotherapy regimen, without dacarbazine, and current radiotherapy planning and delivery techniques for high-risk STS. Adults with large (≥5 cm; median, 12.9 cm), grade 3 extremity STS who were prospectively treated as part of our institutional standard of care from 2008 to 2016 are included. Neoadjuvant chemoradiotherapy consisted of 3 cycles of mesna, doxorubicin, and ifosfamide (MAI) and 44 Gy (22 Gy in 11 fractions between cycles of MAI) after which patients underwent surgical resection and received 3 additional cycles of MAI. Twenty-six patients received the MAI treatment protocol. At a median follow-up of 47.3 months, 23 (88.5%) patients are still alive. Three year locoregional recurrence-free survival, disease-free survival, and overall survival are 95.0%, 64.0%, and 95.0%, respectively. There have been no therapy-related deaths or secondary malignancies. The nonhematologic grade 4 toxicity rate was 7.7%. Neoadjuvant interdigitated MAI radiotherapy followed by resection and 3 cycles of adjuvant MAI has resulted in acceptable and manageable toxicity and highly favorable survival in patients at greatest risk for treatment failure.

  18. Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer.

    Science.gov (United States)

    Fang, T C; Oh, Y S; Szabo, A; Khan, A; Dua, K S

    2016-08-01

    Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available. © 2015 International Society for Diseases of the Esophagus.

  19. Screening for Breast Cancer: Staging and Treatment

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Screening For Breast Cancer Staging and Treatment Past Issues / Summer 2014 Table ... oncology nurse and a registered dietitian. Read More "Screening For Breast Cancer" Articles #BeBrave: A life-saving test / Breast Cancer ...

  20. Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

    Science.gov (United States)

    Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

    2015-08-01

    Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

  1. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer

    NARCIS (Netherlands)

    Lips, Esther H.; Mukhtar, Rita A.; Yau, Christina; de Ronde, Jorma J.; Livasy, Chad; Carey, Lisa A.; Loo, Claudette E.; Vrancken-Peeters, Marie-Jeanne T. F. D.; Sonke, Gabe S.; Berry, Donald A.; van't Veer, Laura J.; Esserman, Laura J.; Wesseling, Jelle; Rodenhuis, Sjoerd; Shelley Hwang, E.

    2012-01-01

    Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene

  2. Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Koontz, Bridget F.; Quaranta, Brian P.; Pura, John A.; Lee, W.R.; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S.; Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W.

    2013-01-01

    Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes

  3. Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koontz, Bridget F., E-mail: Bridget.Koontz@duke.edu [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Quaranta, Brian P. [21st Century Oncology, Asheville, North Carolina (United States); Pura, John A. [Division of Biostatistics, Duke Cancer Institute, Durham, North Carolina (United States); Lee, W.R.; Vujaskovic, Zeljko [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Gerber, Leah [Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Haake, Michael [Southeast Radiation Oncology, Charlotte, North Carolina (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W. [Department of Surgery, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States)

    2013-09-01

    Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

  4. Advanced Age is Not a Contraindication for Treatment With Curative Intent in Esophageal Cancer.

    Science.gov (United States)

    Voncken, Francine E M; van der Kaaij, Rosa T; Sikorska, Karolina; van Werkhoven, Erik; van Dieren, Jolanda M; Grootscholten, Cecile; Snaebjornsson, Petur; van Sandick, Johanna W; Aleman, Berthe M P

    2017-07-31

    The objective of this study is to compare long-term outcomes between younger and older (70 y and above) esophageal cancer patients treated with curative intent. Overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free interval were compared between older (70 y and above) and younger (below 70 y) esophageal cancer patients treated between 1998 and 2013. Treatment consisted of neoadjuvant chemoradiotherapy with surgery or definitive chemoradiotherapy: 36 to 50.4 Gy in 18 to 28 fractions combined with 5-fluorouracil/cisplatin or carboplatin/paclitaxel. The study comprised 253 patients, of whom 76 were 70 years and older. Median age was 64 years (range, 41 to 83). Most patients had stage II-IIIA disease (83%). Planned treatment was neoadjuvant chemoradiotherapy with surgery for 169 patients (41 patients aged 70 y and older) and definitive chemoradiotherapy for 84 patients (31 patients aged 70 y and older). The compliance to radiotherapy was 92%, with no difference between older and younger patients. In 33 patients (13 patients aged 70 y and older) planned surgery was not performed. Median follow-up was 4.9 years. Three-year OS was 42%. The multivariable analysis showed no statistical difference in OS or in DFS comparing older and younger patients: OS (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.61-1.28), DFS (HR, 0.87; 95% CI, 0.60-1.25). Elderly showed a longer locoregional recurrence-free interval; HR, 0.53 (95% CI, 0.30-0.92; P=0.02) and a higher pathologic complete response rate (50% vs. 25%; P=0.02). Long-term outcomes of older esophageal cancer patients (70 y and above) selected for treatment with neoadjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy were comparable with the outcomes of their younger counterparts. Advanced age alone should not be a contraindication for potentially curative chemoradiotherapy-based treatment in esophageal cancer patients.

  5. Evaluation of Sentinel Node Biopsy in Locally Advanced Breast Cancer Patients Who Become Clinically Node-Negative after Neoadjuvant Chemotherapy: A Preliminary Study

    International Nuclear Information System (INIS)

    Thomas, Sh.; Prakash, A.; Goyal, V.; Agarwal, Sh.; Choudhury, M.; Popli, M.B.

    2011-01-01

    Introduction. Controversy continues over the appropriate timing of sentinel lymph node (SLN) biopsy in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy. We evaluated the feasibility and accuracy of SLN biopsy in LABC patients with cytology-proven axillary nodal metastasis who become clinically node-negative after neoadjuvant chemotherapy. Materials. 30 consecutive patients with LABC, who had become clinically node-negative after 3 cycles of neoadjuvant chemotherapy, were included in the study. They were then subjected to SLN biopsy, axillary lymph node dissection, and breast surgery. Results. Sentinel nodes were successfully identified in 26 of the 30 patients, resulting in an identification rate of 86.67%, sensitivity of 83.33%, false negative rate of 20%, negative predictive value of 72.73%, and an overall accuracy of 88.46%. No complications were observed as a result of dye injection. Conclusions. SLN biopsy is feasible and safe in LABC patients with cytology-positive nodes who become clinically node-negative after neoadjuvant chemotherapy. Our accuracy rate, identification rate, and false negative rate are comparable to those in node-negative LABC patients. SLN biopsy as a therapeutic option in LABC after neoadjuvant chemotherapy is a promising option which should be further investigated

  6. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial

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    Shen Kui

    2012-11-01

    Full Text Available Abstract Background The purpose of this study is to assess the predictive accuracy of a multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and cyclophosphamide combination chemotherapy on gene expression data from patients who received these drugs as neoadjuvant treatment. Methods Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC followed by four cycles of docetaxel/capecitabine (TX on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H. The chemotherapy predictor (TFEC-MGP was developed from publicly available gene expression data of 42 breast cancer cell-lines with corresponding in vitro chemotherapy sensitivity results for the four chemotherapy drugs. No predictor was developed for treatment with trastuzumab. The predictive performance of TFEC-MGP in distinguishing cases with pathologic complete response from those with residual disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area under the receiver-operating characteristic curve (AU-ROC was used as the metric of predictive performance. Genomic predictions were performed blinded to clinical outcome. Results The AU-ROC was 0.70 (95% CI: 0.57-0.82 for the FEC/TX group (n=66 and 0.43 (95% CI: 0.20-0.66 for the FEC/TX plus H group (n=25. Among the patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86 for estrogen receptor (ER-negative (n=28 and it was 0.59 (95% CI: 0.36-0.82 for ER-positive cancers (n=37. ER status was not reported for one patient. Conclusions Our results indicate that the cell line derived 291-probeset genomic predictor of response to FEC/TX combination chemotherapy shows good performance in a blinded validation study, particularly in ER-negative patients.

  7. Systemic immune–inflammation index as a useful prognostic indicator predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

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    Chen L

    2017-12-01

    with low SII had better 1-, 3- and 5-year rates of DFS and OS than those with high SII. In addition, patients with low SII were likely to receive DFS and OS benefits from neoadjuvant chemotherapy and postoperative chemotherapy.Conclusion: SII may qualify as a noninvasive, cost-effective, convenient and reproducible prognostic indicator for patients with advanced gastric cancer undergoing neoadjuvant chemotherapy. It may help clinicians to identify those patients who will benefit from treatment strategy decisions. Keywords: neoadjuvant chemotherapy, gastric cancer, systemic immune–inflammation index, SII, prognosis

  8. Primary vaginal cancer: role of MRI in diagnosis, staging and treatment

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    Sunil, J; Klopp, A H; Devine, C E; Sagebiel, T; Viswanathan, C; Bhosale, P R

    2015-01-01

    Primary carcinoma of the vagina is rare, accounting for 1–3% of all gynaecological malignancies. MRI has an increasing role in diagnosis, staging, treatment and assessment of complications in gynaecologic malignancy. In this review, we illustrate the utility of MRI in patients with primary vaginal cancer and highlight key aspects of staging, treatment, recurrence and complications. PMID:25966291

  9. Impact of neo-adjuvant Sorafenib treatment on liver transplantation in HCC patients - a prospective, randomized, double-blind, phase III trial

    International Nuclear Information System (INIS)

    Hoffmann, Katrin; Ganten, Tom; Gotthardtp, Daniel; Radeleff, Boris; Settmacher, Utz; Kollmar, Otto; Nadalin, Silvio; Karapanagiotou-Schenkel, Irini; Kalle, Christof von; Jäger, Dirk; Büchler, Markus W; Schemmer, Peter

    2015-01-01

    Liver Transplantation (LT) is treatment of choice for patients with hepatocellular carcinoma (HCC) within MILAN Criteria. Tumour progression and subsequent dropout from waiting list have significant impact on the survival. Transarterial chemoembolization (TACE) controls tumour growth in the treated HCC nodule, however, the risk of tumour development in the untreated liver is increased by simultaneous release of neo-angiogenic factors. Due to its anti-angiogenic effects, Sorafenib delays the progression of HCC. Aim of this study was to determine whether combination of TACE and Sorafenib improves tumour control in HCC patients on waiting list for LT. Fifty patients were randomly assigned on a 1:1 ratio in double-blinded fashion at four centers in Germany and treated with TACE plus either Sorafenib (n = 24) or placebo (n = 26). The end of treatment was development of progressive disease according to mRECIST criteria or LT. The primary endpoint of the trial was the Time-to-Progression (TTP). Other efficacy endpoints were Tumour Response, Progression-free Survival (PFS), and Time-to-LT (TTLT). The median time of treatment was 125 days with Sorafenib and 171 days with the placebo. Fourteen patients (seven from each group) developed tumour progression during the course of the study period. The Hazard Ratio of TTP was 1.106 (95% CI: 0.387, 3.162). The results of the Objective Response Rate, Disease Control Rate, PFS, and TTLT were comparable in both groups. The incidence of AEs was comparable in the placebo group (n = 23, 92%) and in the Sorafenib group (n = 23, 96%). Twelve patients (50%) on Sorafenib and four patients (16%) on placebo experienced severe treatment-related AEs. The TTP is similar after neo-adjuvant treatment with TACE and Sorafenib before LT compared to TACE and placebo. The Tumour Response, PFS, and TTLT were comparable. The safety profile of the Sorafenib group was similar to that of the placebo group

  10. Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L.

    2011-01-01

    Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failure (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT ≤2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs (≤ 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT ≤2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.

  11. Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Fangberget, A.; Holmen, M.M.; Nilsen, L.B.; Hole, K.H.; Engebraaten, O.; Naume, B.; Smith, H.J.; Olsen, D.R.; Seierstad, T.

    2011-01-01

    To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37-72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. Before NAC, HER2 overexpression was the single significant predictor of pCR (p = 0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42 x 10 -3 mm 2 /s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR. (orig.)

  12. Expression characteristic of CXCR1 in different breast tissues and the relevance between its expression and efficacy of neo-adjuvant chemotherapy in breast cancer.

    Science.gov (United States)

    Xue, Miao-Qun; Liu, Jun; Sang, Jian-Feng; Su, Lei; Yao, Yong-Zhong

    2017-07-25

    To investigate chemokine receptor CXCR1 expression characteristic in different breast tissues and analyze the relationship between CXCR1 expression changes in breast cancer tissue and efficacy of neo-adjuvant chemotherapy. Chemokine receptor CXCR1 was lowly expressed in normal breast tissues and breast fibroadenoma, but highly expressed in breast cancer. It was significantly correlated with pathological stage, tumor cell differentiation, and lymph node metastasis (P breast cancer tissues decreased. Among these 104 breast cancer patients with different molecular subtypes, the survival rate with Luminal A was the highest, followed by the Luminal B breast cancer, TNBC was the worst. 104 cases with breast carcinoma, 20 cases with normal breast and 20 cases with breast fibroadenoma were included and followed up. Immunohistochemistry was used to detect the expression of CXCR1 in the various tissues. The relationship between the CXCR1 expression changes in breast cancer biopsies and surgical specimens, as well as the efficacy of neo-adjuvant chemotherapy, was analyzed. Chemokine receptor CXCR1 could be used as an indicator to predict benign or malignant breast disease, and it can even predict the malignancy degree of breast cancer, as well as its invasive ability and prognosis.

  13. Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

    Science.gov (United States)

    Mabuchi, Yasushi; Yahata, Tamaki; Kobayashi, Aya; Tanizaki, Yuko; Minami, Sawako; Ino, Kazuhiko

    2015-06-01

    Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  14. 18F-fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response

    International Nuclear Information System (INIS)

    Ueda, Shigeto; Saeki, Toshiaki; Shigekawa, Takashi

    2012-01-01

    The background of this study was to assess the usefulness of positron emission tomography combined with computed tomography using 18 F-fluorodeoxyglucose (FDG positron emission tomography (PET)/CT) for optimizing chemotherapy during neoadjuvant chemotherapy for primary breast cancer. One hundred and eight patients (110 tumors) with breast cancer (≥2 cm, stages II and III) received neoadjuvant chemotherapy consisting of an anthracycline-based regimen and taxane. The maximal value of the baseline standardized uptake value (SUV) and the change in SUV after four cycles of an anthracycline-based regimen relative to baseline SUV were assessed for predicting pathological complete response (pCR) after sequential taxane. Tumors with pCR had significantly higher baseline SUV (9.3±3.7 SD) compared to those with non-pCR (7.2±3.8 SD) (p=0.02), but there was a considerable overlap between two groups. On PET scan after four cycles of chemotherapy, thirty-three patients (33.7%) with a 72.1% or greater reduction in SUV were considered as responders and the performance in predicting pCR had a sensitivity of 88.9% and specificity of 78.7%. The baseline SUV could not be a useful indicator for predicting pCR due to the wide range in sensitivity. On the other hand, a relative change in SUV after completion of an anthracycline-based regimen could be useful for predicting pCR. (author)

  15. Long-term treatment results for nasopharyngeal carcinoma: The Sahlgrenska Univ. Hospital experience

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    Taheri-Kadkhoda, Zahra; Bjoerk-Eriksson, Thomas; Mercke, Claes [Dept. of Oncology, Sahlgrenska Univ. Hospital, Goeteborg (Sweden); Johansson, Karl-Axel [Dept. of Radiophysics, Sahlgrenska Univ. Hospital, Goeteborg (Sweden)

    2007-08-15

    Nasopharyngeal carcinoma (Nc) is a rare disease in Sweden. For evaluation of the treatment outcomes in our NPC patients, 52 new cases that were referred to our department between 1991 and 2002 were retrospectively analysed. Tumor stage, according to the 1997 AJCC staging system, was I in five, II in ten, III in 12 and IV in 25 patients. Majority of the patients (87%) had World Health Organization type II-III tumors. Neoadjuvant chemotherapy was delivered in 33 patients. Thirty-two patients received hyperfractionated accelerated radiation therapy with a median dose of 64.6Gy (1.7Gy/fr bid). Conventional external irradiation with a median dose of 66Gy (2Gy/fr) was delivered to 18 patients. An intracavitary brachy-boost of 4.5-12Gy was delivered to 40 patients. Two patients were excluded from the analysis due to treatment refusal. For the patients with tumor stages I-IVB, the 5-year disease-free and overall survival rates were 61% and 55%, respectively. The 5-year local, regional, and distant relapse-free survival rates were 70%, 92% and 77%, respectively. The most frequent late side effects were xerostomia (98%), otitis (70%) and hearing deterioration (64%). Our data suggest that optimization of the treatment outcomes in NPC patients requires implementation of new therapeutic strategies.

  16. Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy

    International Nuclear Information System (INIS)

    Pai, Howard Huaihan; Ludgate, Charles; Pickles, Tom; Paltiel, Chuck M.Sc.; Agranovich, Alex; Berthelet, Eric; Duncan, Graeme; Kim-Sing, Charmaine; Kwan, Winkle; Lim, Jan; Liu, Mitchell; Tyldesley, Scott

    2006-01-01

    Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival

  17. Surgical treatment of advanced stage Freiberg disease

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    Emin Özkul

    2014-09-01

    Full Text Available Objective: Freiberg disesase is an avascular necrosis of the 2nd and 3rd metatarsal head and which kind of surgical option to be used is controversial in symptomatic patients. In this study the results of the advanced stage Freiberg’s disease patients, who were treated with surgery were evaluated. Methods: 12 patients (8 female, 4 male whose pain could not be solved with conservative method and underwent surgery (6 debridement, 3 osteotomy, 3 excision of the metatarsal head were included in this study. Themean age of the patients 19.1 (range 13- 31 and the mean follow-up 30.8(range 25-94 months. According to the Smillie classification 3 patients had type 5, 8 patients had type 4 and 1 patient had type 3 osteonecrosis. The results of the patients were evaluated according to Lesser Metatarsophalangeal-Interphalangeal Scale. Results: According to Lesser MetatarsophalangealInterphalangeal Scale 3 patients (%25 had excellent, 6 patients (%50 had good and 3 patients had poor results were obtained. 2 of 3 patients with poor results were type 5, and 1 patient was type 4 and all three patients underwent joint debridement. Conclusion:The method of surgical treatment of Freiberg disease determined according to the stage of the disease. Debridement alone in the treatment of patients with late stage is not enough, it should be combined with other methods.

  18. Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum

    International Nuclear Information System (INIS)

    Glynne-Jones, R.; Hava, N.; Goh, V.; Bosompem, S.; Bridgewater, J.

    2015-01-01

    In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT

  19. The Role of Concomitant Radiation Boost in Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

    Science.gov (United States)

    Badakhshi, Harun; Ismail, Mahmoud; Boskos, Christos; Zhao, Kuaile; Kaul, David

    2017-06-01

    This study analyzed the impact of concomitant boost on long-term clinical outcomes in locally advanced rectal cancer. A total of 141 patients (median age=61 years) were treated with neoadjuvant chemoradiotherapy. Median total dose was 50.4 Gy. Forty-three patients received a concomitant boost. Concurrent chemotherapy consisted of 5-fluorouracil (5-FU), given as a 24-h continuous infusion. Mean follow-up was 83.7 months. The 3, 5-, and 10-year overall survival (OS) rates were 91.9%, 84.6%, and 52.9%, respectively. Recurrence-free survival (RFS) rates at 3, 5, and 10 years were 91.4%, 88.9%, and 79.3%, respectively. Metastasis-free survival (MFS) rates at 3, 5, and 10 years were 84.6%, 75.4%, and 49.9%, respectively. Overall, 9.9% of all patients achieved pathological complete response. Down-staging of T- or N-stage was achieved in 55.1% and 41.5% of patients. Multivariate analysis revealed that female sex (p=0.011), concomitant boost-radiotherapy (p=0.014), and the presence of fewer than five positive lymph nodes (prectal cancer in terms of local outcomes. Intensified radiotherapy using a concomitant boost has a positive effect on OS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer

    International Nuclear Information System (INIS)

    Urushibara, Masayasu; Kageyama, Yukio; Akashi, Takumi; Otsuka, Yukihiro; Takizawa, Touichiro; Koike, Morio; Kihara, Kazunori

    2007-01-01

    Heat shock proteins (HSPs) play crucial roles in cellular responses to stressful conditions. Expression of HSPs in invasive or high-risk superficial bladder cancer was investigated to identify whether HSPs predict pathological response to neoadjuvant chemoradiotherapy (CRT). Immunohistochemistry was used to assess expression levels of HSP27, HSP60, HSP70, HSP90 and p53 in 54 patients with invasive or high-risk superficial bladder cancer, prior to low-dose neoadjuvant CRT, followed by radical or partial cystectomy. Patients were classified into two groups (good or poor responders) depending on pathological response to CRT, which was defined as the proportion of morphological therapeutic changes in surgical specimens. Good responders showed morphological therapeutic changes in two-thirds or more of tumor tissues. In contrast, poor responders showed changes in less than two-thirds of tumor tissues. Using a multivariate analysis, positive HSP60 expression prior to CRT was found to be marginally associated with good pathological response to CRT (P=0.0564). None of clinicopathological factors was associated with HSP60 expression level. In the good pathological responders, the 5-year cause-specific survival was 88%, which was significantly better than survival in the poor responders (51%) (P=0.0373). Positive HSP60 expression prior to CRT may predict good pathological response to low-dose neoadjuvant CRT in invasive or high-risk superficial bladder cancer. (author)

  1. Clinical Initial Response of Neoadjuvant Chemotheraphy in Triple Negative, HER-2, and Luminal Types of Breast Cancer in Denpasar (A Preliminary Study

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    Kristianto Yuli Yarso

    2012-01-01

    Full Text Available Objectives: Triple Negative, Luminal, HER-2 subtypes of breast cancer are markers to predict behavior, aggressiveness, and response to chemotherapy. The aim of this study is to understand character and response to standard neoadjuvant chemotherapy in different subtypes of breast cancer. Method: This is a descriptive study of breast cancer subtypes. From 687 patients (2003-2010 351 patients have IHC data which divided into 3 groups, Triple negative, Luminal, and HER-2. We used 10% as a cut off point for ER, PR, while 30% & positive 3 for HER-2. We determined initial clinical response after 3 cycles of neoadjuvant chemotherapy although only 77 got standard neoadjuvant chemotherapy and had clinical response data. We used 50% diameters depreciation & no metastasis as cut off point for respond group. Results: There were 116 (33% Triple Negative, 60 (17% HER-2, and 175 (50% Luminal Subtypes. The mean of age for 351 patients are 48.32 (23-82 years. In this study, it was obtained that no significant difference of means of age (p=0.24 in these 3 groups. Triple negative group significantly more advance in grade if compared with the other two groups (p=0.02. HER-2 group had highest response with standard neoadjuvant chemotherapy (50%, Luminal group had (49%, and Triple negative group had only (15% response. One pCR in HER-2 group. There were no difference ages in subtypes. Triple negative has more advances in grade. HER-2 group has highest response to standard neoadjuvant chemotherapy and Triple negative has lowest response to standard neoadjuvant chemotherapy.

  2. Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

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    Yu-Lin Zhao

    2017-07-01

    Full Text Available Objective: To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion. Methods: A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy. Results: Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, proproliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group; anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group; pro-invasion genes γ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group; anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group. Conclusions: Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

  3. Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893, ISRCTN82191749)

    International Nuclear Information System (INIS)

    Tachezy, Michael; Yekebas, Emre; Gebauer, Florian; Petersen, Cordula; Arnold, Dirk; Trepel, Martin; Wegscheider, Karl; Schafhausen, Phillipe; Bockhorn, Maximilian; Izbicki, Jakob Robert

    2014-01-01

    Median OS after surgery in curative intent for non-metastasized pancreas cancer ranges under study conditions from 17.9 months to 23.6 months. Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or both. Observational and autopsy series report local recurrence rates of up to 87% even after potentially “curative” R0 resection. To achieve better local control, neoadjuvant CRT has been suggested for preoperative tumour downsizing, to elevate the likelihood of curative, margin-negative R0 resection and to increase the OS rate. However, controlled, randomized trials addressing the impact of neoadjuvant CRT survival do not exist. The underlying hypothesis of this randomized, two-armed, open-label, multicenter, phase III trial is that neoadjuvant CRT increases the three-year overall survival by 12% compared to patients undergoing upfront surgery for resectable pancreatic cancer. A rigorous, standardized technique of histopathologically handling Whipple specimens will be applied at all participating centers. Overall, 410 patients (n = 205 in each study arm) will be enrolled in the trial, taking into regard an expected drop out rate of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1 rates, respectively, surgical resectability rate, local and distant disease-free and global survival, and first site of tumor recurrence constitute further essential endpoints of the trial. For the first time, the NEOPA study investigates the impact of neoadjuvant CRT on survival of resectable pancreas head cancer in a prospectively randomized manner. The results of the study have the potential to change substantially the treatment regimen of pancreas cancer. Clinical Trial gov:http://www.clinicaltrials.gov/show/NCT01900327; Clinical Trial gov:http://drks-neu.uniklinik-freiburg.de/drks w eb/navigate.do?navigationId; Clinical Trial gov

  4. Algorithm of physical rehabilitation of athletes in polyclinic stage of treatment of osteochondrosis

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    E. V. MAKAROVA

    2014-12-01

    Full Text Available Purpose: develop an algorithm which improves the physical rehabilitation of athletes with osteochondrosis on polyclinic stage of treatment. Material: processed of scientific literature and Internet. Results: this research analyzes traditional recovery of athletes with spinal osteochondrosis on polyclinic stage of treatment. The practical and clinical study showed that etiopathogenesis injuries and diseases of the musculoskeletal system of athletes of different specialties have similar evidences. Therefore, a recovery of sports working capacity during medical rehabilitation treatment does not differ from ordinary patients. We propose an algorithm of physical rehabilitation, aimed for the fast recovery of health of athletes and return them to the athletic training, and conducting therapeutic exercises with specific objects such as balancing disk and preventive "Osan". Conclusions : established that the physical rehabilitation of athletes at polyclinic stage of treatment similar to the rehabilitation of patients non-athletes, and improved algorithm for the physical rehabilitation of athletes with osteochondrosis in the polyclinic stage of treatment.

  5. Reevaluation of Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Zheng, Yan; Li, Yin; Liu, Xianben; Sun, Haibo; Wang, Zongfei; Zhang, Ruixiang

    2015-01-01

    Abstract The effect of neoadjuvant chemotherapy on the survival of patients with thoracic esophageal squamous cell carcinomas (ESCCs) remains controversial. The optimal management strategy for resectable ESCCs varies regionally based on local randomized controlled trials. A systematic review and meta-analysis was conducted to re-evaluate this controversial issue. A systematic review of the Medline, Embase, and PubMed databases was carried out on data collected between August 1994 and August 2...

  6. A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    Cheng, S.-J.; Lee, J.-J.; Ting, L.-L.; Tseng, I.-Y.; Chang, H.-H.; Chen, H.-M.; Kuo, Y.-S.; Hahn, L.-J.; Kok, S.-H.

    2006-01-01

    Purpose: To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. Methods and Materials: The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. Results: The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p < 0.001), radiation dose (p = 0.029), and tooth extraction (p < 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. Conclusions: More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes

  7. A prospective cohort study of patient-reported vomiting, retching, nausea and antiemetic use during neoadjuvant long-course radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Kristopher Dennis

    2018-03-01

    Full Text Available Background and purpose: Antiemetic guidelines suggest daily prophylaxis with a serotonin3 receptor antagonist (5-HT3RA as an option for patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal cancer, despite the risks that 5-HT3RA-induced constipation may pose. We explored the incidence of patient-reported vomiting, retching, nausea and antiemetic intake among patients in this setting to determine if these risks are justified. Materials and methods: We carried out a single-centre non-randomised prospective cohort study of adult patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma. Patients recorded symptoms and medication intake daily until 7 days following treatment completion. Results: From 33 evaluable patients, we collected 1407 days of patient-reported data. Vomiting was reported by 7 patients (21%, retching by 5(15% and nausea by 21(64%. No patients were administered prophylactic antiemetics. The median number of days with vomiting was 2, and the cumulative number of days for all affected patients was 22 (1.6% of 1407 evaluable days. There were no differences in PTV or small bowel loop V15Gy, V45Gy and V50Gy volumes between patients that did and did not vomit. Conclusions: The cumulative incidence of days with vomiting was only 1.6%. 5-HT3RA prophylaxis during long-course neoadjuvant treatment seems unnecessary. Keywords: Antiemetic, Nausea, Patient-reported outcome, Radiation therapy, Rectal cancer, Vomiting

  8. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

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    Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.

  9. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun

    2015-01-01

    The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited

  10. Neoadjuvant radiotherapy of primary irresectable unicentric Castleman's disease: a case report and review of the literature

    International Nuclear Information System (INIS)

    Vries, Iris AC de; Acht, Marjolein MS van; Demeyere, Thomas BJ; Lybeert, Marnix LM; Zoete, Jean-Paul de; Nieuwenhuijzen, Grard AP

    2010-01-01

    Castleman disease (CD) is a rare benign disorder characterised by hyperplasia of lymphoid tissue that may develop at a single site or throughout the body. The etiology of this disorder is unclear, although the histopathological presentation can be differentiated into a hyaline vascular variant, a plasma cell variant and a mixed variant. Clinically, it has been recorded that 3 manifestations of CD are characterized: a localized unicentric type, a generalized multicentric type and a mixed form. Surgery remains the main treatment for resectable unicentric CD, since removal of the large node is possible without further complications. No consensus has been reached concerning the most adequate treatment for irresectable unicentric CD. Case report of a 67 year old woman. This report, describes the case of a 67-year-old woman with unicentric Castleman disease located in the right lower abdomen. The patient had symptoms of fatigue, dyspnoea and pain in the right lower abdomen. Computed tomography (CT)- examination revealed a tumour, which had grown to form a close relationship with the common iliac vessels and the sacral bone. A Laparotomy procedure revealed that the tumour was an irresectable mass. Neo-adjuvant radiotherapy (40 Gy) was administered in order to downsize the tumour. Six weeks later a new CT-scan revealed a major reduction of the tumour, which enabled a successful radical resection of the tumour to be performed. Histopathological analysis of the tumour showed the hyaline vascular type of CD. Neo-adjuvant radiotherapy should be considered in case of an irresectable unicentric CD

  11. Wastewater treatment in horizontal subsurface flow constructed wetlands using different media (setup stage

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    Abdel Razik A. Zidan

    2015-04-01

    Full Text Available Wastewater treatment through horizontal subsurface flow (HSSF constructed wetlands (CWs using three different treatment media (gravel, pieces of plastic pipes, and shredded tire rubber chips were investigated in Samaha village, Dakahliya, Egypt. The study focused on the wetland setup stage during the first months of its operation (setup stage. In this stage media porosity, bacterial biofilm, and plant roots growth were in progress and it was prior to the operational steady state stage. Objectives of this paper are to study the change in media porosity of HSSF wetland cells in order to estimate duration of wetland setup stage, and to evaluate the use of different bed media on biological oxygen demand (BOD, chemical oxygen demand (COD and total suspended solids (TSS treatment. The results showed that after 180 days of operation, the wetland cells had reached steady porosity and had started stable treatment. Also performance of plastic media bed in pollutants reduction was better than gravel and rubber beds and gravel media was in advanced than rubber media.

  12. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

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    Sclafani, Francesco; Peckitt, Clare [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Cunningham, David, E-mail: david.cunningham@rmh.nhs.uk [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Tait, Diana [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Giralt, Jordi [Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona (Spain); Glimelius, Bengt [University of Uppsala, Uppsala (Sweden); Keränen, Susana Roselló [Biomedical Research Institute INCLIVA, Department of Hematology and Medical Oncology, University of Valencia (Spain); Bateman, Andrew [Southampton General Hospital, Cancer Sciences Unit, University of Southampton (United Kingdom); Hickish, Tamas [Poole Hospital NHS Foundation Trust, Department of Medical Oncology, Bournemouth University (United Kingdom); Tabernero, Josep [Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona (Spain); Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian [The Royal Marsden NHS Foundation Trust, London (United Kingdom)

    2015-10-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.

  13. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    International Nuclear Information System (INIS)

    Sclafani, Francesco; Peckitt, Clare; Cunningham, David; Tait, Diana; Giralt, Jordi; Glimelius, Bengt; Keränen, Susana Roselló; Bateman, Andrew; Hickish, Tamas; Tabernero, Josep; Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian

    2015-01-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term

  14. Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival

    International Nuclear Information System (INIS)

    Gomez, Daniel R.; Liao, Kai-Ping; Swisher, Stephen G.; Blumenschein, George R.; Erasmus, Jeremy J.; Buchholz, Thomas A.; Giordano, Sharon H.; Smith, Benjamin D.

    2015-01-01

    Purpose: Prompt staging and treatment are crucial for non-small cell lung cancer (NSCLC). We determined if predictors of treatment delay after diagnosis were associated with prognosis. Materials and methods: Medicare claims from 28,732 patients diagnosed with NSCLC in 2004–2007 were used to establish the diagnosis-to-treatment interval (ideally ⩽35 days) and identify staging studies during that interval. Factors associated with delay were identified with multivariate logistic regression, and associations between delay and survival by stage were tested with Cox proportional hazard regression. Results: Median diagnosis-to-treatment interval was 27 days. Receipt of PET was associated with delays (57.4% of patients with PET delayed [n = 6646/11,583] versus 22.8% of those without [n = 3908/17,149]; adjusted OR = 4.48, 95% CI 4.23–4.74, p < 0.001). Median diagnosis-to-PET interval was 15 days; PET-to-clinic, 5 days; and clinic-to-treatment, 12 days. Diagnosis-to-treatment intervals <35 days were associated with improved survival for patients with localized disease and those with distant disease surviving ⩾1 year but not for patients with distant disease surviving <1 year. Conclusion: Delays between diagnosing and treating NSCLC are common and associated with use of PET for staging. Reducing time to treatment may improve survival for patients with manageable disease at diagnosis

  15. {sup 99m}Tc-3PRGD{sub 2} SPECT to monitor early response to neoadjuvant chemotherapy in stage II and III breast cancer

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    Ji, Bin; Chen, Bin; Wang, Ting; Chen, Minglong; Ji, Tiefeng; Gao, Shi; Ma, Qingjie [China-Japan Union Hospital of Jilin University, Department of Nuclear Medicine, Changchun (China); Song, Yan [China-Japan Union Hospital of Jilin University, Department of Breast Surgery, Changchun (China); Wang, Xueju [China-Japan Union Hospital of Jilin University, Department of Pathology, Changchun (China)

    2015-08-15

    Monitoring of response to neoadjuvant chemotherapy (NCT) is important for optimal management of patients with breast cancer. {sup 99m}Tc-3PRGD{sub 2} SPECT is a newly developed imaging modality for evaluating tumor vascular status. In this study, we investigated the application of {sup 99m}Tc-3PRGD{sub 2} SPECT in evaluating therapy response to NCT in patients with stage II or III breast cancer. Thirty-three patients were scheduled to undergo {sup 99m}Tc-3PRGD{sub 2} SPECT at baseline, after the first and second cycle of NCT. Four patients had extremely low {sup 99m}Tc-3PRGD{sub 2} uptake at baseline, and were not included in the subsequent studies. Changes in tumor to nontumor (T/N) ratio were compared with pathological tumor responses classified using the residual cancer burden system. Receiver operator characteristic analysis was used to compare the power to identify responders between the end of the first and the end of the second cycle of NCT. The impact of breast cancer subtype on {sup 99m}Tc-3PRGD{sub 2} uptake was evaluated. The correlation between {sup 99m}Tc-3PRGD{sub 2} uptake and pathological tumor response was also evaluated in each breast cancer subtype. Surgery was performed after four cycles of NCT and pathological analysis revealed 18 responders and 15 nonresponders. In patients with clearly visible {sup 99m}Tc-3PRGD{sub 2} uptake at baseline, the sensitivity, specificity, and negative predictive value of {sup 99m}Tc-3PRGD{sub 2} SPECT were 86.7 %, 85.7 % and 86.7 % after the first cycle of NCT, and 92.9 %, 93.3 % and 93.3 % after the second cycle, respectively. Among these patients, the HER-2-positive group demonstrated both higher T/N ratios and a greater change in T/N ratio than patients with other breast cancer subtypes (P < 0.05). A strong correlation was found between changes in T/N ratio and pathological tumor response in the HER-2-positive group (P < 0.03). {sup 99m}Tc-3PRGD{sub 2} SPECT seems to be useful for determining the pathological

  16. Quimioterapia neoadjuvante em câncer localmente avançado do colo do útero Neoadjuvant chemotherapy in locally advanced cancer of the cervix

    Directory of Open Access Journals (Sweden)

    Eduardo Schünemann Jr

    2002-12-01

    Full Text Available OBJETIVOS: avaliar a quimioterapia neoadjuvante no câncer localmente avançado do colo uterino, por meio da sua aceitabilidade, tolerabilidade, toxicidade, taxa de complicações cirúrgicas, taxa de resposta, taxa de operabilidade e sobrevida em 5 anos. MÉTODOS: foram incluídas 60 mulheres com câncer do colo uterino localmente avançado (IIB e IIIB, submetidas à quimioterapia neoadjuvante com doxorrubicina-bleomicina-cisplatina. Aquelas que se tornaram operáveis após a quimioterapia foram submetidas à cirurgia de Wertheim-Meigs, seguida de radioterapia pélvica complementar. Nas pacientes em que a cirurgia não foi possível após a quimioterapia, realizou-se radioterapia. RESULTADOS: o seguimento médio foi de 108 meses. A taxa de resposta global à quimioterapia foi de 80%, sendo 100% para o estádio IIB e 60% para o estádio IIIB. A porcentagem de pacientes operadas, após a quimioterapia foi de 65%. A sobrevida global em 5 anos para todo o grupo foi 62%. No grupo operado (n=34, a sobrevida global foi de 82,14%, independentemente do estádio inicial. No grupo não operado (n=18, a sobrevida em 5 anos foi 16,67%. CONCLUSÕES: A quimioterapia neoadjuvante com doxorrubicina-bleomicina-cisplatina no câncer do colo uterino localmente avançado é segura, com baixo índice de complicações e permitiu uma alta taxa de operabilidade.PURPOSE: to evaluate neoadjuvant chemotherapy in locally advanced cervical cancer as to its acceptability, tolerability, toxicity, surgical complications, operability, response rate, and overall survival in 5 years. METHODS: sixty women with locally advanced cervical cancer (stages IIB and IIIB, who were submitted to neoadjuvant chemotherapy, were included. All patients were treated with doxorubicin-bleomycin-cisplatin. Those who had a good response, allowing a surgical approach, underwent the Wertheim-Meigs procedure. After surgery, they were submitted to pelvic radiotherapy. Those that could not be submitted

  17. EVALUATION OF A TWO-STAGE PASSIVE TREATMENT APPROACH FOR MINING INFLUENCE WATERS

    Science.gov (United States)

    A two-stage passive treatment approach was assessed at bench-scale using two Colorado Mining Influenced Waters (MIWs). The first-stage was a limestone drain with the purpose of removing iron and aluminum and mitigating the potential effects of mineral acidity. The second stage w...

  18. Long-term oncological outcomes of a phase II trial of neoadjuvant chemohormonal therapy followed by radical prostatectomy for patients with clinically localised, high-risk prostate cancer.

    Science.gov (United States)

    Silberstein, Jonathan L; Poon, Stephen A; Sjoberg, Daniel D; Maschino, Alexandra C; Vickers, Andrew J; Bernie, Aaron; Konety, Badrinath R; Kelly, W Kevin; Eastham, James A

    2015-07-01

    To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer. In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only. In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence (BCR-free probability 22%; 95% confidence interval [CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival (HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant. Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

  19. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

  20. Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

    Science.gov (United States)

    Noh, J M; Park, W; Suh, C-O; Keum, K C; Kim, Y B; Shin, K H; Kim, K; Chie, E K; Ha, S W; Kim, S S; Ahn, S D; Shin, H S; Kim, J H; Lee, H-S; Lee, N K; Huh, S J; Choi, D H

    2014-03-18

    To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

  1. Activities of daily living and quality of life during treatment with neoadjuvant chemoradiotherapy and after surgery in patients with esophageal cancer.

    Science.gov (United States)

    Haj Mohammad, Nadia; De Rooij, Sophia; Hulshof, Maarten; Ruurda, Jelle; Wijnhoven, Bas; Erdkamp, Frans; Sosef, Meindert; Gisbertz, Suzanne; van Berge Henegouwen, Mark; Sprangers, Mirjam; van Laarhoven, Hanneke

    2016-11-01

    Neoadjuvant chemoradiation (nCRT) followed by esophagectomy is a treatment with curative intent for resectable esophageal cancer. The aim of this study was to measure activities of daily living (ADL) and quality of life (QoL), and to examine correlates of changes in ADL and QoL. A prospective study was performed with three time points (baseline, 1 week after the end of nCRT, 3-months post-surgery) together with a cross-sectional post-treatment study. ADL was measured with the Amsterdam Linear Disability Score (ALDS), and QoL with the EORTC QLQ-C30 and the OES-18. Regression analysis was performed to identify factors associated with changes in ADL and QoL. Seventy-six patients were included in the prospective study, 79 in the cross-sectional study. After nCRT, ALDS decreased from 90 to 88 (P < 0.01) and remained stable after surgery. Global QoL decreased from 75 to 61 (P < 0.01); no significant changes were observed after surgery. Only timing of the measurement of ALDS was negatively associated with non-maximum ALDS (n = 155, based on both studies) and QoL (n = 76) (P < 0.01). Patients who undergo nCRT plus surgery should be prepared to experience a short-term decline in ADL and QoL. The findings of this study can support patients and healthcare workers to guide expectations. J. Surg. Oncol. 2016;114:684-690. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Physical activity levels in locally advanced rectal cancer patients following neoadjuvant chemoradiotherapy and an exercise training programme before surgery: a pilot study.

    Science.gov (United States)

    Loughney, Lisa; West, Malcolm A; Dimitrov, Borislav D; Kemp, Graham J; Grocott, Michael Pw; Jack, Sandy

    2017-01-01

    The aim of this pilot study was to measure changes in physical activity level (PAL) variables, as well as sleep duration and efficiency in people with locally advanced rectal cancer (1) before and after neoadjuvant chemoradiotherapy (CRT) and (2) after participating in a pre-operative 6-week in-hospital exercise training programme, following neoadjuvant CRT prior to major surgery, compared to a usual care control group. We prospectively studied 39 consecutive participants (27 males). All participants completed standardised neoadjuvant CRT: 23 undertook a 6-week in-hospital exercise training programme following neoadjuvant CRT. These were compared to 16 contemporaneous non-randomised participants (usual care control group). All participants underwent a continuous 72-h period of PA monitoring by SenseWear biaxial accelerometer at baseline, immediately following neoadjuvant CRT (week 0), and at week 6 (following the exercise training programme). Of 39 recruited participants, 23 out of 23 (exercise) and 10 out of 16 (usual care control) completed the study. In all participants ( n  = 33), there was a significant reduction from baseline (pre-CRT) to week 0 (post-CRT) in daily step count: median (IQR) 4966 (4435) vs. 3044 (3265); p  exercise group compared to the usual care control group (80 (13) vs. 78 (15) compared to (69 ((24) vs. 76 (20); p  = 0.022), as well as in sleep duration and lying down time ( p  importance but did not reach statistical significance ( p  > 0.05). An apparent improvement in daily step count and overall PAL in the exercise group was not statistically significant. PAL variables, daily step count, EE and MET significantly reduced following neoadjuvant CRT in all participants. A 6-week pre-operative in-hospital exercise training programme improved sleep efficiency, sleep duration and lying down time when compared to participants receiving usual care. Clinicaltrials.gov NCT01325909.

  3. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

    Science.gov (United States)

    Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

    2018-05-03

    BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

  4. Preoperative staging and treatment options in T1 rectal adenocarcinoma

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Endreseth, Birger H; Isaksen, Vidar

    2009-01-01

    . Results. Local treatment of T1 cancers combined with close follow-up, early salvage surgery or later radical resection of local recurrences or with chemo-radiation may lead to fewer severe complications and comparable, or even better, long-term survival. Accurate preoperative staging and careful selection...... of patients for local or non-operative treatment are mandatory. As preoperative staging, at present, is not sufficiently accurate, strategies for completion, salvage or rescue surgery is important, and must be accepted by the patient before local treatment for cure is initiated. Recommendations......Background. Major rectal resection for T1 rectal cancer offers more than 95% cancer specific five-year survival to patients surviving the first 30 days after surgery. A significant further improvement by development of the surgical technique may not be possible. Improvements in the total survival...

  5. [Radical Resection of Huge Gastrointestinal Stromal Tumor of the Stomach Following Neoadjuvant Chemotherapy with lmatinib - ACase Report].

    Science.gov (United States)

    Hiraki, Yoko; Kato, Hiroaki; Shiraishi, Osamu; Tanaka, Yumiko; Iwama, Mitsuru; Yasuda, Atsushi; Shinkai, Masayuki; Kimura, Yutaka; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

    2017-11-01

    The usefulness and safety of imatinibfor neoadjuvant chemotherapy for resectable gastrointestinal stromal tumor(GIST) has not been established. We reported a case of a huge GIST of the stomach that was safely resected following preoperative imatinibtherapy. A 69-year-old man was hospitalized with abdominal fullness which increased rapidly from a month ago. A CT scan showed a huge tumor containing solid and cystic component which was accompanied by an extra-wall nodule. The tumor was strongly suspected to be originated from the stomach and EUS-FNA revealed GIST. We diagnosed GIST of the stomach and initiated preoperative adjuvant chemotherapy with imatinib because there was a risk for the break of tumor capsule and composite resection of the other organs without prior chemotherapy. After the administration of imatinib4 00 mg/day for 6months, the solid component was decreased in size and its' activity by PET-CT had declined, but the size of the cystic component was not changed and the patient's complaint of fullness was not reduced. Then, after a week cessation of imatinib, we performed surgical removal of the tumor with partial gastrectomy without surgical complication during and after the operation. Imatinibwas resumed 2 weeks later postoperatively and 1 year and 8 months has passed since the operation without recurrence. Neoadjuvant chemotherapy with imatinibhas the potential to become an important therapeutic option for the treatment of huge GISTs.

  6. Immunological tumor status may predict response to neoadjuvant chemotherapy and outcome after radical cystectomy in bladder cancer.

    Science.gov (United States)

    Tervahartiala, Minna; Taimen, Pekka; Mirtti, Tuomas; Koskinen, Ilmari; Ecke, Thorsten; Jalkanen, Sirpa; Boström, Peter J

    2017-10-04

    Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of patients to chemotherapy that are likely to respond to the treatment. To date, there are no validated molecular markers or baseline clinical characteristics to identify these patients. Different inflammatory markers, including tumor associated macrophages with their plastic pro-tumorigenic and anti-tumorigenic functions, have extensively been under interests as potential prognostic and predictive biomarkers in different cancer types. In this immunohistochemical study we evaluated the predictive roles of three immunological markers, CD68, MAC387, and CLEVER-1, in response to NAC and outcome of BC. 41% of the patients had a complete response (pT0N0) to NAC. Basic clinicopathological variables did not predict response to NAC. In contrast, MAC387 + cells and CLEVER-1 + macrophages associated with poor NAC response, while CLEVER-1 + vessels associated with more favourable response to NAC. Higher counts of CLEVER-1 + macrophages associated with poorer overall survival and CD68 + macrophages seem to have an independent prognostic value in BC patients treated with NAC. Our findings point out that CD68, MAC387, and CLEVER-1 may be useful prognostic and predictive markers in BC.

  7. Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging

    Science.gov (United States)

    2013-01-01

    Abstract High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient’s quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist’s role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients’ life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer. PMID:23876415

  8. Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging.

    Science.gov (United States)

    Dieguez, Adriana

    2013-07-22

    High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient's quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist's role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients' life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer.

  9. Performance and Practice Guideline for the Use of Neoadjuvant Systemic Therapy in the Management of Breast Cancer.

    Science.gov (United States)

    Holmes, Dennis; Colfry, A; Czerniecki, Brian; Dickson-Witmer, Diana; Francisco Espinel, C; Feldman, Elizabeth; Gallagher, Kristalyn; Greenup, Rachel; Herrmann, Virginia; Kuerer, Henry; Malik, Manmeet; Manahan, Eric; O'Neill, Jennifer; Patel, Mita; Sebastian, Molly; Wheeler, Amanda; Kass, Rena

    2015-10-01

    The American Society of Breast Surgeons (ASBrS) sought to provide an evidence-based guideline on the use of neoadjuvant systemic therapy (NST) in the management of clinical stage II and III invasive breast cancer. A comprehensive nonsystematic review was performed of selected peer-reviewed literature published since 2000. The Education Committee of the ASBrS convened to develop guideline recommendations. A performance and practice guideline was prepared to outline the baseline assessment and perioperative management of patients with clinical stage II-III breast cancer under consideration for NST. Preoperative or NST is emerging as an important initial strategy for the management of invasive breast cancer. From the surgeon's perspective, the primary goal of NST is to increase the resectability of locally advanced breast cancer, increase the feasibility of breast-conserving surgery and sentinel node biopsy, and decrease surgical morbidity. To ensure optimal patient selection and efficient patient care, the guideline recommends: (1) baseline breast and axillary imaging; (2) minimally invasive biopsies of breast and axillary lesions; (3) determination of tumor biomarkers; (4) systemic staging; (5) care coordination, including referrals to medical oncology, radiation oncology, plastic surgery, social work, and genetic counseling, if indicated; (6) initiation of NST; (7) post-NST breast and axillary imaging; and (8) decision for surgery based on extent of disease at presentation, patient choice, clinical response to NST, and genetic testing results, if performed.

  10. Results of combined modality treatment in patients with primary unresectable cancer of the oral cavity

    International Nuclear Information System (INIS)

    Kawecki, A.; Starosciak, S.; Towpik, E.; Jagielska, B.; Lenartowicz, B.; Pietras, M.; Szutkowski, Z.; Kiprian, D.

    2001-01-01

    Neoadjuvant chemotherapy may improve the results of treatment for primarily unresectable cancer of the oral cavity. The aim of this study was to estimate the tolerance and early results of neoadjuvant chemotherapy followed by surgical resection of oral cavity cancer, with immediate reconstruction and adjuvant radiotherapy. 56 patients hospitalized at the Department of Head and Neck Cancer of the Maria Sklodowska-Curie Memorial Cancer Centre - Institute of Oncology between August 1997 and June 2000 were enrolled for the purpose of the study. When tumour regresion was observed after 2-4 courses of neoadjuvant chemotherapy consisting of cisplatin, 5-fluorouracil, methotrexate, vinblastin, etoposide and leucovorin, the patients were referred for surgical resection with immediate reconstruction, followed by adjuvant radiotherapy. Regression of the primary tumor and lymph nodes of the neck was observed in 41 patients, all of whom were referred for radical surgery followed by adjuvant radiotherapy. The tolerance of combined treatment was acceptable. Complete regression was obtained in 37/56 patients. During observation 12 patients failed due to locoregional progression and 2 due to distant metastases. 23/56 patients (41 %) are alive without evidence of disease. Neoadjuvant chemotherapy allows for radical resection in a majority of patients with primarily unresectable cancer of the oral cavity. The tolerance of treatment is good. What is important, radiotherapy and chemotherapy do not impair wound healing and vascularity of musculo-cutaneous island flaps

  11. Laparoscopic surgery for lower rectal cancer with neoadjuvant preoperative chemoradiotherapy

    International Nuclear Information System (INIS)

    Kondo, Keisaku; Okuda, Junji; Tanaka, Keitaro

    2012-01-01

    Neoadjuvant chemoradiotherapy (NACRT) is an accepted standard treatment for low rectal advanced cancer to improve the local control in western countries. Recently laparoscopy has been recognized as an excellent tool from a view point of its magnification. Therefore, we have performed many laparoscopic surgeries for locally advanced rectal cancer after NACRT, We evaluated our results in this study. We studied 100 patients underwent surgery for locally advanced low rectal cancer after NACRT. Rate of sphincter preserving surgery was 74%. Rate of laparoscopic surgery was 95%. Positive distal resection margins were not identified in all patients. Positive circumferencial resection margins were identified in only two patients. The pathological complete response rate was 15%. The rate of postoperative complications was 15%. Complications were as follows: wound infection (9%), pelvic abscess (2%), ileus (2%) and others (2%), however without mortality. Anastomotic leakage was not observed in all cases, even though we routinely created diverting stoma. Laparoscopic surgery for low rectal cancer after NACRT is considered to be a safe and feasible procedure. (author)

  12. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Galsky, Matthew D; Pal, Sumanta K; Chowdhury, Simon

    2015-01-01

    ). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved......BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had...... clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients...

  13. Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy; Tratamento conservador dos carcinomas de mama localmente avancados T2 e T3, apos quimioterapia neoadjuvante, com quadrantectomia e braquiterapia de alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante

    Energy Technology Data Exchange (ETDEWEB)

    Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia]. E-mail: cefristachi@uol.com.br; Miziara Filho, Miguel Abrao; Soares, Celia Regina; Fogaroli, Ricardo Cesar; Pelosi, Edilson Lopes; Martins, Homero Lavieri Martins [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia; Baracat, Fausto Farah [Hospital do Servidor Publico Estadual de Sao Paulo (HSPE), SP (Brazil). Servico de Ginecologia e Mastologia; Piato, Sebastiao [Irmandade da Santa Casa de Misericordia de Sao Paulo, SP (Brazil). Dept. de Obstetricia e Ginecologia (DOGI)

    2005-07-01

    Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

  14. Role of mammography in evaluating residual cancer of locally advanced breast carcinoma after neo-adjuvant chemotherapy : compared with clinical examination

    International Nuclear Information System (INIS)

    Choi, Byoung Wook; Kim, Eun Kyung; Oh, Ki Keun; Cho, Jae Min; Chung, Hyun Cheol; Lee, Byung Chan; Lee, Kyong Sik; Lee, Yong Hee

    1997-01-01

    To compare the usefulness of mammography and clinical examination in the evaluation of residual cancer of locally-advanced breast carcinoma treated with neoadjuvant chemotherapy. Among 67 patients with locally advanced breast carcinoma who were treated with neoadjuvant chemotherapy, 18, aged 35-67 (mean, 48) years, underwent mammography before and after this therapy. The 18 sets of mammographs were analyzed retrospectively and compared with the results of clinical examination based on histologic diagnosis. On histologic examinations, 16 of 18 patients (89%) were found to have residual cancer, but in one of these 16, mammography did not show this same result. On mammography, residual cancer was found in 16 patients, but in one of this group, histologic examination did not reveal the same finding. Clinically, a complete response was shown by four patients, and a partial response by 11 ; three showed no response. On histolgogic examination, three of the four patients with complete clinical response were found to have residual cancer. Post-treatment mammographic findings showed that 11 patients had measurable mass ; all of these had residual cancer (positive predictive value : 100%). However, five of seven patients in whom no measurable mass was evident also had residual cancer. Seven of 8 patients in whom microcalcifications were seen on mammography were found to have residual cancer (positive predictive value : 88%). The sensitivity of mammography in predicting residual cancer was greater than that of clinical examination (94% vs 81%), even when microscopic residual cancer was considered as a complete response (92% vs 77%). The specificity of mammography was the same as that of clinical examination(50% vs 50%, 20% vs 20%). In evaluating residual cancer of locally-advanced breast carcinoma after neoadjuvant chemotheragy, mammography is more accurate and informative than clincal examination. In predicting residual cancer, however, it is not accurate enough to replace

  15. Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial.

    Science.gov (United States)

    Issa-Nummer, Yasmin; Darb-Esfahani, Silvia; Loibl, Sibylle; Kunz, Georg; Nekljudova, Valentina; Schrader, Iris; Sinn, Bruno Valentin; Ulmer, Hans-Ullrich; Kronenwett, Ralf; Just, Marianne; Kühn, Thorsten; Diebold, Kurt; Untch, Michael; Holms, Frank; Blohmer, Jens-Uwe; Habeck, Jörg-Olaf; Dietel, Manfred; Overkamp, Friedrich; Krabisch, Petra; von Minckwitz, Gunter; Denkert, Carsten

    2013-01-01

    We have recently described an increased lymphocytic infiltration rate in breast carcinoma tissue is a significant response predictor for anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study was to prospectively validate the tumor-associated lymphocyte infiltrate as predictive marker for response to anthracycline/taxane-based NACT. The immunological infiltrate was prospectively evaluated in a total of 313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy), stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer (LPBC) were evaluated by histopathological assessment. Pathological complete response (pCR) rates were analyzed and compared between the defined subgroups using the exact test of Fisher. Patients with lymphocyte-predominant breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to non-LPBC patients (14.3%, pimmunological infiltrate in breast tumor tissue is predictive for response to anthracycline/taxane-based NACT. Patients with LPBC and increased stromal lymphocyte infiltration have significantly increased pCR rates. The lymphocytic infiltrate is a promising additional parameter for histopathological evaluation of breast cancer core biopsies.

  16. Multimodality treatment of locally advanced squamous cell carcinoma of the oesophagus: A comprehensive review and network meta-analysis.

    Science.gov (United States)

    Montagnani, Francesco; Fornaro, Lorenzo; Frumento, Paolo; Vivaldi, Caterina; Falcone, Alfredo; Fioretto, Luisa

    2017-06-01

    Surgery is the mainstay of treatment for oesophageal squamous-cell carcinoma (OSCC) but with poor results. Attempts to improve patient outcome have been made by introducing chemotherapy (CT), radiotherapy (RT), or both (CRT). However, randomized comparisons for all these strategies are not always available. We conducted an extensive literature search for studies comparing surgery with multimodality treatment (i.e. [neo-]adjuvant CT or RT or CRT or definitive CRT). Network meta-analysis was performed in a Bayesian framewor and node-split models were built to assess inconsistency. Twenty-five trials including a total of 3866 OSCC patients were included. Neoadjuvant CRT was associated with the most robust survival advantage across different multimodality treatment options (HR 0.73; 95% credible interval [CrI] 0.63-0.86). Definitive CRT was also significantly more effective than surgery but with greater uncertainties (HR 0.62; 95%CrI 0.41-0.96). Neoadjuvant CT (HR 0.90; 95%CrI 0.76-1.07) and adjuvant CRT (HR 1.00; 95%CrI 0.70-1.40) are associated with a non-significant benefit. To date, neoadjuvant CRT seems to represent the best approach to maximize the benefit of a multimodality approach. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Preoperative CT prediction for Masaoka staging of thymic epithelial tumor

    International Nuclear Information System (INIS)

    Feng Zhan; Huang Zhen; Zhang Liang

    2013-01-01

    Objective: To discuss the value of CT prognosis on the Masaoka staging system of thymic epithelial tumors (TET) before surgical resection. Methods: The CT images of 102 patients with TET proved by surgery and pathology were reviewed retrospectively. The TET were reclassified according to Masaoka stage system. The size, homogeneity, sharp, contour, infiltration of surrounding tissue, and metastasis on CT were analyzed with Logistic analysis. The diagnostic value was also evaluated with a ROC curve. Results: Masaoka pathologic stages were stage Ⅰ for 36 (35.3 %), stage Ⅱ for 27 (26.5 %), stage Ⅲ for 30 (29.4 %), and stage Ⅳ for 9 (8.8 %). A multivariable Logistic regression model showed that TET with larger size of tumor (20/35, P = 0.0371, OR = 4.539), irregular or lobulated tumor contour (26/42, P = 0.0230, OR = 4.870), heterogeneous (21/33, P = 0.0154, OR = 6.020), infiltration of surrounding fat (25/32, P = 0.0019, OR = 14.005), and pleural seeding (11/11, P = 0.0032, OR = 36.153) were more likely to have stage Ⅲ or Ⅳ disease. The area under ROC curve was 0.940. Conclusions: The tumor CT imaging features can differentiate between stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ disease. This helps identified patients more likely to benefit from neoadjuvant therapy. (authors)

  18. Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

    Science.gov (United States)

    Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

    2017-07-01

    Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

  19. The Use of Biodegradable Stents in Malignant Oesophageal Strictures for the Treatment of Dysphagia Before Neoadjuvant Treatment or Radical Radiotherapy: A Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Krokidis, Miltiadis, E-mail: mkrokidis@hotmail.com; Burke, Chris; Spiliopoulos, Stavros; Gkoutzios, Panos [Guy' s and St. Thomas' NHS Trust, St Thomas' Hospital, Department of Radiology (United Kingdom); Hynes, Orla [Guy' s and St. Thomas' NHS Trust, Department of Surgery (United Kingdom); Ahmed, Irfan; Dourado, Renato; Sabharwal, Tarun [Guy' s and St. Thomas' NHS Trust, St Thomas' Hospital, Department of Radiology (United Kingdom); Mason, Robert [Guy' s and St. Thomas' NHS Trust, Department of Surgery (United Kingdom); Adam, Andreas [Guy' s and St. Thomas' NHS Trust, St Thomas' Hospital, Department of Radiology (United Kingdom)

    2013-08-01

    PurposeTo evaluate the clinical results of the use of biodegradable oesophageal stents in malignant strictures.MethodsEleven patients were included in this prospective analysis in which a woven polydioxanone biodegradable oesophageal stent was used. The inclusion criterion was that the patient underwent neoadjuvant treatment or radical radiotherapy after the stent insertion. Primary end points were dysphagia score at discharge, stent patency, and complication rate. Secondary end points were overall survival and surgical outcome of surgery.ResultsThere was a 100 % procedure technical success rate. Early complications occurred in three patients resulting in failure to restore oral nutrition. In the remaining eight patients, dysphagia was significantly improved at discharge. Mean stent patency rate in this group was 71.5 days. Stent dysfunction occurred in five of eight patients (62.5 %); in two of five patients this was due to local inflammatory reaction, and in three of five patients it was due to tumour growth after a mean time of 97.8 days, and a new metallic stent was consequently placed in four of five patients. One patient was successfully treated with esophagectomy. At the end of follow-up (mean time 102.1 days), three of eight stents were patent. The overall patient survival rate was 81.8 %.ConclusionAlthough short-term dysphagia scores improved, biodegradable stents do not appear to offer a clear beneficial effect in most cases of malignant strictures, particularly due to a local inflammatory reaction that may be induced. Technical improvement of the device and delineation of the patient group that would benefit from its use is necessary if further studies are to be conducted in the future.

  20. Segmental mastectomy and radiotherapy as treatment of stage II breast cancer

    International Nuclear Information System (INIS)

    Faria, S.L.; Chiminazzo Junior, H.; Schlupp, W.R.; Cunha, L.S.M. da

    1987-01-01

    The treatment of operable breast cancer with segmental mastectomy and radiotherapy has been described since decade 30. Many recent prospective and retrospective studies have shown the efficacy of this conservative management, particularly in stage I. There are still doubts in its use in stage II. (Author) [pt

  1. MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    LENUS (Irish Health Repository)

    Bibby, Becky A S

    2015-01-01

    Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA\\/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1\\/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1\\/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of

  2. Total mesorectal excision for the treatment of rectal cancer.

    Science.gov (United States)

    Zedan, Ali; Salah, Tareq

    2015-12-01

    In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan's technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan's technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was administered to 67.3% of the

  3. Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.

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    Xuemei Ji

    Full Text Available BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC treated by intensity modulated radiotherapy (IMRT and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS, metastasis-free survival (MFS, relapse-free survival (RFS, and disease-free survival (DFS were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03, patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03, neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.

  4. Breast Cancer Basics and You: Staging and Treatment | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Breast Cancer Breast Cancer Basics and You: Staging and Treatment Past Issues / ... Table of Contents Staging The extent (stage) of breast cancer needs to be determined to help choose the ...

  5. Skin rash in patients treated with neoadjuvant erlotinib (Tarceva in resectable non-small cell lung cancer: Predictor for tumor response and survival?

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    Van Gool MH

    2017-08-01

    Full Text Available Background: Skin rash during treatment with epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKI has been reported to be predictive for response and survival in patients with advanced non-small cell lung cancer (NSCLC. The aim of this analysis was to evaluate whether skin rash during treatment (as a biomarker in a preoperative setting was related to response and survival. Methods: This study was designed as an open-label phase II trial (also known as M06NEL. Patients received preoperative erlotinib (Tarceva 150 mg once daily for 3 weeks. Skin toxicity during treatment was analysed in relation to metabolic and histopathological response, overall survival (OS and progression-free survival (PFS. Results: In total 59 patients (25 male, 34 female were eligible for analysis. In 39 patients (66% skin toxicity occurred. According to National Cancer Institute Common Toxicity Criteria (NCICTC, Grade 1 toxicity was seen in 15 patients (25%, Grade 2 in 19 patients (32% and Grade 3 in five patients (8%. None of the patients showed skin toxicity Grade 4 and 5. The median follow up was 74 months. Thirty-six patients (61% were alive at time of analysis. Twenty-seven patients (46% showed disease progression during follow up. Hazard ratios (HR indicated lower risk of death (HR = 0.66, 95%CI: 0.29 - 1.50 and progression (HR = 0.64, 0.30 - 1.36, although in this small group results were not significant. Skin rash did not adequately predict response. Conclusions: In this neoadjuvant setting with limited treatment time in patients with early stage NSCLC, skin rash was not associated with response and survival and cannot be used as an early biomarker.

  6. Population-based treatment and outcomes of Stage I uterine serous carcinoma

    NARCIS (Netherlands)

    Putten, L.J.M. van der; Hoskins, P.; Tinker, A.; Lim, P.; Aquino-Parsons, C.; Kwon, J.S.

    2014-01-01

    OBJECTIVE: Uterine serous carcinoma (USC) is a rare type of endometrial cancer that often recurs in patients with Stage I disease. Our objective was to evaluate treatment and outcomes in Stage I USC in the context of a population-based study. METHODS: This was a population-based retrospective cohort

  7. Ovarian preservation in locally advanced cervical cancer undergoing neoadjuvant chemotherapy and radical surgery: our experience and analysis of the literature.

    Science.gov (United States)

    Signorelli, Mauro; Bogani, Giorgio; Chiappa, Valentina; Ditto, Antonino; Scaffa, Cono; Martinelli, Fabio; Lorusso, Domenica; Raspagliesi, Francesco

    2018-03-30

    The aim of this study was to estimate the rate of ovarian metastases and recurrences among patients affected by locally advanced stage cancer patients (LACC), undergoing neoadjuvant chemotherapy (NACT) and radical surgery with conservation of ovaries. Retrospective evaluation of consecutive patients affected by LACC (stage IB2- IIB), treated by NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990-2015. Overall, 331 patients were included. Stage at presentation included stage IB2, IIA and IIB in 120 (36.3%), 63 (19%) and 148 (44.7%) patients, respectively. Main histotype was squamous cell carcinoma (n=265, 80.1%) followed by adenocarcinoma/adenosquamous (n=51, 15.4%), and more than half of patients had a grade 3 carcinoma . Overall, 102 (30.8%) women had at least one ovary preserved during surgery, while 229 (69.2%) had bilateral salpingo-oophorectomy. Comparing patients who had ovarian preservation with patients who had not, we observed that the two groups were comparable in terms of baseline characteristics. Survival outcomes were not influenced by ovarian preservation (disease-free (p=0.93) and overall (p=0.65) survivals). One (1%) woman had a localized ovarian recurrence. Our data suggest that ovarian preservation at the time of surgery is a safe option among women with LACC after NACT with no detrimental impact on oncologic outcome. Further prospective studies are warranted.

  8. PSA bounces after neoadjuvant androgen deprivation and external beam radiation: Impact on definitions of failure

    International Nuclear Information System (INIS)

    Zietman, Anthony L.; Christodouleas, John P.; Shipley, William U.

    2005-01-01

    Purpose: To determine the characteristics of prostate specific antigen (PSA) bounces after external beam radiation therapy (EBRT) with neoadjuvant androgen deprivation and their impact on definitions of biochemical failure. Methods and Materials: Characteristics of bounce were calculated for all patients treated by EBRT with neoadjuvant androgen deprivation at our institution between 1992 and 1998 (preexclusion analysis). Calculations were repeated for the subgroup that satisfied additional inclusion/exclusion criteria (postexclusion analysis). The percentage of bounces scoring as false positives according to the ASTRO definition of biochemical failure was compared with those for three alternative definitions (Vancouver, Nadir-plus-two, and Nadir-plus-three) using McNemar's tests. Results: Thirty-nine percent (preexclusion cohort) and 56% (postexclusion cohort) of patients demonstrated a PSA bounce. Twenty percent (preexclusion analysis) and 25% (postexclusion analysis) of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition scored the smallest percentage of bounces as failure, but the difference between this definition and the ASTRO definition reached statistical significance in neither preexclusion nor postexclusion analyses (p ≥ 0.070). Conclusions: A substantial proportion of patients treated by EBRT with neoadjuvant deprivation experienced a PSA bounce. A large percentage of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition is less vulnerable to this bias

  9. Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

    Science.gov (United States)

    Chahal, Harinder S.; Marseille, Elliot A.; Tice, Jeffrey A.; Pearson, Steve D.; Ollendorf, Daniel A.; Fox, Rena K.; Kahn, James G.

    2016-01-01

    IMPORTANCE Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained

  10. Combination of External Beam Radiotherapy (EBRT) With Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of High-Risk Soft Tissue Sarcoma Patients

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    Finkelstein, Steven E., E-mail: steven.finkelstein@moffitt.org [H. Lee Moffitt Cancer Center, Tampa, FL (United States); Iclozan, Cristina; Bui, Marilyn M.; Cotter, Matthew J.; Ramakrishnan, Rupal; Ahmed, Jamil; Noyes, David R.; Cheong, David; Gonzalez, Ricardo J.; Heysek, Randy V.; Berman, Claudia; Lenox, Brianna C.; Janssen, William; Zager, Jonathan S.; Sondak, Vernon K.; Letson, G. Douglas; Antonia, Scott J. [H. Lee Moffitt Cancer Center, Tampa, FL (United States); Gabrilovich, Dmitry I., E-mail: dmitry.gabrilovich@moffitt.org [H. Lee Moffitt Cancer Center, Tampa, FL (United States)

    2012-02-01

    Purpose: The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS). Methods and Material: Seventeen patients with large (>5 cm) high-grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5,040 cGy of EBRT, split into 28 fractions and delivered 5 days per week, combined with intratumoral injection of 10{sup 7} DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle. Clinical evaluation and immunological assessments were performed. Results: The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; 9 patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after 1 year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4{sup +} T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with {sup 111}In labeled DCs demonstrated that these antigen presenting cells need at least 48 h to start migrating from tumor site. Conclusions: Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and needs further testing in clinical trials design to assess clinical efficacy.

  11. The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer

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    Teleki Ivett

    2013-02-01

    Full Text Available Abstract Background Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST are still missing. Deregulation of gap junction channel forming connexins (Cx has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems. Methods The expression of Cx26, Cx32, Cx43, Cx46 and Ki67 was evaluated in 96 breast cancer patients prior to and after neoadjuvant chemotherapy using duplicate cores in tissue microarrays (TMA. Cx plaques of Results In our cohort dominated by hormone receptor (ER/PR positive and HER2 negative cases, only the CPS-EG classification showed prognostic relevance: cases with scores 1–2 had significantly better overall survival (p=0.015 than cases with scores 3–5. Pre-chemotherapy Cx43 expression correlated positively with hormone receptor status both before and after chemotherapy and had a negative correlation with HER2 expression pre-chemotherapy. There was a positive correlation between Cx32 and HER2 expression pre-chemotherapy and between Cx32 and Ki67 expression post-chemotherapy. A negative correlation was found between post-chemotherapy Cx46 and Ki67 expression. Decreased post-chemotherapy Cx26 expression (20% pre- and post-chemotherapy correlated with significantly better survival in the intermediate prognostic subgroups of EWGBSP TR2b (ppre-chemo=0.006; Sataloff TB (ppre-chemo=0.005; ppost-chemo=0.029 and in Miller-Payne G3 (ppre-chemo=0.002; ppost-chemo=0.012 classifications. Pre-chemotherapy, Cx46 expression was the only marker that correlated with overall survival within these subgroups. Conclusion Our results suggest that Cx46 and Cx26 expression

  12. Failure to Achieve a PSA Level ≤1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Mitchell, Darren M.; McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-01-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to ≤1 ng/mL after ≥2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was ≤1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was ≤1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of ≤1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after ≥2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of ≤1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments

  13. Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2-negative breast cancer: NSABP Foundation Study FB-9.

    Science.gov (United States)

    Abraham, Jame; Robidoux, André; Tan, Antoinette R; Limentani, Steven; Sturtz, Keren; Shalaby, Ibrahim; Alcorn, Hope; Buyse, Marc E; Wolmark, Norman; Jacobs, Samuel A

    2015-07-01

    Locally advanced breast cancer (LABC) is a good setting in which to monitor response to neoadjuvant chemotherapy, to downsize the tumor (which facilitates breast-conserving surgery), and to test newer agents in untreated patients. Eribulin (E) has shown activity in patients who have undergone previous taxane, anthracycline, and capecitabine treatment. We aimed to evaluate the neoadjuvant use of E followed by doxorubicin and cyclophosphamide (AC) in patients with HER2-negative LABC, using as a control a randomized group of women who received weekly paclitaxel (WP). Fifty women with LABC were accrued January-August 2013. Patients were randomized (1:2) to receive either WP (N = 19) for 12 treatments or E (N = 31) every 3 weeks for 4 cycles followed by AC every 3 weeks for 4 cycles before surgery. 17/19 patients who took WP and 25/30 who took E completed all cycles. Patients were evaluated by clinical examination and breast MRI at baseline and after completion of E or WP. Surgical pCR in breast and lymph nodes was determined by a local pathologist following chemotherapy. Forty-nine patients received ≥1 dose of neoadjuvant chemotherapy and are included in this analysis. Forty-eight underwent surgery; one had disease that was inoperable (on E) and is included as no-pCR patient. 17/19 of these patients who took WP completed 12 doses; 28/30 on E completed 4 cycles. Six discontinued treatment on WP, E, or AC. Both treatments were well tolerated. pCR on WP = 5/19(26 %) and on E = 5/30(17 %). Both regimens were equally well tolerated with no unexpected toxicities. pCR did not suggest higher activity with E than with other standard regimens in these LABC patients.

  14. PET/CT in staging and treatment response evaluation in lymphomas

    International Nuclear Information System (INIS)

    Bochev, P.

    2015-01-01

    Full text:The introduction of positron emission tomography (PET) and especially PET/CT with FDG in 2001 resulted in new concepts of overall management of patients with lymphoma and changed significantly the staging process and treatment response assessment. The considerable amount of literature and clinical trial data allowed leading cancer organizations like NCCN to incorporate in their current guidelines FDG-PET as a sole imaging modality in the management of Hodgkin‘s lymphoma, and an essential one in the management of FDG avid non-Hodgkin lymphoma (where indications vary based on particular histology). Main indications of FDG PET/CT in lymphoma are initial staging, restaging upon completion of therapy (EOT PET) and treatment response assessment. While staging with FDG and EOT PET restaging alone or combined with CECT have a straight-forward advantage over CT in evaluating small and borderline sized lymph nodes, bone marrow involvement and residual masses, treatment response assessment is rather challenging. By now and after long term trial evaluations, the response assessment is based on a visual assessment five point scale – Deauvillae criteria for response evaluation in HD and combined lugano criteria for NHL. The scale defines PET negative and PET positive cases as a presentation of responders versus non-responders which directly affects management. Although ESMO restricts the use of FDG-PET response evaluation in clinical trials only, NCCN go further, and bases its treatment recommendations on FDG-PET (Interim PET). Nowadays PET/CT is extensively used also in radiotherapy planning, which, in lymphoma patients include initial staging scans on a flat table, in order to assure similar position of future involved sites RT. Despite the extensive use of FDG with the above mentioned indications, neither evidence based guidelines, nor routine clinical practice could recommend follow up of lymphoma patients with FDG-PET. An exception could be made for ositive or

  15. Effect of well-established plasma treatment technology on some physiological characteristics in maize leaves during seedling stage

    International Nuclear Information System (INIS)

    Zhao Hongxiang; Fang Xiangqian; Bian Shaofeng; Zhang Lihua; Tan Guobo; Meng Xiangmeng; Yan Weiping; Liu Yaliang; Sun Ning

    2010-01-01

    In order to provide theoretical references and technical support for application of plasma treatment technology in agriculture, the seeds of maize were treated by well-established plasma treatment technology, then the changes of physiological characteristics of maize leaves during seedling stage were studied. The results indicated that the stress resistance of maize was improved by plasma treatment. The SOD, POD and CAT activities, soluble protein content and soluble sugar content of leaves at two-leave stage, four-leave stage, six-leave stage and eight-leave stage treated by plasma were higher than that of CK, but the MDA content was lower than CK. Although NR activity in leaves at twoleave stage and four-leave stage was slightly lower than CK, but higher than CK at six-leave stage (26.81%) and eightleaves stage (26.75%). Plasma treatment enhanced the nitrogen metabolism capacity, and this tendency was increased remarkable with the growth stages processes. (authors)

  16. ranibizumab in the management of advanced Coats disease Stages 3B and 4: long-term outcomes.

    Science.gov (United States)

    Gaillard, Marie-Claire; Mataftsi, Assimina; Balmer, Aubin; Houghton, Susan; Munier, Francis L

    2014-11-01

    Laser photocoagulation and cryotherapy to completely destroy telangiectatic vessels and ischemic retina in Coats disease is barely applicable in advanced cases with total retinal detachment, and globe survival is notoriously poor in Stages 3B and 4. Anti-vascular endothelial growth factor intravitreal injections may offer new prospects for these patients. This study is a retrospective review of all consecutive patients with Coats disease treated with neoadjuvant or adjuvant intravitreal ranibizumab plus conventional and amblyopia treatment as appropriate. Nine patients (median age, 13 months) presenting Coats Stages 3B and 4 (5 and 4 eyes, respectively) were included. Iris neovascularization resolved within 2 weeks and retinal reapplication within 4 months in all patients. At last follow-up, globe survival was 100% with anatomical success in 8 of the 9 eyes. With a median follow-up of 50 months, fibrotic vitreoretinopathy was developed in 5 of the 9 cases, one leading to tractional retinal detachment and ultimately phthisis bulbi. The remaining 4 of the 9 eyes achieved some vision (range, 0.02-0.063). To the best of the authors' knowledge, this is the largest reported series of late-stage Coats undergoing anti-vascular endothelial growth factor therapy, a homogenous cohort of patients treated with a single agent and with the longest follow-up. This study supports the role of ranibizumab in advanced disease by transient restoration of the hemato-retinal barrier and suppression of neovascularization to facilitate classic treatment. At the last follow-up, the authors report unprecedented anatomical success and functional outcome.

  17. Head and neck squamous cell carcinoma: usefulness of diffusion-weighted MR imaging in the prediction of a neoadjuvant therapeutic effect

    International Nuclear Information System (INIS)

    Kato, Hiroki; Tanaka, Osamu; Hoshi, Hiroaki; Kanematsu, Masayuki; Mizuta, Keisuke; Aoki, Mitsuhiro; Shibata, Toshiyuki; Yamashita, Tomomi; Hirose, Yoshinobu

    2009-01-01

    The purpose of our study was to evaluate the usefulness of diffusion-weighted imaging in predicting the responses to neoadjuvant therapy for head and neck squamous cell carcinomas. Diffusion-weighted, T2-weighted, and gadolinium-enhanced T1-weighted images were obtained from 28 patients with untreated head and neck squamous cell carcinomas with histological proof. A blinded radiologist evaluated the quantitative and qualitative signal intensities and apparent diffusion coefficients (ADCs) in the lesions on each sequence. All patients were treated by neoadjuvant therapies, and the post-therapeutic tumor regression rate was determined. Both the quantitative and qualitative signal intensities on diffusion-weighted images showed positive correlations (r=0.367 and 0.412, p<.05), and the ADCs showed a weak, inversed correlation (r=-0.384, p<.05) with the tumor regression rates. Diffusion-weighted imaging including an assessment by ADCs may be able to predict tumor response to neoadjuvant therapy for head and neck squamous cell carcinomas. (orig.)

  18. Rectal and colon cancer: Not just a different anatomic site.

    Science.gov (United States)

    Tamas, K; Walenkamp, A M E; de Vries, E G E; van Vugt, M A T M; Beets-Tan, R G; van Etten, B; de Groot, D J A; Hospers, G A P

    2015-09-01

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    Directory of Open Access Journals (Sweden)

    Zhang MM

    2016-06-01

    Full Text Available Minmin Zhang,* Wei Wei,* Jianlun Liu, Huawei Yang, Yi Jiang, Wei Tang, Qiuyun Li, Xiaoming Liao Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC, followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT vs taxotere (T, in axillary lymph node (LN-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1 who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1 to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027 and objective remission rate (87% vs 73%, P=0.048 compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001 and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034 but less phlebitis (3% vs 14%, P=0.035. XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. Keywords: breast cancer, capecitabine, docetaxel, neoadjuvant chemotherapy, curative effect, toxic side effects

  20. INTERRELATIONSHIP BETWEEN EFFICIENCY OF CANCER TREATMENT AND STATE OF IMMUNE SYSTEM IN PATIENTS WITH LARYNGEAL AND HYPOPHARYNGEAL CANCER

    Directory of Open Access Journals (Sweden)

    M. N. Stakheyeva

    2013-01-01

    Full Text Available Abstract. We have studied possible interrelationships between immune system state and efficiency of neoadjuvant chemoradiotherapy in patients with cancer of larynx and hypopharynx. The neoadjuvant treatment consisted of 2 courses of paclitaxel (175 mg/m2, carboplatin (AUC-6 in 3-4 weeks, followed by radiation therapy at a multifraction dose schedule (1.2 Gy 2 times daily in 4 h, total cumulated dose was estimated as isoeffective dose of 40 Gy. A better response to chemotherapy by paclitaxel and carboplatin in the patients with cancer of larynx and hypopharynx had been associated with higher percentage of CD56+ cells and IgM levels in peripheral blood, as measured before starting cancer treatment. After completing the neoadjuvant chemo- and radiotherapy, we noted an increase in total lymphocyte counts, CD4+, CD8+, CD56+ cell numbers and IgG levels in the patients with pronounced response to chemotherapy, thus suggesting some induction of immune response in cancer patients during cytostatic therapy. These data presume a relationship between the state of immune system in the patients with head-and-neck cancer, and their response to neoadjuvant chemo- and radiotherapy. On the basis of these findings, one may suggest that immunological mechanisms make take an important part in promotion of antitumor effects produced by standard cancer treatment.