Status on the heavy elements research using the DV-DFS method

International Nuclear Information System (INIS)

Hirata, Masaru; Bastug, T.; Sekine, Rika; Onoe, Jun; Nakamatsu, Hirohide; Mukoyama, Takeshi

1999-03-01

In this review report, we describe recent progress on the heavy elements research using the discrete-variational Dirac-Fock-Slater (DV-DFS) method which is being improved by Kyoto University, Shizuoka University, RIKEN and JAERI. The DV-DFS is a versatile method for interpreting spectroscopic data and predicting chemical bonding of polyatomic systems including heavy elements. This review is based on the lectures given in 74th spring meeting of chemical Society of Japan (March, 1998) and also at the workshop on the XAFS-relativistic electronic structure calculation for the actinides research which was held at Tokai Research Establishment of JAERI (November, 1998). (author)

Survival of Five Strains of Shiga Toxigenic Escherichia coli in a Sausage Fermentation Model and Subsequent Sensitivity to Stress from Gastric Acid and Intestinal Fluid

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Tone Mari Rode

2017-01-01

Full Text Available The ability of foodborne pathogens to exhibit adaptive responses to stressful conditions in foods may enhance their survival when passing through the gastrointestinal system. We aimed to determine whether Escherichia coli surviving stresses encountered during a model dry-fermented sausage (DFS production process exhibit enhanced tolerance and survival in an in vitro gastrointestinal model. Salami sausage batters spiked with five E. coli isolates, including enterohaemorrhagic E. coli strains isolated from different DFS outbreaks, were fermented in a model DFS process (20°C, 21 days. Control batters spiked with the same strains were stored at 4°C for the same period. Samples from matured model sausages and controls were thereafter exposed to an in vitro digestion challenge. Gastric exposure (pH 3 resulted in considerably reduced survival of the E. coli strains that had undergone the model DFS process. This reduction continued after entering intestinal challenge (pH 8, but growth resumed after 120 min. When subjected to gastric challenge for 120 min, E. coli that had undergone the DFS process showed about 2.3 log10⁡​ lower survival compared with those kept in sausage batter at 4°C. Our results indicated that E. coli strains surviving a model DFS process exhibited reduced tolerance to subsequent gastric challenge at low pH.

Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group

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Hayakawa, F; Sakura, T; Yujiri, T; Kondo, E; Fujimaki, K; Sasaki, O; Miyatake, J; Handa, H; Ueda, Y; Aoyama, Y; Takada, S; Tanaka, Y; Usui, N; Miyawaki, S; Suenobu, S; Horibe, K; Kiyoi, H; Ohnishi, K; Miyazaki, Y; Ohtake, S; Kobayashi, Y; Matsuo, K; Naoe, T

2014-01-01

The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR–ABL-negative ALL. Patients aged 15–24 years (n=139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58–75%) and 73% (95% CI 64–80%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, P<0.001). These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR–ABL-negative ALL

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.

Latent class joint model of ovarian function suppression and DFS for premenopausal breast cancer patients.

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Zhang, Jenny J; Wang, Molin

2010-09-30

Breast cancer is the leading cancer in women of reproductive age; more than a quarter of women diagnosed with breast cancer in the US are premenopausal. A common adjuvant treatment for this patient population is chemotherapy, which has been shown to cause premature menopause and infertility with serious consequences to quality of life. Luteinizing-hormone-releasing hormone (LHRH) agonists, which induce temporary ovarian function suppression (OFS), has been shown to be a useful alternative to chemotherapy in the adjuvant setting for estrogen-receptor-positive breast cancer patients. LHRH agonists have the potential to preserve fertility after treatment, thus, reducing the negative effects on a patient's reproductive health. However, little is known about the association between a patient's underlying degree of OFS and disease-free survival (DFS) after receiving LHRH agonists. Specifically, we are interested in whether patients with lower underlying degrees of OFS (i.e. higher estrogen production) after taking LHRH agonists are at a higher risk for late breast cancer events. In this paper, we propose a latent class joint model (LCJM) to analyze a data set from International Breast Cancer Study Group (IBCSG) Trial VIII to investigate the association between OFS and DFS. Analysis of this data set is challenging due to the fact that the main outcome of interest, OFS, is unobservable and the available surrogates for this latent variable involve masked event and cured proportions. We employ a likelihood approach and the EM algorithm to obtain parameter estimates and present results from the IBCSG data analysis.

Long-term outcomes after proton therapy, with concurrent chemotherapy, for stage II–III inoperable non-small cell lung cancer

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Nguyen, Quynh-Nhu; Ly, Ngoc Bui; Komaki, Ritsuko; Levy, Lawrence B.; Gomez, Daniel R.; Chang, Joe Y.; Allen, Pamela K.; Mehran, Reza J.; Lu, Charles; Gillin, Michael; Liao, Zhongxing; Cox, James D.

2015-01-01

Purpose: We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study. Methods: All patients received passive-scatter proton therapy, planned with 4D-CT–based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). Results: The 134 patients (21 stage II, 113 stage III; median age 69 years) had a median gross tumor volume (GTV) of 70 cm 3 (range, 5–753 cm 3 ); 77 patients (57%) received 74 Gy(RBE), and 57 (42%) received 60–72 Gy(RBE) (range, 60–74.1 Gy(RBE)). At a median follow-up time of 4.7 years, median OS times were 40.4 months (stage II) and 30.4 months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5 years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). Conclusion: This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

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Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

2015-01-01

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

Preoperative Tracheostomy Is Associated with Poor Disease-Free Survival in Recurrent Laryngeal Cancer.

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Birkeland, Andrew C; Rosko, Andrew J; Beesley, Lauren; Bellile, Emily; Chinn, Steven B; Shuman, Andrew G; Prince, Mark E; Wolf, Gregory T; Bradford, Carol R; Brenner, J Chad; Spector, Matthew E

2017-09-01

Objectives It is unknown if preoperative tracheostomy for persistent/recurrent laryngeal squamous cell carcinoma (LSCC) plays a role in unrecognized local disease spread and disease recurrence after salvage laryngectomy. The goals of this study were to determine the effect of preoperative tracheostomy on disease-free survival (DFS) in patients with recurrent/persistent LSCC undergoing salvage laryngectomy. Study Design Retrospective case series derived from prospectively maintained database. Setting Tertiary care academic center. Subjects Patients with recurrent/persistent LSCC after radiation/chemoradiation (RT/CRT) who underwent salvage laryngectomy at the University of Michigan from 1997 to 2015. Methods Demographic, clinical, pathologic, and survival data were collected. Kaplan-Meier survival estimates were performed. Results DFS was worse for patients with tracheostomy prior to laryngectomy than patients without a tracheostomy (5 year: 39% vs 67%; P tracheostomy prior to RT/CRT compared to patients with tracheostomy after RT/CRT or patients without a tracheostomy had worse DFS (5-year: 25%, 49%, and 67%, respectively; P tracheostomy was associated with worse DFS. In multivariable analysis, presence of a preoperative tracheostomy had a worse DFS (hazard ratio, 1.63; 95% confidence interval, 1.00-2.67; P = .048). Conclusion Preoperative tracheostomy is associated with disease recurrence in patients with persistent/recurrent LSCC undergoing salvage laryngectomy, particularly in patients who had tracheostomy prior to completion of initial RT/CRT. Notably, preoperative tracheostomy as a causal factor vs marker for disease recurrence is difficult to ascertain. Nevertheless, clinicians should be aware of the increased risk of locoregional recurrence in patients with preoperative tracheostomy when counseling on surgical salvage and when considering the role of additional therapy.

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

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Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

2015-08-01

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

Early or Up-Front Radiotherapy Improved Survival of Localized Extranodal NK/T-Cell Lymphoma, Nasal-Type in the Upper Aerodigestive Tract

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Huang Meijuan; Jiang Yu; Liu Weiping; Li Zhiping; Li Mei; Zhou Lin; Xu Yong; Yu Chunhua; Li Qiu; Peng Feng; Liu Jiyan; Luo Feng; Lu You

2008-01-01

Purpose: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. Methods and Materials: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. Results: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving ≥54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). Conclusion: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease

Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival

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Sung, Hyuna; Ahn, Sei-Hyun; Kang, Daehee; Jeon, Sujee; Lee, Kyoung-Mu; Han, Sohee; Song, Minkyo; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Noh, Dong-Young

2012-01-01

Although the role of microRNA’s (miRNA’s) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07). Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results

Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.

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Tomas Pascual

Full Text Available Metastatic breast cancer (MBC progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs on outcomes from this treatment through a pharmacogenetic analysis.Blood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities, dose reductions or treatment suspensions due to toxicity, progression free survival (PFS and overall survival.We found that CYP3A4 rs35599367 variant (CYP3A4*22 allele carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019. ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031, while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively. Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006.CYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.

Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

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Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

2011-10-01

To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

Isolation of a buprofezin co-metabolizing strain of Pseudomonas sp. DFS35-4 and identification of the buprofezin transformation pathway.

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Chen, Kai; Liu, Xiao-Mei; Li, Rong; Liu, Yuan; Hu, Hai; Li, Shun-Peng; Jiang, Jian-Dong

2011-11-01

Buprofezin is a widely used insecticide that has caused environmental pollution in many areas. However, biodegradation of buprofezin by pure cultures has not been extensively studied, and the transformation pathway of buprofezin remains unclear. In this paper, a buprofezin co-metabolizing strain of DFS35-4 was isolated from a buprofezin-polluted soil in China. Strain DFS35-4 was preliminarily identified as Pseudomonas sp. based on its morphological, physiological, and biochemical properties, as well as 16S rRNA gene analysis. In the presence of 2.0 g l(-1) sodium citrate, strain DFS35-4 degraded over 70% of 50 mg l(-1) buprofezin in 3 days. Strain DFS35-4 efficiently degraded buprofezin in the pH range of 5.0-10.0 and at temperatures between 20 and 30°C. Three metabolites, 2-imino-5-phenyl-3-(propan-2-yl)-1,3,5-thiadiazinan-4-one, 2-imino-5-phenyl-1,3,5-thiadiazinan-4-one, and methyl(phenyl) carbamic acid, were identified during the degradation of buprofezin using gas chromatography-mass spectrometry (GC-MS) and tandem mass spectrometry (MS/MS). A partial transformation pathway of buprofezin in Pseudomonas sp. DFS35-4 was proposed based on these metabolites.

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

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Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

2016-07-01

Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: a comparison of Australian series.

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Wilcox, Shea William; Aherne, Noel J; McLachlan, Craig Steven; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2015-02-01

We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option. © 2015 The Royal Australian and New Zealand College of Radiologists.

Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: a comparison of Australian series

International Nuclear Information System (INIS)

Wilcox, Shea W.; Last, Andrew J.; Aherne, Noel J.; McLachlan, Craig S.; McKay, Michael J.; Shakespeare, Thomas P.

2015-01-01

We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option.

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

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Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

DFS Associates: Simple ways to become a good manufacturer's representative

OpenAIRE

Sandra K. Pharre

2018-01-01

Being one of the trusted manufacturer’s representative firms for RF and microwave products and services, DFS Associates wanted to impart a few insights to consider in becoming a good manufacturer’s representative with this article. Firstly, you need to understand what it does if you’re interested on becoming one where it could be an individual or a small business that can represent a manufacturer’s products and services effectively to the marketplace. You can choose between representing one m...

Gene expression in triple-negative breast cancer in relation to survival.

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Wang, Shuyang; Beeghly-Fadiel, Alicia; Cai, Qiuyin; Cai, Hui; Guo, Xingyi; Shi, Liang; Wu, Jie; Ye, Fei; Qiu, Qingchao; Zheng, Ying; Zheng, Wei; Bao, Ping-Ping; Shu, Xiao-Ou

2018-05-10

The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

Patterns of Failure and Treatment-Related Toxicity in Advanced Cervical Cancer Patients Treated Using Extended Field Radiotherapy With Curative Intent

International Nuclear Information System (INIS)

Rajasooriyar, Chrishanthi; Van Dyk, Sylvia; Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Barkati, Maroie; Narayan, Kailash

2011-01-01

Purpose: The purpose of this study was to evaluate the patterns of failure and overall survival (OS) and disease-free survival (DFS) rates in cervical cancer patients who had metastatic disease in common iliac or para-aortic lymph nodes and were treated with curative intent, using extended field radiotherapy (EFRT). Methods and Materials: This was a retrospective study involving 39 patients treated from January 1996 to June 2007, using EFRT with concurrent chemotherapy and intracavitary brachytherapy. EFRT consisted of 45 Gy in 1.8-Gy fractions. Radiation to involved nodes was boosted to a total dose of 50.4 to 54 Gy. Primary tumor radiation was boosted to a dose of 80 Gy using brachytherapy. Results: Overall, 30 patients (77%) have relapsed. The 5-year OS rate was 26% (95% confidence interval [CI], 11-44). The 5-year DFS rate was 19.4% (95% CI, 8-35). Only 3 patients (7.5%) experienced treatment failure exclusively within the treatment field, and 2 patients underwent salvage treatment. Grade 3 to 4 acute bone marrow and gastrointestinal toxicities were observed in 10 (26%) and 7 (18%) patients, respectively. Conclusions: Concurrent chemotherapy and EFRT treatment was well tolerated. Most patients showed failure at multiple sites and outside the treatment field. Only 3/39 patients had failures exclusively within the treatment field, and 2 underwent salvage treatment.

Peritumoral interstitial fluid flow velocity predicts survival in cervical carcinoma

International Nuclear Information System (INIS)

Hompland, Tord; Lund, Kjersti V.; Ellingsen, Christine; Kristensen, Gunnar B.; Rofstad, Einar K.

2014-01-01

Background and purpose: High tumor interstitial fluid pressure (IFP) is associated with poor outcome in locally advanced carcinoma of the uterine cervix. We have recently developed a noninvasive assay of the IFP of tumors, and in this assay, the outward interstitial fluid flow velocity at the tumor surface (v 0 ) is measured by Gd-DTPA-based DCE-MRI and used as a parameter for IFP. Here, we investigated the independent prognostic significance of v 0 in cervical cancer patients given cisplatin-based concurrent chemoradiotherapy with curative intent. Patients: The study involved 62 evaluable patients from a cohort of 74 consecutive patients (Stage IB through IIIB) with a median follow-up of 5.5 years. Results: The actuarial disease-free survival (DFS) and overall survival (OS) at 5 years were 67% and 76%, respectively. Significant associations were found between v 0 dichotomized about the median value and DFS and OS, both in the total patient cohort and a subcohort of 40 Stage IIB patients. Multivariate analysis involving stage, tumor volume, lymph node status, and v 0 revealed that only v 0 provided independent prognostic information about DFS and OS. Conclusion: This investigation demonstrates a strong, independent prognostic impact of the pretreatment peritumoral fluid flow velocity in cervical cancer

Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia

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Løhmann, Ditte J A; Abrahamsson, Jonas; Ha, Shau-Yin

2016-01-01

Treatment for pediatric acute myeloid leukemia is very toxic and the association between outcome and age and Body Mass Index is unclear. We investigated effect of age and Body Mass Index on toxicity and survival in pediatric acute myeloid leukemia. We studied all patients who completed first...

Long-term results and prognostic factors in patients with stage III-IVA squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy from a single institution study

International Nuclear Information System (INIS)

Kudaka, Wataru; Nagai, Yutaka; Toita, Takafumi

2013-01-01

We evaluated the longer-term efficacy and safety of concurrent chemoradiotherapy (CCRT) incorporating high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a lower cumulative radiotherapy (RT) protocol and analyzed prognostic risk factors for survival among patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IVA squamous cell carcinoma (SCC) of the cervix. Ninety-nine patients with FIGO stage III-IVA SCC of the cervix between 1997 and 2008 were treated with CCRT using cisplatin 20 mg/m 2 for 5 days every 3 weeks or 40 mg/m 2 weekly. Acute and late toxicities were evaluated. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. Median age was 53.5 years. Median follow-up period was 58 months (range 6-170 months). Pathologically complete response was achieved in 93 patients (96.9%). The 5-year OS and DFS were 72.0 and 69.3%, respectively. The 5-year local and distant DFS were 83.0 and 75.1%, respectively. Thirty-one patients (31.3%) experienced recurrence. Multivariate analysis showed that tumor size and pretreatment hemoglobin level remained an independent risk factor for OS and DFS. Acute toxicity was moderate. In terms of late adverse effects, 2 patients (2.0%) suffered from grade 4 late intestinal toxicity because of radiation enterocolitis, with both requiring intestinal surgery. Our study demonstrates that the CCRT schedule in patients with FIGO stage III-IVA SCC is efficacious and safe. In addition, the assessment of tumor size and pretreatment anemia can provide valuable prognostic information. (author)

Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

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Dandekar, Prasad [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Harmer, Clive; Barbachano, Yolanda [Department of Clinical Research and Development, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher [Head and Neck-Thyroid Unit, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom); Newbold, Kate [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Consultant Clinical Oncologist, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom)

2009-06-01

Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

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Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

2016-01-01

The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients

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Xu, H.-X. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Lu, M.-D. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xie, X.-Y. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Yin, X.-Y. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Kuang, M. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, J.-W. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Z.-F. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, G.-J. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

2005-09-01

AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin {<=}35 g/dl, liver function Child's class C and incomplete ablation were found to be significant predictors for OS by univariate analysis. Using multivariate analysis, incomplete ablation was identified to be the most significant independent predictor for OS. Other independent predictors for OS were serum albumin level, serum AFP level and Child-Pugh classification. Recurrence after hepatectomy and prothrombin time >14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended.

Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients

International Nuclear Information System (INIS)

Xu, H.-X.; Lu, M.-D.; Xie, X.-Y.; Yin, X.-Y.; Kuang, M.; Chen, J.-W.; Xu, Z.-F.; Liu, G.-J.

2005-01-01

AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin ≤35 g/dl, liver function Child's class C and incomplete ablation were found to be significant predictors for OS by univariate analysis. Using multivariate analysis, incomplete ablation was identified to be the most significant independent predictor for OS. Other independent predictors for OS were serum albumin level, serum AFP level and Child-Pugh classification. Recurrence after hepatectomy and prothrombin time >14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended

Twenty-five year outcome of sequential abdominopelvic radiotherapy and alkylating agent chemotherapy for ovarian carcinoma

International Nuclear Information System (INIS)

Bellairs, Ellen E.; Twiggs, Leo B.; Potish, Roger A.

1997-01-01

Purpose: A prospective study of sequential surgery, abdominopelvic radiotherapy and single agent alkylating chemotherapy was conducted to evaluate survival and toxicity in the management of ovarian carcinoma. Methods: From 1970-1976, 95 women with stage I-III epithelial ovarian carcinoma were scheduled to receive postoperative radiotherapy consisting of 20.0 Gy to the whole abdomen (1.0 Gy/day), a 29.75 Gy pelvic boost (1.75 Gy/day) and 10 subsequent courses of Melphalan (1 mg/kg/course). Endpoints were overall survival, disease-free survival(DFS), and acute and chronic toxicity. Results: The evaluable 94 patients included 19 stage I, 25 stage II, and 50 stage III. Of the latter, 21 had no palpable disease postoperatively (IIIN) and 29 had postoperative palpable disease (IIIP). Overall survival at 5, 10, 15 and 20 years was 42%, 30%, 23% and 22%. DFS for the entire group was 54% at 5 years and remained 50% from 10 to 25 years. All but two recurrences were noted within the first 27 months. No recurrence or treatment-related deaths occurred after 8 years. After 10 years, the survival of the study group became parallel to the general population. Prognostic factors were only related to stage (p<.001) and the presence of postoperative palpable disease(p<.001). DFS at 25 years was 95 % for stage I, 71% at 5 years and 66% from 10 to 25 years for stage II, and 17% at 5 years and 11% thereafter for stage III patients(p<.001). Although no stage IIIP patients were cured, 25% lived beyond 2 years. Five year DFS was significantly better in IIIN (45%) vs. IIIP (0%) patients (p<.001). The 65 patients without postoperative palpable disease, (stage I-IIIN) achieved DFS at 5 and 25 years of 69%, and 61%, respectively. Of 31 patients undergoing a second-look surgery, 84% were found to be free of tumor. Two recurred at 3.5 and 7 years after surgery. Acute tolerance was acceptable. Chronic toxicity included an 11.7% rate of small bowel obstruction requiring surgery and a 3% rate of

Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

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Chen L

2017-05-01

Full Text Available Li Chen,1 Yanjiao Zuo,1 Lihua Zhu,2 Yuxin Zhang,3 Sen Li,1 Fei Ma,4 Yu Han,5 Hongjiang Song,1 Yingwei Xue11Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, 3Department of General Surgery, Mudanjiang First People’s Hospital, Mudanjiang, 4Department of Breast Surgery, 5Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaBackground: Accurate and useful predictors of gastric carcinoma treated with neoadjuvant chemotherapy are lacking at present. We aim to explore the potential prognostic significance of the neutrophil-to-lymphocyte ratio (NLR in advanced gastric cancer receiving S-1 plus oxaliplatin (SOX or oxaliplatin and capecitabine (XELOX regimen.Methods: We enrolled 91 patients with advanced gastric cancer treated with neoadjuvant chemotherapy from August 2008 to September 2015. The peripheral venous blood samples were collected before neoadjuvant chemotherapy. The NLR was divided into two groups: low NLR <2.17 group and high NLR ≥2.17 group. Univariate analysis on disease-free survival (DFS and overall survival (OS were generated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were assessed by univariate analyses, and the independent prognostic factors were evaluated using multivariate analysis (Cox’s proportional-hazards regression model.Results: The univariate analysis showed that median DFS and median OS were worse for high NLR values than low NLR values before neoadjuvant chemotherapy (median DFS: 19.97 and 26.87 months, respectively, P=0.299; median OS: 25.83 and 29.73 months, respectively, P=0.405. Multivariate analysis showed that the NLR before neoadjuvant

Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases.

Directory of Open Access Journals (Sweden)

Nikol Snoeren

Full Text Available BACKGROUND AND OBJECTIVES: This study was designed to identify and validate gene signatures that can predict disease free survival (DFS in patients undergoing a radical resection for their colorectal liver metastases (CRLM. METHODS: Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France and the University Medical Center Utrecht (The Netherlands. Patients were divided into high and low risk groups. A randomly selected training set was used to find predictive gene signatures. The ability of these gene signatures to predict DFS was tested in an independent validation set comprising the remaining patients. Furthermore, 5 known clinical risk scores were tested in our complete patient cohort. RESULT: No gene signature was found that significantly predicted DFS in the validation set. In contrast, three out of five clinical risk scores were able to predict DFS in our patient cohort. CONCLUSIONS: No gene signature was found that could predict DFS in patients undergoing CRLM resection. Three out of five clinical risk scores were able to predict DFS in our patient cohort. These results emphasize the need for validating risk scores in independent patient groups and suggest improved designs for future studies.

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

Science.gov (United States)

Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2013-01-01

Purpose The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray’s test. Results Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. PMID:24035327

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

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Gunderson, Leonard L., E-mail: gunderson.leonard@mayo.edu [Mayo Clinic Cancer Center, Scottsdale, Arizona (United States); Moughan, Jennifer [Radiation Therapy Oncology Group, Philadelphia, Pennsylvania (United States); Ajani, Jaffer A. [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Pedersen, John E. [Cross Cancer Institute, Edmonton, Alberta (Canada); Winter, Kathryn A. [Radiation Therapy Oncology Group, Philadelphia, Pennsylvania (United States); Benson, Al B. [Northwestern University, Chicago, Illinois (United States); Thomas, Charles R. [Knight Cancer Institute/Oregon Health and Science University, Portland, Oregon (United States); Mayer, Robert J. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Haddock, Michael G. [Mayo Clinic Cancer Center, Rochester, Minnesota (United States); Rich, Tyvin A. [University of Virginia, Charlottesville, Virginia (United States); Willett, Christopher G. [Duke University, Durham, North Carolina (United States)

2013-11-15

Purpose: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. Results: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories.

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

International Nuclear Information System (INIS)

Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2013-01-01

Purpose: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. Results: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories

Dietary patterns and colorectal cancer recurrence and survival: a cohort study.

Science.gov (United States)

Zhu, Yun; Wu, Hao; Wang, Peizhong Peter; Savas, Sevtap; Woodrow, Jennifer; Wish, Tyler; Jin, Rong; Green, Roger; Woods, Michael; Roebothan, Barbara; Buehler, Sharon; Dicks, Elizabeth; McLaughlin, John R; Campbell, Peter T; Parfrey, Patrick S

2013-01-01

To examine the association between dietary patterns and colorectal cancer (CRC) survival. Cohort study. A familial CRC registry in Newfoundland. 529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to 2003 and followed up until April 2010. Participants reported their dietary intake using a food frequency questionnaire. Dietary patterns were identified with factor analysis. Multivariable Cox proportional hazards models were employed to estimate HR and 95% CI for association of dietary patterns with CRC recurrence and death from all causes, after controlling for covariates. Disease-free survival (DFS) among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest vs the lowest quartile HR 1.82, 95% CI 1.07 to 3.09). No associations were observed with the prudent vegetable or the high-sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest vs the lowest quartile: HR 2.29, 95% CI 1.19 to 4.40) whereas the relationship between overall survival (OS) and this pattern was observed among patients with colon cancer only (the highest vs the lowest quartile: HR 2.13, 95% CI 1.03 to 4.43). Potential effect modification was noted for sex (p value for interaction 0.04, HR 3.85 for women and 1.22 for men). The processed meat dietary pattern prior to diagnosis is associated with higher risk of tumour recurrence, metastasis and death among patients with CRC.

Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

DEFF Research Database (Denmark)

Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.

2015-01-01

Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...... for disseminated disease. Methods: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse......, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal...

Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

Science.gov (United States)

Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

2009-02-01

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

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Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

2014-01-01

Purpose Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Patients and Methods Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Results Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Conclusions Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

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Thomas Pavelitz

Full Text Available Colon cancers deficient in mismatch repair (MMR may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Cancer and Leukemia Group B 89803 (Alliance randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV or irinotecan+FU/LV (IFL, with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS, and a secondary endpoint was disease-free survival (DFS. Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.Of 625 tumor cases examined, 70 (11.2% exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11. In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.ClinicalTrials.gov NCT00003835.

Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity

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Zuliani, Antonio Carlos; Cunha, Maercio de Oliveira, E-mail: aczo.rt@gmail.co [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Esteves, Sergio C.B. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Secao de Radioterapia; Teixeira, Julio Cesar [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Tocoginecologia

2010-07-01

Objective: to compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR), high-dose-rate (HDR) brachytherapy and association of HDR and chemotherapy. Methods: between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m2. Results: the five-year progression-free survival (PFS) was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02). The five-year Overall Survival (OS) was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p 0.02). Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. Conclusion: patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups. (author)

Adjuvant radiochemotherapy in locally advanced gastric cancer. Treatment results and analysis of possible prognostic factors

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Martin Sanchez, Mercedes; Perez Escutia, Maria Angeles; Guardado Gonzales, Sandra; Cabezas Mendoza, Ana Maria; Campos Bonel, Arantxa; Perez Montero, Hector; Ambrosi, Rafael d'; Perez-Regadera Gomez, Jose Fermin; Lora Pablos, David

2017-01-01

The aim of this study was to report the clinical outcome and toxicity of radiochemotherapy in locally advanced gastric cancer (LAGC) patients treated according to the Intergroup 116 trial protocol in our institution. We retrospectively reviewed 105 patients with LAGC treated with radical surgery and adjuvant radiochemotherapy. We analyzed overall survival (OS), disease-free survival (DFS), locoregional failure-free survival (LFS), prognostic factors and toxicity. The mean follow-up was 96.48 months. The majority of tumors were T3-T4 (75%) and 86.6% had nodal metastases. The OS, DFS and LFS rates to 3 years were 53.48%, 52.75% and 81.65%, respectively and to 5 years 40%, 46.73% and 76.77% respectively. The univariate analysis showed that N stage < N2, TN stage < IIIA, R0 resection and N-ratio < 3 were statistically significant prognostic factors for OS and DFS, T stage < T4 for OS and N-ratio < 3 for LFS. The group with D2 lymphadenectomy had worse LFS than the D1 group (65.2% vs 88.1%, respectively, p = 0.039) probably due to a significant difference in the proportion node positive patients in the D2 group (94% vs. 78%; p = 0.027). In the multivariate analysis, only R0 resection was statistically significant factor for improved OS (p = 0.018). Acute grade III-IV gastrointestinal and hematologic toxicity rates were 8.5% and 15.2%, respectively and 89.5% completed treatment as planned. Our results are consistent with those of the Intergroup-0116 trial for LAGC in terms of survival. This regimen is well tolerated and with acceptable toxicity. An R0 resection was an independent prognostic factor for improved OS. (orig.) [de

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer.

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Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2014-01-01

Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for

[Disease-free survival related factors in breast cancer].

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Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

2014-10-07

To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Vacuum therapy of trophic ulcer of lower extremities, presented in patients with DFS

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Yurkova R.A.

2017-01-01

Full Text Available the article has analyzed the results of treatment of 67 patients with diabetic foot syndrome (DFS, complicated by feet trophic ulcers, using the vacuum bandages. Patients were divided into 2 groups: the control group had a traditional treatment and the studied one had vacuum bandages applied to the trophic ulcers. The results confirmed an assured decrease in the duration of patients’ treatment and hospitalization in the hospital.

A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a French regional study.

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Sabbagh, Charles; Mauvais, François; Cosse, Cyril; Rebibo, Lionel; Joly, Jean-Paul; Dromer, Didier; Aubert, Christine; Carton, Sophie; Dron, Bernard; Dadamessi, Innocenti; Maes, Bernard; Perrier, Guillaume; Manaouil, David; Fontaine, Jean-François; Gozy, Michel; Panis, Xavier; Foncelle, Pierre Henri; de Fresnoy, Hugues; Leroux, Fabien; Vaneslander, Pierre; Ghighi, Caroline; Regimbeau, Jean-Marc

2014-01-01

Lymph node ratio (LNR) (positive lymph nodes/sampled lymph nodes) is predictive of survival in colon cancer. The aim of the present study was to validate the LNR as a prognostic factor and to determine the optimum LNR cutoff for distinguishing between "good prognosis" and "poor prognosis" colon cancer patients. From January 2003 to December 2007, patients with TNM stage III colon cancer operated on with at least of 3 years of follow-up and not lost to follow-up were included in this retrospective study. The two primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) as a function of the LNR groups and the cutoff. One hundred seventy-eight patients were included. There was no correlation between the LNR group and 3-year OS (P=0.06) and a significant correlation between the LNR group and 3-year DFS (P=0.03). The optimal LNR cutoff of 10% was significantly correlated with 3-year OS (P=0.02) and DFS (P=0.02). The LNR was not an accurate prognostic factor when fewer than 12 lymph nodes were sampled. Clarification and simplification of the LNR classification are prerequisites for use of this system in randomized control trials. An LNR of 10% appears to be the optimal cutoff.

Systematic immunohistochemical screening for mismatch repair and ERCC1 gene expression from colorectal cancers in China: Clinicopathological characteristics and effects on survival.

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Pan Li

Full Text Available We performed a systematic screening of colorectal cancer (CRC tissues to investigate whether mismatch repair (MMR status and ERCC1 protein expression could be predictive of clinical outcomes for these patients following the recommendation of The Evaluation of Genomic Applications in Practice of Prevention (EGAPP.The expression of four MMR genes and ERCC1 were assessed by immunohistochemistry (IHC from cancer tissue samples of 2233 consecutive CRC patients.We observed that most CRC patients with a proficient MMR (pMMR status tended to have simultaneous ERCC1 protein expression (P< 0.001. Stage III CRC patients with deficient MMR (dMMR had higher prognoses than the same stage patients with pMMR (DFS: 74% vs 65%, P = 0.04; OS: 79% vs 69%, P = 0.04. Here, dMMR is also associated with poorer survival for stage II patients after chemotherapy (DFS: 66% vs 78%, P = 0.04. Stage II and III patients that were shown to express ERCC1 protein had higher DFS and OS than those that were deficient in expression (stage II, DFS: 83% vs 70%, P = 0.006; OS 85% vs 73%, P = 0.02. Stage III, DFS: 67% vs56%, P = 0.03; OS: 71% vs 57%, P = 0.04.Our results indicate that dMMR appeared to predictive of a survival benefit for stage III CRC patients. We also found the determination of ERCC1 expression to be useful for predicting DFS or OS for stage II and III CRC patients. In addition, the expression of MMR genes and ERCC1 showed a significant relationship.

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

Science.gov (United States)

Berlin, Jordan D; Feng, Yang; Catalano, Paul; Abbruzzese, James L; Philip, Philip A; McWilliams, Robert R; Lowy, Andrew M; Benson, Al B; Blackstock, A William

2018-01-01

Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated. © 2017 S. Karger AG, Basel.

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

Full Text Available Li Chen,1,* Ying Yan,2,* Lihua Zhu,3 Xiliang Cong,1 Sen Li,1 Shubin Song,1 Hongjiang Song,1 Yingwei Xue1 1Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Internal Oncology, Harbin The First Hospital, Harbin, Heilongjiang, 3Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China *These authors contributed equally to this work Background and objective: A novel systemic immune–inflammation index named SII (SII=N×P/L, which is based on neutrophil (N, platelet (P and lymphocyte (L counts, has emerged and reflects comprehensively the balance of host inflammatory and immune status. We aimed to evaluate the potential prognostic significance of SII in patients with advanced gastric cancer who received neoadjuvant chemotherapy.Subjects and methods: The retrospective analysis included data from 107 patients with advanced gastric cancer undergoing neoadjuvant chemotherapy and 185 patients with pathology-proven gastric cancer. The optimal cutoff value of SII by receiver operating characteristic curve stratified patients into low SII (<600×109/L and high SII (SII ≥600×109/L groups. The clinical outcomes of disease-free survival (DFS and overall survival (OS were calculated by Kaplan–Meier survival curves and compared using log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SII.Results: The results indicated that SII had prognostic significance using the cutoff value of 600×109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Low SII was associated with prolonged DFS and OS, and the mean DFS and OS for patients with low SII were longer than for those with high SII (57.22 vs 41.56 months and 62.25 vs 45.60 months, respectively. Furthermore, we found that patients

Preoperative chemoradiotherapy for locally advanced gastric cancer

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Pepek Joseph M

2013-01-01

Full Text Available Abstract Background To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT for gastric cancer. Methods Patients with gastroesophageal (GE junction (Siewert type II and III or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS, local control (LC and disease-free survival (DFS were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Results Forty-eight patients were included. Most (73% had proximal (GE junction, cardia and fundus tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75% underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Conclusions Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

Preoperative chemoradiotherapy for locally advanced gastric cancer

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Pepek, Joseph M; Chino, Junzo P; Willett, Christopher G; Palta, Manisha; Blazer III, Dan G; Tyler, Douglas S; Uronis, Hope E; Czito, Brian G

2013-01-01

To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated

Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

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Kim, Mi Young; Kim, Jin Hee; Kim, Yong Hoon [Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Byun, Sang Jun [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2016-12-15

To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

Science.gov (United States)

Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-04-20

The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

Long-Term Follow-Up of Preoperative Pelvic Radiation Therapy and Concomitant Boost Irradiation in Locally Advanced Rectal Cancer Patients: A Multi-Institutional Phase II Study (KROG 04-01)

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Lee, Jong Hoon [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of); Department of Radiation Oncology, St. Vincent' s Hospital, Catholic University of Korea, Suwon (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Go-Yang (Korea, Republic of); Nam, Taek-Keun [Department of Radiation Oncology, Chonnam National University Hospital, Hwa-Sun (Korea, Republic of); Yoon, Sei-Chul [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of); Lee, Doo Seok [Department of Colorectal Surgery, Daehang Hospital, Seoul (Korea, Republic of); Park, Ji Won; Oh, Jae Hwan; Chang, Hee Jin [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Go-Yang (Korea, Republic of); Yoon, Mee Sun; Jeong, Jae-Uk [Department of Radiation Oncology, Chonnam National University Hospital, Hwa-Sun (Korea, Republic of); Jang, Hong Seok, E-mail: hsjang11@catholic.ac.kr [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of)

2012-11-15

Purpose: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P = .045) and N (P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P = .025) and overall survival (P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and

Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-year Disease-free Survival and Toxicity Observations

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Donald Blake Fuller

2014-11-01

Full Text Available PURPOSEProstate stereotactic body radiotherapy (SBRT may substantially recapitulate the dose distribution of high-dose-rate (HDR brachytherapy, representing an externally delivered Virtual HDR treatment method. Herein we present 5-year outcomes from a cohort of consecutively treated Virtual HDR SBRT prostate cancer patients.METHODSSeventy-nine patients were treated from 2006 - 2009, 40 low-risk and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in 4 fractions. The planning target volume (PTV included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered > 95% of the PTV (V100 >= 95%, with a minimum 150% PTV dose escalation to create HDR-like PTV dose distribution.RESULTSMedian pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70% but only 3 of them subsequently relapsed, Biochemical-relapse-free survival was 100% and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98% and 92% by Phoenix definition. Local relapse did not occur, distant metastasis-free survival was 100% and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10% and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0% and 1%, respectively, with no grade 3 or higher toxicity. Of patients potent pre-SBRT, 65% remained so at 5 years.CONCLUSIONSVirtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

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Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

Energy Technology Data Exchange (ETDEWEB)

Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia; Skliarenko, Julia; Craig, Tim [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Le, Lisa W. [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brierley, James; Wong, Rebecca; Dinniwell, Robert; Bayley, Andrew J.; Dawson, Laura A.; Ringash, Jolie [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Krzyzanowska, Monika K.; Moore, Malcolm J.; Chen, Eric X. [Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Easson, Alexandra M. [Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Canada); Kassam, Zahra; Cho, Charles [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John, E-mail: John.Kim@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

2014-11-01

Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were

Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

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Rui Guo

Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

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Showalter, Timothy N. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Winter, Kathryn A. [Radiation Therapy Oncology Group, RTOG Statistical Center, Philadelphia, PA (United States); Berger, Adam C., E-mail: adam.berger@jefferson.edu [Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Safran, Howard [Department of Medicine, Miriam Hospital, Brown University Oncology Group, Providence, RI (United States); Hoffman, John P. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Benson, Al B. [Division of Hematology-Oncology, Northwestern University, Chicago, IL (United States); MacDonald, John S. [St. Vincent' s Cancer Care Center, New York, NY (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.

IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

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Duprez, Fréderic; Madani, Indira; Morbée, Lieve; Bonte, Katrien; Deron, Philippe; Domján, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

2012-01-01

Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60–66 Gy (n = 13) at 2 Gy per fraction over 6–7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1–2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15–121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment (≥6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1–2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and

IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

Energy Technology Data Exchange (ETDEWEB)

Duprez, Frederic, E-mail: frederic.duprez@ugent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Madani, Indira; Morbee, Lieve [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien; Deron, Philippe; Domjan, Vilmos [Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

2012-05-01

Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

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Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-01-01

Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

Impact of point A asymmetry on local control and survival for low dose-rate (LDR) brachytherapy in cervical cancer.

Science.gov (United States)

Opfermann, Krisha J; Wahlquist, Amy; Watkins, John; Kohler, Matthew; Jenrette, Joseph

2012-03-01

To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS). A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest. The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS. LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.

Dirty Money: A Matter of Bacterial Survival, Adherence, and Toxicity.

Science.gov (United States)

Vriesekoop, Frank; Chen, Jing; Oldaker, Jenna; Besnard, Flavien; Smith, Reece; Leversha, William; Smith-Arnold, Cheralee; Worrall, Julie; Rufray, Emily; Yuan, Qipeng; Liang, Hao; Scannell, Amalia; Russell, Cryn

2016-11-23

In this study we report the underlying reasons to why bacteria are present on banknotes and coins. Despite the use of credit cards, mobile phone apps, near-field-communication systems, and cryptocurrencies such as bitcoins which are replacing the use of hard currencies, cash exchanges still make up a significant means of exchange for a wide range of purchases. The literature is awash with data that highlights that both coins and banknotes are frequently identified as fomites for a wide range of microorganisms. However, most of these publications fail to provide any insight into the extent to which bacteria adhere and persist on money. We treated the various currencies used in this study as microcosms, and the bacterial loading from human hands as the corresponding microbiome. We show that the substrate from which banknotes are produced have a significant influence on both the survival and adherence of bacteria to banknotes. Smooth, polymer surfaces provide a poor means of adherence and survival, while coarser and more fibrous surfaces provide strong bacterial adherence and an environment to survive on. Coins were found to be strongly inhibitory to bacteria with a relatively rapid decline in survival on almost all coin surfaces tested. The inhibitory influence of coins was demonstrated through the use of antimicrobial disks made from coins. Despite the toxic effects of coins on many bacteria, bacteria do have the ability to adapt to the presence of coins in their environment which goes some way to explain the persistent presence of low levels of bacteria on coins in circulation.

Does HPV status influence survival after vulvar cancer?

DEFF Research Database (Denmark)

Rasmussen, Christina Louise; Sand, Freja Laerke; Hoffmann Frederiksen, Marie

2018-01-01

High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV...... status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic...... search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I2...

Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

Science.gov (United States)

Delishaj, Durim; Fabrini, Maria Grazia; Gonnelli, Alessandra; Morganti, Riccardo; Perrone, Franco; Tana, Roberta; Paiar, Fabiola; Gadducci, Angiolo

2016-01-01

Purpose The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). Material and methods Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity. PMID:28115957

Toxicity of copper nanoparticles and CuCl2 salt to Enchytraeus albidus worms: Survival, reproduction and avoidance responses

International Nuclear Information System (INIS)

Amorim, Mónica João Barros; Scott-Fordsmand, Janeck James

2012-01-01

Environmental effects of copper nanoparticles are little studied in terrestrial ecosystems. In the present article, the toxicity of copper nanoparticles (Cu-NP) on the enchytraeid Enchytraeus albidus is compared to the toxicity of a copper-salt (CuCl 2 ). The effect parameters studied were survival, reproductive output and avoidance behaviour. The results show that Cu-NP were more toxic to E. albidus than the same concentrations of the CuCl 2 -salt. The physic-chemical analysis of the particles indicated that only a small fraction was released as ions. Hence, the results indicated a nanoparticle-specific effect – lower reproductive output and higher avoidance. This was observed as 2–8 fold (significant) lower ECx values for Cu-NP (EC 50-reprod = 95 mg Cu/kg; EC 50-avoid = 241 mg Cu/kg) exposed organisms compared to CuCl 2 (EC 50-reprod = 251 mg Cu/kg; EC 50-avoid = 475 mg Cu/kg) exposed organisms. These results corroborate with a nanoparticle-specific effect. - Highlights: ► Enchytraeus albidus were exposed to Cu-salt and Cu nanoparticles (80 nm) in soil. ► Survival, reproduction and avoidance behaviour were assessed. ► Particles characterization indicated very small ion release. ► Cu nanoparticles toxicity was higher than Cu-salt for reproduction and avoidance. - Toxicity of Cu chloride salt and Cu nanoparticles to Enchytraeus albidus indicated higher toxicity of Cu-NP.

Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study.

Science.gov (United States)

Taylor, Fiona G M; Quirke, Philip; Heald, Richard J; Moran, Brendan J; Blomqvist, Lennart; Swift, Ian R; Sebag-Montefiore, David; Tekkis, Paris; Brown, Gina

2014-01-01

The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.

Prognostic factors in adult soft tissue sarcoma treated with surgery combined with radiotherapy: a retrospective single-center study on 164 patients

Directory of Open Access Journals (Sweden)

Ling Cai

2013-10-01

Full Text Available The aim of the present study is to assess the disease profile, outcome and prognostic factors in patients treated with surgery combined with radiotherapy (RT, with or without chemotherapy (CXT, for soft-tissue sarcoma (STS in a multidisciplinary setting. One hundred and sixty-four patients with STS treated between 1980 and 2010 at the Centre Hospitalier Universitaire Vaudois were enrolled in this retrospective study. Seventy-six percent of patients underwent postoperative RT with (24%, or without (52% CXT, 15% preoperative RT with (5%, or without (10% CXT, surgery alone (7%, or RT alone (2% with or without CXT. The median follow-up was 60 months (range 6-292. Local failure was observed in 18%, and distant failure in 21% of the patients. Overall survival (OS, disease-free survival (DFS, local control (LC and distant metastases-free survival (DMFS were 88%, 68%, 83%, and 79% at 5 years, and 80%, 56%, 76%, and 69% at 10 years, respectively. In univariate analyses, favorable prognostic factors for OS, DFS, and DMFS were tumor size 6 cm or less, World Health Organization (WHO/Zubrod score 0, and stage 2 or less. Age and superficial tumors were favorable only for OS and DMFS respectively. STS involving the extremities had a better outcome regarding DFS and LC. Histological grade 2 or less was favorable for DFS, DMFS, and LC. Radical surgery was associated with better LC and DMFS. RT dose more than 60 Gy was favorable for OS, DFS, and LC. In multivariate analyses, independent factors were age for OS; tumor size for OS, DFS and DMFS; WHO/Zubrod score for OS, DFS and LC; hemoglobin level for DFS; site for DFS and LC; tumor depth for DMFS; histological grade for DFS and LC; surgical procedure for LC and DMFS; and RT dose for OS. This study confirms that in a multidisciplinary setting, STS have a fairly good prognosis. A number of prognostic and predictive factors, including the role of surgery combined with RT, were identified. Regarding RT, a dose of

Prognostic Factors in Adult Soft Tissue Sarcoma Treated with Surgery Combined with Radiotherapy: A Retrospective Single-Center Study on 164 Patients

Science.gov (United States)

Cai, Ling; Mirimanoff, René-Olivier; Mouhsine, Elyazid; Guillou, Louis; Leyvraz, Pierre-Francois; Leyvraz, Serge; Gay, Beatrice; Matzinger, Oscar; Ozsahin, Mahmut; Zouhair, Abderrahim

2013-01-01

The aim of the present study is to assess the disease profile, outcome and prognostic factors in patients treated with surgery combined with radiotherapy (RT), with or without chemotherapy (CXT), for soft-tissue sarcoma (STS) in a multidisciplinary setting. One hundred and sixty-four patients with STS treated between 1980 and 2010 at the Centre Hospitalier Universitaire Vaudois were enrolled in this retrospective study. Seventy-six percent of patients underwent postoperative RT with (24%), or without (52%) CXT, 15% preoperative RT with (5%), or without (10%) CXT, surgery alone (7%), or RT alone (2%) with or without CXT. The median follow-up was 60 months (range 6-292). Local failure was observed in 18%, and distant failure in 21% of the patients. Overall survival (OS), diseasefree survival (DFS), local control (LC) and distant metastases-free survival (DMFS) were 88%, 68%, 83%, and 79% at 5 years, and 80%, 56%, 76%, and 69% at 10 years, respectively. In univariate analyses, favorable prognostic factors for OS, DFS, and DMFS were tumor size 6 cm or less, World Health Organization (WHO)/Zubrod score 0, and stage 2 or less. Age and superficial tumors were favorable only for OS and DMFS respectively. STS involving the extremities had a better outcome regarding DFS and LC. Histological grade 2 or less was favorable for DFS, DMFS, and LC. Radical surgery was associated with better LC and DMFS. RT dose more than 60 Gy was favorable for OS, DFS, and LC. In multivariate analyses, independent factors were age for OS; tumor size for OS, DFS and DMFS; WHO/Zubrod score for OS, DFS and LC; hemoglobin level for DFS; site for DFS and LC; tumor depth for DMFS; histological grade for DFS and LC; surgical procedure for LC and DMFS; and RT dose for OS. This study confirms that in a multidisciplinary setting, STS have a fairly good prognosis. A number of prognostic and predictive factors, including the role of surgery combined with RT, were identified. Regarding RT, a dose of more than

Pathologic Nodal Classification Is the Most Discriminating Prognostic Factor for Disease-Free Survival in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy and Curative Resection

International Nuclear Information System (INIS)

Kim, Tae Hyun; Chang, Hee Jin; Kim, Dae Yong

2010-01-01

Purpose: We retrospectively evaluated the effects of clinical and pathologic factors on disease-free survival (DFS) with the aim of identifying the most discriminating factor predicting DFS in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection. Methods and Materials: The study involved 420 patients who underwent preoperative CRT and curative resection between August 2001 and October 2006. Gender, age, distance from the anal verge, histologic type, histologic grade, pretreatment carcinoembryonic antigen (CEA) level, cT, cN, cStage, circumferential resection margin, type of surgery, preoperative chemotherapy, adjuvant chemotherapy, ypT, ypN, ypStage, and tumor regression grade (TRG) were analyzed to identify prognostic factors associated with DFS. To compare the discriminatory prognostic ability of four tumor response-related pathologic factors (ypT, ypN, ypStage, and TRG), the Akaike information criteria were calculated. Results: The 5-year DFS rate was 75.4%. On univariate analysis, distance from the anal verge, histologic type, histologic grade, pretreatment CEA level, cT, circumferential resection margin, type of surgery, preoperative chemotherapeutic regimen, ypT, ypN, ypStage, and TRG were significantly associated with DFS. Multivariate analysis showed that the four parameters ypT, ypN, ypStage, and TRG were, consistently, significant prognostic factors for DFS. The ypN showed the lowest Akaike information criteria value for DFS, followed by ypStage, ypT, and TRG, in that order. Conclusion: In our study, ypT, ypN, ypStage, and TRG were important prognostic factors for DFS, and ypN was the most discriminating factor.

Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis

International Nuclear Information System (INIS)

Gunderson, Leonard L.; Sargent, Daniel J.; Tepper, Joel E.; O'Connell, Michael J.; Allmer, Cristine; Smalley, Steven R.; Martenson, James A.; Haller, Daniel G.; Mayer, Robert J.; Rich, Tyvin A.; Ajani, Jaffer A.; Macdonald, John S.; Goldberg, Richard M.

2002-01-01

Purpose: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. Materials and Methods: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n=200), NCCTG 86-47-51 (n=656), and INT 114 (n=1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. Results: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. Conclusion: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned

Postoperative chemoradiation for resected gastric cancer - is the Macdonald Regimen Tolerable? a retrospective multi-institutional study

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Kundel, Yulia; Fenig, Eyal; Sulkes, Aaron; Brenner, Baruch; Purim, Ofer; Idelevich, Efraim; Lavrenkov, Konstantin; Man, Sofia; Kovel, Svetlana; Karminsky, Natalia; Pfeffer, Raphael M; Nisenbaum, Bella

2011-01-01

Postoperative chemoradiation as per Intergroup-0116 trial ('Macdonald regimen') is considered standard for completely resected high risk gastric cancer. However, many concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed our experience with its use. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts after complete resection (R0). Postoperative chemoradiation therapy was given according to the original Intergroup-0116 regimen. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of OS and DFS between R0 and R1 pts was done using the log-rank test. Between 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection of locally advanced gastric adenocarcinoma received postoperative chemoradiation; 61% were male and the median age was 63 years (range, 23-86); 78% had T ≥ 3 tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54% completed the entire chemoradiation plan; 46.4% had grade ≥ 3 toxicity and 32% were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity: diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small bowel gangrene (1). The most common hematological toxicity was neutropenia, grade ≥ 3 in 30% of pts and complicated by fever in 15%. The most common non-hematological toxicities were nausea, vomiting and diarrhea. With a median follow-up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are free of disease. Median DFS and OS for R0 were not reached. R0 pts had a significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p = 0.01) compared with R1 pts. In our experience, postoperative chemoradiation as per Intergroup-0116 seems to be substantially toxic

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients

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Choi, M. Y.; Clarke, A. E.; St Pierre, Y.

2017-01-01

, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate...

Survival of added bacterial species and metabolism of toxic compounds in natural environments

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King, V.M.

1987-01-01

Bacteria able to degrade either 2,4-dichlorophenol (DCP) or phenanthrene (PHEN) were isolated from polluted freshwater environments. Two isolates able to degrade each compound were tested for mineralization with a sensitive 14 C assay and for survival in lake water and sewage using a selective medium. One DCP isolate was identified as Alcaligenes paradoxus and the other as Alcaligenes sp. One PHEN isolate was identified as Pseudomonas fluorescens and the other as Pseudomonas sp. All four isolates survived and grew in sterile environments which indicated that starvation would not be a factor in survival of these strains. The number of organisms declined immediately in number in nonsterile lake water. However, they did survive or even grow in nonsterile sewage for a short period before declining in number. Biotic factors appeared to be influential for survival and mineralization of target compounds in many environments. The removal of protozoa, which prey on bacteria, improved survival of the added cells, but had no influence on the mineralization of 10 μg DCP/L. In comparison, degradation of 10 and 25 mg DCP/L stopped after a few days. Yeast nitrogen base appeared to overcome the lack of nutrient regeneration, a function attributed to protozoa. The additional nutrients increased toxicant mineralization, especially when seeded with appropriate species. Thus, protozoa may limit growth of added cells but appear to be needed for mineralization of higher concentrations of DCP

Electronic Cigarettes Are as Toxic to Skin Flap Survival as Tobacco Cigarettes.

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Rau, Aline Sabrina; Reinikovaite, Viktorija; Schmidt, Eric P; Taraseviciene-Stewart, Laima; Deleyiannis, Frederic White-Brown

2017-07-01

Electronic cigarettes (e-cigarettes) have become increasingly popular. However, information about the health risks associated with e-cigarette use is sparse. Currently, no published studies examine the effects of chronic e-cigarette exposure on microcirculation or perfusion. Using a rat skin flap model, we examined the toxic microcirculatory effects e-cigarettes may have in comparison with tobacco cigarettes. Fifty-eight rats were randomized to either exposure to room air, tobacco cigarette smoke, medium-nicotine content (1.2%) e-cigarette vapor, or a high-nicotine content (2.4%) e-cigarette vapor. After 4 weeks of exposure, a random pattern, 3 × 9 cm skin flap was elevated on the dorsum of the rats. At 5 weeks, flap survival was evaluated quantitatively, and the rats were euthanized. Plasma was collected for nicotine and cotinine analysis, and flap tissues were harvested for histopathological analysis. Evaluation of the dorsal skin flaps demonstrated significantly increased necrosis in the vapor and tobacco groups. The average necrosis within the groups was as follows: control 19.23%, high-dose vapor 28.61%, medium-dose vapor 35.93%, and tobacco cigarette 30.15%. Although the e-cigarette and tobacco cigarette groups did not differ significantly, each individual group had significantly more necrosis than the control group (Pe-cigarette exposure groups had similar amounts of flap necrosis and hypoxia when compared with the tobacco cigarette exposure group. Nicotine-containing e-cigarette vapor is similarly toxic to skin flap survival as tobacco cigarettes.

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

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Wilcox SW

2014-08-01

Full Text Available Shea W Wilcox,1,4 Noel J Aherne,2,4 Linus C Benjamin,1 Bosco Wu,1 Thomaz de Campos Silva,3 Craig S McLachlan,4 Michael J McKay,3,5 Andrew J Last,1 Thomas P Shakespeare1–4 1North Coast Cancer Institute, Port Macquarie, NSW, Australia; 2North Coast Cancer Institute, Coffs Harbour, NSW, Australia; 3North Coast Cancer Institute, Lismore, NSW, Australia; 4The University of New South Wales, Rural Clinical School, Sydney, NSW, Australia; 5The University of Sydney, Sydney, NSW, Australia Purpose: Dose-escalated (DE radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS in several studies. In the same group of patients, androgen deprivation therapy (ADT has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT and ADT. Methods and materials: Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results: Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2

Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study

DEFF Research Database (Denmark)

Colleoni, Marco; Giobbie-Hurder, Anita; Regan, Meredith M

2011-01-01

Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged ov...

Toxicity and survival results of a phase II study investigating the role of postoperative chemoradioimmunotherapy for gastric adenocarcinoma

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Bese, N.S.; Yildirim, A.; Oeber, A. [Dept. of Radiation Oncology, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey); Bueyuekuenal, E.; Oezgueroglu, M.; Demir, G.; Mandel, N.M.; Demirelli, F.; Serdengecti, S. [Dept. of Internal Medicine, Medical Oncology Section, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey)

2005-10-01

Background and purpose: to investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients. Patients and methods: 59 pateints, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m{sup 2}/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m{sup 2}/day 5-FU and 25 mg/m{sup 2}/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). Results: median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. Conclusion: although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care. (orig.)

Long-term Outcomes and Quality of Life of 186 Patients With Primary Parotid Carcinoma Treated With Surgery and Radiotherapy at the Daniel den Hoed Cancer Center

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Al-Mamgani, Abrahim, E-mail: a.al-mamgani@erasmusmc.nl [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Rooij, Peter van [Department of Biostatistics, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Verduijn, Gerda M. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Meeuwis, Cees A. [Department of Otorhinolaryngology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Levendag, Peter C. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

2012-09-01

Purpose: To assess the outcomes, toxicity, and quality of life (QOL) of patients with primary parotid carcinoma treated with surgery and postoperative radiotherapy at the Daniel den Hoed Cancer Center. Methods and Materials: Between 1995 and 2010, 186 patients with parotid carcinoma were treated with parotidectomy with or without neck dissection, followed by radiotherapy. Elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. End points were locoregional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), late toxicity, and QOL. Results: After a median follow-up of 58 months (range, 4-172 months), the 5-year Kaplan-Meier estimates for LRC, DFS, CSS, and OS were 89%, 83%, 80%, and 68%, respectively. Forty-five events were reported: 24 distant metastases (DM) and 21 locoregional failures (LRF). Event-free survival rates by histological types were 89%, 78%, 76%, 74%, and 70% for acinic cell, mucoepidermoid, adenoid cystic, adenocarcinoma, and squamous cell carcinoma, respectively. More LRF were reported in patients with squamous cell and high-grade mucoepidermoid carcinoma (21% and 19%, respectively) than in patients with other histological types (p = 0.04) and more DM in patients with adenoid cystic and adenocarcinoma (20% and 19%, respectively) than in patients with other types (p = 0.03). None of the high-risk node-negative patients who received ENI developed regional failure. On multivariate analysis, T stage, N stage, grade, and presence of perineural invasion and facial paralysis correlated significantly with DFS. The 5-year cumulative incidence of grade {>=}2 late toxicity was 8%. QOL scores deteriorate during and shortly after treatment but returned in almost all scales to baseline scores within 6 months. Conclusions: Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects and preservation of good QOL scores. However, in

Long-term Outcomes and Quality of Life of 186 Patients With Primary Parotid Carcinoma Treated With Surgery and Radiotherapy at the Daniel den Hoed Cancer Center

International Nuclear Information System (INIS)

Al-Mamgani, Abrahim; Rooij, Peter van; Verduijn, Gerda M.; Meeuwis, Cees A.; Levendag, Peter C.

2012-01-01

Purpose: To assess the outcomes, toxicity, and quality of life (QOL) of patients with primary parotid carcinoma treated with surgery and postoperative radiotherapy at the Daniel den Hoed Cancer Center. Methods and Materials: Between 1995 and 2010, 186 patients with parotid carcinoma were treated with parotidectomy with or without neck dissection, followed by radiotherapy. Elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. End points were locoregional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), late toxicity, and QOL. Results: After a median follow-up of 58 months (range, 4–172 months), the 5-year Kaplan-Meier estimates for LRC, DFS, CSS, and OS were 89%, 83%, 80%, and 68%, respectively. Forty-five events were reported: 24 distant metastases (DM) and 21 locoregional failures (LRF). Event-free survival rates by histological types were 89%, 78%, 76%, 74%, and 70% for acinic cell, mucoepidermoid, adenoid cystic, adenocarcinoma, and squamous cell carcinoma, respectively. More LRF were reported in patients with squamous cell and high-grade mucoepidermoid carcinoma (21% and 19%, respectively) than in patients with other histological types (p = 0.04) and more DM in patients with adenoid cystic and adenocarcinoma (20% and 19%, respectively) than in patients with other types (p = 0.03). None of the high-risk node-negative patients who received ENI developed regional failure. On multivariate analysis, T stage, N stage, grade, and presence of perineural invasion and facial paralysis correlated significantly with DFS. The 5-year cumulative incidence of grade ≥2 late toxicity was 8%. QOL scores deteriorate during and shortly after treatment but returned in almost all scales to baseline scores within 6 months. Conclusions: Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects and preservation of good QOL scores. However, in

Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

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Zhen-Yu He

Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

Safety of concurrent adjuvant radiotherapy and chemotherapy for locally advanced soft tissue sarcoma.

Science.gov (United States)

Greto, Daniela; Loi, Mauro; Saieva, Calogero; Muntoni, Cristina; Delli Paoli, Camilla; Becherini, Carlotta; Ciabatti, Cinzia; Perna, Marco; Campanacci, Domenico; Terziani, Francesca; Beltrami, Giovanni; Scoccianti, Guido; Bonomo, Pierluigi; Meattini, Icro; Desideri, Isacco; Simontacchi, Gabriele; Mangoni, Monica; Livi, Lorenzo

2018-04-01

This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS). A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2-21.1 years). Local DFS-recurrence-free survival, distant DFS-relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28-72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81-12.58, p = .002 and HR 4.83, CI 1.41-16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02-4.87, p = .045; HR 2.88, 95% CI 1.10-7.52, p = .031; HR 2.59, 95% CI 1.11-6.04, p = .028). Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.

A Single-Institutional Experience of 15 Years of Treating T3 Laryngeal Cancer With Primary Radiotherapy, With or Without Chemotherapy

International Nuclear Information System (INIS)

Al-Mamgani, Abrahim; Tans, Lisa; Rooij, Peter van; Levendag, Peter C.

2012-01-01

Purpose: To retrospectively analyze the outcomes, toxicity, quality of life, and voice quality of patients with T3 laryngeal cancer treated with radiotherapy and to identify subgroups of patients in whom the addition of chemotherapy to radiotherapy is necessary. Methods and Materials: Between March 1996 and November 2009, 170 consecutive patients with T3 tumor were treated with (chemo)radiotherapy. Endpoints of the study were local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), late toxicity, quality of life, and voice handicap index. Results: After a median follow-up time of 32 months (range, 7–172), the 3-year actuarial rates of LC, LRC, DFS, and OS were 73%, 70%, 64%, and 61%, respectively, and the 5-year figures were 68%, 65%, 60%, and 49%, respectively. At last follow-up, 84 patients (49.5%) were still alive, 65 of them (77.3%) without local progression. Laryngectomy was performed in 16 patients, leaving 49 patients with anatomic organ preservation, corresponding to an actuarial laryngectomy-free survival of 58.3% at 3 years. The figures for patients treated with chemoradiotherapy and radiotherapy alone were 76.8% and 53.5%, respectively (p = 0.001). Chemoradiotherapy was the only significant predictor for LC on multivariate analysis. The overall 5-year cumulative incidence of late Grade ≥2 toxicity was 28.2%. Chemoradiotherapy, compared with radiotherapy alone, resulted in slight increase in late toxicity and slight deterioration of quality of life and voice-handicap-index scores. However, the differences were statistically not significant. Conclusion: The addition of chemotherapy to radiotherapy in T3 laryngeal cancer significantly improved LC and laryngectomy-free survival without statistically significant increases in late toxicity or deterioration of quality of life or voice handicap index.

The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma

International Nuclear Information System (INIS)

Kleinberg, Lawrence; Grossman, Stuart A.; Piantadosi, Steven; Zeltzman, Michel; Wharam, Moody

1999-01-01

Purpose: To determine the effects of sequential versus concurrent administration of cranial radiotherapy and cisplatin/carmustine (BCNU) chemotherapy on survival and toxicity in newly diagnosed high-grade astrocytomas. Methods and Materials: From 1988 to 1996, 101 patients were treated on 2 therapeutic protocols for malignant glioma that used the identical chemotherapy regimen but differed in the timing of cranial radiotherapy. The eligibility criteria for the 2 protocols were identical. In the first protocol (1988-1991, 52 patients), cisplatin 120 mg/BCNU 120 mg i.v. over 72 h, was given for 3 monthly cycles prior to cranial radiotherapy. After a response rate of 42%, with a median survival of 13 months was achieved with this sequential regimen, a successor protocol (1992-1996, 49 patients) was developed in which cranial radiotherapy began concurrently with the start of the identical chemotherapy regimen. Chemotherapy was delayed but not discontinued if prolonged grade III/IV hematologic toxicity was experienced, but protocol therapy was discontinued if disease progression or thromboembolic events occurred. Survival outcome and hematologic toxicity were compared for the patients treated on these protocols. Results: Seventy-seven percent of sequentially-treated patients and 68% of concurrently-treated patients completed all planned therapy. Kaplan-Meier survival was similar to concurrent or sequential administration of chemotherapy and radiotherapy (median 12.8 months vs. 13.8 months, respectively). Hematologic toxicity was significantly less in sequentially- versus concurrently-treated patients, with median nadir per cycle (2.9 vs. 1.8 x 10 3 /mm 3 ) (p < 0.001), and incidence of grade 3/4 leukopenia 40% versus 77% (p = 0.002). There was also an increase in platelet transfusion requirements in concurrently-treated patients, but no significant worsening of anemia. We postulate that the worsened leukopenia results from the effects of concurrent radiotherapy on

Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer: 10-years median follow-up

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Maria Antonietta Gambacorta

2018-03-01

Full Text Available Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT in locally advanced rectal cancer (LARC. Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6–8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC, Metastasis Free Survival (MFS, Disease Free Survival (DFS, Disease Specific Survival (DSS and Overall Survival (OS. Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4. Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F. With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2% and gastrointestinal toxicities (10,2%. Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients. Keywords: Rectal cancer, Gefitinib, Log term follow-up, Chemoradiotherapy

Second-line treatment of recurrent HNSCC: tumor debulking in combination with high-dose-rate brachytherapy and a simultaneous cetuximab-paclitaxel protocol

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Ritter, M.; Teudt, I. U.; Meyer, J. E.; Schröder, U.; Kovács, G.; Wollenberg, B.

2016-01-01

After the failure of first-line treatment, the clinical prognosis in head and neck cancer (HNSCC) deteriorates. Effective therapeutic strategies are limited due to the toxicity of previous treatments and the diminished tolerance of surrounding normal tissue. This study demonstrates a promising second-line regimen, with function preserving surgical tumor debulking, followed by a combination of postoperative interstitial brachytherapy and a simultaneous protocol of cetuximab and taxol. From January 2006 to May 2013, 197 patients with HNSCC were treated with brachytherapy at the University Hospital Schleswig-Holstein Campus Lübeck, including 94 patients due to recurrent cancer. Within these, 18 patients were referred to our clinic because of early progressive disease following first- or second-line treatment failure. They received the new palliative regimen. A matched-pair analysis including recurrent tumor stage, status of resection margins, tissue invasion and previous therapy was performed to evaluate this treatment retrospectively. Overall survival (OS), disease-free survival (DFS), functional outcome and treatment toxicity was analyzed on the basis of medical records and follow-up data. DFS and OS of the study group were 8.7 and 14.8 months. Whereas, DFS and OS of the control group, treated only by function preserving tumor debulking and brachytherapy, was 3.9 and 6.1 months respectively. This demonstrates a positive trend through the additional use of the cetuximab-taxane protocol. Furthermore, no increase of therapy induced toxicities was displayed. Pre-treated patients with a further relapse benefit from the ‘cetuximab-taxane recurrency scheme’. It seems to be a valuable complement to interdisciplinary and multimodal tumor therapy, which improves OS and results in acceptable toxicity. The online version of this article (doi:10.1186/s13014-016-0583-0) contains supplementary material, which is available to authorized users

Effects of functionalized fullerenes on bifenthrin and tribufos toxicity to Daphnia magna: Survival, reproduction, and growth rate.

Science.gov (United States)

Brausch, Kathryn A; Anderson, Todd A; Smith, Philip N; Maul, Jonathan D

2010-11-01

Incorporation of carbon nanomaterials into industrial and consumer products is increasing, yet their impact on aquatic ecosystems alone and in chemical mixtures is largely unknown. Carbon nanomaterials may be found in the aquatic environment as mixtures with pesticides because of their proposed use in agriculture as smart delivery systems and nanosensors. The interaction effects of a functionalized fullerene ([1,2-methanofullerene C₆₀]-61-carboxylic acid) (fC₆₀) at 52.8 µg/L and the hydrophobic pesticides bifenthrin and tribufos were examined. The test organism was Daphnia magna, and response variables included 48-h survival, reproduction (bifenthrin, 70-d; tribufos, 21-d), and 10-d growth. Both pesticides reduced D. magna survival and reproduction (p bifenthrin acute toxicity but did not significantly affect chronic endpoints or growth (p > 0.05). Median lethal concentrations (LC50s), median inhibition concentrations (IC50s) for days surviving, and IC50s for reproduction were 0.86, 0.55, and 0.49 µg/L for bifenthrin; 0.22, 0.39, and 0.77 µg/L for fC₆₀-bifenthrin mix; 6.63, 9.89, and 5.79 µg/L for tribufos; and 9.17, 8.17, and 6.59 µg/L for fC₆₀-tribufos mix. Mixtures did not affect instantaneous growth rate (p > 0.05). These results suggest that fC₆₀ had little effect on pesticide chronic toxicity but influenced acute toxicity. Given the widespread application of nanotechnology, the influence of nanomaterials on environmental contaminants is an important consideration. Thus, our results may be useful in the development and use of nanotechnology in agricultural practices. © 2010 SETAC.

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

Science.gov (United States)

Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

2018-05-01

Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

Preoperative Concurrent Radiation Therapy and Chemotherapy for Bulky Stage IB2, IIA, and IIB Carcinoma of the Uterine Cervix With Proximal Parametrial Invasion

International Nuclear Information System (INIS)

Huguet, Florence; Cojocariu, Oana-Maria; Levy, Pierre; Lefranc, Jean-Pierre; Darai, Emile; Jannet, Denis; Ansquer, Yan; Lhuillier, Pierre-Eugene; Benifla, Jean-Louis; Seince, Nathalie; Touboul, Emmanuel

2008-01-01

Purpose: To evaluate toxicity, local tumor control, and survival after preoperative chemoradiation for operable bulky cervical carcinoma. Methods and Materials: Between December 1991 and July 2006, 92 patients with operable bulky stage IB2, IIA, and IIB cervical carcinoma without pelvic or para-aortic nodes on pretreatment imaging were treated. Treatment consisted of preoperative external beam pelvic radiation therapy (EBRT) and concomitant chemotherapy (CT) during the first and fourth weeks of radiation combining 5-fluorouracil and cisplatin. The pelvic radiation dose was 40.5 Gy over 4.5 weeks. EBRT was followed by low-dose rate uterovaginal brachytherapy with a total dose of 20 Gy in 62 patients. After a median rest period of 44 days, all patients underwent Class II modified radical hysterectomy with bilateral pelvic lymphadenectomy. Thirty patients who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy at a dose of 20 Gy. The mean follow-up was 46 months. Results: Pathologic residual tumor was observed in 43 patients. After multivariate analysis, additional preoperative uterovaginal brachytherapy was the single significant predictive factor for pathologic complete response rate (p = 0.019). The 2- and 5-year disease-free survival (DFS) rates were 80.4% and 72.2%, respectively. Pathologic residual cervical tumor was the single independent factor decreasing the probability of DFS (p = 0.020). Acute toxicities were moderate. Two severe ureteral complications requiring surgical intervention were observed. Conclusions: Concomitant chemoradiation followed by surgery for operable bulky stage I-II cervical carcinoma without clinical lymph node involvement can be used with acceptable toxicity. Pathologic complete response increases the probability of DFS

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.

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.

Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

Science.gov (United States)

Falcão, Daniela; Alexandrino, Henrique; Caetano Oliveira, Rui; Martins, João; Ferreira, Luís; Martins, Ricardo; Serôdio, Marco; Martins, Mónica; Tralhão, José Guilherme; Cipriano, Maria Augusta; Castro E Sousa, Francisco

2018-04-11

Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival.

Science.gov (United States)

Löser, Anastassia; Schwarzenböck, Sarah M; Heuschkel, Martin; Willenberg, Holger S; Krause, Bernd J; Kurth, Jens

2018-03-01

Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is regarded as a safe treatment option with promising results for patients with neuroendocrine neoplasia (NEN). We aimed to study the absorbed organ and tumor doses, the renal and hematological toxicity as well as their mutual interaction. Another aim was the identification of adverse effects as possible predictors which may affect survival. A total of 30 (14 female and 16 male) patients with inoperable/metastatic NEN were treated with 7.4 GBq of Lu-DOTATATE. Occurrence of renal and hematological toxicity wasretrospectively studied. Morever, we examined the effects of hematological toxicity on survival after Lu-DOTATATE-PRRT. In 49 treatment cycles, the mean absorbed dose to the kidneys was 5.13±2.12, 4.49±2.49 Gy to the liver, and 14.44±8.97 Gy to the spleen, whereas tumor lesions absorbed a mean dose of 31.43±36.86 Gy. Comparing different localizations of metastases, no significant differences in absorbed dose were observed. Clinical response status revealed regressive disease in 47.6%, stable disease in 38.1%, and progressive disease in 14.3% of cases (n=21). Biochemically, 81.3% of patients showed reduced serotonin values (n=16; P<0.05) following Lu-DOTATATE-PRRT. No severe subacute renal or hematological toxicity occurred (one Common Terminology Criteria for Adverse Events-grade 3 for thrombocytopenia and another one for leukocytopenia). No statistically significant relation between baseline kidney function and post-therapeutic hematological changes was identified. The findings indicate that Lu-DOTATATE-PRRT is a safe and effective treatment method for patients with NEN. Moreover, these data strongly suggest that hematological parameters may affect survival so a further re-evaluation in prospective studies is warranted.

Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers.

Science.gov (United States)

Imhof, Anna; Brunner, Philippe; Marincek, Nicolas; Briel, Matthias; Schindler, Christian; Rasch, Helmut; Mäcke, Helmut R; Rochlitz, Christoph; Müller-Brand, Jan; Walter, Martin A

2011-06-10

To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers. In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Overall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.

Alternative methods for toxicity assessments in fish: comparison of the fish embryo toxicity and the larval growth and survival tests in zebrafish and fathead minnows.

Science.gov (United States)

Jeffries, Marlo K Sellin; Stultz, Amy E; Smith, Austin W; Rawlings, Jane M; Belanger, Scott E; Oris, James T

2014-11-01

An increased demand for chemical toxicity evaluations has resulted in the need for alternative testing strategies that address animal welfare concerns. The fish embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such alternative, and the application of the FET test to other species such as the fathead minnow (Pimephales promelas) has been proposed. In the present study, the performances of the FET test and the larval growth and survival (LGS; a standard toxicity testing method) test in zebrafish and fathead minnows were evaluated. This required that testing methods for the fathead minnow FET and zebrafish LGS tests be harmonized with existing test methods and that the performance of these testing strategies be evaluated by comparing the median lethal concentrations of 2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the test types. The results showed that procedures for the zebrafish FET test can be adapted and applied to the fathead minnow. Differences in test sensitivity were observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions regarding which test types offer the least or most sensitivity could not be made. Overall, these results show that the fathead minnow FET test has potential as an alternative toxicity testing strategy and that further analysis with other toxicants is warranted in an effort to better characterize the sensitivity and feasibility of this testing strategy. © 2014 SETAC.

Prognostic value of preoperative Ca125 and Tag72 serum levels and their correlation to disease relapse and survival in endometrial cancer.

Science.gov (United States)

Myriokefalitaki, Eva; Vorgias, George; Vlahos, George; Rodolakis, Alexandros

2015-09-01

To evaluate preoperative serum levels of Ca125 and Tag72-4 tumour markers and investigate if abnormal levels correlate to mortality and disease-free survival. Retrospective observational study of a cohort of 282 women (mean age 62.3, SD 10.5 years) with primary endometrial cancer included all consecutive cases treated in a tertiary Gynaecological oncology Center. Excluded cases with other cancer or previous cancer treatment, major abdominal pathology or inflammation, endometriosis. Preoperative serum Tag72 and Ca125 levels were determined and evaluated in relation to disease-free survival (DFS) and disease-specific overall survival (DOS). Raised Ca125 correlates to worse overall disease-specific survival (66.1 vs 87.8 months, p = 0.021) and Tag72 correlates to shorter disease-free survival (69.2 vs 67.3 months, p = 0.021) and higher recurrence rate (13.5 vs 6 %, p = 0.021). When both Ca125 and Tag72 are abnormal DFS and DOS are worse. 93.3 % (72.3 months) vs 82.4 %, (61.3 months) p = 0.018 and 96.3 % (74.8 months) vs 88.2 %, (65.9 months) p = 0.021, respectively. This study enhances the value of preoperative tumour markers and their prognostic value. Ca125 and Tag72 appear to be good predictors of poor prognosis in patients with endometrial cancer.

Multi-Institutional Experience of Stereotactic Ablative Radiation Therapy for Stage I Small Cell Lung Cancer

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Verma, Vivek [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska (United States); Simone, Charles B. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Allen, Pamela K. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gajjar, Sameer R. [Baylor College of Medicine, Houston, Texas (United States); Shah, Chirag [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Zhen, Weining [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska (United States); Harkenrider, Matthew M. [Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois (United States); Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Jabbour, Salma K. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey (United States); Matthiesen, Chance L. [Department of Radiation Oncology, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma (United States); Braunstein, Steve E. [Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, California (United States); Lee, Percy [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Dilling, Thomas J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Allen, Bryan G. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Nichols, Elizabeth M. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); and others

2017-02-01

Purpose: For inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population. Methods and Materials: The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes. Results: From 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18 months). The median age and tumor size was 72 years and 2.5 cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50 Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7 months. The DFS rate was 58.3% and 53.2% at 1 and 3 years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3 months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8 months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0 months; P=.02) and OS (31.4 vs 14.3 months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and “elsewhere lung” (20.8%). The median time to each was 5 to 7 months. Conclusions: From the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50�

Outcomes of Risk-Adapted Fractionated Stereotactic Radiotherapy for Stage I Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Lagerwaard, Frank J.; Haasbeek, Cornelis J.A.; Smit, Egbert F.; Slotman, Ben J.; Senan, S.

2008-01-01

Purpose: High local control rates can be achieved using stereotactic radiotherapy in Stage I non-small-cell lung cancer (NSCLC), but reports have suggested that toxicity may be of concern. We evaluated early clinical outcomes of 'risk-adapted' fractionation schemes in patients treated in a single institution. Methods and Materials: Of 206 patients with Stage I NSCLC, 81% were unfit to undergo surgery and the rest refused surgery. Pathologic confirmation of malignancy was obtained in 31% of patients. All other patients had new or growing 18F-fluorodeoxyglucose positron emission tomography positive lesions with radiologic characteristics of malignancy. Planning four-dimensional computed tomography scans were performed and fractionation schemes used (3 x 20 Gy, 5 x 12 Gy, and 8 x 7.5 Gy) were determined by T stage and risk of normal tissue toxicity. Results: Median overall survival was 34 months, with 1- and 2-year survivals of 81% and 64%, respectively. Disease-free survival (DFS) at 1 and 2 years was 83% and 68%, respectively, and DFS correlated with T stage (p = 0.002). Local failure was observed in 7 patients (3%). The crude regional failure rate was 9%; isolated regional recurrence was observed in 4%. The distant progression-free survival at 1 and 2 years was 85% and 77%, respectively. SRT was well tolerated and severe late toxicity was observed in less than 3% of patients. Conclusions: SRT is well tolerated in patients with extensive comorbidity with high local control rates and minimal toxicity. Early outcomes are not inferior to those reported for conventional radiotherapy. In view of patient convenience, such risk-adapted SRT schedules should be considered treatment of choice in patients presenting with medically inoperable Stage I NSCLC

Adjuvant radiochemotherapy in locally advanced gastric cancer. Treatment results and analysis of possible prognostic factors

Energy Technology Data Exchange (ETDEWEB)

Martin Sanchez, Mercedes [Hospital Universitario Ramon y Cajal, Department of Radiation Oncology, Madrid (Spain); Perez Escutia, Maria Angeles; Guardado Gonzales, Sandra; Cabezas Mendoza, Ana Maria; Campos Bonel, Arantxa; Perez Montero, Hector; Ambrosi, Rafael d' ; Perez-Regadera Gomez, Jose Fermin [Hospital Universitario 12 de Octubre, Department of Radiation Oncology, Madrid (Spain); Lora Pablos, David [Hospital Universitario 12 de Octubre, Department of Statistics, Madrid (Spain)

2017-12-15

The aim of this study was to report the clinical outcome and toxicity of radiochemotherapy in locally advanced gastric cancer (LAGC) patients treated according to the Intergroup 116 trial protocol in our institution. We retrospectively reviewed 105 patients with LAGC treated with radical surgery and adjuvant radiochemotherapy. We analyzed overall survival (OS), disease-free survival (DFS), locoregional failure-free survival (LFS), prognostic factors and toxicity. The mean follow-up was 96.48 months. The majority of tumors were T3-T4 (75%) and 86.6% had nodal metastases. The OS, DFS and LFS rates to 3 years were 53.48%, 52.75% and 81.65%, respectively and to 5 years 40%, 46.73% and 76.77% respectively. The univariate analysis showed that N stage < N2, TN stage < IIIA, R0 resection and N-ratio < 3 were statistically significant prognostic factors for OS and DFS, T stage < T4 for OS and N-ratio < 3 for LFS. The group with D2 lymphadenectomy had worse LFS than the D1 group (65.2% vs 88.1%, respectively, p = 0.039) probably due to a significant difference in the proportion node positive patients in the D2 group (94% vs. 78%; p = 0.027). In the multivariate analysis, only R0 resection was statistically significant factor for improved OS (p = 0.018). Acute grade III-IV gastrointestinal and hematologic toxicity rates were 8.5% and 15.2%, respectively and 89.5% completed treatment as planned. Our results are consistent with those of the Intergroup-0116 trial for LAGC in terms of survival. This regimen is well tolerated and with acceptable toxicity. An R0 resection was an independent prognostic factor for improved OS. (orig.) [German] Das Ziel dieser Studie ist es, ueber die klinischen Ergebnisse und die Toxizitaet der adjuvanten Radiochemotherapie bei lokal fortgeschrittenem Magenkarzinom (LFM) entsprechend der Intergroup-0116-Studie in unserem Krankenhaus zu berichten. Es erfolgte eine retrospektive Auswertung von 105 Patienten mit LFM, welche mittels Operation und

Comparison of Effects of Separate and Combined Sugammadex and Lipid Emulsion Administration on Hemodynamic Parameters and Survival in a Rat Model of Verapamil Toxicity.

Science.gov (United States)

Tulgar, Serkan; Kose, Halil Cihan; Demir Piroglu, Isılay; Karakilic, Evvah; Ates, Nagihan Gozde; Demir, Ahmet; Gergerli, Ruken; Guven, Selin; Piroglu, Mustafa Devrim

2016-03-25

Toxicity of calcium channel blockers leads to high patient mortality and there is no effective antidote. The benefit of using 20% lipid emulsion and sugammadex has been reported. The present study measured the effect of sugammadex and 20% lipid emulsion on hemodynamics and survival in a rat model of verapamil toxicity. In this single-blinded randomized control study, rats were separated into 4 groups of 7 rats each: Sugammadex (S), Sugammadex plus 20% lipid emulsion (SL), 20% lipid emulsion (L), and control (C). Heart rates and mean arterial pressures were monitored and noted each minute until death. Average time to death was 21.0±9.57 minutes for group C, 35.57±10.61 minutes for group S, 37.14±16.6 minutes for group L and 49.86±27.56 minutes for group SL. Time to death was significantly longer in other groups than in the control group (psugammadex and lipid emulsion had a positive effect on survival in patients with calcium channel blocker toxicity. Sugammadex and intralipid increased survival in a rat model of verapamil toxicity. The combination of both drugs may decrease cardiotoxicity. Sugammadex alone or combined with 20% lipid emulsion reduce the need for inotropic agents. The mechanism requires clarification with larger studies.

Improved survival for elderly married glioblastoma patients. Better treatment delivery, less toxicity, and fewer disease complications

International Nuclear Information System (INIS)

Putz, Florian; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer; Putz, Tobias; Eyuepoglu, Ilker; Roessler, Karl

2016-01-01

Marital status is a well-described prognostic factor in patients with gliomas but the observed survival difference is unexplained in the available population-based studies. A series of 57 elderly glioblastoma patients (≥70 years) were analyzed retrospectively. Patients received radiotherapy or chemoradiation with temozolomide. The prognostic significance of marital status was assessed. Disease complications, toxicity, and treatment delivery were evaluated in detail. Overall survival was significantly higher in married than in unmarried patients (median, 7.9 vs. 4.0 months; p = 0.006). The prognostic significance of marital status was preserved in the multivariate analysis (HR, 0.41; p = 0.011). Married patients could receive significantly higher daily temozolomide doses (mean, 53.7 mg/m"2 vs. 33.1 mg/m"2; p = 0.020), were more likely to receive maintenance temozolomide (45.7 % vs. 11.8 %; p = 0.016), and had to be hospitalized less frequently during radiotherapy (55.0 % vs. 88.2 %; p = 0.016). Of the patients receiving temozolomide, married patients showed significantly lower rates of hematologic and liver toxicity. Most complications were infectious or neurologic in nature. Complications of any grade were more frequent in unmarried patients (58.8 % vs. 30.0 %; p = 0.041) with the incidence of grade 3-5 complications being particularly elevated (47.1 % vs. 15.0 %; p = 0.004). We found poorer treatment delivery as well as an unexpected severe increase in toxicity and disease complications in elderly unmarried glioblastoma patients. Marital status may be an important predictive factor for clinical decision-making and should be addressed in further studies. (orig.) [de

A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer (1) -survival and toxicity

International Nuclear Information System (INIS)

Su Shengfa; Lu Bing; Zhang Bo; Hu Yinyang; Ouyang Weiwei; Li Huiqin; Wang Gang; Long Jinhua

2011-01-01

Objective: To evaluate the overall survival and safety among patients for stage IV non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT). Methods: From Jan. 2003 to July 2010, 201 patients with stage IV NSCLC were included. All patients were treated with CCTTRT. Those patients who received only one cycle chemotherapy were not included in survival analysis,but analysis of toxicity. One hundred and eighty-two patients were eligible for survival analysis. All patients received platinum-based two-drug chemotherapy. The median number of cycles was 4. The median dose to planning target volume of primary tumor (DT PTV ) was 63 Gy. Treatment-related gastrointestinal and hematological toxicity were scored according to WHO criteria. Radiation-related pneumonitis and esophagitis were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) version 3.0. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model was used to examine the effect of CCTTRT on overall survival. Results: The follow-up rate of 201 patients was 97.5%. with 201, 170 and 134 patients finished 2 =10.10, P =0.001). For patients eligible for survival analysis and received 4 - 5 cycles of systemic chemotherapy, MST of patients treated with DT PTV ≥63 Gy was significantly longer than those treated with DT PTV 2 =20.48, P =0.000) and 16.1 months vs.8.8 months (χ 2 =11.75, P =0.001)]. For patients with single organ metastasis, MST was 16 months for those treated with DT PTV ≥63 Gy and 9 months for those with DT PTV 2 =10.51, P=0.000); for patients with multiple organ metastasis, it was 11 months and 7 months, respectively (χ 2 =7.90, P =0.005). Multivariate analysis showed that concurrent 4 - 5 cycles chemotherapy and DTPTV ≥63 Gy (β =0.243, P=0.019) and improved KPS (β =1.268, P=0.000) were independent factors for survival. For the whole

Comparison of the various conditionings to base of whole-body irradiation, in malignant pediatric haematology: retrospective study of 702 patients from the register of the French Society of marrow transplant and cellular therapy; Comparaison des differents conditionnements a base d'irradiation corporelle totale, en hematologie pediatrique maligne: etude retrospective de 702 patients a partir du registre de la Societe francaise de greffe de moelle et therapie cellulaire

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Maurin, C

2006-10-15

The aim of this work is to list the different conditioning used these last twenty years, in pediatrics for malignant hemopathy, then to evaluate the efficiency and the toxicity of these different conditioning by calculating and comparing the T.R.M. ( treatment related mortality), the D.F.S. (disease free survival) and the global survival. This work suggests a behavior liking homogeneous and adapted. In this study none of the 2 conditionings (T.A.M. or T.B.i.-E.D.X.) seems superior than we consider all the population of the malignant pediatric hemopathy or the only L.A.L.. The T.A.M. is more toxic but limits relapses. The global survival is similar. The adoption of homogeneous practices at the French level even European is a desirable objective. (N.C.)

The association between osteopontin and survival in non-small-cell lung cancer patients: a meta-analysis of 13 cohorts

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Wang Y

2015-11-01

Full Text Available Ying Wang,1,* Jin Yang,1,* Hui Liu,1 Ji-Rui Bi,1 Ying Liu,2 Yan-Yan Chen,2 Ji-Yu Cao,2 You-Jin Lu1 1Department of Respiratory Medicine, the Second Affiliated Hospital of Anhui Medical University, 2Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China *These authors contributed equally to this work Abstract: In the last decade, osteopontin (OPN was identified as one of the important proteins that promote the metastasis of tumor. However, the association between OPN overexpression and clinical outcome of non-small-cell lung cancer (NSCLC was unclear. The purpose of this study is to investigate the role of OPN in NSCLC patients. A total of 13 studies are included to explore the relationship between the OPN elevation and the overall survival (OS and disease-free survival (DFS in NSCLC patients. We searched for related articles in PubMed, Web of Science, Google Scholar, and Cochrane Library databases, which were published before January 31, 2015. Hazard ratio (HR, odds ratio (OR, and 95% confidence interval (CI in the high OPN expression group compared with the low OPN expression group were calculated and analyzed. Primary results were summarized by using a fixed-effects model or a random-effects model. The stratified analyses in subgroups were also performed. Thirteen cohort studies, which involved 1,630 patients, were included. Subgroup analyses were performed by area and test method of OPN. We found that OPN was significantly associated with poor OS (HR =2.20, 95% CI 1.71–2.83, P<0.001 and DFS (HR =2.11, 95% CI 1.62–2.74, P<0.001 in NSCLC patients. OPN overexpression tended to be associated with the presence of advanced tumor TNM stage (III and IV (OR =2.57, 95% CI 1.61–4.11, P<0.001. The Egger’s test suggested that there was no publication bias in OS studies (P=0.062 and DFS studies (P=0.740. These data indicate that OPN seems to have a

Polymorphisms in folate-metabolizing enzymes and response to 5-fluorouracil among patients with stage II or III rectal cancer (INT-0144; SWOG 9304).

Science.gov (United States)

Ulrich, Cornelia M; Rankin, Cathryn; Toriola, Adetunji T; Makar, Karen W; Altug-Teber, Özge; Benedetti, Jacqueline K; Holmes, Rebecca S; Smalley, Stephen R; Blanke, Charles D; Lenz, Heinz-Josef

2014-11-01

Recurrence and toxicity occur commonly among patients with rectal cancer who are treated with 5-fluorouracil (5-FU). The authors hypothesized that genetic variation in folate-metabolizing genes could play a role in interindividual variability. The objective of the current study was to evaluate the associations between genetic variants in folate-metabolizing genes and clinical outcomes among patients with rectal cancer treated with 5-FU. The authors investigated 8 functionally significant polymorphisms in 6 genes (methylenetetrahydrofolate reductase [MTHFR] [C677T, A1298C], SLC19A1 [G80A], SHMT1 [C1420T], dihydrofolate reductase [DHFR] [Del19bp], TS 1494del,and TSER) involved in folate metabolism in 745 patients with TNM stage II or III rectal cancer enrolled in a phase 3 adjuvant clinical trial of 3 regimens of 5-FU and radiotherapy (INT-0144 and SWOG 9304). There were no statistically significant associations noted between polymorphisms in any of the genes and overall survival, disease-free survival (DFS), and toxicity in the overall analyses. Nevertheless, there was a trend toward worse DFS among patients with the variant allele of MTHFR C677T compared with wild-type, particularly in treatment arm 2, in which patients with the MTHFR C677T TT genotype had worse overall survival (hazards ratio, 1.76; 95% confidence interval, 1.06-2.93 [P = .03]) and DFS (hazards ratio, 1.84; 95% confidence interval, 1.12-3.03 [P = .02]) compared with those with homozygous wild-type. In addition, there was a trend toward reduced hematological toxicity among patients with variants of SLC19A1 G80A in treatment arm 1 (P for trend, .06) and reduced esophagitis/stomatitis noted among patients with variants of TSER in treatment arm 3 (P for trend, .06). Genetic variability in folate-metabolizing enzymes was found to be associated only to a limited degree with clinical outcomes among patients with rectal cancer treated with 5-FU. © 2014 American Cancer Society.

Differential impacts of clinical variables and 5-fluorouracil-based adjuvant chemotherapy on 5-year disease-free survival of patients with stage IIa and IIb colon cancer

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Yi-Hung Kuo

2018-01-01

Conclusion: Different predictors of DFS were observed in stage IIa and IIb colon cancer; adjuvant chemotherapy could provide a survival benefit for patients with stage IIb colon cancer who have one of the four factors that were studied in our hospital-based analysis.

Prediction of neoadjuvant radiation chemotherapy response and survival using pretreatment [{sup 18}F]FDG PET/CT scans in locally advanced rectal cancer

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Bang, Ji-In; Ha, Seunggyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kang, Sung-Bum; Oh, Heung-Kwon [Seoul National University Bundang Hospital, Department of Surgery, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Lee, Keun-Wook [Seoul National University Bundang Hospital, Department of Internal Medicine, Seongnam (Korea, Republic of); Lee, Hye-Seung [Seoul National University Bundang Hospital, Department of Pathology, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kim, Jae-Sung [Seoul National University Bundang Hospital, Department of Radiation Oncology, Seongnam (Korea, Republic of); Lee, Ho-Young [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of)

2016-03-15

The aim of this study was to investigate metabolic and textural parameters from pretreatment [{sup 18}F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC). We performed a retrospective review of 74 patients diagnosed with LARC who were initially examined with [{sup 18}F]FDG PET/CT, and who underwent neoadjuvant radiation chemotherapy followed by complete resection. The standardized uptake value (mean, peak, and maximum), metabolic volume (MV), and total lesion glycolysis of rectal cancer lesions were calculated using the isocontour method with various thresholds. Using three-dimensional textural analysis, about 50 textural features were calculated for PET images. Response to neoadjuvant radiation chemotherapy, as assessed by histological tumour regression grading (TRG) after surgery and 3-year DFS, was evaluated using univariate/multivariate binary logistic regression and univariate/multivariate Cox regression analyses. MVs calculated using the thresholds mean standardized uptake value of the liver + two standard deviations (SDs), and mean standard uptake of the liver + three SDs were significantly associated with TRG. Textural parameters from histogram-based and co-occurrence analysis were significantly associated with TRG. However, multivariate analysis revealed that none of these parameters had any significance. On the other hand, MV calculated using various thresholds was significantly associated with 3-year DFS, and MV calculated using a higher threshold tended to be more strongly associated with 3-year DFS. In addition, textural parameters including kurtosis of the absolute gradient (GrKurtosis) were significantly associated with 3-year DFS. Multivariate analysis revealed that GrKurtosis could be a prognostic factor for 3-year DFS. Metabolic and textural parameters from initial [{sup 18}F]FDG PET/CT scans could be indexes to assess

Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

International Nuclear Information System (INIS)

Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; Dam, Go van; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

2014-01-01

Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities

The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy.

Science.gov (United States)

Tian, Yun-Ming; Huang, Wei-Zeng; Yuan, Xia; Bai, Li; Zhao, Chong; Han, Fei

2017-06-27

Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed. The 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3-T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

Source water assessment and nonpoint sources of acutely toxic contaminants: A review of research related to survival and transport of Cryptosporidium parvum

Science.gov (United States)

Walker, Mark J.; Montemagno, Carlo D.; Jenkins, Michael B.

1998-12-01

Amendments to the Safe Drinking Water Act (PL-930123) in 1996 required that public water supply managers identify potential sources of contamination within contributing areas. Nonpoint sources of acutely toxic microbial contaminants, such as Cryptosporidium parvum, challenge current approaches to source identification and management as a first step toward developing management plans for public water supply protection. Little may be known about survival and transport in the field environment, prescribed practices may not be designed to manage such substances, and infective stages may be present in vast numbers and may resist water treatment and disinfection processes. This review summarizes research related to survival and transport of C. parvum oocysts, as an example of an acutely toxic contaminant with nonpoint sources in animal agriculture. It discusses ∥1) significance of infected domesticated animals as potential sources of C. parvum, (2) laboratory and field studies of survival and transport, and (3) approaches to source control in the context of public health protection.

Ten-year outcome including patterns of failure and toxicity for adjuvant whole abdominopelvic irradiation in high-risk and poor histologic feature patients with endometrial carcinoma

International Nuclear Information System (INIS)

Stewart, Kimberly D.; Martinez, Alvaro A.; Weiner, Sheldon; Podratz, Karl; Stromberg, Jannifer S.; Schray, Mark; Mitchell, Christina; Sherman, Alfred; Chen, Peter; Brabbins, Donald A.

2002-01-01

Purpose: To evaluate the long-term results of treatment using adjuvant whole abdominal irradiation (WAPI) with a pelvic/vaginal boost in patients with Stage I-III endometrial carcinoma at high risk of intra-abdominopelvic recurrence, including clear cell (CC) and serous-papillary (SP) histologic features. Methods and Materials: In a prospective nonrandomized trial, 119 patients were treated with adjuvant WAPI between November 1981 and April 2000. All patients were analyzed, including those who did not complete therapy. The mean age at diagnosis was 66 years (range 39-88). Thirty-eight patients (32%) had 1989 FIGO Stage I-II disease and 81 (68%) had Stage III. The pathologic features included the following: 64 (54%) with deep myometrial invasion, 48 (40%) with positive peritoneal cytologic findings, 69 (58%) with high-grade lesions, 21 (18%) with positive pelvic/para-aortic lymph nodes, and 44 (37%) with SP or CC histologic findings. Results: The mean follow-up was 5.8 years (range 0.2-14.7). For the entire group, the 5- and 10-year cause-specific survival (CSS) rate was 75% and 69% and the disease-free survival (DFS) rate was 58% and 48%, respectively. When stratified by histologic features, the 5- and 10-year CSS rate for adenocarcinoma was 76% and 71%, and for serous papillary/CC subtypes, it was 74% and 63%, respectively (p=0.917). The 5- and 10-year DFS rate for adenocarcinoma was 60% and 50% and was 54% and 37% serous papillary/CC subtypes, respectively (p=0.498). For surgical Stage I-II, the 5-year CSS rate was 82% for adenocarcinoma and 87% for SP/CC features (p=0.480). For Stage III, it was 75% and 57%, respectively (p=0.129). Thirty-seven patients had a relapse, with the first site of failure the abdomen/pelvis in 14 (38%), lung in 8 (22%), extraabdominal lymph nodes in 7 (19%), vagina in 6 (16%), and other in 2 (5%). When stratified by histologic variant, 32% of patients with adenocarcinoma and 30% with the SP/CC subtype developed recurrent disease. Most

Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

International Nuclear Information System (INIS)

Hiniker, Susan M.; Agarwal, Rajni; Modlin, Leslie A.; Gray, Christine C.; Harris, Jeremy P.; Million, Lynn; Kiamanesh, Eileen F.; Donaldson, Sarah S.

2014-01-01

Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

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Hiniker, Susan M. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Agarwal, Rajni [Section of Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, California (United States); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gray, Christine C. [Division of Child and Adolescent Psychiatry, Department of Psychiatry, Stanford University, Stanford, California (United States); Harris, Jeremy P.; Million, Lynn [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Kiamanesh, Eileen F. [Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, California (United States); Donaldson, Sarah S., E-mail: sarah2@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States)

2014-05-01

Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival

International Nuclear Information System (INIS)

Näsman, Anders; Nordfors, Cecilia; Grün, Nathalie; Munck-Wikland, Eva; Ramqvist, Torbjörn; Marklund, Linda; Lindquist, David; Dalianis, Tina

2013-01-01

Patients with human papillomavirus DNA positive (HPV DNA +) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPV DNA −) OSCC upon intensive oncological treatment. All HPV DNA + OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16 INK4a , and CD44 in OSCC in correlation to clinical outcome. Pretreatment tumors from 290 OSCC patients, the majority not receiving chemotherapy, were analyzed for HPV DNA by Luminex and for p16 INK4a and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPV DNA + and 211/290 (73%) overexpressed p16 INK4a , which correlated to presence of HPV (P < 0.0001). Presence of HPV DNA, absent/weak CD44 intensity staining correlated to favorable 3-year disease-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis, and likewise for p16 INK4a by univariate analysis. Upon stratification for HPV, HPV DNA + OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPV DNA + OSCC, p16 INK4a + overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPV DNA + and absent/weak CD44 intensity OSCC presented the best survival and this marker combination could possibly be used for selecting patients for tailored deintensified treatment in prospective clinical trials. Absence of/weak CD44 or presence of human papillomavirus (HPV) DNA was shown as a favorable prognostic factors in tonsillar and tongue base cancer. Moreover, patients with the combination of absence of/weak CD44 and presence of HPV DNA presented a very favorable outcome. Therefore, we suggest that this marker combination could potentially be used to single out patients with a high survival that could benefit from a de-escalated oncological treatment

Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study.

Science.gov (United States)

George, Daniel J; Martini, Jean-François; Staehler, Michael; Motzer, Robert J; Magheli, Ahmed; Escudier, Bernard; Gerletti, Paola; Li, Sherry; Casey, Michelle; Laguerre, Brigitte; Pandha, Hardev S; Pantuck, Allan J; Patel, Anup; Lechuga, Maria J; Ravaud, Alain

2018-04-01

Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated. Results: Baseline characteristics were similar in patients with ( n = 191) and without ( n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8 + T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib ( n = 101), but not with placebo ( n = 90). The sensitivity and specificity for CD8 + T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1 + versus PD-L1 - tumors (HR 1.75; P = 0.103). Among all patients with PD-L1 + tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175). Conclusions: Greater CD8 + T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR . ©2018 American Association for Cancer Research.

A randomized phase III trial comparing concomitant chemoradiotherapy versus radiotherapy alone in advanced head and neck cancers - mature results: Yoodhvir Singh Nagar, Lucknow Cancer Institute, India

International Nuclear Information System (INIS)

Singh, S.; Kumar, S.; Datta, N.R.

2003-01-01

To evaluate contribution of concomitant chemoradiotherapy (CTRT) over and above radiotherapy alone (RT) in previously untreated stage III/IV, squamous cell carcinoma of the head and neck (SCCH and N). Patients with cancers of oral cavity (OC), oropharynx (OP), supraglottis (SG) and hypopharynx (HP) were randomized into RT arm or CTRT arm. Radiotherapy was identical in both arms (70Gy/35 fractions/7 weeks). In CTRT arm concomitant cisplatin (35mg/m 2 ) was given weekly for seven cycles. Surgery was reserved for salvage purposes when required. From May 1996 to December 1998, 155 patients (RT=78, CTRT=77) were enrolled and 139 patients (RT1,CTRT=68) were assessable. Over 90% patients in both arms completed planned treatment. The complete response rate was 51% in RT arm and 71% in CTRT arm (p=0.017). The median disease free survival (DFS) and overall survival (OS) in RT arm and CTRT arm were 3 months vs. 11 months (p=0.0009) and 9 months vs. 26 months (p=0.01) respectively. The 5-year DFS and OS in the two arms were 10% vs. 27% (p=0.000) and 16% vs. 29% (p=0.01) respectively. Acute grade III toxicity was comparable in both the arms (12% vs. 16%, p=0.74). Late grade I/II toxicity was higher in CTRT arm (70% vs. 51%, p=0.09). Serious late toxicities were not seen in both arms. On univariate analysis the favorable factors for immediate response were protocol (CTRT better), primary site (SG and OP better than OC and HP), T-stage (T1-T2 better), Nodes (N0 better than N+), Stage (III > IV), KPS (>80) and lesser overall treatment time (OTT). Multivariate analysis retained protocol, T stage, N stage and OTT as factors independently affecting the immediate response. Addition of concomitant weekly cisplatin (35mg/m 2 ) to radiotherapy improves the likelihood of local control, DFS and OS with acceptable acute and late toxicities and can be recommended as a standard form of treatment in advanced SCCH and N

DFS-88, 1988 Tri-Service Data Fusion Symposium. Volume I - Technical Proceedings, Johns Hopkins University, Applied Physics Laboratory, Laurel, Maryland, 17 - 19 May 1988

National Research Council Canada - National Science Library

1988-01-01

The 1988 Tri-Service Data Fusion Symposium (DFS-88) was held at Laurel, Maryland on 17-19 May 1988 under the joint sponsorship of the Data Fusion Sub-Panel of the Joint Directors of Laboratories (JDL/DFSP...

Five-Year Follow-Up of Concomitant Accelerated Hypofractionated Radiation in Advanced Squamous Cell Carcinoma of the Buccal Mucosa: A Retrospective Cohort Study

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Hassan Iqbal

2015-01-01

Full Text Available In resource limited settings, induction chemotherapy with Gemcitabine and Cisplatinum and concurrent hypofractionated chemoradiation for locally advanced carcinoma of buccal mucosa (BMSCC are a cost effective option but remain under reported. The objective of this study was to report long term survival outcome after concurrent hypofractionated radiotherapy in locally advanced BMSCC. Between February 2005 and 2009, 63 patients received treatment. Induction chemotherapy (IC regimen consisted of two drugs: Gemcitabine and Cisplatin. All patients received 55 Gy of radiation in 20 fractions with concurrent single agent Cisplatin (75 mg/m2. Five-year overall survival (OS, disease-free survival (DFS, and progression-free survival (PFS were determined. Based on AJCC staging, 7 (11% patients were stage III, 31 (49% stage IV a, and 25 (40% stage IVb at presentation. After IC, 8 (18% patients had complete radiological response, 33 (73% had partial response, and 4 (9% had stable disease. After concurrent hypofractionated chemoradiation, thirty-nine (62% patients were complete responders and 24 (38% had stable disease. With a minimum follow-up of 60 months, 5-year OS, DFS, and PFS were 30%, 49%, and 30%, respectively. In locally advanced buccal mucosa squamous cell carcinoma, concurrent hypofractionated chemoradiation results in acceptable survival and regimen related toxicity.

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.

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

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

Improved survival for elderly married glioblastoma patients : Better treatment delivery, less toxicity, and fewer disease complications.

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Putz, Florian; Putz, Tobias; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Eyüpoglu, Ilker; Rössler, Karl; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer

2016-11-01

Marital status is a well-described prognostic factor in patients with gliomas but the observed survival difference is unexplained in the available population-based studies. A series of 57 elderly glioblastoma patients (≥70 years) were analyzed retrospectively. Patients received radiotherapy or chemoradiation with temozolomide. The prognostic significance of marital status was assessed. Disease complications, toxicity, and treatment delivery were evaluated in detail. Overall survival was significantly higher in married than in unmarried patients (median, 7.9 vs. 4.0 months; p = 0.006). The prognostic significance of marital status was preserved in the multivariate analysis (HR, 0.41; p = 0.011). Married patients could receive significantly higher daily temozolomide doses (mean, 53.7 mg/m² vs. 33.1 mg/m²; p = 0.020), were more likely to receive maintenance temozolomide (45.7 % vs. 11.8 %; p = 0.016), and had to be hospitalized less frequently during radiotherapy (55.0 % vs. 88.2 %; p = 0.016). Of the patients receiving temozolomide, married patients showed significantly lower rates of hematologic and liver toxicity. Most complications were infectious or neurologic in nature. Complications of any grade were more frequent in unmarried patients (58.8 % vs. 30.0 %; p = 0.041) with the incidence of grade 3-5 complications being particularly elevated (47.1 % vs. 15.0 %; p = 0.004). We found poorer treatment delivery as well as an unexpected severe increase in toxicity and disease complications in elderly unmarried glioblastoma patients. Marital status may be an important predictive factor for clinical decision-making and should be addressed in further studies.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

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Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

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Piccart-Gebhart, Martine; Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I; McCullough, Ann E; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W; Wolff, Antonio C; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D; Perez, Edith A

2016-04-01

Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. © 2015 by American Society of Clinical Oncology.

A retrospective study of 606 cases of nasopharyngeal carcinoma with or without oropharyngeal candidiasis during radiotherapy.

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Wen-Ze Qiu

Full Text Available To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC with or without oropharyngealcandidiasis (OPC during radiotherapy.The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH test and the presence of pseudomembranous (white form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates.Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3-4 mucositis (14.5% vs. 7.4%, P = 0.049, anaemia (11.3% vs. 4.4%, P = 0.020, hepatotoxicity (4.8% vs. 1.1%, P = 0.021 and critical weight loss (85.5% vs. 56.6%, P<0.001 during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS (70.9% vs. 82.6%, P = 0.012, mainly as a result of a reduction in locoregional relapse-free survival (LRFS (87.0%vs. 94.9%, P = 0.025. After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022. Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS.OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful.

Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

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Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

2017-03-14

BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly

Pretreatment depression as a prognostic indicator of survival and nutritional status in patients with head and neck cancer.

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Kim, Shin-Ae; Roh, Jong-Lyel; Lee, Sang-Ah; Lee, Sang-Wook; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2016-01-01

The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC). For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ-H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores ≥ 14 and nutritional status and laboratory data. Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P nutritional status, and survival outcomes in patients with HNSCC. © 2015 American Cancer Society.

Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery

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Sarah E. Sinnett

2017-06-01

Full Text Available Intravenous administration of adeno-associated virus serotype 9 (AAV9/hMECP2 has been shown to extend the lifespan of Mecp2−/y mice, but this delivery route induces liver toxicity in wild-type (WT mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the cisterna magna (ICM. AAV9/hMECP2 (1 × 1012 viral genomes [vg]; ICM extended Mecp2−/y survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 1012 vg of AAV9/hMECP2 induced clasping and abnormal gait. A lower dose mitigated these adverse phenotypes but failed to extend survival of Mecp2−/y mice. Thus, ICM delivery of this vector is impractical as a treatment for Rett syndrome (RTT. To improve the safety of MeCP2 gene therapy, the gene expression cassette was modified to include more endogenous regulatory elements believed to modulate MeCP2 expression in vivo. In Mecp2−/y mice, ICM injection of the modified vector extended lifespan and was well tolerated by the liver but did not rescue RTT behavioral phenotypes. In WT mice, these same doses of the modified vector had no adverse effects on survival or neurological phenotypes. In summary, we identified limitations of the original vector and demonstrated that an improved vector design extends Mecp2−/y survival, without apparent toxicity.

Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy - A singlearm phase II study

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Shawky, H.; Galal, S.

2014-01-01

Purpose: The aim of this study is to investigate efficacy and toxicity of 1 year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Methods: Between June 2010 and February 2012, 19 women with pathologically proven operable TNBC, who had received standard adjuvant chemotherapy before were enrolled. Patients received 1 year of oral capecitabine metronomic therapy (650 mg/m2, twice every day), after standard adjuvant chemotherapy and radiotherapy if indicated. The primary endpoints of this study were disease-free survival rates (DFS) and safety profile. Secondary end point was overall survival (OS). Results: The maximal follow-up was 46.6 months with a median of 30.1 months ±11.525 (95% CI; 28.5-33.5 months). The median DFS was 41.7 months ±2.7 (95% CI; 36.5-46.9). No one developed locoregional recurrence. The actuarial rate of DFS was 88.8% and 82.05% at 2 and 3 years, respectively. At the time of the analyses, no patients had died and the median OS was not reached. Treatment-related adverse events were manageable with only 1 patient (5.3%) suffering from Grade 3/4 hand-foot syndrome and another 1 patient (5.3%) suffering from Grade 3 diarrhea. No Grade 3/4 hematologic toxicity was recorded. All patients received full doses of capecitabine throughout the study and dose reduction was not required in any of our patients. Conclusion: One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy.

Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy--a single-arm phase II study.

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Shawky, Hanan; Galal, Samar

2014-12-01

The aim of this study is to investigate efficacy and toxicity of 1 year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Between June 2010 and February 2012, 19 women with pathologically proven operable TNBC, who had received standard adjuvant chemotherapy before were enrolled. Patients received 1 year of oral capecitabine metronomic therapy (650 mg/m2, twice every day), after standard adjuvant chemotherapy and radiotherapy if indicated. The primary endpoints of this study were disease-free survival rates (DFS) and safety profile. Secondary end point was overall survival (OS). The maximal follow-up was 46.6 months with a median of 30.1 months±11.525 (95% CI; 28.5-33.5 months). The median DFS was 41.7 months±2.7 (95% CI; 36.5-46.9). No one developed locoregional recurrence. The actuarial rate of DFS was 88.8% and 82.05% at 2 and 3 years, respectively. At the time of the analyses, no patients had died and the median OS was not reached. Treatment-related adverse events were manageable with only 1 patient (5.3%) suffering from Grade 3/4 hand-foot syndrome and another 1 patient (5.3%) suffering from Grade 3 diarrhea. No Grade 3/4 hematologic toxicity was recorded. All patients received full doses of capecitabine throughout the study and dose reduction was not required in any of our patients. One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy. Copyright © 2014. Production and hosting by Elsevier B.V.

Concomitant pelvic irradiation and chemotherapy in locally advanced cervical carcinoma. A retrospective study of 92 patients treated at the Curie Institute

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Nguyen, D.; Rochefordiere, A. de la; Chauveinc, L.; Cosset, J.M.; Clough, K.B.; Mouret-Fourme, E.; Guyonnet, M.

2002-01-01

The prognosis of locally advanced cervix cancers is poor with metastatic and local recurrence risks. Recent publications reported that concurrent chemotherapy and pelvic radiation increased local control compared to radiotherapy alone. Chemotherapy could also decrease metastatic recurrences. We report 92 cases of patients with locally advanced cervix cancer treated between 1986 and 1998 at the Institut Curie. Patients and methods. - Concurrent chemo-radiation was exclusive in 51 cases and added to surgery in 41 cases. Chemotherapy with 5FU -Cisplatin-Mitomycin C-Vindesin (protocol A) was performed for 43% of patients and 57% of them received 5FU-Cisplatin alone (protocol B). Results. -Median follow-up was 64 months (6-149 months). Five-year disease-free survival rate was 47% and local control rate was 70%. Disease-free survival was correlated with therapeutic response. After exclusive chemo-radiation, the good responsive patients had a better DFS (54% vs 26%, p=0.018). In the surgery group, those patients with sterilized lymph nodes and tumours had also a higher DFS (76% vs 47%, p=0.036). Toxicity was higher with protocol A. Conclusion. - From our study, it appears that local control of advanced cervix cancers is better with combined chemoradiotherapy but disease-free survival stays low according to the metastatic evolution. Metastasis without local recurrence remained frequent in our study. 5FU-CDDP chemotherapy has a lower toxicity and is as effective as 5FU-CDDP-Mitomycin C-Vindesin protocol, in association with radiotherapy. (author)

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

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Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

2015-01-01

Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence

Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

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Garlipp, Benjamin; Ptok, Henry; Benedix, Frank; Otto, Ronny; Popp, Felix; Ridwelski, Karsten; Gastinger, Ingo; Benckert, Christoph; Lippert, Hans; Bruns, Christiane

2016-12-01

Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

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Feng, Siyang; Wang, Yuanyuan; Cai, Kaican; Wu, Hua; Xiong, Gang; Wang, Haofei; Zhang, Ziliang

2015-01-01

Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC. Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS). 41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib. The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

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Siyang Feng

Full Text Available Epidermal growth factor receptor (EGFR mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC. Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC.Patients with surgically resected stage IB (with high risk factors to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1 to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS.41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122. At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225, respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066. The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would

Clinical impact of tumor location on the colon cancer survival and recurrence: analyses of pooled data from three large phase III randomized clinical trials.

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Aoyama, Toru; Kashiwabara, Kosuke; Oba, Koji; Honda, Michitaka; Sadahiro, Sotaro; Hamada, Chikuma; Maeda, Hiromichi; Mayanagi, Shuhei; Kanda, Mitsuro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

2017-11-01

The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Association of perioperative blood pressure with long-term survival in rectal cancer patients.

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Yu, Hui-Chuan; Luo, Yan-Xin; Peng, Hui; Wang, Xiao-Lin; Yang, Zi-Huan; Huang, Mei-Jin; Kang, Liang; Wang, Lei; Wang, Jian-Ping

2016-04-11

Several studies suggested that hypertension is positively related to cancer incidence and mortality. In this study, we investigated the association between perioperative blood pressure (BP) and long-term survival outcomes in patients with rectal cancer. This study included a cohort of 358 patients with stages I-III rectal cancer who underwent a curative resection between June 2007 and June 2011. Both pre- and postoperative BPs were measured, by which patients were grouped (low BP: cancer-specific survival (CSS). Univariate analysis showed that patients with high preoperative systolic BP had lower 3-year DFS (67.2% vs. 82.1%, P = 0.041) and CSS rates (81.9% vs. 94.8%, P = 0.003) than patients with low preoperative systolic BP, and the associations remained significant in the Cox multivariate analysis, with the adjusted hazard ratios equal to 1.97 [95% confidence interval (CI) = 1.08-3.60, P = 0.028] and 2.85 (95% CI = 1.00-8.25, P = 0.050), respectively. Similarly, in postoperative evaluation, patients with high systolic BP had significantly lower 3-year CSS rates than those with low systolic BP (78.3% vs. 88.9%, P = 0.032) in univariate analysis. Moreover, high pre- and/or postoperative systolic BP presented as risk factors for CSS in the subgroups of patients who did not have a history of hypertension, with and/or without perioperative administration of antihypertensive drugs. High preoperative systolic BP was an independent risk factor for both CSS and DFS rates, and high postoperative systolic BP was significantly associated with a low CSS rate in rectal cancer patients. Additionally, our results suggest that rectal cancer patients may get survival benefit from BP control in perioperative care. However, further studies should be conducted to determine the association between BP and CSS and targets of BP control.

Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

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Tao HM

2016-03-01

Full Text Available Hengmin Tao,1,2 Yumei Wei,1 Wei Huang,1 Xiujuan Gai,1,2 Baosheng Li11Department of 6th Radiation Oncology, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaAim: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF have been involved in the treatment of nasopharyngeal carcinoma (NPC. However, the potential clinical effects and toxicities are still controversial.Methods: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS, 5-year progression-free survival (PFS, 5-year locoregional recurrence-free survival (LRFS, and relevant toxicities were analyzed.Results: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months. The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568. In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773 and 5-year LRFS (88.1% vs 90.8%, P=0.903. Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05.Conclusion: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.Keywords: intensity

Increased platelet-lymphocyte ratio closely relates to inferior clinical features and worse long-term survival in both resected and metastatic colorectal cancer: an updated systematic review and meta-analysis of 24 studies.

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Chen, Nan; Li, Wanling; Huang, Kexin; Yang, Wenhao; Huang, Lin; Cong, Tianxin; Li, Qingfang; Qiu, Meng

2017-05-09

Colorectal cancer (CRC) is one of the most common cancers worldwide. However, the prognostic and clinical value of platelet-lymphocyte ratio (PLR) in colorectal cancer was still unclear, which attracted more and more researchers' considerable attention. We performed a systematic review and meta-analysis to investigate the relationship between PLR and survival as well as clinical features of CRC update to September 2016. The hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) were calculated to access the association. We included 24 eligible studies with a total of 13719 patients. Elevated PLR predicted shorter overall survival (OS) (HR=1.47; 95%CI, 1.28-1.68; p<0.001), poorer disease-free survival (DFS) (HR=1.51; 95% CI, 1.2-1.91; p=0.001), and worse recurrence-free survival (RFS) (HR=1.39; 95% CI, 1.03-1.86; p=0.03), but had nothing to do with Cancer-specific survival (CSS) (HR=1.14; 95% CI, 0.92-1.42; p=0.223). After trim and fill method, the connection between PLR and DFS disappeared (HR=1.143; 95%CI, 0.903-1.447; p=0.267). By subgroup analyze, we found that increased PLR predicated a worse OS and DFS in patients who underwent surgery, and this prognostic role also shown both in metastatic and nonmetastatic patients. In addition, elevated PLR was associated with poorly differentiated tumor (OR=1.51; 95% CI, 1.26-1.81; p<0.001), higher tumor stage (OR=1.25; 95% CI, 1.05-1.49; p=0.012), lymphovascular invasion (LVI) (OR=1.25; 95% CI, 1.09-1.43; p=0.001), and the recurrence of CRC (OR=2.78; 95% CI, 1.36-5.68; p=0.005). We indicated that pretreatment PLR was a good prognostic marker for CRC patients. High PLR was related to worse OS, RFS and poor clinical characteristics.

Prognostic nutritional index as a prognostic biomarker for survival in digestive system carcinomas.

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Zhao, Yang; Xu, Peng; Kang, Huafeng; Lin, Shuai; Wang, Meng; Yang, Pengtao; Dai, Cong; Liu, Xinghan; Liu, Kang; Zheng, Yi; Dai, Zhijun

2016-12-27

The prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patients with various malignancies. We performed a meta-analysis to determine the predictive potential of PNI in digestive system cancers. Twenty-three studies with a total of 7,384 patients suffering from digestive system carcinomas were involved in this meta-analysis. A lower PNI was significantly associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95% Confidence Interval (CI) 1.62-2.07], the poorer disease-free survival (DFS) (HR 1.85, 95% CI 1.19-2.89), and the higher rate of post-operative complications (HR 2.31, 95% CI 1.63-3.28). In conclusion, PNI was allowed to function as an efficient indicator for the prognosis of patients with digestive system carcinomas.

Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino white men with localized prostate cancer: data from CaPSURE.

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Latini, David M; Elkin, Eric P; Cooperberg, Matthew R; Sadetsky, Natalia; Duchane, Janeen; Carroll, Peter R

2006-02-15

Few studies of ethnicity and prostate cancer have included Latino men in analyses of baseline clinical characteristics, treatment selection, and disease-free survival (DFS). The present study examines the impact of Latino ethnicity on these parameters in a large, multiinstitutional database of men with prostate cancer. We compared baseline disease characteristics and clinical outcomes for Latino (N = 138), non-Latino White (NLW, N = 5619), and African-American (AA, N = 608) men with localized prostate cancer by using chi-square and ANOVA for baseline variables and survival analysis to examine differences in time to recurrence. Latino men resembled AA men more than NLW on sociodemographic characteristics. AA men had higher Gleason scores and prostate-specific antigen (PSA) at diagnosis than Latino or NLW men (both P Latino and AA men presented with advanced disease (T3b/T4/N+/M+) versus 4% of NLW (P Latino men did not receive different treatments than NLW or AA men after controlling for clinical and demographic factors; however, AA men were more likely to receive external beam radiation (OR = 1.51, 95% confidence interval [CI] = 0.99-2.31) and hormone treatment (OR = 1.56, 95% CI = 1.05-2.32) then NLW men. For prostatectomy patients, 3-year actuarial DFS rates were 83% for NLW men and 86% for Latino men versus 69% for AA men (P Latinos are more similar to African Americans on sociodemographic characteristics but more similar to NLW on clinical presentation, treatments received, and DFS. Copyright 2006 American Cancer Society.

Toxicity of four veterinary pharmaceuticals on the survival and reproduction of Folsomia candida in tropical soils.

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Zortéa, Talyta; Segat, Julia C; Maccari, Ana Paula; Sousa, José Paulo; Da Silva, Aleksandro S; Baretta, Dilmar

2017-04-01

This study aimed to evaluate the effect of veterinary pharmaceuticals (VPs) used to control endo- and ectoparasites in ruminants, on the survival and reproduction of the collembolan species Folsomia candida. Standard ecotoxicological tests were conducted in Tropical Artificial Soil and the treatments consisted of increasing dosages of four commercial products with different active ingredients: ivermectin, fipronil, fluazuron and closantel. Ecotoxicological effects were related to the class and mode of action of the different compounds. Fipronil and ivermectin were the most toxic compounds causing a significant reduction in the number of juveniles at the lowest doses tested (LOEC reprod values of 0.3 and 0.2 mg kg -1 of dry soil, respectively) and similar low EC 50 values (fipronil: 0.19 mg kg -1 dry soil, CL 95% 0.16-0.22; ivermectin: 0.43 mg kg -1 dry soil, CL 95% 0.09-0.77), although the effects observed in the former compound were possibly related to a low adult survival (LC 50 of 0.62 mg kg -1 dry soil; CL 95% : 0.25-1.06). For the latter compound no significant lethal effects were observed. Fluazuron caused an intermediate toxicity (EC 50 of 3.07 mg kg -1 dry soil, CL 95% : 2.26-3.87), and also here a decrease in adult survival could explain the effects observed at reproduction. Closantel, despite showing a significant reduction on the number of juveniles produced, no dose-response relationship nor effects higher than 50% were observed. Overall, all tested compounds, especially ivermectin, when present in soil even at sub-lethal concentrations, can impair the reproduction of collembolans and possibly other arthropods. However, the actual risk to arthropod communities should be further investigated performing tests under a more realistic exposure (e.g., by testing the dung itself as the contaminated matrix) and by deriving ecotoxicologically relevant exposure concentration in soil derived from the presence of cattle dung. Copyright © 2017 Elsevier

Stereotactic Body Radiotherapy: A Promising Treatment Option for the Boost of Oropharyngeal Cancers Not Suitable for Brachytherapy: A Single-Institutional Experience

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Al-Mamgani, Abrahim, E-mail: a.al-mamgani@erasmusmc.nl [Department of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Groene Hilledijk, Rotterdam (Netherlands); Tans, Lisa; Teguh, David N. [Department of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Groene Hilledijk, Rotterdam (Netherlands); Rooij, Peter van [Department of Biostatistics, Erasmus MC-Daniel den Hoed Cancer Center, Groene Hilledijk, Rotterdam (Netherlands); Zwijnenburg, Ellen M.; Levendag, Peter C. [Department of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Groene Hilledijk, Rotterdam (Netherlands)

2012-03-15

Purpose: To prospectively assess the outcome and toxicity of frameless stereotactic body radiotherapy (SBRT) as a treatment option for boosting primary oropharyngeal cancers (OPC) in patients who not suitable for the standard brachytherapy boost (BTB). Methods and Materials: Between 2005 and 2010, 51 patients with Stage I to IV biopsy-proven OPC who were not suitable for BTB received boosts by means of SBRT (3 times 5.5 Gy, prescribed to the 80% isodose line), after 46 Gy of IMRT to the primary tumor and neck (when indicated). Endpoints of the study were local control (LC), disease-free survival (DFS), overall survival (OS), and acute and late toxicity. Results: After a median follow-up of 18 months (range, 6-65 months), the 2-year actuarial rates of LC, DFS, and OS were 86%, 80%, and 82%, respectively, and the 3-year rates were 70%, 66%, and 54%, respectively. The treatment was well tolerated, as there were no treatment breaks and no Grade 4 or 5 toxicity reported, either acute or chronic. The overall 2-year cumulative incidence of Grade {>=}2 late toxicity was 28%. Of the patients with 2 years with no evidence of disease (n = 20), only 1 patient was still feeding tube dependent and 2 patients had Grade 3 xerostomia. Conclusions: According to our knowledge, this study is the first report of patients with primary OPC who received boosts by means of SBRT. Patients with OPC who are not suitable for the standard BTB can safely and effectively receive boosts by SBRT. With this radiation technique, an excellent outcome was achieved. Furthermore, the SBRT boost did not have a negative impact regarding acute and late side effects.

Invasive Pleomorphic Lobular Histology Is an Adverse Prognostic Factor on Survival in Patients with Breast Cancer.

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Sahin, Suleyman; Karatas, Fatih; Erdem, Gokmen U; Hacioglu, Bekir; Altundag, Kadri

2017-04-01

Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and different subtype of classical invasive lobular carcinoma (ILC). This special variant is characterized by significant cytological atypia and pleomorphism which differs from the cytological uniformity of ILC. IPLC has been shown to have some poor prognostic factors such as axillary node metastasis and higher histological grade which may lead to poor clinical courses including a short relapse time, increased risk of recurrence and a decreased survival. The aim of this study is to investigate the clinicopathological characteristics and prognosis of IPLC in comparison with ILC and also to evaluate if IPLC is a different clinical entity compared to ILC. A total number of 4418 breast cancer patients treated between 1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients diagnosed with pure IPLC. In this present study, clinicopathological characteristics, disease free survival (DFS) and overall survival (OS) of patients with ILC and IPLC were compared. This study design is one of the rare face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased rate of higher histologic grade, extracapsular extension, lymphovascular invasion and lower percentage of hormone positivity than those of patients with ILC. During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence, 5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC group. Patients with IPLC had a worse DFS and OS duration than patients with ILC (P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a special breast cancer subtype. This study suggests that IPLC is a distinct clinical entity with an advanced stage

A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer.

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Xu, Ling; Li, Jiang-Hong; Ye, Jing-Ming; Duan, Xue-Ning; Cheng, Yuan-Jia; Xin, Ling; Liu, Qian; Zhou, Bin; Liu, Yin-Hua

2017-08-20

Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer (AJCC) expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival (DFS) of 769 Stage I-III patients was 89.7%, and the 5-year overall survival (OS) of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups. There were 372 cases (46.7%) assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS (χ2 = 11.319, P= 0.001) and 5-year OS (χ2 = 5.225, P= 0.022). In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS (χ2 = 6.510, P= 0.039) but no significant differences in 5-year OS (χ2 = 5.087, P= 0.079). However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant

Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery

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Sergeant, Gregory; Eijsden, Rudy van; Roskams, Tania; Van Duppen, Victor; Topal, Baki

2012-01-01

Most cancer deaths are caused by metastases, resulting from circulating tumor cells (CTC) that detach from the primary cancer and survive in distant organs. The aim of the present study was to develop a CTC gene signature and to assess its prognostic relevance after surgery for pancreatic ductal adenocarcinoma (PDAC). Negative depletion fluorescence activated cell sorting (FACS) was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumour (T), and non-tumoural pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. ‘Ingenuity Pathway Analysis’ software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS). Using stringent statistical analysis, we retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway, TGF-β1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were overexpressed in CTC. High co-expression of TGF-β1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 6 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 – 3.559)) and OS (p=0.047, HR

Impact of "Killer Immunoglobulin-Like Receptor /Ligand" Genotypes on Outcome following Surgery among Patients with Colorectal Cancer: Activating KIRs Are Associated with Long-Term Disease Free Survival.

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Kemal Beksac

Full Text Available Approximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS. Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4 genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR and A-Bw4 (ligand for inhibitory KIR3DL1 were observed more frequently (p=0.017 and p=0.024; and KIR2DS2 and KIR2DS3 (both activating KIRs were observed less frequently (p=0.005 and p=0.043. Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07. The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023. KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028. The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR : 54/77/98 months (p=0.004. In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.

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André, Thierry; Vernerey, Dewi; Mineur, Laurent; Bennouna, Jaafar; Desrame, Jérôme; Faroux, Roger; Fratte, Serge; Hug de Larauze, Marine; Paget-Bailly, Sophie; Chibaudel, Benoist; Bez, Jeremie; Dauba, Jérôme; Louvet, Christophe; Lepere, Céline; Dupuis, Olivier; Becouarn, Yves; Mabro, May; Egreteau, Joëlle; Bouche, Olivier; Deplanque, Gaël; Ychou, Marc; Galais, Marie Pierre; Ghiringhelli, François; Dourthe, Louis Marie; Bachet, Jean-Baptiste; Khalil, Ahmed; Bonnetain, Franck; de Gramont, Aimery; Taieb, Julien

2018-05-20

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

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Wada, Nobuyuki; Rino, Yasushi; Masuda, Munetaka; Ito, Koichi; Sugino, Kiminori; Mimura, Takashi; Nagahama, Mitsuji; Kitagawa, Wataru; Shibuya, Hiroshi; Ohkuwa, Keiko; Nakayama, Hirotaka; Hirakawa, Shohei

2009-01-01

To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients

Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial.

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Perrone, F; Nuzzo, F; Di Rella, F; Gravina, A; Iodice, G; Labonia, V; Landi, G; Pacilio, C; Rossi, E; De Laurentiis, M; D'Aiuto, M; Botti, G; Forestieri, V; Lauria, R; De Placido, S; Tinessa, V; Daniele, B; Gori, S; Colantuoni, G; Barni, S; Riccardi, F; De Maio, E; Montanino, A; Morabito, A; Daniele, G; Di Maio, M; Piccirillo, M C; Signoriello, S; Gallo, C; de Matteis, A

2015-04-01

Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. NCT00331097

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

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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

Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity.

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Romano, K D; Pugh, K J; Trifiletti, D M; Libby, B; Showalter, T N

In 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. From 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. Median followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. This comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

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Mantini, Giovanna; Tagliaferri, Luca; Mattiucci, Gian Carlo; Balducci, Mario; Frascino, Vincenzo; Dinapoli, Nicola; Di Gesù, Cinzia; Ippolito, Edy; Morganti, Alessio G.; Cellini, Numa

2011-01-01

Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Methods and materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score ≥7 and/or prostate-specific antigen level ≥20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12–38). With a median follow-up of 52 months (range, 20–150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p = NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p = .03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p = NS). Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.

Nasopharyngeal carcinoma in a low incidence European area. A prospective observational analysis from the Head and Neck Study Group of the Italian Society of Radiation Oncology (AIRO)

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Tonoli, S.; Bruschieri, L. [Brescia University, Istituto del Radio, Brescia (Italy); Alterio, D. [European Institute of Oncology, Milan (Italy); Caspiani, O. [Isola Tiberina Hospital, Rome (Italy); Bacigalupo, A. [IRCCS A.O.U. San Martino IST Genoa, Genoa (Italy); Bunkheila, F. [S. Orsola Hospital, Bologna (Italy); Cianciulli, M. [S. Camillo Hospital, Rome (Italy); Merlotti, A. [Busto Arsizio Hospital, Busto Arsizio (Italy); Podhradska, A. [Milan University - Monza S. Gerardo Hospital, Milan (Italy); Rampino, M. [Turin University, Turin (Italy); Cante, D. [Treviglio Hospital, Treviglio (Italy); Gatta, R. [Brescia University, Istituto del Radio, Brescia (Italy); Prato Hospital, Prato (Italy); Magrini, S.M.

2016-12-15

To evaluate the outcomes with respect to long-term survival and toxicity in patients with nasopharyngeal carcinoma (NPC) treated in a European country with low incidence. A prospective observational study carried out by the AIRO Head and Neck group in 12 Italian institutions included 136 consecutive patients treated with radiotherapy (RT) ± chemotherapy (CHT) for NPC (without distant metastasis) between January 1, 2008 and December 31, 2010. The disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) at 5 years were 92 (±2), 91 (±3), and 69 % (±5 %), respectively. Distant failure was the most frequent modality of relapse. The local, regional, and locoregional control at 5 years were 89 (±3), 93 (±3), and 84 % (±4 %), respectively. The incidence of acute and late toxicity and the correlations with different clinical/technical variables were analyzed. Neoadjuvant CHT prolongs radiotherapy overall treatment time (OTT) and decreases treatment adherence during concomitant chemoradiotherapy. An adequate minimum dose coverage to PTV(T) is a predictive variable well related to outcome. Our data do not substantially differ in terms of survival and toxicity outcomes from those reported in larger series of patients treated in countries with higher incidences of NPC. The T stage (TNM 2002 UICC classification) is predictive of DSS and OS. The GTV volume (T ± N) and an adequate minimum PTV(T) coverage dose (D95 %) were also identified as potential predictive variables. Sophisticated technologies of dose delivery (IMRT) with image-guided radiotherapy could help to obtain better minimum PTV(T) coverage dose with increased DFS; distant metastasis after treatment still remains an unresolved issue. (orig.) [German] Bewertung von langfristigem Ueberleben und Toxizitaet bei Patienten mit Nasopharynxkarzinom (NPC), die in einem europaeischen Land mit geringer Inzidenz behandelt wurden. Die prospektive Beobachtungsanalyse, durchgefuehrt von der

Intraoperative Radiotherapy in the Management of Locally Recurrent Extremity Soft Tissue Sarcoma

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Christopher L. Tinkle

2015-01-01

Full Text Available Purpose. To investigate the efficacy and morbidity of limb-sparing surgery with intraoperative radiotherapy (IORT for patients with locally recurrent extremity soft tissue sarcoma (ESTS. Methods and Materials. Twenty-six consecutively treated patients were identified in a single institution retrospective analysis of patients with locally recurrent ESTS treated with IORT following salvage limb-sparing resection from May 2000 to July 2011. Fifteen (58% patients received external beam radiotherapy (EBRT prior to recurrence (median dose 63 Gy, while 11 (42% patients received EBRT following IORT (median dose 52 Gy. The Kaplan-Meier product limit method was used to estimate disease control and survival and subsets were compared using a log rank statistic, Cox’s regression model was used to determine independent predictors of disease outcome, and toxicity was reported according to CTCAE v4.0 guidelines. Results. With a median duration of follow-up from surgery and IORT of 34.9 months (range: 4 to 139 mos., 10 patients developed a local recurrence with 4 subsequently undergoing amputation. The 5-year estimate for local control (LC was 58% (95% CI: 36–75%, for amputation-free was 81% (95% CI: 57–93%, for metastasis-free control (MFC was 56% (95% CI: 31–75%, for disease-free survival (DFS was 35% (95% CI: 17–54%, and for overall survival (OS was 50% (95% CI: 24–71%. Prior EBRT did not appear to influence disease control (LC, p=0.74; MFC, p=0.66 or survival (DFS, p=0.16; OS, p=0.58. Grade 3 or higher acute and late toxicities were reported for 6 (23% and 8 (31% patients, respectively. The frequency of both acute and late grade 3 or higher toxicities occurred equally between patients who received EBRT prior to or after IORT. Conclusions. IORT in combination with oncologic resection of recurrent ESTS yields good rates of local control and limb-salvage with acceptable morbidity. Within the limitations of small subsets, these data suggest

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma.

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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

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

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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

Phase II study of neoadjuvant treatment with doxorubicin, docetaxel, and capecitabine (ATX) in locally advanced or inflammatory breast cancer.

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Manga, Gumersindo Pérez; Shahi, Parham Khosravi; Ureña, Miguel Méndez; Pereira, Rosa Quiben; Plaza, María Isabel Palomero; Peron, Yann Izarzugaza; Val, Ricardo González Del; Carrión, Joaquín Belón; Cañón, Esperanza Pérez; Alfonso, Pilar García

2010-07-01

Pathologic complete response (pCR) after preoperative systemic chemotherapy (PSCh) is associated with better outcome in locally advanced breast cancer (LABC). PSCh included: doxorubicin (A) 50 mg/m(2) i.v. on day 1; docetaxel (T) 30 mg/m(2) i.v. on days 1, 8 and 15; and capecitabine (X) 1,500 mg/m(2)/day p.o. on days 1-14, in a 4-week course repeated for up to four cycles (ATX), followed by surgery. The primary end point of this study was to evaluate the pCR rate. Secondary endpoints included clinical response rate, disease-free survival (DFS), overall survival (OS), and the toxicity profile. A total of 60 patients were included in the analysis. Median age was 49 years, and 63.3% of patients were hormone receptor positive. The median number of cycles of PSCh was four (95% CI: 3-4). Five patients (8.3%) achieved pCR in both breast and nodes, and 16.7% reached pCR only in nodes. The clinical response rate was 77% (27% complete response), but only 18% of the patients underwent conservative surgery. With a median follow-up of 20 months, 3-year DFS and OS were 76 and 90%, respectively. Grade III/IV toxicity included neutropenia (74%), febrile neutropenia (9%), mucositis (12%), and diarrhea (12%). ATX every 28 days for four cycles is associated with a modest activity (low pCR rate) in the neoadjuvant setting of LABC.

Thermoregulatory responses to environmental toxicants: The interaction of thermal stress and toxicant exposure

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Leon, Lisa R.

2008-01-01

Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment. These physiological responses may exacerbate chemical toxicity due to increased permeability of the skin, which facilitates the cutaneous absorption of many environmental toxicants. The core temperature responses that are elicited in response to high ambient temperatures, toxicant exposure or both can also have a profound impact on the ability of an organism to survive the insult. In small rodents, the thermoregulatory response to thermal stress and many environmental toxicants (such as organophosphate compounds) is often biphasic in nature, consisting initially of a regulated reduction in core temperature (i.e., hypothermia) followed by fever. Hypothermia is an important thermoregulatory survival strategy that is used by small rodents to diminish the effect of severe environmental insults on tissue homeostasis. The protective effect of hypothermia is realized by its effects on chemical toxicity as molecular and cellular processes, such as lipid peroxidation and the formation of reactive oxygen species, are minimized at reduced core temperatures. The beneficial effects of fever are unknown under these conditions. Perspective is provided on the applicability of data obtained in rodent models to the human condition

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

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Lima Carmen SP

2011-03-01

Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

Nanomedical strategy to prolong survival period, heighten cure rate, and lower systemic toxicity of S180 mice treated with MTX/MIT.

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Song, Ning; Zhao, Ming; Wang, Yuji; Hu, Xi; Wu, Jianhui; Jiang, Xueyun; Li, Shan; Cui, Chunying; Peng, Shiqi

2016-01-01

In spite of the usual combination form of methotrexate (MTX)/mitoxantrone (MIT) and various complex combination regimens of MTX/MIT with other anticancer drugs, the survival period, cure rate, and systemic toxicity still need to be improved. For this purpose, a nanostructured amino group-modified mesoporous silica nanoparticles (MSNN)-MTX/MIT was designed. In the preparation, the surface of mesoporous silica nanoparticles (MSNs) was modified with amino groups to form MSNN. The covalent modification of the amino groups on the surface of MSNN with MTX resulted in MSNN-MTX. The loading of MIT into the surface pores of MSNN-MTX produced nanostructured MSNN-MTX/MIT. Compared with the usual combination form (MTX/MIT), nanostructured MSNN-MTX/MIT increased the survival period greatly, heightened the cure rate to a great extent, and lowered the systemic toxicity of the treated S180 mice, significantly. These superior in vivo properties of nanostructured MSNN-MTX/MIT over the usual combination form (MTX/MIT) were correlated with the former selectively releasing MTX and MIT in tumor tissue and inside cancer cells in vitro. The chemical structure and the nanostructure of MSNN-MTX/MIT were characterized using infrared and differential scanning calorimeter spectra as well as transmission electron microscope images, respectively.

Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer

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Dolezel, Martin; Odrazka, Karel; Zouhar, Milan; Jansa, Jan; Paluska, Petr; Vaculikova, Miloslava; Sefrova, Jana; Kohlova, Tereza; Vanasek, Jaroslav; Kovarik, Josef

2015-01-01

The purpose of this work was to compare toxicity and cancer control between patients with prostate cancer treated using three-dimensional conformal radiotherapy (3D-CRT) and those treated using intensity-modulated radiation therapy (IMRT). A total of 553 patients with prostate cancer were treated with 3D-CRT 70-74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78-82 Gy (IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT criteria. Biochemical failure was defined using the Phoenix and ASTRO definitions. The 5-year risk of grade 2-4 genitourinary toxicity was 26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB 82) without statistical differences. The 5-year risk of grade 2-4 gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 % (IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT 70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p = 0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk, intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5, and 57.8 %, respectively. Patients treated with IMRT achieved the following results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7 vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached 95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were statistically significant, while C-RFS and DFS were marginally better. Dose escalation with IMRT was associated with improved cancer control in intermediate- and high-risk patients in comparison with 3D-CRT, without compromising toxicity. (orig.) [de

Analysis of outcomes achieved with squamous cell carcinomas of the anus in a single university hospital over the last two decades: Clinical response rate, relapse and survival of 190 patients.

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Gravante, Gianpiero; Stephenson, James Andrew; Elshaer, Mohamed; Osman, Ahmed; Vasanthan, Subramaniam; Mullineux, Joseph H; Gani, Mohamed Akil Dilawar; Sharpe, David; Yeung, Justin; Norwood, Michael; Miller, Andrew; Boyle, Kirsten; Hemingway, David

2018-02-01

We reviewed our series of anal squamous cell carcinomas (ASCC) treated over the last two decades. ASCC patients undergoing treatment at the Leicester Royal Infirmary between 1998 and 2016 were selected. Age, gender, pathological tumor characteristics, treatment adopted, the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) at 5-year follow-up were recorded and calculated. A total of 190 ASCC were reviewed, of these 64.2% (n = 122) received primary radical chemoradiotherapy. Complete response rate was 92.6% (n = 113) and four patients with residual disease underwent a salvage APER. Twenty-eight patients experienced recurrent disease (23.0%) either systemic (n = 8), local (n = 14), or both (n = 6); six had a salvage APER. Complete follow-up data are available for 63.1% patients (77/122). Overall, the locoregional failure rate of primary chemoradiotherapy (residual + recurrent disease) was present in 29 patients (29/122; 23.8%). OS was 41.6% CSS was 69.2% and DFS 60.0% at 5 years follow-up. In our series of ASCC primary chemoradiotherapy had achieved significant initial complete response rates, however, long term-follow ups still present systemic and local recurrences. APR is able to treat 30% of the pelvic recurrences (6/20), the others are either associated with systemic disease or locally inoperable masses. © 2017 Wiley Periodicals, Inc.

Standardized toxicity testing may underestimate ecotoxicity: Environmentally relevant food rations increase the toxicity of silver nanoparticles to Daphnia.

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Stevenson, Louise M; Krattenmaker, Katherine E; Johnson, Erica; Bowers, Alexandra J; Adeleye, Adeyemi S; McCauley, Edward; Nisbet, Roger M

2017-11-01

Daphnia in the natural environment experience fluctuations in algal food supply, with periods when algal populations bloom and seasons when Daphnia have very little algal food. Standardized chronic toxicity tests, used for ecological risk assessment, dictate that Daphnia must be fed up to 400 times more food than they would experience in the natural environment (outside of algal blooms) for a toxicity test to be valid. This disconnect can lead to underestimating the toxicity of a contaminant. We followed the growth, reproduction, and survival of Daphnia exposed to 75 and 200 µg/L silver nanoparticles (AgNPs) at 4 food rations for up to 99 d and found that AgNP exposure at low, environmentally relevant food rations increased the toxicity of AgNPs. Exposure to AgNP at low food rations decreased the survival and/or reproduction of individuals, with potential consequences for Daphnia populations (based on calculated specific population growth rates). We also found tentative evidence that a sublethal concentration of AgNPs (75 µg/L) caused Daphnia to alter energy allocation away from reproduction and toward survival and growth. The present findings emphasize the need to consider resource availability, and not just exposure, in the environment when estimating the effect of a toxicant. Environ Toxicol Chem 2017;36:3008-3018. © 2017 SETAC. © 2017 SETAC.

Toxicity of contaminants in lagoons and pannes of the Indiana Dunes National Lakeshore

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Gillespie, R.; Speelman, J.; Stewart, P.M.

1995-01-01

Contaminants in water and sediments of lagoons and pannes were 2--90 times greater at sites adjacent to slag and coal piles than those at reference sites. One site (Lagoon-US5) had sediments with very high concentrations of toxic organics (e.g. naphthalene, phenanthrene, dibenzofuran). Although analyses indicated a gradient of contaminant concentration with distance from their sources, toxicity assays were somewhat equivocal. With the exception of less reproduction in Ceriodaphnia at one lagoon site (US3 = 0.55 of reference), survival of fathead minnows and reproduction in Ceriodaphnia in lagoon and panne waters varied independently of the contaminant concentration. In fact, there was better Ceriodaphnia reproduction in water from two contaminated sites (Lagoon-US5, Panne-WP1) than in water from reference sites. Fathead minnow survival, Ceriodaphnia survival, Ceriodaphnia reproduction, amphipod survival, and amphipod growth varied among sites in toxicity assays with sediments, 100% mortality of fatheads at Lagoon-US5, 100% mortality of Ceriodaphnia at Lagoon-US3, and less survival of fathead minnows at Lagoon-US3 indicate possible toxicity from contaminants in sediments at these sites. Of all organisms and end-points tested, Ceriodaphnia survival seemed to be most closely associated with concentrations of contaminants in lagoon water and sediments. Amphipod survival also varied with contaminants in sediments, however, survival in sediments of contaminated sites ranged only from 0.90--0.93 of reference sites. Although the results are not consistent among organisms, toxicity assays indicate that sediments from the lagoon site with the highest contaminants (Lagoon-US5) and possibly those from another contaminated lagoon site (Lagoon-US3) could be toxic to aquatic organisms. Water and sediments from contaminated panne sites do not appear to be toxic to aquatic test organisms

Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

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Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Conradi, Lena [Department of General Surgery, University Medical Center of Göttingen (Germany); Weiss, Christian [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sprenger, Thilo [Department of General Surgery, University Medical Center of Göttingen (Germany); Middel, Peter [Institute for Pathology, University Medical Center, Göttingen (Germany); Rau, Tillman [Institute of Pathology, University Hospital Erlangen, Erlangen (Germany); Dellas, Kathrin [Department of Radiotherapy, Lübeck University (Germany); Kitz, Julia [Institute for Pathology, University Medical Center, Göttingen (Germany); Rödel, Franz [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sauer, Rolf [Department of Radiation Oncology, University of Erlangen (Germany); Rüschoff, Josef [Targos Molecular Pathology, Kassel (Germany); Beissbarth, Tim [Department of Medical Statistics, University Medical Center of Göttingen (Germany); Arnold, Dirk [Tumor Biology Center Freiburg, University of Freiburg (Germany); Ghadimi, B. Michael [Department of General Surgery, University Medical Center of Göttingen (Germany); Rödel, Claus [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Liersch, Torsten [Department of General Surgery, University Medical Center of Göttingen (Germany)

2013-12-01

Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

International Nuclear Information System (INIS)

Fokas, Emmanouil; Conradi, Lena; Weiss, Christian; Sprenger, Thilo; Middel, Peter; Rau, Tillman; Dellas, Kathrin; Kitz, Julia; Rödel, Franz; Sauer, Rolf; Rüschoff, Josef; Beissbarth, Tim; Arnold, Dirk; Ghadimi, B. Michael; Rödel, Claus; Liersch, Torsten

2013-01-01

Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino White men with localized prostate cancer: Data from CaPSURE™

OpenAIRE

Latini, DM; Elkin, EP; Cooperberg, MR; Sadetsky, N; DuChane, J; Carroll, PR

2006-01-01

BACKGROUND. Few studies of ethnicity and prostate cancer have included Latino men in analyses of baseline clinical characteristics, treatment selection, and disease-free survival (DFS). The present study examines the impact of Latino ethnicity on these parameters in a large, multiinstitutional database of men with prostate cancer. METHODS. We compared baseline disease characteristics and clinical outcomes for Latino (N = 138), non-Latino White (NLW, N = 5619), and African-American (AA, N = 60...

Radiotherapy with or without chemotherapy in the treatment of anal cancer. 20-year experience from a single institute

Energy Technology Data Exchange (ETDEWEB)

Fakhrian, K.; Sauer, T.; Klemm, S.; Bayer, C.; Haller, B.; Molls, M.; Geinitz, H. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar

2013-01-15

Purpose: To report the efficacy and toxicity of radio(chemo)therapy (RCT) in the management of squamous cell anal carcinoma (SQ-AC) and to evaluate the prognostic factors influencing the outcomes. Patients and methods: A consecutive cohort of 138 patients with cT1-4, cN0-3, cM0 SQ-AC were treated with RCT between 1988 and 2011 at our department. Median follow-up time for surviving patients from the start of RCT was 98 months (range, 1-236 months). Patients were treated with a median radiation dose of 56 Gy (range, 4-61 Gy). Concurrent chemotherapy was administered to 119 patients (86%). Results: The survival rates at 2, 5, and 10 years were 88 {+-} 3, 82 {+-} 4, and 59 {+-} 6%, respectively, with a median overall survival (OS) of 167 months. The cumulative incidence for local recurrence at 2 and 5 years was 8 {+-} 2 and 11 {+-} 3%, respectively. The median disease-free survival (DFS) and colostomy-free survival (CFS) times were 132 and 135 months, respectively. In 19 patients (14%), a distant metastasis was diagnosed after a median time of 19 months. In the multivariate analysis, UICC (International Union Against Cancer) stage I-II, female gender, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and good/moderate histologic differentiation (G1-2) were significantly associated with a better OS, DFS, and CFS. Conformal radiotherapy planning techniques were significantly associated with a lower cumulative incidence of local recurrence (11 {+-} 3% vs. 38 {+-} 19% at 5 years, p = 0.006). A higher radiation dose beyond 54 Gy was not associated with an improvement in outcome, neither for smaller - (T1/T2) nor for larger tumors (T3/T4). Conclusion: RCT leads to excellent outcomes - especially in patients with stage I/II and G1/G2 tumors - with acceptable toxicity. The probable advantages of high-dose radiotherapy should be considered carefully against the risk of a higher rate of toxicity. Future studies are needed to investigate the role of a more

Locally-regionally advanced tonsillar squamous cell carcinoma treated with concurrent chemoradiotherapy

International Nuclear Information System (INIS)

Krstevska, Valentina; Stojkovski, Igor

2013-01-01

Purpose: To perform a retrospective review of stage III-IV squamous cell carcinoma of the tonsil managed by definitive concurrent chemoradiotherapy (CCRT) in order to analyze the patients’ outcome and to evaluate the acute and late toxic effects of this treatment modality. Material and methods: Between January 2005 and December 2010, 36 patients with locally and/or regionally advanced tonsillar cancer underwent three dimensional conformal radiotherapy (3DCRT) with concurrent platinum-based chemotherapy. The dose prescription of the planning target volume for gross tumor and low-risk subclinical disease was 70 Gy and 50 Gy, respectively. Conventional fractionation with a daily dose of 2.0 Gy, 5 times per week was used. Concurrent chemotherapy consisted of cisplatin 30 mg/m2 given on a weekly basis. Acute and late radiotherapy-related toxicities were recorded using European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) grading system. The 3-year locoregional relapse-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up of all patients was 20.5 months (range, 5 to 90 months). The median followup of living patients was 59 months (range, 30 to 90 months). Complete response rates of the primary tumor and of the nodal disease were 72.2% and 64.0%, respectively. A complete composite response was present in 25 patients (69.4%). Treatment failure occurred in 15 out of 25 patients who achieved complete composite response following CCRT. The 3-year LRRFS, DFS, and OS rate was 38.8%, 27.8%, and 27.3%, respectively. Grade 3 mucositis occurred in 58.3% of patients. Xerostomia grade 2 was revealed in 72.2% of patients. Conclusion: Taking into account the low 3-year survival rates observed in our study and the high percentage of grade 2 xerostomia, it can be concluded that in the future, instead of 3DCRT with concurrent

A decision tree-based combination of ezrin-interacting proteins to estimate the prognostic risk of patients with esophageal squamous cell carcinoma.

Science.gov (United States)

He, Jian-Zhong; Wu, Zhi-Yong; Wang, Shao-Hong; Ji, Xia; Yang, Cui-Xia; Xu, Xiu-E; Liao, Lian-Di; Wu, Jian-Yi; Li, En-Min; Zhang, Kai; Xu, Li-Yan

2017-08-01

Our previous studies have highlighted the importance of ezrin in esophageal squamous cell carcinoma (ESCC). Here our objective was to explore the clinical significance of ezrin-interacting proteins, which would provide a theoretical basis for understanding the function of ezrin and potential therapeutic targets for ESCC. We used affinity purification and mass spectrometry to identify PDIA3, CNPY2, and STMN1 as potential ezrin-interacting proteins. Confocal microscopy and coimmunoprecipitation analysis further confirmed the colocalization and interaction of ezrin with PDIA3, CNPY2, and STMN1. Tissue microarray data of ESCC samples (n=263) showed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower for the CNPY2 (OS, P=.003; DFS, P=.011) and STMN1 (OS, P=.010; DFS, P=.002) high-expression groups compared with the low-expression groups. By contrast, overexpression of PDIA3 was significantly correlated with favorable survival (OS, P<.001; DFS, P=.001). Cox regression demonstrated the prognostic value of PDIA3, CNPY2, and STMN1 in ESCC. Furthermore, decision tree analysis revealed that the resulting classifier of both ezrin and its interacting proteins could be used to better predict OS and DFS of patients with ESCC. In conclusion, a signature of ezrin-interacting proteins accurately predicts ESCC patient survival or tumor recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results.

Science.gov (United States)

Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques; Pandha, Hardev S; George, Daniel J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Casey, Michelle; Serfass, Lucile; Pantuck, Allan J; Staehler, Michael

2018-01-01

Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade. Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy. Most subgroups of patients at high risk of recurrent renal cell carcinoma after

Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: a systematic review and meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Leal, Frederico; Figueiredo, Maximiliano Augusto Novis de; Sasse, Andre Deeke, E-mail: sasse@cevon.com.br [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

2015-05-15

Objectives: to investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted. (author)

Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

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McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

2014-11-15

Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

The correlation between the ASTRO consensus panel definition of biochemical failure and clinical outcome for patients with prostate cancer treated with external beam irradiation

International Nuclear Information System (INIS)

Horwitz, Eric M.; Vicini, Frank A.; Ziaja, Ellen L.; Dmuchowski, Carl F.; Stromberg, Jannifer S.; Martinez, Alvaro A.

1998-01-01

Purpose: We reviewed our institution's experience treating patients with external beam irradiation (RT) to determine if the ASTRO Consensus Panel definition of biochemical failure (BF) following radiation therapy correlates with clinical distant metastases free survival (DMFS), disease-free survival (DFS), cause-specific survival (CSS), and local control (LC). Methods and Materials: Between 1/1/87 and 12/31/92, 568 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital (median total dose 66.6 Gy; range: 60-70.4 Gy). Biochemical failure was defined as three consecutive increases in post-treatment prostate specific antigen (PSA) after achieving a nadir. Biochemical failure was recorded as the time midway between the nadir and the first rising PSA. Five-year actuarial rates of clinical DMFS, DFS, CSS, and LC were calculated for patients who were biochemically controlled (BC) versus those who failed biochemically. Median follow-up was 56 months (range: 24-118 months). Results: Five-year actuarial rates of DMFS, DFS, CSS, and LC were significantly greater in patients who were biochemically controlled versus those who were not (p < 0.001). In patients who were BC, the 5-year actuarial rates of DMFS, DFS, CSS, and LC were 99%, 99%, 98%, and 99% respectively. For patients who failed biochemically, the 5-year actuarial rates of DMFS, DFS, CSS, and LC were 74%, 64%, 89%, and 86% respectively. When stratifying by pretreatment PSA, Gleason score, and T stage these differences remained significant for DMFS, DFS, and CSS. The Cox proportional hazards model demonstrated that BC was the single most important predictor of clinical outcome for DMFS, DFS, CSS, and LC. Pretreatment PSA and Gleason score were also independent predictors of outcome for DMFS and DFS. Conclusions: The ASTRO Consensus Panel definition of BF following radiation therapy correlates well with clinical DMFS, DFS

The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins.

Science.gov (United States)

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2011-02-01

To quantify the impact of excision margins on disease-specific survival of patients with primary cutaneous melanoma. Current guidelines recommend narrow margins for the treatment of primary melanoma, although available evidence on this subject is not unequivocal and not always appropriately analyzed. A systematic review of randomized controlled trials (RCT) addressing the issue of wide versus narrow excision margins was performed. Meta-analysis methods for time-to-event data were used to extract hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies, and ultimately to estimate the summary effect of excision margins on patients' survival. The 5 eligible RCT enrolled a total of 3295 patients who were allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor. The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT, respectively. The meta-analysis suggested that narrow margins might be associated with an increased risk of both locoregional disease recurrence (HR: 1.30, CI: 1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06) becomes significant when considering RCT that enrolled patients with thicker melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was analyzed, no risk difference was found. The lack of DSS data from all the available RCT does not allow to draw definitive conclusions. However, current evidence appears sufficient to question the common belief that narrow excision margins are as safe as wide margins in the management of primary melanoma, that calls for further investigation in this field.

Allogeneic Transplantation In Chronic Myeloid Leukemia And The Effect Of Tyrosine Kinase Inhibitors On Survival, A Quasi-Experimental Study

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Mehmet Özen

2017-03-01

Full Text Available Objective: Tyrosine kinase inhibitors (TKIs have changed the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT in chronic myeloid leukemia (CML. Therefore, we aimed to evaluate the effect of TKIs on allo-HSCT in CML. Materials and Methods: In this quasi-experimental study, we compared patient, disease, and transplantation characteristics as well as allo-HSCT outcomes between the pre-TKI era (before 2002 and the post-TKI era (2002 and later in patients with CML. A total of 193 allo- HSCTs were performed between 1989 and 2012. Results: Patients in the post-TKI era had more advanced disease (>chronic phase 1 at the time of transplant and more frequently received reduced-intensity conditioning compared to patients in the pre-TKI era. Relapse/progression occurred more frequently in the year ≥2002 group than in the year <2002 group (48% vs. 32% at 5 years, p=0.01; however, overall survival (OS was similar in these two groups (5-year survival was 50.8% vs. 59.5%, respectively; p=0.3. TKIs (with donor lymphocyte infusions or alone for treatment of relapse after allo-HSCT were available in the post-TKI era and were associated with improved OS. While the rates of hematologic remission at 3 months after allo-HSCT were similar between TKI eras, patients having remission had better disease-free survival (DFS [relative risk (RR: 0.15, confidence interval (CI 95%: 0.09-0.24, p<0.001] and OS (RR: 0.14, CI 95%: 0.09-0.23, p<0.001. Male allo-HSCT recipients had worse DFS (RR: 1.7, CI 95%: 1.2-2.5, p=0.007 and OS (RR: 1.7, CI 95%: 1.1-2.6, p=0.02 than females. Conclusion: TKIs are an effective option for the treatment of relapse after allo-HSCT in CML. Hematologic remission after allo-HSCT is also an important factor for survival in CML patients.

Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure

International Nuclear Information System (INIS)

Stock, Richard G.; Chen, Alex S. J.; Flickinger, John C.; Kalnicki, Shalom; Seski, Jan

1995-01-01

Purpose: The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. Methods and Materials: From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing exploratory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. Results: Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% (p = <0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% (p = 0.0004). The 5-year actuarial overall survival was 58% vs. 46% (p 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS (p = 0.0001) and overall survival (p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. Conclusion: Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine prophylactic paraaortic

Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure

Energy Technology Data Exchange (ETDEWEB)

Stock, Richard G; Chen, Alex S. J.; Flickinger, John C; Kalnicki, Shalom; Seski, Jan

1995-01-01

Purpose: The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. Methods and Materials: From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing exploratory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. Results: Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% (p = <0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% (p = 0.0004). The 5-year actuarial overall survival was 58% vs. 46% (p 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS (p = 0.0001) and overall survival (p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. Conclusion: Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine prophylactic paraaortic

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.

Preoperative Radiotherapy in Resectable Rectal Cancer: A Prospective Randomized Study of Two Different Approaches

International Nuclear Information System (INIS)

EITTA, M.A.; EL- WAHIDI, G.F.; FOUDA, M.A.; ABO EL-NAGA, E.M.; GAD EL-HAK, N.

2010-01-01

Preoperative radiotherapy in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, increasing survival and down-staging effect. Purpose: This prospective study was designed to compare between two different approaches of preoperative radiotherapy, either short course or long course radiotherapy. The primary endpoint is to evaluate the local recurrence rate, overall survival (OS) and disease free survival (DFS). The secondary endpoint is to evaluate down staging, treatment toxicity and ability to do sphincter sparing procedure (SSP), aiming at helping in the choice of the optimal treatment modality. Patients and Methods: This is a prospective randomized study of patients with resectable rectal cancer who presented to the department of Clinical Oncology and Nuclear Medicine, Mansoura University during the time period between June 2007 and September 2009. These patients received preoperative radiotherapy and were randomized into two arms: Arm 1, short course (SCRT) 25Gy/week/5 fractions followed by surgery within one week, and arm 2, long course preoperative radiotherapy (LCRT) 45Gy/5 weeks/25 fractions followed by surgery after 4-6 weeks. Adjuvant chemotherapy was given 4-6 weeks after surgery according to the postoperative pathology. Results: After a median follow-up of 18 months (range 6 to 28 months), we studied the patterns of recurrence. Three patients experienced local recurrence (LR), two out of 14 (14.2%) in arm 1 and one out of 15 patients (6.7%) in arm 2, (p=0.598). Three patients developed distant metastases [two in arm 1 (14.2%) and one in arm 2 (6.7%), p=0.598]. Two-year OS rate was 64±3% and 66±2%, (p= 0.389), and the 2-year DFS rate was 61±2% and 83±2% for arms 1 and 2, respectively (p=0.83). Tumor (T) downstaging was more achieved in LCRT arm with a statistically significant difference, but did not reach statistical significance in node (N) down-staging. SSP was more available in LCRT but with no

A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma.

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Wang, Lu; Wang, Cong; Wang, Jiangfeng; Huang, Xiaochen; Cheng, Yufeng

2017-10-01

A novel systemic immune-inflammation index (SII) based on platelet (P), neutrophil (N), and lymphocyte (L) counts has been reported to be associated with clinical outcomes in several solid tumors. We aimed to investigate its prognostic value in esophageal squamous cell carcinoma (ESCC) and the potential relationship with quality of life (QOL). A total of 280 ESCC patients who underwent esophagectomy were enrolled. SII (SII = P × N/L) was calculated on the basis of data obtained within 1 week before surgery. An optimal cut-off value stratified patients into high (≥560) and low (<560) preoperative SII groups. The widely used EORTC QLQ-C30 and QLQ-OES18 were utilized to assess QOL at cancer diagnosis and 36 months after surgery. Generalized estimating equations (GEEs) were used to evaluate the association of SII with QOL. Kaplan-Meier method and Cox proportional regression were used to analyze the prognostic value of SII. Kaplan-Meier analyses revealed that higher SII correlated significantly with poorer overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001) in patients with ESCC. Multivariate analysis identified SII as an independent prognostic factor for OS (p < 0.001; HR 2.578; 95% CI 1.625-4.088) and DFS (p < 0.001; HR 2.699; 95% CI 1.726-4.223). In addition, patients with high SII exhibited notably deteriorating QOL (p < 0.05). The preoperative SII is a promising biomarker for predicting survival and QOL of patients with ESCC. It may help to identify the high-risk patients for treatment strategy decisions.

Concurrent chemoradiotherapy improves survival outcome in muscle-invasive bladder cancer

International Nuclear Information System (INIS)

Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon

2015-01-01

To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer

Toxin constraint explains diet choice, survival and population dynamics in a molluscivore shorebird.

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van Gils, Jan A; van der Geest, Matthijs; Leyrer, Jutta; Oudman, Thomas; Lok, Tamar; Onrust, Jeroen; de Fouw, Jimmy; van der Heide, Tjisse; van den Hout, Piet J; Spaans, Bernard; Dekinga, Anne; Brugge, Maarten; Piersma, Theunis

2013-07-22

Recent insights suggest that predators should include (mildly) toxic prey when non-toxic food is scarce. However, the assumption that toxic prey is energetically as profitable as non-toxic prey misses the possibility that non-toxic prey have other ways to avoid being eaten, such as the formation of an indigestible armature. In that case, predators face a trade-off between avoiding toxins and minimizing indigestible ballast intake. Here, we report on the trophic interactions between a shorebird (red knot, Calidris canutus canutus) and its two main bivalve prey, one being mildly toxic but easily digestible, and the other being non-toxic but harder to digest. A novel toxin-based optimal diet model is developed and tested against an existing one that ignores toxin constraints on the basis of data on prey abundance, diet choice, local survival and numbers of red knots at Banc d'Arguin (Mauritania) over 8 years. Observed diet and annual survival rates closely fit the predictions of the toxin-based model, with survival and population size being highest in years when the non-toxic prey is abundant. In the 6 of 8 years when the non-toxic prey is not abundant enough to satisfy the energy requirements, red knots must rely on the toxic alternative.

Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial.

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Swain, Sandra M; Tang, Gong; Geyer, Charles E; Rastogi, Priya; Atkins, James N; Donnellan, Paul P; Fehrenbacher, Louis; Azar, Catherine A; Robidoux, André; Polikoff, Jonathan A; Brufsky, Adam M; Biggs, David D; Levine, Edward A; Zapas, John L; Provencher, Louise; Northfelt, Donald W; Paik, Soonmyung; Costantino, Joseph P; Mamounas, Eleftherios P; Wolmark, Norman

2013-09-10

Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

Stimulated human fibroblast cell survival

International Nuclear Information System (INIS)

Smith, B.P.; Gale, K.L.; Einspenner, M.; Greenstock, C.L.; Gentner, N.E.

1992-01-01

Techniques for cloning cultured mammalian cells have supported the most universally-accepted method for measuring the induction of lethality by geno-toxicants such as ionizing radiation: the 'survival of colony-forming ability (CFA)' assay. Since most cultured human cell lines exhibit plating efficiency (i.e. the percentage of cells that are capable of reproductively surviving and dividing to form visible colonies) well below 100%, such assays are in essence 'survival of plating efficiency' assays, since they are referred to the plating (or cloning) efficiency of control (i.e. unirradiated) cells. (author). 8 refs., 2 figs

Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

Energy Technology Data Exchange (ETDEWEB)

Chance, William W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rice, David C. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsao, Anne S. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fontanilla, Hiral P. [Princeton Radiation Oncology, Monroe Township, New Jersey (United States); Liao, Zhongxing; Chang, Joe Y.; Tang, Chad; Pan, Hubert Y.; Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza J. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-01-01

Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but

Effects of Toxic Leachate from Commercial Plastics on Larval Survival and Settlement of the Barnacle Amphibalanus amphitrite.

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Li, Heng-Xiang; Getzinger, Gordon J; Ferguson, P Lee; Orihuela, Beatriz; Zhu, Mei; Rittschof, Daniel

2016-01-19

Plastic pollution represents a major and growing global problem. It is well-known that plastics are a source of chemical contaminants to the aquatic environment and provide novel habitats for marine organisms. The present study quantified the impacts of plastic leachates from the seven categories of recyclable plastics on larval survival and settlement of barnacle Amphibalanus (=Balanus) amphitrite. Leachates from plastics significantly increased barnacle nauplii mortality at the highest tested concentrations (0.10 and 0.50 m(2)/L). Hydrophobicity (measured as surface energy) was positively correlated with mortality indicating that plastic surface chemistry may be an important factor in the effects of plastics on sessile organisms. Plastic leachates significantly inhibited barnacle cyprids settlement on glass at all tested concentrations. Settlement on plastic surfaces was significantly inhibited after 24 and 48 h, but settlement was not significantly inhibited compared to the controls for some plastics after 72-96 h. In 24 h exposure to seawater, we found larval toxicity and inhibition of settlement with all seven categories of recyclable commercial plastics. Chemical analysis revealed a complex mixture of substances released in plastic leachates. Leaching of toxic compounds from all plastics should be considered when assessing the risks of plastic pollution.

Predictive value of the flow cytometric PCNA - assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy

Energy Technology Data Exchange (ETDEWEB)

Wenz, F; Lohr, F; Rudat, V; Dietz, A; Flentje, M; Wannenmacher, M

1995-07-01

Purpose/Objective: Proliferation of surviving tumor cells during fractionated radiotherapy may limit tumor control, especially in rapidly proliferating tumors. It has been widely accepted, that this may play a major role in head and neck tumors. Several methods for the assessment of tumor proliferation have been developed, however, most of them are either laborious, invasive or potentially toxic. Today, the gold standard is the flow cytometric BrdUrd assay. We present a flow cytometric method for detection of PCNA, which is an intranuclear proliferation associated protein, in solid human head and neck tumors and how these data correlate with outcome. Materials and Methods: Pretherapeutic biopsies of 20 inoperable patients with squamous cell carcinoma of the head and neck (T3-4N2M0) were examined. The tissue was disaggregated with pepsin/HCl, antibody staining was performed using the clone PC10. Biparametric flow cytometry was performed after a FITC conjugated secondary antibody and propidiumjodine staining was applied. The PCNA-index (i.e. percentage PCNA-positive cells), the DNA-index and the S-phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of combined accelerated-hyperfractionated radiochemotherapy (66 Gy in 5 wks, concomittant boost of 1.6 Gy/d in wks 4+5, Carboplatin in wks 1+5). The median follow-up time was 14 mths (5 - 28), the clinical partners (V.R., A.D.) were 'blinded' towards the PCNA-values. Results: 13 patients suffered from disease progession and 11 died. The actuarial median survival and disease free survival (DFS) were 14.4 and 10.7 mths, respectively. The PCNA-values ranged from 3.2 to 70% (median 9%), there were 7 aneuploid and 13 euploid tumors. SFP in the euploid tumors ranged from 4 to 14.5% (median 10.5%). Neither SFP nor ploidy had a significant influence on the outcome. The patients were divided according to their PCNA-value in higher (n=10) and lower (n=10) than the median. The survival and DFS were 13

Specific toxicity of 5-thio-D-glucose to hypoxic cells

International Nuclear Information System (INIS)

Schulz, R.J.; Bongiorni, P.

1984-01-01

The toxicity of 5-thio-D-glucose (5TG) to mammalian cells in culture has been studied with respect to oxygen tension, concentration, and temperature. At 37 0 C and at 5 mM concentration of the drug in normal growth medium, survival is 10 -3 for 4-hr exposure to 5 ppm O 2 ; this increases to 0.5 for 24-hr exposure to 200 ppm O 2 . The relationship between survival and oxygen tension is nonlinear with the greatest change occurring between 50 and 100 ppm. The drug is essentially nontoxic to aerated cells. Drug toxicity increases with concentration up to about 5 mM at which point a plateau is reached. The effect of elevated temperature is to reduce the time required to obtain a specific level of survival, but temperatures as high as 42 0 C had only a slight effect on drug toxicity for oxygen tensions higher than 100 ppm. The effect of D-glucose on the toxicity of 5TG was studied, and an inverse relationship was established. At D-glucose concentrations greater than 20 mM the toxicity of 5TG was nullified regardless of oxygen tension or 5TG concentration

Association Between Use of Traditional Chinese Medicine Herbal Therapy and Survival Outcomes in Patients With Stage II and III Colorectal Cancer: A Multicenter Prospective Cohort Study.

Science.gov (United States)

Xu, Yun; Mao, Jun J; Sun, Lingyun; Yang, Lin; Li, Jie; Hao, Yingxu; Li, Huashan; Hou, Wei; Chu, Yuping; Bai, Yu; Jia, Xiaoqiang; Wang, Jinwan; Shen, Lin; Zhang, Ying; Wang, Jianbin; Liu, Jianping; Yang, Yufei

2017-11-01

Chinese cancer patients often use Traditional Chinese Medicine (TCM) herbal medicine during or after active cancer treatments. However, little is known about how TCM herbal medicine impacts cancer outcomes. This study aimed to evaluate the association between TCM herbal therapy and survival outcomes in patients with stage II or III colorectal cancer. We conducted an eight-center prospective cohort study in China among patients who had undergone radical resection for stage II and III colorectal cancer. All patients received comprehensive conventional treatments according to National Comprehensive Cancer Network (NCCN) guidelines, and follow-up visits were conducted over five years. We defined high exposure as a patient's use of TCM individualized herbs for more than one year, ascertained via clinical interviews. The primary outcome was disease-free survival (DFS), with overall survival (OS) as a secondary outcome. Between April 2007 and February 2009, we enrolled 312 patients into the cohort; 166 (53.2%) met the definition of high exposure to TCM herbs. Adjusting for covariates, high exposure to TCM was associated with both better DFS (hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.39 to 0.98) and OS (HR = 0.31, 95% CI = 0.14 to 0.68). In subgroup exploratory analysis, the effects demonstrated that the differences in outcomes were statistically significant in patients who had received chemotherapy. Longer duration of TCM herbal use is associated with improved survival outcomes in stage II and III colorectal cancer patients in China. More research is needed to evaluate the effects and underlying mechanisms of herbal medicine on colorectal cancer outcomes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Low ERCC1 mRNA and protein expression are associated with worse survival in cervical cancer patients treated with radiation alone

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Doll, Corinne M.; Prystajecky, Michael; Eliasziw, Misha; Klimowicz, Alexander C.; Petrillo, Stephanie K.; Craighead, Peter S.; Hao, Desiree; Diaz, Roman; Lees-Miller, Susan P.; Magliocco, Anthony M.

2010-01-01

Purpose: To evaluate the association of excision repair cross-complementation group 1 (ERCC1) expression, using both mRNA and protein expression analysis, with clinical outcome in cervical cancer patients treated with radical radiation therapy (RT). Experimental design: Patients (n = 186) with locally advanced cervical cancer, treated with radical RT alone from a single institution were evaluated. Pre-treatment FFPE biopsy specimens were retrieved from 112 patients. ERCC1 mRNA level was determined by real-time PCR, and ERCC1 protein expression (FL297, 8F1) was measured using quantitative immunohistochemistry (AQUA (registered) ). The association of ERCC1 status with local response, 10-year disease-free (DFS) and overall survival (OS) was analyzed. Results: ERCC1 protein expression levels using both FL297 and 8F1 antibodies were determined for 112 patients; mRNA analysis was additionally performed in 32 patients. Clinical and outcome factors were comparable between the training and validation sets. Low ERCC1 mRNA expression status was associated with worse OS (17.9% vs 50.1%, p = 0.046). ERCC1 protein expression using the FL297 antibody, but not the 8F1 antibody, was significantly associated with both OS (p = 0.002) and DFS (p = 0.010). After adjusting for pre-treatment hemoglobin in a multivariate analysis, ERCC1 FL297 expression status remained statistically significant for OS [HR 1.9 (1.1-3.3), p = 0.031]. Conclusions: Pre-treatment tumoral ERCC1 mRNA and protein expression, using the FL297 antibody, are predictive factors for survival in cervical cancer patients treated with RT, with ERCC1 FL297 expression independently associated with survival. These results identify a subset of patients who may derive the greatest benefit from the addition of cisplatin chemotherapy.

Similar long-term overall and disease-free survival after conventional and extralevator abdominoperineal excision

DEFF Research Database (Denmark)

Klein, Mads; Colov, Emilie Palmgren; Gögenur, Ismail

2016-01-01

, respectively, (log-rank p = 0.59)). In Cox regression, the type of procedure did not affect DFS or OS. Factors of importance for DFS included increasing age, ypN-positive disease and neoadjuvant chemoradiation therapy. Factors of importance for OS included increasing age, circumferential resection margin (CRM...

PBSCT is associated with poorer survival and increased chronic GvHD than BMT in Japanese paediatric patients with acute leukaemia and an HLA-matched sibling donor.

Science.gov (United States)

Shinzato, Aki; Tabuchi, Ken; Atsuta, Yoshiko; Inoue, Masami; Inagaki, Jiro; Yabe, Hiromasa; Koh, Katsuyoshi; Kato, Koji; Ohta, Hideaki; Kigasawa, Hisato; Kitoh, Toshiyuki; Ogawa, Atsushi; Takahashi, Yoshiyuki; Sasahara, Yoji; Kato, Shun-Ichi; Adachi, Souichi

2013-09-01

Peripheral blood stem cells (PBSC) may be used as an alternative to bone marrow (BM) for allogeneic transplantation. Since peripheral blood stem cell bank from unrelated volunteer donor has been started in Japan, use of PBSC allografts may be increased. Therefore we surveyed the outcomes of Japanese leukemia children after PBSC and BM transplantation. This retrospective study compared the outcomes of 661 children (0-18 years) with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) who received their first allogeneic peripheral blood stem cell transplantation (PBSCT; n = 90) or bone marrow transplantation (BMT; n = 571) from HLA-matched siblings between January 1996 and December 2007. Neutrophil recovery was faster after PBSCT than after BMT (ALL: P vs. 9.9%, P = 0.0066; AML: 41.6% vs. 11.1%, P vs. 57.1%, P = 0.0257). The 5-year overall survival (OS) was lower after PBSCT than after BMT for ALL (42.4% vs. 63.7%, P = 0.0032) and AML (49.8% vs. 71.8%, P = 0.0163). Multivariate analysis revealed the use of PBSC was a significant risk factor for DFS and OS. PBSCT and BMT did not differ in relapse rate, acute GvHD for ALL and AML, or in DFS for AML. PBSC allografts in Japanese children engraft faster but are associated with poorer survival and increased chronic GvHD. Copyright © 2013 Wiley Periodicals, Inc.

Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

Science.gov (United States)

Tomasello, Gianluca; Barni, Sandro; Turati, Luca; Ghidini, Michele; Pezzica, Ezio; Passalacqua, Rodolfo; Petrelli, Fausto

2018-02-15

CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of diabetes on oncologic outcome of colorectal cancer patients: colon vs. rectal cancer.

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Justin Y Jeon

Full Text Available BACKGROUND: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum. PATIENTS AND METHODS: This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. RESULTS: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS [hazard ratio (HR 1.17, 95% confidence interval (CI: 1.00-1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS (HR: 1.46, 95% CI: 1.11-1.92, DFS (HR: 1.45, 95% CI: 1.15-1.84 and recurrence-free survival (RFS (HR: 1.32, 95% CI: 0.98-1.76 in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer with DM on OS (P = 0.009 and DFS (P = 0.007. CONCLUSIONS: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.

Identification of causes of oil sands coke leachate toxicity

International Nuclear Information System (INIS)

Puttaswamy, N.; Liber, K.

2010-01-01

The potential causes of oil sands coke leachate toxicity were investigated. Chronic 7-day toxicity tests were conducted to demonstrate that oil sands coke leachates (CL) are acutely toxic to Ceriodaphnia dubia (C. dubia). CLs were generated in a laboratory to perform toxicity identification evaluation (TIE) tests in order to investigate the causes of the CL toxicity. The coke was subjected to a 15-day batch leaching process at 5.5 and 9.5 pH values. The leachates were then filtered and used for chemical and toxicological characterization. The 7-day estimates for the C. dubia survival were 6.3 for a pH of 5.5 and 28.7 per cent for the 9.5 CLs. The addition of EDTA significantly improved survival and reproduction in a pH of 5.5 CL, but not in a pH of 9.5 CL. The toxicity of the pH 5.5 CL was removed with a cationic resin treatment. The toxicity of the 9.5 pH LC was removed using an anion resin treatment. Toxicity re-appeared when nickel (Ni) and vanadium (V) were added back to the resin-treated CLs. Results of the study suggested that Ni and V were acting as primary toxicants in the pH 5.5 CL, while V was the primary cause of toxicity in the pH 9.5 CL.

Radiation therapy for early stage seminoma of testis. Analysis of survival and gastrointestinal toxicity in patients treated with modern megavoltage techniques over 10 years

International Nuclear Information System (INIS)

Yeoh, E.; O'Brein, P.C.; Razali, M.

1993-01-01

Seventy-seven patients treated with megavoltage irradiation to the paraaortic and/or pelvic nodal areas, for stage I and non-bulky ( 34 years), stage (I vs II) and dose of radiation (≤ 30 Gy vs > 30 Gy), showed none of these variables to have a significant influence on overall survival or on the incidence of late complications. The results of these findings are discussed in the light of recent studies of a surveillance policy following orchidectomy for stage I seminoma of the testis. Given that gastrointestinal toxicity is the major toxicity associated with the treatment of stage I patients, the data from this study should assist clinicians and their patients to arrive at an informed decision regarding adjuvant radiotherapy. 15 refs., 1 tab., 2 figs

Impact of cavitron ultrasonic surgical aspirator (CUSA) and bipolar radiofrequency device (Habib-4X) based hepatectomy for hepatocellular carcinoma on tumour recurrence and disease-free survival.

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Huang, Kai-Wen; Lee, Po-Huang; Kusano, Tomokazu; Reccia, Isabella; Jayant, Kumar; Habib, Nagy

2017-11-07

The aim of this study was to evaluate the oncological outcomes of hepatocellular carcinoma patients undergoing liver resection using cavitron ultrasonic surgical aspirator (CUSA) or radiofrequency (RF) based device Habib-4X.
. We prospectively analyzed the data of 280 patients who underwent liver resection for hepatocellular carcinoma at our institution from 2010-2012 with follow up till August 2016. The CUSA was used in the 163 patients whilst Habib-4X in 117 patients. The end points of analysis were oncological outcomes as disease recurrence, disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, which has been compared with all other existing literature on the survival study. Compared with CUSA the reported incidence of recurrence was significantly lower, in Habib-4X group; p Habib-4X group than CUSA group (50.80 vs 45.87 months, p = 0.03). The median OS was better in Habib-4X group than CUSA group (60.57 vs 57.17 months, p = 0.12) though the lesser difference in OS between the groups might be explained by the use of palliative therapies as TACE, percutaneous RFA, etc. in case of recurrence. RF based device Habib-4X, is safe and effective device for resection of hepatocellular carcinoma, in comparison to CUSA with better oncological outcomes, i.e., significantly lesser tumour recurrence and better DFS. This could be explained on the basis of systemic and local immunomodulatory effect involving induction of kupffer cells and effector CD-8 T cells that help in minimizing postoperative complications and bring more advantageous oncological outcomes.

Toxicity of carbon nanotubes to freshwater aquatic invertebrates

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Mwangi, Joseph N.; Wang, Ning; Ingersoll, Christopher G.; Hardesty, Doug K.; Brunson, Eric L.; Li, Hao; Deng, Baolin

2012-01-01

Carbon nanotubes (CNTs) are hydrophobic in nature and thus tend to accumulate in sediments if released into aquatic environments. As part of our overall effort to examine the toxicity of carbon-based nanomaterials to sediment-dwelling invertebrates, we have evaluated the toxicity of different types of CNTs in 14-d water-only exposures to an amphipod (Hyalella azteca), a midge (Chironomus dilutus), an oligochaete (Lumbriculus variegatus), and a mussel (Villosa iris) in advance of conducting whole-sediment toxicity tests with CNTs. The results of these toxicity tests conducted with CNTs added to water showed that 1.00g/L (dry wt) of commercial sources of CNTs significantly reduced the survival or growth of the invertebrates. Toxicity was influenced by the type and source of the CNTs, by whether the materials were precleaned by acid, by whether sonication was used to disperse the materials, and by species of the test organisms. Light and electron microscope imaging of the surviving test organisms showed the presence of CNTs in the gut as well as on the outer surface of the test organisms, although no evidence was observed to show penetration of CNTs through cell membranes. The present study demonstrated that both the metals solubilized from CNTs such as nickel and the "metal-free" CNTs contributed to the toxicity.

Latent Toxicity of Endothall to Anadromous Salmonids During Seawater Challenge.

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Courter, Lauren A; Garrison, Thomas M; Courter, Ian I

2016-05-01

Limited evidence exists on the latent effects of toxicant exposure on the seawater adaptability of anadromous salmon and steelhead. It is unclear whether such an effect exists for the widely used and relatively non-toxic herbicide endothall. Coho salmon, Oncorhynchus kisutch (coho), Chinook salmon, O. tshawytscha (Chinook), and anadromous rainbow trout, O. mykiss (steelhead) were subjected to a 10-day seawater challenge following freshwater treatments [0-12 mg acid equivalent (a.e)./L at 96 h]. Mean survival resulted in 82 % (n = 225), 84 % (n = 133), 90 % (n = 73) and 59 % (n = 147) survival for 0, 3-5, 6-8, and 9-12 mg a.e./L, respectively. Our results indicate a lower toxicity threshold compared with previously reported acute toxicity results, but higher compared with previous seawater challenge studies. We demonstrate the utility of the seawater challenge assay to accurately define toxic effects of pesticides on salmonids with complex life-histories.

Head and neck soft tissue sarcomas treated with radiation therapy

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Lucas K. Vitzthum

2016-06-01

Full Text Available Head and neck soft tissue sarcomas (HNSTSs are rare and heterogeneous cancers in which radiation therapy (RT has an important role in local tumor control (LC. The purpose of this study was to evaluate outcomes and patterns of treatment failure in patients with HNSTS treated with RT. A retrospective review was performed of adult patients with HNSTS treated with RT from January 1, 1998, to December 31, 2012. LC, locoregional control (LRC, disease-free survival (DFS, overall survival (OS, and predictors thereof were assessed. Forty-eight patients with HNSTS were evaluated. Five-year Kaplan-Meier estimates of LC, LRC, DFS, and OS were 87, 73, 63, and 83%, respectively. Angiosarcomas were found to be associated with worse LC, LRC, DFS, and OS. Patients over the age of 60 had lower rates of DFS. HNSTSs comprise a diverse group of tumors that can be managed with various treatment regimens involving RT. Angiosarcomas have higher recurrence and mortality rates.

A zebrafish model for uremic toxicity: role of the complement pathway.

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Berman, Nathaniel; Lectura, Melisa; Thurman, Josh; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Reinecke, James; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

2013-01-01

Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p 50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement. Copyright © 2013 S. Karger AG, Basel.

Feeding behavior of the invasive bivalve Limnoperna fortunei (Dunker, 1857 under exposure to toxic cyanobacteria Microcystis aeruginosa

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V Gazulha

Full Text Available The aim of this study was to test the effects of cyanobacteria toxicity on feeding behavior of the golden mussel Limnoperna fortunei. First, it was tested the hypothesis that L. fortunei preferentially graze on non-toxic phytoplankton and reject toxic cyanobacteria. Second, it was tested the hypothesis that toxic cyanobacteria negatively affect feeding and survival of L. fortunei. The present study is the first to evaluate the effects of toxic cyanobacteria on L. fortunei feeding and survival. In the short-term grazing, golden mussel filtration rates were evaluated in the presence of toxic and non-toxic strains of cyanobacteria Microcystis aeruginosa, and non-toxic phytoplankton Nitzschia palea. Highest filtration rates were registered when mussels fed on Nitzschia. Despite that, golden mussel expelled Nitzschia cells in large quantities and preferentially ingested Microcystis cells, both toxic and non-toxic strains. In the long-term grazing, mussels were exposed to toxic and non-toxic strains of Microcystis during 5 days. Filtration rates were not significantly different for toxic and non-toxic Microcystis throughout exposure period. The results have demonstrated cyanobacteria toxicity is not the main factor influencing L. fortunei feeding behavior. Survival of L. fortunei feeding on toxic cyanobacteria shows the potential of this invasive bivalve as a vector to the transference of cyanotoxins to higher trophic levels.

Adjuvant radiochemotherapy in patients with locally advanced high-risk cervical cancer

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Heinzelmann, F.; Henke, G.; Grafenstein, M. von; Weidner, N.; Paulsen, F.; Bamberg, M.; Weinmann, M. [Tuebingen Univ. (Germany). Dept. of Radiation Oncology; Staebler, A. [Tuebingen Univ. (Germany). Div. of Gynecologic Pathology; Brucker, S. [Tuebingen Univ. (Germany). Dept. of Gynecology

2012-07-15

Background and purpose: The aim of this retrospective study was to analyze the outcome of patients with locally advanced cervical carcinoma treated by adjuvant radiochemotherapy and to determine risk factors for local and distant relapse. Furthermore, acute and late effects of treatment were recorded. Patients and methods: A total of 72 patients with FIGO stages I-III cervical carcinoma were treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial involvement, positive margins, or tumor bulk were eligible. Patients were irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority of patients received platinum-based chemotherapy. Results: After a median follow-up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively. Nine of the 72 patients had pelvic recurrences including only 1 isolated local failure; 23 of the 72 patients presented with distant relapse. The majority of relapses occurred within the first 3 years after adjuvant treatment. The number of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS. Treatment was well tolerated with transient acute hematologic ({proportional_to}30%) and gastrointestinal ({proportional_to}30%) grade 3 toxicity. Small bowel obstruction ({proportional_to}6%) was the only important late sequelae. Conclusion: Adjuvant radiochemotherapy in patients with advanced cervical cancer and several risk factors is highly effective to prevent local relapse. Future efforts to improve outcome should be placed on improvement of systemic control especially in subgroups with high-risk features for distant relapse. Combined treatment was well tolerated with moderate acute and late toxicity. (orig.)

Surgical Management of Metastatic Colorectal Cancer: A Single-Centre Experience on Oncological Outcomes of Pulmonary Resection vs Cytoreductive Surgery and HIPEC.

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Wong, Evelyn Yi Ting; Tan, Grace Hwei Ching; Ng, Deanna Wan Jie; Koh, Tina Puay Theng; Kumar, Mrinal; Teo, Melissa Ching Ching

2017-12-01

Metastasectomy is accepted as standard of care for selected patients with colorectal pulmonary metastases (CLM); however, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) is not universally accepted. We aim to compare oncological outcomes of patients with CLM and CPM after pulmonary resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and disease-free survival (DFS). A retrospective review of 49 CLM patients who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in a single institution from January 2003 to March 2015, was performed. The 5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM patients had longer median operative time (8.38 vs. 1.75 h, p CPM patients by multivariate analysis. There were no independent prognostic factors for DFS in CLM patients by multivariate analysis, but peritoneal cancer index score, bladder involvement, and higher nodal stage at presentation of the initial malignancy were independent prognostic factors for DFS in CPM patients. OS and DFS for CPM patients after CRS and HIPEC are comparable to CLM patients after lung resection, although morbidity appears higher. The prognostic factors affecting survival after surgery are different between CPM and CLM patients and must be considered when selecting patients for metastasectomy.

Chronic toxicity of copper and ammonia to juvenile freshwater mussels (Unionidae)

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Wang, N.; Ingersoll, C.G.; Greer, I.E.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; Brumbaugh, W.G.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

2007-01-01

The objectives of the present study were to develop methods for conducting chronic toxicity tests with juvenile mussels under flow-through conditions and to determine the chronic toxicity of copper and ammonia to juvenile mussels using these methods. In two feeding tests, two-month-old fatmucket (Lampsilis siliquoidea) and rainbow mussel (Villosa iris) were fed various live algae or nonviable algal mixture for 28 d. The algal mixture was the best food resulting in high survival (???90%) and growth. Multiple copper and ammonia toxicity tests were conducted for 28 d starting with two-month-old mussels. Six toxicity tests using the algal mixture were successfully completed with a control survival of 88 to 100%. Among copper tests with rainbow mussel, fatmucket, and oyster mussel (Epioblasma capsaeformis), chronic value ([ChV], geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) ranged from 8.5 to 9.8 ??g Cu/L for survival and from 4.6 to 8.5 ??g Cu/L for growth. Among ammonia tests with rainbow mussel, fatmucket, and wavy-rayed lampmussel (L. fasciola), the ChV ranged from 0.37 to 1.2 mg total ammonia N/L for survival and from 0.37 to 0.67 mg N/L for growth. These ChVs were below the U.S. Environmental Protection Agency 1996 chronic water quality criterion (WQC) for copper (15 ??g/L; hardness 170 mg/L) and 1999 WQC for total ammonia (1.26 mg N/L; pH 8.2 and 20??C). Results indicate that toxicity tests with two-month-old mussels can be conducted for 28 d with >80% control survival; growth was frequently a more sensitive endpoint compared to survival; and the 1996 chronic WQC for copper and the 1999 chronic WQC for total ammonia might not be adequately protective of the mussel species tested. However, a recently revised 2007 chronic WQC for copper based on the biotic ligand model may be more protective in the water tested. ?? 2007 SETAC.

Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.

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Nafar, F; Clarke, J P; Mearow, K M

2017-05-01

Alzheimer's disease is a progressive neurodegenerative disease that has links with other conditions that can often be modified by dietary and life-style interventions. In particular, coconut oil has received attention as having potentially having benefits in lessening the cognitive deficits associated with Alzheimer's disease. In a recent report, we showed that neuron survival in cultures co-treated with coconut oil and Aβ was rescued compared to cultures exposed only to Aβ. Here we investigated treatment with Aβ for 1, 6 or 24 h followed by addition of coconut oil for a further 24 h, or treatment with coconut oil for 24 h followed by Aβ exposure for various periods. Neuronal survival and several cellular parameters (cleaved caspase 3, synaptophysin labeling and ROS) were assessed. In addition, the influence of these treatments on relevant signaling pathways was investigated with Western blotting. In terms of the treatment timing, our data indicated that coconut oil rescues cells pre-exposed to Aβ for 1 or 6 h, but is less effective when the pre-exposure has been 24 h. However, pretreatment with coconut oil prior to Aβ exposure showed the best outcomes. Treatment with octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment. Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. This was supported by observations that a PI3-Kinase inhibitor blocked the rescue effect of CoOil on Aβ amyloid toxicity. Further studies into the mechanisms of action of coconut oil and its constituent medium chain fatty acids are warranted

Chemotherapy-related leukopenia as a biomarker predicting survival outcomes in locally advanced cervical cancer.

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Bogani, Giorgio; Sabatucci, Ilaria; Maltese, Giuseppa; Lecce, Francesca; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Indini, Alice; Leone Roberti Maggiore, Umberto; Borghi, Chiara; Fucà, Giovanni; Ditto, Antonino; Raspagliesi, Francesco; Lorusso, Domenica

2017-01-01

To investigate the impact of hematologic toxicity and leukopenia in locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy (NACT). Data of consecutive patients undergoing platinum-based NACT followed by surgery were retrospectively searched in order to evaluate the impact of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival outcomes were evaluated using Kaplan-Meir and Cox hazard models. Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in 11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12-57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate analysis, no factor was independently associated with disease-free survival; while a trend toward worse prognosis was observed for patients experiencing grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly, grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81 (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate analysis. Magnitude of leukopenia correlated with survival (p<0.001). Although, our data have to be confirmed by prospective investigations, the present study shows an association between the occurrence of leukopenia and survival outcomes. NACT-related immunosuppression might reduce the response against the tumor, thus promoting cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

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Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

1997-01-01

Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

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Peulen, Heike; Karlsson, Kristin; Lindberg, Karin; Tullgren, Owe; Baumann, Pia; Lax, Ingmar; Lewensohn, Rolf; Wersäll, Peter

2011-01-01

Purpose: To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases. Patients and materials: Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1–97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3. Results: Grade 3–4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan–Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively. Conclusions: Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.

Comparison of Glasgow prognostic score and prognostic index in patients with advanced non-small cell lung cancer.

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Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-03-01

Previous studies have shown that Glasgow prognostic score (GPS) and prognostic index (PI) are also powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to compare the prognostic value between GPS and PI. We enrolled consecutive patients with advanced NSCLC in this prospective cohort. GPS and PI were calculated before the onset of chemotherapy. The prognosis outcomes included 1-, 3-, and 5-year progression-free survival and overall survival (OS). The performance of two scores in predicting prognosis was analyzed regarding discrimination and calibration. 138 patients were included in the study. The area under the receiver operating characteristic curve for GPS predicting 1-year DFS was 0.62 (95 % confidence interval (CI) 0.56-0.68, P statistic showed good fit of the predicted 1-year DFS to the actual 1-year DFS by GPS (χ(2) = 4.326, P = 0.462), while no fit was found between the predicted 1-year DFS and the actual 1-year DFS by PI (χ(2) = 15.234, P = 0.091). Similar results of calibration power were found for predicting 3-year DFS, 5-year DFS, 1-year OS, 3-year OS, and 5-year OS by GPS and PI. GPS is more accurate than PI in predicting prognosis for patients with advanced NSCLC. GPS can be used as a useful and simple tool for predicting prognosis in patients with NSCLC. However, GPS only can be used for preliminary assessment because of low predicting accuracy.

Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but Not overall survival in patients with salivary gland adenoid cystic carcinoma—a propensity score matched study

International Nuclear Information System (INIS)

Hsieh, Cheng-En; Lin, Chien-Yu; Lee, Li-Yu; Yang, Lan-Yan; Wang, Chun-Chieh; Wang, Hung-Ming; Chang, Joseph Tung-Chieh; Fan, Kang-Hsing; Liao, Chun-Ta; Yen, Tzu-Chen; Fang, Ku-Hao; Tsang, Yan-Ming

2016-01-01

To compare the long-term outcomes in patients with salivary gland adenoid cystic carcinoma (SGACC) treated with post-operative chemoradiotherapy (POCRT) versus post-operative radiotherapy (PORT). We retrospectively reviewed the records of 91 SGACC patients treated with surgery followed by PORT (n = 58) or POCRT (n = 33) between 2000 and 2013. Treatment outcomes between groups were compared using propensity score matching (1:1 nearest neighbor). The median radiation dose was 66 Gy, and patients were followed up for a median of 71 months. Cisplatin-based concurrent regimens were the most commonly used chemotherapy schedules. In the entire study cohort, patients undergoing POCRT showed a trend toward higher locoregional control (LRC) rates than those treated with PORT alone at both 5 and 8 years (97 and 97 % versus 84 and 79 %, respectively; P = .066). Distant metastases were the most common form of treatment failure and occurred in 31 (34 %) patients (PORT, n = 17; POCRT, n = 14). After propensity score matching (33 pairs), patients receiving POCRT had 5- and 8 year LRC rates of 97 and 97 %, respectively, compared with 79 and 67 % for patients treated with PORT alone (P = .017). The two groups did not differ significantly in terms of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). However, a significantly better opioid-requiring pain-free survival (ORPFS) was achieved in POCRT group (P = .038). Subgroup analyses revealed that patients with stage III − IV disease (P = .040 and .017), positive surgical margins (P = .011 and .050), or perineural invasion (P = .013 and .035) had significantly higher 5- and 8 year LRC and ORPFS when treated with POCRT, respectively. In SGACC patients, adding concurrent chemotherapy to PORT may increase LRC and ORPFS rates, particularly in presence of stage III − IV disease, positive surgical margins, or perineural invasion. However, no significant differences in DMFS, DFS, and OS were

Toxicity and utilization of chemical weapons: does toxicity and venom utilization contribute to the formation of species communities?

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Westermann, Fabian L; McPherson, Iain S; Jones, Tappey H; Milicich, Lesley; Lester, Philip J

2015-08-01

Toxicity and the utilization of venom are essential features in the ecology of many animal species and have been hypothesized to be important factors contributing to the assembly of communities through competitive interactions. Ants of the genus Monomorium utilize a variety of venom compositions, which have been reported to give them a competitive advantage. Here, we investigate two pairs of Monomorium species, which differ in the structural compositions of their venom and their co-occurrence patterns with the invasive Argentine ant. We looked at the effects of Monomorium venom toxicity, venom utilization, and aggressive physical interactions on Monomorium and Argentine ant survival rates during arena trials. The venom toxicity of the two species co-occurring with the invasive Argentine ants was found to be significantly higher than the toxicity of the two species which do not. There was no correlation between venom toxicity and Monomorium survival; however, three of the four Monomorium species displayed significant variability in their venom usage which was associated with the number of Argentine ant workers encountered during trials. Average Monomorium mortality varied significantly between species, and in Monomorium smithii and Monomorium antipodum, aggressive interactions with Argentine ants had a significant negative effect on their mortality. Our study demonstrates that different factors and strategies can contribute to the ability of a species to withstand the pressure of a dominant invader at high abundance, and venom chemistry appears to be only one of several strategies utilized.

Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer

International Nuclear Information System (INIS)

Hentschel, Maria; Appold, Steffen; Baumann, Michael; Schreiber, Andreas; Abolmaali, Nasreddin; Abramyuk, Andrij; Doerr, Wolfgang; Kotzerke, Joerg; Zoephel, Klaus

2011-01-01

Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV max ), the average SUV (SUV mean ) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV max of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT (ΔSUV max10/20 ≥ 50%) than for patients with ΔSUV max20 max from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV max , especially ΔSUV max10/20 , for an early estimation of therapy outcome. Confirmatory studies are warranted. (orig.)

Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia

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Raza, S.; Ahmed, P.; Khan, B.

2008-01-01

To compare survival in Acute Promyelocytic Leukemia (APL) patients treated with or without All-Trans Retinoic Acid (ATRA). Longitudinal, comparative study. All consecutive newly diagnosed patients of acute promyelocytic leukemia, treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between May 2001 and April 2007, were included and given chemotherapy according to availability of ATRA. Diagnosis was confirmed on morphology/ karyotyping/ molecular analysis. Eligibility criteria included confirmed morphologic diagnosis and/or by demonstration of t(15;17) and/or PML/RAR macro re-arrangement, no prior chemotherapy, normal hepatic and renal function, Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and no contraindications to ATRA (history of sensitivity to Vit. A or other retinoids). All patients having history of cardiac failure (LVEF 150 macro mol/L and pregnancy were excluded from this study. Survival was calculated from the date of chemotherapy to death or last follow-up according to Kaplan-Meier and Cox (Proportional hazard) regression analysis methods. During the 6 years study period, 31 newly diagnosed patients with acute promyelocytic leukemia received treatment at AFBMTC. Seventeen patients received anthracycline-based remission induction and consolidation chemotherapy, while 14 received ATRA-based remission induction, consolidation and by two years maintenance therapy. Overall Survival (OS), Disease Free Survival (DFS) and mortality were 29.4%, 29.4% and 70.6% respectively in 17 patients who received anthracycline based chemotherapy, whereas in patients who received ATRA-based chemotherapy OS, DFS and mortality was 71.4%, 64.2% and 28.6% respectively. Major causes of mortality were septicemia and chemotherapy related toxicity. Response to ATRA-based chemotherapy in patient cohort was better as compared with anthracycline based chemotherapy (71.4% vs. 29.4%) in terms of survival and mortality. (author)

Beneficial effects of anti-EGFR agents, Cetuximab or Nimotuzumab, in combination with concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma.

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Lin, Mei; You, Rui; Liu, You-Ping; Zhang, Yi-Nuan; Zhang, Hao-Jiong; Zou, Xiong; Yang, Qi; Li, Chao-Feng; Hua, Yi-Jun; Yu, Tao; Cao, Jing-Yu; Li, Ji-Bin; Mo, Hao-Yuan; Guo, Ling; Lin, Ai-Hua; Sun, Ying; Qian, Chao-Nan; Ma, Jun; Mai, Hai-Qiang; Chen, Ming-Yuan

2018-05-01

This study aimed to evaluate the efficacy and safety in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) plus Cetuximab (CTX) or Nimotuzumab (NTZ) compared to those receiving induction chemotherapy (IC) plus CCRT. From January 2008 to December 2013, 715 eligible patients were enrolled in the study. Using propensity scores to adjust for gender, age, Karnofsky performance status (KPS), tumor stage, node stage, and clinical stage, a well-balanced cohort was created by matching each patient who received CTX/NTZ plus CCRT (137 patients) with two patients who underwent IC plus CCRT (274 patients). The primary endpoint was overall survival (OS), and other outcome variables included disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional relapse-free survival (LRRFS). The median follow-up was 57.0 months and 55.0 months for the CTX/NTZ plus CCRT group and IC plus CCRT group, respectively. No significant differences were found between the CTX/NTZ plus CCRT group and the IC plus CCRT group in 3-year OS (95.5% vs. 94.7%, P = 0.083), 3-year DFS (93.3% vs. 86.1%, P = 0.104), 3-year DMFS (96.2% vs. 92.5%, P = 0.243) and 3-year LRRFS (97.0% vs. 95.1%, P = 0.297). Patients undergoing IC plus CCRT suffered from severe hematologic toxicity and diarrhea compared with those treated with CTX/NTZ plus CCRT. The combination of CTX/NTZ with CCRT is comparable to IC plus CCRT treatment in survival outcomes for locoregionally advanced NPC patients but has a better safety profile than IC plus CCRT treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Percutaneous Lung Thermal Ablation of Non-surgical Clinical N0 Non-small Cell Lung Cancer: Results of Eight Years’ Experience in 87 Patients from Two Centers

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Palussiere, Jean; Lagarde, Philippe; Aupérin, Anne; Deschamps, Frédéric; Chomy, François; Baere, Thierry de

2015-01-01

PurposeTo evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery.Materials and MethodsEighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analysesResultsMedian follow-up was 30.5 months (interquartile range 16.7–51) and tumor size was 21 mm (range 10–54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % at 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS.ConclusionsOversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression

Percutaneous Lung Thermal Ablation of Non-surgical Clinical N0 Non-small Cell Lung Cancer: Results of Eight Years’ Experience in 87 Patients from Two Centers

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Palussiere, Jean, E-mail: J.Palussiere@bordeaux.unicancer.fr [Institut Bergonié, Comprehensive Cancer Centre, Department of Interventional Radiology (France); Lagarde, Philippe, E-mail: P.Lagarde@bordeaux.unicancer.fr [Institut Bergonié, Comprehensive Cancer Center, Radiation Oncology Department (France); Aupérin, Anne, E-mail: auperin@igr.fr [Institut Gustave-Roussy, Unit of Biostatistics and Epidemiology (France); Deschamps, Frédéric, E-mail: frederic.deschamps@igr.fr [Institut Gustave-Roussy, Department of Interventional Radiology (France); Chomy, François, E-mail: F.Chomy@bordeaux.unicancer.fr [Institut Bergonié, Comprehensive Cancer Center, Department of medical oncology (France); Baere, Thierry de, E-mail: debaere@igr.fr [Institut Gustave-Roussy, Department of Interventional Radiology (France)

2015-02-15

PurposeTo evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery.Materials and MethodsEighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analysesResultsMedian follow-up was 30.5 months (interquartile range 16.7–51) and tumor size was 21 mm (range 10–54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % at 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS.ConclusionsOversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression.

Study of the relative toxicity of anions, with Polycelis nigra as test animal

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Jones, J R.E.

1942-01-01

A brief review is given of existing knowledge regarding the physiological effects of anions, and literature dealing with their relative toxicity. The degree of toxicity of twenty-seven anions to Polycelis nigra (Mueller) has been assessed, by determining in each case the molar concentration the animal survives for 48 hr. at 15-18/sup 0/C. On this basis their order of increasing toxicity is as follows; commas separate ions of similar degree of toxicity: Cltoxic than cations. Even the most toxic anion (OH) is far less toxic than ionic copper, silver, or gold. The respiration rate of Polycelis is heavily depressed by cyanide, but the survival time is three days or longer, as long as the respiration rate is not less than about 16% of the normal value. With further depression the survival time shortens rapidly, and at 9% normal is under 4 hr. The normal respiration rate of Polycelis nigra is 0.165 cc O/sub 2//g./hr. This is not very much less than that of the trout. Polycelis is considerably the more resistant to cyanide. This is probably connected with its capability of surviving very many hours in water containing a very reduced supply of oxygen. 34 references, 6 figures, 1 table.

Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

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White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John

2014-05-01

The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Gang; Wang, Qian; Li, Zhengyan; Liu, Chaoxu; He, Xianli

2018-01-01

Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96-3.13) and OS (pooled HR =2.66, 95% CI: 2.04-3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78-3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer.

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

Science.gov (United States)

Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

2015-01-01

Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

Surgical Management and Prognostic Factors of Vulvovaginal Melanoma.

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Ditto, Antonino; Bogani, Giorgio; Martinelli, Fabio; Di Donato, Violante; Laufer, Joel; Scasso, Santiago; Chiappa, Valentina; Signorelli, Mauro; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2016-07-01

The aim of the study was to evaluate the surgical management and the role of different prognostic factors on survival outcomes of women affected by genital (i.e., vulvar and vaginal) melanoma. Data of patients undergoing primary surgical treatment for genital melanoma were evaluated in this retrospective study. Baseline, pathological, and postoperative variables were tested to identify prognostic factors. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Overall, 98 patients met the inclusion criteria. Sixty-seven (68%) and 31 (32%) patients in this study population were diagnosed with vulvar and vaginal melanoma, respectively. Median (range) DFS and OS were 12 (1-70) and 22 (1-70) months, respectively. Considering factors influencing DFS, we observed that at multivariate analysis, only vaginal localization (hazard ratio [HR] = 3.72; 95% CI = 1.05-13.2) and number of mitoses (HR = 1.24; 95% CI = 1.11-1.39) proved to be associated with worse DFS. Nodal status was the only independent factor influencing 5-year OS in patients with vulvar (HR = 1.76; 95% CI = 1.22-2.54; p = .002) and vaginal (HR = 3.65; 95% CI = 1.08-12.3; p = .03) melanoma. Genital melanomas are characterized by a poor prognosis. Number of mitoses and lymph node status are the main factors influencing survival. Surgery is the mainstay of treatment. A correct and prompt diagnosis is paramount.

The correlation between the levels of tissue inhibitor of metalloproteinases 1 in plasma and tumour response and survival after preoperative radiochemotherapy in patients with rectal cancer

International Nuclear Information System (INIS)

Oblak, Irena; Velenik, Vaneja; Anderluh, Franc; Mozina, Barbara; Ocvirk, Janja

2013-01-01

The aim of this study was to analyse whether the level of tissue inhibitor of metalloproteinases (TIMP) 1 is associated with the tumour response and survival to preoperative radiochemotherapy in rectal cancer patients. Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I– III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA). Median follow-up time was 68 months (range: 3–93 months) while in survivors it was 80 months (range: 68–93 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22–523 ng/mL) and the mean level (±standard deviation) was 192 (±87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP>12 mg/L and in those who died from rectal cancer or had cT4 tumours. No correlation was established for age, gender, carcinoembriogenic antigene (CEA) level, platelets count, histopathological grade, response to preoperative therapy, resectability and disease reappearance. On univariate analysis, various parameters favourably influenced one or more survival endpoints: TIMP-1 <170 ng/mL, CRP <12 mg/L, platelets count <290 10E9/L, CEA <3.4mg/L, age <69 years, male gender, early stage disease (cN0 and/or cT2–3), radical surgery (R0) and response to preoperative radiochemotherapy. In multivariate model, LRC was favourably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage. Although we did not find any association between pretreatment serum TIMP-1 levels and primary tumour response to preoperative

Improved survival for elderly married glioblastoma patients. Better treatment delivery, less toxicity, and fewer disease complications

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Putz, Florian; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Radiation Oncology, Erlangen (Germany); Putz, Tobias [University of Bamberg, Professorship of Demography, Bamberg (Germany); Eyuepoglu, Ilker; Roessler, Karl [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany)

2016-11-15

Marital status is a well-described prognostic factor in patients with gliomas but the observed survival difference is unexplained in the available population-based studies. A series of 57 elderly glioblastoma patients (≥70 years) were analyzed retrospectively. Patients received radiotherapy or chemoradiation with temozolomide. The prognostic significance of marital status was assessed. Disease complications, toxicity, and treatment delivery were evaluated in detail. Overall survival was significantly higher in married than in unmarried patients (median, 7.9 vs. 4.0 months; p = 0.006). The prognostic significance of marital status was preserved in the multivariate analysis (HR, 0.41; p = 0.011). Married patients could receive significantly higher daily temozolomide doses (mean, 53.7 mg/m{sup 2} vs. 33.1 mg/m{sup 2}; p = 0.020), were more likely to receive maintenance temozolomide (45.7 % vs. 11.8 %; p = 0.016), and had to be hospitalized less frequently during radiotherapy (55.0 % vs. 88.2 %; p = 0.016). Of the patients receiving temozolomide, married patients showed significantly lower rates of hematologic and liver toxicity. Most complications were infectious or neurologic in nature. Complications of any grade were more frequent in unmarried patients (58.8 % vs. 30.0 %; p = 0.041) with the incidence of grade 3-5 complications being particularly elevated (47.1 % vs. 15.0 %; p = 0.004). We found poorer treatment delivery as well as an unexpected severe increase in toxicity and disease complications in elderly unmarried glioblastoma patients. Marital status may be an important predictive factor for clinical decision-making and should be addressed in further studies. (orig.) [German] Fuer verheiratete Patienten mit malignen Gliomen ist ein verbessertes Gesamtueberleben gut beschrieben. Die zugrunde liegenden Mechanismen konnten bislang jedoch in den verfuegbaren bevoelkerungsbezogenen Arbeiten nicht erklaert werden. Eine Serie von 57 aelteren Patienten mit

Determinants of long-term outcome in patients undergoing simultaneous resection of synchronous colorectal liver metastases.

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Qi Lin

Full Text Available BACKGROUND: It remains unclear which patients can benefit from simultaneous resection of synchronous colorectal liver metastases (SCRLMs. This study aimed to examine the prognostic value of patient- and tumor-related factors in predicting long-term outcomes of patients undergoing simultaneous resection of SCRLMs and to help patients select a suitable therapeutic regimen and proper surveillance. METHODS: Clinicopathological and outcome data of 154 consecutive SCRLM patients who underwent simultaneous resection between July 2003 and July 2013 were collected from our prospectively established SCRLM data and analyzed with univariate and multivariate methods, and the prognostic index (PI was formulated based on the regression coefficients (β of the Cox model. The patients were classified into high- and low-risk groups according to the PI value; the cut-off point was the third quartile. RESULTS: The 5-year overall survival rate was 46%, and the 5-year disease-free survival rate was 35%. Five factors were found to be independent predictors of poor overall survival (OS by multivariate analysis: positive lymph node status, vascular invasion, BRAF mutation, the distribution of bilobar liver metastases (LMs and non-R0 resection of LMs. Compared to low PI (≤5.978, high PI (>5.978 was highly predictive of shorter OS. Three factors were found to be independent predictors of poor disease-free survival (DFS by multivariate analysis: tumor deposits, BRAF mutation and bilobar LM distribution. We also determined the PI for DFS. Compared to low PI (≤2.945, high PI (>2.945 was highly predictive of shorter DFS. CONCLUSIONS: Simultaneous resection of SCRLM may lead to various long-term outcomes. Patients with low PI have longer OS and DFS, while those with high PI have shorter OS and DFS. Thus, patients with high PI may receive more aggressive treatment and intensive surveillance, This model needs further validation.

Prognostic value of the standardized uptake value for {sup 18}F-fluorodeoxyglucose in patients with stage IIIB melanoma

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Bastiaannet, E.; Hoekstra, H.J. [University of Groningen, Department of Surgical Oncology, University Medical Centre Groningen, PO Box 30.001, Groningen (Netherlands); Hoekstra, O.S. [VU Amsterdam, Nuclear Medicine and PET Research, University Medical Centre, Amsterdam (Netherlands); Jong, J.R. de; Brouwers, A.H. [University of Groningen, Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, Groningen (Netherlands); Suurmeijer, A.J.H. [University of Groningen, Department of Pathology, University Medical Centre Groningen, Groningen (Netherlands)

2012-10-15

FDG PET/CT is an excellent tool to detect melanoma metastases and also allows quantification of FDG uptake using standardized uptake value (SUV). The aim of this study was to prospectively investigate the potential prognostic value of SUV for disease-free survival (DFS) and disease-specific survival (DSS) for patients with stage IIIB melanoma. From November 2003 to March 2008, all consecutive patients were included in the present study. Inclusion criteria were: palpable, histology- or cytology-proven lymph node metastases of melanoma, and referred to the University Medical Centre Groningen for FDG PET and CT examination. Patients without distant metastases were evaluated. Multivariable survival analysis was performed to determine whether SUV was associated with DFS and DSS (Cox proportional hazard analysis). In 80 patients (without distant metastases, 65 %) SUV could be measured. Overall 5-year DFS was 41 % (95% CI 26-56 %) and 24 % (95% CI 12-38 %) in patients with a low and high SUVmean (p = 0.02), respectively. Overall 5-year DSS was 48 % (95% CI 31-62 %) and 30 % (95% CI 17-45 %) in patients with a low and high SUVmean (p = 0.04), respectively. In the multivariable analysis, SUVmean was associated with DFS (hazard ratio 1.7; p = 0.048), but was not associated with DSS (hazard ratio 1.6; p = 0.1). The number of positive nodes, extranodal growth and gender were also associated with survival. FDG uptake in clinically overt nodal melanoma metastases is inversely associated with DFS. Univariate analysis showed an association with DSS. However, after adjustment for potential confounders this association was no longer significant. If these findings are confirmed in larger studies, SUVmean could potentially be used (in addition to the number of positive nodes, tumour size and extranodal growth) as a factor in deciding on adjuvant systemic treatment. (orig.)

Stereotactic Robotic Body Radiotherapy for Patients With Unresectable Hepatic Oligorecurrence.

Science.gov (United States)

Berkovic, Patrick; Gulyban, Akos; Nguyen, Paul Viet; Dechambre, David; Martinive, Philippe; Jansen, Nicolas; Lakosi, Ferenc; Janvary, Levente; Coucke, Philippe A

2017-12-01

The purpose of this study was to analyze local control (LC), liver progression-free survival (PFS), and distant PFS (DFS), overall survival (OS), and toxicity in a cohort of patients treated with stereotactic body radiotherapy (SBRT) with fiducial tracking for oligorecurrent liver lesions; and to evaluate the potential influence of lesion size, systemic treatment, physical and biologically effective dose (BED), treatment calculation algorithms and other parameters on the obtained results. Unoperable patients with sufficient liver function had [18F]-fluorodeoxyglucose-positron emission tomography-computed tomography and liver magnetic resonance imaging to confirm the oligorecurrent nature of the disease and to further delineate the gross tumor volume (GTV). An intended dose of 45 Gy in 3 fractions was prescribed on the 80% isodose and adapted if risk-related. Treatment was executed with the CyberKnife system (Accuray Inc) platform using fiducials tracking. Initial plans were recalculated using the Monte Carlo algorithm. Patient and treatment data were processed using the Kaplan-Meier method and log rank test for survival analysis. Between 2010 and 2015, 42 patients (55 lesions) were irradiated. The mean GTV and planning target volume (PTV) were 30.5 cc and 96.8 cc, respectively. Treatments were delivered 3 times per week in a median of 3 fractions to a PTV median dose of 54.6 Gy. The mean GTV and PTV D98% were 51.6 Gy and 51.2 Gy, respectively. Heterogeneity corrections did not influence dose parameters. After a median follow-up of 18.9 months, the 1- and 2-year LC/liver PFS/DFS/OS were 81.3%/55%/62.4%/86.9%, and 76.3%/42.3%/52%/78.3%, respectively. Performance status and histology had a significant effect on LC, whereas age (older than 65 years) marginally influenced liver PFS. Clinical target volume physical dose V45 Gy > 95%, generalized equivalent uniform dose (a = -30) > 45 Gy and a BED (α/β = 10) V105 Gy > 96% showed statistically significant effect on

MRI target delineation may reduce long-term toxicity after prostate radiotherapy.

Science.gov (United States)

Sander, Lotte; Langkilde, Niels Christian; Holmberg, Mats; Carl, Jesper

2014-06-01

Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n=72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n=73) had MRI target delineation and a nickel-titanium stent as fiducial. At 36 months no difference in overall survival (92% in both groups, p=0.29) or in PSA-relapse free survival was found between the groups (MRI=89% and CT=94%, p=0.67). A significantly smaller CTV was found in the MRI group (p=0.02). Urinary retention and frequency were significantly reduced in the MRI group (p=0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.

Survival of experimentally induced Toxoplasma gondii tissue cysts in vacuum packed goat meat and dry fermented goat meat sausages.

Science.gov (United States)

Neumayerová, Helena; Juránková, Jana; Saláková, Alena; Gallas, Leo; Kovařčík, Kamil; Koudela, Břetislav

2014-05-01

Ingestion of raw or undercooked meat is a potential source of human toxoplasmosis. The aim of this study was to determine the viability of Toxoplasma gondii cysts in vacuum packed (VP) goat meat and in dry fermented sausages (DFS), and evaluate certain physical and chemical parameters, like water activity (aw), pH value, content of salt, dry matter and fat. A portion of muscle tissue from experimentally infected animals was used for production of VP meat with or without addition of 2.5% curing salt, and stored at 4 °C or at -20 °C. Results of bioassay showed that, samples of vacuum packed Toxoplasma positive meat without salt addition were alive after six weeks at 4 °C. Incubation at -20 °C supported the viability after 3 h, but not after 4 h. After 7 days in 2.5% of curing salt, samples of T. gondii VP goat meat were still viable, but not after 14 days at 4 °C. All the DFS samples were not positive for infective cysts which mean that, they do not pose a risk of T. gondii transmission. These data suggest that vacuum packaging increases the survival of T. gondii cysts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prognostic impact of chemotherapy-induced amenorrhea on premenopausal breast cancer: a meta-analysis of the literature

Science.gov (United States)

Zhou, Qiong; Yin, Wenjin; Du, Yueyao; Shen, Zhenzhou; Lu, Jingsong

2015-01-01

Abstract Objective: We conducted this meta-analysis of published data to assess the exact prognostic value of adjuvant chemotherapy-induced amenorrhea (CIA) as a prognostic factor for premenopausal breast cancer. Methods: We searched for all relevant studies published before May 2014 in the PubMed, OVID, and EMBASE databases. Relative risks (RRs) were used to estimate the association between CIA and various survival outcomes, including disease-free survival (DFS) and overall survival (OS). Results: This meta-analysis identified 13 eligible studies including 5,513 cases and 2,008 controls for DFS and 5 eligible studies including 2,331 cases and 776 controls for OS. Results demonstrated that CIA is associated with improved DFS (RR, 0.67; 95% CI, 0.61-0.74; P < 0.001) and OS (RR, 0.60; 95% CI, 0.50-0.72; P < 0.001). In subgroup analyses, CIA was found to affect DFS (RR, 0.73; 95% CI, 0.61-0.88; P = 0.001) in estrogen receptor (ER)–positive patients; however, similar results were not observed in ER-negative patients (for DFS: RR, 0.97; 95% CI, 0.66-1.41; P = 0.858). Participants with CIA achieved a significantly better prognosis than participants without CIA, irrespective of nodal status, chemotherapy regimen, endocrine therapy, or publication year. Conclusions: This meta-analysis clarifies that CIA contributes to improved prognosis in premenopausal women with ER-positive breast cancer and is at least partially responsible for the benefits of adjuvant chemotherapy in these women, which induce chemical castration. PMID:25783467

Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery

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Kirienko, Margarita; Fogliata, Antonella; Sollini, Martina [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Cozzi, Luca [Humanitas Clinical and Research Center, Radiotherapy and Radiosurgery, Rozzano, Milan (Italy); Antunovic, Lidija [Humanitas Clinical and Research Center, Nuclear Medicine, Rozzano, Milan (Italy); Lozza, Lisa [Orobix Srl, Bergamo (Italy); Voulaz, Emanuele [Humanitas Clinical and Research Center, Thoracic Surgery, Rozzano, Milan (Italy); Rossi, Alexia [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Humanitas Clinical and Research Center, Radiology, Rozzano, Milan (Italy); Chiti, Arturo [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Humanitas Clinical and Research Center, Nuclear Medicine, Rozzano, Milan (Italy)

2018-02-15

Radiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery. A cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built. The Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65-0.85), 0.68 (95%CI: 0.57-0.80), and 0.68 (95%CI: 0.58-0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51-0.69), 0.64 (95%CI: 0.53-0.75), and 0.65 (95%CI: 0.50-0.72) for the CT, the PET, and the PET+CT images, respectively. A radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery. (orig.)

Fluoride bioaccumulation and toxic effects on the survival and behavior of the endangered white-clawed crayfish Austropotamobius pallipes (Lereboullet).

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Aguirre-Sierra, Arantxa; Alonso, Alvaro; Camargo, Julio A

2013-08-01

Laboratory experiments were performed to examine the toxic effects of fluoride (F(-)) on the survival and behavior of white-clawed crayfish (Austropotamobius pallipes). Body fluoride contents (bioaccumulation) of test crayfish were also examined. No significant differences between male and female crayfish regarding mortality, escape (tail-flip) response, and fluoride bioaccumulation were detected. For mortality, 48-, 72-, 96-, 120-, 144-, 168-, and 192-h median lethal concentrations (LC50) were estimated to be 93.0, 55.3, 42.7, 36.5, 32.9, 30.6, and 28.9 mg F(-)/l, respectively. For the escape response, 48-, 72-, 96-, 120-, 144-, 168- and 192-h median effective concentrations (EC50) were estimated to be 18.4, 11.1, 8.6, 7.4, 6.7, 6.2 and 5.9 mg F(-)/l, respectively. Average food consumption in test crayfish tended to decrease with increasing water fluoride concentration with a 192-h lowest-observed effect concentration of 10.7 mg F(-)/l. These results indicate that the escape response was the most sensitive end point to fluoride toxicity followed by food consumption and mortality. Fluoride bioaccumulation in test crayfish increased with increasing water fluoride concentration and exposure time. The exoskeleton accumulated more fluoride than muscle. A comparison of the obtained results with previous data for other freshwater invertebrates shows that white-clawed crayfish are relatively tolerant to fluoride toxicity. We conclude that fluoride pollution in freshwater ecosystems should not be viewed as an important risk factor contributing to the catastrophic decrease of A. pallipes in many European countries. Our results indicate that fluoride bioaccumulation in A. pallipes might be used as a bioindicator of fluoride pollution in freshwater ecosystems where it is present.

Leptomeningeal enhancement on preoperative brain MRI in patients with glioblastoma and its clinical impact.

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Kim, Hakyoung; Lim, Do Hoon; Kim, Tae Gyu; Lee, Jung-Il; Nam, Do-Hyun; Seol, Ho Jun; Kong, Doo-Sik; Choi, Jung Won; Suh, Yeon-Lim; Kim, Sung Tae

2018-02-23

Leptomeningeal enhancement (LME) on preoperative brain magnetic resonance imaging (MRI) does not always indicate leptomeningeal seeding (LMS). With Stupp's regimen, authors have treated glioblastoma patients with LME on preoperative brain MRI but here we tried to find the clinical impact of LME. From 2005 to 2015, 290 patients with glioblastoma have been treated with Stupp's regimen at Samsung Medical Center. Among these, 33 patients showed LME on preoperative brain MRI. We compared the clinical outcomes between the patients with or without LME on preoperative brain MRI and analyzed the clinical results according to changes of LME at following MRI. The median survival was 23 months, and 2-year overall survival (OS) and disease-free survival (DFS) rate was 46.3% and 19.6%, respectively. Prognostic factors for OS and DFS were Karnofsky performance status, extent of resection and adjuvant chemotherapy. MGMT promoter methylation status was a significant prognostic factor for DFS. However, LME was not a significant prognostic factor for OS (P = 0.156) or DFS (P = 0.193). Among the 33 patients with LME on preoperative MRI, 21 (63.6%) showed persistent LME at the next MRI. A statistically significant difference in 2-year survival was evident between patients with and without persistent LME (OS, 17.3% and 70.1%, respectively, P = 0.044; DFS, 5.3% and 54.0%, respectively, P = 0.006). The most common pattern of failure was local recurrence. However, patients with persistent LME displayed a higher incidence of LMS than patients without LME. LME on preoperative brain MRI did not affect the clinical results in glioblastoma patients treated with the Stupp's regimen. However, persistence of LME was associated with poor survival and high possibility of LMS. For these patients, the postoperative adjuvant treatment should focus on palliative aim or more aggressive treatment scheme should be followed to overcome the disastrous results. © 2018 John Wiley & Sons Australia, Ltd.

Pesticide Toxicity Index: a tool for assessing potential toxicity of pesticide mixtures to freshwater aquatic organisms

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Nowell, Lisa H.; Norman, Julia E.; Moran, Patrick W.; Martin, Jeffrey D.; Stone, Wesley W.

2014-01-01

Pesticide mixtures are common in streams with agricultural or urban influence in the watershed. The Pesticide Toxicity Index (PTI) is a screening tool to assess potential aquatic toxicity of complex pesticide mixtures by combining measures of pesticide exposure and acute toxicity in an additive toxic-unit model. The PTI is determined separately for fish, cladocerans, and benthic invertebrates. This study expands the number of pesticides and degradates included in previous editions of the PTI from 124 to 492 pesticides and degradates, and includes two types of PTI for use in different applications, depending on study objectives. The Median-PTI was calculated from median toxicity values for individual pesticides, so is robust to outliers and is appropriate for comparing relative potential toxicity among samples, sites, or pesticides. The Sensitive-PTI uses the 5th percentile of available toxicity values, so is a more sensitive screening-level indicator of potential toxicity. PTI predictions of toxicity in environmental samples were tested using data aggregated from published field studies that measured pesticide concentrations and toxicity to Ceriodaphnia dubia in ambient stream water. C. dubia survival was reduced to ≤ 50% of controls in 44% of samples with Median-PTI values of 0.1–1, and to 0% in 96% of samples with Median-PTI values > 1. The PTI is a relative, but quantitative, indicator of potential toxicity that can be used to evaluate relationships between pesticide exposure and biological condition.

Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials.

Science.gov (United States)

Mocellin, Simone; Nitti, Donato

2015-05-01

The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival. We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for both overall (OS), disease-specific (DSS) and disease-free survival (DFS). The quality of the available evidence was assessed using the GRADE system. Eight RCTs enrolling 2515 patients were eligible. The meta-analysis of four RCTs (n=1599) showed a significant impact of D2 versus D1 lymphadenectomy on DSS (summary HR=0.807, CI: 0.705-0.924, P=0.002), the corresponding number-to-treat being equal to ten. This effect remained clinically valuable even after adjustment for postoperative mortality. However, the quality of evidence was graded as moderate due to inconsistency issues. When OS and DFS were considered, the meta-analysis of respectively five (n=1653) and three RCTs (n=1332) found no significant difference between D2 and D1 lymph node dissection (summary HR=0.911, CI: 0.708-1.172, P=0.471, and summary HR=0.946, CI: 0.840-1.066, P=0.366, respectively). However, at subgroup analysis D2 type resulted superior to D1 type lymphadenectomy in terms of OS considering the two RCTs carried out in Eastern countries (summary HR=0.627, CI: 0.396-0.994, P=0.047). As regards the D3 vs D2 comparison, the meta-analysis of the three available RCTs (n=862) showed no significant impact of more extended lymphadenectomy on OS (summary HR=0.990, CI: 0.814-1.205, P=0.924). Our findings support the superiority of D2 versus D1 lymphadenectomy in terms of survival benefit. However, this advantage is mainly limited to DSS, the level of evidence is moderate, and the interaction with other factors affecting patient survival (such as

NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction

International Nuclear Information System (INIS)

Wennberg, Berit M.; Baumann, Pia; Gagliardi, Giovanna

2011-01-01

Background. In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Material and methods. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction α/β = 3 Gy was used and the USC parameters used were: α/β = 3 Gy, D 0 = 1.0 Gy, n = 10, α 0.206 Gy-1 and d T = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether 'high doses to small volumes' or 'low doses to large volumes' are most important for lung toxicity. Results and Discussion. NTCP analysis with the LKB-model using parameters m = 0.4, D50 = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D 50 = 20 Gy n = 0.93 with LQ correction and n 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

International Nuclear Information System (INIS)

Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

1981-01-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

Science.gov (United States)

McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

2016-01-01

Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

Paclitaxel-Based Chemoradiotherapy in the Treatment of Patients With Operable Esophageal Cancer

International Nuclear Information System (INIS)

Kelsey, Chris R.; Chino, Junzo P.; Willett, Christopher G.; Clough, Robert W.; Hurwitz, Herbert I.; Morse, Michael A.; Bendell, Johanna C.; D'Amico, Thomas A.; Czito, Brian G.

2007-01-01

Purpose: To compare a neoadjuvant regimen of cisplatin/5-fluorouracil (5-FU) and concurrent radiation therapy (RT) with paclitaxel-based regimens and RT in the management of operable esophageal (EC)/gastroesophageal junction (GEJ) cancer. Methods and Materials: All patients receiving neoadjuvant chemotherapy (CT) and RT for EC/GEJ cancer at Duke University between January 1995 and December 2004 were included. Clinical end points were compared for patients receiving paclitaxel-based regimens (TAX) vs. alternative regimens (non-TAX). Local control (LC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Chi-square analysis was performed to test the effect of TAX on pathologic complete response (pCR) rates and toxicity. Results: A total of 109 patients received CT-RT followed by esophagectomy (95 M; 14 F). Median RT dose was 45 Gy (range, 36-66 Gy). The TAX and non-TAX groups comprised 47% and 53% of patients, respectively. Most (83%) TAX patients received three drug regimens including platinum and a fluoropyrimidine. In the non-TAX group, 89% of the patients received cisplatin and 5-FU. The remainder received 5-FU or capecitabine alone. Grade 3-4 toxicity occurred in 41% of patients receiving TAX vs. 24% of those receiving non-TAX (p = 0.19). Overall pCR rate was 39% (39% with TAX vs. 40% with non-TAX, p = 0.9). Overall LC, DFS, and OS at 3 years were 80%, 34%, and 37%, respectively. At 3 years, there were no differences in LC (75% vs. 85%, p = 0.33) or OS (37% vs. 37%, p = 0.32) between TAX and non-TAX groups. Conclusions: In this large experience, paclitaxel-containing regimens did not improve pCR rates or clinical end points compared to non-paclitaxel-containing regimens

Test of the acute lethal toxicity of pollutants to marine fish and invertebrates

International Nuclear Information System (INIS)

1989-01-01

This reference method describes the measurement of the acute lethal toxicity of pollutants to marine animals (fish and invertebrates) by a static (non-continuous flow) method. Procedures are given for the determination of the toxicity curve (survival time-concentration relationship) and for the estimation of median lethal concentrations (LC50). The method is suitable for use with fish and macro-invertebrate species. It is not suitable for planktonic organisms nor for determining the toxicity of oil, oil dispersants or other petroleum products. Those methods are described in Reference Methods Nos. 44 and 45, respectively. The test animals are exposed, in groups of approximately ten, to each of several concentrations of the pollutant. The animals are observed, at intervals, for several days, the test solutions being renewed regularly. A record is maintained of the survival times of individual animals exposed to each concentration of pollutant. The medial survival time of each group of animals is determined from a graphical plot of the raw data after a log-probability transformation. Median survival times and their confidence limits are plotted against concentrations of test substance to give a toxicity curve. Additionally, the same experimental data can be used to estimate the median lethal concentration (LC50) of the test substance to the animals after different periods of exposure. 3 refs, 5 figs, 3 tabs

A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

Science.gov (United States)

Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

2017-10-01

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

Thermal Stress and Toxicity | Science Inventory | US EPA

Science.gov (United States)

Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at subthermoneutral temperatures of —22 °C. When exposed to chemical toxicants under these relatively cool conditions, rodents typically undergo a regulated hypothermic response, characterized by preference for cooler ambient temperatures and controlled reduction in core temperature. Reducing core temperature delays the clearance of most toxicants from the body; however, a mild hypothermia also improves recovery and survival from the toxicant. Raising ambient temperature to thermoneutrality and above increases the rate of clearance of the toxicant but also exacerbates toxicity. Furthermore, heat stress combined with work or exercise is likely to worsen toxicity. Body temperature of large mammals, including humans, does not decrease as much in response to exposure to a toxicant. However, heat stress tan nonetheless worsen toxic outcome in humans through a variety of mechanisms. For example, heat-induced sweating and elevation in skin blood flow accelerates uptake of some insecticides. Epidemiological studies suggest that thermal stress may exacerbate the toxicity of airborne pollutants such as ozone and particulate matter. Overall, translating results of studies in rodents to that of humans is a formidable

How Saccharomyces cerevisiae copes with toxic metals and metalloids.

Science.gov (United States)

Wysocki, Robert; Tamás, Markus J

2010-11-01

Toxic metals and metalloids are widespread in nature and can locally reach fairly high concentrations. To ensure cellular protection and survival in such environments, all organisms possess systems to evade toxicity and acquire tolerance. This review provides an overview of the molecular mechanisms that contribute to metal toxicity, detoxification and tolerance acquisition in budding yeast Saccharomyces cerevisiae. We mainly focus on the metals/metalloids arsenic, cadmium, antimony, mercury, chromium and selenium, and emphasize recent findings on sensing and signalling mechanisms and on the regulation of tolerance and detoxification systems that safeguard cellular and genetic integrity.

Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

Energy Technology Data Exchange (ETDEWEB)

Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2013-06-01

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Matsuyama, Takaharu; Kato, Koji

2002-01-01

A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 μg/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

Energy Technology Data Exchange (ETDEWEB)

Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

2002-07-01

A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

The distribution of fruit and seed toxicity during development for eleven neotropical trees and vines in Central Panama.

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Noelle G Beckman

Full Text Available Secondary compounds in fruit mediate interactions with natural enemies and seed dispersers, influencing plant survival and species distributions. The functions of secondary metabolites in plant defenses have been well-studied in green tissues, but not in reproductive structures of plants. In this study, the distribution of toxicity within plants was quantified and its influence on seed survival was determined in Central Panama. To investigate patterns of allocation to chemical defenses and shifts in allocation with fruit development, I quantified variation in toxicity between immature and mature fruit and between the seed and pericarp for eleven species. Toxicity of seed and pericarp was compared to leaf toxicity for five species. Toxicity was measured as reduced hyphal growth of two fungal pathogens, Phoma sp. and Fusarium sp., and reduced survivorship of brine shrimp, Artemia franciscana, across a range of concentrations of crude extract. I used these measures of potential toxicity against generalist natural enemies to examine the effect of fruit toxicity on reductions of fruit development and seed survival by vertebrates, invertebrates, and pathogens measured for seven species in a natural enemy removal experiment. The seed or pericarp of all vertebrate- and wind-dispersed species reduced Artemia survivorship and hyphal growth of Fusarium during the immature and mature stages. Only mature fruit of two vertebrate-dispersed species reduced hyphal growth of Phoma. Predispersal seed survival increased with toxicity of immature fruit to Artemia during germination and decreased with toxicity to fungi during fruit development. This study suggests that fruit toxicity against generalist natural enemies may be common in Central Panama. These results support the hypothesis that secondary metabolites in fruit have adaptive value and are important in the evolution of fruit-frugivore interactions.

The distribution of fruit and seed toxicity during development for eleven neotropical trees and vines in Central Panama.

Science.gov (United States)

Beckman, Noelle G

2013-01-01

Secondary compounds in fruit mediate interactions with natural enemies and seed dispersers, influencing plant survival and species distributions. The functions of secondary metabolites in plant defenses have been well-studied in green tissues, but not in reproductive structures of plants. In this study, the distribution of toxicity within plants was quantified and its influence on seed survival was determined in Central Panama. To investigate patterns of allocation to chemical defenses and shifts in allocation with fruit development, I quantified variation in toxicity between immature and mature fruit and between the seed and pericarp for eleven species. Toxicity of seed and pericarp was compared to leaf toxicity for five species. Toxicity was measured as reduced hyphal growth of two fungal pathogens, Phoma sp. and Fusarium sp., and reduced survivorship of brine shrimp, Artemia franciscana, across a range of concentrations of crude extract. I used these measures of potential toxicity against generalist natural enemies to examine the effect of fruit toxicity on reductions of fruit development and seed survival by vertebrates, invertebrates, and pathogens measured for seven species in a natural enemy removal experiment. The seed or pericarp of all vertebrate- and wind-dispersed species reduced Artemia survivorship and hyphal growth of Fusarium during the immature and mature stages. Only mature fruit of two vertebrate-dispersed species reduced hyphal growth of Phoma. Predispersal seed survival increased with toxicity of immature fruit to Artemia during germination and decreased with toxicity to fungi during fruit development. This study suggests that fruit toxicity against generalist natural enemies may be common in Central Panama. These results support the hypothesis that secondary metabolites in fruit have adaptive value and are important in the evolution of fruit-frugivore interactions.

NADH-Cytochrome b5 Reductase 3 Promotes Colonization and Metastasis Formation and Is a Prognostic Marker of Disease-Free and Overall Survival in Estrogen Receptor-Negative Breast Cancer

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Lund, Rikke R; Leth-Larsen, Rikke; Caterino, Tina Di

2015-01-01

(NRH2). The altered expression levels were validated at the protein and transcriptional levels, and analysis of breast cancer biopsies from two cohorts of patients demonstrated a significant correlation between high CYB5R3 expression and poor disease-free and overall survival in patients with estrogen...... receptor-negative tumors (DFS: p = .02, OS: p = .04). CYB5R3 gene knock-down using siRNA in metastasizing cells led to significantly decreased tumor burden in lungs when injected intravenously in immunodeficient mice. The cellular effects of CYB5R3 knock-down showed signaling alterations associated...

A large cohort study reveals the association of elevated peripheral blood lymphocyte-to-monocyte ratio with favorable prognosis in nasopharyngeal carcinoma.

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Jing Li

Full Text Available BACKGROUND: Nasopharyngeal carcinoma (NPC is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20-30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients. METHODS: A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS, disease-free survival (DFS, distant metastasis-free survival (DMFS and loco-regional recurrence-free survival (LRRFS, respectively. RESULTS: Univariate analysis revealed that higher LMR level (≥ 5.220 was significantly associated with superior OS, DFS and DMFS (P values <0.001. The higher lymphocyte count (≥ 2.145 × 10(9/L was significantly associated with better OS (P = 0.002 and DMFS (P = 0.031, respectively, while the lower monocyte count (<0.475 × 10(9/L was associated with better OS (P = 0.012, DFS (P = 0.011 and DMFS (P = 0.003, respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.558, 95% confidence interval or 95% CI = 0.417-0.748; P<0.001, DFS (HR = 0.669, 95% CI = 0.535-0.838; P<0.001 and DMFS (HR = 0.543, 95% CI = 0.403-0.732; P<0.001, respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053 and DMFS (P = 0.080. CONCLUSIONS: The

Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex

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Rui Feng

2018-03-01

Full Text Available Nattokinase (NK, which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK, nattokinase-tauroursodeoxycholate (NK-TUDCA complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state, tail injury, and the body weight of mice, it was found that the NK-TUDCA complex (NK: 10 kIU/ml; TUDCA: 10 mg/ml; pH 5.0 had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NK-TUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK. Keywords: Nattokinase, Tauroursodeoxycholate, Complex, Toxicity test, In vitro thrombolytic test

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

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Schmiegelow, K.; Attarbaschi, Andishe; Barzilai, Shlomit

2016-01-01

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi ...

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

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Pasquier, David, E-mail: d-pasquier@o-lambret.fr [Academic Radiation Oncology Department, Centre Oscar Lambret, Lille (France); Barney, Brandon [Mayo Clinic, Rochester, Minnesota (United States); Sundar, Santhanam [Department of Oncology, Nottingham University Hospitals National Health Service Trust, Nottingham (United Kingdom); Poortmans, Philip [Department of Radiation Oncology, Radboud university medical center, Nijmegen (Netherlands); Villa, Salvador [Radiation Oncology, Catalan Institute of Oncology, H. Universitari Germans Trías, Badalona, Barcelona (Spain); Nasrallah, Haitam [Division of Oncology, Rambam Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Ghadjar, Pirus [Department of Radiation Oncology, Bern University Hospital, Bern (Switzerland); Lassen-Ramshad, Yasmin [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Senkus, Elżbieta [Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk (Poland); Oar, Andrew [Genesis Cancer Care, Southport (Australia); Roelandts, Martine [Institut Jules Bordet, Brussels (Belgium); Amichetti, Maurizio [Provincial Agency for Proton Therapy, Trento (Italy); Vees, Hansjoerg [Department of Radiation Oncology, Hopital de Sion, Sion (Switzerland); Zilli, Thomas [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

2015-07-15

Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease

Role of major resection in pulmonary metastasectomy for colorectal cancer in the Spanish prospective multicenter study (GECMP-CCR).

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Hernández, J; Molins, L; Fibla, J J; Heras, F; Embún, R; Rivas, J J

2016-05-01

Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival when compared with limited pulmonary resection. Data of 522 patients (64.2% men, mean age 64.5 years) who underwent pulmonary resections with curative intent for CRC metastases over a 2-year period were reviewed. All patients were followed for a minimum of 3 years. Disease-specific survival (DSS) and disease-free survival (DFS) were assessed with the Kaplan-Meier method. Factors associated with DSS and DFS were analyzed using a Cox proportional hazards regression model. A total of 394 (75.6%) patients underwent wedge resection, 19 (3.6%) anatomic segmentectomy, 5 (0.9%) lesser resections not described, 100 (19.3%) lobectomy, and 4 (0.8%) pneumonectomy. Accordingly, 104 (19.9%) patients were treated with major anatomic resection and 418 (80.1%) with lesser resection. Operations were carried out with video-assisted thoracoscopic surgery (VATS) in 93 patients. The overall DSS and DFS were 55 and 28.3 months, respectively. Significant differences in DSS and DFS in favor of major resection versus lesser resection (DSS median not reached versus 52.2 months, P = 0.03; DFS median not reached versus 23.9 months, P < 0.001) were found. In the multivariate analysis, major resection appeared to be a protective factor in DSS [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.41-0.96, P = 0.031] and DFS (HR 0.5, 95% CI 0.36-0.75, P < 0.001). The surgical approach (VATS versus open surgical resection) had no effect on outcome. Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results. © The Author 2016. Published by Oxford University Press

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients.

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Pasquier, David; Barney, Brandon; Sundar, Santhanam; Poortmans, Philip; Villa, Salvador; Nasrallah, Haitam; Boujelbene, Noureddine; Ghadjar, Pirus; Lassen-Ramshad, Yasmin; Senkus, Elżbieta; Oar, Andrew; Roelandts, Martine; Amichetti, Maurizio; Vees, Hansjoerg; Zilli, Thomas; Ozsahin, Mahmut

2015-07-15

Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this

Prognostic Significance of Nodal Location and Ratio in Stage IIIC Endometrial Carcinoma Among a Multi-Institutional Academic Collaboration.

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Mayadev, Jyoti; Elshaikh, Mohamed A; Christie, Alana; Nagel, Christa; Kennedy, Vanessa; Khan, Nadia; Lea, Jayanthi; Ghanem, Ahmad; Miller, David; Xie, Xian-Jin; Folkert, Michael; Albuquerque, Kevin

2018-04-20

Stage IIIC endometrial carcinoma (EC) represents pathologically heterogenous patients with single/multiple pelvic (stage IIIC1) or paraaortic (stage IIIC2) lymph nodes (LNs). There is an increasing trend to offer adjuvant chemotherapy (CT) +/- radiation (RT) uniformly to these patients, regardless of substage. We investigate the prognostic significance of positive LN (pLN) number, ratio (%pLN), location (IIC1 vs. IIC2), and adjuvant treatment on patterns of failure and survival in a large collaborative multi-institutional series. Clinical data for stage III EC patients such as patient characteristics, surgery/pathologic details, adjuvant therapies (including CT, RT, and chemotherapy and radiation), and outcomes (including pelvic control [PC], disease-free survival [DFS], distant DFS, and overall survival [OS]) were collected from 3 academic institutions. Log-rank analyses, Cox regression univariate and multivariate analyses were performed. Of the 264 patients queried for stage III disease, 237 (73%) had pLN, and complete LN sampling for analysis. The mean number of pLN in the combined data were 3.9, with 26.1% of all LN sampled positive; 121 patients (51%) staged IIIC1, and 116 patients (49%) staged IIIC2. There was a significant difference in number of pLN (P=0.0006) and total LN sampled by institution (range, 13 to 35; P=0.0004), without a difference in %pLN (P=0.35). Ninety-seven of 220 (44.1%) have ≥20% pLN. While controlling for substage and institution, a decrease in DFS (hazard ratio [HR], 1.1; P=0.007), and OS (HR, 1.1; P=0.01) was observed with every increase of 10% in the pLN ratio. There was a significant difference in DFS (HR, 1.8; P=0.003), PC (HR, 1.9; P=0.004), and distant DFS (HR, 1.6; P=0.03), as well as a trend for decreased OS (HR, 1.6; P=0.08) for substage IIIC2 versus IIIC1 disease; 5 years DFS 40% versus 45%, OS 50% versus 57%. Patients received no adjuvant therapy (10%), CT alone (27%), RT alone (16%), or chemotherapy and radiation (47

The impact of IGF-1R expression on the outcomes of patients with breast cancer: a meta-analysis

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Yan, Shunchao; Jiao, Xin; Li, Kai; Li, Wusheng; Zou, Huawei

2015-01-01

Purpose The value of insulin-like growth factor 1 receptor (IGF-1R) for predicting survival of patients with breast cancer remains controversial. The purpose of this study was to perform a meta-analysis of the published data to attempt to clarify the impact of IGF-1R. Methods Studies published between January 1, 1990 and October 1, 2014 were identified using an electronic search to aggregate the available survival results. Studies were included if they reported detecting IGF-1R expression in the primary breast cancer and analyzed patient survival data according to IGF-1R status. The principal outcome measures were hazard ratios (HRs) for survival of IGF-1R-positive patients. Combined HRs and 95% confidence intervals (CIs) were estimated using fixed- or random-effects models according to between-study heterogeneity. Results Ten studies, involving 5,406 patients, satisfied our inclusion criteria. Data from five studies provided the impact of IGF-1R on overall survival (OS), three studies the impact on breast cancer-specific survival (BCSS), and seven studies the impact on disease-free survival (DFS). The results of meta-analysis showed that for DFS, membranous IGF-1R positivity was not a significant predictor. The combined HR for OS/BCSS was 0.63 (95% CI: 0.42–0.95, P=0.03), indicating that membranous IGF-1R positivity was a significant predictor of better survival. IGF-1R cytoplasmic positivity was significantly associated with longer DFS and OS/BCSS (combined HR: 0.56, 95% CI: 0.35–0.89, P=0.01; combined HR: 0.55, 95% CI: 0.35–0.85, P=0.008, respectively). The results of subgroup analysis suggested that membranous IGF-1R positivity in hormone-receptor-positive breast cancer was correlated with favorable DFS (combined HR: 0.61, 95% CI: 0.41–0.92, P=0.02) and OS/BCSS (combined HR: 0.73, 95% CI: 0.57–0.93, P=0.01). Membranous IGF-1R positivity in triple-negative breast cancer predicted worse DFS (combined HR: 1.86, 95% CI: 1.03–3.34, P=0.04). Membranous

Comparison and avoidance of toxicity of penetrating cryoprotectants.

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Edyta A Szurek

Full Text Available The objective of this study was to elucidate the toxicity of widely used penetrating cryoprotective agents (CPAs to mammalian oocytes. To this end, mouse metaphase II (M II oocytes were exposed to 1.5 M solutions of dimethylsulfoxide (DMSO, ethylene glycol (EG, or propanediol (PROH prepared in phosphate buffered saline (PBS containing 10% fetal bovine serum. To address the time- and temperature-dependence of the CPA toxicity, M II oocytes were exposed to the aforementioned CPAs at room temperature (RT, ∼23°C and 37°C for 15 or 30 minutes. Subsequently, the toxicity of each CPA was evaluated by examining post-exposure survival, fertilization, embryonic development, chromosomal abnormalities, and parthenogenetic activation of treated oocytes. Untreated oocytes served as controls. Exposure of MII oocytes to 1.5 M DMSO or 1.5 M EG at RT for 15 min did not adversely affect any of the evaluated criteria. In contrast, 1.5 M PROH induced a significant increase in oocyte degeneration (54.2% and parthenogenetic activation (16% under same conditions. When the CPA exposure was performed at 37°C, the toxic effect of PROH further increased, resulting in lower survival (15% and no fertilization while the toxicity of DMSO and EG was still insignificant. Nevertheless, it was possible to completely avoid the toxicity of PROH by decreasing its concentration to 0.75 M and combining it with 0.75 M DMSO to bring the total CPA concentration to a cryoprotective level. Moreover, combining lower concentrations (i.e., 0.75 M of PROH and DMSO significantly improved the cryosurvival of MII oocytes compared to the equivalent concentration of DMSO alone. Taken together, our results suggest that from the perspective of CPA toxicity, DMSO and EG are safer to use in slow cooling protocols while a lower concentration of PROH can be combined with another CPA to avoid its toxicity and to improve the cryosurvival as well.

A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery

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Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De-Sen

2016-01-01

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment. PMID:27008710

A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery.

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Peng, Jian-Hong; Fang, Yu-Jing; Li, Cai-Xia; Ou, Qing-Jian; Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De Sen

2016-04-19

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.

Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma

International Nuclear Information System (INIS)

Makita, Chiyoko; Kikuchi, Yasuhiro; Hareyama, Masato; Murakami, Masao; Fuwa, Nobukazu; Hata, Masaharu; Inoue, Tomio; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Suzuki, Motohisa; Ishikawa, Yojiro; Azami, Yusuke; Kato, Takahiro; Tsukiyama, Iwao

2014-01-01

We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma. The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement. Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal

Integrative genomic analysis identifies ancestry-related expression quantitative trait loci on DNA polymerase β and supports the association of genetic ancestry with survival disparities in head and neck squamous cell carcinoma.

Science.gov (United States)

Ramakodi, Meganathan P; Devarajan, Karthik; Blackman, Elizabeth; Gibbs, Denise; Luce, Danièle; Deloumeaux, Jacqueline; Duflo, Suzy; Liu, Jeffrey C; Mehra, Ranee; Kulathinal, Rob J; Ragin, Camille C

2017-03-01

African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated. Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase β (POLB) gene (false discovery rate [FDR] ancestry (P = .002). An association was observed between these eQTLs and OS (P ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. Cancer 2017;123:849-60. © 2016 American Cancer Society. © 2016 American Cancer Society.

A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

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Sayan, Mutlay; Nelson, Carl; Gagne, Havaleh; Rubin, Deborah; Heimann, Ruth [Dept. of Radiation Oncology, University of Vermont Medical Center, Burlington (United States); Wilson, Karen [University of Vermont Cancer Center, Burlington (United States)

2017-03-15

Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

Unresectable Carcinoma of the Paranasal Sinuses: Outcomes and Toxicities

International Nuclear Information System (INIS)

Hoppe, Bradford S.; Nelson, Carl J.; Gomez, Daniel R.; Stegman, Lauren D.; Wu, Abraham J.; Wolden, Suzanne L.; Pfister, David G.; Zelefsky, Michael J.; Shah, Jatin P.; Kraus, Dennis H.; Lee, Nancy Y.

2008-01-01

Purpose: To evaluate long-term outcomes and toxicity in patients with unresectable paranasal sinus carcinoma treated with radiotherapy, with or without chemotherapy. Methods and Materials: Between January 1990 and December 2006, 39 patients with unresectable Stage IVB paranasal sinus carcinoma were treated definitively with chemotherapy plus radiotherapy (n = 35, 90%) or with radiotherapy alone (n = 4, 10%). Patients were treated with three-dimensional conformal radiotherapy (n = 18, 46%), intensity-modulated radiotherapy (n = 12, 31%), or conventional radiotherapy (n = 9, 23%) to a median treatment dose of 70 Gy. Most patients received concurrent platinum-based chemotherapy (n = 32, 82%) and/or concomitant boost radiotherapy (n = 29, 74%). Results: With a median follow-up of 90 months, the 5-year local progression-free survival, regional progression-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 21%, 61%, 51%, 14%, and 15%, respectively. Patients primarily experienced local relapse (n = 25, 64%), mostly within the irradiated field (n = 22). Nine patients developed neck relapses; however none of the 4 patients receiving elective neck irradiation had a nodal relapse. In 13 patients acute Grade 3 mucositis developed. Severe late toxicities occurred in 2 patients with radionecrosis and 1 patient with unilateral blindness 7 years after intensity-modulated radiation therapy (77 Gy to the optic nerve). The only significant factor for improved local progression-free survival and overall survival was a biologically equivalent dose of radiation ≥65 Gy. Conclusions: Treatment outcomes for unresectable paranasal sinus carcinoma are poor, and combined-modality treatment is needed that is both more effective and associated with less morbidity. The addition of elective neck irradiation may improve regional control

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

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Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

2016-01-01

Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

Age and associated fibrocystic changes are prognostically significant in patients with small node-negative (T1a,bN0) invasive breast cancer.

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Durak, Merih Guray; Gonzalez-Angulo, Ana M; Hanrahan, Emer O; Broglio, Kristine R; Valero, Vicente; Hortobagyi, Gabriel N; Hunt, Kelly K; Sahin, Aysegul A

2011-01-01

Some patients with small (≤1.0 cm) node-negative (T1a,bN0) invasive breast cancer (IBC) who undergo only local therapy experience recurrences. There is limited information on prognostic factors in these patients. We sought to identify prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with T1a,bN0 IBC. Histologic sections from 273 T1a,bN0 IBC patients treated at M. D. Anderson Cancer Center (MDACC) between 1980 and 1999 were reviewed. Microscopic tumor size; multifocality; histologic type, grade of tumor; presence, type, grade of associated ductal carcinoma in situ (DCIS); presence of fibrocystic changes (FCC) with/without atypia; and lymphovascular invasion were identified. The Kaplan-Meier method was used to evaluate DFS and OS. Median patient age was 58 years, median follow-up period was 10.8 years, and median tumor size was 0.8 cm. Multifocal disease was identified in 26% of cases. At 10 years, the DFS and OS rates were 91% and 88%, respectively. Twenty-one percent of patients had extensive (>50%), and 30% had grade 3 DCIS. Nonproliferative FCC and proliferative FCC with/without atypia were present in 80%, 36%, and 38% of patients, respectively. In univariate analysis, age at diagnosis (p < 0.0001), grade (p = 0.015), and percent (p = 0.046) of DCIS were significantly associated with DFS; presence of FCC was associated with longer DFS and OS. In multivariable models, age and presence of FCC remained significantly associated with survival. Age at diagnosis and associated FCC are significant factors in predicting recurrence in patients with T1a,bN0 IBC. Adjuvant systemic therapy should be discussed with and considered for young patients with T1a,bN0 IBC. © 2011 Wiley Periodicals, Inc.

Prevalence of molecular subtypes and prognosis of invasive breast cancer in north-east of Morocco: retrospective study

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Bennis Sanae

2012-08-01

Full Text Available Abstract Background Breast carcinoma is known as a heterogeneous disease because gene expression analyses identify several subtypes and the molecular profiles are prognostic and predictive for patients. Our aim, in this study, is to estimate the prevalence of breast cancer subtypes and to determine the relationship between clinico-pathological characteristics, overall survival (OS and disease free survival (DFS for patients coming from north-east of Morocco. Methods We reviewed 366 cases of breast cancer diagnosed between January 2007 to June 2010 at the Department of pathology. Age, size tumor, metastatic profile, node involvement profile, OS and DFS were analyzed on 181 patients. These last parameters were estimated by Kaplan-Meier analysis and log-rank test to estimate outcome differences among subgroups. Results The average age was 45 years, our patients were diagnosed late (57% stage III, 17.5% stage IV with a high average tumor size. Luminal A subtype was more prevalent (53.6% associated with favorable clinic-pathological characteristics, followed by luminal B (16.4%, Her2-overexpressing (12.6%, basal-like (12.6% and unclassified subtype (4.9%. Survival analysis showed a significant difference between subtypes. The triple negative tumors were associated with poor prognosis (49% OS, 39% DFS, whereas the luminal A were associated with a better prognosis (88% OS, 59% DFS. The luminal B and the Her2-overexpressing subtypes were associated with an intermediate prognosis (77% and 75% OS, and 41% and 38% DFS respectively. Conclusion This study showed that molecular classification by immunohistochemistry was necessary for therapeutic decision and prognosis of breast carcinoma. The luminal A subtype was associated with favorable biological characteristics and a better prognosis than triple negative tumors that were associated with a poor prognosis and unfavorable clinic-pathological characteristics.

Profile of prognostic factors in 1022 Indian women with early-stage breast cancer treated with breast-conserving therapy

International Nuclear Information System (INIS)

Dinshaw, Ketayun A.; Budrukkar, Ashwini N.; Chinoy, Roshan F.; Sarin, Rajiv; Badwe, Rajendra M.S.; Hawaldar, Rohini; Shrivastava, Shyam Kishore

2005-01-01

Purpose: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. Methods and Materials: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). Results: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women. The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age ≤40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). Conclusion: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment

Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy

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Choi, Yunseon; Ahn, Ki Jung; Park, Sung Kwang; Cho, Heung Lae; Lee, Ji Young

2017-01-01

This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m2 (range, 17.7 to 35.9 kg/m2). The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m2) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes

Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy

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Choi, Yunseon; Ahn, Ki Jung; Park, Sung Kwang; Cho, Heung Lae; Lee, Ji Young [Inje University Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

2017-03-15

This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m2 (range, 17.7 to 35.9 kg/m2). The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m2) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

Long noncoding RNA metastasis-associated lung adenocarcinoma ...

African Journals Online (AJOL)

Manal S. Fawzy

2016-09-22

Sep 22, 2016 ... Real-time polymerase chain reaction (PCR) was performed in accordance ... overall survival (OS) and disease-free survival (DFS) were. 15.4 ± 5.17 ..... [2] Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, · Jouvet A ...

The correlation between the astro consensus panel definition of biochemical failure and clinical outcome for patients with prostate cancer treated with external beam irradiation

International Nuclear Information System (INIS)

Horwitz, Eric M.; Vicini, Frank A.; Ziaja, Ellen L.; Dmuchowski, Carl F.; Stromberg, Jannifer S.; Matter, Richard C.; Martinez, Alvaro A.

1997-01-01

Purpose: The ASTRO Consensus Panel on PSA After Radiation Therapy recently recommended a definition of biochemical failure (BF) following treatment of prostate cancer with radiation therapy. We reviewed our institution's experience treating patients with external beam irradiation (RT) to determine if the Consensus Panel definition correlates with clinical distant metastases free survival (DMFS), disease free survival (DFS), cause specific survival (CSS), and local control (LC) rates for a large group of patients from the PSA era. Methods And Materials: Between 1/1/87 and 12/31/92, 653 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital. Of these patients, 568 had a minimum follow-up of 2 years and constitute the study population. The median pre-treatment PSA and Gleason score was 11 ng/ml and 6, respectively. The median dose to the prostate using megavoltage RT was 66.6 Gy (range: 60-70.4 Gy) using a four field or arc technique. No patient received hormonal therapy either prior to, during, or after radiotherapy unless local or distant failure was documented. Pre-treatment and post-treatment serum PSA levels were recorded. Biochemical failure was defined as three consecutive increases in post-treatment PSA after achieving a nadir. Biochemical failure was recorded as the time midway between the nadir and first increase in PSA. Five year actuarial rates of DMFS, DFS, CSS, and LC were calculated for patients who were biochemically controlled (BC) versus those who failed biochemically. Results: Median follow-up was 56 months (range: 24-118 months). The overall 5 year actuarial rates of DMFS, DFS, CSS, and LC were significantly better in patients who were biochemically controlled versus those who were not (p< 0.001). The median time to DM within the BF group was 21 months (range: 2-112 months). When stratifying by pre-treatment PSA, Gleason score, and T stage, these

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

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Hauspy, Jan; Beiner, Mario E; Harley, Ian; Rosen, Barry; Murphy, Joan; Chapman, William; Le, Lisa W; Fyles, Anthony; Levin, Wilfred

2011-03-01

To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

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Yuwei Wang

2014-01-01

Full Text Available Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP. CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS and overall survival (OS were analyzed using Kaplan-Meier method (log-rank test and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50 of patients were characterized as CIMP positive. Univariate analysis showed stage III (P=0.049 and CIMP positive (P=0.014 patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P=0.019. In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P=0.023. Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy.

Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy.

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Holgersson, Georg; Bergström, Stefan; Liv, Per; Nilsson, Jonas; Edlund, Per; Blomberg, Carl; Nyman, Jan; Friesland, Signe; Ekman, Simon; Asklund, Thomas; Henriksson, Roger; Bergqvist, Michael

2015-10-01

To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000. Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Interaction of chemical cues from fish tissues and organophosphorous pesticides on Ceriodaphnia dubia survival

International Nuclear Information System (INIS)

Maul, Jonathan D.; Farris, Jerry L.; Lydy, Michael J.

2006-01-01

Cladocera are frequently used as test organisms for assessing chemical and effluent toxicity and have been shown to respond to stimuli and cues from potential predators. In this study, the interactive effects of visual and chemical cues of fish and two organophosphorous pesticides on survival of Ceriodaphnia dubia were examined. A significant chemical cue (homogenized Pimephales promelas) and malathion interaction was observed on C. dubia survival (P = 0.006). Chemical cue and 2.82 μg/L malathion resulted in a 76.0% reduction in survival compared to malathion alone (P < 0.01). Furthermore, potentiation of malathion toxicity varied based on the source of chemical cues (i.e., epithelial or whole body). It is unclear in this study whether these chemical cues elicited a predation-related stress in C. dubia. Future research should examine the mechanism of this interaction and determine what role, if any, stress responses by C. dubia might play in the interaction. - Potentiation of organophosphorous pesticide toxicity to Ceriodaphnia dubia by fathead minnow (Pimephales promelas) chemical cues was observed

Oxidative stress-induced autophagy: Role in pulmonary toxicity

International Nuclear Information System (INIS)

Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

2014-01-01

Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic

Oxidative stress-induced autophagy: Role in pulmonary toxicity

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Malaviya, Rama [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

2014-03-01

Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

Intensity-modulated radiotherapy with simultaneous modulated accelerated boost technique and chemotherapy in patients with nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Fareed, Muhammad M; AlAmro, Abdullah S; Bayoumi, Yasser; Tunio, Mutahir A; Ismail, Abdul S; Akasha, Rashad; Mubasher, Mohamed; Al Asiri, Mushabbab

2013-01-01

To present our experience of intensity-modulated radiotherapy (IMRT) with simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Sixty eight patients of NPC were treated between April 2006 and December 2011 including 45 males and 23 females with mean age of 46 (range 15–78). Stage distribution was; stage I 3, stage II 7, stage III 26 and stage IV 32. Among 45 (66.2%) evaluated patients for presence of Epstein-Barr virus (EBV), 40 (88.8%) were positive for EBV. Median radiation doses delivered to gross tumor volume (GTV) and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume (CTV) and 50.4 Gy to clinically negative neck. In addition 56 (82.4%) patients with bulky tumors (T4/N2+) received neoadjuvant chemotherapy 2–3 cycles (Cisplatin/Docetaxel or Cisplatin/Epirubicin or Cisplatin/5 Flourouracil). Concurrent chemotherapy with radiation was weekly Cisplatin 40 mg/m 2 (40 patients) or Cisplatin 100 mg/m 2 (28 patients). With a median follow up of 20 months (range 3–43), one patient developed local recurrence, two experienced regional recurrences and distant failure was seen in 3 patients. Estimated 3 year disease free survival (DFS) was 94%. Three year DFS for patients with EBV was 100% as compared to 60% without EBV (p = 0.0009). Three year DFS for patients with undifferentiated histology was 98% as compared to 82% with other histologies (p = 0.02). Acute grade 3 toxicity was seen as 21 (30.9%) having G-III mucositis and 6 (8.8%) with G-III skin reactions. Late toxicity was minimal and loss of taste was seen in 3 patients (7.5%) at time of analysis. IMRT with SMART in combination with chemotherapy is feasible and effective in terms of both the clinical response and safety profile. EBV, histopathology and nodal involvement were found important prognostic factors for locoregional recurrence

125I Monotherapy Using D90 Implant Doses of 180 Gy or Greater

International Nuclear Information System (INIS)

Kao, Johnny; Stone, Nelson N.; Lavaf, Amir; Dumane, Vishruta; Cesaretti, Jamie A.; Stock, Richard G.

2008-01-01

Purpose: The purpose of this study was to characterize the oncologic results and toxicity profile of patients treated with 125 I implants using the dose delivered to 90% of the gland from the dose-volume histogram (D90) of greater than 144 Gy. Methods and Materials: From June 1995 to Feb 2005, a total of 643 patients were treated with 125 I monotherapy for T1-T2 prostate cancer with a D90 of 180 Gy or greater (median, 197 Gy; range, 180-267 Gy). Implantations were performed using a real-time ultrasound-guided seed-placement method and intraoperative dosimetry to optimize target coverage and homogeneity by using modified peripheral loading. We analyzed biochemical disease-free survival (bDFS) of 435 patients who had a minimum 2-year prostate-specific antigen follow-up (median follow-up, 6.7 years; range, 2.0-11.1 years). Results: Five-year bDFS rates for the entire cohort using the American Society for Therapeutic Radiology and Oncology and Phoenix definitions were 96.9% and 96.5%, respectively. Using the Phoenix definition, 5-year bDFS rates were 97.3% for low-risk patients and 92.8% for intermediate/high-risk patients. The positive biopsy rate was 4.1%. The freedom rate from Grade 2 or higher rectal bleeding at 5 years was 88.5%. Acute urinary retention occurred in 10.7%, more commonly in patients with high pretreatment International Prostate Symptom Scores (p < 0.01). In patients who were potent before treatment, 73.4% remained potent at 5 years after implantation. Conclusions: Patients with a minimum D90 of 180 Gy had outstanding local control based on prostate-specific antigen control and biopsy data. Toxicity profiles, particularly for long-term urinary and sexual function, were excellent and showed that D90 doses of 180 Gy or greater performed using the technique described were feasible and tolerable

Prognostic value of preoperative intratumoral FDG uptake heterogeneity in patients with epithelial ovarian cancer

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Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Lee, Hyunjong; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

2017-01-15

To investigate the prognostic value of intratumoral FDG uptake heterogeneity (IFH) derived from PET/CT in patients with epithelial ovarian cancer (EOC). We retrospectively reviewed patients with pathologically proven epithelial ovarian cancer who underwent preoperative {sup 18}F-FDG PET/CT scans. PET/CT parameters such as maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}), sum of all metabolic tumour volume (MTV), cumulative total lesion glycolysis (TLG) and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with disease-free survival (DFS). Clinicopathological data were reviewed for 61 eligible patients. The median duration of DFS was 13 months (range, 6-26 months), and 18 (29.5 %) patients experienced recurrence. High IFH values were associated with tumour recurrence (P = 0.005, hazard ratio 4.504, 95 % CI 1.572-12.902). The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P = 0.002, log-rank test). Moreover, there were significant differences in DFS (P = 0.009) and IFH (P = 0.040) between patients with and without recurrence. Preoperative IFH measured by {sup 18}F-FDG PET/CT was significantly associated with EOC recurrence. FDG-based heterogeneity could be a useful and potential predicator of EOC recurrence before treatment. (orig.)

Prognostic significance of serum lactate dehydrogenase levels in Ewing's sarcoma: A meta-analysis.

Science.gov (United States)

Li, Suoyuan; Yang, Qing; Wang, Hongsheng; Wang, Zhuoying; Zuo, Dongqing; Cai, Zhengdong; Hua, Yingqi

2016-12-01

A number of studies have investigated the role of serum lactate dehydrogenase (LDH) levels in patients with Ewing's sarcoma, although these have yielded inconsistent and inconclusive results. Therefore, the present study aimed to systematically review the published studies and conduct a meta-analysis to assess its prognostic value more precisely. Cohort studies assessing the prognostic role of LDH levels in patients with Ewing's sarcoma were included. A pooled hazard ratio (HR) with 95% confidence intervals (CIs) of overall survival (OS) or 5-year disease-free survival (DFS) was used to assess the prognostic role of the levels of serum LDH. Nine studies published between 1980 and 2014, with a total of 1,412 patients with Ewing's sarcoma, were included. Six studies, with a total of 644 patients, used OS as the primary endpoint and four studies, with 795 patients, used 5-year DFS. Overall, the pooled HR evaluating high LDH levels was 2.90 (95% CI: 2.09-4.04) for OS and 2.40 (95% CI: 1.93-2.98) for 5-year DFS. This meta-analysis demonstrates that high levels of serum LDH are associated with lower OS and 5-year DFS rates in patients with Ewing's sarcoma. Therefore, serum LDH levels are an effective biomarker of Ewing's sarcoma prognosis.

Use of various acute, sublethal and early life-stage tests to evaluate the toxicity of refinery effluents

International Nuclear Information System (INIS)

Sherry, J.; Scott, B.; Dutka, B.

1997-01-01

The toxicities of effluents from three Ontario, Canada, refineries were assessed with microbes, plants, invertebrates, and fish. Acute toxicity was assessed by the Microtox test, an assay based on electron transport activity in submitochondrial particles, and Daphnia magna (water flea); growth of Selenastrum capricornutum (alga); growth of Lemna minor (aquatic plant); germination of Lactuca sativa (nonaquatic plant); survival, growth, and maturation of Panagrellus redivivus (nematode); and genotoxicity in the SOS-Chromotest. Only the Microtox test and the submitochondrial particle test detected acute toxicity in the effluent samples. Reduced survival and sublethal responses were caused by some effluents, but not all effluents were toxic, and none caused a response in all of the tests applied. The results suggest that the effluent treatment systems used at Ontario refineries have largely eliminated acute toxicity to the organisms in their test battery. Although reduced survival and sublethal effects were detected in some of the effluents, the effects were minor. Some of the tests provided evidence, albeit weak, of variations in the responses of the test organisms to a temporal series of effluent samples. Not unexpectedly, there were also minor differences in the responses of the tests to effluents from the three refineries. The fathead minnow test seems to be a sensitive indicator of the sublethal toxicity of Ontario refinery effluents

Comparison of survival and toxicities of concurrent radiotherapy with Carboplatin/Paclitaxel or Cisplatin/Etoposide in unresectable stage III non-small cell lung cancers: retrospective analysis in the Department of Pneumology of CHU Nancy between 2008 and 2014

International Nuclear Information System (INIS)

Huet, Dimitri

2015-01-01

In concomitant chemo-radiotherapy treatment for inoperable stage III NSCLC, different combinations of chemotherapies have been recommended. The objective of this study was to compare progression-free survival, overall survival, and tolerability of two treatment regimens: Cisplatin-etoposide concomitant radio-chemotherapy versus concomitant carboplatin-Paclitaxel based radio-chemotherapy in these patients. A retrospective analysis of 62 patients treated with concomitant radio-chemotherapy for inoperable stage III NSCLC has been carried out in the Department of Pneumology (University Hospital of Nancy). The patients were divided into 2 groups according to the chemotherapy protocol, group 1: Cisplatin-etoposide (27 patients) and group 2: Carboplatin-Paclitaxel (35 patients). The two groups were comparable in terms of age and gender (mean age 58 in group 1 versus age 61 in group 2, and 85 pc of men in group 1 versus 80 pc in group 2). The median overall survival was 19 months in group 1 versus 15.3 months in group 2 (p = 0.22). The median progression-free survival was higher in group 1, 9 months versus 3.3 months in group 2 (p = 0.01). Hematologic toxicity was higher in group 1 than in group 2 (neutropenia 85.2 pc versus 54.3 pc, p = 0.01, anemia 92.3 pc versus 54.3 pc, p = 0.001). Radiation esophagitis and radiation pneumonitis rates were higher in group 1 than in group 2: 44.4 pc versus 11.4 pc (p = 0.01), and 44.4 pc versus 11.4 pc (p = 0.001) respectively. In this mono-centric and retrospective study, the Cisplatin-etoposide - thoracic radiotherapy combination to treat inoperable stage III NSCLC was associated with a significantly higher progression-free survival than the Carboplatin-Paclitaxel-radiotherapy combination. This increase in survival was accompanied by a significantly higher hematological and organ toxicity [fr

Intensity-modulated radiotherapy for stage IVA/IVB nasopharyngeal carcinoma. Clinical outcomes and patterns of failure in an endemic area in China

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Zeng, Lei; Tian, Yun-Ming; Sun, Xue-Ming; Huang, Ying; Chen, Chun-Yan; Han, Fei; Liu, Shuai; Lan, Mei; Guan, Ying [Collaborative Innovation Center of Cancer Medicine, State Key Laboratory Oncology in South China, Guangzhou (China); Sun Yat-Sen University Cancer Center, Department of Radiation Oncology, Guangzhou (China); Deng, Xiao-Wu; Lu, Tai-Xiang [Sun Yat-Sen University Cancer Center, Department of Radiation Oncology, Guangzhou (China); Collaborative Innovation Center of Cancer Medicine, State Key Laboratory Oncology in South China, Guangzhou (China)

2014-11-15

The purpose of this study was to analyze the mode of relapse patterns and survival of 209 patients with stage IVA and IVB nasopharyngeal carcinoma (NPC). A total of 209 patients who underwent magnetic resonance imaging (MRI) and were subsequently histologically diagnosed with nondisseminated stage IV NPC received intensity-modulated radiotherapy (IMRT) as their primary treatment and were included in this retrospective study. Median follow-up time was 65 months (range, 3-108 months). The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates for patients with stage IVA and stage IVB NPC were 72.7 vs. 60.0 % (p = 0.319), 62.9 vs. 51.3 % (p = 0.070), 82.9 vs. 93.1 % (p = 0.070), 82.9 vs. 82.9 % (p = 0.897), 76.4 vs. 58.5 % (p = 0.003), respectively. Age older than 44 years was found to be a statistically significant adverse independent prognostic factor for OS. Patients with advanced N status had worse OS, DFS, and DMFS rates. Patients with a primary gross tumor volume (GTV-P) ≥ 55.11 ml had worse OS, DFS, and LRRFS rates. The results of treating stage IVA NPC with IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for patients with stage IVA and IVB NPC, and more effective systemic chemotherapy should be explored. (orig.) [German] Ziel dieser Studie war die Analyse der Rezidivmuster und des Ueberlebens von 209 Patienten mit nasopharyngealem Karzinom (NPC) im Stadium IVA und IVB. Insgesamt 209 Patienten, die mittels MRT und anschliessender histologischer Untersuchung mit nichtdisseminiertem NPC im Stadium IV diagnostiziert worden waren, erhielten eine intensitaetsmodulierte Strahlentherapie (IMRT) als Primaerbehandlung und wurden in diese retrospektive Studie aufgenommen. Die mediane Follow-up-Dauer betrug 65 Monate (Bereich 3-108 Monate). Das 5-Jahres-Gesamtueberleben (OS), das

The prognostic value of HPV combined p16 status in patients with anal squamous cell carcinoma: a meta-analysis.

Science.gov (United States)

Sun, Guorui; Dong, Xiaoyuan; Tang, Xiaolong; Qu, Hui; Zhang, Hao; Zhao, Ensheng

2018-01-30

Human papillomavirus (HPV) DNA and p16 expression have been identified to be related to the progression of anal squamous cell carcinoma (ASCC). However, the prognostic relevance of combined detection, particularly HPV-/p16+ and HPV+/p16- signatures, is unknown. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Data were collected from studies comparing overall survival (OS) and disease-free survival (DFS) / disease-specific survival (DSS) / relapse-free survival (RFS) / progression-free survival (PFS) in ASCC patients with HPV and p16 status. The electronic databases of MEDLINE and EMBASE were searched from their inception till 31 May 2017. Study-specific risk estimates were pooled using a fixed-effects model for OS and DFS/DSS/RFS/PFS. Four studies involving a total of 398 ASCC cases were included in this meta-analysis. The pooled results showed that HPV+/p16+ cancers were significantly associated with improved OS (HR = 0.30, 95% CI: 0.17-0.51) and DFS/DSS/RFS/PFS (HR = 0.23, 95% CI: 0.14-0.36). However, patients with HPV-/p16+ or HPV+/p16- do not have a comparably good prognosis compared with HPV+/p16+ patients. The meta-analysis indicated that concomitant detection of HPV-DNA and p16 expression may be of prognostic or therapeutic utility in the evaluation of factors contributing to ASCC. Testing tumor specimens for HPV-DNA and p16 expression might indirectly affect treatment decisions.

Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

International Nuclear Information System (INIS)

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

2016-01-01

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H 4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H 4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H 4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H 4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60

Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

Directory of Open Access Journals (Sweden)

David Thomson

2012-01-01

Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

Energy Technology Data Exchange (ETDEWEB)

Bishop, Andrew J. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Greenfield, Brad [Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas (United States); Mahajan, Anita [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Paulino, Arnold C. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas (United States); Okcu, M. Fatih [Department of Pediatrics, Texas Children' s Cancer and Hematology Center, Baylor College of Medicine, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Chintagumpala, Murali [Department of Pediatrics, Texas Children' s Cancer and Hematology Center, Baylor College of Medicine, Houston, Texas (United States); Kahalley, Lisa S. [Section of Psychology, Texas Children' s Cancer and Hematology Center, Baylor College of Medicine, Houston, Texas (United States); McAleer, Mary F.; McGovern, Susan L. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Whitehead, William E. [Department of Neurosurgery, Texas Children' s Cancer and Hematology Center, Baylor College of Medicine, Houston, Texas (United States); Grosshans, David R., E-mail: dgrossha@mdanderson.org [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

2014-10-01

Purpose: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity. Methods and Materials: We reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity. Results: At 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742; nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction. Conclusions: Survival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function.

Human cytomegalovirus and Epstein-Barr virus infection impact on 18F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy

International Nuclear Information System (INIS)

Sole, Claudio V.; Calvo, Felipe A.; Ferrer, Carlos; Alvarez, Emilio; Carreras, Jose L.; Ochoa, Enrique

2015-01-01

It has long been debated whether human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with rectal cancer. The gene products of HCMV and EBV contribute to cell-cycle progression, mutagenesis, angiogenesis and immune evasion. The aim of this prospective study was to analyse the association between infection of a tumour by HCMV and EBV and clinical, histological, metabolic ( 18 F-FDG uptake), volumetric (from CT) and molecular (KRAS status) features and long-term outcomes in a homogeneously treated group of patients with locally advanced rectal cancer. HCMV and EBV were detected in pretreatment biopsies using polymerase chain reaction (PCR). The Cox proportional hazards regression model was used to explore associations between viral infection and disease-free survival (DFS) and overall survival (OS). We analysed 37 patients with a median follow-up of 74 months (range 5-173 months). Locoregional control, OS and DFS at 5 years were 93 %, 74 % and 71 %, respectively. Patients with HCMV/EBV coinfection had a significantly higher maximum standardized uptake value than patients without viral coinfection (p = 0.02). Significant differences were also observed in staging and percentage relative reduction in tumour volume between patients with and without HCMV infection (p < 0.01) and EBV infection (p < 0.01). KRAS wildtype status was significantly more frequently observed in patients with EBV infection (p <0.01) and HCMV/EBV co-infection (p = 0.04). No significant differences were observed in OS or DFS between patients with and without EBV infection (p = 0.88 and 0.73), HCMV infection (p = 0.84 and 0.79), and EBV/CMV coinfection (p = 0.24 and 0.39). This pilot study showed that viral infections were associated with metabolic staging differences, and differences in the evolution of metabolic and volumetric parameters and KRAS mutations. Further findings of specific features will help determine the best candidates for metabolic and volumetric staging and

Human cytomegalovirus and Epstein-Barr virus infection impact on {sup 18}F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy

Energy Technology Data Exchange (ETDEWEB)

Sole, Claudio V. [Instituto de Radiomedicina, Department of Radiation Oncology, Santiago (Chile); School of Medicine Complutense University, Madrid (Spain); Calvo, Felipe A. [Hospital General Universitario Gregorio Maranon, Department of Oncology, Madrid (Spain); School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Ferrer, Carlos [Hospital Provincial de Castellon, Institute of Oncology, Castellon de la Plana (Spain); School of Medicine Cardenal Herrera-CEU University, Castellon de la Plana (Spain); Alvarez, Emilio [School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Department of Pathology, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Carreras, Jose L. [School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Department of Radiology and Medical Physics, Madrid (Spain); Ochoa, Enrique [Hospital Provincial de Castellon, Institute of Oncology, Castellon de la Plana (Spain)

2014-10-01

It has long been debated whether human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with rectal cancer. The gene products of HCMV and EBV contribute to cell-cycle progression, mutagenesis, angiogenesis and immune evasion. The aim of this prospective study was to analyse the association between infection of a tumour by HCMV and EBV and clinical, histological, metabolic ({sup 18}F-FDG uptake), volumetric (from CT) and molecular (KRAS status) features and long-term outcomes in a homogeneously treated group of patients with locally advanced rectal cancer. HCMV and EBV were detected in pretreatment biopsies using polymerase chain reaction (PCR). The Cox proportional hazards regression model was used to explore associations between viral infection and disease-free survival (DFS) and overall survival (OS). We analysed 37 patients with a median follow-up of 74 months (range 5-173 months). Locoregional control, OS and DFS at 5 years were 93 %, 74 % and 71 %, respectively. Patients with HCMV/EBV coinfection had a significantly higher maximum standardized uptake value than patients without viral coinfection (p = 0.02). Significant differences were also observed in staging and percentage relative reduction in tumour volume between patients with and without HCMV infection (p < 0.01) and EBV infection (p < 0.01). KRAS wildtype status was significantly more frequently observed in patients with EBV infection (p <0.01) and HCMV/EBV co-infection (p = 0.04). No significant differences were observed in OS or DFS between patients with and without EBV infection (p = 0.88 and 0.73), HCMV infection (p = 0.84 and 0.79), and EBV/CMV coinfection (p = 0.24 and 0.39). This pilot study showed that viral infections were associated with metabolic staging differences, and differences in the evolution of metabolic and volumetric parameters and KRAS mutations. Further findings of specific features will help determine the best candidates for metabolic and volumetric staging and

[Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

Science.gov (United States)

Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

2015-06-01

To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

Treatment outcome after adjuvant radiotherapy following surgery for patients with stage I endometrial cancer

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Kim, Ji Young; Lee, Kyung Ja; Park, Kyung Ran [Dept. of Radiation Oncology, Ewha Womans University School of Medicine, Seoul (Korea, Republic of); and others

2016-12-15

The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0–50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.

Toxicity and bioaccumulation of sediment-associated contaminants using freshwater invertebrates: A review of methods and applications

Science.gov (United States)

Ingersoll, C.G.; Ankley, G.T.; Benoit, D.A.; Brunson, E.L.; Burton, G.A.; Dwyer, F.J.; Hoke, R.A.; Landrum, P.F.; Norberg-King, T. J.; Winger, P.V.

1995-01-01

This paper reviews recent developments in methods for evaluating the toxicity and bioaccumulation of contaminants associated with freshwater sediments and summarizes example case studies demonstrating the application of these methods. Over the past decade, research has emphasized development of more specific testing procedures for conducting 10-d toxicity tests with the amphipod Hyalella azteca and the midge Chironomus tentans. Toxicity endpoints measured in these tests are survival for H. azteca and survival and growth for C. tentans. Guidance has also been developed for conducting 28-d bioaccumulation tests with the oligochaete Lumbriculus variegatus, including determination of bioaccumulation kinetics for different compound classes. These methods have been applied to a variety of sediments to address issues ranging from site assessments to bioavailability of organic and inorganic contaminants using field-collected and laboratory-spiked samples. Survival and growth of controls routinely meet or exceed test acceptability criteria. Results of laboratory bioaccumulation studies with L. variegatus have been confirmed with comparisons to residues (PCBs, PAHs, DDT) present from synoptically collected field populations of oligochaetes. Additional method development is currently underway to develop chronic toxicity tests and to provide additional data-confirming responses observed in laboratory sediment tests with natural benthic populations.

Clinical outcomes for T1-2N0-1 oral tongue cancer patients underwent surgery with and without postoperative radiotherapy

International Nuclear Information System (INIS)

Shim, Su Jung; Cha, Jihye; Koom, Woong Sub; Kim, Gwi Eon; Lee, Chang Geol; Choi, Eun Chang; Keum, Ki Chang

2010-01-01

The aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T 1-2 N 0-1 oral tongue squamous cell carcinoma (OSCC) and to evaluate survival and prognostic factors. Retrospective analysis of 86 patients with T 1-2 N 0-1 OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3%) received postoperative radiotherapy (PORT). Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed. The median follow-up was 45 months. The five-year overall survival (OS) and disease-free survival (DFS) rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth). In the risk group, there was no local failure in patients with postoperative radiotherapy. In T 1-2 N 0-1 OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

NARCIS (Netherlands)

Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; de Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

2014-01-01

Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across

Toxicity of silicon carbide nanowires to sediment-dwelling invertebrates in water or sediment exposures

Science.gov (United States)

Mwangi, Joseph N.; Wang, Ning; Ritts, Andrew; Kunz, James L.; Ingersoll, Christopher G.; Li, Hao; Deng, Baolin

2011-01-01

Silicon carbide nanowires (SiCNW) are insoluble in water. When released into an aquatic environment, SiCNW would likely accumulate in sediment. The objective of this study was to assess the toxicity of SiCNW to four freshwater sediment-dwelling organisms: amphipods (Hyalella azteca), midges (Chironomus dilutus), oligochaetes (Lumbriculus variegatus), and mussels (Lampsilis siliquoidea). Amphipods were exposed to either sonicated or nonsonicated SiCNW in water (1.0 g/L) for 48 h. Midges, mussels, and oligochaetes were exposed only to sonicated SiCNW in water for 96 h. In addition, amphipods were exposed to sonicated SiCNW in whole sediment for 10 d (44% SiCNW on dry wt basis). Mean 48-h survival of amphipods exposed to nonsonicated SiCNW in water was not significantly different from the control, whereas mean survival of amphipods exposed to sonicated SiCNW in two 48-h exposures (0 or 15% survival) was significantly different from the control (90 or 98% survival). In contrast, no effect of sonicated SiCNW was observed on survival of midges, mussels, or oligochaetes. Survival of amphipods was not significantly reduced in 10-d exposures to sonicated SiCNW either mixed in the sediment or layered on the sediment surface. However, significant reduction in amphipod biomass was observed with the SiCNW either mixed in sediment or layered on the sediment surface, and the reduction was more pronounced for SiCNW layered on the sediment. These results indicated that, under the experimental conditions, nonsonicated SiCNW in water were not acutely toxic to amphipods, sonicated SiCNW in water were acutely toxic to the amphipods, but not to other organisms tested, and sonicated SiCNW in sediment affected the growth but not the survival of amphipods.

Mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3) overexpression is an early event in esophageal tumorigenesis and is a predictor of poor disease prognosis

International Nuclear Information System (INIS)

Hasan, Raghibul; Sharma, Rinu; Saraya, Anoop; Chattopadhyay, Tushar K; DattaGupta, Siddartha; Walfish, Paul G; Chauhan, Shyam S; Ralhan, Ranju

2014-01-01

Mitogen-activated protein kinase kinase kinase3 (MAP3K3/MEKK3) was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. Here in we determined the clinical significance of MEKK3 in ESCC. Immunohistochemical analysis of MEKK3 expression was carried out in archived tissue sections from 93 ESCCs, 47 histologically normal and 61 dysplastic esophageal tissues and correlated with clinicopathological parameters and disease prognosis over up to 7.5 years for ESCC patients. MEKK3 expression was significantly increased in esophageal dysplasia and ESCC in comparison with normal mucosa (p trend < 0.001). Kaplan Meier survival analysis showed significantly reduced median disease free survival median DFS = 10 months in patients with MEKK3 positive ESCCs compared to patients with no immunopositivity (median DFS = 19 months, p = 0.04). ESCC patients with MEKK3 positive and lymph node positive tumors had median DFS = 9 months, as compared to median DFS = 21 months in patients who did not show the alterations (p = 0.01). In multivariate Cox regression analysis, combination of MEKK3 overexpression and node positivity [p = 0.015, hazard ratio (HR) = 2.082, 95% CI = 1.154 - 3.756] emerged as important predictor of reduced disease free survival and poor prognosticator for ESCC patients. Alterations in MEKK3 expression occur in early stages of development of ESCC and are sustained during disease progression; MEKK3 in combination with lymph node positivity has the potential to serve as adverse prognosticator in ESCC

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

Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

Science.gov (United States)

Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

2010-04-07

Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

The impact of IGF-1R expression on the outcomes of patients with breast cancer: a meta-analysis

Directory of Open Access Journals (Sweden)

Yan S

2015-01-01

Full Text Available Shunchao Yan,1 Xin Jiao,2 Kai Li,1 Wusheng Li,1 Huawei Zou11Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang, People’s Republic of ChinaPurpose: The value of insulin-like growth factor 1 receptor (IGF-1R for predicting survival of patients with breast cancer remains controversial. The purpose of this study was to perform a meta-analysis of the published data to attempt to clarify the impact of IGF-1R.Methods: Studies published between January 1, 1990 and October 1, 2014 were identified using an electronic search to aggregate the available survival results. Studies were included if they reported detecting IGF-1R expression in the primary breast cancer and analyzed patient survival data according to IGF-1R status. The principal outcome measures were hazard ratios (HRs for survival of IGF-1R-positive patients. Combined HRs and 95% confidence intervals (CIs were estimated using fixed- or random-effects models according to between-study heterogeneity.Results: Ten studies, involving 5,406 patients, satisfied our inclusion criteria. Data from five studies provided the impact of IGF-1R on overall survival (OS, three studies the impact on breast cancer-specific survival (BCSS, and seven studies the impact on disease-free survival (DFS. The results of meta-analysis showed that for DFS, membranous IGF-1R positivity was not a significant predictor. The combined HR for OS/BCSS was 0.63 (95% CI: 0.42–0.95, P=0.03, indicating that membranous IGF-1R positivity was a significant predictor of better survival. IGF-1R cytoplasmic positivity was significantly associated with longer DFS and OS/BCSS (combined HR: 0.56, 95% CI: 0.35–0.89, P=0.01; combined HR: 0.55, 95% CI: 0.35–0.85, P=0.008, respectively. The results of subgroup analysis suggested that membranous IGF-1R positivity in hormone-receptor-positive breast cancer was

Polysialic Acid Neural Cell Adhesion Molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines

International Nuclear Information System (INIS)

Amoureux, Marie-Claude; Coulibaly, Béma; Chinot, Olivier; Loundou, Anderson; Metellus, Philippe; Rougon, Geneviève; Figarella-Branger, Dominique

2010-01-01

Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure. Although patient survival is limited to one year on average, significant variability in outcome is observed. The assessment of biomarkers is needed to gain better knowledge of this type of tumor, help prognosis, design and evaluate therapies. The neurodevelopmental polysialic acid neural cell adhesion molecule (PSA-NCAM) protein is overexpressed in various cancers. Here, we studied its expression in GBM and evaluated its prognosis value for overall survival (OS) and disease free survival (DFS). We set up a specific and sensitive enzyme linked immunosorbent assay (ELISA) test for PSA-NCAM quantification, which correlated well with PSA-NCAM semi quantitative analysis by immunohistochemistry, and thus provides an accurate quantitative measurement of PSA-NCAM content for the 56 GBM biopsies analyzed. For statistics, the Spearman correlation coefficient was used to evaluate the consistency between the immunohistochemistry and ELISA data. Patients' survival was estimated by using the Kaplan-Meier method, and curves were compared using the log-rank test. On multivariate analysis, the effect of potential risk factors on the DFS and OS were evaluated using the cox regression proportional hazard models. The threshold for statistical significance was p = 0.05. We showed that PSA-NCAM was expressed by approximately two thirds of the GBM at variable levels. On univariate analysis, PSA-NCAM content was an adverse prognosis factor for both OS (p = 0.04) and DFS (p = 0.0017). On multivariate analysis, PSA-NCAM expression was an independent negative predictor of OS (p = 0.046) and DFS (p = 0.007). Furthermore, in glioma cell lines, PSA-NCAM level expression was correlated to the one of olig2, a transcription factor required for gliomagenesis. PSA-NCAM represents a valuable biomarker for the prognosis of GBM patients

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

Science.gov (United States)

Chang, Wei-Chin; Lin, Chun-Shu; Yang, Cheng-Yu; Lin, Chih-Kung; Chen, Yuan-Wu

2018-04-01

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

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Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko, E-mail: midoris@med.kitasato-u.ac.jp

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

International Nuclear Information System (INIS)

Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

2013-01-01

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

International Nuclear Information System (INIS)

Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

2011-01-01

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

HER-2 immunohistochemical expression as prognostic marker in high-grade T1 bladder cancer (T1G3

Directory of Open Access Journals (Sweden)

Luca Bongiovanni

2013-06-01

Full Text Available Objectives: To evaluate if the Human epidermal growth factor receptor 2 (HER-2 expression levels may be used as potential prognostic marker in high grade T1 blad- der cancer (T1G3 Methods: Specimens from transurethral resection of bladder tumour (TURBT of 103 patients with high-grade T1 bladder cancer were collected. This pathologic database was reviewed. Four-year follow-up data were matched with pathologic data. Eighty-three patients entered the study. HER-2 staining was performed. Patients were grouped for HER-2 status. Statistical analysis included Kaplan Meier survival analysis and Log-rank test. Results: Pathological review of TURBT specimens confirmed high-grade T1 transitional cell bladder cancer in all patients. Median follow-up was 12 months (mean 23,5; range 3-48. Twenty-one patients (25.4% present strong HER-2 expression (3+, 28 (33.7% moderate expression (2+, 26 (33.7% weak staining (1+ and 8 (9.6% negative expression (0. Thirty- one patients of 83 (37.4% had not evidence of disease, 41 (49.4% recurred, 11 (13.2% had a progression of disease. Forty-one patients had high grade T1 recurrence. Patients with HER-2 status 0 did not showed progression of disease. Patients with HER-2 status 3+, undergoing cys- tectomy because progression of disease, had a pathological stage > pT2 and a nodal involve- ment. Median Disease-Free Survival (DFS for all patients was 12 months (DFS probability (pDFS = 49.3%; 95% CI, -11.1/+10.1. Median DFS in HER-2 groups was 8 (pDFS 37.5%; 95% CI,-28.8/+29.9, 24 (pDFS 46.1%; 95% CI,-19.5/+17.5, 20 (pDFS 46.4%; 95% CI,-18.8/+16.9 and 10 months (pDFS 47.6%; 95% CI,-21.9/+19.1 respectively in HER-2 status 0,1+,2+,3+. Log-Rank test is not statistically significant (p = 0,39. Conclusions: This study showed that HER-2 expression does not represent a prognostic mark- er of recurrence/progression of disease in high-grade T1 bladder cancer.

Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

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Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan); Ozaki, Norio [Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Noda, Yukihiro, E-mail: ynoda@meijo-u.ac.jp [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan)

2016-09-01

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation

Intensity-modulated arc therapy with cisplatin as neo-adjuvant treatment for primary irresectable cervical cancer. Toxicity, tumour response and outcome

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Vandecasteele, K.; Eijkeren, M. van; Meerleer, G. de [Ghent University Hospital (Belgium). Dept. of Radiotherapy; Makar, A.; Broecke, R. van den; Tummers, P. [Ghent University Hospital (Belgium). Dept. of Gynecology; Delrue, L. [Ghent University Hospital (Belgium). Dept. of Radiology; Denys, H. [Ghent University Hospital (Belgium). Dept. of Medical Oncology; Lambein, K. [Ghent University Hospital (Belgium). Dept. of Pathology; Lambert, B. [Ghent University Hospital (Belgium). Dept. of Nuclear Medicine

2012-07-15

Purpose: The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy {+-} cisplatin (IMAT {+-} C) followed by hysterectomy for locally advanced cervical cancer. Patients and methods: A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT {+-} C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated. Results: All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%. Conclusion: Surgery after IMAT {+-} C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising. (orig.)

Modelling the impact of toxic and disturbance stress on white-tailed eagle (Haliaeetus albicilla) populations.

Science.gov (United States)

Korsman, John C; Schipper, Aafke M; Lenders, H J Rob; Foppen, Ruud P B; Hendriks, A Jan

2012-01-01

Several studies have related breeding success and survival of sea eagles to toxic or non-toxic stress separately. In the present investigation, we analysed single and combined impacts of both toxic and disturbance stress on populations of white-tailed eagle (Haliaeetus albicilla), using an analytical single-species model. Chemical and eco(toxico)logical data reported from laboratory and field studies were used to parameterise and validate the model. The model was applied to assess the impact of ∑PCB, DDE and disturbance stress on the white-tailed eagle population in The Netherlands. Disturbance stress was incorporated through a 1.6% reduction in survival and a 10-50% reduction in reproduction. ∑PCB contamination from 1950 up to 1987 was found to be too high to allow the return of white-tailed eagle as a breeding species in that period. ∑PCB and population trends simulated for 2006-2050 suggest that future population growth is still reduced. Disturbance stress resulted in a reduced population development. The combination of both toxic and disturbance stress varied from a slower population development to a catastrophical reduction in population size, where the main cause was attributed to the reduction in reproduction of 50%. Application of the model was restricted by the current lack of quantitative dose-response relationships between non-toxic stress and survival and reproduction. Nevertheless, the model provides a first step towards integrating and quantifying the impacts of multiple stressors on white-tailed eagle populations.

Retrospective study of adjuvant icotinib in postoperative lung cancer patients harboring epidermal growth factor receptor mutations.

Science.gov (United States)

Yao, Shuyang; Zhi, Xiuyi; Wang, Ruotian; Qian, Kun; Hu, Mu; Zhang, Yi

2016-09-01

Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR-mutated NSCLC patients undergoing resection of stage IB-IIIA. Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy. Survival factors were evaluated by univariate and Cox regression analysis. The median follow-up time was 30 months (range 24-41). At the data cut-off, five patients (25%) had recurrence or metastasis and one patient had died of the disease. The two-year disease-free survival (DFS) rate was 85%. No recurrence occurred in the high-risk stage IB subgroup during the follow-up period. In univariate analysis, the micropapillary pattern had a statistically significant effect on DFS ( P = 0.040). Multivariate logistic regression analysis showed that there was no independent predictor. Drug related adverse events (AEs) occurred in nine patients (45.0%). The most common AEs were skin-related events and diarrhea, but were relatively mild. No grade 3 AEs or occurrences of intolerable toxicity were observed. Icotinib as adjuvant therapy is effective in patients harboring EGFR mutations after complete resection, with an acceptable AE profile. Further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Application of rotifer Brachionus plicatilis in detecting the toxicity of harmful algae

Science.gov (United States)

Yan, Tian; Wang, Yunfeng; Wang, Liping; Chen, Yang; Han, Gang; Zhou, Mingjiang

2009-05-01

The toxicity of seven major HAB (harmful algal bloom) species/strains, Prorocentrum donghaiense, Phaeocystis globosa, Prorocentrum micans, Alexandrium tamarense (AT-6, non-PSP producer), Alexandrium lusitanicum, Alexandrum tamarense (ATHK) and Heterosigma akashiwo were studied against rotifer Brachionus plicatilis under laboratory conditions. The results show that P. donghaiense, P. globosa, P. micans, A. tamarense (AT-6), or A. lusitanicum could maintain the individual survival and reproduction, as well as the population increase of the rotifer, but the individual reproduction would decrease when exposed to these five algae at higher densities for nine days; H. akashiwo could decrease the individual survival and reproduction, as well as population increase of the rotifer, which is similar to that of the starvation group, indicating that starvation might be its one lethal factor except for the algal toxins; A. tamarense (ATHK) has strong lethal effect on the rotifer with 48h LC50 at 800 cells/mL. The experiment on ingestion ability indicated by gut pigment change shows that P. donghaiense, P. globosa, P. micans, A. tamarense (AT-6) and A. lusitanicum can be taken by the rotifers as food, but A. tamarense (ATHK) or H. akashiwo can be ingested by the rotifers. The results indicate that all the indexes of individual survival and reproduction, population increase, gut pigment change of the rotifers are good and convenient to be used to reflect the toxicities of HAB species. Therefore, rotifer is suggested as one of the toxicity testing organisms in detecting the toxicity of harmful algae.

A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study

International Nuclear Information System (INIS)

Poulsen, Michael G.; Denham, James W.; Peters, Lester J.; Lamb, David S.; Spry, Nigel A.; Hindley, Andrew; Krawitz, Hedley; Hamilton, Chris; Keller, Jacqui; Tripcony, Lee; Walker, Quenten

2001-01-01

Purpose: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. Patients and methods: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Results: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P=0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P=0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P=0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P<0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P<0.05), except for the mucous membrane where late effects were similar in both arms. Conclusions: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm

Toxicity of copper to the collembolan Folsomia fimetaria in relation to the age of soil contamination.

NARCIS (Netherlands)

Bruus Pedersen, M.; van Gestel, C.A.M.

2001-01-01

The toxicity of copper to the collembolan Folsomia fimetaria L. was studied in soil incubated with copper sulfate for different periods before the introduction of collembolans, to assess the effect of aging of contamination on the toxicity of copper. Adult survival, reproduction, and juvenile size

Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

Energy Technology Data Exchange (ETDEWEB)

Ordonez, R.; Federico, M. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Valenciano, A. [Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Bordon, E. [Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Rodriguez-Gallego, C. [Hospital Universitario de Gran Canaria Dr. Negrin, Immunology Department, Las Palmas de Gran Canaria (Spain)

2014-02-15

A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

International Nuclear Information System (INIS)

Ordonez, R.; Federico, M.; Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C.; Valenciano, A.; Bordon, E.; Rodriguez-Gallego, C.

2014-01-01

A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

Prognostic significance of standardized uptake value and metabolic tumour volume on {sup 18}F-FDG PET/CT in oropharyngeal squamous cell carcinoma

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Kim, Ji Won; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Centre, Seoul (Korea, Republic of); Oh, Jungsu S.; Kim, Jae Seung [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Centre, Seoul (Korea, Republic of); Kim, Sang Yoon [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Centre, Seoul (Korea, Republic of); Biomedical Research Institute, Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2015-08-15

Standardized uptake value (SUV) and metabolic tumour volume (MTV) measured by {sup 18}F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers. However, their prognostic significance in oropharyngeal squamous cell carcinoma (OPSCC) has been investigated in only a few studies and with small cohorts. In the present study we evaluated the ability of SUV, MTV, and total lesion glycolysis (TLG) measured on pretreatment {sup 18}F-FDG PET/CT to predict recurrence and survival outcomes in OPSCC. The study included 221 patients with OPSCC who underwent pretreatment {sup 18}F-FDG PET/CT imaging and received definitive treatment at our tertiary referral centre. The PET imaging parameters SUV{sub max}, SUV{sub peak}, MTV and TLG were measured in primary tumours with focal {sup 18}F-FDG uptake. Clinical and imaging variables significantly associated with overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate analyses using the Cox proportional hazards model. Overall 5-year OS and DFS rates were 72.0 % and 79.5 %, respectively, during a median follow-up of 61 months (range 18 - 122 months). The cut-off values of tumour SUV{sub max}, SUV{sub peak}, MTV and TLG for prediction of DFS were 7.55, 6.80, 11.06 mL and 78.56 g, respectively. Univariate analyses showed that age >60 years, advanced tumour stage, and high tumour SUV{sub max}, SUV{sub peak}, MTV and TLG were significantly associated with decreased OS and DFS (P < 0.05 each). Age, tumour SUV{sub max} and MTV remained independent variables for OS and DFS (P < 0.05 each) in the multivariate analyses. SUV{sub max} and MTV measured on pretreatment {sup 18}F-FDG PET/CT may be useful in predicting the clinical outcomes in OPSCC patients. This study investigated the clinical prognostic value of imaging parameters from pretreatment {sup 18}F-FDG PET/CT in 221 patients who underwent definitive treatment for oropharyngeal squamous cell carcinoma. High maximum standardized

C-reactive protein as predictor of recurrence in patients with rectal cancer undergoing chemoradiotherapy followed by surgery.

Science.gov (United States)

Toiyama, Yuji; Inoue, Yasuhiro; Saigusa, Susumu; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

2013-11-01

The clinical significance of the systemic inflammatory response (SIR) in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy (CRT), to the best of our knowledge, has not been thus far investigated. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and C-Reactive protein (CRP) levels for 84 patients with rectal cancer undergoing CRT were available as indicators of SIR status. The impact of SIR status on the prognosis of these patients was assessed. Elevated NLR, CRP, carcinoembryonic antigen (CEA) and pathological TNM stage III [ypN(+)] were identified as significant prognostic factors for poor overall survival (OS), with CRP and ypN(+) being validated as independent predictors of OS. Elevated CRP and CEA levels were significant predictive factors for poor disease-free survival (DFS), and an elevated CRP level was identified as the only independent predictive factor for DFS. In addition, an elevated CRP level predicted for poorer OS and DFS in patients with pathological TNM stage I-II [ypN(-)]. CRP is a promising predictor of recurrence and prognosis in patients with rectal cancer treated by CRT.

Multimodality therapy in advanced head and neck cancer: Response and toxicity

International Nuclear Information System (INIS)

Chang, H.; Leone, L.; Tefft, M.; Nigri, P.T.

1987-01-01

This study utilizes preoperative XRT with DDP, followed by radical surgery (group I) or radical dose of XRT with DDP (group II) and adjuvant chemotherapy with 5-FU infusion and DDP at 4-week intervals, six cycles. The authors report the response and toxicity in 37 patients (eight SIII, 28 SIV). Complete tumor clearance (CTC) was 90% (33 of 37). In group I, eight of 17 (47%) showed no tumor on the surgical specimen; one of eight recurred in 16 months. Nine with residual tumor achieved CTC with surgery; two recurred (5, 8 months). Nine of 17 are alive with no evidence of disease (NED) (median survival, 13 months); five died without disease. In group II, 16 of 20 (80%) had CTC (eight negative biopsy, eight clinical CR); eight of 16 recurred. Median time to recur was 5 months (3 - 16 months). Four PR died within 6 months. Eight had NED with a median survival of 25 months (18 - 33 months), one died with NED, and four PR and seven recurrent patients died with disease. Actuarial survival between group I and group II shows no significant difference so far. Toxicity was not excessive. This treatment schedule produced excellent tumor clearance rate. Survival information is very preliminary; longer follow-up is necessary

Limb sparing approach: Adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma

International Nuclear Information System (INIS)

Merimsky, Ofer; Soyfer, Vjacheslav; Kovner, Felix; Bickels, Jacob; Issakov, Josephine; Flusser, Gideon; Meller, Isaac; Ofer, Oded; Kollender, Yehuda

2005-01-01

Background: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). Patients and methods: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. Results: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. Conclusions: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory

Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

Energy Technology Data Exchange (ETDEWEB)

Nowell, Lisa H., E-mail: lhnowell@usgs.gov [U.S. Geological Survey, California Water Science Center, Placer Hall, 6000 J Street, Sacramento, CA 95819 (United States); Norman, Julia E., E-mail: jnorman@usgs.gov [U.S. Geological Survey, Oregon Water Science Center, 2130 SW 5" t" h Avenue, Portland, OR 97201 (United States); Ingersoll, Christopher G., E-mail: cingersoll@usgs.gov [U.S. Geological Survey, Columbia Environmental Research Center, 4200 New Haven Road, Columbia, MO 65021 (United States); Moran, Patrick W., E-mail: pwmoran@usgs.gov [U.S. Geological Survey, Washington Water Science Center, 934 Broadway, Suite 300, Tacoma, WA 98402 (United States)

2016-04-15

Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical/chemical characteristics

Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

International Nuclear Information System (INIS)

Nowell, Lisa H.; Norman, Julia E.; Ingersoll, Christopher G.; Moran, Patrick W.

2016-01-01

Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical/chemical characteristics

Toxicity of common ions to marine organisms

International Nuclear Information System (INIS)

Pillard, D.A.; DuFresne, D.L.; Evans, J.

1995-01-01

Produced waters from oil and gas drilling operations are typically very saline, and these may cause acute toxicity to marine organisms due to osmotic imbalances as well as to an excess or deficiency of specific common ions. In order to better understand the relationship between toxicity and ion concentration, laboratory toxicity tests were conducted using mysid shrimp (Mysidopsis bahia), sheepshead minnow (Cyprinodon variegatus), and inland silverside (Menidia beryllina). For each species the ionic concentration of standard laboratory water was proportionally increased or decreased to produce test solutions with a range of salinities. Organisms were exposed for 48 hours. Individual ions (sodium, potassium, calcium, magnetsium, strontium, chloride, bromide, sulfate, bicarbonate, and borate) were also manipulated to examine individual ion toxicity. The three test species differ in their tolerance of salinity. Mysid shrimp show a marked decrease in survival at salinities less than approximately 5 ppt. Both fish species tolerated low salinity water, however, silversides were less tolerant of saline waters (salinity greater than 40 ppt). There were also significant differences in the responses of the organisms to different ions. The results show that the salinity of the test solution may play an important role in the responses of the organisms to the produced water effluent. Predictable toxicity/ion relationships developed in this study can be used to estimate whether toxicity in a produced water is a result of common ions, salinity, or some other unknown toxicant

Magnetic resonance imaging-detected extramural venous invasion in rectal cancer before and after preoperative chemoradiotherapy. Diagnostic performance and prognostic significance

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun Sun [Chung-Ang University Hospital, Department of Radiology, Seoul (Korea, Republic of); Chung-Ang University, College of Medicine and Graduate School of Medicine, Seoul (Korea, Republic of); National Cancer Centre, Department of Radiology, Goyang-si, Gyeonggi-do (Korea, Republic of); Kim, Min Ju; Hur, Bo Yun [National Cancer Centre, Department of Radiology, Goyang-si, Gyeonggi-do (Korea, Republic of); Park, Sung Chan; Hyun, Jong Hee; Chang, Hee Jin; Baek, Ji Yeon; Kim, Dae Yong; Oh, Jae Hwan [National Cancer Centre, Centre for Colorectal Cancer, Goyang, Gyeonggi-do (Korea, Republic of); Kim, Sun Young [National Cancer Centre, Centre for Colorectal Cancer, Goyang, Gyeonggi-do (Korea, Republic of); University of Ulsan College of Medicine, Department of Oncology, Asan Medical Centre, Seoul (Korea, Republic of)

2018-02-15

We evaluated the diagnostic performance of magnetic resonance imaging (MRI) in terms of identifying extramural venous invasion (EMVI) in rectal cancer patients with preoperative chemoradiotherapy (CRT) and its prognostic significance. During 2008-2010, 200 patients underwent surgery following preoperative CRT for rectal cancer. Two radiologists independently reviewed all pre- and post-CRT MRI retrospectively. We investigated diagnostic performance of pre-CRT MR-EMVI (MR-EMVI) and post-CRT MR-EMVI (yMR-EMVI), based on pathological EMVI as the standard of reference. We assessed correlation between MRI findings and patients' prognosis, such as disease-free survival (DFS) and overall survival (OS). Additionally, subgroup analysis in MR- or yMR-EMVI-positive patients was performed to confirm the significance of the severity of EMVI in MRI on patient's prognosis. The sensitivity and specificity of yMR-EMVI were 76.19% and 79.75% (area under the curve: 0.830), respectively. In univariate analysis, yMR-EMVI was the only significant MRI factor in DFS (P = 0.027). The mean DFS for yMR-EMVI (+) patients was significantly less than for yMR-EMVI (-) patients: 57.56 months versus 72.46 months. yMR-EMVI demonstrated good diagnostic performance. yMR-EMVI was the only significant EMVI-related MRI factor that correlated with patients' DFS in univariate analysis; however, it was not significant in multivariate analysis. (orig.)

High Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Breast Cancer: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Miao Zhang

2017-01-01

Full Text Available Background. We aimed to evaluate the correlation of platelet-to-lymphocyte ratio (PLR with prognosis and clinicopathological characteristics of breast cancer. Methods. The PubMed and Embase databases were searched. Hazard ratio (HR with 95% confidence interval (CI was used to summarize disease-free survival (DFS and overall survival (OS. Odds ratio (OR was used to summarize tumor clinicopathological characteristics. Results. High PLR was associated with poor DFS and OS (DFS: HR = 1.47, 95% CI = 1.16–1.85, and Tau2 = 0.070; OS: HR = 1.88, 95% CI = 1.27–2.80, and Tau2 = 0.192. A Galbraith plot indicated that the studies by Allan et al. and Cihan et al. contributed the heterogeneity of DFS and OS, respectively. There were significant differences in the incidence of high PLR between stage II–IV and stage I groups (OR = 1.86, 95% CI = 1.20–2.90, and Tau2 < 0.001, between lymph node-positive and lymph node-negative groups (OR = 1.52, 95% CI = 1.22–1.91, and Tau2 =0.014, and between metastasis-positive and metastasis-negative groups (OR = 4.24, 95% CI = 2.73–6.59, and Tau2 < 0.001. Conclusions. Our results indicated that PLR was associated with poor prognosis of breast cancer and adequately predicted clinicopathological characteristics.

Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials

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M. Kripp

2015-01-01

Full Text Available Purpose. The addition of cetuximab to radiochemotherapy (RCT failed to improve complete response rates in locally advanced rectal cancer (LARC. We report the long-term results in patients treated within two sequential clinical trials. Methods. Patients receiving neoadjuvant RCT using capecitabine and irinotecan (CapIri within a phase I/II trial or CapIri + cetuximab within a phase II trial were evaluated for analysis of disease-free survival (DFS and overall survival (OS. KRAS exon 2 mutational status had been analyzed in patients receiving cetuximab. Results. 37 patients from the CapIri trial and 49 patients from the CapIri-cetuximab treatment group were evaluable. Median follow-up time was 75.2 months. The 5-year DFS rate was 82% (CapIri and 79% (CapIri-cetuximab (P=0.62. The median OS was 127.4 months. 5-year OS was 73% for both groups (CapIri and CapIri-cetuximab (P=0.61. No significant difference in DFS (P=0.86 or OS (P=0.39 was noticed between patients receiving CapIri and those receiving CapIri-cetuximab with KRAS wild-type tumors. Conclusions. As the addition of cetuximab did not improve neither DFS nor OS it should not play a role in the perioperative treatment of patients with LARC, not even of patients with (KRAS WT tumors.

Urethra-Sparing, Intraoperative, Real-Time Planned, Permanent-Seed Prostate Brachytherapy: Toxicity Analysis

Energy Technology Data Exchange (ETDEWEB)

Zilli, Thomas [Department of Radiation Oncology, Centre hospitalier de l' Universite de Montreal-Hopital Notre-Dame, Montreal, QC (Canada); Taussky, Daniel, E-mail: daniel.taussky.chum@ssss.gouv.qc.ca [Department of Radiation Oncology, Centre hospitalier de l' Universite de Montreal-Hopital Notre-Dame, Montreal, QC (Canada); Donath, David; Le, Hoa Phong; Larouche, Renee-Xaviere; Beliveau-Nadeau, Dominique; Hervieux, Yannick; Delouya, Guila [Department of Radiation Oncology, Centre hospitalier de l' Universite de Montreal-Hopital Notre-Dame, Montreal, QC (Canada)

2011-11-15

Purpose: To report the toxicity outcome in patients with localized prostate cancer undergoing {sup 125}I permanent-seed brachytherapy (BT) according to a urethra-sparing, intraoperative (IO), real-time planned conformal technique. Methods and Materials: Data were analyzed on 250 patients treated consecutively for low- or intermediate-risk prostate cancer between 2005 and 2009. The planned goal was urethral V{sub 150} = 0. Acute and late genitourinary (GU), gastrointestinal (GI), and erectile toxicities were scored with the International Prostate Symptom Score (IPSS) questionnaire and Common Terminology Criteria for Adverse Events (version 3.0). Median follow-up time for patients with at least 2 years of follow-up (n = 130) was 34.4 months (range, 24-56.9 months). Results: Mean IO urethra V{sub 150} was 0.018% {+-} 0.08%. Mean prostate D{sub 90} and V{sub 100} on day-30 computed tomography scan were 158.0 {+-} 27.0 Gy and 92.1% {+-} 7.2%, respectively. Mean IPSS peak was 9.5 {+-} 6.3 1 month after BT (mean difference from baseline IPSS, 5.3). No acute GI toxicity was observed in 86.8% of patients. The 3-year probability of Grade {>=}2 late GU toxicity-free survival was 77.4% {+-} 4.0%, with Grade 3 late GU toxicity encountered in only 3 patients. Three-year Grade 1 late GI toxicity-free survival was 86.1% {+-} 3.2%. No patient presented Grade {>=}2 late GI toxicity. Of patients with normal sexual status at baseline, 20.7% manifested Grade {>=}2 erectile dysfunction after BT. On multivariate analysis, elevated baseline IPSS (p = 0.016) and high-activity sources (median 0.61 mCi) (p = 0.033) predicted increased Grade {>=}2 late GU toxicity. Conclusions: Urethra-sparing IO BT results in low acute and late GU toxicity compared with the literature. High seed activity and elevated IPSS at baseline increased long-term GU toxicity.

Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

Science.gov (United States)

Nowell, Lisa H.; Norman, Julia E.; Ingersoll, Christopher G.; Moran, Patrick W.

2016-01-01

Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical

Toxicity of stormwater treatment pond sediments to Hyallela azteca (Amphipoda)

Science.gov (United States)

Karouna-Renier, N.K.; Sparling, D.W.

1997-01-01

Stormwater wetlands are created to contain runoff from human developments and are designed to retain contaminants such as heavy metals, petroleum hydrocarbons, silt, pesticides, and nutrients before the runoff enter natural waterways. Because of this design, stormwater wetlands have a potential of becoming toxic sinks to organisms utilizing the wetlands for habitat. We conducted a 10-day sediment bioassay on Hyallela azteca as part of a larger study on the possible hazards of stormwater wetlands to aquatic invertebrates. Water and sediments from 10 wetlands separated into reference, residential, commercial, and highway land uses were used. No differences in survival were observed among land use categories, possibly because the ratio of acid volatile sulfides/simultaneously extractable metals (AVS/SEM) was > 1.0 for all of the ponds tested; values > 1 in this ratio are indications that toxic metals may not be bioavailable. Survival and growth rates correlated positively with AVS.

Local superficial radiotherapy in the management of minimal stage IA mycosis fungoides

International Nuclear Information System (INIS)

Wilson, Lynn D.; Kacinski, Barry M.; Jones, Glenn W.

1997-01-01

Purpose/Objective: To evaluate the impact of local superficial radiotherapy (LSR) with respect to local control, survival, and toxicity for patients with minimal stage IA Mycosis Fungoides. Materials and Methods: Between 1954 and 1996 a total of 21 patients were identified as receiving curative local superficial radiation for minimal stage IA Mycosis Fungoides. All patients had pathologic documentation at diagnosis and at the time of suspected recurrences. No patient received prior radiation. Ten patients were treated with 100-280Kv (AL), and 11 with 4-12Mev electrons. Nine patients had failed prior therapies (Steroids:4; PUVA:3; BCNU:1; UVB:1), and 6 received adjuvant therapy after completion of LSR (PUVA:5, Steroids:1). Minimum follow-up was 1 year. Results: The median follow-up was 36 months (13-246), and the median age when commencing LSR was 55 years (27-73). All patients were Caucasian and 11 were male A total of 32 lesions were identified in 21 patients; 13 patients had unilesional disease, 5 patients had 2 lesions, and 3 had 3 lesions. A total of 33 fields were treated with a median treatment surface area of 107cm 2 (11-785). The median surface dose was 20 Gy (6-40), with 17 patients receiving a dose ≥ 20 Gy. The median fraction number was 5 for all fields, but was 10 for the fields receiving 20-40 Gy. The complete response rate was 97%, and all patients were alive at last evaluation. All failures were cutaneous. One patient had persistent disease (treated with 6 Gy), and 3 failed locally at 52 months (8 Gy), 16 months (20 Gy), and 4 months (20 Gy) respectively. None of these patients received adjuvant therapy. Two patients failed in distant skin sites and were salvaged. The actuarial DFS for the entire group at 5 and 10 years was 75 and 64% respectively, with local control of 75% at both time intervals. For the 13 patients with unilesional disease, the DFS was 85% at 10 years. For those treated with doses ≥ 20 Gy, the DFS was 91% as was local control

Prognostic value and staging classification of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

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Ling-Long Tang

Full Text Available BACKGROUND: The development of intensity-modulated radiotherapy (IMRT has revolutionized the management of nasopharyngeal carcinoma (NPC. The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN metastasis in NPC in the IMRT era. MATERIAL AND METHODS: We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492 of the patients with stage III or IV disease. RESULTS: The incidence of RLN metastasis was 64.2% (481/749. Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001 and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001 rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively, but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively. Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020, and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively. In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994. CONCLUSIONS: In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN

Carcinoma microsatellite instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for stage II rectal cancer.

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Yang, Liu; Sun, Yan; Huang, Xin-En; Yu, Dong-Sheng; Zhou, Jian-Nong; Zhou, Xin; Li, Dong-Zheng; Guan, Xin

2015-01-01

Rectal cancers with high microsatellite-instable have clinical and pathological features that differentiate them from microsatellite-stable or low- frequency carcinomas, which was studied rarely in stage II rectal cancer, promoting the present investigation of the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II rectal cancer. Data of 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2008 to 2012 were retrospectively collected. All patients experienced a total mesorectal excision (TME) operation. Survival analysis were analyzed using the Cox regression method. Five-year rate of disease-free survival (DFS) was noted in 390 (84.8%) of 460 patients with stage II rectal cancer. Of 460 tissue specimens, 97 (21.1%) exhibited high-frequency microsatellite instability. Median age of the patients was 65 (50-71) and 185 (40.2%) were male. After univariate and multivariate analysis, microsatellite instability (p= 0.001), female sex (pchemotherapy (pchemotherapy, those cancers displaying high-frequency microsatellite instability had a better 5-year rate of DFS than tumors exhibiting microsatellite stability or low-frequency instability (HR, 13.61 [95% CI, 1.88 to 99.28]; p= 0.010), while in 259 patients who received adjuvant chemotherapy, there was no DFS difference between the two groups (p= 0.145). Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; pchemotherapy and gender. Fluorouracil-based adjuvant chemotherapy benefits patients of stage II rectal cancer with microsatellite-stable or low microsatellite-instable, but not those with high microsatellite- instable. Additionally, free of adjuvant chemotherapy, carcinomas with high microsatellite

Selenium toxicity to honey bee (Apis mellifera L. pollinators: effects on behaviors and survival.

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Kristen R Hladun

Full Text Available We know very little about how soil-borne pollutants such as selenium (Se can impact pollinators, even though Se has contaminated soils and plants in areas where insect pollination can be critical to the functioning of both agricultural and natural ecosystems. Se can be biotransferred throughout the food web, but few studies have examined its effects on the insects that feed on Se-accumulating plants, particularly pollinators. In laboratory bioassays, we used proboscis extension reflex (PER and taste perception to determine if the presence of Se affected the gustatory response of honey bee (Apis mellifera L., Hymenoptera: Apidae foragers. Antennae and proboscises were stimulated with both organic (selenomethionine and inorganic (selenate forms of Se that commonly occur in Se-accumulating plants. Methionine was also tested. Each compound was dissolved in 1 M sucrose at 5 concentrations, with sucrose alone as a control. Antennal stimulation with selenomethionine and methionine reduced PER at higher concentrations. Selenate did not reduce gustatory behaviors. Two hours after being fed the treatments, bees were tested for sucrose response threshold. Bees fed selenate responded less to sucrose stimulation. Mortality was higher in bees chronically dosed with selenate compared with a single dose. Selenomethionine did not increase mortality except at the highest concentration. Methionine did not significantly impact survival. Our study has shown that bees fed selenate were less responsive to sucrose, which may lead to a reduction in incoming floral resources needed to support coworkers and larvae in the field. If honey bees forage on nectar containing Se (particularly selenate, reductions in population numbers may occur due to direct toxicity. Given that honey bees are willing to consume food resources containing Se and may not avoid Se compounds in the plant tissues on which they are foraging, they may suffer similar adverse effects as seen in other

Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

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Lo, Andrea C.; Morris, W. James; Lapointe, Vincent; Hamm, Jeremy; Keyes, Mira; Pickles, Tom; McKenzie, Michael; Spadinger, Ingrid

2014-01-01

Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72 months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P 0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a 1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure

Clinical outcomes for T1-2N0-1 oral tongue cancer patients underwent surgery with and without postoperative radiotherapy

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Choi Eun

2010-05-01

Full Text Available Abstract Background The aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T1-2N0-1 oral tongue squamous cell carcinoma (OSCC and to evaluate survival and prognostic factors. Methods Retrospective analysis of 86 patients with T1-2N0-1 OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3% received postoperative radiotherapy (PORT. Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed. Results The median follow-up was 45 months. The five-year overall survival (OS and disease-free survival (DFS rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth. In the risk group, there was no local failure in patients with postoperative radiotherapy. Conclusions In T1-2N0-1 OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features.

Short-term toxicity of polystryrene microplastics on mysid shrimps Neomysis japonica

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Wang, Mingxin; Wang, Xiao; Luo, Xianxiang; Zheng, Hao

2017-04-01

Plastic debris especially microplastics (MPs) have become a global concern for the aggravating pollution in the oceans. In this study, the physico-chemical properties of fluorescently labeled polystyrene (PS) beads and the effects of PS-MPs on the survival of mysid shrimps (Neomysis japonica) were investigated. PS-MPs were identified to have spherical shape, uniform size and stable green fluorescence. The results showed that PS beads had little effects on the mortality of shrimps under a short-term (72 h) exposure with concentrations of 50 μg L-1 and 500 μg L-1. However, PS-MPs had severe short-term toxicity on the survival of mysid shrimps, resulting in 30% mortality especially in a 72 h exposure with the higher concentration of 1000 μg L-1. These findings provide new insights into the toxic effects of MPs on marine invertebrates.

Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.

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Wang, Tong; Ma, Yuanyuan; Wang, Liang; Liu, Hong; Chen, Meixuan; Niu, Ruifang

2015-08-01

The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup.

Monitoring the effectiveness of remediation techniques using sediment toxicity tests with the amphipod Eohaustorius estuarius

International Nuclear Information System (INIS)

Doe, K.G.; Jackman, P.M.; Lee, K.

2002-01-01

The results of a controlled oil release experiment of weathered crude oil was presented. The released oil was applied to a tidal saltwater marsh at Conrod's Beach, Nova Scotia, Canada. The study included 3 replicate blocks which included 2 unoiled treatments and 4 oiled treatments for each block. One unoiled site had no treatment, the second unoiled site had nutrient addition to examine the effect of nutrients. The oiled treatments included natural attenuation, nutrient addition, nutrient addition with plants, and nutrient addition with a garden aerator to introduce oxygen. A standard lab procedure was used to analyze the sediments to determine the effectiveness of the technique as well as the toxic effects on the survival of the amphipod Eohaustorius estuarius. Test results indicated that the unoiled sites were non-toxic, with a slight decrease in survival in the treatment with nutrient addition. All the oiled sites were very toxic at first, but toxicity decreased gradually with time. Treatment with nutrient addition with a garden aerator proved to be the most complete and fastest detoxification method. 8 refs., 4 tabs., 2 figs

Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

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Sanguedolce, Francesca; Cormio, Antonella; Massenio, Paolo; Pedicillo, Maria C; Cagiano, Simona; Fortunato, Francesca; Calò, Beppe; Di Fino, Giuseppe; Carrieri, Giuseppe; Bufo, Pantaleo; Cormio, Luigi

2018-04-01

The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

Lithium Improves Survival of PC12 Pheochromocytoma Cells in High-Density Cultures and after Exposure to Toxic Compounds

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Cinzia Fabrizi

2014-01-01

Full Text Available Autophagy is an evolutionary conserved mechanism that allows for the degradation of long-lived proteins and entire organelles which are driven to lysosomes for digestion. Different kinds of stressful conditions such as starvation are able to induce autophagy. Lithium and rapamycin are potent autophagy inducers with different molecular targets. Lithium stimulates autophagy by decreasing the intracellular myo-inositol-1,4,5-triphosphate levels, while rapamycin acts through the inhibition of the mammalian target of rapamycin (mTOR. The correlation between autophagy and cell death is still a matter of debate especially in transformed cells. In fact, the execution of autophagy can protect cells from death by promptly removing damaged organelles such as mitochondria. Nevertheless, an excessive use of the autophagic machinery can drive cells to death via a sort of self-cannibalism. Our data show that lithium (used within its therapeutic window stimulates the overgrowth of the rat Pheochromocytoma cell line PC12. Besides, lithium and rapamycin protect PC12 cells from toxic compounds such as thapsigargin and trimethyltin. Taken together these data indicate that pharmacological activation of autophagy allows for the survival of Pheochromocytoma cells in stressful conditions such as high-density cultures and exposure to toxins.

Concentration addition and independent action model: Which is better in predicting the toxicity for metal mixtures on zebrafish larvae.

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Gao, Yongfei; Feng, Jianfeng; Kang, Lili; Xu, Xin; Zhu, Lin

2018-01-01

The joint toxicity of chemical mixtures has emerged as a popular topic, particularly on the additive and potential synergistic actions of environmental mixtures. We investigated the 24h toxicity of Cu-Zn, Cu-Cd, and Cu-Pb and 96h toxicity of Cd-Pb binary mixtures on the survival of zebrafish larvae. Joint toxicity was predicted and compared using the concentration addition (CA) and independent action (IA) models with different assumptions in the toxic action mode in toxicodynamic processes through single and binary metal mixture tests. Results showed that the CA and IA models presented varying predictive abilities for different metal combinations. For the Cu-Cd and Cd-Pb mixtures, the CA model simulated the observed survival rates better than the IA model. By contrast, the IA model simulated the observed survival rates better than the CA model for the Cu-Zn and Cu-Pb mixtures. These findings revealed that the toxic action mode may depend on the combinations and concentrations of tested metal mixtures. Statistical analysis of the antagonistic or synergistic interactions indicated that synergistic interactions were observed for the Cu-Cd and Cu-Pb mixtures, non-interactions were observed for the Cd-Pb mixtures, and slight antagonistic interactions for the Cu-Zn mixtures. These results illustrated that the CA and IA models are consistent in specifying the interaction patterns of binary metal mixtures. Copyright © 2017 Elsevier B.V. All rights reserved.

Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates

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Malzoni, Carlos Eduardo

1996-01-01

The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author)

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.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

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Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer

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Hentschel, Maria [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Appold, Steffen; Baumann, Michael [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Schreiber, Andreas [Hospital Dresden-Friedrichstadt, Department of Radiotherapy, Dresden (Germany); Abolmaali, Nasreddin [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Institute and Polyclinic of Diagnostic Radiology, Dresden (Germany); Abramyuk, Andrij [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Doerr, Wolfgang [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Kotzerke, Joerg; Zoephel, Klaus [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany)

2011-07-15

Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV{sub max}), the average SUV (SUV{sub mean}) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV{sub max} of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT ({delta}SUV{sub max10/20} {>=} 50%) than for patients with {delta}SUV{sub max20} < 50% (2-year OS = 38%; p = 0.02; 2-year LRC 40%; p = 0.06). A pretreatment GTV PET below the median of 10.2 ml predicted a better 2-year OS (34% for GTV PET {>=} 10.2 ml vs 83% for GTV PET < 10.2 ml; p = 0.02). The decrease of SUV{sub max} from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV{sub max}, especially {delta}SUV{sub max10/20}, for an early estimation of therapy outcome. Confirmatory studies are warranted. (orig.)

Stereotactic radiotherapy of meningiomas. Symptomatology, acute and late toxicity

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Henzel, M.; Gross, M.W.; Failing, T.; Strassmann, G.; Engenhart-Cabillic, R. [Dept. of Radiation Oncology, Univ. of Gisssen (Germany); Dept. of Radiation Oncology, Marburg Univ. (Germany); Hamm, K.; Surber, G.; Kleinert, G. [Dept. of Stereotactic Neurosurgery and Radiosurgery, Helios Klinikum Erfurt (Germany)

2006-07-15

Background and purpose: stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity. Patients and methods: between 1997-2003, 224 patients were treated with SRT (n= 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system. Results: the median follow-up was 36 months (range, 12-100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III ) was rarely seen (2.5%). Clinically significant late morbidity (III -IV ) or new cranial nerve palsies did not occur. Conclusion: SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended. (orig.)

Impact of the Ki-67 labeling index and p53 expression status on disease-free survival in pT1 urothelial carcinoma of the bladder.

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Vetterlein, Malte W; Roschinski, Julia; Gild, Philipp; Marks, Phillip; Soave, Armin; Doh, Ousman; Isbarn, Hendrik; Höppner, Wolfgang; Wagner, Walter; Shariat, Shahrokh F; Brausi, Maurizio; Büscheck, Franziska; Sauter, Guido; Fisch, Margit; Rink, Michael

2017-12-01

The identification of protein biomarkers to guide treatment decisions regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer (NMIBC) has been of increasing interest. Evidence of the impact of tumor suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic outcomes in bladder cancer patients at highest risk of recurrence and progression is partially contradictory. We sought to mirror contemporary expression patterns of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer. Patients from four Northern German institutions with a primary diagnosis of pT1 bladder cancer between 2009 and 2016 and complete data regarding p53 or Ki-67 expression status were included for final analyses. Baseline patient characteristics (age, gender, age-adjusted Charlson comorbidity index) and tumor characteristics [diagnostic sequence, tumor focality, concomitant carcinoma in situ, 1973 World Health Organization (WHO) grading, lymphovascular invasion, adjuvant instillation therapy] were abstracted by retrospective chart review. Immunohistochemistry for detection of p53 and Ki-67 expression was performed according to standardized protocols. Microscopic analyses were performed by central pathologic review. First, we compared patients with positive vs. negative p53 expression and Ki-67 labeling index [>40% vs. ≤40%; cutoffs based on best discriminative ability in univariable Cox regression analysis with disease-free survival (DFS) as endpoint] with regard to baseline and tumor characteristics. Second, we evaluated the effect of biomarker positivity on DFS by plotting univariable Kaplan-Meier curves and performing uni- and multivariable Cox regression analyses. Of 102 patients with complete information on p53 status, 44 (43.1%) were p53 positive, and they more often harbored concomitant carcinoma in situ (50.0% vs. 27.6%; P=0.032) and 1973 WHO grade 3 (97.7% vs. 69.0%; P=0.001) compared to their p53 negative counterparts. Of 79

Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy.

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Mei, Lin; Ontiveros, Evelena P; Griffiths, Elizabeth A; Thompson, James E; Wang, Eunice S; Wetzler, Meir

2015-07-01

Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20-40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including l-asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

The prognostic significance of lymphovascular invasion in patients with resectable gastric cancer: a large retrospective study from Southern China

International Nuclear Information System (INIS)

Li, Peng; He, Hao-Qiang; Zhu, Chong-Mei; Ling, Yi-Hong; Hu, Wan-Ming; Zhang, Xin-Ke; Luo, Rong-Zhen; Yun, Jing-Ping; Xie, Dan; Li, Yuan-Fang; Cai, Mu-Yan

2015-01-01

The focus of this study was to assess the impact of lymphovascular invasion (LVI) on both the recurrence of cancer and the long-term survival of Chinese patients with resectable gastric cancer (GC). A retrospective analysis of the clinicopathological data for 1148 GC patients who had undergone gastrectomy with regional lymphadenectomy was performed. The primary objective was to assess the correlation between LVI and post-surgery outcomes for each patient. This was done by routine H & E staining for LVI on patients’ disease-free survival (DFS) and disease-specific survival (DSS). LVI was detected in 404 (35.2%) of the 1148 GC patients. The presence of LVI was significantly correlated with the level of CA19-9, the tumor size, the Lauren classification, tumor differentiation, gastric wall invasive depth, lymph node involvement, distant metastasis and an advanced TNM stage. There was a lower DFS and DSS in the patients with LVI as compared to the patients without LVI. A multivariate analysis also identified LVI as an independent prognostic factor of both DSS and DFS. The presence of LVI is a risk factor for the recurrence of cancer and an independent indicator of a poor outcome in GC patients following surgery. The LVI status should be taken into consideration when determining the best approach for the treatment of the individual

Year of treatment as independent predictor of relapse-free survival in patients with localized prostate cancer treated with definitive radiotherapy in the PSA era

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Kupelian, Patrick; Thames, Howard; Levy, Larry; Horwitz, Eric; Martinez, Alvaro; Michalski, Jeff; Pisansky, Thomas; Sandler, Howard; Shipley, William; Zelefsky, Michael; Zietman, Anthony; Kuban, Deborah

2005-01-01

Purpose: To study the use of the year of therapy as an independent predictor of outcomes, serving as a proxy for time-related changes in therapy and tumor factors in the treatment of prostate cancer. Accounting for these changes would facilitate the retrospective comparison of outcomes for patients treated in different periods. Methods and Materials: Nine institutions combined data on 4,537 patients with Stages T1 and T2 adenocarcinoma of the prostate who had a pretherapy prostate-specific antigen (PSA) level and biopsy Gleason score, and who had received ≥60 Gy external beam radiotherapy without neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. All patients were treated between 1986 and 1995. Two groups were defined: those treated before 1993 (Yr ≤92) vs. 1993 and after (Yr ≥93). Patients treated before 1993 had their follow-up truncated to make the follow-up time similar to that for patients treated in 1993 and after. Therefore, the median follow-up time was 6.0 years for both groups (Yr ≤92 and Yr ≥93). Two separate biochemical failure endpoints were used. Definition A consisted of the American Society for Therapeutic Radiology Oncology endpoint (three PSA rises backdated, local failure, distant failure, or hormonal therapy). Definition B consisted of PSA level greater than the current nadir plus two, local failure, distant failure, or hormonal therapy administered. Multivariate analyses for factors affecting PSA disease-free survival (PSA-DFS) rates using both endpoints were performed for all cases using the following variables: T stage (T1b, T1c, T2a vs. T2b, T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), radiation dose (continuous variable), and year of treatment (continuous variable). The year variable (defined as the current year minus 1960) ranged from 26 to 35. To evaluate the effect of radiation dose, the multivariate analyses were repeated with the 3,897 cases who had received

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

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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.

The Essential Role of Radiotherapy in the Treatment of Merkel Cell Carcinoma: A Study From the Rare Cancer Network

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Ghadjar, Pirus, E-mail: pirus.ghadjar@insel.ch [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern (Switzerland); Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Institute of Oncology (Netherlands); Poortmans, Philipp [Department of Radiation Oncology, Institute Verbeeten, Tilburg (Netherlands); Zaucha, Renata [Department of Oncology and Radiotherapy, Medical University, Gdansk (Poland); Krengli, Marco [Department of Radiotherapy, University Hospital Maggiore della Carita, Novara (Italy); Lagrange, Jean L. [Service de Radiotherapie, Hopital Henri-Mondor, Creteil (France); Oezsoy, Orhan [Department of Radiation Oncology, CHCVs-RSV, Sion (Switzerland); Nguyen, Tan D. [Department of Radiation Oncology, Institut Jean Godinot, Reims (France); Miralbell, Raymond [Department of Radiation Oncology, Hopitaux Universitaires de Geneve, Geneva (Switzerland); Baize, Adele [Department de Radio-Oncologie, Institut Jules Bordet, Bruxelles (Belgium); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Collen, Timothy [Department of Radiation Oncology, Kantonsspital St. Gallen (Switzerland); Scandolaro, Luciano [Radioterapia, Azienda Ospedale Sant' Anna, Como (Italy); Untereiner, Michel [Centre Francois Baclesse, Luxembourg (Luxembourg); Goldberg, Hadassah [Oncology Departement, Rambam Medical Center, Haifa (Israel); Pesce, Gianfranco A. [Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Opedale San Giovanni, Bellinzona (Switzerland); Anacak, Yavuz [Department of Radiation Oncology, EGE University, Izmir (Turkey); Friedrich, Esther E.; Aebersold, Daniel M. [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern (Switzerland); Beer, Karl T. [Radio Onkologiezentrum Biel (Switzerland)

2011-11-15

Purpose: To evaluate the role of postoperative radiotherapy (RT) in Merkel cell carcinoma (MCC). Methods and Materials: A retrospective multicenter study was performed in 180 patients with MCC treated between February 1988 and September 2009. Patients who had had surgery alone were compared with patients who received surgery and postoperative RT or radical RT. Local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were assessed together with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. Results: Seventy-nine patients were male and 101 patients were female, and the median age was 73 years old (range, 38-93 years). The majority of patients had localized disease (n = 146), and the remaining patients had regional lymph node metastasis (n = 34). Forty-nine patients underwent surgery for the primary tumor without postoperative RT to the primary site; the other 131 patients received surgery for the primary tumor, followed by postoperative RT (n = 118) or a biopsy of the primary tumor followed by radical RT (n = 13). Median follow-up was 5 years (range, 0.2-16.5 years). Patients in the RT group had improved LRFS (93% vs. 64%; p < 0.001), RRFS (76% vs. 27%; p < 0.001), DMFS (70% vs. 42%; p = 0.01), DFS (59% vs. 4%; p < 0.001), and CSS (65% vs. 49%; p = 0.03) rates compared to patients who underwent surgery for the primary tumor alone; LRFS, RRFS, DMFS, and DFS rates remained significant with multivariable Cox regression analysis. However OS was not significantly improved by postoperative RT (56% vs. 46%; p = 0.2). Conclusions: After multivariable analysis, postoperative RT was associated with improved outcome and seems to be an important component in the multimodality treatment of MCC.

Outcomes of surgically treated human papillomavirus-related oropharyngeal squamous cell carcinoma with N3 disease.

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Zenga, Joseph; Haughey, Bruce H; Jackson, Ryan S; Adkins, Douglas R; Aranake-Chrisinger, John; Bhatt, Neel; Gay, Hiram A; Kallogjeri, Dorina; Martin, Eliot J; Moore, Eric J; Paniello, Randal C; Rich, Jason T; Thorstad, Wade L; Nussenbaum, Brian

2017-09-01

To evaluate outcomes for patients with pathological N3 (pN3) neck disease from human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and determine variables predictive of survival. Retrospective case series with chart review. This study was conducted between 1998 and 2013 and included patients with HPV-related OPSCC treated with surgery with or without adjuvant therapy and who had pN3 nodal disease. The primary outcome was disease-specific survival (DSS). Secondary outcomes included overall survival (OS), disease-free survival (DFS), adverse events, and gastrostomy tube rates. Thirty-nine patients were included, of whom 36 (90%) underwent adjuvant therapy. Median follow-up was 39 months (range, 2-147 months). Mean age was 56 years, and 87% were male. Seventeen patients (44%) underwent selective neck dissection, whereas six (15%) underwent radical (n = 2) or extended radical (n = 4) neck dissection. Ninety-two percent had extracapsular extension. Five-year Kaplan-Meier estimated DSS, OS, and DFS were 89% (95% confidence interval [CI]: 79%-99%), 87% (95% CI: 75%-99%), and 84% (95% CI: 72%-96%), respectively. The disease recurrence rate was 10% (5% regional, 5% distant metastasis). Patients with less than 5 pathologically positive lymph nodes (P = .041) had improved DFS. Patients with HPV-related OPSCC and pN3 nodal disease treated with surgery and adjuvant therapy have very favorable long-term survival and regional control. Patients with five or more pathologically positive lymph nodes may be at higher risk for recurrence. 4. Laryngoscope, 127:2033-2037, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

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Pouliliou, Stamatia E.; Lialiaris, Theodoros S.; Dimitriou, Thespis; Giatromanolaki, Alexandra; Papazoglou, Dimitrios; Pappa, Aglaia; Pistevou, Kyriaki; Kalamida, Dimitra; Koukourakis, Michael I.

2015-01-01

Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2 [4h] ) and 24 hours (SF2 [24h] ) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2 (4h) was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio (30min) (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio (4h) /γH2AX-ratio (30min) ) showed a significant direct association with high toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with efficient DSB repair ability

Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

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Pouliliou, Stamatia E. [Department of Radiotherapy/Oncology, Radiobiology and Radiopathology Unit, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Lialiaris, Theodoros S. [Department of Medical Genetics, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Dimitriou, Thespis [Department of Anatomy, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Giatromanolaki, Alexandra [Department of Pathology, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Papazoglou, Dimitrios [Department of Internal Medicine, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Pappa, Aglaia [Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Pistevou, Kyriaki [Department of Radiotherapy/Oncology, Aristotle University of Thessalonica, Thessalonica (Greece); Kalamida, Dimitra [Department of Radiotherapy/Oncology, Radiobiology and Radiopathology Unit, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece); Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy/Oncology, Radiobiology and Radiopathology Unit, School of Health Sciences, Democritus University of Thrace, Alexandroupolis (Greece)

2015-07-01

Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2{sub [4h]}) and 24 hours (SF2{sub [24h]}) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2{sub (4h)} was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio{sub (30min)} (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio{sub (4h)}/γH2AX-ratio{sub (30min)}) showed a significant direct association with high toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with

Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck

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Yang H

2013-10-01

Full Text Available Hua Yang,* Li-Qiong Diao,* Mei Shi, Rui Ma, Jian-Hua Wang, Jian-Ping Li, Feng Xiao, Ying Xue, Man Xu, Bin ZhouDepartment of Radiotherapy Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China*These authors contributed equally to this workObjectives: Long-term locoregional control following intensity-modulated radiotherapy (IMRT for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN remains challenging. This study aimed to assess the efficacy and toxicity of IMRT with and without chemotherapy or surgery in locally advanced SCCHN.Materials and methods: Between January 2007 and January 2011, 61 patients with locally advanced SCCHN were treated with curative IMRT in the Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University; 28% underwent definitive IMRT and 72% postoperative IMRT, combined with simultaneous cisplatin-based chemotherapy in 58%. The mean doses of definitive and postoperative IMRT were 70.8 Gy (range, 66–74 Gy. Outcomes were analyzed using Kaplan–Meier curves. Acute and late toxicities were graded according to Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer radiation morbidity scoring criteria.Results: At a median follow-up of 35 months, 3-year local recurrence-free survival (LRFS, regional recurrence-free survival (RRFS, distant metastasis-free survival (DMFS, disease-free survival (DFS, and overall survival (OS were 83.8%, 86.1%, 82.4%, 53.2%, and 62%, respectively. Postoperative IMRT (n = 44, 72% had significantly higher LRFS/OS/DMFS than definitive IMRT (n = 17, 28%; P < 0.05. IMRT combined with chemotherapy (n = 35, 58% had significantly higher LRFS/OS/DMFS than IMRT alone (n = 26, 42%; P < 0.05. One year after radiotherapy, the incidence of xerostomia of grade 1, 2, or 3 was 13.1%, 19.7%, and 1.6%, respectively. No grade 4 acute or late toxicity was observed.Conclusion: IMRT combined with

Biological Mechanism of Silver Nanoparticle Toxicity

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Armstrong, Najealicka Nicole

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further

MRI-detected skull-base invasion. Prognostic value and therapeutic implication in intensity-modulated radiotherapy treatment for nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Cheng, Yi-Kan; Jiang, Ning; Yue, Dan; Tang, Ling-Long; Zhang, Fan; Lin, Li; Liu, Xu; Chen, Lei; Ma, Jun; Liu, Li-Zhi

2014-01-01

With advances in imaging and radiotherapy, the prognostic value of skull-base invasion in nasopharyngeal carcinoma (NPC) needs to be reassessed. We aimed to define a classification system and evaluate the prognostic value of the classification of magnetic resonance imaging (MRI)-detected skull-base invasion in NPC treated with intensity-modulated radiotherapy (IMRT). We retrospectively reviewed 749 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated NPC and treated with IMRT. MRI-detected skull-base invasion was not found to be an independent prognostic factor for overall survival (OS), distant metastasis-free survival (DMFS), local relapse-free survival (LRFS), or disease-free survival (DFS; p > 0.05 for all). Skull-base invasion was classified according to the incidence of each site (type I sites inside pharyngobasilar fascia and clivus vs. type II sites outside pharyngobasilar fascia). The 5-year OS, DMFS, LRFS, and DFS rates in the classification of skull-base invasion in NPC were 83 vs. 67 %, 85 vs.75 %, 95 vs. 88 %, and 76 vs. 62 %, respectively (p [de

Why do pathological stage IA lung adenocarcinomas vary from prognosis?: a clinicopathologic study of 176 patients with pathological stage IA lung adenocarcinoma based on the IASLC/ATS/ERS classification.

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Zhang, Jie; Wu, Jie; Tan, Qiang; Zhu, Lei; Gao, Wen

2013-09-01

Patients with pathological stage IA adenocarcinoma (AC) have a variable prognosis, even if treated in the same way. The postoperative treatment of pathological stage IA patients is also controversial. We identified 176 patients with pathological stage IA AC who had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China, between 2000 and 2006. No patient had preoperative treatment. The histologic subtypes of all patients were classified according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary lung AC classification. Patients' 5-year overall survival (OS) and 5-year disease-free survival (DFS) were calculated using Kaplan-Meier and Cox regression analyses. One hundred seventy-six patients with pathological stage IA AC had an 86.6% 5-year OS and 74.6% 5-year DFS. The 10 patients with micropapillary predominant subtype had the lowest 5-year DFS (40.0%).The 12 patients with solid predominant with mucin production subtype had the lowest 5-year OS (66.7%). Univariate and multivariate analysis showed that sex and prognositic groups of the IASLC/ATS/ERS histologic classification were significantly associated with 5-year DFS of pathological stage IA AC. Our study revealed that sex was an independent prognostic factor of pathological stage IA AC. The IASLC/ATS/ERS classification of lung AC identifies histologic categories with prognostic differences that could be helpful in clinical therapy.

Overexpression of Wilms Tumor 1 Gene as a Negative Prognostic Indicator in Acute Myeloid Leukemia

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Mi, Ruihua; Ding, Jing; Wang, Xianwei; Hu, Jieying; Fan, Ruihua; Wei, Xudong; Song, Yongping; Zhao, Richard Y.

2014-01-01

Chromosomal aberrations are useful in assessing treatment options and clinical outcomes of acute myeloid leukemia (AML) patients. However, 40∼50% of the AML patients showed no chromosomal abnormalities, i.e., with normal cytogenetics aka the CN-AML patients. Testing of molecular aberrations such as FLT3 or NPM1 can help to define clinical outcomes in the CN-AML patients but with various successes. Goal of this study was to test the possibility of Wilms’ tumor 1 (WT1) gene overexpression as an additional molecular biomarker. A total of 103 CN-AML patients, among which 28% had overexpressed WT1, were studied over a period of 38 months. Patient’s response to induction chemotherapy as measured by the complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were measured. Our data suggested that WT1 overexpression correlated negatively with the CR rate, DFS and OS. Consistent with previous reports, CN-AML patients can be divided into three different risk subgroups based on the status of known molecular abnormalities, i.e., the favorable (NPM1mt/no FLT3ITD), the unfavorable (FLT3ITD) and the intermediate risk subgroups. The WT1 overexpression significantly reduced the CR, DFS and OS in both the favorable and unfavorable groups. As the results, patients with normal WT1 gene expression in the favorable risk group showed the best clinical outcomes and all survived with complete remission and disease-free survival over the 37 month study period; in contrast, patients with WT1 overexpression in the unfavorable risk group displayed the worst clinical outcomes. WT1 overexpression by itself is an independent and negative indicator for predicting CR rate, DFS and OS of the CN-AML patients; moreover, it increases the statistical power of predicting the same clinical outcomes when it is combined with the NPM1 mt or the FLT3 ITD genotypes that are the good or poor prognostic markers of CN-AML. PMID:24667279

Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage 'pure' and 'mixed' lobular breast cancer.

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Carbognin, Luisa; Sperduti, Isabella; Brunelli, Matteo; Marcolini, Lisa; Nortilli, Rolando; Pilotto, Sara; Zampiva, Ilaria; Merler, Sara; Fiorio, Elena; Filippi, Elisa; Manfrin, Erminia; Pellini, Francesca; Bonetti, Franco; Pollini, Giovanni Paolo; Tortora, Giampaolo; Bria, Emilio

2016-03-22

The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery. Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67. At a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8%, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21%); 10-years DFS and OS were 75.1, 66.5, and 30.2% (p = 0.01) and 84.3, 76.4 and 59% (p = 0.003), for patients with a Ki67 21%, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85%, OS 100%). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology. Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC.

Epidermal growth factor receptor overexpression and outcomes in early breast cancer: A systematic review and a meta-analysis.

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Gonzalez-Conchas, Galileo A; Rodriguez-Romo, Laura; Hernandez-Barajas, David; Gonzalez-Guerrero, Juan F; Rodriguez-Fernandez, Ivan A; Verdines-Perez, Adrian; Templeton, Arnoud J; Ocana, Alberto; Seruga, Bostjan; Tannock, Ian F; Amir, Eitan; Vera-Badillo, Francisco E

2018-01-01

The epidermal growth factor receptor (EGFR) is a member of the ErbB family of membrane tyrosine-kinase receptors. Studies exploring the prognostic role of EGFR-overexpression in early breast cancer have shown variable results, and the true prognostic value of EGFR is unknown. A systematic review of identified publications exploring the association between EGFR-overexpression (as defined from different techniques and cut-offs) and outcomes [disease-free (DFS) and, overall survival (OS)] in women with early breast cancer. The hazard ratios (HR) for DFS and OS were weighted and pooled in a meta-analysis using generic inverse variance and random effects modeling. Fifty-three studies comprising 21,418 women were included. EGFR-overexpression was found in 27% of the patients. Primary analysis included studies reporting HRs from multivariable analyses (10 studies including 4857 patients with HRs for OS and 17 studies comprising 8747 patients with HRs for DFS), EGFR-overexpression was associated with worse OS (HR 1.98, 95% CI: 1.59-2.47, p overexpression on DFS was greater in women with triple negative tumors compared to women with non-triple negative tumors (HR 2.35 versus HR 1.45, respectively; p = .01). Analysis looking at odd ratios for both 5-year and 10-year for DFS and OS showed similar results. EGFR-overexpression appears to be associated with reduced OS and DFS in women with early breast cancer. Patients with triple negative and EGFR-overexpression have poorer OS and DFS than those with triple negative tumors and normal EGFR expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.

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Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P; Iacobuzio-Donahue, Christine A; Kerner, Zachary; Baylin, Stephen B; Wolfgang, Christopher L; Ahuja, Nita

2016-12-27

We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes.

Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

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Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

2014-07-01

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

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

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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.

Survival and prognostic factors after moderately hypofractionated palliative thoracic radiotherapy for non-small cell lung cancer

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Oorschot, B. van; Assenbrunner, B.; Beckmann, G.; Flentje, M.; Schuler, M.

2014-01-01

Survival and prognostic variables in patients with advanced or metastatic non-small cell lung cancer (NSCLC) requiring thoracic palliative radiotherapy using a moderately hypofractionated regime (13-15 x 3 Gy) were evaluated. From March 2006 to April 2012, 120 patients with a physician estimated prognosis of 6-12 months were treated with this regime using CT-based 3D conformal radiotherapy. We collected data on patient characteristics, comorbidities, toxicity, and treatment parameters. Radiotherapy was completed as prescribed in 114 patients (95.0 %, premature termination 5.0 %). Acute grade 3 toxicity was seen in 6.4 % of patients. The median survival of all patients was 5.8 months. Nonmetastatic patients survived significantly longer than patients with metastatic disease (median 11.7 months vs 4.7 months, p = 0.0001) and 18.6 % of nonmetastatic patients survived longer than 2 years. In 12.7 % radiotherapy started less than 30 days before death and 14.2 % of patients received radiotherapy within 14 days before death. In the multivariate analysis, good general condition, nonmetastatic disease, and a stable or improved general condition at the end of radiotherapy were significant. The treatment parameters, age, and comorbidities were not statistically significant. Our data confirm considerable effectiveness of 13 x 3 Gy with conformal radiotherapy for patients with locally confined NSCLC not fit for radical treatment and raise doubt for this regimen in metastatic patients and ECOG ≥ 2 when burden, acute toxicity, and resources are considered. (orig.) [de

The reproductive and developmental toxicity of High Flash Aromatic Naphtha.

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McKee, R H; Wong, Z A; Schmitt, S; Beatty, P; Swanson, M; Schreiner, C A; Schardein, J L

1990-01-01

Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--High Flash Aromatic Naphtha. A program was initiated to assess the toxicological properties of High Flash Aromatic Naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted to assess the potential for developmental toxicity in the mouse and for reproductive toxicity in the rat. In the developmental toxicity study in CD-1 mice, exposure of dams by inhalation to near lethal levels (1500 ppm) resulted in fetal mortality, reduced weight, delayed ossification, and an increased incidence of cleft palate. At 500 ppm, a level at which maternal weight gain was slightly reduced, fetal weight gain was also reduced, but there was no other evidence of developmental effects. The lowest exposure level (100 ppm) did not cause any maternal or developmental toxicity. There was no consistent evidence of reproductive toxicity in rats, even at exposure levels which resulted in significantly reduced parental weight gain. In addition, when parental exposure was stopped on GD (gestation day) 20, birth weights as well as postnatal survival were generally similar to control values, even in the 1500 ppm exposure group. Postnatal weight gain was also similar to controls early in weaning, but, if maternal exposure was reinitiated, weight gain was reduced in the high exposure group. However, when exposure was continued until delivery, pups in the high exposure group exhibited reduced litter size, birth weight and poor survival. Thus it was likely that the reduction in fetal weight

The Role of Pretreatment FDG-PET in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy

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Liu, Wen-Shan; Wu, Ming-Fang; Tseng, Hsien-Chun; Liu, Jung-Tung; Weng, Jui-Hung; Li, Yueh-Chun; Lee, Jong-Kang

2012-01-01

Purpose: Pretreatment with 2- [ 18 F] fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) was evaluated as a predictor of local failure-free survival (LFFS), disease-free survival (DFS), and overall survival (OS) in patients with nonkeratinizing nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) alone or concurrently with chemotherapy (CCRT). Patients and Methods: Seventy-five M0 NPC patients who received FDG-PET before treatment were analyzed. The primary tumor FDG uptake was measured as the maximum standardized uptake value (SUVmax). The LFFS, DFS, and OS were calculated by the Kaplan-Meier method, and the differences were evaluated on log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. Results: Eighteen patients received IMRT alone and 57 received CCRT. The mean SUVmax was significantly higher in 12 patients with locoregional or distant failure than in those without failure (p 18 F-FDG uptake (SUVmax >5) indicates poor outcome in patients with NPC.

Effect of Nanoparticles on the Survival and Development of Vitrified Porcine GV Oocytes.

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Li, W J; Zhou, X L; Liu, B L; Dai, J J; Song, P; Teng, Y

BACKGROUND: Some mammalian oocytes have been successfully cryopreserved by vitrification. However, the survival and developmental rate of vitrified oocytes is still low. The incorporation of nanoparticles into cryoprotectant (CPA) may improve the efficiency of vitrification by changing the properties of solutions. The toxicity of different concentrations of hydroxy apatite (HA), silica dioxide (SO 2 ), aluminum oxide (Al 2 O 3 ) and titanium dioxide (TiO 2 ) nanoparticles (20 nm in diameter) to oocytes was tested and the toxicity threshold value of each nanoparticle was determined. Porcine GV oocytes were vitrified in optimized nano-CPA, and effects of diameter and concentration of nanoparticles on the survival rate and developmental rate of porcine GV oocytes were compared. HA nanoparticles have demonstrated the least toxicity among four nanoparticles and the developmental rate of GV-stage porcine oocytes was 100% when its concentration was lower than 0.5%. By adding 0.1% HA into VS, the developmental rate of GV-stage porcine oocytes (22%) was significantly higher than other groups. The effect of vitrification in nano-CPA on oocytes was related to the concentration of HA nanoparticles rather than their size. By adding 0.05% HA nanoparticles (60nm in diameter), the developmental rate increased dramatically from 14.7% to 30.4%. Nano-cryopreservation offers a new way to improve the effect of survival and development of oocytes, but the limitation of this technology shall not be ignored.

Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience

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Avinash Pandey

2016-01-01

Full Text Available Background: Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge. Aim: To evaluate outcomes of epithelial ovarian carcinoma. Objectives: To calculate disease-free survival (DFS, overall survival (OS, and factors affecting outcomes. Materials and Methods: Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan-Meir survival was used to determine disease-free and OS. Log-rank test used to evaluate factors affecting outcome. Results: Median follow-up is 26 months. 93/102 patients (91% underwent cytoreductive surgery, of which 37 had primary cytoreduction (40% while 56 had interval cytoreduction. 21/93 (23%, 57/93 (61%, and 15/93 (16% patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel-platinum was used in 35/63 (56% patients while 28/63 patients (44% received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01, OS was 54 versus 26 months (P = 0.01.40/88 (45% patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2-18 months. Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69. Conclusion: Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression.

Once-Daily Radiation Therapy for Inflammatory Breast Cancer

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Brown, Lindsay; Harmsen, William; Blanchard, Miran; Goetz, Matthew; Jakub, James; Mutter, Robert; Petersen, Ivy; Rooney, Jessica; Stauder, Michael; Yan, Elizabeth; Laack, Nadia

2014-01-01

Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC

Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 Polymorphisms in Breast Carcinoma

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Gabbouj Sallouha

2008-04-01

Full Text Available Abstract Background Xenobiotic Metabolizing Enzymes (XMEs contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients. Methods The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients. Results The mEH (C/C mutant and the NAT2 slow acetylator genotypes were significantly associated with breast carcinoma risk (p = 0.02; p = 0.01, respectively. For NAT2 the association was more pronounced among postmenopausal patients (p = 0.006. A significant association was found between CYP2D6 (G/G wild type and breast carcinoma risk only in postmenopausal patients (p = 0.04. Association studies of genetic markers with the rates of breast carcinoma specific overall survival (OVS and the disease-free survival (DFS revealed among all breast carcinoma patients no association to DFS but significant differences in OVS only with the mEH gene polymorphisms (p = 0.02. In addition, the mEH wild genotype showed a significant association with decreased OVS in patients with axillary lymph node-negative patients (p = 0.03 and with decreasesd DFS in patients with axillary lymph node-positive patients (p = 0.001. However, the NAT2 intermediate acetylator genotype was associated with decreased DFS in axillary lymph node-negative patients. Conclusion The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.

CYP39A1 polymorphism is associated with toxicity during intensive induction chemotherapy in patients with advanced head and neck cancer

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Melchardt, Thomas; Hufnagl, Clemens; Magnes, Teresa; Weiss, Lukas; Hutarew, Georg; Neureiter, Daniel; Schlattau, Alexander; Moser, Gerhard; Gaggl, Alexander; Tränkenschuh, Wolfgang; Greil, Richard; Egle, Alexander

2015-01-01

Induction chemotherapy incorporating docetaxel, cisplatin and 5- fluorouracil before radiotherapy may improve the outcome of patients with advanced head and neck cancer. Nevertheless, the addition of docetaxel increases hematological toxicity and infectious complications. Therefore, genetic markers predicting toxicity and efficacy of this treatment regimen may help to identify patients, who would have the most benefit from this intensive treatment. A cohort of 78 patients with advanced head and neck cancer treated with induction chemotherapy was assessed for clinical outcome and toxicity during treatment with curative intention. Genetic polymorphisms primary associated with treatment efficacy (ERCC2-rs13181, rs1799793, ERCC1-rs3212986, rs11615, XRCC1-rs25487) or with docetaxel caused toxicity (CYP39A1-rs7761731, SLCO1B3-rs11045585) were evaluated in all patients. The results of these analyses were correlated with the clinical outcome of the patients (loco regional control, progression free survival, overall survival) and treatment related toxicity during induction chemotherapy. Median progression free survival and overall survival was 20 and 31 months in an intention to treat analysis, respectively. Overall response rate to induction chemotherapy was high with 78.1 % of all patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. Genotype A of the CYP39A1 rs7761731 polymorphism was associated with a higher incidence of leucopenia and infections or death during induction chemotherapy. Intensive induction chemotherapy results in a high response rate in the majority of patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. The CYP39A1 polymorphism rs7761731 may help to identify patients at high risk for treatment related toxicity

Benefit of Adjuvant Chemotherapy After Curative Resection of Lung Metastasis in Colorectal Cancer.

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Park, Hyung Soon; Jung, Minkyu; Shin, Sang Joon; Heo, Su Jin; Kim, Chang Gon; Lee, Min Goo; Beom, Seung Hoon; Lee, Chang Young; Lee, Jin Gu; Kim, Dae Joon; Ahn, Joong Bae

2016-03-01

The survival benefit of adjuvant chemotherapy after colorectal cancer (CRC) lung metastasectomy is uncertain. We enrolled 221 CRC patients who underwent pulmonary metastasectomy between October 2002 and July 2013, including those with previous liver metastasis that had been curatively resected. Disease-free survival (DFS) and overall survival (OS) were calculated from the day of lung metastasectomy. Among all patients, 176 (79.6%) received adjuvant chemotherapy after lung metastasectomy. Median follow-up was 34.7 months from the time of lung metastasectomy [95% confidence interval (95% CI), 7.4-90.9 months]. Patients treated with adjuvant chemotherapy had longer DFS compared with surgery alone (median 32.7 vs 11.2 months respectively, P = 0.076). Multivariate analysis revealed previous liver metastasis, preoperative carcinoembryonic antigen ≥5 ng/mL, disease-free interval chemotherapy as independent risk factors for recurrence. Low-risk patients who had 0-1 risk factors received a significant survival benefit from adjuvant chemotherapy [hazard ratio (HR) 0.54; 95% CI 0.32-0.91, P = 0.020]; however, high-risk patients with ≥2 risk factors did not (HR 1.02; 95% CI 0.48-2.14, P = 0.964). Patients treated with adjuvant chemotherapy showed no OS benefit compared with patients who received surgery alone (median 89.6 vs 86.8 months respectively, P = 0.833). CRC patients received lung metastasectomy could have a DFS benefit from adjuvant chemotherapy, especially in low-risk patients. Larger, prospective studies are needed to evaluate the role of adjuvant chemotherapy after CRC lung metastasectomy.

The Prognostic Value of the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging System in HER2-Enriched Subtype Breast Cancer, a Retrospective Analysis.

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Zhou, Bin; Xu, Ling; Ye, Jingming; Xin, Ling; Duan, Xuening; Liu, Yinhua

2017-08-01

The American Joint Committee on Cancer (AJCC) released its 8th edition of tumor staging which is to be implemented in early 2018. The present study aimed to analyze the prognostic value of AJCC 8th edition Cancer Staging System in HER2-enriched breast cancer, on a retrospective cohort. This study was a retrospective single-center study of HER2-enriched breast cancer cases diagnosed from January 2008 to December 2014. Clinicopathological features and follow up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore prognostic factors for disease outcome. We restaged patients based on the 8th edition of the AJCC cancer staging system and analyzed prognostic value of the Anatomic Stage Group and the Prognostic Stage Group. The study enrolled 170 HER2-enriched subtype breast cancer patients with 5-year disease free survival (DFS) of 85.1% and 5-year overall survival (OS) of 86.8%. Prognostic stages of 117 cases (68.8%) changed compared with anatomic stages, with 116 upstaged cases and 1 downstaged case. The Anatomic Stage Groups had a significant prognostic impact on DFS (χ 2 =16.752, panalysis, both stage groups were independent predictors of OS. Both Anatomic and Prognostic Stage Groups in the 8th edition of the AJCC breast cancer staging system had prognostic value in HER2-enriched subtype breast cancer. The Prognostic Stage system was a breakthrough on the basis of anatomic staging system. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

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Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A.; Beham-Schmid, C.; Groell, R.; Smolle-Juettner, F.M.; Renner, H.; Quehenberger, F.

1999-01-01

All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [de

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

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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.

Impact of changes in the treatment of nasopharyngeal carcinoma: an experience of 30 years

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Santos, J.A.; Gonzalez, C.; Cuesta, P.; De la Fuente, I.; Carrion, J.R.

1995-01-01

Two hundred and twenty-eight patients with nasopharyngeal carcinoma were treated in a single institution in a 31-year period. Overall survival (OS), disease-free survival (DFS), and complete response (CR) rates were analyzed. In addition, survival and control rates from 1960 to 1975 and from 1976 to 1991 were evaluated. In the latter group, a comparative study was performed between patients treated with neoadjuvant chemotherapy (NCT) before radiotherapy (RT) (45) and patients treated with radiotherapy alone (45). OS at 5 and 10 years were 42 and 34%, and DFS rates were 35 and 30%, respectively. CR was achieved in 184 patients (81%). Tumor progression and survival were strongly associated with T-category. Use of fashioned blocks, age and T-category were the most important factors influencing survival in a multivariate analysis. In the patients treated with NCT, rates of CR and OS were not significantly different when compared with the concurrent RT alone group. Ninety-nine patients had recurrence (54%) and 58 received rescue treatment. Modern radiotherapy techniques have greatly assisted in the improvement of tumor control rates. Chemotherapy must be further evaluated and new treatments for relapsed patients are needed

Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

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Seyed Jalal Hosseinimehr

2014-01-01

Full Text Available Background. In this study, the radiosensitizing effect of resveratrol as a natural product was investigated on cell toxicity induced by 131I in thyroid cancer cell. Methods. Human thyroid cancer cell and human nonmalignant fibroblast cell (HFFF2 were treated with 131I and/or resveratrol at different concentrations for 48 h. The cell proliferation was measured by determination of the percent of the survival cells using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results. Findings of this study show that resveratrol enhanced the cell death induced by 131I on thyroid cancer cell. Also, resveratrol exhibited a protective effect on normal cells against 131I toxicity. Conclusion. This result indicates a promising effect of resveratrol on improvement of cellular toxicity during iodine therapy.

Treatment and outcome in cancer cervix patients treated between 1979 and 1994: A single institutional experience

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Shyamkishore Shrivastava

2013-01-01

Materials and Methods: This is a retrospective study of 6234 patients with carcinoma of the cervix treated with radical intent between 1979 and 1994. All the work-up, staging investigations, treatment details, radiation protocols, outcomes, and toxicities were noted, compiled, and analyzed. Results: With a mean age of 46 years (range: 18-90 years; median: 45 years, 669 (11% patients were in stage Ib, 284 (5% were in stage IIa, 1891 (30% were in stage IIb, 69 (1% were in stage IIIa, and 3321 (53% were in stage IIIb. With a median follow-up of 68 months (57-79 months for the entire group, there was no significant difference in the outcome of 953 patients with international federation of gynecology and obstetrics (FIGO Ib-IIa treated after radical surgery, pre-operative radiation therapy (pre-op RT + Sx or after radical radiation; their disease-free survival (DFS was 60-62% at 8 years. In our series of 1891 patients with stage IIb and 3321 with stage IIIb, a respective DFS of 56% and 40% was achieved at 8 years. Conclusion: Over the last two decades, with the acquisition of newer facilities and inception of Joint Clinics, there has been a significant refinement in the treatment protocols and outcome. Improving radiation strategies to improve therapeutic ratio is the key to success.

Long term survival with whole abdominopelvic irradiation (WAI) in platinum-refractory ovarian cancer

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Cmelak, Anthony J.; Cox, Richard S.; Kapp, Daniel S.

1996-01-01

Purpose: To evaluate the efficacy and toxicity of WAI in persistent or recurrent epithelial ovarian carcinoma after initial chemotherapy. Methods and Materials: Between 1970 and 1995, 41 women with persistent or recurrent ovarian carcinoma after initial surgical debulking and chemotherapy were treated with WAI. Median age was 57 years (range 27-75). Initial FIGO stages were I and II - 5 patients (12%), III - 26 (64%), and IV - 10 (24%). Tumor grade was 1 - 4 (10%), II - 16 (39%), and III - 20 (49%). Four to eighteen (median eight) cycles of chemotherapy had been given prior to WAI. Thirty-one patients had received platinum-based regimens, and 22 of these had failed within six months after completion of chemotherapy (platinum-refractory). Prior to WAI, 11 (27%) patients had microscopic residual disease, 21 (51%) had gross residual disease up to 1.5 cm, and 9 (22%) had tumors greater than 1.5 cm in maximal diameter. Median doses of 28 Gy to the abdomen and 48 Gy to the pelvis were delivered using an open-field technique with appropriate liver and kidney shielding. Results: With follow-up of 1 month to 16.5 years, the 5-year actuarial disease specific survival was 47% in all 41 patients, and 49% in 22 platinum-refractory patients. Both disease bulk at WAI (p -4 ) and initial stage (p=0.005) were of prognostic value. Five-year disease specific survivals were stage I and II - 100%, stage III - 55%, and stage IV - 27%. Five-year disease specific survival of all nonbulky (less than 1.5 cm) patients was 40%; 0% for patients with disease greater than 1.5 cm. Five-year disease specific survival for grade I - 66%, II - 59%, and III - 33%. Stage I, II, or III patients with residual disease bulk of 1.5 cm or less before WAI had a 10-year actuarial disease specific survival of 50%. Twelve patients (29%) failed to complete the planned course of WAI due to acute toxicity (most often due to prolonged thrombocytopenia). Late bowel toxicity included obstruction in one patient and

Treatment outcome and prognostic factors of Stage IIIb squamous cell carcinoma of the uterine cervix treated with radiation therapy. Establish of historical controls

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Yokoyama, Takashi; Kataoka, Masaaki; Mogami, Hiroshi; Nogawa, Takayoshi; Chiba, Take; Hiura, Masamichi

2001-01-01

Neoadjuvant chemotherapy (NAC) and concurrent chemoradiotherapy (CCR) have been used to treat advanced squamous cell carcinoma of the uterine cervix. While the effectiveness of these therapies should be evaluated by a prospective randomized control study, no such study had ever been performed at the National Shikoku Cancer Center Hospital. For this reason, the authors assessed the results of radiotherapy after introduction of RALS (remote-controlled afterloading system) for patients with Stage IIIb squamous cell carcinoma of the uterine cervix and establish historical controls. The subjects were 95 patients (median age: 68 years) who had been treated at this hospital between 1983 and 1993. Twelve patients with PS4, severe complications, and active double cancer, received palliative external irradiation alone to the pelvis and 1 received palliative intracavitary received irradiation alone. The other 82 patients had external irradiation to the pelvis and intracavitary irradiation as curative irradiation. Thus, palliative irradiation and curative irradiation were performed in 13 cases and 82 cases, respectively. The overall survival rate (OAS), disease-specific survival rate (DDS), and disease-free survival rate (DFS) at 5 years in the palliative irradiation group were 7.7%, 16.8%, and 0%, respectively. In the curative irradiation group, OAS, DDS, and DFS were 56.1%, 65.9%, and 61.9%, respectively. Comparisons between the two groups showed significant differences each of the survival rates, and the outcome in the palliative irradiation group was very poor. Risk factors for recurrence were investigated, by comparing DFS among the 82 curatively irradiated cases, but no independent risk factors were identified by multivariate analysis. Exclusive of the patients with PS4, severe complications, active double cancer, and palliative irradiation, 62 patients were defined as historical controls. The survival rates of 62 patients were significantly better than those of the

Prognostic impact of proliferation for resected early stage 'pure' invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation.

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Carbognin, Luisa; Sperduti, Isabella; Fabi, Alessandra; Dieci, Maria Vittoria; Kadrija, Dzenete; Griguolo, Gaia; Pilotto, Sara; Guarneri, Valentina; Zampiva, Ilaria; Brunelli, Matteo; Orvieto, Enrico; Nortilli, Rolando; Fiorio, Elena; Parolin, Veronica; Manfrin, Erminia; Caliò, Anna; Nisticò, Cecilia; Pellini, Francesca; Scarpa, Aldo; Pollini, Giovanni Paolo; Conte, Pierfranco; Tortora, Giampaolo; Bria, Emilio

2017-10-01

The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC). Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well. Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap. Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology. Copyright © 2017 Elsevier Ltd. All rights reserved.

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

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Fujisawa, Yasuhiro; Otsuka, Fujio

2012-10-01

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

The role of multiploidy as unfavorable prognostic variable in colorectal cancer.

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Cosimelli, M; D'Agnano, I; Tedesco, M; D'Angelo, C; Botti, C; Giannarelli, D; Vasselli, S; Cavaliere, F; Zupi, G; Cavaliere, R

1998-01-01

To analyze the prognostic value of DNA multiploidy in a prospective study on frozen surgical tissue samples from primary colorectal cancer. Survival data from eleven prospective studies collectively comprising about thirteen hundred patients showed that aneuploidy correlated with a 5-year disease-free survival (DFS) significantly poorer than diploidy, and showed the limited prognostic value of results from retrospective studies employing paraffin-embedded material. Multiple tumor samples of fresh/frozen surgical tissues from 120 colorectal cancer patients who had undergone radical surgery were taken for flow cytometric analysis of DNA content, and proliferative activity, shown as percentage of cells in S-phase (%S). The minimum follow-up of this series was 30 months. Univariate and multivariate analyses determined the independent significance of both clinical and biological variable on DFS. Values of %S equal to or higher than 17.3 correlated with a 5-year DFS poorer than values lower than 17.3 (44.5% vs 85.2% respectively; p = .03), even if only in patients younger than 64. The subgroup with multiploid tumors showed a significantly poorer 5-year DFS (44.5% vs. 62.6% in the non multiploid patients; p = .02). Subgrouping the Dukes'B stage alone by multiploidy, the difference in DFS was much more evident (31.2% vs. 68% respectively; p = .0004) and multivariate analysis showed multiploidy as the only significant variable. Above all, adjuvant therapy did not absolutely modify the unfavorable outcome of the multiploid Dukes'B patients. The prospective evaluation of ploidy allowed us to identify a very high-risk subgroup of patients with multiploid tumors. This biological characterization was easy to demonstrate and, above all in node-negative patients, reliable and very effective in terms of prognosis. The presence of multiploidy should result in a more aggressive therapeutic approach in the adjuvant setting.

Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer.

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Šišić, Ibrahim; Pojskić, Belma; Mekić Abazović, Alma; Kovčin, Vladimir

2015-08-01

To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). A total of 63 patients were treated for mCRC in the period January 2009 - January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bežanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer

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Ibrahim Šišić

2015-08-01

Full Text Available Aim To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus, leucovorin (folfox between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC. Methods A total of 63 patients were treated for mCRC in the period January 2009 – January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients and at the Department of Oncology of the Clinical Hospital Centre Bežanijska kosa in Belgrade, Serbia, in the period January 2005 – January 2006 (second group, 33 patients. The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D, 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS, progression free survival, hematological and non-hematological toxicity. Results Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. Conclusion Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy.

Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy

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Lewandowski, Robert J.; Memon, Khairuddin; Hickey, Ryan; Gates, Vanessa L.; Atassi, Bassel; Vouche, Michael; Atassi, Rohi; Desai, Kush; Hohlastos, Elias; Sato, Kent; Habib, Ali [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Mulcahy, Mary F.; Kircher, Sheetal; Newman, Steven B.; Nimeiri, Halla; Benson, Al B. [Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States); Marshall, Karen; Williams, Melissa; Salzig, Krystina; Salem, Riad [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States)

2014-10-15

The aim of this study was to analyze the safety, treatment characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for unresectable colorectal carcinoma (CRC) liver metastases refractory to standard of care therapy. A total of 214 patients with CRC metastases were treated with Y90 radioembolization over 12 years. Toxicity was assessed using National Cancer Institute common terminology criteria. Overall survival was analyzed from date of diagnosis of primary cancer, hepatic metastases and from the first Y90. Uni/multivariate analyses were performed. Substratification by era of chemotherapeutics was performed. Most patients were male (60 %) and <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3 lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11 %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP toxicities were observed in 5 % and 3 % of patients, respectively. Median overall survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary cancer, hepatic metastases and first Y90, respectively. Survival was significantly longer in patients: (1) who received ≤2 cytotoxic drugs (n = 104) than those who received 3 (n = 110) (15.2 vs. 7.5 months, p = 0.0001); and (2) who received no biologic agents (n = 52) compared with those that did (n = 162) (18.6 vs. 9.4 months, p = 0.0001). Multivariate analyses identified ≤2 cytotoxic agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of extrahepatic disease and albumin >3 g/dL as independent predictors of survival. In this largest metastatic CRC series published to date, Y90 radioembolization was found to be safe; survival varied by prior therapy. Further studies are required to further refine the role of Y90 in metastatic CRC. (orig.)

Clinical and pathological features of patients with resected synovial sarcoma: A multicenter retrospective analysis of the Anatolian Society of Medical Oncology

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Yetisyigit Tarkan

2014-01-01

Conclusion: Our study confirms that high mitotic activity is significantly associated with decreased DFS. The question of whether the chemotherapy provides a survival advantage in patients having adverse prognostic factors requires confirmation in randomized trials.

Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

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Zheng, Xiangpeng; Schipper, Matthew; Kidwell, Kelley; Lin, Jules; Reddy, Rishindra; Ren, Yanping; Chang, Andrew; Lv, Fanzhen; Orringer, Mark; Spring Kong, Feng-Ming

2014-01-01

Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery

Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

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Zheng, Xiangpeng [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Schipper, Matthew [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Kidwell, Kelley [Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Lin, Jules; Reddy, Rishindra [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Ren, Yanping [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Chang, Andrew [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Lv, Fanzhen [Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai (China); Orringer, Mark [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Spring Kong, Feng-Ming, E-mail: Fkong@gru.edu [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States)

2014-11-01

Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

Modelling survival: exposure pattern, species sensitivity and uncertainty.

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Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B; Van den Brink, Paul J; Veltman, Karin; Vogel, Sören; Zimmer, Elke I; Preuss, Thomas G

2016-07-06

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

The toxicity of different lead salts to Enchytraeus crypticus in relation to bioavailability in soil.

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Zhang, Lulu; Van Gestel, Cornelis A M

2017-08-01

The present study aimed to assess the bioavailability and toxicity of lead nitrate and lead chloride to Enchytraeus crypticus in a natural standard soil. Worms were exposed to Pb-spiked soil for 21 d, and survival and reproduction were related to total, 0.01 M CaCl 2 -extractable, and porewater Pb concentrations in the soil and internal concentrations in the surviving animals. The Pb availability for Pb(NO 3 ) 2 and PbCl 2 was similar, as confirmed by Langmuir and Freundlich isotherms. The Pb concentrations in surviving worms increased with increasing Pb concentrations in the soil and did not differ for the 2 Pb salts. Lead was toxic to E. crypticus at median lethal concentrations (LC50s) of 543 and 779 mg Pb/kg dry soil and median effect concentrations (EC50s) of 189 and 134 mg Pb/kg dry soil, for Pb(NO 3 ) 2 and PbCl 2 , respectively. Mortality of E. crypticus was related to internal Pb concentrations in the worms rather than to total or available Pb concentrations in the soil, whereas reproduction toxicity was better explained from Pb concentrations in 0.01 M CaCl 2 extracts or porewater of the test soil than from total Pb concentrations in the soil or Pb concentrations in the worms. Overall, the bioavailability and toxicity of Pb(NO 3 ) 2 and PbCl 2 to E. crypticus in LUFA 2.2 soil did not differ. Environ Toxicol Chem 2017;36:2083-2091. © 2017 SETAC. © 2017 SETAC.

Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

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Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-06-01

Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

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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.

Risk Factors Associated with Disease Recurrence in Patients with Stage III/IV Squamous Cell Carcinoma of the Oral Cavity Treated with Surgery and Postoperative Radiotherapy.

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Noble, Anisha R; Greskovich, John F; Han, Jaehong; Reddy, Chandana A; Nwizu, Tobenna I; Khan, Mumtaz F; Scharpf, Joseph; Adelstein, David J; Burkey, Brian B; Koyfman, Shlomo A

2016-02-01

The purpose of the present study was to identify variables associated with high risk of failure in patients with locally advanced squamous cell carcinoma of the oral cavity (SCC-OC). This retrospective study included 191 patients with stage III-IVb SCC-OC treated with post-operative radiotherapy (RT) or chemoradiotherapy (CRT) between 1995 and 2013. Disease-free (DFS) and overall survival (OS) were analyzed; variables associated with inferior DFS were identified. Seventy-five patients (39%) recurred. DFS and five-year OS were 52% and 54%, respectively. Poorly differentiated tumors (p=0.03), recurrent tumors (p=0.02) and high nodal ratio (p=0.02) were associated with an increased risk of recurrence. CRT was associated with improved DFS in patients with positive margins and/or extracapsular extension (p=0.021). Tumors that are recurrent, high grade, or have high nodal ratio are at risk of recurrence. Presence of these disease features should be taken into consideration for better risk stratification. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Presence survival spores of Bacillus thuringiensis varieties in grain warehouse

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Sánchez-Yáñez Juan Manuel

2016-08-01

Full Text Available Genus Bacillus thuringiensis (Bt synthesized spores and crystals toxic to pest-insects in agriculture. Bt is comospolitan then possible to isolate some subspecies or varieties from warehouse. The aims of study were: i to isolate Bt varieties from grain at werehouse ii to evaluate Bt toxicity on Spodoptera frugiperda and Shit-ophilus zeamaisese iii to analyze Bt spores persistence in Zea mays grains at werehouse compared to same Bt on grains exposed to sun radiation. Results showed that at werehouse were recovered more than one variety of Bt spores. According to each isolate Bt1 o Bt2 were toxic to S. frugiperda or S. zeamaisese. One those Bt belong to var morrisoni. At werehouse these spores on Z. mays grains surviving more time, while the same spores exposed to boicide sun radiation they died.

Promising survival with three-dimensional conformal radiation therapy for non-small cell lung cancer

International Nuclear Information System (INIS)

Armstrong, John; Raben, Adam; Zelefsky, Michael; Burt, Michael; Leibel, Steve; Burman, Chandra; Kutcher, Gerard; Harrison, Louis; Hahn, Cathy; Ginsberg, Robert; Rusch, Valerie; Kris, Mark; Fuks, Zvi

1997-01-01

Purpose: Local failure is a major obstacle to the cure of locally advanced non small-cell lung cancer. Three-dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially representing an enhancement of the therapeutic ratio of radiation therapy for lung cancer. We performed this analysis of 45 non-small cell lung cancer patients treated with 3-DCRT alone, to evaluate the ability of computer derived lung dose volume histograms to predict serious pulmonary toxicity, to assess the feasibility of this approach, and to examine the resulting survival. Methods: There were 28 males (62%) and 17 females (38%). The median age was 65 (range: 38-82). Tumor stage was Stage I/II in 13%, IIIa in 42%, and IIIb in 44%. The histology was squamous in 44%, adenocarcinoma in 36%, and other non-small cell histologies in the others. Only 47% of patients. had combined favorable prognostic factors (i.e. KPS ≤ 80, and ≤5% wt. loss). The median dose of radiation to gross disease was 70.2 Gy (range: 52.2-72 Gy) delivered in fractions of 1.8 Gy, 5 days per week. Results: Seven patients did not complete 3-DCRT due to disease progression outside the port. Follow-up data are mature: the median follow up of the 6 survivors is 43.5 months (35-59). Thoracic progression occurred in 46%. Median survival (all 45 patients.) is 15.7 months and survival is 32% at 2 years and 12% at 59 months. Pulmonary toxicity ≥grade 3 occurred in 9% of patients. Dose volume histograms were available in 31 patients and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% ((3(8))) of patients with >30% of lung volume receiving ≥25 Gy, versus 4% ((1(23))) of patients with ≤30% lung receiving ≥25 Gy (P = 0.04). Grade 3 or higher pulmonary toxicity occurred in 29% ((4(14))) of patients with a predicted pulmonary normal tissue

Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT)

International Nuclear Information System (INIS)

Goyal, Sharad; Daroui, Parima; Khan, Atif J; Kearney, Thomas; Kirstein, Laurie; Haffty, Bruce G

2013-01-01

The aim of this study was to report 3-year outcomes of toxicity, cosmesis, and local control using a once daily fractionation scheme (49.95 Gy in 3.33 Gy once daily fractions) for accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT). Between July 2008 and August 2010, women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study. Women were treated with APBI using 3–5 photon beams, delivering 49.95 Gy over 15 once daily fractions over 3 weeks. Patients were assessed for toxicities, cosmesis, and local control rates before APBI and at specified time points. Thirty-four patients (mean age 60 years) with Tis 0 (n = 9) and T1N0 (n = 25) breast cancer were treated and followed up for an average of 39 months. Only 3% (1/34) patients experienced a grade 3 subcutaneous fibrosis and breast edema and 97% of the patients had good/excellent cosmetic outcome at 3 years. The 3-year rate of ipsilateral breast tumor recurrence (IBTR) was 0% while the rate of contralateral breast events was 6%. The 3-year disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) was 94%, 100%, and 100%, respectively. Our novel accelerated partial breast fractionation scheme of 15 once daily fractions of 3.33 Gy (49.95 Gy total) is a remarkably well-tolerated regimen of 3D-CRT-based APBI. A larger cohort of patients is needed to further ascertain the toxicity of this accelerated partial breast regimen