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Sample records for locally advanced metastatic

  1. Vandetanib in locally advanced or metastatic differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Leboulleux, Sophie; Bastholt, Lars; Krause, Thomas

    2012-01-01

    No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting....

  2. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Tyrrell, C J; Kaisary, A V; Iversen, P

    1998-01-01

    To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer.......To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer....

  3. A Review of Immune Checkpoint Inhibitors for the Management of Locally Advanced or Metastatic Urothelial Carcinoma.

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    Hanna, Kirollos S

    2017-11-01

    Urothelial carcinoma (UC) is the second most common malignancy of the genitourinary system and the sixth most common cancer in the United States. The overall incidence of UC appears to be on the decline, but death rates have remained stable. Stage IV metastatic disease is associated with only a 5% survival rate at 5 years. Gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin are the preferred regimens for individuals with advance, metastatic disease and a good performance status and organ function. Second-line therapies in this setting are limited. During the course of 1 year, five immune checkpoint inhibitors were approved for treatment of cancers in the locally advanced or metastatic setting: atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for UC. Based on the limited data, pembrolizumab and atezolizumab may be the drugs of choice, as they are supported by the most influential data to date; however, further research is warranted. Ongoing clinical trials will further assess the benefits of inducing cellular immunity in the treatment of UC. These therapies mark a new landscape in the treatment of UC. In this article, the available data on immune checkpoint inhibitors for the treatment of locally advanced or metastatic UC and their place in therapy are reviewed. © 2017 Pharmacotherapy Publications, Inc.

  4. Management of locally advanced and metastatic colon cancer in elderly patients.

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    Kurniali, Peter C; Hrinczenko, Borys; Al-Janadi, Anas

    2014-02-28

    Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patient's functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer.

  5. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

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    Robinson, Bruce G; Paz-Ares, Luis; Krebs, Annetta; Vasselli, James; Haddad, Robert

    2010-06-01

    Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

  6. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

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    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  7. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ma Yue

    2011-03-01

    Full Text Available Abstract Background The objectives of the present study are to investigate the efficacy and safety profile of gemcitabine-based combinations in the treatment of locally advanced and metastatic pancreatic adenocarcinoma (LA/MPC. Methods We performed a computerized search using combinations of the following keywords: "chemotherapy", "gemcitabine", "trial", and "pancreatic cancer". Results Thirty-five trials were included in the present analysis, with a total of 9,979 patients accrued. The analysis showed that the gemcitabine-based combination therapy was associated with significantly better overall survival (OS (ORs, 1.15; p = 0.011, progression-free survival (PFS (ORs, 1.27; p Conclusions Gemcitabine in combination with capecitabine or oxaliplatin was associated with enhanced OS and ORR as compared with gemcitabine in monotherapy, which are likely to become the preferred standard first-line treatment of LA/MPC.

  8. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.

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    Wells, Samuel A; Gosnell, Jessica E; Gagel, Robert F; Moley, Jeffrey; Pfister, David; Sosa, Julie A; Skinner, Michael; Krebs, Annetta; Vasselli, James; Schlumberger, Martin

    2010-02-10

    PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

  9. Targeted therapies for locally advanced or metastatic squamous cell carcinoma of the lung.

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    Stinchcombe, Thomas E

    2013-12-01

    Most patients with squamous cell carcinoma (SCC) present with advanced or metastatic disease at the time of diagnosis. Given the low prevalence of oncogenic driver mutations in SCC, I do not routinely perform molecular testing. The times that I perform molecular testing in SCC are for patients with SCC and a light or never smoking history, adenosquamous histology, or when the histological diagnosis is not definitive. For patients with a good performance status and adequate organ function, a platinum doublet is the standard therapy, and I generally use carboplatin and gemcitabine or carboplatin and paclitaxel. In the second-line setting for patients who are chemotherapy candidates, I will use docetaxel on a weekly or every three week schedule. Erlotinib is a treatment option in the third-line setting. My preference is for patients to participate in clinical trials because the development of novel therapies for patients with SCC has been slow compared with nonsquamous non-small cell lung cancer. Ongoing investigations into the genomics of SCC will hopefully identify driver mutations or alterations in pathways essential for oncogenesis and tumor growth and will lead to the development of targeted therapies. The complexity of the genomics of SCC will make the development of targeted therapies challenging.

  10. Evaluation of dynamic serum thiol/disulfide homeostasis in locally advanced and metastatic gastric cancer

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    Mutlu Hizal

    2018-04-01

    Full Text Available Background: Gastric cancer is one the most diagnosed cancer and the third leading cause of death from cancer worldwide. As an indicator of antioxidant capacity thiol/disulfide homeostasis regulates detoxification, cell signal mechanisms, apoptosis, transcription and antioxidant defense mechanisms. Disregulation of thiol/disulfide homeostasis identified in other cancer types by recent data. In this study, we aimed to evaluate the thiol/disulfide homeostasis in advanced gastric cancer patients. Methods: The patients who diagnosed with gastric cancer and healthy control subjects were included to study. Serum samples for the thiol-disulphide test were obtained at the time of diagnosis. Thiol-disulphide homeostasis tests were measured by the automated spectrophotometric method. Thiol-disulphide homeostasis was also measured according to clinical and laboratory features. Results: Thirty newly diagnosed advanced gastric adenocarcinoma patients and 28 healthy controls were enrolled in the study. The native thiol (NT and total thiol (TT levels of patients' group were significantly lower compared with controls (p = 0.001 and p < 0.001. In the CEA high (≥5.4 ng/ml group, DS/NT ratio were higher compared with CEA low (<5.4 ng/ml group (p = 0.024. In CA.19-9 high (≥28.3 kU/L group, both DS and DS/NT ratio were significantly higher compared with a CA19-9 low(<28.3 kU/L group (p < 0.05 both. The correlation between CEA and DS levels was also significant (p = 0.02. There was also a positive correlation between CEA levels and DS/NT ratio (p = 0.01. Conclusion: Derangements of thiol/disulfide homeostasis may have a role in gastric cancer pathogenesis and the higher level of oxidative stress may relate to extensive and aggressiveness of the advanced disease. The diagnostic and prognostic values of thiol/disulfide products need to identify with further studies. Keywords: Thiol, Disulfide, Oxidative stress, Gastric cancer, Metastatic

  11. Overall Survival of Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Nimotuzumab in the Real World.

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    Saumell, Yaimarelis; Sanchez, Lizet; González, Sandra; Ortiz, Ramón; Medina, Edadny; Galán, Yaima; Lage, Agustin

    2017-12-01

    Despite improvements in surgical techniques and treatments introduced into clinical practice, the overall survival of patients with esophageal squamous cell carcinoma remains low. Several epidermal growth factor receptor inhibitors are being evaluated in the context of clinical trials, but there is little evidence of effectiveness in real-world conditions. This study aimed at assessing the effectiveness of nimotuzumab combined with onco-specific treatment in Cuban real-life patients with locally advanced or metastatic esophageal squamous cell carcinoma. A comparative and retrospective effectiveness study was performed. The 93 patients treated with nimotuzumab were matched, with use of propensity score matching, with patients who received a diagnosis of locally advanced or metastatic squamous cell carcinoma of the esophagus in three Cuban provinces reported between 2011 and 2015 to the National Cancer Registry. The Kaplan-Meier method was used to estimate event-time distributions. Log-rank statistics were used for comparisons of overall survival between groups. A two-component mixture model assuming a Weibull distribution was fitted to assess the effect of nimotuzumab on short-term and long-term survival populations. There was an increase in median overall survival in patients treated with nimotuzumab (11.9 months versus 6.5 months without treatment) and an increase in the 1-year survival rate (54.0% versus 21.9% without treatment). The 2-year survival rates were 21.1% for patients treated with nimotuzumab and 0% in the untreated cohort. There were statistically significant differences in survival between groups treated and not treated with nimotuzumab, both in the short-term survival population (6.0 months vs 4.0 months, p = 0.009) and in the long-term survival population (18.0 months vs 11.0 months, p = 0.001). Our study shows that nimotuzumab treatment concurrent with chemoradiotherapy increases the survival of real-world patients with locally advanced

  12. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy

    DEFF Research Database (Denmark)

    Bellmunt, Joaquim; von der Maase, Hans; Mead, Graham M

    2012-01-01

    The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival....

  13. Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

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    Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

    2014-06-01

    The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

  14. Gemcitabine and cisplatin in locally advanced and metastatic bladder cancer; 3- or 4-week schedule?

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    Als, Anne Birgitte; Sengeløv, Lisa; Von Der Maase, Hans

    2008-01-01

    BACKGROUND: Chemotherapy with gemcitabine and cisplatin (GC) is an active regimen in advanced transitional cell carcinoma (TCC). Traditionally, GC has been administered as a 4-week schedule. However, an alternative 3-week schedule may be more feasible. Long-term survival data for the alternative 3......-week schedule and comparisons of the feasibility and toxicity between the two schedules have not previously been published. MATERIAL AND METHODS: We performed a retrospective analysis of patients with stage IV TCC, treated with GC by a standard 4-week or by an alternative 3-week schedule. RESULTS...

  15. Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

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    Michael, M; Chander, S; McKendrick, J; MacKay, J R; Steel, M; Hicks, R; Heriot, A; Leong, T; Cooray, P; Jefford, M; Zalcberg, J; Bressel, M; McClure, B; Ngan, S Y

    2014-11-11

    Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

  16. Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer

    DEFF Research Database (Denmark)

    Roberts, J. T.; Maase, Hans von der; Sengeløv, Lisa

    2006-01-01

    Purpose: To compare long-term survival in patients with locally advanced       and metastatic transitional cell carcinoma (TCC) of the urothelium treated       with gemcitabine plus cisplatin (GC) or       methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND       METHODS: Efficacy.......       CONCLUSIONS: Long-term overall and progression-free survival following       treatment with GC or MVAC are similar. These results strengthen the role       of GC as a standard of care in patients with locally advanced and       metastatic transitional-cell carcinoma (TCC)....

  17. Predictive factors for response and prognostic factors for long-term survival in consecutive, single institution patients with locally advanced and/or metastatic transitional cell carcinoma following cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    Jessen, Christian; Agerbaek, Mads; Von Der Maase, Hans

    2009-01-01

    PURPOSE: The study was undertaken to identify pre-treatment clinical and histopathological factors of importance for response and survival after cisplatin-based combination chemotherapy, in patients with locally advanced or metastatic transitional cell carcinoma of the urothelium. PATIENTS...

  18. Evaluation of the efficacy and toxicity of protocol cisplatin, 5-fluorouracil, leucovorin compared to protocol fluorouracil, doxorubicin and mitomycin C in locally advanced and metastatic gastric cancer

    Directory of Open Access Journals (Sweden)

    Andrić Zoran

    2012-01-01

    Full Text Available Introduction. Still there is no consensus on the choice of the most efficient and the least toxic chemotherapy regimen in the treatment of advanced gastric cancer. Nowadays few therapy protocols are available for treating this disease. Objective. Study was conducted to compare the efficacy and toxicity of FAM (flurouracil, doxorubicin, mitomycin C with CDDP and FU/FA (cisplatin, 5-fluorouracil, leucovorin protocols in patients with locally advanced and metastatic gastric cancer. Methods. This randomized study involved a group of 50 patients with locally advanced or metastatic gastric cancer, who had not previously undergone chemotherapy treatment. Progression free survival, overall survival and drug toxicity were evaluated. For statistical analysis chi-square test, Kaplan-Meier curve and the log rank test were used. Results. The overall response rate was 20% in the group treated with FAM and 24% in the group treated with CDDP, FU/FA (4% of patients from each group had complete response, but without significant statistical difference. Median survival was 10.9 months in the FAM group and 11.8 months in CDDP, FU/FA group, with no statistically significant difference. Non-haematological and haematological toxicities of CDDP, FU/FA were considerably less frequent than of FAM, and there was no treatment related deaths in any of the groups. Conclusion. Both investigated regimens demonstrated moderate efficacy. The study shows in favour of justified application of both protocols, while in regard to toxicity CDDP and FU/FA can be recommended as preferable treatment for locally advanced and metastatic gastric cancer. New strategies should be considered for better efficacy in the treatment of advanced gastric cancer. New strategies are necessary with the goal to achieve a better therapeutic effect.

  19. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

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    Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

    1998-01-01

    The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

  20. Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

    International Nuclear Information System (INIS)

    Russo, Francesca; Bearz, Alessandra; Pampaloni, Gianni; The investigators of the Italian Pemetrexed monotherapy of NSCLC group

    2008-01-01

    The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC. Overall, 95 patients received pemetrexed 500 mg/m 2 i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria. Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression. Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities

  1. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.

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    Wells, Samuel A; Robinson, Bruce G; Gagel, Robert F; Dralle, Henning; Fagin, James A; Santoro, Massimo; Baudin, Eric; Elisei, Rossella; Jarzab, Barbara; Vasselli, James R; Read, Jessica; Langmuir, Peter; Ryan, Anderson J; Schlumberger, Martin J

    2012-01-10

    There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments. Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).

  2. Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

    International Nuclear Information System (INIS)

    Salazar, Omar M.; Sandhu, Taljit S.; Lattin, Paul B.; Chang, Jung H.; Lee, Choon K.; Groshko, Gayle A.; Lattin, Cheryl J.

    2008-01-01

    Purpose: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. Methods and Materials: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy 10 ). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy 10 . Respiration gating was used in 46%. Results: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. Conclusions: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older

  3. Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

    Directory of Open Access Journals (Sweden)

    Xiaohui Zeng

    Full Text Available BACKGROUND: Maintenance gefitinib significantly prolonged progression-free survival (PFS compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC after four chemotherapeutic cycles (21 days per cycle of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. METHODS AND FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP threshold of $16,349 (3 × per-capita gross domestic product of China. The sensitivity analyses all suggested that the model was robust. CONCLUSIONS: Maintenance gefitinib

  4. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

    Science.gov (United States)

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

    2015-06-01

    To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

  5. Randomized phase III study comparing paclitaxel/cisplatin/ gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987

    NARCIS (Netherlands)

    J. Bellmunt (Joaquim); H. von der Maase (Hans); G.M. Mead (Graham); I. Skoneczna (I.); M. de Santis (Maria); G. Daugaard (Gedske); J. Boehle; C. Chevreau (Christine); L. Paz-Ares (Luis); L.R. Laufman (Leslie); E. Winquist (Eric); R. Raghavan (Raghu); S. Marreaud (Sandrine); S. Collette (Sandra); R. Sylvester (Richard); R. de Wit (Ronald)

    2012-01-01

    textabstractPurpose: The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival.

  6. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

    Science.gov (United States)

    Dirix, Luc Y; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E; Somer, Robert; Smakal, Martin; Emens, Leisha A; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja; Grote, Hans Juergen; Chin, Kevin; Hamilton, Erika P

    2018-02-01

    Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

  7. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1).

    Science.gov (United States)

    Bonnefoi, H; Grellety, T; Tredan, O; Saghatchian, M; Dalenc, F; Mailliez, A; L'Haridon, T; Cottu, P; Abadie-Lacourtoisie, S; You, B; Mousseau, M; Dauba, J; Del Piano, F; Desmoulins, I; Coussy, F; Madranges, N; Grenier, J; Bidard, F C; Proudhon, C; MacGrogan, G; Orsini, C; Pulido, M; Gonçalves, A

    2016-05-01

    Several expression array studies identified molecular apocrine breast cancer (BC) as a subtype that expresses androgen receptor (AR) but not estrogen receptor α. We carried out a multicentre single-arm phase II trial in women with AR-positive, estrogen, progesterone receptor and HER2-negative (triple-negative) metastatic or inoperable locally advanced BC to assess the efficacy and safety of abiraterone acetate (AA) plus prednisone. Patients with a metastatic or locally advanced, centrally reviewed, triple-negative and AR-positive (≥10% by immunohistochemistry, IHC) BC were eligible. Any number of previous lines of chemotherapy was allowed. AA (1000 mg) was administered once a day with prednisone (5 mg) twice a day until disease progression or intolerance. The primary end point was clinical benefit rate (CBR) at 6 months defined as the proportion of patients presenting a complete response (CR), partial response (PR) or stable disease (SD) ≥6 months. Secondary end points were objective response rate (ORR), progression-free survival (PFS) and safety. One hundred and forty-six patients from 27 centres consented for IHC central review. Of the 138 patients with sufficient tissue available, 53 (37.6%) were AR-positive and triple-negative, and 34 of them were included from July 2013 to December 2014. Thirty patients were eligible and evaluable for the primary end point. The 6-month CBR was 20.0% [95% confidence interval (CI) 7.7%-38.6%], including 1 CR and 5 SD ≥6 months, 5 of them still being under treatment at the time of analysis (6.4+, 9.2+, 14.5+, 17.6+, 23.4+ months). The ORR was 6.7% (95% CI 0.8%-22.1%). The median PFS was 2.8 months (95% CI 1.7%-5.4%). Fatigue, hypertension, hypokalaemia and nausea were the most common drug-related adverse events; the majority of them being grade 1 or 2. AA plus prednisone treatment is beneficial for some patients with molecular apocrine tumours and five patients are still on treatment. NCT01842321. © The Author 2016

  8. Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens.

    Science.gov (United States)

    Perez-Gracia, Jose Luis; Loriot, Yohann; Rosenberg, Jonathan E; Powles, Thomas; Necchi, Andrea; Hussain, Syed A; Morales-Barrera, Rafael; Retz, Margitta M; Niegisch, Günter; Durán, Ignacio; Théodore, Christine; Grande, Enrique; Shen, Xiaodong; Wang, Jingjing; Nelson, Betty; Derleth, Christina L; van der Heijden, Michiel S

    2017-12-19

    Patients with metastatic urothelial carcinoma (mUC) who progress after platinum-based chemotherapy have had few treatment options and uniformly poor outcomes. Atezolizumab (anti-programmed death-ligand 1) was approved in the USA for cisplatin-ineligible and platinum-treated mUC based on IMvigor210, a phase 2, single-arm, two-cohort study. To evaluate the efficacy and safety of atezolizumab by the number of prior lines of systemic therapy in patients with pretreated mUC. IMvigor210 enrolled 315 patients with mUC with progression during or following platinum-based therapy at 70 international sites between May 2014 and November 2014. Key inclusion criteria included age ≥18 yr, creatinine clearance ≥30ml/min, and Eastern Cooperative Oncology Group performance status 0-1, with no limit on prior lines of treatment. Patients in this cohort received atezolizumab 1200mg intravenously every 3 wk until loss of clinical benefit. Centrally assessed Response Evaluation Criteria In Solid Tumors v1.1 objective response rate (ORR), median duration of response, overall survival (OS), and adverse events were evaluated by prior treatment. Potential differences between subgroups were evaluated using log-rank (for OS) and chi-square (for ORR and adverse events frequencies) testing. Three hundred and ten patients were efficacy and safety evaluable (median follow-up, 21 mo). Objective responses and prolonged OS occurred across all prespecified subgroups; median duration of response was not reached in most subgroups. In patients without prior systemic mUC therapy (first-line subgroup), ORR was 25% (95% confidence interval: 14-38), and median OS was 9.6 mo (95% confidence interval: 5.9-15.8). No significant differences in efficacy or toxicity by therapy line were observed. Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with mUC across all lines of therapy evaluated. We investigated effects of previous treatment in patients with metastatic

  9. Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

    Directory of Open Access Journals (Sweden)

    Rinaldo Massimo

    2011-02-01

    Full Text Available Abstract Background To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Methods Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. Results From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03; patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p Conclusions In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. Trial registration ClinicalTrials.gov NCT00540800.

  10. Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study.

    Science.gov (United States)

    Croitoru, Adina; Gramaticu, Iulia; Dinu, Ioana; Gheorghe, Liana; Alexandrescu, Sorin; Buica, Florina; Luca, Ioana; Becheanu, Gabriel; Herlea, Vlad; Simionov, Iulia; Hrehoret, Doina; Lupescu, Ioana; Popescu, Irinel; Diculescu, Mircea

    2012-09-01

    This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.

  11. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study.

    Science.gov (United States)

    Necchi, A; Joseph, R W; Loriot, Y; Hoffman-Censits, J; Perez-Gracia, J L; Petrylak, D P; Derleth, C L; Tayama, D; Zhu, Q; Ding, B; Kaiser, C; Rosenberg, J E

    2017-12-01

    Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients. Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively. In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression. In this single-arm study, patients who continued atezolizumab beyond RECIST v1

  12. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Cho, Jae Yong; Schellens, Jan H M; Soria, Jean Charles; Wen, Patrick Y; Zielinski, Christoph; Cabanillas, Maria E; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima; Keam, Bhumsuk

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.

  13. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600–Mutant Anaplastic Thyroid Cancer

    Science.gov (United States)

    Subbiah, Vivek; Kreitman, Robert J.; Wainberg, Zev A.; Cho, Jae Yong; Schellens, Jan H.M.; Soria, Jean Charles; Wen, Patrick Y.; Zielinski, Christoph; Cabanillas, Maria E.; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E–mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E–mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E–mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease. PMID:29072975

  14. Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer

    DEFF Research Database (Denmark)

    Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick

    2014-01-01

    change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse......OBJECTIVE: To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics....... PATIENTS AND METHODS: The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3...

  15. Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial.

    Science.gov (United States)

    Nuzzo, Francesco; Morabito, Alessandro; Gravina, Adriano; Di Rella, Francesca; Landi, Gabriella; Pacilio, Carmen; Labonia, Vincenzo; Rossi, Emanuela; De Maio, Ermelinda; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; Thomas, Renato; Rinaldo, Massimo; Botti, Gerardo; Di Bonito, Maurizio; Di Maio, Massimo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

    2011-02-16

    To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm. In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. ClinicalTrials.gov NCT00540800.

  16. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer

    International Nuclear Information System (INIS)

    Miller, Kathy; Cortes, Javier; Hurvitz, Sara A.; Krop, Ian E.; Tripathy, Debu; Verma, Sunil; Riahi, Kaveh; Reynolds, Joseph G.; Wickham, Thomas J.; Molnar, Istvan; Yardley, Denise A.

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab – however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody–liposomal doxorubicin conjugate that specifically targets HER2-overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations. HERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is

  17. Unusual metastatic localizations of differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Ben Rais, N.; Ghfir, I.

    2007-01-01

    Full text: Introduction: The majority of thyroid cancers have a slow evolution, a more often loco-regional extension, and a good forecast. Remote metastases, when they exist, generally touch the osseous skeleton and/or pulmonary tissue. However, unusual metastatic localizations much more exceptional are possible. The authors report through these work five cases of atypical metastasis of differentiated thyroid carcinoma followed in Nuclear Medicine department of Ibn Sina hospital in Rabat under the directives of Professor N Ben Rais. Materials and methods: Our five patients had initially undergone a total thyroidectomy for differentiated thyroid carcinoma histologically confirmed. They had profited 4 weeks after the surgical gesture from a reference isotopic exploration (131 Iodine whole body scan and thyroglobulin dosage). The paraclinic assessment was supplemented by a computed tomography (CT). Results: Revealing symptomatology in the first 69 year old patient was dominated by blindness associated with an elective up-take of radioactive 131-Iodine on the level of hypophyseal gland extending to the sphenoid bone. The second 55 year old patient reported right basithoracic pains resisting to the usual antalgic treatment with a bulky mass driving back the kidney right to the bottom at CT with and important up-take 131-Iodine at whole body scan; a surrenalectomy was thus carried out with conservation of the kidney. The three other patients presented at the clinical examination dermohypodermic nodular lesions of various localizations whose anatomopathologic study had confirmed their thyroid metastatic origin. In the 5 patients the rate of thyroglobulin was considerably high. An activity of 3,7 GBq 131-Iodine was managed with the 5 patients. The evolution was marked, in the short run, at the first patient by a recovery partial of the sight, the disappearance of pain in the second patient and a remarkable reduction of thyroglobulin level for all our patients. Conclusion

  18. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial.

    Science.gov (United States)

    Heery, Christopher R; O'Sullivan-Coyne, Geraldine; Madan, Ravi A; Cordes, Lisa; Rajan, Arun; Rauckhorst, Myrna; Lamping, Elizabeth; Oyelakin, Israel; Marté, Jennifer L; Lepone, Lauren M; Donahue, Renee N; Grenga, Italia; Cuillerot, Jean-Marie; Neuteboom, Berend; Heydebreck, Anja von; Chin, Kevin; Schlom, Jeffrey; Gulley, James L

    2017-05-01

    Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data. This study used a standard 3 + 3 cohort design and assigned patients sequentially at trial entry according to the 3 + 3 dose-escalation algorithm and depending on the number of dose-limiting toxicities during the first 3-week assessment period (the primary endpoint). Patient eligibility criteria included age 18 years or older, Eastern Cooperative Oncology Group performance status 0-1, metastatic or locally advanced previously treated solid tumours, and adequate end-organ function. Avelumab was given as a 1-h intravenous infusion every 2 weeks. Patients in the dose-limiting toxicity analysis set were assessed for the primary endpoint of dose-limiting toxicity, and all patients enrolled in the dose-escalation part were assessed for the secondary endpoints of safety (treatment-emergent and treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0), pharmacokinetic and pharmacodynamic profiles (immunological effects), best overall response by Response Evaluation Criteria, and antidrug antibody formation. The population for the pharmacokinetic analysis included a subset of patients with rich pharmacokinetic samples from two selected disease-specific expansion cohorts at the same study site who had serum samples obtained at multiple early timepoints. This trial is registered with ClinicalTrials.gov, number NCT

  19. Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Brose, Marcia S; Schlumberger, Martin; Nutting, Christopher M; Sherman, Steven I; Shong, Young Kee; Smit, Johannes WA; Reike, Gerhard; Chung, John; Kalmus, Joachim; Kappeler, Christian

    2011-01-01

    The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC. DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI-refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles), whereas safety will be evaluated every 28 days (1 cycle) for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS); patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate, response rate, duration of response, safety, and

  20. Phase II study on paclitaxel in patients with recurrent, metastatic or locally advanced vulvar cancer not amenable to surgery or radiotherapy: a study of the EORTC-GCG (European Organisation for Research and Treatment of Cancer--Gynaecological Cancer Group)

    NARCIS (Netherlands)

    Witteveen, P. O.; van der Velden, J.; Vergote, I.; Guerra, C.; Scarabeli, C.; Coens, C.; Demonty, G.; Reed, N.

    2009-01-01

    No standard treatment options are available for patients with advanced, recurrent or metastatic vulvar carcinoma not amenable for locoregional treatment. In this phase II study, patients with advanced vulvar cancer received paclitaxel (Taxol) every 3 weeks for up to 10 cycles. Primary objective was

  1. Patterns of metastatic progression after definitive radiation therapy for early-stage and locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Jensen, Garrett L; Tang, Chad; Hess, Kenneth R; Liao, Zhongxing; Gomez, Daniel R

    2017-06-01

    Current preclinical models of metastatic disease (particularly oligometastases) suggest that metastases appear in a hierarchical order. We attempted to identify systematic patterns of metastasis in non-small cell lung cancer (NSCLC) after radiation therapy (XRT). We analyzed 1074 patients treated from 12/21/1998 through 8/20/2012 with ≥60 Gy definitive radiation for initially non-metastatic NSCLC. Location and time of metastases were recorded. Regional nodal failure was noted, as was subsequent distal failure. For further analysis, we considered only the five most common sites of metastasis (bone, brain, liver, adrenal, and lung). Metastatic progression over time was defined and patterns elucidated with Chi square tests. Histologic findings were analyzed with Wilcoxon rank sum tests. A significant multistep linear progression was not apparent. Having a first metastasis in lung or bone was associated with respective 16% (median 2.4 months) and 15% likelihoods (median 7.9 months) of secondary brain metastasis. Initial metastasis in the brain led to metastasis in another organ 29.3% of the time, most often in the lung, bone, and liver (medians 3.6, 7.9, and 3.1 months). Adenocarcinoma was more likely than squamous to metastasize to the brain (18 vs. 9%) and any of the five major sites (41 vs. 27%). We did not appreciate dominant patterns suggesting a multi-step hierarchical order of metastasis. Rather, our findings suggest that certain subgroups may develop different patterns of spread depending on a variety of factors.

  2. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

    OpenAIRE

    Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E.; Somer, Robert; Smakal, Martin; Emens, Leisha A.; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja

    2017-01-01

    Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 week...

  3. Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    Konski, Andre; Meyer, Joshua E.; Joiner, Michael; Hall, Michael J.; Philip, Philip; Shields, Anthony; McSpadden, Erin; Choi, Minsig; Adaire, Beth; Duncan, Gail; Meropol, Neal J.; Cescon, Terrence P.; Cohen, Steven J.

    2014-01-01

    Purpose: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0–1 who had received 0–1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 and 8, E once PO QD, and twice daily RT fractions separated by at least 4 h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. Conclusion: This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients

  4. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial.

    Science.gov (United States)

    Johnston, Stephen Rd; Kilburn, Lucy S; Ellis, Paul; Dodwell, David; Cameron, David; Hayward, Larry; Im, Young-Hyuck; Braybrooke, Jeremy P; Brunt, A Murray; Cheung, Kwok-Leung; Jyothirmayi, Rema; Robinson, Anne; Wardley, Andrew M; Wheatley, Duncan; Howell, Anthony; Coombes, Gill; Sergenson, Nicole; Sin, Hui-Jung; Folkerd, Elizabeth; Dowsett, Mitch; Bliss, Judith M

    2013-09-01

    The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation. In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 mg intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratification was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea). Between March 26, 2004, and Aug 6, 2010, 723 patients underwent randomisation: 243 were assigned to receive fulvestrant plus anastrozole, 231 to fulvestrant plus placebo, and 249 to exemestane. Median PFS was 4·4 months (95% CI 3·4-5·4) in patients assigned to

  5. Efficacy and tolerability of chemotherapy with modified dose-dense TCF regimen (TCF-dd) in locally advanced or metastatic gastric cancer: final results of a phase II trial.

    Science.gov (United States)

    Tomasello, Gianluca; Liguigli, Wanda; Poli, Rossana; Lazzarelli, Silvia; Brighenti, Matteo; Negri, Federica; Curti, Alessandra; Martinotti, Mario; Olivetti, Lucio; Rovatti, Massimo; Donati, Gianvito; Passalacqua, Rodolfo

    2014-10-01

    We previously studied a dose-dense TCF (TCF-dd) regimen demonstrating its feasibility and an activity comparable to epirubicin-based chemotherapy and TCF q3w in terms of overall survival and time to progression (TTP). We report here the final results of a phase II study of chemotherapy with a modified TCF-dd regimen in locally advanced or metastatic gastric cancer (MGC). Patients with histologically confirmed measurable MGC, not previously treated for advanced disease, received docetaxel 70 mg/m(2) day 1, cisplatin 60 mg/m(2) day 1, l-folinic acid 100 mg/m(2) days 1 and 2, followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus days 1 and 2, and then 600 mg/m(2) as a 22-h continuous infusion days 1 and 2, every 14 days, plus pegfilgrastim 6 mg on day 3. Patients aged ≥65 years received the same schedule with a dose reduction of 30 %. Study duration: December 2007-November 2010. Forty-six consecutive patients were enrolled (78 % male, 22 % female; median age, 66 years, range, 38-76 years; ECOG PS: 0, 48 %, 1, 46 %). Primary endpoint was overall response rate (ORR). A median of four cycles (range, one to six) was administered. Forty-three patients were evaluated for response (93.5 %) and all for toxicity: 3 complete response (CR), 25 partial response (PR), 10 stable disease (SD), and 5 progressive disease (PD) were observed, for an ORR by intention to treat (ITT) of 61 % (95 % CI 47-75). Median overall survival (OS) was 17.63 months (95 % CI, 13.67-20.67); median progression-free survival was 8.9 months (95 % CI, 6.5-13.4). Twenty-one patients (46.0 %) were treated at full doses without any delay, thus respecting the dose-dense criterion. Most frequent grade 3-4 toxicities were neutropenia (20 %), leukopenia (4 %), thrombocytopenia (2 %), anemia (2 %), febrile neutropenia (6 %), asthenia (22 %), diarrhea (4 %), nausea/vomiting (11 %), and hypokalemia (6 %). Overall, TCF-dd was shown to be safe. The TCF-dd regimen in locally advanced or MGC

  6. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial.

    Science.gov (United States)

    Tap, William D; Papai, Zsuzsanna; Van Tine, Brian A; Attia, Steven; Ganjoo, Kristen N; Jones, Robin L; Schuetze, Scott; Reed, Damon; Chawla, Sant P; Riedel, Richard F; Krarup-Hansen, Anders; Toulmonde, Maud; Ray-Coquard, Isabelle; Hohenberger, Peter; Grignani, Giovanni; Cranmer, Lee D; Okuno, Scott; Agulnik, Mark; Read, William; Ryan, Christopher W; Alcindor, Thierry; Del Muro, Xavier F Garcia; Budd, G Thomas; Tawbi, Hussein; Pearce, Tillman; Kroll, Stew; Reinke, Denise K; Schöffski, Patrick

    2017-08-01

    doxorubicin plus evofosfamide and 323 to doxorubicin alone), all of whom were included in the intention-to-treat analysis. The overall survival endpoint was not reached (hazard ratio 1·06, 95% CI 0·88-1·29; p=0·527), with a median overall survival of 18·4 months (95% CI 15·6-22·1) with doxorubicin plus evofosfamide versus 19·0 months (16·2-22·4) with doxorubicin alone. The most common grade 3 or worse adverse events in both groups were haematological, including anaemia (150 [48%] of 313 patients in the doxorubicin plus evofosfamide group vs 65 [21%] of 308 in the doxorubicin group), neutropenia (47 [15%] vs 92 [30%]), febrile neutropenia (57 [18%] vs 34 [11%]), leucopenia (22 [7%] vs 17 [6%]), decreased neutrophil count (31 [10%] vs 41 [13%]), and decreased white blood cell count (39 [13%] vs 33 [11%]). Grade 3-4 thrombocytopenia was more common in the combination group (45 [14%]) than in the doxorubicin alone group (four [1%]), as was grade 3-4 stomatitis (26 [8%] vs seven [2%]). Serious adverse events were reported in 145 (46%) of 313 patients in the combination group and 99 (32%) of 308 in the doxorubicin alone group. Five (2%) patients died from treatment-related causes in the combination group (sepsis [n=2], septic shock [n=1], congestive cardiac failure [n=1], and unknown cause [n=1]) versus one (<1%) patient in the doxorubicin alone group (lactic acidosis [n=1]). The addition of evofosfamide to doxorubicin as first-line therapy did not improve overall survival compared with single-drug doxorubicin in patients with locally advanced, unresectable, or metastatic soft-tissue sarcomas and so this combination cannot be recommended in this setting. Threshold Pharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer.

    Science.gov (United States)

    Welslau, Manfred; Diéras, Veronique; Sohn, Joo-Hyuk; Hurvitz, Sara A; Lalla, Deepa; Fang, Liang; Althaus, Betsy; Guardino, Ellie; Miles, David

    2014-03-01

    This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale). In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm. Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life. © 2013 American Cancer Society.

  8. Local recurrence of metastatic brain tumor after surgery

    International Nuclear Information System (INIS)

    Shinoura, Nobusada; Yamada, Ryoji; Okamoto, Koichiro; Nakamura, Osamu; Shitara, Nobuyuki; Karasawa, Katsuyuki

    2006-01-01

    We analyzed factors associated with the local recurrence of brain metastases after surgery. Forty-seven patients with 67 metastatic brain tumors underwent surgery between 1994 and 2001. The survival time in the ''no recurrence'' group (34.7 months) was significantly longer than that in the recurrence group (21.9 months) (p=0.0008; log rank test). The factors affecting the local recurrence of brain metastases after surgery were as follows: cyst (p=0.0156), dural invasion (p=0.0029) of tumors, failure to totally remove tumors (p=0.0040), and lack of post-surgical irradiation (p<0.0001). Sex, age, tumor histology, tumor size, pre-surgical radiation, dose (≥45 vs <45, ≥50 vs <50 Gy) and the method (local vs whole brain) of post-surgical radiation did not affect the local recurrence rate of brain metastases after surgery. To avoid early recurrences of metastatic brain tumors, the factors associated with local recurrence should be considered in providing optimal treatment of tumors by surgery. (author)

  9. Chyle fistula in advanced and metastatic thyroid cancer.

    Science.gov (United States)

    Duque, Carlos S; Sánchez, Juan Guillermo; Dionigi, Gianlorenzo

    2017-10-01

    Chyle fistula (CF) is a rare but challenging condition for the surgeon and the patient's health. A retrospective review of single surgeon's case load in a 12-year period is presented, reviewing the case of those patients presenting with a CF. Three patients were found during this study period from more than 1,050 surgeries performed due to thyroid cancer. Patients underwent extensive lymph node dissection for advanced, metastatic and infiltrative disease. In all patients, a long hospital stay and surgical re-interventions were required. A description of the management of CF is presented along with a review of current Literature.

  10. Surgical Management of Advanced and Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach

    Directory of Open Access Journals (Sweden)

    Brian M. Shinder

    2017-05-01

    Full Text Available The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2 has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease. Several prospective trials examining the role of adjuvant therapy are underway. Lastly, the first immune checkpoint inhibitor was approved for metastatic renal cell carcinoma (mRCC in 2015, providing a new treatment mechanism and new opportunities for combining systemic therapy with surgery. This review discusses current and historical literature regarding the surgical management of patients with advanced and mRCC and explores approaches for optimizing patient selection.

  11. CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2018-05-22

    Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

  12. Management of unresectable, locally advanced pancreatic adenocarcinoma.

    Science.gov (United States)

    Salgado, M; Arévalo, S; Hernando, O; Martínez, A; Yaya, R; Hidalgo, M

    2018-02-01

    The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

  13. Targeted treatment of advanced and metastatic breast cancer with lapatinib

    Directory of Open Access Journals (Sweden)

    Brendan Corkery

    2008-09-01

    Full Text Available Brendan Corkery1,2, Norma O’Donovan2, John Crown1,21St. Vincent’s University Hospital, Dublin, Ireland; 2National Institute for Cellular Biotechnology, Dublin City University, Dublin, IrelandAbstract: Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated.Keywords: HER-2, EGFR, erbB, lapatinib, Tykerb®, tyrosine kinase

  14. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs). Recent insights and advances

    International Nuclear Information System (INIS)

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, R.T.

    2012-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. (author)

  15. The management of localized and locally advanced prostate cancer - 1995

    International Nuclear Information System (INIS)

    Forman, Jeffrey D.

    1995-01-01

    Purpose/Objectives: The intent of this course is to review the issues involved in the management of non-metastatic adenocarcinoma of the prostate. - The value of pre-treatment prognostic factors including stage, grade and PSA value will be presented, and their value in determining therapeutic strategies will be discussed. - Controversies involving the simulation process and treatment design will be presented. The value of CT scanning, Beams-Eye View, 3-D planning, intravesicle, intraurethral and rectal contrast will be presented. The significance of prostate and patient movement and strategies for dealing with them will be presented. - The management of low stage, low to intermediate grade prostate cancer will be discussed. The dose, volume and timing of irradiation will be discussed as will the role of neo-adjuvant hormonal therapy, neutron irradiation and brachy therapy. The current status of radical prostatectomy and cryotherapy will be summarized. - Treatment of locally advanced, poorly differentiated prostate cancer will be presented including a discussion of neo-adjuvant and adjuvant hormones, dose-escalation and neutron irradiation. - Strategies for post-radiation failures will be presented including data on cryotherapy, salvage prostatectomy and hormonal therapy (immediate, delayed and/or intermittent). New areas for investigation will be reviewed. - The management of patients post prostatectomy will be reviewed. Data on adjuvant radiation and therapeutic radiation for biochemical or clinically relapsed patients will be presented. This course hopes to present a realistic and pragmatic overview for treating patients with non-metastatic prostatic cancer

  16. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    Science.gov (United States)

    2017-04-18

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  17. Should Aggressive Surgical Local Control Be Attempted in All Patients with Metastatic or Pelvic Ewing's Sarcoma?

    Science.gov (United States)

    Thorpe, Steven W.; Weiss, Kurt R.; Goodman, Mark A.; Heyl, Alma E.; McGough, Richard L.

    2012-01-01

    In previous reports, patients with Ewing's sarcoma received radiation therapy (XRT) for definitive local control because metastatic disease and pelvic location were thought to preclude aggressive local treatment. We sought to determine if single-site metastatic disease should be treated differently from multicentric-metastatic disease. We also wanted to reinvestigate the impact of XRT, pelvic location, and local recurrence on outcomes. Our results demonstrated a significant difference in overall survival (OS) between patients with either localized disease or a single-metastatic site and patients with multicentric-metastatic disease (P = 0.004). Local control was also found to be an independent predictor of outcomes as demonstrated by a significant difference in OS between those with and without local recurrence (P = 0.001). Axial and pelvic location did not predict a decreased OS. Based on these results, we concluded that pelvic location and the diagnosis of metastatic disease at diagnosis should not preclude aggressive local control, except in cases of multicentric-metastatic disease. PMID:22550427

  18. [Management of localized, locally advanced and metastatic pancreatic adenocarcinoma].

    Science.gov (United States)

    Delpero, Jean-Robert; Turrini, Olivier; Raoul, Jean-Luc

    2015-03-01

    Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

  19. Radiation therapy in the management of locally advanced and disseminated breast cancer

    International Nuclear Information System (INIS)

    Chu, F.C.H.

    1980-01-01

    Radiation theraoy should be fully used in the management of advanced breast cancer. Locally advanced primary or recurrent carcinoma, with limited extent, should be treated aggressively, aimed at permanent control. Palliative treatment of incurable or metastatic lesions relieves symptoms and improves patient's quality of survival. Some metastatic lesions involving vital structures may create emergencies. Prompt institution of radiation therapy may reverse the serious complication and save the patient's life

  20. Local Treatment of Metastatic Prostate Cancer: What is the Evidence So Far?

    Directory of Open Access Journals (Sweden)

    Pedro Leonel Almeida

    2018-01-01

    Full Text Available Background. Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic prostate cancer (mPCa at diagnosis which, in young and fit patients, will become invariably resistant to the established treatments. Progression will lead to an impairment in patients’ quality of life and disease-related death. Methods. The authors intend to perform a literature review of the advantages of primary treatment of mPCa. Articles were retrieved and filtered for relevance from PubMed, SciELO, and ScienceDirect until March 2017. Results. Primary treatment is currently indicated only in cases of nonmetastatic PCa. Nonetheless, there might be some benefits in doing local treatment in mPCa in order to control local disease, prevent new metastasis, and improve the efficacy of chemotherapy and hormonotherapy with similar complications rate when compared to locally confined cancer. Independent factors that have a negative influence are age above 70 years, cT4 stage or high-grade disease, PSA≥20 ng/ml, and pelvic lymphadenopathies. The presence of 3 or more of these factors conditions CSS and OS is the same between patients who performed local treatment and those who did not. Metastasis degree and location number can also influence outcome. Meanwhile, patients with visceral metastases have worse results. Conclusions. There is growing evidence supporting local treatment in cases of metastatic prostate cancer at diagnosis in the context of a multimodal approach. However, it should be kept in mind that most of the existing studies are retrospective and it would be important to make consistent prospective studies with well-defined patient selection criteria in order to sustain the existing data and understand the main indications to select patients and perform primary treatment in mPCa.

  1. Local Treatment of Metastatic Prostate Cancer: What is the Evidence So Far?

    Science.gov (United States)

    Leonel Almeida, Pedro; Jorge Pereira, Bruno

    2018-01-01

    Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic prostate cancer (mPCa) at diagnosis which, in young and fit patients, will become invariably resistant to the established treatments. Progression will lead to an impairment in patients' quality of life and disease-related death. The authors intend to perform a literature review of the advantages of primary treatment of mPCa. Articles were retrieved and filtered for relevance from PubMed, SciELO, and ScienceDirect until March 2017. Primary treatment is currently indicated only in cases of nonmetastatic PCa. Nonetheless, there might be some benefits in doing local treatment in mPCa in order to control local disease, prevent new metastasis, and improve the efficacy of chemotherapy and hormonotherapy with similar complications rate when compared to locally confined cancer. Independent factors that have a negative influence are age above 70 years, cT4 stage or high-grade disease, PSA ≥ 20 ng/ml, and pelvic lymphadenopathies. The presence of 3 or more of these factors conditions CSS and OS is the same between patients who performed local treatment and those who did not. Metastasis degree and location number can also influence outcome. Meanwhile, patients with visceral metastases have worse results. There is growing evidence supporting local treatment in cases of metastatic prostate cancer at diagnosis in the context of a multimodal approach. However, it should be kept in mind that most of the existing studies are retrospective and it would be important to make consistent prospective studies with well-defined patient selection criteria in order to sustain the existing data and understand the main indications to select patients and perform primary treatment in mPCa.

  2. Nodal imaging in the neck: recent advances in US, CT and MR imaging of metastatic nodes

    International Nuclear Information System (INIS)

    Nakamura, Takashi; Sumi, Misa

    2007-01-01

    The presence of lymph node metastasis in the neck in patients with head and neck cancer is an important prognostic determinant in staging cancers and in planning surgery and chemo- and radiotherapy for the cancer patients. Therefore, metastatic nodes should be effectively differentiated from benign lymphadenopathies and nodal lymphomas. Here, we review recent advances in the diagnostic imaging of metastatic nodes in the neck, with emphasis placed on the diagnostic performance of MR imaging, Doppler sonography, and CT. (orig.)

  3. The role of radiotherapy in the local treatment of a straightaway metastatic breast cancer

    International Nuclear Information System (INIS)

    Ali, D.

    2010-01-01

    Breast cancer is diagnosed when it is already metastatic in about 6 per cent of cases. The author discusses comparative studies which showed that a surgical treatment of the primitive tumour resulted in a global survival benefit for the patients. As the role of radiotherapy in such a situation, either alone or with surgery, is not well documented, he intends to discuss the interest of radiotherapy within the frame of the local treatment of a straightaway metastatic breast cancer. Short communication

  4. Metastatic cervical lymphadenopathy from uterine leiomyosarcoma with good local response to radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Oh, Yoon Kyeong; Park, Hee Chul; Kee, Keun Hong; Jeon, Ho Jong; Park, You Hwan; Chung, Choon Hai

    2000-01-01

    The metastasis of uterine leiomyosarcoma to the neck node has not been reported previously and the radiotherapy has been rarely used for the metastatic lesion of the other sites. We report a case of neck metastasis from a uterine leiomyosarcoma, which developed 10 months after surgery and postoperative pelvic radiotherapy. It also involved the parapharyngeal space, adjacent spine, and spinal canal. The metastatic neck mass was inoperable, and was treated by neck radiotherapy (6,000 cGy) and chemotherapy including taxol and carboplatin. The mass has regressed progressively to a nearly impalpable state. She has never developed spinal cord compression syndrome, and has maintained good swallowing for eight months since the neck radiotherapy and chemotherapy. Since the extensive metastatic neck mass showed good local response to high dose radiotherapy and chemotherapy, both treatments may be considered for an unresectable metastatic leiomyosarcoma

  5. A phase II study of weekly irinotecan in patients with locally advanced or metastatic HER2- negative breast cancer and increased copy numbers of the topoisomerase 1 (TOP1) gene

    DEFF Research Database (Denmark)

    Kümler, Iben; Balslev, Eva; Stenvang, Jan

    2015-01-01

    breast cancer and increased expression of the topoisomerase 1 gene have a high likelihood of obtaining a clinical benefit from treatment with irinotecan. Trial recruitment is two-staged as 19 patients are planned to participate in the first part. If less than 7 patients have clinical benefit the trial...... is a topoisomerase 1 inhibitor used for decades for the treatment of colorectal cancer. Four studies have investigated the efficacy of irinotecan monotherapy in breast cancer and all have included non-biomarker selected patients. In these studies response rates for irinotecan ranged from 5%-23% and are thus......BACKGROUND: About 20% of patients with primary breast cancer develop metastatic disease during the course of the disease. At this point the disease is considered incurable and thus treatment is aimed at palliation and life prolongation. As many patients will have received both an anthracycline...

  6. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study

    DEFF Research Database (Denmark)

    Andersson, Michael; Lidbrink, Elisabeth; Bjerre, Karsten

    2011-01-01

    To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer.......To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer....

  7. Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

    Science.gov (United States)

    Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Koch, Michael D.; Lynch, Douglas W.; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E.; Jaggi, Meena

    2012-01-01

    MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. PMID:22914648

  8. Sorafenib for Metastatic Thyroid Cancer

    Science.gov (United States)

    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  9. Gemcitabine Plus Docetaxel Versus Docetaxel in Patients With Predominantly Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Randomized, Phase III Study by the Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Nielsen, Dorte L; Bjerre, Karsten D; Jakobsen, Erik H

    2011-01-01

    PURPOSE The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer. PATIENTS AND METHODS Predominantly human epidermal growth factor receptor 2 (HER2) -negative patients were randomly assigned...

  10. First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study.

    Science.gov (United States)

    Tomasello, Gianluca; Valeri, Nicola; Ghidini, Michele; Smyth, Elizabeth C; Liguigli, Wanda; Toppo, Laura; Mattioli, Rodolfo; Curti, Alessandra; Hahne, Jens C; Negri, Federica M; Panni, Stefano; Ratti, Margherita; Lazzarelli, Silvia; Gerevini, Fabiana; Colombi, Chiara; Panni, Andrea; Rovatti, Massimo; Treccani, Leonardo; Martinotti, Mario; Passalacqua, Rodolfo

    2017-12-19

    Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy. HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression. From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment. Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required.Clinical trial information: 2009-016962-10.

  11. Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma.

    Science.gov (United States)

    Jones, Robin L; Katz, Daniela; Loggers, Elizabeth T; Davidson, Darin; Rodler, Eve T; Pollack, Seth M

    2017-08-29

    Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma.

  12. Local bone pain and osseous scintigraphic findings in patients with metastatic bone tumor

    International Nuclear Information System (INIS)

    Imaeda, Takeyoshi; Iinuma, Gen; Hirota, Keiichi; Inoue, Akemi; Sone, Yasuhiro; Seki, Matsuzo; Suzuki, Masao; Doi, Hidetaka

    1988-01-01

    Local bone pain and osseous scintigraphic findings were evaluated in patients with cancer of the lung, breast or prostate. (1) In 77-92% out of the patients with local pain, metastatic bone lesions were detected. (2) The sacrum and scapulae were the frequent sites of pain as estimated from the metastatic bone lesions. On the other hand, the incidence of pain was low in the ribs, cervical vertebrae, skull and femurs. (3) When calculated by the weight of red bone marrow, the most likely sites for bone metastases consisted of the scapulae, clavicles, sternum, humeri, ribs and cervical vertebrae, somewhat different from previous reports. Those bones involved were all proximate to the heart. (4) Extensive bone metastases were already detected in more than 50% of patients who complain of pain in the metastatic bone lesion. On the other hand, extensive bone metastases occurred in less than 6% of patients who didn't complain of pain. (5) The appearance of pain in the metastatic bone lesion was earlier in only 3% and was later in 71% than the detection of abnormal radioisotope accumulation on scintigram. (6) Majority of the patients with pain in the metastatic bone lesion showed a high degree of abnormal radioisotope accumulation which measured more than 5 cm in diameter on scintigram. On the other hand, the abnormal radioisotope accumulation in most of patients without pain was mild and mostly measured less than 5 cm in diameter. (7) The positive rate of bone metastasis amounted to 29% by plain X-ray and 41% by local bone pain as compaired to positive bone scintigram. (author)

  13. Local bone pain and osseous scintigraphic findings in patients with metastatic bone tumor

    Energy Technology Data Exchange (ETDEWEB)

    Imaeda, Takeyoshi; Iinuma, Gen; Hirota, Keiichi; Inoue, Akemi; Sone, Yasuhiro; Seki, Matsuzo; Suzuki, Masao; Doi, Hidetaka

    1988-12-01

    Local bone pain and osseous scintigraphic findings were evaluated in patients with cancer of the lung, breast or prostate. (1) In 77-92% out of the patients with local pain, metastatic bone lesions were detected. (2) The sacrum and scapulae were the frequent sites of pain as estimated from the metastatic bone lesions. On the other hand, the incidence of pain was low in the ribs, cervical vertebrae, skull and femurs. (3) When calculated by the weight of red bone marrow, the most likely sites for bone metastases consisted of the scapulae, clavicles, sternum, humeri, ribs and cervical vertebrae, somewhat different from previous reports. Those bones involved were all proximate to the heart. (4) Extensive bone metastases were already detected in more than 50% of patients who complain of pain in the metastatic bone lesion. On the other hand, extensive bone metastases occurred in less than 6% of patients who didn't complain of pain. (5) The appearance of pain in the metastatic bone lesion was earlier in only 3% and was later in 71% than the detection of abnormal radioisotope accumulation on scintigram. (6) Majority of the patients with pain in the metastatic bone lesion showed a high degree of abnormal radioisotope accumulation which measured more than 5 cm in diameter on scintigram. On the other hand, the abnormal radioisotope accumulation in most of patients without pain was mild and mostly measured less than 5 cm in diameter. (7) The positive rate of bone metastasis amounted to 29% by plain X-ray and 41% by local bone pain as compaired to positive bone scintigram.

  14. Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.

    Science.gov (United States)

    Esteban, E; Majem, M; Martinez Aguillo, M; Martinez Banaclocha, N; Dómine, M; Gómez Aldaravi, L; Juan, O; Cajal, R; Gonzalez Arenas, M C; Provencio, M

    2015-06-01

    The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients. All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations. From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%). The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in

  15. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    International Nuclear Information System (INIS)

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-01-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  16. [Advances in radiation oncology for metastatic bone disease].

    Science.gov (United States)

    Thariat, Juliette; Fric, Danièle; Kerr, Christine; Leysalle, Axel; Angellier, Gaelle; Dejean, Catherine; Tuillier, Titien; Bensadoun, René-Jean; Lagrange, Jean-Léon

    2013-11-01

    Irradiation of bone metastases primarily aims at alleviating pain, preventing fracture in the short term. The higher doses and more conformal dose distribution achievable while saving healthy tissue with new irradiation techniques have induced a paradigm shift in the management of bone metastases in a growing number of clinical situations. A search of the English and French literature was conducted using the keywords: bone metastases, radiotherapy, interventional radiology, vertebroplasty, radiofrequency, chemoembolization. RESULTS-DISCUSSION: Stereotactic irradiation yields pain relief rates greater than 90% in Phase I/II and retrospective studies. IMRT (static, rotational, helical) and stereotactic irradiation yield local control rates of 75-90% at 2 years. Some situations previously evaluated as palliative are currently treated more aggressively with optimized radiation sometimes combined modality interventional radiology. A recommendation can only be made for stereotactic irradiation in vertebral oligometastases or reirradiation. In the absence of a sufficient level of evidence, the increasing use of conformal irradiation techniques can only reflect the daily practice and the patient benefit while integrating economic logic care. The impact of these aggressive approaches on survival remains to be formally demonstrated by interventional prospective studies or observatories including quality of life items and minimal 2-year follow-up.

  17. Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

    International Nuclear Information System (INIS)

    Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

    2012-01-01

    The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

  18. Management of Locally Advanced Renal Cell Carcinoma with Invasion of the Duodenum

    Directory of Open Access Journals (Sweden)

    Andrew T. Schlussel

    2013-01-01

    Full Text Available Renal cell carcinoma (RCC is rare but aggressive, with greater than 20% of patients presenting with stage III or IV, disease. Surgical resection of the primary tumor regardless of stage is the treatment of choice, and en bloc resection of involved organs provides the only potential chance for cure. This case report describes a patient with metastatic right-sided RCC with invasion of the inferior vena cava and duodenum managed by en block resection and pancreaticoduodenectomy. This report will review the workup and treatment of locally advanced RCC, as well as the role of cytoreductive nephrectomy in the setting of metastatic disease.

  19. Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection

    International Nuclear Information System (INIS)

    Delpero, J.R.; Turrini, O.

    2006-01-01

    Induction chemoradiotherapy (CRT) may down-stage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a RO resection. Patients and methods. We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neo-adjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. Results. The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The RO resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. Conclusion. Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic disease

  20. Advances in local anesthesia in dentistry.

    Science.gov (United States)

    Ogle, Orrett E; Mahjoubi, Ghazal

    2011-07-01

    Local pain management is the most critical aspect of patient care in dentistry. The improvements in agents and techniques for local anesthesia are probably the most significant advances that have occurred in dental science. This article provides an update on the most recently introduced local anesthetic agents along with new technologies used to deliver local anesthetics. Safety devices are also discussed, along with an innovative method for reducing the annoying numbness of the lip and tongue following local anesthesia. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Rate of PSA rise predicts metastatic versus local recurrence after definitive radiotherapy

    International Nuclear Information System (INIS)

    Sartor, C.I.; Strawderman, M.H.; Lin, X.; Kish, K.E.; McLaughlin, P.W.; Lichter, A.S.; Sandler, H.S.

    1995-01-01

    Objective: A rising PSA following treatment for adenocarcinoma of the prostate indicates eventual clinical failure, but the rate of rise can be quite different from patient to patient, as can the pattern of clinical failure. We sought to determine whether the rate of PSA rise could differentiate future local vs. metastatic failure. Materials and Methods: PSA values from our series of 671 patients treated between 1987 and 1994 with 3-D conformal radiotherapy for localized adenocarcinoma were analyzed. Patients who had a pre-treatment PSA and >4 post-treatment PSA values available, had received no hormonal therapy, and had information detailing clinical outcome were used in this analysis. First site of failure was determined by abnormal DRE or biopsy, abnormal bone scan or radiographic evidence of metastasis as directed by clinical symptoms or follow-up clinical exam. Each patient's PSA pattern was defined by the function PSA(t)=C 1 e - a 1 (t) + C 2 e a 2 (t) where -a 1 relates to the rate of decline and a 2 to the rate of rise, if any. Univariate analysis was used to determine the correlation between initial PSA or rising PSA and clinical failure. Adjacent category logistic regression analysis was used to analyze the rate of rise and pattern of clinical failure. Results: 671 patients were reviewed; 401 patients met the requirements and 2667 PSA values were analyzed. We confirmed the finding of others that pre-treatment PSA is a prognostic indicator: patients presenting with PSA 3-20ng/ml had a relative risk of 9 (p=0.03) and PSA>20ng/ml had a RR of 26 (p=0.002) for clinical failure when compared to presenting PSA 2 >1.5/year predicted metastatic as opposed to local failure when compared to PSA rise with a 2 between 0.5-1.5/yr or 1.5 log(ng/ml)/year vs. 0.5-1.5 log(ng/ml)/yr or <0.5 log(ng/ml)/yr. Conclusions: The rate of rise of PSA following definitive radiotherapy can predict clinical failure patterns, with a rapidly rising PSA indicating metastatic as opposed to

  2. The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer.

    Science.gov (United States)

    Susko, Matthew; Lee, Jason; Salama, Joseph; Thomas, Samantha; Uronis, Hope; Hsu, David; Migaly, John; Willett, Christopher; Czito, Brian; Palta, Manisha

    2016-10-01

    The optimal approach to patients with locally recurrent, non-metastatic rectal cancer is unclear. This study evaluates the outcomes and toxicity associated with pelvic re-irradiation. Patients undergoing re-irradiation for locally recurrent, non-metastatic, rectal cancer between 2000 and 2014 were identified. Acute and late toxicities were assessed using common terminology criteria for adverse events version 4.0. Disease-related endpoints included palliation of local symptoms, surgical outcomes, and local progression-free survival (PFS), distant PFS and overall survival (OS) using the Kaplan-Meier method. Thirty-three patients met the criteria for inclusion in this study. Two (6 %) experienced early grade 3+ toxicity and seven (21 %) experienced late grade 3+ toxicity. Twenty-three patients presented with symptomatic local recurrence and 18 (78 %) reported symptomatic relief. Median local PFS was 8.7 (95 % CI 3.8-15.2) months, with a 2-year rate of 15.7 % (4.1-34.2), and median time to distant progression was 4.4 (2.2-33.3) months, with a 2-year distant PFS rate of 38.9 % (20.1-57.3). Median OS time for patients was 23.1 (11.1-33.0) months. Of the 14 patients who underwent surgery, median survival was 32.3 (13.8-48.0) months compared with 13.3 (2.2-33.0) months in patients not undergoing surgery (p = 0.10). A margin-negative (R0) resection was achieved in 10 (71 %) of the surgeries. Radiation treatment modality (intensity-modulated radiation therapy, three-dimensional conformal radiotherapy, intraoperative radiation therapy) did not influence local or distant PFS or OS. Re-irradiation is a beneficial treatment modality for the management of locally recurrent, non-metastatic rectal cancer. It is associated with symptom improvement, low rates of toxicity, and similar benefits among radiation modalities.

  3. Comparison of metastatic disease after local tumour treatment with radiotherapy or surgery in various tumour models

    International Nuclear Information System (INIS)

    Ruiter, J. de; Cramer, S.J.; Lelieveld, P.; Putten, L.M. van

    1982-01-01

    Spontaneous metastases in lymph nodes and/or the lung were obtained after tumour cell inoculation of four mouse tumours and one rat tumour into the foot-pads of syngeneic animals or their F 1 hybrids. Following local radiotherapy with doses of 45-80 Gy, significantly more mice died with metastases than following local amputation of the tumour-bearing foot when the 2661 carcinoma was involved. No significant difference was observed after these treatments for the other tumours. The enhancement of metastatic growth after local radiotherapy in the 2661 carcinoma seems not to be due to incomplete killing of tumour cells in the foot. The presence of irradiated normal structures and tumour tissue after radiotherapy promoted the outgrowth of 2661 carcinoma cells which were outside the radiation field at the time of treatment. Evidently, even under similar experimental conditions, radiotherapy may enhance the growth of metastases from some tumours and not from others. (author)

  4. Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Kim, Esther S; Scott, Lesley J

    2017-06-01

    Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates. Neutropenia was the most commonly reported any-grade and grade ≥ 3 adverse event. It was infrequently associated with febrile neutropenia (<2%) and generally manageable with a palbociclib dose delay, interruption or reduction, without the routine use of growth factors, and without affecting efficacy. In conclusion, oral palbociclib combination therapy is a valuable emerging option for use in patients with HR-positive, HER2-negative advanced or metastatic breast cancer.

  5. Combination of retrograde superselective intra-arterial chemotherapy and Seldinger method in locally advanced oral cancer

    Directory of Open Access Journals (Sweden)

    Masataka Uehara

    2015-01-01

    Full Text Available The nonsurgical strategies for locally advanced oral cancer are desirable. Superselective intra-arterial infusion with radiotherapy was utilized for this purpose, and there are two types of superselective intra-arterial infusion methods: The Seldinger method and the retrograde superselective intra-arterial chemotherapy (HFT method. In one case, the HFT method was applied to locally advanced tongue cancer, and the Seldinger method was used for additional administration of cisplatin (CDDP to compensate for a lack of drug flow in the HFT method. In another case, the HFT method was applied to locally advanced lower gingival cancer. The Seldinger method was applied to metastatic lymph nodes. In both cases, additional administration of CDDP using the Seldinger method resulted in a complete response. The combination of the HFT and Seldinger methods was useful to eradicate locally advanced oral cancer because each method compensated for the defects of the other.

  6. Using Local Data To Advance Quantitative Literacy

    Directory of Open Access Journals (Sweden)

    Stephen Sweet

    2008-07-01

    Full Text Available In this article we consider the application of local data as a means of advancing quantitative literacy. We illustrate the use of three different sources of local data: institutional data, Census data, and the National College Health Assessment survey. Our learning modules are applied in courses in sociology and communication, but the strategy of using local data can be integrated beyond these disciplinary boundaries. We demonstrate how these data can be used to stimulate student interests in class discussion, advance analytic skills, as well as develop capacities in written and verbal communication. We conclude by considering concerns that may influence the types of local data used and the challenges of integrating these data in a course in which quantitative analysis is not typically part of the curriculum.

  7. Zoledronic acid in metastatic chondrosarcoma and advanced sacrum chordoma: two case reports

    Directory of Open Access Journals (Sweden)

    Capasso Elena

    2009-01-01

    Full Text Available Abstract Introduction Chondrosarcomas and chordomas are usually chemoresistant bone tumors and may have a poor prognosis when advanced. They are usually associated with worsening pain difficult to control. Patients and Methods Zoledronic acid was used in a 63-year-old man with metastatic chondrosarcoma and in a 66-year-old woman with a diagnosis of sacrum chordoma both reporting severe pain related to tumor. Results In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, zoledronic acid only produced significant clinical benefit. Conclusion Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor response to other treatments. Evaluation on larger series are needed to confirm the clinical effect of this bisphosphonate on such tumors.

  8. Advanced design of local ventilation systems

    Energy Technology Data Exchange (ETDEWEB)

    Kulmala, I. [VTT Manufacturing Technology, Espoo (Finland). Safety Technology

    1997-12-31

    Local ventilation is widely used in industry for controlling airborne contaminants. However, the present design practices of local ventilation systems are mainly based on empirical equations and do not take quantitatively into account the various factors affecting the performance of these systems. The aim of this study was to determine the applicability and limitations of more advanced fluid mechanical methods to the design and development of local ventilation systems. The most important factors affecting the performance of local ventilation systems were determined and their effect was studied in a systematic manner. The numerical calculations were made with the FLUENT computer code and they were verified by laboratory experiments, previous measurements or analytical solutions. The results proved that the numerical calculations can provide a realistic simulation of exhaust openings, effects of ambient air flows and wake regions. The experiences with the low-velocity local supply air showed that these systems can also be modelled fairly well. The results were used to improve the efficiency and thermal comfort of a local ventilation unit and to increase the effective control range of exhaust hoods. In the simulation of the interaction of a hot buoyant source and local exhaust, the predicted capture efficiencies were clearly higher than those observed experimentally. The deviations between measurements and non-isothermal flow calculations may have partly been caused by the inability to achieve grid independent solutions. CFD simulations is an advanced and flexible tool for designing and developing local ventilation. The simulations can provide insight into the time-averaged flow field which may assist us in understanding the observed phenomena and to explain experimental results. However, for successful calculations the applicability and limitations of the models must be known. (orig.) 78 refs.

  9. The influence of whole-body and local irradiation modified by hyperglycemia on metastatic Walker carcinosarcoma 256 in rats

    International Nuclear Information System (INIS)

    Kutlimuratov, A.B.; Ivashkin, A.V.; Zakirkhodzhaev, U.D.

    1990-01-01

    It has been shown that the local radiation therapy, and also radiation therapy modified by the short-term hyperglycemia really increase the life-span of rats with Walker 256 carcinosarcoma. At the same time the metastatic process also increases, especially after the modified radiation therapy. The total irradiation of experimental animals in a dose of 50 sGy before the modified radiation therapy considerably decreases the frequency of metastatic process. A conclusion is drawn that the total irradiation has a prophylactic influence on metastases under conditions of modified radiation therapy

  10. Local AREA networks in advanced nuclear reactors

    International Nuclear Information System (INIS)

    Bicknell, J.; Keats, A.B.

    1984-01-01

    The report assesses Local Area Network Communications with a view to their application in advanced nuclear reactor control and protection systems. Attention is focussed on commercially available techniques and systems for achieving the high reliability and availability required. A basis for evaluating network characteristics in terms of broadband or baseband type, medium, topology, node structure and access method is established. The reliability and availability of networks is then discussed. Several commercial networks are briefly assessed and a distinction made between general purpose networks and those suitable for process control. The communications requirements of nuclear reactor control and protection systems are compared with the facilities provided by current technology

  11. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Hao Y

    2016-06-01

    Full Text Available Yanni Hao,1 Verena Wolfram,2 Jennifer Cook2 1Novartis Pharmaceuticals, East Hanover, NJ, USA; 2Adelphi Values, Bollington, UK Background: Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods: Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases, online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center, and web sites of health technology assessment (HTA bodies. Publications were selected based on the search strategy and the overall study objectives. Results: A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D. Other utility measures, such as the direct methods standard gamble (SG, time trade-off (TTO, and visual analog scale (VAS, were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23, Functional Assessment of Cancer Therapy – General questionnaire (FACT-G, and Utility-Based Questionnaire-Cancer (UBQ-C; most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex

  12. Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

    Science.gov (United States)

    Smith, J. Joshua; Garcia-Aguilar, Julio

    2015-01-01

    Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

  13. Locally advanced (neglected) breast cancer: the reality? relevance of two cases and reflection how to optimise the multidisciplinary approach

    International Nuclear Information System (INIS)

    Monnier, L.; Even, C.; Kirova, Y.M.; Even, C.; Cottu, P.H.

    2009-01-01

    The standard treatment for breast cancer patients with untreated locally advanced breast cancer is neo-adjuvant chemotherapy or hormonal treatment. In some cases, this treatment is followed by surgery and/or radiotherapy when the multidisciplinary approach is present. In some cases of patients presenting metastatic diseases, the radiotherapy is forgotten or proposed late when the local disease is extremely advanced with symptoms and decreased quality of life. Two cases of extremely advanced non operable T4 stage breast cancer are reported and the importance of multidisciplinary approach is discussed. The place and the right time of radiotherapy in this multidisciplinary strategy is reported. (authors)

  14. Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

    Science.gov (United States)

    Soekmadji, Carolina; Corcoran, Niall M; Oleinikova, Irina; Jovanovic, Lidija; Ramm, Grant A; Nelson, Colleen C; Jenster, Guido; Russell, Pamela J

    2017-10-01

    The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation. © 2017 Wiley Periodicals, Inc.

  15. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    LENUS (Irish Health Repository)

    Teo, Minyuen

    2013-03-01

    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  16. Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Wen-Jen Hwu

    2011-12-01

    Full Text Available Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine. Other studies combining temozolomide with either interferon- alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach

  17. Locally advanced rectal cancer: management challenges

    Directory of Open Access Journals (Sweden)

    Kokelaar RF

    2016-10-01

    Full Text Available RF Kokelaar, MD Evans, M Davies, DA Harris, J Beynon Department of Colorectal Surgery, Singleton Hospital, Swansea, UK Abstract: Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC, and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer. Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0 resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. Keywords: rectal cancer, exenteration, pelvic sidewall, sacrectomy

  18. Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Cho, Kwan Ho

    2004-01-01

    Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

  19. Resilience and hope during advanced disease: a pilot study with metastatic colorectal cancer patients.

    Science.gov (United States)

    Solano, Joao Paulo Consentino; da Silva, Amanda Gomes; Soares, Ivan Agurtov; Ashmawi, Hazem Adel; Vieira, Joaquim Edson

    2016-08-02

    The balance between hope-hopelessness plays an important role in the way terminally ill patients report quality of life, and personal resilience may be related to hope at the end of life. The objective of this study was to explore associations between personal resilience, hope, and other possible predictors of hope in advanced cancer patients. A cross-sectional pilot study was carried out with metastatic colorectal cancer patients in a tertiary hospital. The patients answered the Connor-Davidson Resilience Scale, Herth Hope Index, Barthel Index, an instrument addressing family and social support, visual-numeric scales for pain and suffering, a two-item screening for depression, socio-demographic and socio-economic information about the family. Forty-four patients were interviewed (mean age 56 years; range 29-86). A strong correlation was noted between resilience and hope (0.63; p hope and independence for activities of daily living, support from family and community, and pain and suffering levels. Of the 44 patients, 20 presented with depressive symptoms. These depressive patients had lower resilience (p = 0.005) and hope (p = 0.003), and higher scores of suffering (p hope kept stable after adjusting for age, gender, and presence of depression (p hope, resilience-fostering interventions should be most valued in palliative care settings and should be commenced as soon as possible with cancer patients. Patients with advanced stages of non-malignant conditions would also probably benefit from such interventions.

  20. Immunohistochemical analysis based Ep-ICD subcellular localization index (ESLI) is a novel marker for metastatic papillary thyroid microcarcinoma

    International Nuclear Information System (INIS)

    Kunavisarut, Tada; Kak, Ipshita; MacMillan, Christina; Ralhan, Ranju; Walfish, Paul G

    2012-01-01

    Thyroid cancer is among the fastest growing malignancies; almost fifty-percent of these rapidly increasing incidence tumors are less than or equal to 1cm in size, termed papillary thyroid microcarcinoma (PTMC). The management of PTMC remains a controversy due to differing natural history of these patients. Epithelial cell adhesion molecule (EpCAM) is comprised of an extracellular domain (EpEx), a single transmembrane domain and an intracellular domain (Ep-ICD). Our group reported nuclear Ep-ICD correlated with poor prognosis in thyroid cancer (Ralhan et al., BMC Cancer 2010,10:331). Here in, we hypothesized nuclear and cytoplasmic accumulation of Ep-ICD and loss of membranous EpEx may aid in distinguishing metastatic from non-metastatic PTMC, which is an important current clinical challenge. To test our hypothesis, Ep-ICD and EpEx expression levels were analyzed in PTMC and the staining was correlated with metastatic potential of these carcinomas. Thirty-six PTMC patients (tumor size 0.5 - 1cm; metastatic 8 cases and non-metastatic 28 cases) who underwent total thyroidectomy were selected. The metastatic group consisted of patients who developed lymph node or distant metastasis at diagnosis or during follow up. The patients’ tissues were stained for Ep-ICD and EpEx using domain specific antibodies by immunohistochemistry and evaluated. PTMC patients with metastasis had higher scores for nuclear and cytoplasmic Ep-ICD immunostaining than the patients without metastasis (1.96 ± 0.86 vs. 1.22 ± 0.45; p = 0.007 and 5.37 ± 0.33 vs. 4.72 ± 1.07; p = 0.016, respectively). Concomitantly, the former had lower scores for membrane EpEx than the non-metastatic group (4.64 ± 1.08 vs. 5.64 ± 1.51; p = 0.026). An index of aggressiveness, Ep-ICD subcellular localization index (ESLI), was defined as sum of the IHC scores for accumulation of nuclear and cytoplasmic Ep-ICD and loss of membranous EpEx; ESLI = [Ep − ICD nuc + Ep − ICD cyt + loss of membranous EpEx]. Notably

  1. An Unusual Case of Locally Advanced Glycogen-Rich Clear Cell Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Beatriz Martín-Martín

    2011-09-01

    Full Text Available Glycogen-rich clear cell (GRCC is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC. The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months’ follow-up.

  2. Cetuximab in locally advanced head-and-neck cancer: defining the population

    Science.gov (United States)

    Ho, C.

    2010-01-01

    Encouraging data for targeted therapy in head-and-neck squamous cell carcinoma are opening new options for treatment. Phase III trials of cetuximab, an antibody directed against the epidermal growth factor receptor (egfr) have demonstrated benefit in the locally advanced and metastatic settings. Recognizing the importance of emerging therapies, Cancer Care Ontario published guideline recommendations for egfr-targeted therapy in stage iii and iv head-and-neck cancer. The present paper takes a further look at the population for whom an offer of cetuximab therapy may be appropriate. PMID:20697514

  3. Dramatic Tumor Shrinkage of Locally Advanced and Inoperable Adenoid Cystic Carcinoma after Intra-arterial Chemotherapy

    Directory of Open Access Journals (Sweden)

    Fu-Jen Hsueh

    2015-06-01

    Full Text Available Adenoid cystic carcinoma is rare and usually arises in the salivary glands. It grows slowly, but is characterized by easy perineural invasion with local infiltration and distant metastasis. In metastatic setting, the efficacy of intravenous chemotherapy is limited. Herein, we report one male patient who had a advanced, inoperable adenoid cystic carcinoma with lung metastasis, presenting with right buccal unhealed ulcer, pain and poor intake, whose loco-regional tumors responded dramatically after intra-arterial chemotherapy and his symptoms were almost completely relieved. We also make a literature review for treatment of adenoid cystic carcinoma.

  4. Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Pérez, Juan E; Machiavelli, Mario R; Romero, Alberto O; Romero Acuña, Luis A; Domínguez, María E; Fasce, Hebe; Flores Acosta, Luis; Marrone, Nora; Romero Acuña, Juan M; Langhi, Mario J; Amato, Sonia; Bologna, Fabrina; Ortiz, Eduardo H; Leone, Bernardo A; Lacava, Juan A; Vallejo, Carlos T

    2002-08-01

    A phase II trial was performed to evaluate the efficacy and toxicity of the novel combination of vinorelbine and paclitaxel as first-line chemotherapy in patients with stages IIIB and IV non-small-cell lung cancer. From January 1997 to September 1999, 34 patients (9 stage IIIB and 25 stage IV) received a regimen consisting of the following: vinorelbine 30 mg/m2 20 minutes intravenous (i.v.) infusion, days 1 and 8; and paclitaxel 135 mg/m2 3-hour i.v. (starting 1 hour after vinorelbine) on day 1. Cycles were repeated every 28 days until progression of disease or unacceptable toxicity development. The median age was 57 years (range 41-70 years); median performance status was 1. Histology was as follows: squamous cell in 24 (71%), large cell in 1 (3%), and adenocarcinoma in 9 (26%). All patients are evaluable for toxicity, whereas 30 are evaluable for response (4 patients refused treatment). Objective response was recorded in 4 of 30 patients (13%, 95% CI 1-25%). No complete response was observed. Partial response was recorded in 4 patients (13%), no change in 10 patients (34%), and progressive disease in 16 patients (53%). The median time to treatment failure was 4 months and median survival was 9 months. The limiting toxicity was myelosuppression: leukopenia in 23 patients (68%), whereas neutropenia was observed in 25 patients (78%). Peripheral neurotoxicity developed in 14 patients (41%) (without G3 or G4 episodes), and constipation (G1-G2: 10 patients), myalgia (G1-G2: 11 patients), diarrhea (G1-G2: 7 patients), and stomatitis were observed in 7 patients. Vinorelbine-paclitaxel combination showed only modest activity against locoregionally advanced or metastatic NSCLC.

  5. Prognostic implication of the metastatic lesion-to-ovarian cancer standardised uptake value ratio in advanced serous epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Chung, Hyun Hoon; Lee, Maria; Kim, Hee-Seung; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang; Cheon, Gi Jeong

    2017-01-01

    To evaluate the prognostic value of metabolic activity of metastatic lesions measured by 18 F-flurodeoxyglucose ( 18 F-FDG) uptake on preoperative positron emission tomography/computed tomography (PET/CT) in patients with advanced serous epithelial ovarian cancer (EOC). Clinico-pathological variables and PET/CT parameters such as the maximum standardised uptake value of the ovarian cancer (SUV ovary ), metastatic lesions (SUV meta ), and the metastatic lesion-to-ovarian cancer standardised uptake value ratio (SUV meta /SUV ovary ) were assessed in International Federation of Gynaecology and Obstetrics (FIGO) stage III, IV patients. Clinico-pathological data were retrospectively reviewed for 94 eligible patients. The median progression-free survival (PFS) was 18.5 months (range, 6-90 months), and 57 (60.6%) patients experienced recurrence. Older age [P = 0.017, hazard ratio (HR) 1.036, 95% CI 1.006-1.066], residual disease after surgery (P = 0.024, HR 1.907, 95% CI 1.087-3.346), and high SUV meta /SUV ovary (P = 0.019, HR 2.321, 95% CI 1.148-4.692) were independent risk factors of recurrence. Patients with high SUV meta /SUV ovary showed a significantly worse PFS than those with low SUV meta /SUV ovary (P = 0.007, log-rank test). Preoperative SUV meta /SUV ovary was significantly associated with recurrence and has an incremental prognostic value for PFS in patients with advanced serous EOC. (orig.)

  6. Treatment of locally advanced/locally recurrent breast cancer and inflammatory breast cancer

    International Nuclear Information System (INIS)

    Murakami, Masao

    2000-01-01

    reported that 60% to 80% of patients with inflammatory breast cancer responded to induction chemotherapy and local control was achieved in approximately 70% of patients by chemotherapy with anthracyclines followed by surgery, postoperative adjuvant chemotherapy, and postoperative radiation therapy. The outcome was improved by induction chemotherapy, and local recurrence within 5 years after mastectomy was observed in 80% to 90% of patients, with local recurrence preceding the occurrence of distant metastasis in 25% to 30%, and is distant metastasis being observed simultaneously in 25%. Local recurrence is treated by radiation therapy, surgery, hyperthermia, and/or chemo-endocrino-therapy. Solitary recurrence can be controlled by resection, while multiple/diffuse recurrence requires radiation therapy. It is unknown whether the combination with chemotherapy improves the prognosis. Intra-arterial administration of antineoplastic agents is used as a method of local control in locally advanced breast cancer. Although intra-arterial administration is known to be superior to systemic administration in terms of primary effect, no differences have been observed in terms of survival rate or response rate. Intra-arterial administration is expected to be effective against distant metastatic lesions. The rate of occurrence of adverse reactions is similar to or less than after systemic administration. Combination therapy consisting of surgery, irradiation, and intra-arterial chemotherapy has been used in the authors' hospital to treat unresectable locally advanced breast cancer and postoperative recurrence of breast cancer. Surgery is performed for locally advanced breast cancer if tumor reduction is observed, and radiation therapy (single anterior 3 MV X-ray dose of 50 Gy / 25 Fr and boost irradiation of 10 Gy) is given depending on the results of the pathological examination. Radiation therapy is given for locally recurrent breast cancer after intra-arterial administration of

  7. Self-perceived competence among medical residents in skills needed to care for patients with advanced dementia versus metastatic cancer.

    Science.gov (United States)

    Manu, Erika; Marks, Adam; Berkman, Cathy S; Mullan, Patricia; Montagnini, Marcos; Vitale, Caroline A

    2012-06-01

    To examine medical residents' perceived competence in caring for patients with dementia we conducted an online survey of all 120 second, third and fourth-year residents in Internal Medicine, Medicine/Pediatrics, and Family Medicine at University of Michigan. A structured survey elicited residents' training, experience, confidence, and perceived career needs for skills in estimating prognosis, symptom management, and communication in caring for patients with dementia, compared to patients with metastatic cancer. Among the 61 (51 %) respondents, a majority report lower confidence in assessing prognosis and eliciting treatment wishes in patients with dementia (vs. metastatic cancer), and in performing skills integral to the care of patients with dementia, including the ability to assess caregiver needs, decisional capacity, advise on place of care, and manage agitation, despite viewing these skills as important to their future careers. These findings support the need for enhanced education on optimal care of patients with advanced dementia.

  8. Cf-252 neutron brachytherapy: an advance for bulky localized cancer therapy

    International Nuclear Information System (INIS)

    Maruyama, Y.

    1984-01-01

    The physical and radiobiogical basis as well as the rationale for neutron brachytherapy, using Cf-252, in human cancer therapy is reviewed. Cf-252 brachytherapy represents an economical and effective form of neutron radiotherapy that is readily and safely applied clinically. It can be used anywhere in the world without unusual personnel, equipment or facilities, or prohibitive expenses or maintenance costs. Used on bulky head and neck, thoracic, abdominal, pelvic, brain and appendage cancers, it overcomes hypoxic radioresistance and produces remarkable rates of tumor clearance. It is easily combined with photon radiotherapy and in proper schedules and doses, it can control advanced but still localized regional cancers to produce tumor cure. It will clear the local manifestations of recurrent or metastatic tumors or advanced stages of primary tumors and therefore in conjunction with other adjuvant therapies offers much more effective tumor control and palliation than present conventional therapy. (Auth.)

  9. Significance of Metabolic Super scan in Patients With Locally Advanced Bladder Cancer

    International Nuclear Information System (INIS)

    Kotb, M.H.; El-Kholy, E.; Omar, W.; El-Refaei, S.; Taher, A.N.; El-Marakby, H.

    2011-01-01

    Non-metastatic metabolic related skeletal changes are predicted in patients with locally advanced bladder cancer. Renal impairment may be a contributing factor in such abnormalities. The aim of this study was to verify the presence of metabolic bone disease in patients with different pathological subgroups of locally advanced bladder cancer and determine its clinical impact, and to correlate these metabolic super scan features with variable laboratory tests of bone bio markers and renal functions. In this study, a total of 350 patients (mean age = 58±8.4 y) with histopathologically proven locally advanced bladder cancer; 238 transitional cell carcinoma (TCC), 100 squamous cell carcinoma (SCC), 7 adenocarcinoma, 2 mucinous adenocarcinoma, 2 undifferentiated carcinoma and 1 leiomyosarcoma. The patients were referred to the Nuclear Medicine Unit, National Cancer Institute, Cairo, Egypt, between July 2006 and December 2009. Whole body bone scan was obtained 3 hours following IV administration of 555-925 MBq Tc-99m MDP. Serum alkaline phosphatase (ALP), calcium and parathormone (PTH) levels were monitored as markers for bone metabolism while serum creatinine was used to monitor kidney function. The exclusion criteria included patients who had liver disease or those taking calcium or vitamin D supplement or any medication that affects bone metabolism. All bone scan results in the study were verified by correlation with other radiological imaging, laboratory data and follow-up for at least 12 months. According to bone scan results, patients were classified into four groups: group A: normal scan (n=223), group B: metabolic super scan features (MSS) (n=70), group C: metastatic bone disease (n=45) and group D: bone scan with indeterminate lesions (n=12). Osteomalacic MSS features were detected in 20 % of the studied patients (locally advanced bladder cancer) compared to 14.5% who had bone metastases. Contrary to metastases which showed high prevalence in TCC (P<0.001), MSS

  10. Preoperative chemoradiotherapy for locally advanced gastric cancer

    International Nuclear Information System (INIS)

    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

  11. Preoperative chemoradiotherapy for locally advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    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.

  12. Monitoring treatment response and metastatic relapse in advanced bladder cancer by liquid biopsy analysis

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Christensen, Emil; Nordentoft, Iver Kristiansen

    2017-01-01

    of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84......DNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0-932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions. PATIENT...

  13. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer.

    Science.gov (United States)

    Hao, Yanni; Wolfram, Verena; Cook, Jennifer

    2016-01-01

    Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases), online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center), and web sites of health technology assessment (HTA) bodies. Publications were selected based on the search strategy and the overall study objectives. A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D). Other utility measures, such as the direct methods standard gamble (SG), time trade-off (TTO), and visual analog scale (VAS), were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL) instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Cancer 23 (EORTC QLQ-BR23), Functional Assessment of Cancer Therapy - General questionnaire (FACT-G), and Utility-Based Questionnaire-Cancer (UBQ-C); most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified within the journal articles. Most

  14. Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

    Science.gov (United States)

    Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

    2018-03-01

    Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

  15. Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer

    DEFF Research Database (Denmark)

    Cerbone, L; Sternberg, C N; Sengeløv, L

    2016-01-01

    BACKGROUND/OBJECTIVE: Lapatinib is a potent HER1 and HER2 inhibitor. Gemcitabine-cisplatin (GC) is a standard chemotherapy regimen for advanced/metastatic bladder cancer. This phase I study examined the safety of lapatinib in combination with GC in patients with bladder cancer. The primary aim...... × 3 patients), 1 of the 6 patients presented DLTs (grade 4, treatment-related febrile neutropenia and renal failure). Twelve patients received 6 cycles. CONCLUSIONS: Lapatinib at 750-1,250 mg combined with GC appears safe and tolerable. The MTD of lapatinib combined with GC in bladder cancer was 1...

  16. Advancements in the Treatment of Metastatic Breast Cancer (MBC: The Role of Ixabepilone

    Directory of Open Access Journals (Sweden)

    Massimo Cristofanilli

    2012-01-01

    Full Text Available Successful management of breast cancer in the metastatic setting is often confounded by resistance to chemotherapeutics, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially concerning. As such, a therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease. Notably, treating in the neoadjuvant setting might allow clinicians to explore the predictive value of biomarkers and response to treatment, as pharmacogenomic approaches to therapy continue to evolve. In this article, we review the efficacy and safety data of ixabepilone as a monotherapy and as a component of combination therapy for metastatic and primary breast cancer.

  17. Patterns of failure following bone marrow transplantation for metastatic breast cancer: the role of consolidative local therapy

    International Nuclear Information System (INIS)

    Shah, Amit B.; Hartsell, William F.; Ghalie, Richard; Kaizer, Herbert

    1995-01-01

    Purpose: The purpose of this analysis is to evaluate the patterns of failure and the role of local therapy in conjunction with bone marrow transplantation (BMT) for metastatic or recurrent breast cancer. Methods and Materials: Between June 1986 and November 1991, 46 patients with hormone unresponsive metastatic or recurrent breast cancer underwent high dose chemotherapy (HDC) with hematopoietic stem cell support. The most commonly used preparative regimen consisted of thiotepa (750 mg/m 2 ), cisplatin (150 mg/m 2 ), and cyclophosphamide (120 mg/kg) followed by autologous BMT. Consolidative surgery or irradiation was considered in patients whose cancer responded to BMT and had localized sites of disease. Results: Six patients (13%) died of BMT-related complications. Of the remaining 40 patients, 22 were candidates for consolidative therapy, and 18 of those patients received consolidative irradiation (17 patients) or surgery (1 patient) to one or more sites. At median follow-up of 27 months (range, 20-78), 12 of 18 (67%) patients have continuous local control at the 22 consolidated sites (1 of 4 controlled at chest wall sites, 7 of 8 at regional nodal sites, 7 of 7 at localized bone sites, and 1 of 3 at lung/mediastinal sites). Toxicity of consolidative irradiation was mainly limited to myelosuppression in 6 of 17 patients. Two patients did not complete the consolidative local therapy, one because of hematologic toxicity and one because of rapid systemic tumor progression during treatment. Conclusion: In patients with localized areas of extravisceral metastases, consolidative irradiation is feasible with acceptable hematologic toxicity. Consolidative irradiation can result in continuous local control, especially in isolated bone metastases and in regional nodal sites; however, the advantage is less clear in patients undergoing consolidative irradiation for chest wall failures. Because distant visceral metastases still remain a major site of failure after this HDC

  18. Prognostic implication of the metastatic lesion-to-ovarian cancer standardised uptake value ratio in advanced serous epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-11-15

    To evaluate the prognostic value of metabolic activity of metastatic lesions measured by {sup 18}F-flurodeoxyglucose ({sup 18}F-FDG) uptake on preoperative positron emission tomography/computed tomography (PET/CT) in patients with advanced serous epithelial ovarian cancer (EOC). Clinico-pathological variables and PET/CT parameters such as the maximum standardised uptake value of the ovarian cancer (SUV{sub ovary}), metastatic lesions (SUV{sub meta}), and the metastatic lesion-to-ovarian cancer standardised uptake value ratio (SUV{sub meta}/SUV{sub ovary}) were assessed in International Federation of Gynaecology and Obstetrics (FIGO) stage III, IV patients. Clinico-pathological data were retrospectively reviewed for 94 eligible patients. The median progression-free survival (PFS) was 18.5 months (range, 6-90 months), and 57 (60.6%) patients experienced recurrence. Older age [P = 0.017, hazard ratio (HR) 1.036, 95% CI 1.006-1.066], residual disease after surgery (P = 0.024, HR 1.907, 95% CI 1.087-3.346), and high SUV{sub meta}/SUV{sub ovary} (P = 0.019, HR 2.321, 95% CI 1.148-4.692) were independent risk factors of recurrence. Patients with high SUV{sub meta}/SUV{sub ovary} showed a significantly worse PFS than those with low SUV{sub meta}/SUV{sub ovary} (P = 0.007, log-rank test). Preoperative SUV{sub meta}/SUV{sub ovary} was significantly associated with recurrence and has an incremental prognostic value for PFS in patients with advanced serous EOC. (orig.)

  19. Treatment of locally advanced breast carcinoma with high-dose external beam supervoltage radiotherapy

    International Nuclear Information System (INIS)

    Brufman, G.; Weshler, Z.; Prosnitz, L.R.; Fuks, Z.

    1981-01-01

    Between 1960 and 1978, 87 patients with locally advanced Tsub(3-4)Nsub(0-3)M 0 carcinoma of the breast were treated with 5,000 to 8,000 rad of external beam supervoltage radiotherapy. Initial clinical eradication of the tumour was observed in 76 of 87 cases (87%), but the actuarial probability of local control at 5 yr was only 53%. Furthermore, the actuarial probability of disease-free survival was 25% at 5 yr and 13% at 10 yr. Most of the patients eventually succumbed to metastatic breast carcinoma and the actuarial survival at 5 yr was 43% and at 10 yr, 16%. The addition of adjuvant low-dose chemotherapy, given to 13 patients, did not affect the rates of local control, survival or disease-free survival. The most common long-term complication was extensive and deforming radiation-induced fibrosis of the treated breast. The actuarial probability of 10-yr survival without a local recurrence and without severe fibrosis of the treated breast was only 17.5%. The role of adjuvant high-dose chemotherapy in the treatment of locally advanced breast carcinoma and the possible use of improved radiotherapy techniques to achieve a more effective long-term local control and a more desirable cosmetic end result are discussed. (author)

  20. Source localization with an advanced gravitational wave detector network

    International Nuclear Information System (INIS)

    Fairhurst, Stephen

    2011-01-01

    We derive an expression for the accuracy with which sources can be localized using a network of gravitational wave detectors. The result is obtained via triangulation, using timing accuracies at each detector and is applicable to a network with any number of detectors. We use this result to investigate the ability of advanced gravitational wave detector networks to accurately localize signals from compact binary coalescences. We demonstrate that additional detectors can significantly improve localization results and illustrate our findings with networks comprised of the advanced LIGO, advanced Virgo and LCGT. In addition, we evaluate the benefits of relocating one of the advanced LIGO detectors to Australia.

  1. Successful Treatment of Advanced Metastatic Prostate Cancer following Chemotherapy Based on Molecular Profiling

    Directory of Open Access Journals (Sweden)

    Charles E. Myers

    2012-03-01

    Full Text Available After Taxotere fails, treatment options for metastatic prostate cancer are limited. The three drugs with FDA approval in this setting, Jevtana, Provenge and Zytiga, are associated with median survivals of less than 2 years. In part, the impact on survival is the result of low response rates, indicating a significant proportion of patients exhibiting de novo resistance to these agents. An alternate approach is to let treatment selection be governed by gene expression profiling so that the treatment is tailored to the specific patient. Here, we report a case of metastatic prostate cancer with a dramatic response to treatment selected based on molecular profiling. This patient had failed LHRH agonist, bicalutamide, Taxotere, and doxorubicin. Molecular profiling showed overexpression of the androgen receptor and he had a dramatic response of measurable disease to second-line hormonal therapy with ketoconazole, estrogen and Leukine.

  2. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2017-09-26

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  3. 3'-Deoxy-3'-18F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    Challapalli, Amarnath; Barwick, Tara; Merchant, Shairoz; Pearson, Rachel A.; Howell, Elizabeth C.; Maxwell, Ross J.; Mauri, Francesco; Sumpter, Katherine; Aboagye, Eric O.; Sharma, Rohini

    2015-01-01

    3'-Deoxy-3'- 18 F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CT KSF ) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PET KSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35 %). Maximum standardised uptake value at 60 min post-injection (SUV 60,max ) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV 60,max increase of ≥ 12 % resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100 %, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV 60,max were not predictive of survival. FLT PET/CT detected changes in proliferation, with early increase in SUV 60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer. (orig.)

  4. Impact of radiation dose and standardized uptake value of (18)FDG PET on nodal control in locally advanced cervical cancer

    DEFF Research Database (Denmark)

    Ramlov, Anne; Kroon, Petra S; Jürgenliemk-Schulz, Ina M

    2015-01-01

    BACKGROUND: Despite local control now exceeding 90% with image-guided adaptive brachytherapy (IGABT), regional and distant metastases continue to curb survival in locally advanced cervical cancer. As regional lymph nodes often represent first site of metastatic spread, improved nodal control could...... improve survival. The aim of this study was to examine optimal volume and dose of external beam radiotherapy (EBRT) to maximize regional control including dose contribution from IGABT. MATERIAL AND METHODS: In total 139 patients from the EMBRACE study were analyzed. Individual nodal dose was determined...

  5. Intraoperative Radiotherapy (IORT) for Locally Advanced Colorectal Cancer

    International Nuclear Information System (INIS)

    Kim, Myung Se; Kim, Sung Kyu; Kim, Jae Hwang; Kwan, Koing Bo; Kim, Heung Dae

    1991-01-01

    Colorectal cancer is the second most frequent malignant tumor in the United States and fourth most frequent tumor in Korea. Surgery has been used as a primary treatment modality but reported overall survivals after curative resection were from 20% to 50%. Local recurrence is the most common failure in the treatment of locally advanced colorectal cancer. Once recurrence has developed, surgery has rarely the role and the five year survival of locally advanced rectal cancer is less than 5%, this indicated that significant improvement of local control could be achieved. We performed 6 cases of IORT for locally advanced colorectal cancer which is he first experience in Korea. Patient's eligibility, treatment applicator, electron energy, dose distribution on the surface and depth within the treatment field and detailed skills are discussed. We hope that our IORT protocol can reduce local failure and increase the long term survival significantly

  6. Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

    International Nuclear Information System (INIS)

    Nguyen, Xuan Canh; Nguyen, Van Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

    2014-01-01

    To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUV pt ), maxSUV of whole-body tumors (maxSUV wb ) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSCLC were enrolled. Seventeen patients had Stage IIIA, 21 Stage IIIB, and 45 Stage IV. maxSUV pt , maxSUV wb , sumaxSUV, age, gender, tumor-cell type, T stage, N stage, overall stage, primary tumor size, and specific treatment were analyzed for correlation with overall survival. Median follow-up duration was 13 months. Fifty patients were dead during a median follow-up time of 11 months and 33 patients were alive with a median time of 15 months. Univariate analysis revealed that overall survival was significantly correlated with sumaxSUV (≥35 vs. <35, P = 0.004), T stage (T4 vs. T1-T3, P = 0.025), overall stage (IV vs. III, P = 0.002), gender (male vs. female, P = 0.029) and specific treatment (no vs. yes, P = 0.011). maxSUV pt and maxSUV wb were not correlated with overall survival with P value of 0.139 and 0.168, respectively. Multivariate analysis identified sumaxSUV, T stage, gender, and specific treatment as independent prognostic indicators. Patients with a sumaxSUV of ≥35 were 1.921 times more likely to die than those with a sumaxSUV of < 35 (P = 0.047). Median survival time was 14 months for patients with sumaxSUV ≥ 35 compared with 20 months for those with sumaxSUV < 35. In patients with metastatic NSCLC, sumaxSUV with cut-off of 35 was much more significant for survival prognosis (P = 0.021). sumaxSUV is a new prognostic measure, independent of tumor stage, gender, and specific treatment in advanced NSCLC. sumaxSUV may be better than maxSUV pt and maxSUV wb in

  7. A STUDY OF LOCALLY ADVANCED CARCINOMA OF BREAST

    Directory of Open Access Journals (Sweden)

    Prabhakar Jenna

    2017-08-01

    Full Text Available BACKGROUND Worldwide, breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women. Locally advanced breast cancer constitutes more than 50-70% of the patients presenting for treatment has two common problems in treatment. Achieving local control and prolonging survival by preventing or delaying distant metastasis. Today, treatment of LABC requires a combination of systemic and local/regional therapies. The aim of the study is to study the clinicopathological presentation, age distribution and various modes of management of locally advanced breast carcinoma. Worldwide breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women. Locally advanced breast cancer constitutes more than 50-70% of the patients presenting treatment. MATERIALS AND METHODS The present study includes 50 patients who attended Department of General Surgery for a period of three years. RESULTS The patients were regularly followed up and at the end of the study 35 (70% of the patients were doing well. 4(8% of the patients developed distant metastasis and 3 (6% of the patients developing local recurrence. 8 (16% of the patients were lost follow up. CONCLUSION About half of the cases presenting with breast cancer are in locally advanced stages. Multimodality therapy is the effective treatment of locally advanced carcinoma of breast. Breast cancer management is a challenge and improvement in therapies are needed for disease-free interval and overall survival period.

  8. Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC

    DEFF Research Database (Denmark)

    Schytte, Tine; Hansen, Olfred; Stohlberg-Rohr, Thomine

    2010-01-01

        Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity   Backgro......    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity......   Background: Lung and oesophageal toxicity have been regarded as main toxicity in definitive radiotherapy (RT) of non-small cell lung cancer (NSCLC), whereas cardiac toxicity has not been offered much concern. This is probably due to the poor prognosis for patients with unresectable NSCLC. In this study we...

  9. Value of intraoperative radiotherapy in locally advanced rectal cancer

    NARCIS (Netherlands)

    Ferenschild, Floris T. J.; Vermaas, Maarten; Nuyttens, Joost J. M. E.; Graveland, Wilfried J.; Marinelli, Andreas W. K. S.; van der Sijp, Joost R.; Wiggers, Theo; Verhoef, Cornelis; Eggermont, Alexander M. M.; de Wilt, Johannes H. W.

    PURPOSE: This study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer. METHODS: Between 1987 and 2002, 123 patients with initial unresectable

  10. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Science.gov (United States)

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  11. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    International Nuclear Information System (INIS)

    Pandit-Taskar, Neeta; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Osborne, Joseph R.; O'Donoghue, Joseph A.; Beylergil, Volkan; Ruan, Shutian; Cheal, Sarah M.; Lyashchenko, Serge; Gonen, Mithat; Lewis, Jason S.; Holland, Jason P.; Reuter, Victor E.; Loda, Massimo F.; Smith-Jones, Peter M.; Weber, Wolfgang A.; Larson, Steven M.; Bander, Neil H.; Scher, Howard I.; Morris, Michael J.

    2014-01-01

    conventional imaging modality was negative. 89 Zr-huJ591 PET imaging of prostate-specific membrane antigen expression is safe and shows good localization of disease in prostate cancer patients. Liver is the critical organ for dosimetry, and 7 ± 1 days is the optimal imaging time. A larger study is underway to determine lesion detection in an expanded cohort of patients with metastatic prostate cancer. (orig.)

  12. {sup 89}Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pandit-Taskar, Neeta; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Osborne, Joseph R. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); O' Donoghue, Joseph A. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Beylergil, Volkan; Ruan, Shutian; Cheal, Sarah M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Lyashchenko, Serge [Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Gonen, Mithat [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Lewis, Jason S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Holland, Jason P. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Harvard Medical School, Department of Radiology of Massachusetts General Hospital, Boston, MA (United States); Reuter, Victor E. [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Cornell Medical College, Department of Pathology, New York, NY (United States); Loda, Massimo F. [Dana-Farber Cancer Institute, Boston, MA (United States); Broad Institute of Harvard and MIT, Cambridge, MA (United States); Smith-Jones, Peter M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Department of Psychiatry and Behavioral Science of Stony Brook University, Stony Brook, NY (United States); Weber, Wolfgang A.; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Bander, Neil H. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States); Weill Cornell Medical College, Department of Urology, New York, NY (United States); Scher, Howard I.; Morris, Michael J. [Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY (United States); Weill Cornell Medical College, Department of Medicine, New York, NY (United States)

    2014-11-15

    {sup 89}Zr-huJ591 study, while the conventional imaging modality was negative. {sup 89}Zr-huJ591 PET imaging of prostate-specific membrane antigen expression is safe and shows good localization of disease in prostate cancer patients. Liver is the critical organ for dosimetry, and 7 ± 1 days is the optimal imaging time. A larger study is underway to determine lesion detection in an expanded cohort of patients with metastatic prostate cancer. (orig.)

  13. [A Case of Locally Advanced Thoracic Esophageal Cancer with Larynx Preservation and Curative Resection via Combined Modality Therapy].

    Science.gov (United States)

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

    2017-11-01

    Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.

  14. Olaparib in Treating Patients With Metastatic or Advanced Urothelial Cancer With DNA-Repair Defects

    Science.gov (United States)

    2018-06-14

    Abnormal DNA Repair; ATM Gene Mutation; ATR Gene Mutation; BAP1 Gene Mutation; BARD1 Gene Mutation; BLM Gene Mutation; BRCA1 Gene Mutation; BRCA2 Gene Mutation; BRIP1 Gene Mutation; CHEK1 Gene Mutation; CHEK2 Gene Mutation; FANCC Gene Mutation; FANCD2 Gene Mutation; FANCE Gene Mutation; FANCF Gene Mutation; MEN1 Gene Mutation; Metastatic Urothelial Carcinoma; MLH1 Gene Mutation; MSH2 Gene Mutation; MSH6 Gene Mutation; MUTYH Gene Mutation; NPM1 Gene Mutation; PALB2 Gene Mutation; PMS2 Gene Mutation; POLD1 Gene Mutation; POLE Gene Mutation; PRKDC Gene Mutation; RAD50 Gene Mutation; RAD51 Gene Mutation; SMARCB1 Gene Mutation; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; STK11 Gene Mutation; Urothelial Carcinoma

  15. Intraoperative radiotherapy for locally advanced refractory cancer

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Mitsuyuki; Takahashi, Masaji; Ono, Koji; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

    1983-05-01

    Clinical results of intraoperative radiotherapy (IOR) in carcinoma of the stomach and prostate, and malignant soft tissue tumors are reported. The 5-year survival rate was found to be increased by IOR in stages II-IV gastric cancer. From the analysis of the clinical results of prostatic cancer, a single dose of 3,500 rad was considered to be a potential curative dose for the tumor less than 3 cm in diameter. The local recurrence rate of patients with malignant soft tissue tumors who received a single dose ranging from 3,000 to 4,500 rad was 5.9 and the 5-year survival rate was 64.6 %.

  16. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

    NARCIS (Netherlands)

    Bui-Nguyen, B.; Butrynski, J.E.; Penel, N.; Blay, J.Y.; Isambert, N.; Milhem, M.; Kerst, J.M.; Reyners, A.K.; Litiere, S.; Marreaud, S.; Collin, F.; Graaf, W.T.A. van der

    2015-01-01

    PURPOSE: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour

  17. Localised perforation of locally advanced transverse colon cancer with spontaneous colocutaneous fistula formation: a clinical challenge.

    Science.gov (United States)

    Wadhwani, Nikita; Diwakar, Deepak Kumar

    2018-04-19

    Colon cancer can present with complications such as obstruction, perforation and bleeding. The clinical presentation has been recognised as an independent prognostic factor for morbidity and mortality. 1 We present a rare case of localised perforation of a locally advanced colon cancer arising from mid-transverse colon in an elderly woman in the absence of widely metastatic disease with eventual cutaneous involvement of the overlying skin by direct extension, resulting in formation of colocutaneous fistula. The management of such cases is complex as usually tailored to the situation encountered. 2 This case was a clinical challenge to choose between initial palliative resection and curative R0 resection following neoadjuvant chemotherapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Local advanced transitional cell cancer and squamous cell cancer of ...

    African Journals Online (AJOL)

    Case report: A 51-year-old man presented with a locally advanced squamous cell cancer of the periurethral tissues as well as an underlying isolated transitional cell cancer of the urethra. Chemotherapy with Gemcitabin and Cisplatinum together with local radiation to the pelvis and the perineum was given. There was ...

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

    Science.gov (United States)

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

    2015-01-01

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

  20. Study of metastatic lymph nodes in advanced gastric cancer with spiral computed tomograph

    International Nuclear Information System (INIS)

    Su Yijuan

    2008-01-01

    Objective: To study the characteristics of spiral computed tomography (SCT) in the diagnosis of lymph nodes metastases in gastric cancer. Methods: The characteristics of spiral computed tomography (SCT) of metastatic lymph nodes in 35 gastric cancer patients were analyzed and compared with operation and pathology. Results: A total amount of 379 lymph nodes (positive 173, negative 206) were detected by SCT and confirmed by pathology in metastasis-positive or metastasis-negative patients. The positive rate with diameter of lymph nodes ≥ 10 mm is 62.7%. The positive rate with ir- regular shape and uneven enhancement lymph nodes were 96.3% and 89.4%. If the attenuation values, more than or equal to 25 HU in plain scan or 70 HU in arterial phase or 80 HU in venous phase, were used as the threshold to detect the metastasis-positive lymph nodes, the positive rate were 55.7%, 56.3%, 67.8% respectively. Conclusion: SCT is valuable in judging the metastasis in gastric cancer. The reference of diameter ≥ 10mm, combining with the shape and the attenuation values can dramatically improve the diagnosis of lymph node metastasis in gastric cancer. (authors)

  1. Recent Advances in Wireless Indoor Localization Techniques and System

    Directory of Open Access Journals (Sweden)

    Zahid Farid

    2013-01-01

    Full Text Available The advances in localization based technologies and the increasing importance of ubiquitous computing and context-dependent information have led to a growing business interest in location-based applications and services. Today, most application requirements are locating or real-time tracking of physical belongings inside buildings accurately; thus, the demand for indoor localization services has become a key prerequisite in some markets. Moreover, indoor localization technologies address the inadequacy of global positioning system inside a closed environment, like buildings. Based on this, though, this paper aims to provide the reader with a review of the recent advances in wireless indoor localization techniques and system to deliver a better understanding of state-of-the-art technologies and motivate new research efforts in this promising field. For this purpose, existing wireless localization position system and location estimation schemes are reviewed, as we also compare the related techniques and systems along with a conclusion and future trends.

  2. Radiotherapy Boost Following Conservative Surgery for Locally Advanced Breast Cancer

    International Nuclear Information System (INIS)

    Cendales, Ricardo; Ospino, Rosalba; Torres, Felipe; Cotes, Martha

    2009-01-01

    Nearly half of breast cancer patients in developing countries present with a locally advanced cancer. Treatment is centered on a multimodal approach based on chemotherapy, surgery and radiotherapy. The growing use of neoadjuvant chemotherapy has led to a more conservative surgical approach; nonetheless, it is not yet considered as a standard. There are no clear recommendations on the use of a radiotherapy boost in such situation. A Medline search was developed. Most articles are retrospective series. Survival free of locoregional relapse in patients treated with neoadjuvant chemotherapy, breast conserving surgery and radiotherapy is good. All articles described a boost administered to nearly all patients without regard to their prognostic factors, given that a locally advanced tumor is already considered as a poor prognostic factor. Even tough the poor level of evidence, a recommendation can be made: radiotherapy boost should be administered to all patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and breast conserving surgery.

  3. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

    International Nuclear Information System (INIS)

    Tey, Jeremy; Back, Michael F.; Shakespeare, Thomas P.; Mukherjee, Rahul K.; Lu, Jiade J.; Lee, Khai Mun; Wong, Lea Choung; Leong, Cheng Nang; Zhu Ming

    2007-01-01

    Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives

  4. Metastatic spinal cord compression from basal cell carcinoma of the skin treated with surgical decompression and vismodegib: case report and review of Hedgehog signalling pathway inhibition in advanced basal cell carcinoma.

    Science.gov (United States)

    McGrane, J; Carswell, S; Talbot, T

    2017-01-01

    We report a case of a 66-year-old man with locally advanced and metastatic basal cell carcinoma (BCC) causing spinal cord compression, which was treated with spinal surgery and subsequent vismodegib. The patient presented with a large fungating chest wall lesion and a metastasis in T8 that was causing cord compression. He had neurosurgical decompression of the T8 lesion and fixation of the spine. Punch biopsy from the fungating chest wall lesion showed a BCC with some malignant squamous differentiation (basosquamous). Histopathological examination of the metastatic lesion in T8 at the time of surgical decompression identified features identical to the punch biopsy. The patient was referred to the oncology clinic for adjuvant treatment. In light of his metastatic disease and the large area over his chest wall that could not fully be covered by radiotherapy, he was treated with the novel oral Hedgehog signalling pathway (HHSP) inhibitor vismodegib, which led to marked improvement. © 2016 British Association of Dermatologists.

  5. Clinical experience with intraoperative radiotherapy for locally advanced colorectal cancer

    International Nuclear Information System (INIS)

    Shibamoto, Yuta; Takahashi, Masaharu; Abe, Mitsuyuki

    1988-01-01

    Intraoperative radiotherapy (IORT) was performed on 20 patients with colorectal cancer. IORT with a single dose of 20 to 40 Gy was delivered to the residual tumor, tumor bed, and/or lymphnode regions. Although most of the patients had advanced lesions, local control was achieved in 67 % of the patients when IORT was combined with tumor resection, and 4 patients survived more than 5 years. There were no serious complications, except for contracture or atrophy of the psoas muscle seen in 2 patients. IORT combined with external beam radiotherapy should be a useful adjuvant therapy to surgery for locally advanced colorectal cancer. (author)

  6. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

    Directory of Open Access Journals (Sweden)

    Sergio Szyldergemajn

    2009-09-01

    Full Text Available The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m2 administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

  7. The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature.

    Science.gov (United States)

    Chauvin, Anaïs; Wang, Chang-Shu; Geha, Sameh; Garde-Granger, Perrine; Mathieu, Alex-Ane; Lacasse, Vincent; Boisvert, François-Michel

    2018-01-01

    Colorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders. The lack of evidence available in clinical practice to predict NRCT resistance to 5-FU and to guide clinical practice therefore encourages the search for biomarkers of this resistance. From twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before NRCT with 5-FU of locally advanced non-metastatic rectal cancer patients, we extracted and analysed the tumor proteome of these patients. From clinical data, we were able to classify the twenty-three patients in our cohort into three treatment response groups: non-responders (NR), partial responders (PR) and total responders (TR), and to compare the proteomes of these different groups. We have highlighted 384 differentially abundant proteins between NR and PR, 248 between NR and TR and 417 between PR and TR. Among these proteins, we have identified many differentially abundant proteins identified as having a role in cancer (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed in TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: overexpressed in NR). We have also identified that DPYD, the main degradation enzyme of 5-FU, was overexpressed in NR, as well as several ribosomal and mitochondrial proteins also overexpressed in NR. Data are available via ProteomeXchange with identifier PXD008440. From these retrospective study, we implemented a protein extraction protocol from FFPE biopsy to highlight protein differences between different response groups to RCTN with 5-FU in patients with locally advanced non-metastatic rectal cancer

  8. Epidemiology and therapies for metastatic sarcoma

    Science.gov (United States)

    Amankwah, Ernest K; Conley, Anthony P; Reed, Damon R

    2013-01-01

    Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. PMID:23700373

  9. The effect of local control on metastatic dissemination in carcinoma of the prostate: Long-term results in patients treated with 125I implantation

    International Nuclear Information System (INIS)

    Fuks, Z.; Leibel, S.A.; Wallner, K.E.; Begg, C.B.; Fair, W.R.; Anderson, L.L.; Hilaris, B.S.; Whitmore, W.F.

    1991-01-01

    The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse (p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure

  10. Locally advanced breast cancer (stage III and stage IV)

    International Nuclear Information System (INIS)

    Baracat, F.F.; Grabert, H.; Lima, G.R. de; Pontes, M.; Ferraro, O.; Santana, A.; Brook, E.S.

    1987-01-01

    The results concerning to the treatment of 193 patients with locally advanced breast cancer-stage III and stage IV are analysed. All the patients were treated with radical radiotherapy plus total mastectomy about 6 weeks later; 53 pacients received also chemotherapy (CMF - 12 courses) and 52 were oophorectomized. (M.A.C) [pt

  11. An approach to the management of locally advanced breast cancer ...

    African Journals Online (AJOL)

    Locally advanced breast cancer (LABC) comprises a heterogeneous group of diseases. It incorporates a subset of stage IIB (T3N0) disease, stage III disease and inflammatory breast cancer. In the developed world, 7% of breast cancer patients have stage III disease at diagnosis. In developing countries, LABC constitutes ...

  12. Clinical impact of radiotherapy for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Sawaki, Akira; Hoki, Noriyuki; Ito, Satoko

    2009-01-01

    Although a randomized controlled trial for locally advanced pancreatic cancer (PC) has demonstrated a survival advantage for treatment with gemcitabine alone, chemoradiotherapy remains the treatment of choice for locally advanced disease in Japan. The aim of this study was to compare the survival benefits associated with gemcitabine and concurrent chemoradiotherapy in locally advanced unresectable PC. Seventy-seven patients with locally advanced unresectable PC were retrospectively enrolled from April 2001 to December 2006. All cases were histologically proven, and patients received gemcitabine chemotherapy (n=30) or concurrent chemoradiotherapy (based on 5-fluorouracil, n=28, or gemcitabine, n=19, as a radiosensitizer) at Aichi Cancer Center Hospital. Patients who received chemoradiotherapy had significantly better performance status than those who had chemotherapy. Tumor response was 0% for chemotherapy and 13% chemoradiotherapy, but survival benefit was similar among patients in the chemotherapy group (overall response (OS) 12 months; progression-free survival (PFS), 3 months) and those in the chemoradiotherapy group (OS, 13 months; PFS, 5 months). Two-year survival was 21% for chemotherapy patients and 19% for chemoradiotherapy patients. Severe toxicities (Grade 3-4 National Cancer Institute-Common Toxicity Criteria, version 3.0) were significantly more frequent for chemoradiotherapy than for chemotherapy. Gemcitabine chemotherapy showed similar survival benefit compared to 5-fluorouracil- and gemcitabine-based chemoradiotherapy. (author)

  13. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    International Nuclear Information System (INIS)

    Martinez, Steve R.; Beal, Shannon H.; Chen, Steven L.; Canter, Robert J.; Khatri, Vijay P.; Chen, Allen; Bold, Richard J.

    2010-01-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and ≥10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  14. Locally advanced pancreatic duct adenocarcinoma: pancreatectomy with planned arterial resection based on axial arterial encasement.

    Science.gov (United States)

    Perinel, J; Nappo, G; El Bechwaty, M; Walter, T; Hervieu, V; Valette, P J; Feugier, P; Adham, M

    2016-12-01

    Pancreatectomy with arterial resection for locally advanced pancreatic duct adenocarcinoma (PDA) is associated with high morbidity and is thus considered as a contraindication. The aim of our study was to report our experience of pancreatectomy with planned arterial resection for locally advanced PDA based on specific selection criteria. All patients receiving pancreatectomy for PDA between October 2008 and July 2014 were reviewed. The patients were classified into group 1, pancreatectomy without vascular resection (66 patients); group 2, pancreatectomy with isolated venous resection (31 patients), and group 3, pancreatectomy with arterial resection for locally advanced PDA (14 patients). The primary selection criteria for arterial resection was the possibility of achieving a complete resection based on the extent of axial encasement, the absence of tumor invasion at the origin of celiac trunk (CT) and superior mesenteric artery (SMA), and a free distal arterial segment allowing reconstruction. Patient outcomes and survival were analyzed. Six SMA, two CT, four common hepatic artery, and two replaced right hepatic artery resections were undertaken. The preferred arterial reconstruction was splenic artery transposition. Group 3 had a higher preoperative weight loss, a longer operative time, and a higher incidence of intraoperative blood transfusion. Ninety-day mortality occurred in three patients in groups 1 and 2. There were no statistically significant differences in the incidence, grade, and type of complications in the three groups. Postoperative pancreatic fistula and postpancreatectomy hemorrhage were also comparable. In group 3, none had arterial wall invasion and nine patients had recurrence (seven metastatic and two loco-regional). Survival and disease-free survival were comparable between groups. Planned arterial resection for PDA can be performed safely with a good outcome in highly selected patients. Key elements for defining the resectability is based on

  15. Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base.

    Science.gov (United States)

    Zumsteg, Zachary S; Luu, Michael; Yoshida, Emi J; Kim, Sungjin; Tighiouart, Mourad; David, John M; Shiao, Stephen L; Mita, Alain C; Scher, Kevin S; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

    2017-12-01

    There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression. This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available. In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017;123:4583-4593. © 2017 American Cancer Society. © 2017 American Cancer Society.

  16. Utility values associated with advanced or metastatic non-small cell lung cancer: data needs for economic modeling.

    Science.gov (United States)

    Brown, Jacqueline; Cook, Keziah; Adamski, Kelly; Lau, Jocelyn; Bargo, Danielle; Breen, Sarah; Chawla, Anita

    2017-04-01

    Cost-effectiveness analyses often inform healthcare reimbursement decisions. The preferred measure of effectiveness is the quality adjusted life year (QALY) gained, where the quality of life adjustment is measured in terms of utility. Areas covered: We assessed the availability and variation of utility values for health states associated with advanced or metastatic non-small cell lung cancer (NSCLC) to identify values appropriate for cost-effectiveness models assessing alternative treatments. Our systematic search of six electronic databases (January 2000 to August 2015) found the current literature to be sparse in terms of utility values associated with NSCLC, identifying 27 studies. Utility values were most frequently reported over time and by treatment type, and less frequently by disease response, stage of disease, adverse events or disease comorbidities. Expert commentary: In response to rising healthcare costs, payers increasingly consider the cost-effectiveness of novel treatments in reimbursement decisions, especially in oncology. As the number of therapies available to treat NSCLC increases, cost-effectiveness analyses will play a key role in reimbursement decisions in this area. Quantifying the relationship between health and quality of life for NSCLC patients via utility values is an important component of assessing the cost effectiveness of novel treatments.

  17. Localization of gravitational wave sources with networks of advanced detectors

    International Nuclear Information System (INIS)

    Klimenko, S.; Mitselmakher, G.; Pankow, C.; Vedovato, G.; Drago, M.; Prodi, G.; Mazzolo, G.; Salemi, F.; Re, V.; Yakushin, I.

    2011-01-01

    Coincident observations with gravitational wave (GW) detectors and other astronomical instruments are among the main objectives of the experiments with the network of LIGO, Virgo, and GEO detectors. They will become a necessary part of the future GW astronomy as the next generation of advanced detectors comes online. The success of such joint observations directly depends on the source localization capabilities of the GW detectors. In this paper we present studies of the sky localization of transient GW sources with the future advanced detector networks and describe their fundamental properties. By reconstructing sky coordinates of ad hoc signals injected into simulated detector noise, we study the accuracy of the source localization and its dependence on the strength of injected signals, waveforms, and network configurations.

  18. Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain.

    Science.gov (United States)

    Upadhyay, Urvashi M; Tyler, Betty; Patta, Yoda; Wicks, Robert; Spencer, Kevin; Scott, Alexander; Masi, Byron; Hwang, Lee; Grossman, Rachel; Cima, Michael; Brem, Henry; Langer, Robert

    2014-11-11

    Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

  19. Management of Locally Advanced Cancer Cervix an Indian Perspective.

    Science.gov (United States)

    Singh, J K; Chauhan, Richa

    2015-01-01

    Cervical cancer has a major impact on the lives of Indian women with an estimated 122, 844 new cases of cervical cancer in the year 2012. About 80% of these cases present in a locally advanced stage leading to high morbidity and mortality. Because of lack of public awareness and infrastructure for screening and early detection in developing countries, this late presentation is likely to continue in the coming years. Radiation therapy has been the treatment of choice for patients with locally advanced cancer cervix. Many clinical trials and meta-analyses have shown a significant improvement in overall and progression-free survival with decreased local and distant recurrences with the use of concurrent chemotherapy with radiation. Most of these trials have been done in women from developed countries where the patient and disease profile are entirely different from ours. Recently, few trials from India have also shown promising results in locally advanced cancer cervix with concurrent chemoradiotherapy but toxicities remain a major concern. Further exploration is required for the use of concurrent chemo radiation prior to incorporating it into routine clinical practice.

  20. Fatal Metastatic Cutaneous Squamous Cell Carcinoma Evolving from a Localized Verrucous Epidermal Nevus

    Directory of Open Access Journals (Sweden)

    Hassan Riad

    2013-10-01

    Full Text Available A malignant transformation is known to occur in many nevi such as a sebaceous nevus or a basal cell nevus, but a verrucous epidermal nevus has only rarely been associated with neoplastic changes. Keratoacanthoma, multifocal papillary apocrine adenoma, multiple malignant eccrine poroma, basal cell carcinoma and cutaneous squamous cell carcinoma (CSCC have all been reported to develop from a verrucous epidermal nevus. CSCC has also been reported to arise from other nevoid lesions like a nevus comedonicus, porokeratosis, a sebaceous nevus, an oral sponge nevus and an ichthyosiform nevus with CHILD syndrome. Here we report a case of progressive poorly differentiated CSCC arising from a localized verrucous epidermal nevus, which caused both spinal cord and brain metastasis.

  1. Local mechanical properties of bladder cancer cells measured by AFM as a signature of metastatic potential

    Science.gov (United States)

    Abidine, Y.; Laurent, V. M.; Michel, R.; Duperray, A.; Verdier, C.

    2015-10-01

    The rheological properties of bladder cancer cells of different invasivities have been investigated using a microrheological technique well adapted in the range [1-300Hz] of interest to understand local changes in the cytoskeleton microstructure, in particular actin fibres. Drugs disrupting actin and acto-myosin functions were used to study the resistance of such cancer cells. Results on a variety of cell lines were fitted with a model revealing the importance of two parameters, the elastic shear plateau modulus G N 0 as well as the glassy transition frequency f T. These parameters are good markers for invasiveness, with the notable exception of the cell periphery, which is stiffer for less invasive cells, and could be of importance in cancer metastasis.

  2. Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer.

    Science.gov (United States)

    Shaib, Walid L; Ip, Andrew; Cardona, Kenneth; Alese, Olatunji B; Maithel, Shishir K; Kooby, David; Landry, Jerome; El-Rayes, Bassel F

    2016-02-01

    Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC. Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized. ©AlphaMed Press.

  3. Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma

    International Nuclear Information System (INIS)

    Lind, Pehr A.; Bystroem, Per; Isaksson, Bengt; Almstroem, Markus; Permert, Johan; Johnsson, Anders; Albiin, Nils

    2008-01-01

    Background. The optimal care for patients with unresectable, non-metastatic pancreatic adenocarcinoma (PAC) is debated. We treated 17 consecutive cases with preoperative radiochemotherapy (RCT) as a means for downstaging their tumours and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period. Methods. The patients had biopsy proven, unresectable, non-metastatic PAC which engaged ≥ 50% of the circumference of a patent mesenteric/portal vein for a distance ≥ 2 cm and/or 2 d1; capecitabine 2 000 mg/m 2 d1-14 q 3 w) followed by 3-D conformal radiotherapy (50.4 Gy; 1.8 Gy fractions) with reduced Xelox (d1-5 q 1 w X 6). Results. No incident of RCT-related CTC Grade 3-4 haematologic and six cases of non-haematologic side-effects were diagnosed. Sixteen patients completed the RCT and were rescanned with CT and reevaluated for surgery 4 weeks post-RCT. Five cases were diagnosed with new metastases to the liver. Eleven patients were accepted for surgery whereof eight underwent a curative R 0 -resection. The median overall survival for the latter group was 29 months, which compared favourably with our control group of patients undergoing direct curative surgery for primarily resectable PAC (median OS: 16 months; RO-rate: 75%). Perioperative morbidity was similar in the two cohorts but the duration of surgery was longer (576 vs. 477 min) and the op blood loss was greater (3288 vs. 1460 ml) in the RCT-cohort (p < 0.05). The 30-day mortality was zero in both groups. Conclusion. Preoperative RCT in patients with locally advanced PAC resulted in a high rate of curative resections and promising median survival in our treatment series. This trimodality approach merits further exploration in new studies, which are currently underway at our Dept

  4. Conformal radiotherapy of locally advanced bile duct carcinoma

    International Nuclear Information System (INIS)

    Bouras, N.; Caudry, M.; Bonnel, C.; Trouette, R.; Demeaux, H.; Maire, J.P.; Saric, J.; Rullier, E.

    2002-01-01

    Purpose. - Retrospective study of 23 patients treated with conformal radiotherapy for a locally advanced bile duct carcinoma. Patients and methods. - Eight cases were irradiated after a radical resection (RO), because they were N+; seven after microscopically incomplete resection (R1) ; seven were not resected (R2). A dose of 45 of 50 Gy was delivered, followed by a boost up to 60 Gy in R1 and R2 groups. Concomitant chemotherapy was given in 15 cases. Results.-Late toxicity included a stenosis of the duodenum, and one of the biliary anastomosis. Two patients died from cholangitis, the mechanism of which remains unclear. Five patients are in complete remission, six had a local relapse, four developed a peritoneal carcinosis, and six distant metastases. Actuarial survival rate is 75%, 28% and 7% at 1, 3 and 5 years, respectively (median: 16.5 months). Seven patients are still alive with a 4 to 70 months follow-up. Survival is similar in the 3 small subgroups. The poor local control among RON+ cases might be related to the absence of a boost to the 'tumor bed'. In R1 patients, relapses were mainly distant metastases, where'as local and peritoneal recurrences predominated in R2. Conclusion. - Conformal radio-chemotherapy delivering 60 Gy represents a valuable palliative approach in locally advanced biliary carcinoma. (authors)

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

    International Nuclear Information System (INIS)

    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)

  6. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok

    2014-01-01

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  7. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  8. Dabrafenib for Treating Unresectable, Advanced or Metastatic BRAF V600 Mutation-Positive Melanoma: An Evidence Review Group Perspective.

    Science.gov (United States)

    Fleeman, Nigel; Bagust, Adrian; Beale, Sophie; Boland, Angela; Dickson, Rumona; Dwan, Kerry; Richardson, Marty; Dundar, Yenal; Davis, Helen; Banks, Lindsay

    2015-09-01

    The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014. The clinical evidence for dabrafenib was derived from an ongoing phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BREAK-3) involving 230 patients randomized 2:1 to receive either dabrafenib or dacarbazine. A significant improvement in median progression-free survival (PFS) but not overall survival (OS) was reported in the dabrafenib arm compared with dacarbazine. Vemurafenib is considered a more appropriate comparator than is dacarbazine. The clinical evidence for vemurafenib was derived from a completed phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BRIM-3) involving 675 patients randomized 1:1 to receive either vemurafenib or dacarbazine. A significant improvement in median PFS and OS was reported in the vemurafenib arm compared with dacarbazine. As there is no direct evidence comparing dabrafenib versus vemurafenib, the company presented an indirect treatment comparison (ITC) that demonstrated no statistical differences between dabrafenib and vemurafenib for PFS or OS. The ERG expressed concerns with the ITC, mainly in relation to the validity of the assumptions underpinning the methodology; the ERG concluded this resulted in findings that are unlikely to be robust or reliable. Dabrafenib and

  9. [Modern aspects of surgical treatment of locally advanced pelvic cancer].

    Science.gov (United States)

    Solovyov, I A; Vasilchenko, M V; Lychev, A B; Ambartsumyan, S V; Alekseev, V V

    2015-09-01

    The aim of investigation is to improve surgical treatment of patients with locally advanced pelvic cancer. The basis of investigation is 186 patients with locally advanced pelvic cancer. The average age of patients is 65.2 ± 5.2 years (from 43.7 to 88.4 years). Among them are 112 women and 74 men. In the period from 2007 to 2015 they were carried out combined (101 patients) and expanded (85 patients) surgical intervention in the department of naval surgery of the Military medical academy after S.M.Kirov. Pelvic evisceration was performed in 63 cases. Both patients were performed isolated vascular hyperthermic chemical pelvic perfusion. Indications for plastic surgery of peritoneum pelvic were: total infralitoral pelvic evisceration (9 patients), dorsal infralitoral pelvic evisceration (11 cases) and expanded abdominoperineal rectum extirpation (34 patients). Plastic surgery with autogenouse tissues was performed to 43 patients, with reticulate explants--to 11 patients. The rate of postoperative complications was 40.2%. The rate of postoperative lethality was 8%. Expanded and combined operations of pelvic at patients with locally advanced cancer without absolute contra-indications can be performed irrespective of age. Plastic surgery of peritoneum pelvic after total and dorsal infralitoral pelvic evisceration and expanded abdominoperineal rectum extirpation indicated in all cases. The easiest method is plastic surgery with greater omentum or peritoneum pelvic. Plastic surgery with reticulate explants is performed when autoplastic is impossible.

  10. Does advanced lung inflammation index (ALI) have prognostic significance in metastatic non-small cell lung cancer?

    Science.gov (United States)

    Ozyurek, Berna Akinci; Ozdemirel, Tugce Sahin; Ozden, Sertac Buyukyaylaci; Erdoğan, Yurdanur; Ozmen, Ozlem; Kaplan, Bekir; Kaplan, Tugba

    2018-01-22

    Lung cancer is the most commonly diagnosed and death-related cancer type and is more frequent in males. Non-small-cell lung cancer (NSCLC) accounts for about 85% of all case. In this study, it was aimed to research the relationship between advanced lung inflammation index (ALI) and the primary mass maximum standardized uptake value (SUVmax) and C-reactive protein (CRP) at initial diagnosis and the prognostic value of ALI in determining the survival in metastatic NSCLC. A total of 112 patients diagnosed as stage 4 non-small-lung cancer in our hospital between January 2006 and December 2013 were included in this study. ALI was calculated as body mass index (BMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR). The patients were divided into two groups as ALI ALI ≥ 18 (low inflammation). The log-rank test and Cox proportional hazard model were used to identify predictors of mortality. Evaluation was made of 94 male and 18 female patients with a mean age of 59.7 ± 9.9 years. A statistically significant negative relationship was determined between ALI and CRP values (P ALI and SUVmax values (P = .436). The median survival time in patients with ALI ALI ≥ 18, it was 16 months (P = .095). ALI is an easily calculated indicator of inflammation in lung cancer patients. Values <18 can be considered to predict a poor prognosis. © 2018 John Wiley & Sons Ltd.

  11. Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

    Science.gov (United States)

    Shiomi-Mouri, Yukako; Kousaka, Junko; Ando, Takahito; Tetsuka, Rie; Nakano, Shogo; Yoshida, Miwa; Fujii, Kimihito; Akizuki, Miwa; Imai, Tsuneo; Fukutomi, Takashi; Kobayashi, Katsumasa

    2016-01-01

    Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p CEA and CA15-3.

  12. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara

    2014-01-01

    cancer that had progressed within the past 14 months. Adult patients (≥18 years of age) with this type of cancer were enrolled from 77 centres in 18 countries. To be eligible for inclusion, participants had to have at least one measurable lesion by CT or MRI according to Response Evaluation Criteria...... cancer. Adverse events were consistent with the known safety profile of sorafenib. These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer. FUNDING: Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals...

  13. A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.

    Science.gov (United States)

    Goncalves, Priscila H; Heilbrun, Lance K; Barrett, Michael T; Kummar, Shivaani; Hansen, Aaron R; Siu, Lillian L; Piekarz, Richard L; Sukari, Ammar W; Chao, Joseph; Pilat, Mary Jo; Smith, Daryn W; Casetta, Lindsay; Boerner, Scott A; Chen, Alice; Lenkiewicz, Elizabeth; Malasi, Smriti; LoRusso, Patricia M

    2017-05-16

    Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. Thirty patients were enrolled. Median age of patients was 53 years (range 21-73). Median number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3), oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC.

  14. Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma

    Science.gov (United States)

    2018-03-22

    Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage III Major Salivary Gland Cancer AJCC v7; Stage III Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Tongue Carcinoma

  15. Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

    Science.gov (United States)

    Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

    2015-02-01

    Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  16. Radiotherapy for advanced breast cancer. Immediate results

    International Nuclear Information System (INIS)

    Lederman, M.V.; Silveira Filho, L.; Martorelli Filho, B.

    1976-01-01

    Seventy-four patients with advanced breast cancer were submited to local radiotherapy of the affected regions. The response of 155 metastatic lesions are recorded. Early results are good, with objective and functional clinical improvement [pt

  17. Radiotherapy for advanced breast cancer. Immediate results

    Energy Technology Data Exchange (ETDEWEB)

    Lederman, M V; Silveira Filho, L; Martorelli Filho, B [Sao Paulo Univ. (Brazil). Faculdade de Medicina

    1976-01-01

    Seventy-four patients with advanced breast cancer were submited to local radiotherapy of the affected regions. The response of 155 metastatic lesions are recorded. Early results are good, with objective and functional clinical improvement.

  18. The role of sequential chemoradiation for local advanced oropharyngeal carcinoma

    International Nuclear Information System (INIS)

    Masterson, Liam; Tanweer, Faiz

    2013-01-01

    This study aims to assess survival, prognostic indicators, and pattern of failure for advanced oropharyngeal cancer treated by induction chemotherapy followed by concomitant chemoradiation (sequential CRT). A retrospective review of 80 consecutive patients who underwent chemoradiation [doublet cisplatin and 5-fluorouracil (PF)] for local advanced oropharyngeal carcinoma at a tertiary center from March 2003 to July 2008 is reported. Seven studies utilizing a similar protocol were reviewed, and all outcomes are collated. At a median follow-up of 32 months, the 3-year overall survival was 75%. Tumor size (p<0.001), age at presentation (p<0.002), and failure to complete the full course of induction chemotherapy (p<0.01) were all found to be significant factors affecting survival. Induction chemotherapy followed by concomitant chemoradiation utilizing doublet PF is an effective treatment for local advanced oropharyngeal carcinoma. At present, the addition of a taxane to the PF regimen cannot be assumed to provide benefit until further evidence emerges from a representative controlled trial. (author)

  19. A combined modality therapeutic approach to metastatic anal squamous cell carcinoma with systemic chemotherapy and local therapy to sites of disease: case report and review of literature.

    Science.gov (United States)

    Gnanajothy, Rosana; Warren, Graham W; Okun, Sherry; Peterson, Lindsay L

    2016-06-01

    Cases of metastatic anal carcinoma managed with a combination of systemic chemotherapy and local therapies to both solitary sites of metastases and the primary site have been reported in the literature. We present a case of a 55-year-old male with metastatic anal squamous cell carcinoma to the liver treated with induction chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU) followed by liver resection and radiation to the anal primary with concurrent 5FU and mitomycin. This approach resulted in control of disease without evidence of recurrence, and no increased toxicities now 19 months from initial diagnosis to time of reporting. This novel approach resulted in a good treatment response as documented by imaging and symptom improvement and a long disease free interval.

  20. A multidisciplinary treatment strategy for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Kimura, F.; Yanagi, Hidenori; Atono, R.

    2012-01-01

    The aim of this study is to examine the therapeutic effects and adverse events of preoperative chemoradiation therapy (CRT) for locally advanced rectal cancer in different radiation doses and fractions. A total of 142 consecutive patients with locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the rectum were treated with preoperative CRT and were operated radically. 121 patients with resectable cT3 or N1-2 rectal adenocarcinoma were assigned to receive pelvic radiation with single fractions of 2.5 Gy twice daily to a total dose of 25 Gy (Short CRT). Surgery was undergone within two weeks. 21 patients with clinical unresectable or marginally resectable cT4 rectal cancer were assigned to receive preoperative pelvic radiation therapy 45 to 50.4 Gy at 1.8 Gy per day. Surgery was performed 6 to 8 weeks after completion of neoadjuvant therapy (Long CRT). We examined retrospectively the preoperative therapeutic effect and adverse event of Short CRT and Long CRT. Short CRT; Overall R0 resection rate was 98%. Anus preserving rate was 95%. pCR rate was 5%. Median follow-up was 62 months. The actuarial 5-year-local-control rate was 94%. Overall survival for 5 years was 92%. Long neoadjuvant chemoradiation therapy (NCRT); Overall R0 resection rate was 90%. Anus preserving rate was 86%. pCR rate was 24%. Median follow-up was 60 months. The actuarial 5-year-local-control rate was 88%. Overall survival rate for 5 years was 88%. Radiation related adverse event such as pelvic infection and skin trouble was significantly higher in the long CRT group. Local control in primarily resectable rectal cancer after short chemoradiation was excellent. Long chemoradiation for unresectable or marginal cT4 rectum cancer was higher response ratio, but induced more radiation related adverse event than short course CRT. (author)

  1. Locally advanced colon cancer with cutaneous invasion: case report.

    Science.gov (United States)

    Tenreiro, Nádia; Ferreira, Cátia; Silva, Silvia; Marques, Rita; Ribeiro, Artur; Sousa, Paulo Jorge; Luís, Fernando Próspero

    2017-03-01

    Locally advanced colon cancer with direct abdominal wall and skin invasion is an extremely rare finding with most data being derived from case reports, historical autopsy-based or single-center retrospective studies. We present a unique case of a colon cancer with direct cutaneous invasion and colocutaneous fistulization. Eighty-six year old Caucasian female with multiple comorbidities, referred to Surgical Consultation due to ulcerated skin lesion in the abdomen. She had a long-standing large umbilical hernia but with no previous episodes of incarceration or occlusive symptoms. She denied any digestive or constitutional symptoms. Physical examination showed a large non-reducible umbilical hernia, with an associated painless firm mass within the hernia sac and cutaneous ulcerated growth. Colonoscopy revealed transverse colon cancer (endoscopic biopsy of the tumor and skin punch biopsy confirmed adenocarcinoma of the colon). Computed tomography showed a tumoral mass within the umbilical hernia, with cutaneous infiltration and enlarged regional lymph nodes. Rapid local progression led to colocutaneous fistula with total fecal diversion. We performed an extended right hemicolectomy with en bloc excision of the hernia sac and infiltrating cutaneous mass. In the current era of widespread use of screening colonoscopies, initial diagnosis of locally advanced colon cancer is decreasing. However, this unique case presented an opportunity to recall the advantages of multivisceral resections.

  2. Intraoperative radiation therapy for locally advanced gynecological malignancies

    International Nuclear Information System (INIS)

    Haddock, M.G.; Petersen, I.A.; Webb, M.J.; Wilson, T.O.; Podratz, K.C.; Gunderson, L.L.

    1996-01-01

    Purpose: Evaluate disease control and survival in patients with locally advanced gynecological malignancies who received intraoperative radiation therapy with electrons (IOERT) as a component of treatment. Methods and Materials: Between March 1983 and June 1995, 63 patients (pts) with locally advanced primary (9 pts) or recurrent (54 pts) gynecological malignancies received IOERT as a component of attempted curative therapy. The site of origin was uterine cervix in 40 pts, uterine corpus in 16 pts, vagina in 5 pts, and ovary in 2 pts. Thirty-eight patients with recurrent disease had been previously irradiated (median prior RT dose 5040 cGy, range 900-8400). External beam radiotherapy (EBRT) was given to 43 of 63 pts either before or after IOERT (900-6570 cGy, median 4960 cGy). Chemotherapy was given to 21 pts prior to IOERT and following IOERT in 2 pts. IOERT doses ranged from 800 cGy to 2500 cGy with a median of 1750 cGy. The median IOERT dose was 2000 cGy in 20 patients with gross residual disease and 1500 cGy in 43 patients with microscopic residual disease. Endpoints included central control within the IOERT cone, local control, distant failure, disease free survival and overall survival. Variables evaluated for impact on disease outcome included tumor grade, primary site, prior RT, IOERT dose, EBRT dose, residual disease at time of IOERT, and use of chemotherapy. Results: Survival and disease control data are presented in the table below. There was no impact of any disease or treatment related variable on local or central failure. Pts with microscopic residual disease at the time of IOERT had significantly fewer distant metastases than pts with gross residual (5 yr 31% vs. 77%, p = 0.001) and improved survival (5 yr 37% vs. 10%, p = 0.02). Patients with recurrent disease after previous RT had survival and disease control rates which were similar to those seen in pts without priot RT. Toxicity ≥ grade 3 due to IOERT was observed in 11 pts (17%). Conclusion: A

  3. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Kim, Jun-Sang; Kim, Jae-Sung; Cho, Moon-June; Song, Kyu-Sang; Yoon, Wan-Hee

    2002-01-01

    Purpose: Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer. Methods and Materials: Between July 1999 and March 2001, 45 patients with locally advanced rectal cancer (cT3/T4 or N+) were treated with preoperative chemoradiation. Radiation of 45 Gy/25 fractions was delivered to the pelvis, followed by a 5.4 Gy/3 fractions boost to the primary tumor. Chemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m 2 /day) and leucovorin (20 mg/m 2 /day), each of which was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation. Results: Thirty-eight patients received definitive surgery. Primary tumor and node downstaging occurred in 63% and 90% of patients, respectively. The overall downstaging rate, including both primary tumor and nodes, was 84%. A pathologic complete response was achieved in 31% of patients. Twenty-one patients had tumors located initially 5 cm or less from the anal verge; among the 18 treated with surgery, 72% received sphincter-preserving surgery. No Grade 3 or 4 hematologic toxicities developed. Other Grade 3 toxicities were as follows: hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%). Conclusion: These preliminary results suggest that preoperative chemoradiation with capecitabine is a safe, well-tolerated, and effective neoadjuvant treatment modality for locally advanced rectal cancer. In addition, this preoperative treatment has a considerable downstaging effect on the tumor and can increase the possibility of sphincter preservation in distal rectal cancer

  4. Treatments Results and Prognostic Factors in Locally Advanced Hypopharyngeal Cancer

    International Nuclear Information System (INIS)

    Yoon, Mee-Sun; Chung, Woong-Ki; Ahn, Sung-Ja; Nam, Taek-Keun; Song, Ju-Young; Nah, Byung-Sik; Lim, Sang Cheol; Lee, Joon Kyoo

    2007-01-01

    The purpose of this study is to present the treatment results and to identify possible prognostic indicators in patients with locally advanced hypopharyngeal carcinoma. Materials and Methods: Between October 1985 to December 2000, 90 patients who had locally advanced stage IV hypopharyngeal carcinoma were studied retrospectively. Twelve patients were treated with radiotherapy alone, 65 patients were treated with a combination of chemotherapy and radiotherapy, and 13 patients were treated with surgery and postoperative radiotherapy with or without neoadjuvant chemotherapy. Total radiation dose ranged from 59.0 to 88.2 Gy (median 70 Gy) for radiotherapy alone. Most patients had ciplatin and 5-fluorouracil, and others had cisplatin and peplomycin or vincristin. Median follow-up period was 15 months. Kaplan-Meier method was used for survival rate and Cox proportional hazard model for multivariate analysis of prognostic factors. Results: Overall 3- and 5-year survival rates were 27% and 17%, respectively. The 2-year locoregional control rates were 33% for radiotherapy alone, 32% for combined chemotherapy and radiotherapy, and 81% for combined surgery and radiotherapy (p=0.006). The prognostic factors affecting overall survival were T stage, concurrent chemo radiation and treatment response. Overall 3- and 5-year laryngeal preservation rates in combined chemotherapy and radiotherapy were 26% and 22%, respectively. Of these, the 5-year laryngeal preservation rates were 52% for concurrent chemo radiation group (n=11), and 16% for neoadjuvant chemotherapy and radiotherapy (n=54, p=0.012). Conclusion: Surgery and postoperative radiotherapy showed better results than radiotherapy alone or with chemotherapy. Radiotherapy combined with concurrent chemotherapy is an effective modality to achieve organ preservation in locally advanced hypopharyngeal cancer. Further prospective randomized studies will be required

  5. A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study

    International Nuclear Information System (INIS)

    Bridgewater, John; Lopes, Andre; Beare, Sandra; Duggan, Marian; Lee, Dymphna; Ricamara, Maravic; McEntee, Delyth; Sukumaran, Ajithkumar; Wasan, Harpreet; Valle, Juan W.

    2016-01-01

    Combined treatment with cisplatin and gemcitabine (CisGem) is the standard of care for patients with advanced biliary tract cancer (ABC). Selumetinib (AZD6244, ARRY-142886) potently and selectively inhibits MEK1/2, an intracellular kinase and has shown activity in ABC. The objective of the ABC-04 trial was to establish the recommended dose of selumetinib in combination with CisGem in patients with ABC. Eligible patients were ≥ 18 years, had histologically or cytologically-confirmed unresectable recurrent or metastatic biliary tract, gallbladder or ampullary carcinoma, WHO performance status 0–2, and adequate major organ function. Patients may have had prior surgery, radiotherapy or adjuvant chemotherapy, but no prior CisGem and no prior chemotherapy for locally advanced or metastatic disease. Patients received cisplatin 25 mg/m 2 plus gemcitabine 1000 mg/m 2 intravenously on days 1 and 8 of a 21-day cycle. Selumetinib capsules were taken daily. Patients received up to 8 cycles of CisGem and could receive selumetinib until disease progression. A dose de-escalation scheme was used to determine the recommended dose of selumetinib. The first dose level was 75 mg bd. Patients were recruited in cohorts of 3 and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. Thirteen patients were recruited, of whom 12 were evaluable for DLT (1 did not start treatment). All evaluable patients received the starting dose of selumetinib 75 mg bd and one patient experienced a DLT (cardiac chest pain). The median number of days selumetinib was taken (adjusted for the number of days of dose interruptions) was 171.5 (IQR: 75.5 to 344). Two patients remained on treatment at 14 and 19 months post registration. There were 3 temporary and 1 permanent interruptions of selumetinib in cycle 1. Eight patients were evaluable for objective response (RECIST v1.1): 3 had a partial response and 5 stable disease. The median PFS was 6.4 months (IQR 5.2 to 13.7). Toxicities

  6. Radio(chemotherapy in locally advanced nonsmall cell lung cancer

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    Markus Glatzer

    2016-03-01

    Full Text Available Definitive radiochemotherapy is the standard treatment for many patients with locally advanced nonsmall cell lung cancer (NSCLC. Treatment outcomes have improved over the last decades. Several treatment regimens have been shown effective and safe. This review summarises the results of significant studies between 1996 and 2015 on concomitant and sequential radiochemotherapy regimens and radiation dose per fraction. Beside therapy regimens, optimised radiotherapy planning is indispensable to improve outcome and minimise radiation-induced toxicity. An insight into the rationale of radiotherapy planning for stage III NSCLC is also provided.

  7. Locally advanced transverse colon cancer with Trousseau’s syndrome

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    V. A. Aliyev

    2012-01-01

    Full Text Available Migratory venous thrombosis is a manifestation of the rare paraneoplastic syndrome in patients with malignant neoplasms. The paper describes successful surgical treatment in a young patient with a colon tumor associated with Trousseau’s syndrome. The latter manifesting itself as ischemia forced urgent surgeons to amputate the lower third of the left leg. Locally advanced transverse colon cancer spreading to the great vessels was subsequently diagnosed. All paraneoplastic manifestations disappeared after tumor removal. The patient was professionally given surgical, anesthesiological, and resuscitative aids that not only improved his quality of life, but also gave the chance to prolong it.

  8. Hypofractionated radiotherapy as local hemostatic agent in advanced cancer

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    Malik Tariq Rasool

    2011-01-01

    Full Text Available Purpose : Tumor bleeding continues to remain a challenge in an oncological setting, and radiotherapy has been studied as a local hemostatic agent. We studied the role of local radiotherapy in controlling bleeding at our center. Materials and Methods : We reviewed 25 treated cases (cancer urinary bladder: 12, lung cancer: 5, cervical cancer: 4, uterine cancer: 1, rectal cancer: 2, schwanoma: 1 at our center from March 2008 to December 2010. All patients had either an advanced or recurrent disease. Radiotherapy schedule was either 20 Gray in 5 fractions or 15 Gray in 5 fractions and was delivered with Cobalt 60. Results and Conclusion : Of 25 patients, 22 (88% responded, and there was complete cessation of bleeding. Both 15 Gray and 20 Gray dose schedule had equal efficacy. Treatment was well tolerated without any intermission. Radiotherapy is a safe and effective option in controlling tumor bleeding.

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  10. Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer

    Directory of Open Access Journals (Sweden)

    Ivelina Gueorguieva

    2016-12-01

    Full Text Available Objective: Galunisertib (LY2157299 monohydrate, an inhibitor of the transforming growth factor β (TGFβ pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC dry-milled (RCD and RC slurry-milled (RCS processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG process. The secondary objective was to report the safety profile after a single dose of the three formulations. Methods: Patients with advanced or metastatic cancer were enrolled into this single-center, 3-period, 6-sequence crossover study. Patients were assigned sequentially to 1 of 6 sequences in blocks of 6 to ensure that all 6 sequences have the same number of completers. A patient entering a sequence received a different galunisertib formulation as a single 150 mg dose orally during each of the 3 periods. Each period was separated from the next by a washout interval of at least 48 hours. Pharmacokinetic (PK parameters, including area under curve (AUC and Cmax, were computed using standard non-compartmentalized methods of analysis. For comparison of exposures between formulations, log-transformed AUC and Cmax values were analyzed using a linear mixed-effects model. Safety assessments included adverse event monitoring, physical examinations, and laboratory tests. Results: Of the 14 patients who entered and completed the study, 13 patients were included in the final statistical analysis. AUC(0-tlast, AUC(0-48 h, and AUC(0-∞ for the RC formulations and the HSWG formulation were similar. Cmax was reduced by approximately 22% and tmax was longer by at least 1.00 h for the RCD and RCS formulations compared with the HSWG formulation. The RC formulations demonstrated a safety profile after a single dose similar to the HSWG formulation. Conclusions

  11. Preoperative Intensity-Modulated Radiotherapy Combined with Temozolomide for Locally Advanced Soft-Tissue Sarcoma

    International Nuclear Information System (INIS)

    Jakob, Jens; Wenz, Frederik; Dinter, Dietmar J.; Stroebel, Philipp; Hohenberger, Peter

    2009-01-01

    Purpose: To evaluate the toxicity and efficacy of preoperative intensity-modulated radiotherapy (IMRT) combined with temozolomide to improve local tumor control in soft-tissue sarcoma (STS). Patients and Methods: A cohort of 15 consecutive patients with nonmetastasized, primary high-grade or locally recurrent Stage III (n = 14) or IIb (n = 1) STS not amenable to surgical resection without significant organ or extremity function loss was prospectively investigated. Median tumor size was 9.8 cm, and most tumors were non-extremity sarcomas. Patients preoperatively received 50 mg/m 2 of temozolomide during IMRT (50.4 Gy). Resection was intended 6 weeks thereafter. Toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, and response was assessed by Response Evaluation Criteria in Solid Tumors. Results: Of 15 patients, 14 completed preoperative treatment. No Grade 4 toxicities occurred. Nausea and vomiting were the most frequent Grade 3 toxicities. The most frequent toxicities of any grade were dermatologic, gastrointestinal, and hematologic. Response was partial response in 5, stable disease in 7, and progressive disease in 2 patients. Ten patients underwent surgery: 7 were resected with clear margins (R0), and 2 patients had an R1 resection; in 1 patient the tumor was not resectable. Postoperative complications occurred in 4 patients. Five patients did not undergo surgery because of intercurrent metastatic disease, unresectable disease, or refusal. Conclusions: Preoperative chemoradiation with temozolomide and IMRT can be administered safely and with promising efficacy in patients with locally advanced STS.

  12. Effects on functional outcome after IORT-containing multimodality treatment for locally advanced primary and locally recurrent rectal cancer

    NARCIS (Netherlands)

    Mannaerts, GHH; Rutten, HJT; Martijn, H; Hanssens, PEJ; Wiggers, T

    2002-01-01

    Purpose: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer, much attention is focused on. the oncologic outcome. Little is known about the functional outcome. In this study, the functional outcome after a multimodality treatment for locally advanced

  13. Accelerated Hyperfractionated Radiotherapy for Locally Advanced Uterine Cervix Cancers

    International Nuclear Information System (INIS)

    Seo, Young Seok; Cho, Chul Koo; Yoo, Seong Yul

    2008-01-01

    To assess the efficacy of the use of accelerated hyperfractionated radiotherapy (AHRT) for locally advanced uterine cervix cancers. Between May 2000 and September 2002, 179 patients were identified with FIGO stage IIB, IIIB, and IVA cancers. Of the 179 patients, 45 patients were treated with AHRT (AHRT group) and 134 patients were treated with conventional radiotherapy (CRT group), respectively. Patients undergoing the AHRT regimen received a dose of 30 Gy in 20 fractions (1.5 Gyx2 fractions/day) to the whole pelvis. Subsequently, with a midline block, we administered a parametrial boost with a dose of 20 Gy using 2 Gy fractions. Patients also received two courses of low-dose-rate brachytherapy, up to a total dose of 85∼90 Gy to point A. In the CRT group of patients, the total dose to point A was 85∼90 Gy. The overall treatment duration was a median of 37 and 66 days for patients that received AHRT and CRT, respectively. Statistical analysis was calculated by use of the Kaplan-Meier method, the log-rank test, and Chi-squared test. For patients that received cisplatin-based concurrent chemotherapy and radiotherapy, the local control rate at 5 years was 100% and 79.2% for the AHRT and CRT group of patients, respectively (p=0.028). The 5-year survival rate for patients with a stage IIB bulky tumor was 82.6% and 62.1% for the AHRT group and CRT group, respectively (p=0.040). There was no statistically significant difference for severe late toxicity between the two groups (p=0.561). In this study, we observed that treatment with AHRT with concurrent chemotherapy allows a significant advantage of local control and survival for locally advanced uterine cervix cancers

  14. Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review.

    Science.gov (United States)

    Quintana, Miguel; Toriz, José A; Novick, Diego; Jones, Kyla; Botello, Brenda S; Silva, Juan Alejandro

    2017-07-31

    Little evidence is available on the management and cost of treating patients with advanced or metastatic gastric cancer (GC). This study evaluates patient characteristics, treatment patterns, and resource utilization for these patients in Mexico. Data were collected from three centers of investigation (tertiary level). Patients were ≥18 years of age, diagnosed between 1 January 2009 and 1 January 2015, had advanced or metastatic GC, received first-line fluoropyrimidine/platinum, and had ≥3 months follow-up after discontinuing first-line treatment. Data were summarized using descriptive statistics. The study sample totaled 180. Patients' mean age was 57.2 years (±12.4) and 57.0% were male; 151 (83.9%) patients received second-line chemotherapy. A total of 16 and 19 regimens were identified in first- and second-line therapy. Of the sample, 51 (28.3%) received third-line therapy, and <10% received more than three lines of active chemotherapy. Supportive care received in first- and second-line chemotherapy, included pain interventions (12.2 and 7.9%), nutritional support (3.3 and 1.3%), radiotherapy (6.1 and 16.6%), and transfusions (13.3 and 10.6%), respectively. Using Mexican Institute of Social Security (IMSS) tariffs, the average total cost per patient-month in first- and second-line therapy was US$1230 [95% confidence interval (CI) 1034-1425] and US$1192 (95% CI 913-1471), respectively. Administration and acquisition of chemotherapy comprised the majority of costs. This study shows considerable variation in first- and second-line chemotherapy regimens of patients with advanced or metastatic GC. Understanding GC treatment patterns in Mexico will help address unmet needs.

  15. Alterative Expression and Localization of Profilin 1/VASPpS157 and Cofilin 1/VASPpS239 Regulates Metastatic Growth and is Modified by DHA Supplementation

    Science.gov (United States)

    Ali, Mehboob; Heyob, Kathryn; Jacob, Naduparambil K.; Rogers, Lynette K.

    2016-01-01

    Profilin 1, cofilin 1, and vasodialator stimulated phosphoprotein (VASP) are actin binding proteins (ABP) which regulate actin remodelling and facilitate cancer cell metastases. MiR~17–92 is highly expressed in metastatic tumors and profilin1 and cofilin1 are predicted targets. Docosahexaenoic acid (DHA) inhibits cancer cell proliferation and adhesion. These studies tested the hypothesis that the metastatic phenotype is driven by changes in ABPs including alternative phosphorylation and/or changes in subcellular localization. Additionally, we tested the efficacy of DHA supplementation to attenuate or inhibit these changes. Human lung cancer tissue sections were analyzed for F-actin content and expression and cellular localization of profilin1, cofilin1 and VASP (S157 or S239 phosphorylation). The metastatic phenotype was investigated in A549 and MLE12 cells lines using 8 Br-cAMP as a metastasis inducer and DHA as a therapeutic agent. Migration was assessed by wound assay and expression measured by western blot and confocal analysis. MiR~17–92 expression was measured by qRT-PCR. Results indicated increased expression and altered cellular distribution of profilin1/VASPpS157 but no changes in cofilin1/VASPpS239 in the human malignant tissues compared to normal tissues. In A549 and MLE12 cells, the expression patterns of profilin1/VASPpS157 or cofilin1/VASPpS239 suggested an interaction in regulation of actin dynamics. Furthermore, DHA inhibited cancer cell migration and viability, ABP expression and cellular localization, and modulated expression of miR~17–92 in A549 cells with minimal effects in MLE12 cells. Further investigations are warranted to understand ABP interactions, changes in cellular localization, regulation by miR~17–92, and DHA as a novel therapeutic. PMID:27496138

  16. Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

    Science.gov (United States)

    Yamada, Yoshiaki; Itoh, Youko; Aoki, Shigeyuki; Nakamura, Kogenta; Taki, Tomohiro; Naruse, Katsuya; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Kato, Yoshiharu; Watanabe, Masahito; Nishikawa, Genya; Minami, Miwako; Nakahira, Mariko; Ukai, Sayaka; Sawada, Masaki; Kitamura, Akiko; Honda, Nobuaki

    2009-11-01

    We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients' oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium.

  17. Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy

    International Nuclear Information System (INIS)

    Douglas, James G.; Laramore, George E.; Austin-Seymour, Mary; Koh Wuijin; Stelzer, Keith; Griffin, Thomas W.

    2000-01-01

    skull involvement (p < 0.001), lymph node metastases at the time of treatment (p < 0.01), biopsy only prior to neutron radiotherapy (p = 0.03), and recurrent tumors (p = 0.04) were found to be associated with a diminished cause-specific survival as ascertained by multivariate analysis. Patients with base of skull involvement and positive lymph nodes at presentation had an increased rate of the development of distant metastases at 5 years, (p < 0.01 and p <0.001, respectively). No statistical difference in outcome was observed between major and minor salivary gland sites. Conclusions: Fast neutron radiotherapy is an effective treatment for locally advanced ACC of the head and neck region with acceptable toxicity. Further improvements in local-regional control are not likely to impact survival until more effective systemic agents are developed to prevent and/or treat distant metastatic disease

  18. Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report.

    Science.gov (United States)

    Bezpalko, Kseniya; Mohamed, Mohamed A; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth

    2015-01-01

    At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Postoperative chemoradiotherapy in high risk locally advanced gastric cancer

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    Song, Sang Hyuk; Chie, Eui Kyu; Kim, Kyu Bo; Lee, Hyuk Joon; Yang, Han Kwang; Han, Sae Won; Oh, Do Youn; Im, Seok Ah; Bang, Yung Jue; Ha, Sung W. [Seoul National University College of Medicine, Seoul(Korea, Republic of)

    2012-12-15

    To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy. Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy). The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Loco-regional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity. Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.

  20. Conformal radiotherapy for locally advanced juvenile nasopharyngeal angio-fibroma

    Directory of Open Access Journals (Sweden)

    Supriya Mallick

    2015-01-01

    Full Text Available Purpose: To assess the efficacy of radiation in the treatment of juvenile nasopharyngeal angiofibroma (JNA. Materials and Methods: Data were retrieved for JNA treated with radiotherapy from 1987-2012. The demographics, treatment and outcome data were recorded in predesigned proforma. Results: Data of 32 patients were retrieved. Median age was 17 years (range: 12-33 years. All patients received radiation because of refractory, residual or unresectable locally advanced disease. All patients were planned with a three-dimensional conformal technique (3DCRT. The median radiation dose was 30 Gray (range: 30-45 Gray. Median follow-up was 129 months (range: 1-276 months. At the last follow-up, 13 patients were found to have a radiological complete response. Two patients progressed 38 and 43 months after completion of treatment and opted for alternative treatment. One patient developed squamous cell carcinoma of the nasal ale 15 years after radiation. Conclusion: Conformal radiotherapy shows promise as an alternative treatment approach for locally advanced JNA and confers long-term disease control with minimal toxicity.

  1. Treatment results of incomplete chemoradiotherapy in locally advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Gao Y

    2013-04-01

    Full Text Available Ying Gao,1,* Fei Gao,2,* Zi Liu,1 Li-ping Song1 1Department of Radiotherapy Oncology, First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Second Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, People’s Republic of China *These authors contributed equally to this work Objective: Regimens that combine chemotherapy and radiotherapy increase toxicity and compromise a patient’s ability to adhere to the treatment plan. We evaluated the efficacy and safety of a partially completed chemoradiation regimen prescribed for locally advanced carcinoma of the cervix. Methods: Medical records of 156 patients with locally advanced cervical cancer stage IIB–IVA who received chemoradiation with cisplatin (40 mg/m2 and 5-fluorouracil (500 mg/m2 from October 2006 to October 2008 were collected. The treatment protocol called for two cycles of chemotherapy. External beam radiation therapy was administered using a 10-MeV electron beam. Local control, disease free survival, overall survival, and toxicities were evaluated. Results: With a median follow-up of 37.5 months, 89 patients (57% completed the planned protocol. Sixty seven patients (43% completed fewer than two cycles. The 3-year local control rate was significantly better in the patient group that completed the prescribed plan (92.1% compared to 80.6%; P = 0.033. No statistical significance was observed between the groups that completed or did not complete the two cycle protocol with regard to disease free survival (80.9% and 73.2%, respectively; P = 0.250, overall survival (84.3% and 79.1%; P = 0.405, and progression survival (3.4% and 3.0%; P = 0.892. Differences in acute hematologic toxicity and subcutaneous toxicity were observed between the two groups. Conclusions: Completion of two cycles of 5-fluorouracil and cisplatin with radiotherapy was effective, safe, and responsible for better local control

  2. Locally advanced prostate cancer: a population-based study of treatment patterns.

    Science.gov (United States)

    Lowrance, William T; Elkin, Elena B; Yee, David S; Feifer, Andrew; Ehdaie, Behfar; Jacks, Lindsay M; Atoria, Coral L; Zelefsky, Michael J; Scher, Howard I; Scardino, Peter T; Eastham, James A

    2012-05-01

    Study Type--Therapy (practice patterns). Level of Evidence 2b. What's known on the subject? And what does the study add? The treatment of locally advanced prostate cancer varies widely even though there is level one evidence supporting the use of multimodality therapy as compared with monotherapy. This study defines treatment patterns of locally advanced prostate cancer within the United States and identifies predicators of who receives multimodality therapy rather than monotherapy. • To identify treatment patterns and predictors of receiving multimodality therapy in patients with locally advanced prostate cancer (LAPC). • The cohort comprised patients ≥66 years with clinical stage T3 or T4 non-metastatic prostate cancer diagnosed between 1998 and 2005 identified from the Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims. • Treatments were classified as radical prostatectomy (RP), radiation therapy (RT) and androgen deprivation therapy (ADT) received within 6 and 24 months of diagnosis. • We assessed trends over time and used multivariable logistic regression to identify predictors of multimodality treatment. • Within the first 6 months of diagnosis, 1060 of 3095 patients (34%) were treated with a combination of RT and ADT, 1486 (48%) received monotherapy (RT alone, ADT alone or RP alone), and 461 (15%) received no active treatment. • The proportion of patients who received RP increased, exceeding 10% in 2005. • Use of combined RT and ADT and use of ADT alone fluctuated throughout the study period. • In all 6% of patients received RT alone in 2005. • Multimodality therapy was less common in patients who were older, African American, unmarried, who lived in the south, and who had co-morbidities or stage T4 disease. • Treatment of LAPC varies widely, and treatment patterns shifted during the study period. • The slightly increased use of multimodality therapy since 2003 is encouraging, but

  3. Hypothyroidism after Radiotherapy of Locally Advanced Head and Neck Cancer

    International Nuclear Information System (INIS)

    Lee, Jeong Eun; Eun; Kim, Jae Chul; Park, In Kyu; Yea, Ji Woon

    2010-01-01

    The aim of the present study was to retrospectively evaluate the incidence of hypothyroidism in locally advanced head and neck cancer patients who received radiotherapy (RT) either with or without neck dissection. From January 2000 to December 2005, 115 patients with locally advanced head and neck cancer and who received definitive RT or postoperative RT including standard anterior low-neck field were recruited to be part of this study. Nineteen patients had undergone ipsilateral neck dissection, whereas, 18 patients underwent bilateral neck dissection, and 78 patients were received RT alone. Patients' ages ranged from 28 to 85 years (median, 59 years) and there were a total of 73 male and 42 female patients. The primary tumor sites were the oral cavity, oropharynx, hypopharynx, larynx, and other sites in 18, 40, 28, 22 and 7 patients, respectively. Radiation dose to the thyroid gland ranged from 44 Gy to 66 Gy with a median dose of 50 Gy. Follow-up time ranged from 2 to 91 months, with a median of 29 months. The 1- and 3- year incidence of hypothyroidism was 28.7% (33 patients) and 33.0% (38 patients), respectively. The median time to detection of hypothyroidism was 8.5 months (range, 0 to 36 months). A univariate analysis revealed that neck node dissection was a risk factor for hypothyroidism (p=0.037). However, no factor was statistically significant from the results of a multivariate analysis. Patients treated for advanced head and neck cancer with radiotherapy with or without neck dissection will develop hypothyroidism. It is important to check the thyroid function periodically in these patients especially with the risk factor of neck node dissection.

  4. Hypothyroidism after Radiotherapy of Locally Advanced Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun; Eun; Kim, Jae Chul; Park, In Kyu [Kyungpook National Yonsei University School of Medicine, Daegu (Korea, Republic of); Yea, Ji Woon [Dongguk University Gyeongju Hospital, Gyeongju (Korea, Republic of)

    2010-11-15

    The aim of the present study was to retrospectively evaluate the incidence of hypothyroidism in locally advanced head and neck cancer patients who received radiotherapy (RT) either with or without neck dissection. From January 2000 to December 2005, 115 patients with locally advanced head and neck cancer and who received definitive RT or postoperative RT including standard anterior low-neck field were recruited to be part of this study. Nineteen patients had undergone ipsilateral neck dissection, whereas, 18 patients underwent bilateral neck dissection, and 78 patients were received RT alone. Patients' ages ranged from 28 to 85 years (median, 59 years) and there were a total of 73 male and 42 female patients. The primary tumor sites were the oral cavity, oropharynx, hypopharynx, larynx, and other sites in 18, 40, 28, 22 and 7 patients, respectively. Radiation dose to the thyroid gland ranged from 44 Gy to 66 Gy with a median dose of 50 Gy. Follow-up time ranged from 2 to 91 months, with a median of 29 months. The 1- and 3- year incidence of hypothyroidism was 28.7% (33 patients) and 33.0% (38 patients), respectively. The median time to detection of hypothyroidism was 8.5 months (range, 0 to 36 months). A univariate analysis revealed that neck node dissection was a risk factor for hypothyroidism (p=0.037). However, no factor was statistically significant from the results of a multivariate analysis. Patients treated for advanced head and neck cancer with radiotherapy with or without neck dissection will develop hypothyroidism. It is important to check the thyroid function periodically in these patients especially with the risk factor of neck node dissection.

  5. Locally advanced cervix carcinoma - innovation in combined modality therapy

    International Nuclear Information System (INIS)

    Swift, Patrick S.

    1996-01-01

    Locally advanced cervical carcinoma continues to be a challenge to the clinician due to local failure as well as systemic metastases. Standard intracavitary and external beam techniques result in local control rates of only 35-65%, with long term survival rates of 25-60% in patients with state IIIA-IVA disease, indicating the need to identify new treatment strategies. Optimization programs for remote-afterloading interstitial brachytherapy allow the delivery of higher local doses of radiation to volumes that more closely approximate tumor target volumes as identified on MR scans, leading to improved therapeutic ratios. Identification of subsets of patients more likely to fail standard therapy, either locally or systemically, may be possible through such techniques as in vivo measurements of hypoxia with Eppendorf oxygen electrodes, interstitial fluid pressure measurements, the Comet assay, and nitroimidazole binding methods. Traditional chemotherapies, administered in either a neoadjuvant role or concomitantly with radiation have been disappointing in prospective trials. A variety of new agents are being investigated to determine if they can increase the frequency or duration of complete response. The taxanes, with response rates of 17-23% by themselves, are being assessed as potential radiosensitizers. The camptotheicin CRT-11 (Irinotecan) has demonstrated activity in platinum resistant cervix cancer, with response rates of 24%. Bioradiotherapeutic approaches, using 13-cis-retinoic acid and interferon-2a, are undergoing phase II studies. Neoangiogenesis inhibitors and vaccines against HPV are also being examined. The aggressive pursuit of techniques that help identify those patients most likely to fail, that allow the delivery of higher radiation doses more safely to the target volume, and that incorporate the use of more effective systemic therapies is necessary to improve the outcome for this disease

  6. Pre-operative radiochemotherapy of locally advanced rectal cancer

    Institute of Scientific and Technical Information of China (English)

    Xiao-Nan Sun; Qi-Chu Yang; Jian-Bin Hu

    2003-01-01

    AIM: To evaluate results of pre-operative radiochemotherapy followed by surgery for 15 patients with locally advanced un-resectable rectal cancer.METHODS: 15 patients with advanced non-resectable rectal cancer were treated with pre-operative irriadiation of 40-46 Gy plus concomitant chemotherapy (5-FU+LV and 5′-DFuR) (RCS group). For comparison, 27 similar patients,treated by preoperative radiotherapy (40-50 Gy) plus surgery were served as control (RS group).RESULTS: No radiochemotherapy or radiotherapy was interrupted and then was delayed because of toxicities in both groups. The radical resectability rate was 73.3% in the RCS group and 37.0% (P=0.024) in RS group. Sphincter preservation rates were 26.6% and 3.7% respectively (P=0.028). Sphincter preservation rates of lower rectal cancer were 27.3 % and 0.0 % respectively (P=0.014). Response rates of RCS and RS groups were 46.7 % and 18.5 %(P=0.053). The tumor downstage rates were 8 (53.3%)and 9 (33.3%) in these groups (P=0.206). The 3-year overall survival rates were 66.7 % and 55.6% (P=0.485), and the disease free survival rates were 40.1% and 33.2%(P=0.663). The 3-year local recurrent rates were 26.7%and 48.1% (P=0.174). No obvious late effects were found in either groups.CONCLUSION: High resectability is possible following preoperative radiochemotherapy and can have more sphincters preserved. It is important to improve the quality of the patients′ life even without increasing the survival or local control rates. Preoperative radiotherapy with concomitant full course chemotherapy (5-Fu+LV and 5′-DFuR) is effective and safe.

  7. Exclusive radiation therapy for locally advanced laryngeal carcinoma

    International Nuclear Information System (INIS)

    Antognoni, P.; Bossi, A.; Molteni, M.; Richetti, A.; Tordiglione, M.

    1990-01-01

    The authors analyse a retrospective series of 90 consecutive patients (pts) affected with locally advanced laryngeal carcinoma (T3-4, N0-3 - TNM, UICC 1978) who were radically irradiated from November 1979 to December 1986 at the Radiotherapy Department of the General Hospital of Varese. All the patients were treated with 60 Co and two opposed parallel lateral fields and progressive shrinkage: 66 conventional fractionation (2 Gy once a day, 5 times a week), 24 with an accelerated hyperfractionated regimen (1.5 Gy twice a day, 5 times a week). The median total dose delivered to the tumor and clinically involved nodes was 64 Gy (1678 reu, CRE). Median follow-up was 21 months (range: 3-113). The 5-year overall survival (Kaplan-Meier) was 40.5%. The 5-year disease-free survival, for 47 patients in complete remission at the end of radiotherapy, was 51.9% after irradiation alone and 56.7% with salvage surgery. There were no statistically significant differences in survival according to local spread (T3 vs T4), nodal status (N0 vs N1-3) and dose fractionation regimen (conventional vs accelerated hyper-fractionated). Isoeffect (CRE) values above 1751 reu obtained a 3-year loco-regional control rate was 33.3%. Relevant late sequelae were not observed. Our findings suggest that primary radiotherapy with salvage surgery in reserve could be considered as an effective choice for locally advanced laryngeal carcinoma, at least in selected groups of patients

  8. Changes in survival in locally advanced laryngeal carcinoma over past three decades

    International Nuclear Information System (INIS)

    EL-Zawahry, I.M.Sh.

    2013-01-01

    Laryngeal cancer is the commonest carcinoma of the head and neck region with Squamous-cell carcinomas (SCC) in 90 % of cases (Birchall Met al 2008) The incidence of laryngeal cancer was relatively about 160,000 new cases per year. The disease predominantly affects men; about 2.4% of all cancer cases and 2.1% of all cancer deaths worldwide ,also in United States in 2012 the Es)mated new cases is 12,360 and deaths from laryngeal cancer is 3,650. The majority of patients with SCC of larynx present with locally advanced (LA) disease.(American Cancer Society, 2012) The incidence of laryngeal cancer in the Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK), Faculty of Medicine, Cairo University from year 2005 - 2008 is 3.1%per year. Advanced laryngeal cancer is generally considered as the disease in stages III and IV based on the primary tumor extension and/or the presence of metastatic lymph node(s) in the neck and it accounts for roughly 40% to 50% of patients with laryngeal cancer (Chen AY, et al 2006). From the second half of the 20th century total laryngectomy combined with a neck dissection was considered a treatment of choice for advanced laryngeal cancer (Genden EM et al, 2007). In most institutions, postoperative radiotherapy as adjuvant treatment following ablative surgery with radiation doses up to 60-66 Gy has also become the standard approach for patients with stage III-IV laryngeal cancer (Corvo R , 2007). However, the treatment of advanced laryngeal cancer seams to be a permanent challenge, but the management of patients with advanced laryngeal cancer has become more complex as other modalities including induction chemotherapy followed by radiotherapy or concurrent chemo-radiotherapy have evolved with the goal of preserving the larynx and reserved total laryngectomy as a salvage procedure for cases with less than 50% response to induction chemotherapy or in those who have persistent disease following concurrent chemo

  9. Imaging of Spinal Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Lubdha M. Shah

    2011-01-01

    Full Text Available Metastases to the spine can involve the bone, epidural space, leptomeninges, and spinal cord. The spine is the third most common site for metastatic disease, following the lung and the liver. Approximately 60–70% of patients with systemic cancer will have spinal metastasis. Materials/Methods. This is a review of the imaging techniques and typical imaging appearances of spinal metastatic disease. Conclusions. Awareness of the different manifestations of spinal metastatic disease is essential as the spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT best delineates osseous integrity, while MRI is better at assessing soft tissue involvement. Physiologic properties, particularly in treated disease, can be evaluated with other imaging modalities such as FDG PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease.

  10. Prognostic nomograms for predicting survival and distant metastases in locally advanced rectal cancers.

    Directory of Open Access Journals (Sweden)

    Junjie Peng

    Full Text Available To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.A total of 883 patients with stage II-III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS, local recurrence (LR and distant metastases (DM. Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients.The 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73] and 0.68 (95% CI = [0.64, 0.72] on the original dataset, and 0.76 (95% CI = [0.67, 0.86] and 0.73 (95% CI = [0.63, 0.83] on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category.The prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.

  11. Recent advances in technologies for the detection of occult metastatic cells in bone marrow of breast cancer patients

    International Nuclear Information System (INIS)

    Braun, Stephan; Harbeck, Nadia

    2001-01-01

    Approximately half of breast cancer patients with stage I–III disease will suffer metastatic disease despite resection with tumour-free margins. In 30–40% of these patients, individual carcinoma cells can already be detected at the time of primary therapy in cytological bone marrow preparations using immunocytochemistry. Numerous prospective clinical studies have shown that the presence of occult metastatic cells in bone marrow is prognostically relevant to patient survival. Only a few studies failed to do so, thus stimulating a critical discussion on the methodology and clinical value of bone marrow analysis. The potential for obtaining improved prognostic information on patient outcome, for monitoring tumour cell eradication during adjuvant and palliative systemic therapy, and for specifically targeting tumour biological therapies are intriguing clinical opportunities that may be afforded by bone marrow analysis. Standardized and robust methodology is a prerequisite for clinical application of these techniques, however

  12. Results of preoperative concurrent chemoradiotherapy for locally advanced rectal cancer

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    Choi, Sang Gyu; Kim, Su Ssan; Bae, Hoon Sik [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2007-03-15

    We performed a retrospective non-randomized clinical study of locally advanced rectal cancer, to evaluate the anal sphincter preservation rates, down staging rates and survival rates of preoperative chemoradiotherapy. From January 2002 to December 2005, patients with pathologically confirmed rectal cancer with clinical stage T2 or higher, or patients with lymph node metastasis were enrolled in this study. A preoperative staging work-up was conducted in 36 patients. All patients were treated with preoperative chemoradiotherapy, and curative resection was performed for 26 patients at Hallym University Sacred Heart Hospital. Radiotherapy treatment planning was conducted with the use of planning CT for all patients. A total dose of 45.0 {approx} 52.2 Gy conventionally fractionated three-dimensional radiotherapy was delivered to the whole pelvis. Chemotherapy was given at the first and fifth week of radiation therapy with continuous infusion i.v. 5-FU (Fluorouracil) and LV (Leucovorine). Surgical resection was performed 2 to 4 weeks after the completion of the chemoradiotherapy regimen. The complete resection rate with negative resection margin was 100% (26/26). However, a pathologically complete response was not seen after curative resection. Surgery was done by LAR (low anterior resection) in 23 patients and APR (abdomino-perineal resection) in 3 patients. The sphincter preservation rate was 88.5% (23/26), down staging of the tumor occurred in 12 patients (46.2%) and down-sizing of the tumor occurred in 19 patients (73%). Local recurrence after surgical resection developed in 1 patient, and distant metastasis developed in 3 patients. The local recurrence free survival rate, distant metastasis free survival rate, and progression free survival rate were 96.7%, 87% and 83.1%, respectively. Treatment related toxicity was minimal except for one grade 3, one grade 4 anemia, one grade 3 leukopenia, and one grade 3 ileus. Preoperative concurrent chemoradiotherapy for locally

  13. Improved local control with neoadjuvant chemotherapy for locally advanced rectal carcinoma: Long-term analysis

    International Nuclear Information System (INIS)

    Nakfoor, Bruce M.; Willett, Christopher G.; Kaufman, S. Donald; Shellito, Paul C.; Daly, William J.

    1996-01-01

    Objective: Since 1979, our institution has treated locally advanced rectal cancer with preoperative irradiation followed by resection with or without intraoperative radiation therapy (IORT). In 1986, our preoperative treatment policy was changed to include bolus 5-FU chemotherapy concurrent with irradiation in hopes of improving resectability, downstaging and/or local control rates. We report the long-term results with the addition of 5-FU chemotherapy to preoperative irradiation. Materials and Methods: From 1979 - 1994, 200 patients with locally advanced rectal carcinoma (primary or recurrent) received preoperative irradiation, resection and IORT if indicated. Bolus 5-FU (500mg/m 2 /day) chemotherapy was administered for three days during weeks one and five of irradiation. The change in treatment policy was limited to the addition of 5-FU chemotherapy: the radiation techniques (four-field), doses (50.4 Gy), and indications for intraoperative radiation (microscopic residual, gross residual, tumor adherence) remained constant. The median follow-up for the entire group of patients was 33 months (.95 months - 199 months), and the minimum follow-up was 1.5 years. Tabular results are 5-year actuarial calculations. Results: One hundred and five patients received preoperative 5-FU chemotherapy and irradiation whereas 95 patients underwent preoperative irradiation alone. Sixty-five percent of the patients were able to undergo complete resections, and 53% had transmural disease upon pathologic examination. The addition of chemotherapy did not affect the rates of resectability or tumor downstaging. However, the 10-year local control rate was significantly improved for those patients who received preoperative chemotherapy: 77% vs. 44% (p<0.01) (see figure). When stratified by extent of resection and stage, those patients who underwent complete resections or had transmural disease had significantly improved local control rates when compared to the non-chemotherapy group: No

  14. Fast neutron irradiation for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Smith, F.P.; Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-01-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials

  15. Fast neutron irradiation for locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F.P. (Georgetown Univ. Medical Center, Washington, DC); Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-11-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.

  16. Intra-arterial chemotherapy for locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Aota, Yasuhiro; Yoshida, Kazuhiko

    1999-01-01

    A total of 83 patients with locally advanced bladder cancer (T1, n=5; T2, n=28; T3a, n=21; T3b, n=21; T4, n=8) were treated with intra-arterial (i.a.) cisplatin and adriamycin (or epirubicin) chemotherapy. In 51 of the 83 cases, we combined this treatment with radiotherapy. The pathological complete response (CR) rate was 68% for all patients, 84% for i.a. chemotherapy combined with radiotherapy and only 41% for i.a. chemotherapy. The 5-year survival rate was 57% for all patients, 71% for i.a. chemotherapy combined with radiotherapy and only 44% for i.a. chemotherapy. The 5-year survival as a function of the clinical stage was 82% for T1+T2, 66% for T3a, 28% for T3b, 25% for T4 (T1+T2 vs. T3b: p<0.001, T1+T2 vs. T4: p<0.0001, T3a vs. T3b: p<0.0263, T3a vs. T4: p<0.0214, T3b vs. T4: p<0.029). In 46% of all patients, we succeeded in preserving the bladder; especially noteworthy, is that in 65% of the patients undergoing i.a. chemotherapy combined with radiotherapy, we succeeded in preserving the bladder. These results demonstrate that i.a. chemotherapy combined with radiotherapy is a useful method for locally advanced bladder cancer which may make preservation of the bladder function feasible. (author)

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

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

    1998-03-01

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

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  19. Epidemiology and therapies for metastatic sarcoma

    Directory of Open Access Journals (Sweden)

    Amankwah EK

    2013-05-01

    Full Text Available Ernest K Amankwah,1 Anthony P Conley,2 Damon R Reed2 1Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Sarcoma Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma, adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. Keywords: chemotherapy, pediatric sarcoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, synovial sarcoma

  20. The role of radiotherapy for locally advanced gallbladder carcinoma

    International Nuclear Information System (INIS)

    Shin, Hyun Soo; Seong, Jin Sil

    2000-01-01

    A retrospective review of 72 patients with locally advanced gallbladder carcinoma, between January 1900 and December 1996, was performed. Survival results and prognostic factors are analyzed for the patients treated with a various modalities. The patients were classified by treatment modality: group 1 included to 27 patients treated with palliative surgery alone, and group 2 for 11 patient treated with palliative surgery and radiotherapy; group 3 for 18 patients not treated by any treatment modality, and group 4 for 16 patients treated with radiotherapy alone. Age distribution ranged from 35 to 80 years with a mean of 63 years. The stage was classified by TNM and Nevin's staging system; all patients had an advanced stage more than III. Palliative surgery was done in 3B patients and adjuvant radiation therapy (Rl1 was followed in 11. For 34 patients, in whom no resection was tried, definitive RT was done in 16. Radiation delivered to tumor site and draining nodes up to 45-612 Gy using 10 MY linear accelerator. Chemotherapy was given to 25 patients with 5-FU based regimens. Median survival time was 10.3 months and 3-year survival rates (3-YSR) were 13.0% in all patients. Survival rates according to the treatment modalities were as followed; in palliative surgery alone, 3-YSR was 2.5%; in palliative surgery and adjuvant RT, 3-YSR was 45.5%; in no treatment group, 3YSR were 8.3%; and definitive RT was 13.1%. It was better survival in additional RT after palliative surgery group than palliative surgery alone (p=0.0009). It was better survival in definitive RT group than no treatment group (p=0.022). Significant prognostic factors by multivariate analysis were treatment modalities, the type of tumor and TNM stage. Significant prognostic factors by multivariate analysis were treatment modalities, the type of tumor and the presence of jaundice. It is suggested that RT could be potentially effective as adjuvant treatment modalities after palliative surgery or primary

  1. Neoadjuvant chemotherapy and radiotherapy in locally advanced hypopharyngeal cancer

    International Nuclear Information System (INIS)

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

    2000-01-01

    To see the relationship between the response to chemotherapy and the final outcome of neoadjuvant chemotherapy and radiotherapy in patients with locally advanced hypopharyngeal cancer. A retrospective analysis was done for thirty-two patients with locally advanced hypopharyngeal cancer treated in the Seoul National University Hospital with neoadjuvant chemotherapy and radiotherapy from August 1979 to July 1997. The patients were treated with Co-60 teletherapy unit or 4MV or 6MV photon beam produced by linear accelerator. Daily fractionation was 1.75 to 2 Gy, delivered five times a week. Total dose ranged from 60.8 Gy to 73.8 Gy. Twenty-nine patients received continuous infusion of cisplatin and 5-FU. Other patients were treated with cisplatin combined with bleomycin or vinblastin. Twenty-four (75%) patients received all three prescribed cycles of chemotherapy delivered three weeks apart. Six patients received two cycles, and two patients received only one cycle. The overall 2-year and 5-year survival rates are 65.6% and 43.0, respectively. 5-year local control rate is 34%. Organ preservation for more than five years is achieved in 12 patients (38%). After neoadjuvant chemotherapy, 24 patients achieved more than partial remission (PR); the response rate was 75% (24/32). Five patients had complete remission (CR), 19 patients PR, and 8 patients no response (NR). Among the 19 patients who had PR to chemotherapy, 8 patients achieved CR after radiotherapy. Among the 8 non-responders to chemotherapy, 2 patients achieved CR, and 6 patients achieved PR after radiotherapy, There was no non-responder after radiotherapy. The overall survival rates were 60% for CR to chemotherapy group, 35.1 % for PR to chemotherapy group, and 50% for NR to chemotherapy group. respectively (p=0.93). There were significant difference in five-year overall survival rates between the patients with CR and PR after neoadjuvant chemotherapy and radiotherapy (73.3% vs. 14.7%, p< 0.01). The prognostic

  2. A block matching-based registration algorithm for localization of locally advanced lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, 23298 (United States)

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  3. A block matching-based registration algorithm for localization of locally advanced lung tumors

    International Nuclear Information System (INIS)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm 3 ), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0.001). Left

  4. PET/CT comparing 68Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

    International Nuclear Information System (INIS)

    Janssen, Ingo; Chen, Clara C.; Millo, Corina M.; Herscovitch, Peter; Ling, Alexander; Taieb, David; Lin, Frank I.; Adams, Karen T.; Wolf, Katherine I.; Pacak, Karel; Fojo, Antonio T.; Buchmann, Inga; Kebebew, Electron

    2016-01-01

    Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). 68 Ga-DOTA(0)-Tyr(3)-octreotate ( 68 Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of 68 Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. This prospective study included 22 patients (15 men, 7 women; aged 50.0 ± 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent 68 Ga-DOTATATE, 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) PET/CT scan and only 11 patients underwent an additional 18 F-fluorodopamine ( 18 F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. 68 Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). 18 F-FDG PET/CT, 18 F-FDOPA PET/CT, 18 F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %; p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively. The results of this study demonstrate the superiority of 68 Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. (orig.)

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  6. Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer.

    Science.gov (United States)

    Zhao, Shanshan; Geybels, Milan S; Leonardson, Amy; Rubicz, Rohina; Kolb, Suzanne; Yan, Qingxiang; Klotzle, Brandy; Bibikova, Marina; Hurtado-Coll, Antonio; Troyer, Dean; Lance, Raymond; Lin, Daniel W; Wright, Jonathan L; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2017-01-01

    Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential. Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum. Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. Prospects for Observing and Localizing Gravitational-Wave Transients with Advanced LIGO and Advanced Virgo

    Science.gov (United States)

    Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Ain, A.; Ajith, P.; Allen, B.; Allocca, A.; Altin, P. A.; Amariutei, D. V.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Ashton, G.; Ast, M.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Babak, S.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Baune, C.; Bavigadda, V.; Bazzan, M.; Behnke, B.; Bejger, M.; Belczynski, C.; Bell, A. S.; Bell, C. J.; Berger, B. K.; Bergman, J.; Bergmann, G.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Birney, R.; Biscans, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blair, C. D.; Blair, D.; Blair, R. M.; Bloemen, S.; Bock, O.; Bodiya, T. P.; Boer, M.; Bogaert, G.; Bogan, C.; Bohe, A.; Bojtos, P.; Bond, C.; Bondu, F.; Bonnand, R.; Bork, R.; Boschi, V.; Bose, S.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Calderón Bustillo, J.; Callister, T.; Calloni, E.; Camp, J. B.; Cannon, K. C.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Casanueva Diaz, J.; Casentini, C.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C.; Cerboni Baiardi, L.; Cerretani, G.; Cesarini, E.; Chakraborty, R.; Chalermsongsak, T.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Chen, H. Y.; Chen, Y.; Cheng, C.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, S.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Cleva, F.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Collette, C. G.; Constancio, M.; Conte, A.; Conti, L.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J.-P.; Countryman, S. T.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Craig, K.; Creighton, J. D. E.; Cripe, J.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dal Canton, T.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Darman, N. S.; Dattilo, V.; Dave, I.; Daveloza, H. P.; Davier, M.; Davies, G. S.; Daw, E. J.; Day, R.; DeBra, D.; Debreczeni, G.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Pozzo, W.; Denker, T.; Dent, T.; Dereli, H.; Dergachev, V.; DeRosa, R.; De Rosa, R.; DeSalvo, R.; Dhurandhar, S.; Díaz, M. C.; Di Fiore, L.; Di Giovanni, M.; Di Lieto, A.; Di Palma, I.; Di Virgilio, A.; Dojcinoski, G.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Douglas, R.; Downes, T. P.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dwyer, S. E.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J. M.; Eikenberry, S. S.; Engels, W.; Essick, R. C.; Etzel, T.; Evans, M.; Evans, T. M.; Everett, R.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Fang, Q.; Farinon, S.; Farr, B.; Farr, W. M.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Fiori, I.; Fisher, R. P.; Flaminio, R.; Fletcher, M.; Fournier, J.-D.; Franco, S.; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gabbard, H. A. G.; Gair, J. R.; Gammaitoni, L.; Gaonkar, S. G.; Garufi, F.; Gatto, A.; Gaur, G.; Gehrels, N.; Gemme, G.; Gendre, B.; Genin, E.; Gennai, A.; George, J.; Gergely, L.; Germain, V.; Ghosh, A.; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glaefke, A.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gonzalez Castro, J. M.; Gopakumar, A.; Gordon, N. A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Groot, P.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hacker, J. J.; Hall, B. R.; Hall, E. D.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Hartman, M. T.; Haster, C.-J.; Haughian, K.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Hofman, D.; Hollitt, S. E.; Holt, K.; Holz, D. E.; Hopkins, P.; Hosken, D. J.; Hough, J.; Houston, E. A.; Howell, E. J.; Hu, Y. M.; Huang, S.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Idrisy, A.; Indik, N.; Ingram, D. R.; Inta, R.; Isa, H. N.; Isac, J.-M.; Isi, M.; Islas, G.; Isogai, T.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jang, H.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; K, Haris; Kalaghatgi, C. V.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Karki, S.; Kasprzack, M.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawazoe, F.; Kéfélian, F.; Kehl, M. S.; Keitel, D.; Kelley, D. B.; Kells, W.; Kennedy, R.; Key, J. S.; Khalaidovski, A.; Khalili, F. Y.; Khan, S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, C.; Kim, J.; Kim, K.; Kim, N.; Kim, N.; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Koehlenbeck, S. M.; Kokeyama, K.; Koley, S.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kowalska, I.; Kozak, D. B.; Kringel, V.; Krishnan, B.; Królak, A.; Krueger, C.; Kuehn, G.; Kumar, P.; Kuo, L.; Kutynia, A.; Lackey, B. D.; Landry, M.; Lange, J.; Lantz, B.; Lasky, P. D.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lebigot, E.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Lee, K.; Lenon, A.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levin, Y.; Levine, B. M.; Li, T. G. F.; Libson, A.; Littenberg, T. B.; Lockerbie, N. A.; Logue, J.; Lombardi, A. L.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lück, H.; Lundgren, A. P.; Luo, J.; Lynch, R.; Ma, Y.; MacDonald, T.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magana-Sandoval, F.; Magee, R. M.; Mageswaran, M.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Mandel, I.; Mandic, V.; Mangano, V.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marion, F.; Márka, S.; Márka, Z.; Markosyan, A. S.; Maros, E.; Martelli, F.; Martellini, L.; Martin, I. W.; Martin, R. M.; Martynov, D. V.; Marx, J. N.; Mason, K.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Meidam, J.; Melatos, A.; Mendell, G.; Mendoza-Gandara, D.; Mercer, R. A.; Merilh, E.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Mezzani, F.; Miao, H.; Michel, C.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, J.; Millhouse, M.; Minenkov, Y.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moggi, A.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, B. C.; Moore, C. J.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mossavi, K.; Mours, B.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D. J.; Murray, P. G.; Mytidis, A.; Nardecchia, I.; Naticchioni, L.; Nayak, R. K.; Necula, V.; Nedkova, K.; Nelemans, G.; Neri, M.; Neunzert, A.; Newton, G.; Nguyen, T. T.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Nocera, F.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Oberling, J.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oliver, M.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; O'Shaughnessy, R.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Paris, H. R.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patrick, Z.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Penn, S.; Pereira, R.; Perreca, A.; Phelps, M.; Piccinni, O.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Poggiani, R.; Post, A.; Powell, J.; Prasad, J.; Predoi, V.; Premachandra, S. S.; Prestegard, T.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prodi, G. A.; Prokhorov, L.; Punturo, M.; Puppo, P.; Pürrer, M.; Qi, H.; Qin, J.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rakhmanov, M.; Rapagnani, P.; Raymond, V.; Razzano, M.; Re, V.; Read, J.; Reed, C. M.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Rew, H.; Ricci, F.; Riles, K.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, J. D.; Romano, R.; Romanov, G.; Romie, J. H.; Rosińska, D.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sanchez, E. J.; Sandberg, V.; Sandeen, B.; Sanders, J. R.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Schilling, R.; Schmidt, J.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schönbeck, A.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Scott, J.; Scott, S. M.; Sellers, D.; Sentenac, D.; Sequino, V.; Sergeev, A.; Serna, G.; Setyawati, Y.; Sevigny, A.; Shaddock, D. A.; Shah, S.; Shahriar, M. S.; Shaltev, M.; Shao, Z.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sigg, D.; Silva, A. D.; Simakov, D.; Singer, A.; Singer, L. P.; Singh, A.; Singh, R.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, J. R.; Smith, N. D.; Smith, R. J. E.; Son, E. J.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Srivastava, A. K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Stone, R.; Strain, K. A.; Straniero, N.; Stratta, G.; Strauss, N. A.; Strigin, S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sun, L.; Sutton, P. J.; Swinkels, B. L.; Szczepanczyk, M. J.; Tacca, M.; Talukder, D.; Tanner, D. B.; Tápai, M.; Tarabrin, S. P.; Taracchini, A.; Taylor, R.; Theeg, T.; Thirugnanasambandam, M. P.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Tomlinson, C.; Tonelli, M.; Torres, C. V.; Torrie, C. I.; Töyrä, D.; Travasso, F.; Traylor, G.; Trifirò, D.; Tringali, M. C.; Trozzo, L.; Tse, M.; Turconi, M.; Tuyenbayev, D.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; van den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van der Sluys, M. V.; van Heijningen, J. V.; van Veggel, A. A.; Vardaro, M.; Vass, S.; Vasúth, M.; Vaulin, R.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Verkindt, D.; Vetrano, F.; Viceré, A.; Vinciguerra, S.; Vine, D. J.; Vinet, J.-Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, M.; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, M.; Wang, X.; Wang, Y.; Ward, R. L.; Warner, J.; Was, M.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Weßels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; White, D. J.; Whiting, B. F.; Williams, R. D.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Wright, J. L.; Wu, G.; Yablon, J.; Yam, W.; Yamamoto, H.; Yancey, C. C.; Yap, M. J.; Yu, H.; Yvert, M.; Zadrożny, A.; Zangrando, L.; Zanolin, M.; Zendri, J.-P.; Zevin, M.; Zhang, F.; Zhang, L.; Zhang, M.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, X. J.; Zucker, M. E.; Zuraw, S. E.; Zweizig, J.; LIGO Scientific Collaboration; Virgo Collaboration

    2016-02-01

    We present a possible observing scenario for the Advanced LIGO and Advanced Virgo gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We determine the expected sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron-star systems, which are considered the most promising for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5 deg2 to 20 deg2 will require at least three detectors of sensitivity within a factor of ˜ 2 of each other and with a broad frequency bandwidth. Should the third LIGO detector be relocated to India as expected, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

  8. Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA.

    Science.gov (United States)

    Abbott, B P; Abbott, R; Abbott, T D; Abernathy, M R; Acernese, F; Ackley, K; Adams, C; Adams, T; Addesso, P; Adhikari, R X; Adya, V B; Affeldt, C; Agathos, M; Agatsuma, K; Aggarwal, N; Aguiar, O D; Aiello, L; Ain, A; Ajith, P; Akutsu, T; Allen, B; Allocca, A; Altin, P A; Ananyeva, A; Anderson, S B; Anderson, W G; Ando, M; Appert, S; Arai, K; Araya, A; Araya, M C; Areeda, J S; Arnaud, N; Arun, K G; Asada, H; Ascenzi, S; Ashton, G; Aso, Y; Ast, M; Aston, S M; Astone, P; Atsuta, S; Aufmuth, P; Aulbert, C; Avila-Alvarez, A; Awai, K; Babak, S; Bacon, P; Bader, M K M; Baiotti, L; Baker, P T; Baldaccini, F; Ballardin, G; Ballmer, S W; Barayoga, J C; Barclay, S E; Barish, B C; Barker, D; Barone, F; Barr, B; Barsotti, L; Barsuglia, M; Barta, D; Bartlett, J; Barton, M A; Bartos, I; Bassiri, R; Basti, A; Batch, J C; Baune, C; Bavigadda, V; Bazzan, M; Bécsy, B; Beer, C; Bejger, M; Belahcene, I; Belgin, M; Bell, A S; Berger, B K; Bergmann, G; Berry, C P L; Bersanetti, D; Bertolini, A; Betzwieser, J; Bhagwat, S; Bhandare, R; Bilenko, I A; Billingsley, G; Billman, C R; Birch, J; Birney, R; Birnholtz, O; Biscans, S; Bisht, A; Bitossi, M; Biwer, C; Bizouard, M A; Blackburn, J K; Blackman, J; Blair, C D; Blair, D G; Blair, R M; Bloemen, S; Bock, O; Boer, M; Bogaert, G; Bohe, A; Bondu, F; Bonnand, R; Boom, B A; Bork, R; Boschi, V; Bose, S; Bouffanais, Y; Bozzi, A; Bradaschia, C; Brady, P R; Braginsky, V B; Branchesi, M; Brau, J E; Briant, T; Brillet, A; Brinkmann, M; Brisson, V; Brockill, P; Broida, J E; Brooks, A F; Brown, D A; Brown, D D; Brown, N M; Brunett, S; Buchanan, C C; Buikema, A; Bulik, T; Bulten, H J; Buonanno, A; Buskulic, D; Buy, C; Byer, R L; Cabero, M; Cadonati, L; Cagnoli, G; Cahillane, C; Calderón Bustillo, J; Callister, T A; Calloni, E; Camp, J B; Cannon, K C; Cao, H; Cao, J; Capano, C D; Capocasa, E; Carbognani, F; Caride, S; Casanueva Diaz, J; Casentini, C; Caudill, S; Cavaglià, M; Cavalier, F; Cavalieri, R; Cella, G; Cepeda, C B; Cerboni Baiardi, L; Cerretani, G; Cesarini, E; Chamberlin, S J; Chan, M; Chao, S; Charlton, P; Chassande-Mottin, E; Cheeseboro, B D; Chen, H Y; Chen, Y; Cheng, H-P; Chincarini, A; Chiummo, A; Chmiel, T; Cho, H S; Cho, M; Chow, J H; Christensen, N; Chu, Q; Chua, A J K; Chua, S; Chung, S; Ciani, G; Clara, F; Clark, J A; Cleva, F; Cocchieri, C; Coccia, E; Cohadon, P-F; Colla, A; Collette, C G; Cominsky, L; Constancio, M; Conti, L; Cooper, S J; Corbitt, T R; Cornish, N; Corsi, A; Cortese, S; Costa, C A; Coughlin, M W; Coughlin, S B; Coulon, J-P; Countryman, S T; Couvares, P; Covas, P B; Cowan, E E; Coward, D M; Cowart, M J; Coyne, D C; Coyne, R; Creighton, J D E; Creighton, T D; Cripe, J; Crowder, S G; Cullen, T J; Cumming, A; Cunningham, L; Cuoco, E; Canton, T Dal; Danilishin, S L; D'Antonio, S; Danzmann, K; Dasgupta, A; Da Silva Costa, C F; Dattilo, V; Dave, I; Davier, M; Davies, G S; Davis, D; Daw, E J; Day, B; Day, R; De, S; DeBra, D; Debreczeni, G; Degallaix, J; De Laurentis, M; Deléglise, S; Del Pozzo, W; Denker, T; Dent, T; Dergachev, V; De Rosa, R; DeRosa, R T; DeSalvo, R; Devine, R C; Dhurandhar, S; Díaz, M C; Fiore, L Di; Giovanni, M Di; Girolamo, T Di; Lieto, A Di; Pace, S Di; Palma, I Di; Virgilio, A Di; Doctor, Z; Doi, K; Dolique, V; Donovan, F; Dooley, K L; Doravari, S; Dorrington, I; Douglas, R; Dovale Álvarez, M; Downes, T P; Drago, M; Drever, R W P; Driggers, J C; Du, Z; Ducrot, M; Dwyer, S E; Eda, K; Edo, T B; Edwards, M C; Effler, A; Eggenstein, H-B; Ehrens, P; Eichholz, J; Eikenberry, S S; Eisenstein, R A; Essick, R C; Etienne, Z; Etzel, T; Evans, M; Evans, T M; Everett, R; Factourovich, M; Fafone, V; Fair, H; Fairhurst, S; Fan, X; Farinon, S; Farr, B; Farr, W M; Fauchon-Jones, E J; Favata, M; Fays, M; Fehrmann, H; Fejer, M M; Fernández Galiana, A; Ferrante, I; Ferreira, E C; Ferrini, F; Fidecaro, F; Fiori, I; Fiorucci, D; Fisher, R P; Flaminio, R; Fletcher, M; Fong, H; Forsyth, S S; Fournier, J-D; Frasca, S; Frasconi, F; Frei, Z; Freise, A; Frey, R; Frey, V; Fries, E M; Fritschel, P; Frolov, V V; Fujii, Y; Fujimoto, M-K; Fulda, P; Fyffe, M; Gabbard, H; Gadre, B U; Gaebel, S M; Gair, J R; Gammaitoni, L; Gaonkar, S G; Garufi, F; Gaur, G; Gayathri, V; Gehrels, N; Gemme, G; Genin, E; Gennai, A; George, J; Gergely, L; Germain, V; Ghonge, S; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, S; Giaime, J A; Giardina, K D; Giazotto, A; Gill, K; Glaefke, A; Goetz, E; Goetz, R; Gondan, L; González, G; Gonzalez Castro, J M; Gopakumar, A; Gorodetsky, M L; Gossan, S E; Gosselin, M; Gouaty, R; Grado, A; Graef, C; Granata, M; Grant, A; Gras, S; Gray, C; Greco, G; Green, A C; Groot, P; Grote, H; Grunewald, S; Guidi, G M; Guo, X; Gupta, A; Gupta, M K; Gushwa, K E; Gustafson, E K; Gustafson, R; Hacker, J J; Hagiwara, A; Hall, B R; Hall, E D; Hammond, G; Haney, M; Hanke, M M; Hanks, J; Hanna, C; Hannam, M D; Hanson, J; Hardwick, T; Harms, J; Harry, G M; Harry, I W; Hart, M J; Hartman, M T; Haster, C-J; Haughian, K; Hayama, K; Healy, J; Heidmann, A; Heintze, M C; Heitmann, H; Hello, P; Hemming, G; Hendry, M; Heng, I S; Hennig, J; Henry, J; Heptonstall, A W; Heurs, M; Hild, S; Hirose, E; Hoak, D; Hofman, D; Holt, K; Holz, D E; Hopkins, P; Hough, J; Houston, E A; Howell, E J; Hu, Y M; Huerta, E A; Huet, D; Hughey, B; Husa, S; Huttner, S H; Huynh-Dinh, T; Indik, N; Ingram, D R; Inta, R; Ioka, K; Isa, H N; Isac, J-M; Isi, M; Isogai, T; Itoh, Y; Iyer, B R; Izumi, K; Jacqmin, T; Jani, K; Jaranowski, P; Jawahar, S; Jiménez-Forteza, F; Johnson, W W; Jones, D I; Jones, R; Jonker, R J G; Ju, L; Junker, J; Kagawa, T; Kajita, T; Kakizaki, M; Kalaghatgi, C V; Kalogera, V; Kamiizumi, M; Kanda, N; Kandhasamy, S; Kanemura, S; Kaneyama, M; Kang, G; Kanner, J B; Karki, S; Karvinen, K S; Kasprzack, M; Kataoka, Y; Katsavounidis, E; Katzman, W; Kaufer, S; Kaur, T; Kawabe, K; Kawai, N; Kawamura, S; Kéfélian, F; Keitel, D; Kelley, D B; Kennedy, R; Key, J S; Khalili, F Y; Khan, I; Khan, S; Khan, Z; Khazanov, E A; Kijbunchoo, N; Kim, C; Kim, H; Kim, J C; Kim, J; Kim, W; Kim, Y-M; Kimbrell, S J; Kimura, N; King, E J; King, P J; Kirchhoff, R; Kissel, J S; Klein, B; Kleybolte, L; Klimenko, S; Koch, P; Koehlenbeck, S M; Kojima, Y; Kokeyama, K; Koley, S; Komori, K; Kondrashov, V; Kontos, A; Korobko, M; Korth, W Z; Kotake, K; Kowalska, I; Kozak, D B; Krämer, C; Kringel, V; Krishnan, B; Królak, A; Kuehn, G; Kumar, P; Kumar, Rahul; Kumar, Rakesh; Kuo, L; Kuroda, K; Kutynia, A; Kuwahara, Y; Lackey, B D; Landry, M; Lang, R N; Lange, J; Lantz, B; Lanza, R K; Lartaux-Vollard, A; Lasky, P D; Laxen, M; Lazzarini, A; Lazzaro, C; Leaci, P; Leavey, S; Lebigot, E O; Lee, C H; Lee, H K; Lee, H M; Lee, H W; Lee, K; Lehmann, J; Lenon, A; Leonardi, M; Leong, J R; Leroy, N; Letendre, N; Levin, Y; Li, T G F; Libson, A; Littenberg, T B; Liu, J; Lockerbie, N A; Lombardi, A L; London, L T; Lord, J E; Lorenzini, M; Loriette, V; Lormand, M; Losurdo, G; Lough, J D; Lousto, C O; Lovelace, G; Lück, H; Lundgren, A P; Lynch, R; Ma, Y; Macfoy, S; Machenschalk, B; MacInnis, M; Macleod, D M; Magaña-Sandoval, F; Majorana, E; Maksimovic, I; Malvezzi, V; Man, N; Mandic, V; Mangano, V; Mano, S; Mansell, G L; Manske, M; Mantovani, M; Marchesoni, F; Marchio, M; Marion, F; Márka, S; Márka, Z; Markosyan, A S; Maros, E; Martelli, F; Martellini, L; Martin, I W; Martynov, D V; Mason, K; Masserot, A; Massinger, T J; Masso-Reid, M; Mastrogiovanni, S; Matichard, F; Matone, L; Matsumoto, N; Matsushima, F; Mavalvala, N; Mazumder, N; McCarthy, R; McClelland, D E; McCormick, S; McGrath, C; McGuire, S C; McIntyre, G; McIver, J; McManus, D J; McRae, T; McWilliams, S T; Meacher, D; Meadors, G D; Meidam, J; Melatos, A; Mendell, G; Mendoza-Gandara, D; Mercer, R A; Merilh, E L; Merzougui, M; Meshkov, S; Messenger, C; Messick, C; Metzdorff, R; Meyers, P M; Mezzani, F; Miao, H; Michel, C; Michimura, Y; Middleton, H; Mikhailov, E E; Milano, L; Miller, A L; Miller, A; Miller, B B; Miller, J; Millhouse, M; Minenkov, Y; Ming, J; Mirshekari, S; Mishra, C; Mitrofanov, V P; Mitselmakher, G; Mittleman, R; Miyakawa, O; Miyamoto, A; Miyamoto, T; Miyoki, S; Moggi, A; Mohan, M; Mohapatra, S R P; Montani, M; Moore, B C; Moore, C J; Moraru, D; Moreno, G; Morii, W; Morisaki, S; Moriwaki, Y; Morriss, S R; Mours, B; Mow-Lowry, C M; Mueller, G; Muir, A W; Mukherjee, Arunava; Mukherjee, D; Mukherjee, S; Mukund, N; Mullavey, A; Munch, J; Muniz, E A M; Murray, P G; Mytidis, A; Nagano, S; Nakamura, K; Nakamura, T; Nakano, H; Nakano, Masaya; Nakano, Masayuki; Nakao, K; Napier, K; Nardecchia, I; Narikawa, T; Naticchioni, L; Nelemans, G; Nelson, T J N; Neri, M; Nery, M; Neunzert, A; Newport, J M; Newton, G; Nguyen, T T; Ni, W-T; Nielsen, A B; Nissanke, S; Nitz, A; Noack, A; Nocera, F; Nolting, D; Normandin, M E N; Nuttall, L K; Oberling, J; Ochsner, E; Oelker, E; Ogin, G H; Oh, J J; Oh, S H; Ohashi, M; Ohishi, N; Ohkawa, M; Ohme, F; Okutomi, K; Oliver, M; Ono, K; Ono, Y; Oohara, K; Oppermann, P; Oram, Richard J; O'Reilly, B; O'Shaughnessy, R; Ottaway, D J; Overmier, H; Owen, B J; Pace, A E; Page, J; Pai, A; Pai, S A; Palamos, J R; Palashov, O; Palomba, C; Pal-Singh, A; Pan, H; Pankow, C; Pannarale, F; Pant, B C; Paoletti, F; Paoli, A; Papa, M A; Paris, H R; Parker, W; Pascucci, D; Pasqualetti, A; Passaquieti, R; Passuello, D; Patricelli, B; Pearlstone, B L; Pedraza, M; Pedurand, R; Pekowsky, L; Pele, A; Peña Arellano, F E; Penn, S; Perez, C J; Perreca, A; Perri, L M; Pfeiffer, H P; Phelps, M; Piccinni, O J; Pichot, M; Piergiovanni, F; Pierro, V; Pillant, G; Pinard, L; Pinto, I M; Pitkin, M; Poe, M; Poggiani, R; Popolizio, P; Post, A; Powell, J; Prasad, J; Pratt, J W W; Predoi, V; Prestegard, T; Prijatelj, M; Principe, M; Privitera, S; Prodi, G A; Prokhorov, L G; Puncken, O; Punturo, M; Puppo, P; Pürrer, M; Qi, H; Qin, J; Qiu, S; Quetschke, V; Quintero, E A; Quitzow-James, R; Raab, F J; Rabeling, D S; Radkins, H; Raffai, P; Raja, S; Rajan, C; Rakhmanov, M; Rapagnani, P; Raymond, V; Razzano, M; Re, V; Read, J; Regimbau, T; Rei, L; Reid, S; Reitze, D H; Rew, H; Reyes, S D; Rhoades, E; Ricci, F; Riles, K; Rizzo, M; Robertson, N A; Robie, R; Robinet, F; Rocchi, A; Rolland, L; Rollins, J G; Roma, V J; Romano, R; Romie, J H; Rosińska, D; Rowan, S; Rüdiger, A; Ruggi, P; Ryan, K; Sachdev, S; Sadecki, T; Sadeghian, L; Sago, N; Saijo, M; Saito, Y; Sakai, K; Sakellariadou, M; Salconi, L; Saleem, M; Salemi, F; Samajdar, A; Sammut, L; Sampson, L M; Sanchez, E J; Sandberg, V; Sanders, J R; Sasaki, Y; Sassolas, B; Sathyaprakash, B S; Sato, S; Sato, T; Saulson, P R; Sauter, O; Savage, R L; Sawadsky, A; Schale, P; Scheuer, J; Schmidt, E; Schmidt, J; Schmidt, P; Schnabel, R; Schofield, R M S; Schönbeck, A; Schreiber, E; Schuette, D; Schutz, B F; Schwalbe, S G; Scott, J; Scott, S M; Sekiguchi, T; Sekiguchi, Y; Sellers, D; Sengupta, A S; Sentenac, D; Sequino, V; Sergeev, A; Setyawati, Y; Shaddock, D A; Shaffer, T J; Shahriar, M S; Shapiro, B; Shawhan, P; Sheperd, A; Shibata, M; Shikano, Y; Shimoda, T; Shoda, A; Shoemaker, D H; Shoemaker, D M; Siellez, K; Siemens, X; Sieniawska, M; Sigg, D; Silva, A D; Singer, A; Singer, L P; Singh, A; Singh, R; Singhal, A; Sintes, A M; Slagmolen, B J J; Smith, B; Smith, J R; Smith, R J E; Somiya, K; Son, E J; Sorazu, B; Sorrentino, F; Souradeep, T; Spencer, A P; Srivastava, A K; Staley, A; Steinke, M; Steinlechner, J; Steinlechner, S; Steinmeyer, D; Stephens, B C; Stevenson, S P; Stone, R; Strain, K A; Straniero, N; Stratta, G; Strigin, S E; Sturani, R; Stuver, A L; Sugimoto, Y; Summerscales, T Z; Sun, L; Sunil, S; Sutton, P J; Suzuki, T; Swinkels, B L; Szczepańczyk, M J; Tacca, M; Tagoshi, H; Takada, S; Takahashi, H; Takahashi, R; Takamori, A; Talukder, D; Tanaka, H; Tanaka, K; Tanaka, T; Tanner, D B; Tápai, M; Taracchini, A; Tatsumi, D; Taylor, R; Telada, S; Theeg, T; Thomas, E G; Thomas, M; Thomas, P; Thorne, K A; Thrane, E; Tippens, T; Tiwari, S; Tiwari, V; Tokmakov, K V; Toland, K; Tomaru, T; Tomlinson, C; Tonelli, M; Tornasi, Z; Torrie, C I; Töyrä, D; Travasso, F; Traylor, G; Trifirò, D; Trinastic, J; Tringali, M C; Trozzo, L; Tse, M; Tso, R; Tsubono, K; Tsuzuki, T; Turconi, M; Tuyenbayev, D; Uchiyama, T; Uehara, T; Ueki, S; Ueno, K; Ugolini, D; Unnikrishnan, C S; Urban, A L; Ushiba, T; Usman, S A; Vahlbruch, H; Vajente, G; Valdes, G; van Bakel, N; van Beuzekom, M; van den Brand, J F J; Van Den Broeck, C; Vander-Hyde, D C; van der Schaaf, L; van Heijningen, J V; van Putten, M H P M; van Veggel, A A; Vardaro, M; Varma, V; Vass, S; Vasúth, M; Vecchio, A; Vedovato, G; Veitch, J; Veitch, P J; Venkateswara, K; Venugopalan, G; Verkindt, D; Vetrano, F; Viceré, A; Viets, A D; Vinciguerra, S; Vine, D J; Vinet, J-Y; Vitale, S; Vo, T; Vocca, H; Vorvick, C; Voss, D V; Vousden, W D; Vyatchanin, S P; Wade, A R; Wade, L E; Wade, M; Wakamatsu, T; Walker, M; Wallace, L; Walsh, S; Wang, G; Wang, H; Wang, M; Wang, Y; Ward, R L; Warner, J; Was, M; Watchi, J; Weaver, B; Wei, L-W; Weinert, M; Weinstein, A J; Weiss, R; Wen, L; Weßels, P; Westphal, T; Wette, K; Whelan, J T; Whiting, B F; Whittle, C; Williams, D; Williams, R D; Williamson, A R; Willis, J L; Willke, B; Wimmer, M H; Winkler, W; Wipf, C C; Wittel, H; Woan, G; Woehler, J; Worden, J; Wright, J L; Wu, D S; Wu, G; Yam, W; Yamamoto, H; Yamamoto, K; Yamamoto, T; Yancey, C C; Yano, K; Yap, M J; Yokoyama, J; Yokozawa, T; Yoon, T H; Yu, Hang; Yu, Haocun; Yuzurihara, H; Yvert, M; Zadrożny, A; Zangrando, L; Zanolin, M; Zeidler, S; Zendri, J-P; Zevin, M; Zhang, L; Zhang, M; Zhang, T; Zhang, Y; Zhao, C; Zhou, M; Zhou, Z; Zhu, S J; Zhu, X J; Zucker, M E; Zweizig, J

    2018-01-01

    We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and [Formula: see text] credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5-[Formula: see text] requires at least three detectors of sensitivity within a factor of [Formula: see text] of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

  9. Prospects for Observing and Localizing Gravitational-Wave Transients with Advanced LIGO and Advanced Virgo

    Science.gov (United States)

    Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; hide

    2016-01-01

    We present a possible observing scenario for the Advanced LIGO and Advanced Virgo gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We determine the expected sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron-star systems, which are considered the most promising for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5 sq. deg to 20 sq. deg will require at least three detectors of sensitivity within a factor of approximately 2 of each other and with a broad frequency bandwidth. Should the third LIGO detector be relocated to India as expected, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

  10. Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA

    Science.gov (United States)

    Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Akutsu, T.; Allen, B.; Allocca, A.; Altin, P. A.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Ando, M.; Appert, S.; Arai, K.; Araya, A.; Araya, M. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Asada, H.; Ascenzi, S.; Ashton, G.; Aso, Y.; Ast, M.; Aston, S. M.; Astone, P.; Atsuta, S.; Aufmuth, P.; Aulbert, C.; Avila-Alvarez, A.; Awai, K.; Babak, S.; Bacon, P.; Bader, M. K. M.; Baiotti, L.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Baune, C.; Bavigadda, V.; Bazzan, M.; Bécsy, B.; Beer, C.; Bejger, M.; Belahcene, I.; Belgin, M.; Bell, A. S.; Berger, B. K.; Bergmann, G.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Billman, C. R.; Birch, J.; Birney, R.; Birnholtz, O.; Biscans, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blackman, J.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bloemen, S.; Bock, O.; Boer, M.; Bogaert, G.; Bohe, A.; Bondu, F.; Bonnand, R.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, S.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Broida, J. E.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Brunett, S.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cabero, M.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Calderón Bustillo, J.; Callister, T. A.; Calloni, E.; Camp, J. B.; Cannon, K. C.; Cao, H.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Casanueva Diaz, J.; Casentini, C.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C. B.; Cerboni Baiardi, L.; Cerretani, G.; Cesarini, E.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Cheeseboro, B. D.; Chen, H. Y.; Chen, Y.; Cheng, H.-P.; Chincarini, A.; Chiummo, A.; Chmiel, T.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, A. J. K.; Chua, S.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Cleva, F.; Cocchieri, C.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Collette, C. G.; Cominsky, L.; Constancio, M.; Conti, L.; Cooper, S. J.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J.-P.; Countryman, S. T.; Couvares, P.; Covas, P. B.; Cowan, E. E.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cullen, T. J.; Cumming, A.; Cunningham, L.; Cuoco, E.; Canton, T. Dal; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dasgupta, A.; Da Silva Costa, C. F.; Dattilo, V.; Dave, I.; Davier, M.; Davies, G. S.; Davis, D.; Daw, E. J.; Day, B.; Day, R.; De, S.; DeBra, D.; Debreczeni, G.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Pozzo, W.; Denker, T.; Dent, T.; Dergachev, V.; De Rosa, R.; DeRosa, R. T.; DeSalvo, R.; Devine, R. C.; Dhurandhar, S.; Díaz, M. C.; Fiore, L. Di; Giovanni, M. Di; Girolamo, T. Di; Lieto, A. Di; Pace, S. Di; Palma, I. Di; Virgilio, A. Di; Doctor, Z.; Doi, K.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Douglas, R.; Dovale Álvarez, M.; Downes, T. P.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dwyer, S. E.; Eda, K.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Eisenstein, R. A.; Essick, R. C.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Everett, R.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Farinon, S.; Farr, B.; Farr, W. M.; Fauchon-Jones, E. J.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Fernández Galiana, A.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Fiori, I.; Fiorucci, D.; Fisher, R. P.; Flaminio, R.; Fletcher, M.; Fong, H.; Forsyth, S. S.; Fournier, J.-D.; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Frey, V.; Fries, E. M.; Fritschel, P.; Frolov, V. V.; Fujii, Y.; Fujimoto, M.-K.; Fulda, P.; Fyffe, M.; Gabbard, H.; Gadre, B. U.; Gaebel, S. M.; Gair, J. R.; Gammaitoni, L.; Gaonkar, S. G.; Garufi, F.; Gaur, G.; Gayathri, V.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; George, J.; Gergely, L.; Germain, V.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glaefke, A.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gonzalez Castro, J. M.; Gopakumar, A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Grado, A.; Graef, C.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Groot, P.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hacker, J. J.; Hagiwara, A.; Hall, B. R.; Hall, E. D.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Hartman, M. T.; Haster, C.-J.; Haughian, K.; Hayama, K.; Healy, J.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Henry, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hirose, E.; Hoak, D.; Hofman, D.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Houston, E. A.; Howell, E. J.; Hu, Y. M.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Indik, N.; Ingram, D. R.; Inta, R.; Ioka, K.; Isa, H. N.; Isac, J.-M.; Isi, M.; Isogai, T.; Itoh, Y.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Kagawa, T.; Kajita, T.; Kakizaki, M.; Kalaghatgi, C. V.; Kalogera, V.; Kamiizumi, M.; Kanda, N.; Kandhasamy, S.; Kanemura, S.; Kaneyama, M.; Kang, G.; Kanner, J. B.; Karki, S.; Karvinen, K. S.; Kasprzack, M.; Kataoka, Y.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawai, N.; Kawamura, S.; Kéfélian, F.; Keitel, D.; Kelley, D. B.; Kennedy, R.; Key, J. S.; Khalili, F. Y.; Khan, I.; Khan, S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, C.; Kim, H.; Kim, J. C.; Kim, J.; Kim, W.; Kim, Y.-M.; Kimbrell, S. J.; Kimura, N.; King, E. J.; King, P. J.; Kirchhoff, R.; Kissel, J. S.; Klein, B.; Kleybolte, L.; Klimenko, S.; Koch, P.; Koehlenbeck, S. M.; Kojima, Y.; Kokeyama, K.; Koley, S.; Komori, K.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kotake, K.; Kowalska, I.; Kozak, D. B.; Krämer, C.; Kringel, V.; Krishnan, B.; Królak, A.; Kuehn, G.; Kumar, P.; Kumar, Rahul; Kumar, Rakesh; Kuo, L.; Kuroda, K.; Kutynia, A.; Kuwahara, Y.; Lackey, B. D.; Landry, M.; Lang, R. N.; Lange, J.; Lantz, B.; Lanza, R. K.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Lee, H. W.; Lee, K.; Lehmann, J.; Lenon, A.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levin, Y.; Li, T. G. F.; Libson, A.; Littenberg, T. B.; Liu, J.; Lockerbie, N. A.; Lombardi, A. L.; London, L. T.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lück, H.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macfoy, S.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magaña-Sandoval, F.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Mandic, V.; Mangano, V.; Mano, S.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marchio, M.; Marion, F.; Márka, S.; Márka, Z.; Markosyan, A. S.; Maros, E.; Martelli, F.; Martellini, L.; Martin, I. W.; Martynov, D. V.; Mason, K.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matichard, F.; Matone, L.; Matsumoto, N.; Matsushima, F.; Mavalvala, N.; Mazumder, N.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGrath, C.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; McRae, T.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Meidam, J.; Melatos, A.; Mendell, G.; Mendoza-Gandara, D.; Mercer, R. A.; Merilh, E. L.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Metzdorff, R.; Meyers, P. M.; Mezzani, F.; Miao, H.; Michel, C.; Michimura, Y.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, A. L.; Miller, A.; Miller, B. B.; Miller, J.; Millhouse, M.; Minenkov, Y.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Miyakawa, O.; Miyamoto, A.; Miyamoto, T.; Miyoki, S.; Moggi, A.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, B. C.; Moore, C. J.; Moraru, D.; Moreno, G.; Morii, W.; Morisaki, S.; Moriwaki, Y.; Morriss, S. R.; Mours, B.; Mow-Lowry, C. M.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, S.; Mukund, N.; Mullavey, A.; Munch, J.; Muniz, E. A. M.; Murray, P. G.; Mytidis, A.; Nagano, S.; Nakamura, K.; Nakamura, T.; Nakano, H.; Nakano, Masaya; Nakano, Masayuki; Nakao, K.; Napier, K.; Nardecchia, I.; Narikawa, T.; Naticchioni, L.; Nelemans, G.; Nelson, T. J. N.; Neri, M.; Nery, M.; Neunzert, A.; Newport, J. M.; Newton, G.; Nguyen, T. T.; Ni, W.-T.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Noack, A.; Nocera, F.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Oberling, J.; Ochsner, E.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohashi, M.; Ohishi, N.; Ohkawa, M.; Ohme, F.; Okutomi, K.; Oliver, M.; Ono, K.; Ono, Y.; Oohara, K.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; O'Shaughnessy, R.; Ottaway, D. J.; Overmier, H.; Owen, B. J.; Pace, A. E.; Page, J.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Paris, H. R.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patricelli, B.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Peña Arellano, F. E.; Penn, S.; Perez, C. J.; Perreca, A.; Perri, L. M.; Pfeiffer, H. P.; Phelps, M.; Piccinni, O. J.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Poe, M.; Poggiani, R.; Popolizio, P.; Post, A.; Powell, J.; Prasad, J.; Pratt, J. W. W.; Predoi, V.; Prestegard, T.; Prijatelj, M.; Principe, M.; Privitera, S.; Prodi, G. A.; Prokhorov, L. G.; Puncken, O.; Punturo, M.; Puppo, P.; Pürrer, M.; Qi, H.; Qin, J.; Qiu, S.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rajan, C.; Rakhmanov, M.; Rapagnani, P.; Raymond, V.; Razzano, M.; Re, V.; Read, J.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Rew, H.; Reyes, S. D.; Rhoades, E.; Ricci, F.; Riles, K.; Rizzo, M.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, R.; Romie, J. H.; Rosińska, D.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Sago, N.; Saijo, M.; Saito, Y.; Sakai, K.; Sakellariadou, M.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sampson, L. M.; Sanchez, E. J.; Sandberg, V.; Sanders, J. R.; Sasaki, Y.; Sassolas, B.; Sathyaprakash, B. S.; Sato, S.; Sato, T.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Scheuer, J.; Schmidt, E.; Schmidt, J.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schönbeck, A.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Schwalbe, S. G.; Scott, J.; Scott, S. M.; Sekiguchi, T.; Sekiguchi, Y.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sequino, V.; Sergeev, A.; Setyawati, Y.; Shaddock, D. A.; Shaffer, T. J.; Shahriar, M. S.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shibata, M.; Shikano, Y.; Shimoda, T.; Shoda, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sieniawska, M.; Sigg, D.; Silva, A. D.; Singer, A.; Singer, L. P.; Singh, A.; Singh, R.; Singhal, A.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, B.; Smith, J. R.; Smith, R. J. E.; Somiya, K.; Son, E. J.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Spencer, A. P.; Srivastava, A. K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Stevenson, S. P.; Stone, R.; Strain, K. A.; Straniero, N.; Stratta, G.; Strigin, S. E.; Sturani, R.; Stuver, A. L.; Sugimoto, Y.; Summerscales, T. Z.; Sun, L.; Sunil, S.; Sutton, P. J.; Suzuki, T.; Swinkels, B. L.; Szczepańczyk, M. J.; Tacca, M.; Tagoshi, H.; Takada, S.; Takahashi, H.; Takahashi, R.; Takamori, A.; Talukder, D.; Tanaka, H.; Tanaka, K.; Tanaka, T.; Tanner, D. B.; Tápai, M.; Taracchini, A.; Tatsumi, D.; Taylor, R.; Telada, S.; Theeg, T.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thrane, E.; Tippens, T.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Toland, K.; Tomaru, T.; Tomlinson, C.; Tonelli, M.; Tornasi, Z.; Torrie, C. I.; Töyrä, D.; Travasso, F.; Traylor, G.; Trifirò, D.; Trinastic, J.; Tringali, M. C.; Trozzo, L.; Tse, M.; Tso, R.; Tsubono, K.; Tsuzuki, T.; Turconi, M.; Tuyenbayev, D.; Uchiyama, T.; Uehara, T.; Ueki, S.; Ueno, K.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Ushiba, T.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; Van Den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van Heijningen, J. V.; van Putten, M. H. P. M.; van Veggel, A. A.; Vardaro, M.; Varma, V.; Vass, S.; Vasúth, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Venugopalan, G.; Verkindt, D.; Vetrano, F.; Viceré, A.; Viets, A. D.; Vinciguerra, S.; Vine, D. J.; Vinet, J.-Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Voss, D. V.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, M.; Wakamatsu, T.; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, M.; Wang, Y.; Ward, R. L.; Warner, J.; Was, M.; Watchi, J.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Weßels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; Whiting, B. F.; Whittle, C.; Williams, D.; Williams, R. D.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Woehler, J.; Worden, J.; Wright, J. L.; Wu, D. S.; Wu, G.; Yam, W.; Yamamoto, H.; Yamamoto, K.; Yamamoto, T.; Yancey, C. C.; Yano, K.; Yap, M. J.; Yokoyama, J.; Yokozawa, T.; Yoon, T. H.; Yu, Hang; Yu, Haocun; Yuzurihara, H.; Yvert, M.; Zadrożny, A.; Zangrando, L.; Zanolin, M.; Zeidler, S.; Zendri, J.-P.; Zevin, M.; Zhang, L.; Zhang, M.; Zhang, T.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, S. J.; Zhu, X. J.; Zucker, M. E.; Zweizig, J.

    2018-04-01

    We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5-20 deg^2 requires at least three detectors of sensitivity within a factor of ˜ 2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

  11. Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

    Science.gov (United States)

    Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

    2016-04-01

    Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

  12. Metastatic Cancer

    Science.gov (United States)

    Metastatic cancer is cancer that spreads from its site of origin to another part of the body. Learn how cancer spreads, possible symptoms, common sites where cancer spreads, and how to find out about treatment options.

  13. Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Icro Meattini

    2014-01-01

    Full Text Available Neoadjuvant chemotherapy (NAC is widely used in locally advanced breast cancer (BC treatment. The role of postmastectomy radiotherapy (PMRT after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6% underwent PMRT and 72 cases (42.4% did not receive radiation. At a median follow-up period of 7.7 years (range 2–16 for the whole cohort, median time to locoregional recurrence (LRR was 3.3 years (range 0.7–12.4. The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P=0.035, extracapsular extension (HR 2.18, 1.37–3.46; P=0.009, and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P=0.003. Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P=0.015. Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy.

  14. Post-operative radiation therapy for locally advanced hypopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Nishimura, Hideki; Sasaki, Ryohei; Yoshida, Takeshi

    2011-01-01

    We retrospectively analyzed the treatment outcomes of post-operative radiation therapy (PORT) after radical surgery for locally advanced hypopharyngeal carcinoma. From August 2000 to July 2009, 62 patients with hypopharyngeal squamous cell carcinoma were treated with radical surgery followed by PORT in our institute. All patients were followed up for more than 6 months or until any events. All patients underwent a total laryngectomy and neck node dissection prior to PORT. There were 55 male and 7 female patients, with ages ranging from 45 to 82 years (median: 64). Pathologic stage was IVA in 55 and IVB in 7 patients. Irradiation dose ranged from 46 to 70 Gy (median: 60). Twenty-four patients received concurrent chemotherapy. The median follow-up period for surviving patients was 43 months. The 3-year overall and relapse-free survival rates were 56% and 51%, respectively. There was 1 patient with local recurrence and 9 patients with neck node recurrence, and the 3-year loco-regional control rate was 85%. There were 16 patients with distant metastases and the 3-year freedom form distant metastasis rate was 71%. Patients with extra nodal invasion (ENI) had a statistically poorer prognosis (p=0.008). The incidence rate of loco-regional recurrence and distant metastasis were statistically higher in the patients with ENI (p=0.017 and p=0.009, respectively). PORT with concurrent chemotherapy is deemed to be a standard treatment for such high-risk patients. Conformal and precise radiation treatment such as IMRT might also be considered for such high-risk patients in the near future. (author)

  15. Localization by whole-body autoradiography of intact and fragmented radiolabeled antibodies in a metastatic human colonic cancer model

    International Nuclear Information System (INIS)

    Fand, Irwin; Sharkey, R.M.; Grundy, J.P.; Goldenberg, D.M.

    1992-01-01

    In this report, we have employed macroautoradiography to compare the tumor targeting of 125 I-labeled anti-carcinoembryonic antigen (CEA) MAb (NP-4) to 125 I-labeled anti-colon-specific antigen-p (CSAp) MAb (Mu-9) and their labeled F(ab') 2 and Fab' fragments, in nude mice each bearing large dorsal human colonic tumor xenografts, and small nodular tumors in the liver and lungs. Using intact MAbs (NP-4 and Mu-9), clearance of background radioactivity was delayed to 3-7 days post-treatment. Treatment with F(ab') 2 and Fab' fragments of both NP-4 and Mu-9 MAbs, however, promoted clearance of background 125 I-radioactivity which was well advanced by 6-24 h and complete by 24-48 h after injection. Localization of 125 I-radioactivity in large and micrometastatic tumor perimeters was the most characteristic uptake pattern observed for both intact and fragmented MAbs. Qualitative analysis of macroautoradiographic images and quantitative densitometry indicated that the higher tumor-to-blood ratios achieved with labeled F(ab') 2 and Fab' fragments at early time points, compared to labeled whole immunoglobulin, appeared to be more a function of rapid plasma clearance, tumor mass, location of xenografts and specific tumor growth patterns than increased tumor penetrance by lower molecular weight univalent and bivalent immune fragments. (Author)

  16. Daily concurrent preoperative chemoradiotherapy using superselective intra-arterial infusion via superficial temporal artery for advanced oral cancer. Histological evaluation of metastatic cervical lymph nodes

    International Nuclear Information System (INIS)

    Mitsudo, Kenji; Yamamoto, Noriyuki; Shigetomi, Toshio

    2010-01-01

    Superselective intra-arterial chemotherapy via a superficial temporal artery has become feasible for daily concurrent radiotherapy and chemotherapy in patients with oral cancer. In this study, histopathological effects on metastatic cervical lymph nodes in cases of advanced oral cancer using superselective intra-arterial chemoradiotherapy were evaluated. Thirty-seven oral cancer patients with cervical lymph node metastasis were treated with preoperative chemoradiotherapy using superselective intra-arterial infusion via the superficial temporal artery. The treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m 2 ; cisplatin, total 100-150 mg/m 2 ) and concurrent radiotherapy (total 40-60 Gy) for 4-6 weeks, followed by surgery. In cases in which the catheter was inserted into the facial artery, grade III or IV (Oboshi-Shimosato classification) in the cervical lymph node metastasis was obtained in 20 (83.3%) of 24 patients. And, forty-six (88.5%) of 52 metastatic lymph nodes showed grade III or IV. This method was an effective regimen for oral cancer with cervical lymph node metastasis. (author)

  17. C-reactive protein in patients with advanced metastatic renal cell carcinoma: Usefulness in identifying patients most likely to benefit from initial nephrectomy

    International Nuclear Information System (INIS)

    Ito, Hiroki; Kishida, Takeshi; Miura, Takeshi; Kubota, Yoshinobu; Yao, Masahiro; Shioi, Koichi; Murakami, Takayuki; Takizawa, Akitoshi; Sano, Futoshi; Kawahara, Takashi; Mizuno, Nobuhiko; Makiyama, Kazuhide; Nakaigawa, Noboru

    2012-01-01

    C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied. We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests. ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0–1 and ≥2). The retrospective design is a limitation of this study. Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC

  18. Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician's choice: Results from the randomised phase III BEACON trial.

    Science.gov (United States)

    Twelves, Chris; Cortés, Javier; O'Shaughnessy, Joyce; Awada, Ahmad; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Véronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; Rugo, Hope S

    2017-05-01

    Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician's choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL. HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m 2 every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (≥5 points) in HRQoL scores were compared. Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P Patients in both arms had a decline in HRQoL at disease progression. NCT01492101. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  20. Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis.

    Science.gov (United States)

    Chirila, Costel; Mitra, Debanjali; Colosia, Ann; Ling, Caroline; Odom, Dawn; Iyer, Shrividya; Kaye, James A

    2017-08-01

    Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials. A systematic literature review identified relevant trials. Separate analyses were conducted for each palbociclib combination using a Bayesian approach. Treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). Sixty-five unique studies met inclusion criteria. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all comparators in treatment-naïve patients (hazard ratios [HRs] ranged from 0.41 to 0.58). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and, in previously treated patients, yielded significantly longer PFS than most comparators (HRs ranged from 0.26 to 0.46); the exception was everolimus plus exemestane, with similar PFS (HR, 1.04; 95% credible interval [CrI], 0.58-1.76). Palbociclib plus fulvestrant was associated with significantly lower odds of discontinuation due to adverse events than everolimus plus exemestane (odds ratio, 0.14; 95% CrI, 0.05-0.39). The results suggest that the two palbociclib combinations yielded significantly greater PFS than endocrine therapy in treatment-naïve and previously treated patients with advanced/metastatic breast cancer. Palbociclib plus fulvestrant was associated with significantly less toxicity than everolimus plus exemestane.

  1. Patients with advanced and metastatic renal cell carcinoma treated with targeted therapy in the Czech Republic: twenty cancer centres, six agents, one database.

    Science.gov (United States)

    Poprach, Alexandr; Bortlíček, Zbyněk; Büchler, Tomáš; Melichar, Bohuslav; Lakomý, Radek; Vyzula, Rostislav; Brabec, Petr; Svoboda, Marek; Dušek, Ladislav; Gregor, Jakub

    2012-12-01

    The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

  2. Role of radiation therapy in locally advanced thymoma

    International Nuclear Information System (INIS)

    Urgesi, A.; Monetti, U.; Rossi, G.; Ricardi, U.; Casadio, C.

    1990-01-01

    The records of all patients treated for thymoma in the Department of Radiotherapy of Torino University between 1970 and 1988 were reviewed. There were 59 in stage 3 and 18 in stage 4a; 74 patients were operated before radiotherapy and 3 had a pre-operative irradiation followed by surgery and post-operative boost. Complete resection was possible in 55.9 per cent of stage 3 cases and in none with stage 4a. Subtotal resection was done in 36.6 per cent of stage 3 patients and 83.3 per cent in stage 4a. 8 patients had only biopsy: 5 in stage 3 (8.5 per cent) and 3 in stage 4a (16.6 per cent). Post-operative radiation doses ranged between 39.6 and 46 Gy to the whole mediastinum followed by a 10-16 Gy boost on smaller fields in cases presenting residual disease after surgery. The pre-operative dose was 30 Gy followed by a post-operative boost of 16-24 Gy. Conventional fraction sizes of 1.8-2 Gy were always used. The 10 years survival rate was 58.3 per cent. There was a significant difference between stage 3 (70.9 per cent) and stage 4a (26.3 per cent)(p<0.0004). Survival of patients in stage 3 was not significantly affected by the type of surgery. No significant difference in survival or recurrence rate was observed in patients with different histologies and in patients with or without myasthenia. Thoracic relapses occurred in 15. 2 per cent of stage 3 patients and in 50 per cent of stage 4a patients (p<0.01). Only 7 relapses (9.1 per cent) were within the limits of the radiation field. Radiotherapy seems to be effective in reducing the risk of local recurrence and prolonging survival in patients operated upon for locally advanced thymoma. More patients are alive and free of disease at 10 years than those who received radical surgery. (author). 26 refs.; 4 figs.; 5 tabs

  3. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

    Science.gov (United States)

    Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

    2013-09-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

  4. Case Report: Locally advanced skin cancer in an albino, a treatment ...

    African Journals Online (AJOL)

    Case Report: Locally advanced skin cancer in an albino ... headache, anorexia, weight loss, night sweats, dizziness, change in ... This was the case with our patient, whose five ... We need more interventional studies in treatment of locally.

  5. Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rash, Dominique L. [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States); Lee, Yongsook C. [Department of Radiation Oncology, University of Kansas School of Medicine, Kansas City, Kansas (United States); Kashefi, Amir [Division of Nuclear Medicine, Department of Radiology, University of California Davis Medical Center, Sacramento, California (United States); Durbin-Johnson, Blythe [Division of Biostatistics, Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, California (United States); Mathai, Mathew; Valicenti, Richard [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States); Mayadev, Jyoti S., E-mail: jyoti.mayadev@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States)

    2013-10-01

    Purpose: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. Methods and Materials: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. Results: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. Conclusions: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

  6. Outcomes of colon resection in patients with metastatic colon cancer.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Hwang, Grace; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Carmichael, Joseph C

    2016-08-01

    Patients with advanced colorectal cancer have a high incidence of postoperative complications. We sought to identify outcomes of patients who underwent resection for colon cancer by cancer stage. The National Surgical Quality Improvement Program database was used to evaluate all patients who underwent colon resection with a diagnosis of colon cancer from 2012 to 2014. Multivariate logistic regression analysis was performed to investigate patient outcomes by cancer stage. A total of 7,786 colon cancer patients who underwent colon resection were identified. Of these, 10.8% had metastasis at the time of operation. Patients with metastatic disease had significantly increased risks of perioperative morbidity (adjusted odds ratio [AOR]: 1.44, P = .01) and mortality (AOR: 3.72, P = .01). Patients with metastatic disease were significantly younger (AOR: .99, P colon cancer have metastatic disease. Postoperative morbidity and mortality are significantly higher than in patients with localized disease. Published by Elsevier Inc.

  7. Nuclear-specific AR-V7 Protein Localization is Necessary to Guide Treatment Selection in Metastatic Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Scher, Howard I; Graf, Ryon P; Schreiber, Nicole A; McLaughlin, Brigit; Lu, David; Louw, Jessica; Danila, Daniel C; Dugan, Lyndsey; Johnson, Ann; Heller, Glenn; Fleisher, Martin; Dittamore, Ryan

    2017-06-01

    Circulating tumor cells (CTCs) expressing AR-V7 protein localized to the nucleus (nuclear-specific) identify metastatic castration-resistant prostate cancer (mCRPC) patients with improved overall survival (OS) on taxane therapy relative to the androgen receptor signaling inhibitors (ARSi) abiraterone acetate, enzalutamide, and apalutamide. To evaluate if expanding the positivity criteria to include both nuclear and cytoplasmic AR-V7 localization ("nuclear-agnostic") identifies more patients who would benefit from a taxane over an ARSi. The study used a cross-sectional cohort. Between December 2012 and March 2015, 193 pretherapy blood samples, 191 of which were evaluable, were collected and processed from 161 unique mCRPC patients before starting a new line of systemic therapy for disease progression at the Memorial Sloan Kettering Cancer Center. The association between two AR-V7 scoring criteria, post-therapy prostate-specific antigen (PSA) change (PTPC) and OS following ARSi or taxane treatment, was explored. One criterion required nuclear-specific AR-V7 localization, and the other required an AR-V7 signal but was agnostic to protein localization in CTCs. Correlation of AR-V7 status to PTPC and OS was investigated. Relationships with survival were analyzed using multivariable Cox regression and log-rank analyses. A total of 34 (18%) samples were AR-V7-positive using nuclear-specific criteria, and 56 (29%) were AR-V7-positive using nuclear-agnostic criteria. Following ARSi treatment, none of the 16 nuclear-specific AR-V7-positive samples and six of the 32 (19%) nuclear-agnostic AR-V7-positive samples had ≥50% PTPC at 12 weeks. The strongest baseline factor influencing OS was the interaction between the presence of nuclear-specific AR-V7-positive CTCs and treatment with a taxane (hazard ratio 0.24, 95% confidence interval 0.078-0.79; p=0.019). This interaction was not significant when nuclear-agnostic criteria were used. To reliably inform treatment selection

  8. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Wu Xiwei

    2012-03-01

    Full Text Available Abstract Background MicroRNAs (miRNAs have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC, and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Methods The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. Results More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. Conclusions Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

  9. Clinicopathologic factors associated with de novo metastatic breast cancer.

    Science.gov (United States)

    Shen, Tiansheng; Siegal, Gene P; Wei, Shi

    2016-12-01

    While breast cancers with distant metastasis at presentation (de novo metastasis) harbor significantly inferior clinical outcomes, there have been limited studies analyzing the clinicopathologic characteristics in this subset of patients. In this study, we analyzed 6126 breast cancers diagnosed between 1998 and 2013 to identify factors associated with de novo metastatic breast cancer. When compared to patients without metastasis at presentation, race, histologic grade, estrogen/progesterone receptor (ER/PR) and HER2 statuses were significantly associated with de novo metastasis in the entire cohort, whereas age, histologic grade, PR and HER2 status were the significant parameters in the subset of patients with locally advanced breast cancer (Stage IIB/III). The patients with de novo metastatic breast cancer had a significant older mean age and a lower proportion of HER2-positive tumors when compared to those with metastatic recurrence. Further, the HER2-rich subtype demonstrated a drastically higher incidence of de novo metastasis when compared to the luminal and triple-negative breast cancers in the entire cohort [odds ratio (OR)=5.68 and 2.27, respectively] and in the patients with locally advanced disease (OR=4.02 and 2.12, respectively), whereas no significant difference was seen between de novo metastatic cancers and those with metastatic recurrence. Moreover, the luminal and HER2-rich subtypes showed bone-seeking (OR=1.92) and liver-homing (OR=2.99) characteristics, respectively, for the sites of de novo metastasis, while the latter was not observed in those with metastatic recurrence. Our data suggest that an algorithm incorporating clinicopathologic factors, especially histologic grade and receptor profile, remains of significant benefit during decision making in newly diagnosed breast cancer in the pursuit of precision medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Can concurrent chemoradiotherapy replace surgery and postoperative radiation for locally advanced stage III/IV tonsillar squamous cell carcinoma?

    Science.gov (United States)

    Park, Geumju; Lee, Sang-Wook; Kim, Sang Yoon; Nam, Soon Yuhl; Choi, Seung-Ho; Kim, Sung-Bae; Roh, Jong-Lyel; Yoon, Dok Hyun; Kim, Su Ssan; Park, Jin-Hong; Kim, Young Seok; Yoon, Sang Min; Song, Si Yeol; Kim, Jong Hoon; Choi, Eun Kyung; DO Ahn, Seung

    2013-03-01

    To compare surgery and postoperative radiotherapy (PORT) with the non-surgical combination of chemotherapy and radiation therapy (CCRT) for locally advanced squamous cell carcinoma (SCC) of the tonsil by measuring treatment outcomes and treatment-related complications. The records of 114 patients with non-metastatic stage III/IV tonsillar SCC treated between July, 1998 and December, 2010 were reviewed retrospectively. Among the 114 patients, 65 received PORT and 49 received CCRT. In the PORT group, treatment included wide surgical resection of the tumor with neck dissection and administration of PORT to the primary tumor bed with a median dose of 60 Gy. In the CCRT group, a median dose of 70 Gy was delivered to the gross tumor, and 46 patients received concurrent chemotherapy with i.v. cisplatin. The median follow-up time was 58 months in the PORT group and 44 months in the CCRT group. There was no significant difference between PORT and CCRT in terms of 5-year locoregional recurrence-free survival (88.4% vs. 91.4%, p=0.68), distant metastasis-free survival (88.9% vs. 92.3%, p=0.60), disease-free survival (79.5% vs. 84.2%, p=0.63) or overall survival (78.9% vs. 88.9%, p=0.45). More CCRT patients than PORT patients experienced grade 3 (or higher) hematological toxicities and grade 2 pharyngitis during treatment. Chronic toxicity, manifested as swallowing difficulty, dry mouth and trismus, was similar between the two treatment groups. CCRT provides similar levels of local and distant control in patients with locally advanced tonsillar SCC as PORT, yet fails to show any superiority in preserving functions such as swallowing, saliva production, and mastication.

  11. Clinical impact of FDG PET-CT on the management of patients with locally advanced cervical carcinoma

    International Nuclear Information System (INIS)

    Fleming, S.; Cooper, R.A.; Swift, S.E.; Thygesen, H.H.; Chowdhury, F.U.; Scarsbrook, A.F.; Patel, C.N.

    2014-01-01

    Aim: To evaluate the impact of staging FDG PET-CT on the initial management of patients with locally advanced cervical carcinoma (LACC) and any prognostic variables predicting survival. Materials and methods: Retrospective analysis of consecutive patients undergoing FDG PET-CT for staging of LACC in a single tertiary referral centre, between April 2008 and August 2011. Comparison was made between MRI and PET-CT findings and any subsequent impact on treatment intent or radiotherapy planning was evaluated. Results: Sixty-three patients underwent FDG PET-CT for initial staging of LACC. Major impact on management was found in 20 patients (32%), a minor impact in five (8%), and no impact in 38 (60%). In those patients where PET-CT had a major impact, 12 had more extensive local nodal involvement, five had occult metastatic disease, two had synchronous tumours, and one patient had equivocal lymph nodes on MRI characterized as negative. PET-positive nodal status at diagnosis was found to be a statistically significant predictor of relapse-free survival (p < 0.05). Conclusion: Staging FDG PET-CT has a major impact on the initial management of approximately one-third of patients with LACC by altering treatment intent and/or radiotherapy planning. PET-defined nodal status is a poor prognostic indicator. - Highlights: • Cervical carcinoma is one of the commonest cancers in women worldwide. • Locally advanced cervical carcinoma is usually treated with chemo-radiotherapy. • FDG PET-CT can have a major impact on management in up to one-third of patients. • It may alter treatment intent or radiotherapy-planning by detecting occult disease. • PET nodal status at diagnosis is an important predictor of relapse-free survival

  12. Clinical review: surgical management of locally advanced and recurrent colorectal cancer.

    LENUS (Irish Health Repository)

    Courtney, D

    2014-01-01

    Recurrent and locally advanced colorectal cancers frequently require en bloc resection of involved organs to achieve negative margins. The aim of this review is to evaluate the most current literature related to the surgical management of locally advanced and recurrent colorectal cancer.

  13. Early experience of proton beam therapy combined with chemotherapy for locally advanced oropharyngeal cancer

    International Nuclear Information System (INIS)

    Ishikawa, Youjirou; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Makita, Chiyoko; Suzuki, Motohisa; Azami, Yusuke; Kikuchi, Yasuhiro; Fuwa, Nobukazu

    2013-01-01

    Between 2009 and 2012, 10 patients with advanced oropharyngeal cancer underwent proton therapy combined with chemotherapy. The initial results of this therapy were 8 complete response (CR) and 2 partial response (PR), local recurrence was detected 1 patient. Proton beam therapy combined with chemotherapy is thought to be an effective treatment for locally advanced oropharyngeal cancer. (author)

  14. MDCT of primary, locally recurrent, and metastatic duodenal gastrointestinal stromal tumours (GISTs): A single institution study of 25 patients with review of literature

    International Nuclear Information System (INIS)

    Cheng, J.M.; Tirumani, S.H.; Shinagare, A.B.; Jagannathan, J.P.; Hornick, J.L.; Raut, C.P.; Ramaiya, N.H.

    2014-01-01

    Aim: To describe the multidetector computed tomography (MDCT) features of primary, locally recurrent, and metastatic duodenal gastrointestinal stromal tumours (GISTs). Materials and methods: In this institutional review board-approved, Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant, retrospective study, 25 patients [13 men, 12 women; mean age 56 years (34–74 years)] with histopathologically confirmed duodenal GISTs seen at Dana Farber Cancer Institute and Brigham and Women's Hospital from December 1999 to October 2009 were identified. The MDCT of primary tumours in six patients and follow-up imaging in all the 25 patients was reviewed by two radiologists in consensus. Electronic medical records were reviewed to document the clinical characteristics and management. Results: The mean size of the primary tumour was 3.7 cm (range 2.5–5.6 cm). Three of six primary tumours were in the second and third portions of the duodenum, one in the third portion, one in the third and fourth portions, and one in the fourth portion. Three of six of the tumours were exophytic, two were both exophytic and intraluminal, and one was intramural. The tumours were well-circumscribed, round or oval masses, with few lobulations, and were either homogeneously hyper-enhancing or heterogeneously isodense at MDCT. None of the tumours had necrosis, haemorrhage, calcification, or loco regional lymphadenopathy on imaging. Sixteen of 25 (64%) patients developed metastatic disease, the most common sites being liver (14/16; 87.5%) and peritoneum (5/16; 31%). Conclusion: Duodenal GISTs are well-circumscribed, round or oval masses, and occur in the second through fourth portions of the duodenum, without lymphadenopathy or duodenal obstruction. Duodenal GISTS metastasize frequently to the liver and peritoneum

  15. Nuclear medicine imaging of locally advanced laryngeal and hypopharyngeal cancer

    Science.gov (United States)

    Medvedeva, A.; Chernov, V.; Zeltchan, R.; Sinilkin, I.; Bragina, O.; Chijevskaya, S.; Choynzonov, E.; Goldberg, A.

    2017-09-01

    The diagnostic capabilities of nuclear medicine imaging in the detection and assessment of the spread of laryngeal/hypopharyngeal cancer were studied. A total of 40 patients with histologically verified laryngeal and hypopharyngeal cancer and 20 patients with benign laryngeal lesions were included into the study. Submucosal injections of 99mTc-MIBI and 99mTc-Alotech were made around the tumor. Single photon emission computed tomography (SPECT) was performed 20 minutes after the injection of 99mTc-MIBI. Sentinel lymph nodes (SLNs) were detected in 26 patients. In 18 hours after the injection of 99mTc-Alotech, SPECT was performed. In 24 hours after the injection of 99mTc-Alotech, intraoperative SLN detection was performed using Gamma Finder II. SPECT with 99mTc-MIBI revealed laryngeal and hypopharyngeal tumors in 38 of the 40 patients. The 99mTc-MIBI uptake in metastatic lymph nodes was visualized in 2 (17%) of the 12 patients. Twenty eight SLNs were detected by SPECT and 31 SLNs were identified using the intraoperative gamma probe. The percentage of 99mTc-Alotech in the SLN was 5-10% of the radioactivity in the injection site by SPECT and 18-33% by intraoperative gamma probe detection. Thus, SPECT with 99mTc-MIBI is an effective tool for the diagnosis of laryngeal/hypopharyngeal cancer. The sensitivity, specificity and accuracy of this technique were 95%, 80% and 92%, respectively. The use of 99mTc-Alotech for the detection of SLNs in patients with laryngeal/hypopharyngeal cancer is characterized by 92.8% sensitivity.

  16. 3'-Deoxy-3'-{sup 18}F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Challapalli, Amarnath; Barwick, Tara; Merchant, Shairoz [Imperial College London (ICL), Department of Surgery and Cancer, London (United Kingdom); Pearson, Rachel A.; Howell, Elizabeth C.; Maxwell, Ross J. [Newcastle University, Northern Institute for Cancer Research, Newcastle (United Kingdom); Mauri, Francesco [Imperial College Healthcare NHS Trust, Department of Pathology, London (United Kingdom); Sumpter, Katherine [Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals NHS Foundation Trust, London (United Kingdom); Aboagye, Eric O. [Imperial College London (ICL), Department of Surgery and Cancer, London (United Kingdom); ICL, Hammersmith Hospital, Department of Surgery and Cancer, London (United Kingdom); Sharma, Rohini [ICL, Department of Investigative Medicine, London (United Kingdom)

    2015-05-01

    3'-Deoxy-3'-{sup 18}F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CT{sub KSF}) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PET{sub KSF} images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35 %). Maximum standardised uptake value at 60 min post-injection (SUV{sub 60,max}) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV{sub 60,max} increase of ≥ 12 % resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100 %, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV{sub 60,max} were not predictive of survival. FLT PET/CT detected changes in proliferation, with early increase in SUV{sub 60,max} predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer. (orig.)

  17. Patient-reported Quality of Life and Treatment Satisfaction in Patients With HR+/HER2- Advanced/Metastatic Breast Cancer.

    Science.gov (United States)

    Wood, Robert; Mitra, Debanjali; de Courcy, Jonathan; Iyer, Shrividya

    2017-08-01

    Globally, around 1.67 million new cases of breast cancer are diagnosed each year, with advanced breast cancer (ABC-Stage III) and metastatic breast cancer (MBC-Stage IV) together accounting for up to 22% of incident cases. Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 - ) breast cancer comprises 66% of ABC/MBC. Understanding disease-specific health-related quality of life and patient satisfaction with treatments currently available for HR + /HER2 - ABC/MBC in clinical practice is essential for assessing potential unmet need in this patient population. Data on treatment patterns in patients with HR + /HER2 - ABC/MBC were collected from oncology practices across the United States and Europe in a cross-sectional study in a clinical practice setting, the Adelphi Real World Advanced Breast Cancer Disease Specific Programme. A subset of patients included in the study completed several self-reported tools, including the Functional Assessment of Cancer Therapy-Breast and the Cancer Therapy Satisfaction Questionnaire. Analyses were conducted using data from the overall cohort and stratified by current treatment, metastatic sites, and number of prior therapy lines. Overall, 739 patients were recruited by 173 oncologists; 83% of patients had MBC, with the balance having ABC. The majority of patients with MBC had visceral metastases without bone metastases, and similar percentages of the total study population (≈40%) were receiving chemotherapy and endocrine therapy. Patients receiving only endocrine therapy had significantly better cancer-specific quality of life than did those receiving chemotherapy. Endocrine therapy also associated with fewer concerns about side effects and higher treatment satisfaction than chemotherapy. Statistically lower scores, indicating poorer well-being, were observed in patients with both bone and visceral metastases compared with those with either bone-only or visceral-only metastases for all but the

  18. A PHASE-II AND PHARMACOKINETIC STUDY WITH ORAL PIRITREXIM FOR METASTATIC BREAST-CANCER

    NARCIS (Netherlands)

    DEVRIES, EGE; GIETEMA, JA; WORKMAN, P; SCOTT, JE; CRAWSHAW, A; DOBBS, HJ; DENNIS, [No Value; MULDER, NH; SLEIJFER, DT; WILLEMSE, PHB

    Piritrexim is a lipid-soluble antifolate which, like methotrexate, has a potent capacity to inhibit dihydrofolate reductase. We performed a multicentre phase 11 study with piritrexim in patients with locally advanced or metastatic breast cancer. Twenty-four patients of which sixteen had received

  19. Gemcitabine concurrent with radiation therapy for locally advanced ...

    African Journals Online (AJOL)

    Background: Management of advanced head and neck carcinoma is a challenging proposition. Presently concomitant chemoirradiation has become the standard of care in such patients. Many chemotherapeutic drugs have shown radio-sensitising effects when used concomitantly along with radiation. The present study ...

  20. Neoadjuvant chemotherapy in Albinos with locally advanced skin ...

    African Journals Online (AJOL)

    advanced skin cancer at a Blantyre Hospital: - Case. Series. I A. Chidothe , ... posing difficulties for standard of care for units that do not have access to functional RT ... 3: A 19 year old boy presented with a 5 year history of a left parietal ulcer.

  1. Enhanced skin toxicity with concomitant cetuximab and radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bujor, L.; Grillo, I.M.; Pimentel, N. [Hospital Santa Maria, Radioterapia, Lisboa (Portugal); Macor, C.; Catarina, M. [Hospital Santa Maria, ORL, Lisboa (Portugal); Ribeiro, L. [Hospital Santa Maria, Oncologia, Lisboa (Portugal)

    2009-10-15

    Purpose: When associated with radiotherapy the monoclonal antibodies such as cetuximab might be exacerbate skin toxicity. The aim of this study was to retrospectively analyze acute dermatological toxicity in ten consecutive patients with locally advanced head and neck squamous cell carcinoma treated from march 2008 to May 2009 according to Bonner protocol. Patients and methods: We have treated with radiotherapy and cetuximab ten patients with locally advanced head and neck squamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity, stage 3-4B and non metastatic. All our patients were 3D planned and scheduled for conventional fractionation 70 Gy/35 fractions over 47 days, five days weekly. Uninvolved neck received 50 Gy and gross nodal disease received 70 Gy as the primary tumor. Cetuximab was administered one week before radiotherapy at a loading dose of 400 mg per square meter of body surface area over 120 minutes, followed by weekly 60 minutes infusions at 250 mg per square meter for the duration of radiotherapy. Results: In eight patients (80%) grade 3 radiation dermatitis occurred as early as with 28 Gy at a median dose of 42 Gy (range 28-60 Gy). the median radiotherapy dose was 6 Gy with an overall treatment time of 57.7 days (range 41-70 days). were administered 78 cycles of cetuximab, one patient discontinued after five cycles due to infusion reactions. There was no correlation between toxicity and acne-like rash due to cetuximab. Conclusion: Our results albeit in disagreement with the original study are rather similar with the experience of other European centers that encounter grade 3-4 radiation dermatitis in 49% of their patients or Australian centers that reported 79% of same degree of toxicity. (authors)

  2. Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713.

    Science.gov (United States)

    Leichman, Cynthia Gail; McDonough, Shannon L; Smalley, Stephen R; Billingsley, Kevin G; Lenz, Heinz-Josef; Beldner, Matthew A; Hezel, Aram F; Velasco, Mario R; Guthrie, Katherine A; Blanke, Charles D; Hochster, Howard S

    2018-03-01

    Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Enhanced skin toxicity with concomitant cetuximab and radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Bujor, L.; Grillo, I.M.; Pimentel, N.; Macor, C.; Catarina, M.; Ribeiro, L.

    2009-01-01

    Purpose: When associated with radiotherapy the monoclonal antibodies such as cetuximab might be exacerbate skin toxicity. The aim of this study was to retrospectively analyze acute dermatological toxicity in ten consecutive patients with locally advanced head and neck squamous cell carcinoma treated from march 2008 to May 2009 according to Bonner protocol. Patients and methods: We have treated with radiotherapy and cetuximab ten patients with locally advanced head and neck squamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity, stage 3-4B and non metastatic. All our patients were 3D planned and scheduled for conventional fractionation 70 Gy/35 fractions over 47 days, five days weekly. Uninvolved neck received 50 Gy and gross nodal disease received 70 Gy as the primary tumor. Cetuximab was administered one week before radiotherapy at a loading dose of 400 mg per square meter of body surface area over 120 minutes, followed by weekly 60 minutes infusions at 250 mg per square meter for the duration of radiotherapy. Results: In eight patients (80%) grade 3 radiation dermatitis occurred as early as with 28 Gy at a median dose of 42 Gy (range 28-60 Gy). the median radiotherapy dose was 6 Gy with an overall treatment time of 57.7 days (range 41-70 days). were administered 78 cycles of cetuximab, one patient discontinued after five cycles due to infusion reactions. There was no correlation between toxicity and acne-like rash due to cetuximab. Conclusion: Our results albeit in disagreement with the original study are rather similar with the experience of other European centers that encounter grade 3-4 radiation dermatitis in 49% of their patients or Australian centers that reported 79% of same degree of toxicity. (authors)

  4. Optimization of Acquisition time of 68Ga-PSMA-Ligand PET/MRI in Patients with Local and Metastatic Prostate Cancer.

    Science.gov (United States)

    Lütje, Susanne; Blex, Sebastian; Gomez, Benedikt; Schaarschmidt, Benedikt M; Umutlu, Lale; Forsting, Michael; Jentzen, Walter; Bockisch, Andreas; Poeppel, Thorsten D; Wetter, Axel

    2016-01-01

    The aim of this optimization study was to minimize the acquisition time of 68Ga-HBED-CC-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with local and metastatic prostate cancer (PCa) to obtain a sufficient image quality and quantification accuracy without any appreciable loss. Twenty patients with PCa were administered intravenously with the 68Ga-HBED-CC-PSMA ligand (mean activity 99 MBq/patient, range 76-148 MBq) and subsequently underwent PET/MRI at, on average, 168 min (range 77-320 min) after injection. PET and MR imaging data were acquired simultaneously. PET acquisition was performed in list mode and PET images were reconstructed at different time intervals (1, 2, 4, 6, 8, and 10 min). Data were analyzed regarding radiotracer uptake in tumors and muscle tissue and PET image quality. Tumor uptake was quantified in terms of the maximum and mean standardized uptake value (SUVmax, SUVmean) within a spherical volume of interest (VOI). Reference VOIs were drawn in the gluteus maximus muscle on the right side. PET image quality was evaluated by experienced nuclear physicians/radiologists using a five-point ordinal scale from 5-1 (excellent-insufficient). Lesion detectability linearly increased with increasing acquisition times, reaching its maximum at PET acquisition times of 4 min. At this image acquisition time, tumor lesions in 19/20 (95%) patients were detected. PET image quality showed a positive correlation with increasing acquisition time, reaching a plateau at 4-6 min image acquisition. Both SUVmax and SUVmean correlated inversely with acquisition time and reached a plateau at acquisition times after 4 min. In the applied image acquisition settings, the optimal acquisition time of 68Ga-PSMA-ligand PET/MRI in patients with local and metastatic PCa was identified to be 4 min per bed position. At this acquisition time, PET image quality and lesion detectability reach a maximum while SUVmax and SUVmean do not change

  5. Optimization of Acquisition time of 68Ga-PSMA-Ligand PET/MRI in Patients with Local and Metastatic Prostate Cancer.

    Directory of Open Access Journals (Sweden)

    Susanne Lütje

    Full Text Available The aim of this optimization study was to minimize the acquisition time of 68Ga-HBED-CC-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI in patients with local and metastatic prostate cancer (PCa to obtain a sufficient image quality and quantification accuracy without any appreciable loss.Twenty patients with PCa were administered intravenously with the 68Ga-HBED-CC-PSMA ligand (mean activity 99 MBq/patient, range 76-148 MBq and subsequently underwent PET/MRI at, on average, 168 min (range 77-320 min after injection. PET and MR imaging data were acquired simultaneously. PET acquisition was performed in list mode and PET images were reconstructed at different time intervals (1, 2, 4, 6, 8, and 10 min. Data were analyzed regarding radiotracer uptake in tumors and muscle tissue and PET image quality. Tumor uptake was quantified in terms of the maximum and mean standardized uptake value (SUVmax, SUVmean within a spherical volume of interest (VOI. Reference VOIs were drawn in the gluteus maximus muscle on the right side. PET image quality was evaluated by experienced nuclear physicians/radiologists using a five-point ordinal scale from 5-1 (excellent-insufficient.Lesion detectability linearly increased with increasing acquisition times, reaching its maximum at PET acquisition times of 4 min. At this image acquisition time, tumor lesions in 19/20 (95% patients were detected. PET image quality showed a positive correlation with increasing acquisition time, reaching a plateau at 4-6 min image acquisition. Both SUVmax and SUVmean correlated inversely with acquisition time and reached a plateau at acquisition times after 4 min.In the applied image acquisition settings, the optimal acquisition time of 68Ga-PSMA-ligand PET/MRI in patients with local and metastatic PCa was identified to be 4 min per bed position. At this acquisition time, PET image quality and lesion detectability reach a maximum while SUVmax and SUVmean do not change

  6. Advanced techniques and armamentarium for dental local anesthesia.

    Science.gov (United States)

    Clark, Taylor M; Yagiela, John A

    2010-10-01

    Computer-controlled local anesthetic delivery (C-CLAD) devices and systems for intraosseous (IO) injection are important additions to the dental anesthesia armamentarium. C-CLAD using slow infusion rates can significantly reduce the discomfort of local anesthetic infusion, especially in palatal tissues, and facilitate palatal approaches to pulpal nerve block that find special use in cosmetic dentistry, periodontal therapy, and pediatric dentistry. Anesthesia of single teeth can be obtained using either C-CLAD intraligamentary injections or IO injections. Supplementary IO anesthesia is particularly suited for providing effective pain control of teeth diagnosed with irreversible pulpitis. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Radiation therapy for unresectable locally advanced breast cancer

    International Nuclear Information System (INIS)

    Horikawa, Noriko; Inoue, Masayoshi; Uehara, Tomoko; Miyasaka, T.; Miyasaka, M.; Tabata, Yoji; Sakamoto, Nobuyuki; Nakagawa, Y.

    2013-01-01

    Thirteen cases of inoperable advanced breast cancer were treated with radiotherapy between 2002 to 2012 at Nara Prefectural Hospital. All cases were treated by radiotherapy and chemo-endocrine therapy. Patients received 60-81 Gy (median 60 Gy) to the primary breast tumor. Response of the breast tumors were complete response in 3 cases (23%), partial response in 8 cases (62%) and stable disease in 2 cases (15%) (response rate: 85%). All breast tumors had been controlled and skin troubles were reduced. Radiotherapy for breast cancer is useful for primary tumor control and improved quality of life (QOL). Radiotherapy should be considered to be useful modality in the treatment of advanced breast cancer. (author)

  8. MANAGEMENT AND SURVIVAL IN ADVANCED PROSTATE ...

    African Journals Online (AJOL)

    hi-tech

    2000-05-05

    May 5, 2000 ... Patients: Fifty nine patients with advanced cancer of prostate (extra prostatic locally advanced and metastatic ... Conclusion: Survival in the undifferentiated and poorly differentiated prostrate cancer. Gleasons grades 4 and 5 .... with its pulsatile release from the hypothalamus and desensitises the pituitary ...

  9. Advanced carrier sensing to resolve local channel congestion

    NARCIS (Netherlands)

    Schmidt, Robert K.; Brakemeier, Achim; Leinmüller, Tim; Kargl, Frank; Schäfer, Günther

    Communication performance in VANETs under high channel load is significantly degraded due to packet collisions and messages drops, also referred to as local channel congestion. So far, research was focused on the control of transmit power and the limitation of the messages rate to mitigate the

  10. Three cases of unresectable locally advanced breast cancer treated with local injection of the new radiosensitization (KORTUC)

    International Nuclear Information System (INIS)

    Shimbo, Taijyu; Yosikawa, Nobuhiko; Yoshioka, H.; Tanaka, Y.; Yoshida, Ken; Uesugi, Yasuo; Narumi, Yoshifumi; Inomata, Taisuke

    2013-01-01

    New radiosensitization therapy named Kochi Oxydol-Radiation Therapy for Unresectabe carcinomas (KORTUC) using a new agent containing 0.5% hydrogen peroxide and 0.83% sodium hyaluronate is the world first treatment developed in Japan. The agent was injected into tumor two times per week under ultrasonographic guidance. Unresectable locally advanced breast cancer is radiation resistance. The local control is difficult in a conventional radiation therapy. In 3 cases, KORTUC was enforced safety, and remarkable effects was admitted. (author)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  12. #3653 Sequencing of plasma cfDNA from patients with locally advanced bladder cancer for surveillance and therapeutic efficacy monitoring

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Christensen, Emil; Sharma, Shruti

    ), 340 (67-2838) moderate and 223 (29-2955) low-impact SNVs or insertion-deletions (InDels) per tumor. High-impact mutations in known cancer genes such as TP53 (60%), KDM6A (34%), ARID1A (32%), RB1 (28%), BRCA2 (26%), FGFR3 (22%) and ERCC2 (20%) were identified with no significant difference between......, 50 patients diagnosed with locally advanced muscle-invasive bladder cancer (MIBC) and scheduled for chemotherapy were prospectively recruited between 2013 and 2017. In total, 42 patients received four cycles of cisplatin-based NAC prior to cystectomy and 82% showed response (pathologic downstaging......). Eight patients received 2-6 cycles of cisplatin-based first-line chemotherapy due to diagnosis of T4b or lymph node metastasis prior to cystectomy (3CR, 2PR, 2PD, 1 ongoing). So far, 8/50 patients (16%) experienced disease relapse and three patients had metastatic progression. The mean follow-up time...

  13. Feasibility of Electromagnetic Transponder Use to Monitor Inter- and Intrafractional Motion in Locally Advanced Pancreatic Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Shinohara, Eric T., E-mail: eric.t.shinohara@vanderbilt.edu [Department of Radiation Oncology, The Vanderbilt Clinic, Nashville, TN (United States); Kassaee, Alireza [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Vapiwala, Neha; Plastaras, John P. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Drebin, Jeff [Department of Surgery, University of Pennsylvania, Philadelphia, PA (United States); Wan, Fei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Metz, James M. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

    2012-06-01

    Purpose: The primary objective of this study was to determine the feasibility of electromagnetic transponder implantation in patients with locally advanced unresectable pancreatic cancer. Secondarily, the use of transponders to monitor inter- and intrafractional motion, and the efficacy of breath holding for limiting target motion, were examined. Methods and Materials: During routine screening laparoscopy, 5 patients without metastatic disease were implanted with transponders peri-tumorally. The Calypso System's localization and tracking modes were used to monitor inter- and intrafractional motion, respectively. Intrafractional motion, with and without breath holding, was also examined using Calypso tracking mode. Results: Transponder implantation was well tolerated in all patients, with minimal migration, aside from 1 patient who expulsed a single transponder. Interfractional motion based on mean shifts from setup using tattoos/orthogonal imaging to transponder based localization from 164 treatments was significant in all dimensions. Mean shift (in millimeters), followed by the standard deviation and p value, were as follows: X-axis: 4.5 mm (1.0, p = 0.01); Y axis: 6.4 mm (1.9, p = 0.03); and Z-axis 3.9 mm (0.6, p = 0.002). Mean intrafractional motion was also found to be significant in all directions: superior, 7.2 mm (0.9, p = 0.01); inferior, 11.9 mm (0.9, p < 0.01); anterior: 4.9 mm (0.5, p = 0.01); posterior, 2.9 mm (0.5, p = 0.02); left, 2.2 mm (0.4, p = 0.02); and right, 3.1 mm (0.6, p = 0.04). Breath holding during treatment significantly decreased tumor motion in all directions. Conclusions: Electromagnetic transponder implantation appears to be safe and effective for monitoring inter- and intrafractional motion. Based on these results a larger clinical trial is underway.

  14. Feasibility of Electromagnetic Transponder Use to Monitor Inter- and Intrafractional Motion in Locally Advanced Pancreatic Cancer Patients

    International Nuclear Information System (INIS)

    Shinohara, Eric T.; Kassaee, Alireza; Mitra, Nandita; Vapiwala, Neha; Plastaras, John P.; Drebin, Jeff; Wan, Fei; Metz, James M.

    2012-01-01

    Purpose: The primary objective of this study was to determine the feasibility of electromagnetic transponder implantation in patients with locally advanced unresectable pancreatic cancer. Secondarily, the use of transponders to monitor inter- and intrafractional motion, and the efficacy of breath holding for limiting target motion, were examined. Methods and Materials: During routine screening laparoscopy, 5 patients without metastatic disease were implanted with transponders peri-tumorally. The Calypso System’s localization and tracking modes were used to monitor inter- and intrafractional motion, respectively. Intrafractional motion, with and without breath holding, was also examined using Calypso tracking mode. Results: Transponder implantation was well tolerated in all patients, with minimal migration, aside from 1 patient who expulsed a single transponder. Interfractional motion based on mean shifts from setup using tattoos/orthogonal imaging to transponder based localization from 164 treatments was significant in all dimensions. Mean shift (in millimeters), followed by the standard deviation and p value, were as follows: X-axis: 4.5 mm (1.0, p = 0.01); Y axis: 6.4 mm (1.9, p = 0.03); and Z-axis 3.9 mm (0.6, p = 0.002). Mean intrafractional motion was also found to be significant in all directions: superior, 7.2 mm (0.9, p = 0.01); inferior, 11.9 mm (0.9, p < 0.01); anterior: 4.9 mm (0.5, p = 0.01); posterior, 2.9 mm (0.5, p = 0.02); left, 2.2 mm (0.4, p = 0.02); and right, 3.1 mm (0.6, p = 0.04). Breath holding during treatment significantly decreased tumor motion in all directions. Conclusions: Electromagnetic transponder implantation appears to be safe and effective for monitoring inter- and intrafractional motion. Based on these results a larger clinical trial is underway.

  15. Prospects for Observing and Localizing Gravitational-Wave Transients with Advanced LIGO and Advanced Virgo

    NARCIS (Netherlands)

    Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Phythian-Adams, A.T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Aggarwal, N.T.; Aguiar, O. D.; Ain, A.; Ajith, P.; Allen, B.; Allocca, A.; Altin, P. A.; Amariutei, D. V.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Ashton, G.; Ast, M.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Babak, S.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, R.D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Baune, C.; Bavigadda, V.; Bazzan, M.; Behnke, B.; Bejger, M.; Belczynski, C.; Bell, A. S.; Bell, C. J.; Berger, B. K.; Bergman, J.; Bergmann, G.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Birch, M.J.; Birney, R.; Biscans, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blair, C. D.; Blair, C. D.; Blair, R. M.; Bloernen, S.; Bock, O.; Bodiya, T. P.; Boer, M.; Bogaert, J.G.; Bogan, C.; Bohe, A.; Bojtos, P.; Bond, T.C; Bondu, F.; Bonnand, R.; Bork, R.; Boschi, V.; Bose, S.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Brooks, A. F.; Brown, A.D.; Brown, D.; Brown, N. M.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Calderon Bustillo, J.; Callister, T. A.; Calloni, E.; Camp, J. B.; Cannon, K. C.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Diaz, J. Casanueva; Casentini, C.; Caudill, S.; Cavaglia, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C. B.; Baiardi, L. Cerboni; Cerretani, G.; Cesarini, E.; Chakraborty, R.; Chalermsongsak, T.; Chamberlin, S. J.; Chan, M.; Chao, D. S.; Charlton, P.; Chassande-Mottin, E.; Chen, H. Y.; Chen, Y; Cheng, C.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Qian; Chua, S. E.; Chung, E.S.; Ciani, G.; Clara, F.; Clark, J. A.; Cleva, F.; Coccia, E.; Cohadon, P. -F.; Coila, A.; Collette, C. G.; Constancio, M., Jr.; Conte, A.; Conti, L.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, A.C.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J. -P.; Countryman, S. T.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Craig, K.; Creighton, J. D. E.; Cripe, J.; Crowder, S. G.; Cumming, A.; Cunningham, A.L.; Cuoco, E.; Dal Canton, T.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Darman, N. S.; Dattilo, V.; Dave, I.; Daveloza, H. P.; Davier, M.; Davies, G. S.; Daw, E. J.; Day, R.; Debra, D.; Debreczeni, G.; Degallaix, J.; De laurentis, M.; Deleglise, S.; Del Pozzo, W.; Denker, T.; Dent, T.; Dereli, H.; Dergachev, V.A.; DeRosa, R. T.; Rosa, R.; DeSalvo, R.; Dhurandhar, S.; Diaz, M. C.; Di Fiore, L.; Giovanni, M.G.; Di Lieto, A.; Di Palma, I.; Di Virgilio, A.; Dojcinoski, G.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Douglas, R.; Downes, T. P.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dwyer, S. E.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H. -B.; Ehrens, P.; Eichholz, J. M.; Eikenberry, S. S.; Engels, W.; Essick, R. C.; Etze, T.; Evans, T. M.; Evans, T. M.; Everett, R.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.M.; Fang, Q.; Farinon, S.; Farr, B.; Farr, W. M.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Fiori, I.; Fisher, R. P.; Flaminio, R.; Fletcher, M; Fournier, J. -D.; Franco, S; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gabbard, H. A. G.; Gair, J. R.; Garnrnaitoni, L.; Gaonkar, S. G.; Garufi, F.; Gatto, A.; Gaur, G.; Gehrels, N.; Gemme, G.; Gendre, B.; Genin, E.; Gennai, A.; George, J.; Gergely, L.; Germain, V.; Ghosh, A.; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.P.; Glaefke, A.; Goetz, E.; Goetz, R.; Gondan, L.; Gonzalez, Idelmis G.; Castro, J. M. Gonzalez; Gopakumar, A.; Gordon, N. A.; Gorodetsky, M. L.; Gossan, S. E.; Lee-Gosselin, M.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.M.; Greco, G.; Green, A. C.; Groot, P.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hacker, J. J.; Buffoni-Hall, R.; Hall, E. D.; Hammond, G.L.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, P.J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Hartman, M. T.; Haster, C. -J.; Haughian, K.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Hofman, D.; Hollitt, S. E.; Holt, K.; Holz, D. E.; Hopkins, P.; Hosken, D. J.; Hough, J.; Houston, E. A.; Howell, E. J.; Hu, Y. M.; Huang, S.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Idrisy, A.; Indik, N.; Ingram, D. R.; Inta, R.; Isa, H. N.; Isac, J. -M.; Isi, M.; Islas, G.; Isogai, T.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jang, D.H.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jimenez-Forteza, F.; Johnson, W.; Jones, I.D.; Jones, R.; Jonker, R. J. G.; Ju, L.; Haris, K.; Kalaghatgi, C. V.; Kalogera, V.; Kandhasamy, S.; Kang, G.H.; Kanner, J. B.; Karki, S.; Kasprzack, M.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawazoe, F.; Kefelian, F.; Kehl, M. S.; Keite, D.; Kelley, D. B.; Kells, W.; Kennedy, R.E.; Key, J. S.; Khalaidovski, A.; Khalili, F. Y.; Khan., S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, C.; Kirmo, J.; Kina, K.; Kim, Namjun; Kim, Namjun; Kim, Y.M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Koehlenbeck, S. M.; Kokeyama, K.; Koley, S.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kowalska, I.; Kozak, D. B.; Kringel, V.; Krishnan, B.; Krolak, A.; Krueger, C.; Kuehn, G.; Kumar, P.; Kuo, L.; Kutynia, A.; Lackey, B. D.; Landry, M.; Lange, J.; Lantz, B.; Lasky, P. D.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C.H.; Lee, K.H.; Lee, M.H.; Lee, K.; Lenon, A.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levin, Y.; Levine, B. M.; Li, T. G. F.; Libson, A.; Littenberg, T. B.; Lockerbie, N. A.; Logue, J.; Lombardi, A. L.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lueck, H.; Lundgren, A. P.; Luo, J.; Lynch, R.; Ma, Y.; MacDonald, T.T.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magana-Sandoval, F.; Magee, R. M.; Mageswaran, M.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Mandel, I.; Mandic, V.; MaIlga, V.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marion, F.; Marka, S.; Marka, Z.; Markosyan, A. S.; Maros, E.; Martelli, F.; Martellini, L.; Martin, I. W.; Martin, R.M.; Martynov, D. V.; Marx, J. N.; Mason, K.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Meidam, J.; Melatos, A.; Mendell, G.; Mendoza-Gandara, D.; Mercer, R. A.; Merilh, E. L.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Mezzani, F.; Miao, H.; Michel, C.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, J.; Millhouse, M.; Minenkov, Y.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moggi, A.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, B.C.; Moore, J.C.; Moraru, D.; Gutierrez Moreno, M.; Morriss, S. R.; Mossavi, K.; Mours, B.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, S.D.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D. J.; Murray, P.G.; Mytidis, A.; Nardecchia, I.; Naticchioni, L.; Nayak, R. K.; Necula, V.; Nedkova, K.; Nelemans, G.; Gutierrez-Neri, M.; Neunzert, A.; Newton-Howes, G.; Nguyen, T. T.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Nocera, F.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Oberling, J.; Ochsner, E.; O'De, J.; Oelker, E.; Ogin, G. H.; Oh, J.; Oh, S. H.; Ohme, F.; Oliver, M. B.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; O'Shaughnessy, R.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Paris, H. R.; Parker, W.S; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patrick, Z.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Penn, S.; Pereira, R.R.; Perreca, A.; Phelps, M.; Piccinni, O. J.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Poggiani, R.; Post, A.; Powell, J.; Prasad, J.; Predoi, V.; Premachandra, S. S.; Prestegard, T.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prodi, G. A.; Prokhorov, L. G.; Punturo, M.; Puppo, P.; Puerrer, M.; Qi, H.; Qin, J.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rakhmanov, M.; Rapagnani, P.; Raymond, V.; Razzano, M.; Re, V.; Read, J.; Reed, C. M.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Rew, H.; Ricci, F.; Riles, K.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, J. D.; Romano, R.; Romanov, G.; Romie, J. H.; Rosinska, D.; Rowan, S.; Ruediger, A.; Ruggi, P.; Ryan, K.A.; Sachdev, P.S.; Sadecki, T.; Sadeghian, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sanchez, E. J.; Sandberg, V.; Sandeen, B.; Sanders, J. R.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Schilling, R.; Schmidt, J; Schmidt, P.; Schnabel, R.B.; Schofield, R. M. S.; Schoenbeck, A.; Schreiber, K.E.C.; Schuette, D.; Schutz, B. F.; Scott, J.; Scott, M.S.; Sellers, D.; Sentenac, D.; Sequino, V.; Sergeev, A.; Serna, G.; Setyawati, Y.; Sevigny, A.; Shaddock, D. A.; Shah, S.; Shahriar, M. S.; Shaltev, M.; Shao, Z.M.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sigg, D.; Silva, António Dias da; Simakov, D.; Singer, A; Singer, L. P.; Sillgh, A.; Singh, R.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, R. J. E.; Smith, N.D.; Smith, R. J. E.; Son, E. J.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Srivastava, A. K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Stone, J.R.; Strain, K. A.; Straniero, N.; Stratta, G.; Strauss, N. A.; Strigin, S. E.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sun, L.; Sutton, P. J.; Swinkels, B. L.; Szczepanczyk, M. J.; Tacca, M.D.; Talukder, D.; Tanner, D. B.; Tapai, M.; Tarabrin, S. P.; Taracchini, A.; Taylor, W.R.; Theeg, T.; Thirugnanasambandam, M. P.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Tomlinson, C.; Tonelli, M.; Torres, C. V.; Torrie, C. I.; Toeyrae, D.; Travasso, F.; Traylor, G.; Trifiro, D.; Tringali, M. C.; Trozzo, L.; Tse, M.; Turconi, M.; Tuyenbayev, D.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bake, N.; Van Beuzekom, Martin; van den Brand, J. F. J.; Van Den Broeck, C.F.F.; Vander-Hyde, D. C.; van der Schaaf, L.; van der Sluys, M. V.; van Heijningen, J. V.; van Veggel, A. A.; Vardaro, M.; Vass, S.; Vasuth, M.; Vaulin, R.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P.J.; Venkateswara, K.; Verkindt, D.; Vetrano, F.; Vicere, A.; Vinciguerra, S.; Vine, D. J.; Vinet, J. -Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, MT; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, M.; Wang, X.; Wang, Y.; Ward, R. L.; Warner, J.; Was, M.; Weaver, B.; Wei, L. -W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.M.; Wessels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; White, D. J.; Whiting, B. F.; Williams, D.R.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Wright, J.L.; Wu, G.; Yablon, J.; Yam, W.; Yamamoto, H.; Yancey, C. C.; Yap, M. J.; Yu, H.; Yvert, M.; Zadrozny, A.; Zangrando, L.; Zanolin, M.; Zendri, J. -P.; Zevin, M.; Zhang, F.; Zhang, L.; Zhang, M.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, X. J.; Zucker, M. E.; Zuraw, S. E.; Zweizigl, J.

    2016-01-01

    We present a possible observing scenario for the Advanced LIGO and Advanced Virgo gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We determine the

  16. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    Energy Technology Data Exchange (ETDEWEB)

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1

  17. Preliminary results of multicenter phase II trial of docetaxel (Taxotere) in combination with doxorubicin as first line chemotherapy in Indonesian patients with advanced or metastatic breast cancer.

    Science.gov (United States)

    Muthalib, A; Darwis, I; Prayogo, N; Sutjipto

    2000-05-01

    Docetaxel and doxorubicin have produced a high degree of activity in previously untreated/treated patients with metastatic breast cancer (MBC). The efficacy of Taxotere (T) single agent as 2nd line chemotherapy is well established in large randomized phase III studies. The objective of this study is to confirm the efficacy and safety of a combination of Taxotere with doxorubicin as 1st line chemotherapy in Indonesian MBC patients. TREATMENT AND METHOD: Eighteen patients age < or = 70 years with advanced or metastatic breast cancer (MBC) with no prior taxane chemotherapy or prior cumulative doxorubicin (D) of no more than 250 mg/m2 and no heart disease were enrolled in this phase II study of D (50 mg/m2) IV bolus followed one hour later by Taxotere (T) 60 mg/m2 IV infusion over 1 hour every 3 weeks for 6 cycles treatments. A 3-day oral corticosteroid premedication was administered starting one day before the infusion of each cycle. Left ventricular ejection fraction (LVEF) was evaluated at baseline and after cycle 6. 18 patients (pts) have been treated with 108 cycles administered. Median age was 46 years (31-58), WHO PS 0 = 50%, 1 = 50% and number of organs involved were: 2 (72%), 3 (22%) and 4 (6%). After 3 cycles, partial (PR) and no change (NC) responses occurred in 15 pts (83.3%) and 3 pts (16.7%). The best overall response after 6 cycles, including complete (CR) and partial (PR) responses, occurred in 13 pts (72.2%) including 3 CRs and 10 PRs. Two patients with extensive liver metastases at the baseline had a complete disappearance after 6 cycles. No patients developed congestive heart failure (CHF). Grade 3/4 hematological toxicities included leukopenia in 18 pts (100%), febrile neutropenia in 6 pts (33%), leukopenia with infection in 2 pts (11%), leukopenia with fever in 1 pt (5.5%), and anemia in 6 pts (33.3%). Nonhematological toxicities grade 3/4 included alopecia (61%), asthenia (4.6%), nausea/vomiting (2.7%), pain (2.7%), stomatitis (2.7%), and

  18. Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.

    Science.gov (United States)

    Zhang, Jingjing; Wang, Hao; Jacobson Weiss, Orit; Cheng, Yuejuan; Niu, Gang; Li, Fang; Bai, Chunmei; Zhu, Zhaohui; Chen, Xiaoyuan

    2018-04-13

    Radiolabeled somatostatin analogue therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogues in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-human study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analogue, lutetium-177-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate ( 177 Lu-DOTA-EB-TATE). Methods: Eight patients (6 males and 2 females; age range, 27-61 y) with advanced metastatic neuroendocrine tumors were recruited. Five patients received a single dose 0.35-0.70 GBq (9.5-18.9 mCi) of 177 Lu-DOTA-EB-TATE and underwent serial whole body planar and single-photon emission computed tomography-computed tomography (SPECT-CT) scans at 2, 24, 72, 120 and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177 Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24 and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Results: Administration of 177 Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared with 177 Lu-DOTATATE, 177 Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved 7.9-fold increase of tumor dose delivery. The total body effective doses were 0.205 ± 0.161 mSv/MBq for 177 Lu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for 177 Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receiving 177 Lu-DOTA-EB-TATE than those receiving 177 Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By introducing an albumin binding moiety, 177 Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NET

  19. Five versus ten fractions per week radiotherapy in locally advanced head and neck cancer

    Directory of Open Access Journals (Sweden)

    Ramanjis Viranna Tallari

    2017-01-01

    Conclusions: After induction chemotherapy, HFRT seems to be more efficacious than CFRT in locally advanced HNSCC, by increasing significantly the probability of progression-free survival and locoregional control.

  20. Advances in dental local anesthesia techniques and devices: An update

    Science.gov (United States)

    Saxena, Payal; Gupta, Saurabh K.; Newaskar, Vilas; Chandra, Anil

    2013-01-01

    Although local anesthesia remains the backbone of pain control in dentistry, researches are going to seek new and better means of managing the pain. Most of the researches are focused on improvement in the area of anesthetic agents, delivery devices and technique involved. Newer technologies have been developed that can assist the dentist in providing enhanced pain relief with reduced injection pain and fewer adverse effects. This overview will enlighten the practicing dentists regarding newer devices and methods of rendering pain control comparing these with the earlier used ones on the basis of research and clinical studies available. PMID:24163548

  1. Advances in dental local anesthesia techniques and devices: An update.

    Science.gov (United States)

    Saxena, Payal; Gupta, Saurabh K; Newaskar, Vilas; Chandra, Anil

    2013-01-01

    Although local anesthesia remains the backbone of pain control in dentistry, researches are going to seek new and better means of managing the pain. Most of the researches are focused on improvement in the area of anesthetic agents, delivery devices and technique involved. Newer technologies have been developed that can assist the dentist in providing enhanced pain relief with reduced injection pain and fewer adverse effects. This overview will enlighten the practicing dentists regarding newer devices and methods of rendering pain control comparing these with the earlier used ones on the basis of research and clinical studies available.

  2. Locally Advanced Basal Cell Carcinoma with Intraocular Invasion

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2018-01-01

    Full Text Available We present a 103 - year - old patient, with duration of complaints of about ten years. The initial complaint had been presented as a small nodule, located on the eyebrow, which subsequently ulcerated and encompassed larger regions of the upper and lower eyelids. For the past three years, the patient also had complaints of a worsening of his vision, without seeking for medical help. Within the dermatological examination, an intraocular and periocular localised tumour was established, characterised by a raised peripheral edge and central ulceration. More careful examination revealed that the bulb was fully consumed. The patient refused further diagnosis and treatment. Advanced basal cell carcinomas with intraocular invasion are rare in general. If the patient refuses surgery, radiotherapy and systemic therapy with modern medications such as Vismodegib or Sonidegib are available as treatment options.

  3. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Tyrrell, C J; Kaisary, A V

    2000-01-01

    Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide mo...

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

    Science.gov (United States)

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

    2007-09-15

    The objective of the current study was to determine the histologic and molecular changes that occurred in patients with high-risk, localized prostate cancer (PCa) after neoadjuvant docetaxel chemotherapy. Patients who had locally advanced PCa (serum preoperative [initial] prostate-specific antigen [iPSA] level >or=15 ng/mL, or clinical >or=T2b disease, or biopsy Gleason score [GS] >or=8) and no evidence of metastatic disease received 6 doses of intravenous docetaxel (40 mg/m(2)) administered weekly for 6 weeks followed by radical prostatectomy (RP). The Wilcoxon signed-rank test was used to compare pretreatment and posttreatment markers. Twenty-eight patients completed chemotherapy and underwent RP at the Cleveland Clinic; none achieved a pathologic complete response. Pretreatment diagnostic prostate biopsies (PBx) were reviewed in all patients, and unstained sections of formalin-fixed tissue were available from 11 patients. The median patient age was 62 years (range, 49-72 years), and the median iPSA was 6.8 ng/mL (range, 2.5-24 ng/mL). At a median follow-up of 49.5 months (range, 23-72 months), 12 patients (43%) remained clinically and biochemically free of disease with no additional therapy, and 16 patients (57%) had biochemical failure. The pretreatment GS was 6 in 2 patients (7%), 7 in 10 patients (36%), 8 in 11 patients (39%) and 9 in 5 patients (18%). Two patients (7.1%) had organ-confined disease, and 23 patients (82.1%) had extraprostatic extension. Four patients (14.3%) had positive lymph nodes, and 11 patients (39.3%) had seminal vesicle involvement. Immunohistochemical (IHC) staining for a panel of markers involved in various cellular functions (alpha-methylacyl-coenzyme A racemase [AMACR], beta-tubulin I, beta-tubulin III, cyclin D1, p27, p21, Ki-67, p53, Bcl-2, and an apoptosis detection kit [ApopTag]) was performed on a tissue microarray that contained the posttreatment (RP) tissue specimens and on the PBx specimens, if available. When the IHC

  5. Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

    Science.gov (United States)

    Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

    2012-01-01

    Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

  6. ATN-224 enhances antitumor efficacy of oncolytic herpes virus against both local and metastatic head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ji Young Yoo

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most frequent cancer worldwide, and the 5-year survival rates are among the worst of the major cancers. Oncolytic herpes simplex viruses (oHSV have the potential to make a significant impact in the targeted treatment of these patients. Here, we tested antitumor efficacy of RAMBO, an oHSV armed with the antiangiogenic Vstat120, alone and in conjunction with ATN-224, a copper chelator against HNSCC in vitro and in vivo animal models. We found that all tested HNSCC cells responded well to virus treatment and were sensitive to RAMBO-mediated oncolytic destruction. In vivo, RAMBO had a significant antiangiogenic and antitumorigenic effect. Physiologic levels of copper inhibited viral replication and HNSCC cell killing. Chelation of copper using ATN-224 treatment significantly improved serum stability of RAMBO and permitted systemic delivery in HNSCC tumor xenografts models. Furthermore, our results show that the combination of ATN-224 and RAMBO strongly inhibits lung metastases in a mouse model of HNSCC. These findings suggest that combining ATN-224 with RAMBO has potential for clinical trials in both early and advanced HNSCC patients.

  7. Multidetector CT of Locally Invasive Advanced Gastric Cancer: Value of Oblique Coronal Reconstructed Images for the Assessment of Local Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jin Hee; Kim, Ah Yong; Kim, Hye Jin; Yook, Jeong Hwan; Yu, Eun Sil; Jang, Yoon Jin; Park, Seong Ho; Shin, Yong Moon; Ha, Hyun Kwon [Asan Medical Center, Seoul (Korea, Republic of)

    2010-01-15

    To evaluate the diagnostic value of oblique coronal reconstructed CT images to determine the local invasion of advanced gastric cancer (AGC). Thirty-four consecutive patients, who were suspected to have locally invasive advanced gastric cancer (more than T3 stage) on a preoperative MDCT scan and underwent a diagnostic or curative laparotomy, were enrolled in this study. Two reviewers performed an independent blind review of three series of MDCT images in random order; axial (AXI), conventional coronal (CCI), and oblique coronal (OCI) (parallel to long axis of gastric body and pancreas) images. In assessing the local invasion, the reader's confidence for the local invasion of AGC was graded using a five point scale (1 = definitely negative, 5 = definitely positive: T4). With surgical findings and histopathological proofs as reference standards, the diagnostic performance of the three different plans of CT images was employed for the verification of local invasion of AGC on a preoperative CT scan using the receiver operating characteristic (ROC) method. Agreements between the two reviewers were analyzed using weighted kappa statistics. Results: In 19 out of 34 patients, local invasion was confirmed surgically or histopathologically (13 pancreas invasion, 6 liver invasion, 4 major vascular invasion, 3 colon and mesocolon invasion, and 2 spleen invasion). The diagnostic performance of OCI was superior to AXI or CCI in the local invasion of AGC. The differences in the area under the curve of AXI (0.770 {+-} 0.087, 0.700 {+-} 0.094), CCI (0.884 {+-} 0.058, 0.958 {+-} 0.038), and OCI (0.954 {+-} 0.050, 0.956 {+-} 0.049), were statistically significant for both reviewers. Inter-observer agreement was excellent for OCI ({kappa}= .973), which was greater than CCI (({kappa}= .839), and AXI (({kappa}= .763). On a CT scan, OCI might be a useful imaging technique in evaluating locally invasive advanced gastric cancer.

  8. Advances in local and ablative treatment of oligometastasis in prostate cancer.

    Science.gov (United States)

    Yao, Henry Hi; Hong, Matthew Kh; Corcoran, Niall M; Siva, Shankar; Foroudi, Farshad

    2014-12-01

    Oligometastasis is a state of limited metastatic disease that may be amenable to aggressive local therapy to achieve long-term survival. This review aims to explore the role of ablative radiotherapy and surgical management of prostate cancer (CaP) patients with oligometastasis. We performed a systematic review of the literature from November 2003 to November 2013 in the PubMed and EMBASE databases using structured search terms. From our literature search, we identified 13 cases of oligometastatic CaP managed by surgery. The longest disease-free survival documented was 12 years following pulmonary metastasectomy. We also found 12 studies using radiotherapy to treat oligometastatic CaP with median follow-up ranging from 6 to 43 months. Local control rates and overall survival at 3 years range from 66 to 90% and from 54 to 92%, respectively. Most patients did not report any significant toxicity. The limited current literature suggests oligometastatic CaP may be amenable to more aggressive local ablative therapy to achieve prolonged local control and delay to androgen deprivation therapy (ADT). There is a larger body of evidence supporting the use of radiotherapy than surgery in this disease state. However, no direct comparison with ADT is available to suggest an improvement in overall survival. Further studies are required to determine the role of aggressive-targeted local therapy in oligometastatic CaP. © 2014 Wiley Publishing Asia Pty Ltd.

  9. Salvage Lenvatinib Therapy in Metastatic Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Iñiguez-Ariza, Nicole M; Ryder, Mabel M; Hilger, Crystal R; Bible, Keith C

    2017-07-01

    Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only five months and <20% one-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding the use of lenvatinib in ATC. The aim of this study was to delineate clinical outcomes in a series of patients with advanced ATC in response to lenvatinib therapy. A retrospective analysis was conducted involving all lenvatinib-treated Mayo Clinic ATC patients in 2015. Of 28 distinct ATC patients seen in 2015, three (11%) with metastatic disease of ECOG performance status 2-3 were treated with lenvatinib. Two patients were male; age range at ATC diagnosis was 57-84 years. All three patients attained successful local control of their disease with surgery and/or combined chemoradiotherapy. Lenvatinib was offered as the second, third, or fourth line of therapy at the time of metastatic disease progression. Two patients incurred minor responses to therapy, with structural regression of distant metastatic tumor disease soon after starting lenvatinib treatment (at one to two months), while one patient achieved stable disease, but no Response Evaluation Criteria In Solid Tumors partial responses resulted. Overall survival after starting lenvatinib was two, six, and seven months. Fatigue and hypertension were prominent, and one patient developed pulmonary emboli while on lenvatinib. This initial single-institution experience suggests that lenvatinib may have some disease-modifying activity in metastatic ATC that is otherwise refractory to cytotoxic chemotherapy. Unfortunately, observed benefits were transient, and toxicities were prominent. Clinical trials are required

  10. Wall conditioning and leak localization in the advanced toroidal facility

    International Nuclear Information System (INIS)

    Langley, R.A.; Glowienka, J.C.; Mioduszewski, P.K.; Murakami, M.; Rayburn, T.F.; Simpkins, J.E.; Schwenterly, S.W.; Yarber, J.L.

    1989-01-01

    The Advanced Toroidal Facility (ATF) vacuum vessel and its internal components have been conditioned for plasma operation by baking, discharge cleaning with hydrogen and helium, and gettering with chromium and titanium. The plasma-facing surface of ATF consists mainly of stainless steel with some graphite; the outgassing area is dominated by the graphite because of its open porosity. Since this situation is somewhat different from that in other fusion plasma experiments, in which a single material dominates both the outgassing area and the plasma-facing area, different cleaning and conditioning techniques are required. The situation was aggravated by air leaks in the vacuum vessel, presumably resulting from baking and from vibration during plasma operation. The results of the various cleaning and conditioning techniques used are presented and compared on the basis of residual gas analysis and plasma performance. A technique for detecting leaks from the inside of the vacuum vessel is described; this technique was developed because access to the outside of the vessel is severely restricted by external components. 10 refs., 6 figs., 2 tabs

  11. Wall conditioning and leak localization in the Advanced Toroidal Facility

    International Nuclear Information System (INIS)

    Langley, R.A.; Glowienka, J.C.; Mioduszewski, P.K.; Murakami, M.; Rayburn, T.F.; Simpkins, J.E.; Schwenterly, S.W.; Yarber, J.L.

    1990-01-01

    The Advanced Toroidal Facility (ATF) vacuum vessel and its internal components have been conditioned for plasma operation by baking, discharge cleaning with hydrogen and helium, and gettering with chromium and titanium. The plasma-facing surface of ATF consists mainly of stainless steel with some graphite; the outgassing area is dominated by the graphite because of its open porosity. Since this situation is somewhat different from that in other fusion plasma experiments, in which a single material dominates both the outgassing area and the plasma-facing area, different cleaning and conditioning techniques are required. The situation was aggravated by air leaks in the vacuum vessel, presumably resulting from baking and from vibration during plasma operation. The results of the various cleaning and conditioning techniques used are presented and compared on the basis of residual gas analysis and plasma performance. A technique for detecting leaks from the inside of the vacuum vessel is described. This technique was developed because access to the outside of the vessel is severely restricted by external components

  12. PET/CT-guided percutaneous biopsy of FDG-avid metastatic bone lesions in patients with advanced lung cancer: a safe and effective technique

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Wei; Hao, Bing; Chen, Hao-jun; Zhao, Long; Luo, Zuo-ming; Wu, Hua; Sun, Long [The First Affiliated Hospital of Xiamen University, Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Hospital, Xiamen (China)

    2017-01-15

    {sup 18}F-FDG PET/CT should be performed before a diagnostic biopsy site is chosen in patients with a high clinical suspicion of aggressive, advanced tumour. The aim of this study was to evaluate the safety and efficacy of {sup 18}F-FDG PET/CT in guiding biopsy of bone metastases in patients with advanced lung cancer. PET/CT-guided percutaneous core biopsies were performed in 51 consecutive patients with suspected lung cancer and {sup 18}F-FDG-avid bone lesions after whole-body {sup 18}F-FDG PET/CT scans. Generally, one tissue sample was obtained from each patient. The final diagnoses were established on the basis of the histology results. The histopathological and molecular testing results were systematically evaluated. A total of 53 samples were obtained for histological examination or molecular testing as a second biopsy was required in two patients in whom the pathological diagnosis was unclear following the first biopsy. The pathological diagnosis and lung cancer classification were confirmed in 48 patients. The epidermal growth factor receptor mutation status was determined in 23 biopsies, and the mutation rate was 30.4 % (7/23). The anaplastic lymphoma kinase mutation status was determined in 19 biopsies, and the mutation rate was 31.6 % (6/19). Two of the 51 biopsies were positive for non-Hodgkin's lymphoma and one was positive for metastatic renal cell carcinoma. The first-time diagnostic success rate of biopsy was 96.1 % (49/51) and the overall diagnostic success rate and sensitivity were 100 %. All 51 patients were eventually confirmed as having stage IV disease. No serious complications were encountered and the average biopsy time was 30 min. PET/CT-guided percutaneous biopsy of {sup 18}F-FDG-avid bone metastases is an effective and safe method that yields a high diagnostic success rate in the evaluation of hypermetabolic bone lesions in patients with suspected advanced lung cancer. (orig.)

  13. Evolution of Randomized Trials in Advanced/Metastatic Soft Tissue Sarcoma: End Point Selection, Surrogacy, and Quality of Reporting.

    Science.gov (United States)

    Zer, Alona; Prince, Rebecca M; Amir, Eitan; Abdul Razak, Albiruni

    2016-05-01

    Randomized controlled trials (RCTs) in soft tissue sarcoma (STS) have used varying end points. The surrogacy of intermediate end points, such as progression-free survival (PFS), response rate (RR), and 3-month and 6-month PFS (3moPFS and 6moPFS) with overall survival (OS), remains unknown. The quality of efficacy and toxicity reporting in these studies is also uncertain. A systematic review of systemic therapy RCTs in STS was performed. Surrogacy between intermediate end points and OS was explored using weighted linear regression for the hazard ratio for OS with the hazard ratio for PFS or the odds ratio for RR, 3moPFS, and 6moPFS. The quality of reporting for efficacy and toxicity was also evaluated. Fifty-two RCTs published between 1974 and 2014, comprising 9,762 patients, met the inclusion criteria. There were significant correlations between PFS and OS (R = 0.61) and between RR and OS (R = 0.51). Conversely, there were nonsignificant correlations between 3moPFS and 6moPFS with OS. A reduction in the use of RR as the primary end point was observed over time, favoring time-based events (P for trend = .02). In 14% of RCTs, the primary end point was not met, but the study was reported as being positive. Toxicity was comprehensively reported in 47% of RCTs, whereas 14% inadequately reported toxicity. In advanced STS, PFS and RR seem to be appropriate surrogates for OS. There is poor correlation between OS and both 3moPFS and 6moPFS. As such, caution is urged with the use of these as primary end points in randomized STS trials. The quality of toxicity reporting and interpretation of results is suboptimal. © 2016 by American Society of Clinical Oncology.

  14. Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer

    NARCIS (Netherlands)

    Rombouts, S. J. E.; Vogel, J. A.; van Santvoort, H. C.; van Lienden, K. P.; van Hillegersberg, R.; Busch, O. R. C.; Besselink, M. G. H.; Molenaar, I. Q.

    2015-01-01

    BackgroundLocally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic

  15. A review of recent advances in numerical modelling of local scour problems

    DEFF Research Database (Denmark)

    Sumer, B. Mutlu

    2014-01-01

    A review is presented of recent advances in numerical modelling of local scour problems. The review is organized in five sections: Highlights of numerical modelling of local scour; Influence of turbulence on scour; Backfilling of scour holes; Scour around complex structures; and Scour protection ...

  16. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    Blackstock, A. William; Farmer, Michael R.; Lovato, James; Mishra, Girish; Melin, Susan A.; Oaks, Timothy; Aklilu, Mabea; Clark, Paige B.; Levine, Edward A.

    2006-01-01

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival

  17. Postoperative adjuvant chemoradiation in completely resected locally advanced gastric cancer

    International Nuclear Information System (INIS)

    Arcangeli, Giorgio; Saracino, Biancamaria; Arcangeli, Giancarlo; Angelini, Francesco; Marchetti, Paolo; Tirindelli Danesi, Donatella

    2002-01-01

    Background: The 5-year survival of patients with completely resected node-positive gastric cancer ranges from 15% to 25%. We explored the feasibility of a chemoradiation regime consisting of concomitant hyperfractionated radiotherapy and 5-fluorouracil protracted venous infusion (5-FU PVI). Materials and Methods: Forty patients received a total or partial gastrectomy operation and D2 nodal resection for Stage III gastric cancer; they were then irradiated by linac with 6-15-MV photons. The target included the gastric bed, the anastomosis, stumps, and regional nodes. A total dose of 55 Gy was given in 50 fractions using 1.1 Gy b.i.d. All patients received a concomitant 200 mg/m2/day 5-FU PVI. Patients were examined during the follow-up period as programmed. Toxicity was recorded according to RTOG criteria. Results: After a median follow-up of 75.6 months (range: 22-136 months), 24 (60%) patients had died, and 16 (40%) were alive and free of disease. The 5-year actuarial incidence of relapse was 39%, 22%, and 2% for distant metastases, out-field peritoneal seeding, and in-field local regional recurrences, respectively. The 5-year actuarial cause-specific survival was 43%. Three patients survived more than 11 years. Acute ≥ Grade 3 toxicity consisted of hematologic (22.5%) and gastrointestinal toxicity (nausea and vomiting 22.5%, diarrhea 2.8%, and abdominal pain 2.6%). No late toxicity was observed. Conclusion: This regime of concomitant 5-FU PVI and hyperfractionated radiotherapy was well tolerated and resulted in successful locoregional control and satisfactory survival

  18. Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    Nguyen, Nam P; Desai, Anand; Smith-Raymond, Lexie; Jang, Siyoung; Vock, Jacqueline; Vinh-Hung, Vincent; Chi, Alexander; Vos, Paul; Pugh, Judith; Vo, Richard A; Ceizyk, Misty

    2014-01-01

    In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications

  19. Adjuvant hysterectomy after radiochemotherapy for locally advanced cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hass, Peter [Universitaetsklinikum Magdeburg, Department of Radiation Oncology, Magdeburg (Germany); Eggemann, Holm; Costa, Serban Dan; Ignatov, Atanas [Otto-von-Guericke University, Department of Obstetrics and Gynecology, Magdeburg (Germany)

    2017-12-15

    External beam radiation therapy (EBRT) with concomitant chemotherapy (cCT) (=RCT) plus intracavitary (±interstitial) brachytherapy (iBT) is standard of care for advanced cervical cancer. The aim of this study was to evaluate morbidity and survival outcome of simple adjuvant hysterectomy (AH) after EBRT/cCT and to compare it with the standard treatment. Patients with FIGO stage III cervical cancer were treated with EBRT/cCT and then divided in two groups: group 1 was further treated with standard intracavitary/interstitial BT, while group 2 underwent AH. From 881 women with cervical cancer, 248 were eligible for analysis: 161 received iBT and 87 underwent AH. The median follow-up of the study was 53 months. Clinical and pathological characteristics were well balanced in the two groups. After EBRT/cCT, complete clinical response was observed in 121 (48.8%) of 246 patients. Clinical complete response was observed in 81 (50.3%) of 161 patients in group 1. At 6 weeks after EBRT/cCT, 40 (46.0%) of 87 patients in the surgery group had pathological complete response. Intra- and postoperative complications were observed in 10 (11.5%) of 87 cases. The rates of locoregional recurrence and metastasis were similar in both groups. Progression-free (PFS) and disease-specific overall survival (DOS) for these patients were similar between the control and surgery group. Interestingly, PFS and DOS were significantly improved by AH for the patients with residual tumor. AH could improve survival in patients with residual disease after RCT and is characterized by a low complication rate. (orig.) [German] Die Teletherapie (EBRT) mit begleitender Chemotherapie (cCT), entsprechend einer Radiochemotherapie (RCT), plus intrakavitaere (± interstitielle) Brachytherapie (iBT) ist Standard in der Behandlung des fortgeschrittenen Zervixkarzinoms. Ziel dieser Studie war es, die Morbiditaet und das Ueberleben zwischen der einfachen adjuvanten Hysterektomie (AH) nach EBRT/cCT und dem

  20. Effects on functional outcome after IORT-containing multimodality treatment for locally advanced primary and locally recurrent rectal cancer

    International Nuclear Information System (INIS)

    Mannaerts, Guido H.H.; Rutten, Harm J.T.; Martijn, Hendrik; Hanssens, Patrick E.J.; Wiggers, Theo

    2002-01-01

    Purpose: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer, much attention is focused on the oncologic outcome. Little is known about the functional outcome. In this study, the functional outcome after a multimodality treatment for locally advanced primary and locally recurrent rectal cancer is analyzed. Methods and Materials: Between 1994 and 1999, 55 patients with locally advanced primary and 66 patients with locally recurrent rectal cancer were treated with high-dose preoperative external beam irradiation, followed by extended surgery and intraoperative radiotherapy. To assess long-term functional outcome, all patients still alive (n = 97) were asked to complete a questionnaire regarding ongoing morbidity, as well as functional and social impairment. Seventy-six of the 79 patients (96%) returned the questionnaire. The median follow-up was 14 months (range: 4-60 months). Results: The questionnaire revealed fatigue in 44%, perineal pain in 42%, radiating pain in the leg(s) in 21%, walking difficulties in 36%, and voiding dysfunction in 42% of the patients as symptoms of ongoing morbidity. Functional impairment consisted of requiring help with basic activities in 15% and sexual inactivity in 56% of the respondents. Social handicap was demonstrated by loss of former lifestyle in 44% and loss of professional occupation in 40% of patients. Conclusions: As a result of multimodality treatment, the majority of these patients have to deal with long-term physical morbidity, the need for help with daily care, and considerable social impairment. These consequences must be weighed against the chance of cure if the patient is treated and the disability eventually caused by uncontrolled tumor progression if the patient is not treated. These potential drawbacks should be discussed with the patient preoperatively and taken into account when designing a treatment strategy

  1. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer

    NARCIS (Netherlands)

    Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Cho, Jae Yong; Schellens, Jan H M; Soria, Jean Charles; Wen, Patrick Y; Zielinski, Christoph; Cabanillas, Maria E; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima; Keam, Bhumsuk

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit.

  2. Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Nikaedo Sueli M

    2004-09-01

    Full Text Available Abstract Background Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC can be achieved with cisplatin-based chemotherapy (CT, its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. Methods In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years, younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2, and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2. We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Results Analysis was by intention to treat. Main toxicities (grade 3–4 was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP and overall survival (OS were 27.0 (95% CI: 10.1 to 43.7 weeks and 30.1 (95% CI: 24.4 to 35.8 weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%, with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Conclusion Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions.

  3. SIAH and EGFR, Two RAS Pathway Biomarkers, are Highly Prognostic in Locally Advanced and Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Lauren L. Siewertsz van Reesema

    2016-09-01

    Funding: This work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang; Center for Innovative Technology (CIT-Commonwealth Research Commercialization Fund (CRCF (MF14S-009-LS to A.H. Tang, and National Cancer Institute (CA140550 to A.H. Tang.

  4. Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Pereira, José Rodrigues; Martins, Sandro J; Nikaedo, Sueli M; Ikari, Flora K

    2004-01-01

    Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m 2 , on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m 2 or 90 mg/m 2 ), and older patients were allocated to lower cisplatin doses (60 mg/m 2 or 70 mg/m 2 ). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Analysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions

  5. Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report

    Directory of Open Access Journals (Sweden)

    Patricia Miranda Romero

    2015-02-01

    Full Text Available Trastuzumab emtansina (T-DM1 is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC, who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS and the overall survival (OS. It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 €. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at € 70,490,850. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients

  6. Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

    Science.gov (United States)

    2018-03-05

    Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  7. Conformal radiotherapy of locally advanced bile duct carcinoma; Radiotherapie conformationnelle des cholangiocarcinomes de la voie biliaire principale localement evolues

    Energy Technology Data Exchange (ETDEWEB)

    Bouras, N.; Caudry, M.; Bonnel, C.; Trouette, R.; Demeaux, H.; Maire, J.P. [Centre Hospitalier Universitaire, Hopital Saint-Andre, Service de Radiotherapie, 33 - Bordeaux (France); Saric, J.; Rullier, E. [Centre Hospitalier Universitaire, Hopital Saint-Andre, Service de Chirurgie Viscerale et de Transplantation Hepatique, 33 - Bordeaux (France)

    2002-02-01

    Purpose. - Retrospective study of 23 patients treated with conformal radiotherapy for a locally advanced bile duct carcinoma. Patients and methods. - Eight cases were irradiated after a radical resection (RO), because they were N+; seven after microscopically incomplete resection (R1) ; seven were not resected (R2). A dose of 45 of 50 Gy was delivered, followed by a boost up to 60 Gy in R1 and R2 groups. Concomitant chemotherapy was given in 15 cases. Results.-Late toxicity included a stenosis of the duodenum, and one of the biliary anastomosis. Two patients died from cholangitis, the mechanism of which remains unclear. Five patients are in complete remission, six had a local relapse, four developed a peritoneal carcinosis, and six distant metastases. Actuarial survival rate is 75%, 28% and 7% at 1, 3 and 5 years, respectively (median: 16.5 months). Seven patients are still alive with a 4 to 70 months follow-up. Survival is similar in the 3 small subgroups. The poor local control among RON+ cases might be related to the absence of a boost to the 'tumor bed'. In R1 patients, relapses were mainly distant metastases, where'as local and peritoneal recurrences predominated in R2. Conclusion. - Conformal radio-chemotherapy delivering 60 Gy represents a valuable palliative approach in locally advanced biliary carcinoma. (authors)

  8. Concomitant chemo-radiotherapy for the locally advanced rectum cancer; Chimioradiotherapie concomitante dans le cancer du rectum localement evolue

    Energy Technology Data Exchange (ETDEWEB)

    Haoui, M.; Aksil, N.; Boualga, K.; Moussaoui, D.; Ladj, O. [Service de radiotherapie-oncologie, centre anti-cancer, Blida (Algeria)

    2010-10-15

    The authors report a retrospective study which aimed at assessing the use of a concomitant chemo-radiotherapy, its tolerance and its feasibility in the case of a locally advanced rectum cancer. Based on data obtained among 62 patients presenting a rectum cancer, they analyse the results in terms of tolerance (cases of leukopenia, anemia, diarrhea, radiodermatitis), of relapses, and survival. Toxicity is acceptable and the concomitant treatment renders the tumour operable in many cases. Short communication

  9. Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

    Science.gov (United States)

    Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

    2017-09-01

    The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

  10. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Kristiansen, C.; Loft, A.; Berthelsen, Anne Kiil

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography Udgivelsesdato: 2008/1...... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared to histopathologic...

  11. PET/CT and Histopathologic Response to Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Loft, Annika; Berthelsen, Anne K

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography....... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral(R) (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared...

  12. Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Janjan, Nora A.; Crane, Christopher N.; Feig, Barry W.; Cleary, Karen; Dubrow, Ronelle; Curley, Steven A.; Ellis, Lee M.; Vauthey, Jean-Nicolas; Lenzi, Renato; Lynch, Patrick; Wolff, Robert; Brown, Thomas; Pazdur, Richard; Abbruzzese, James; Hoff, Paulo M.; Allen, Pamela; Brown, Barry; Skibber, John

    2000-01-01

    Rationale: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. Methods and Materials: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m 2 ) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). Results: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per

  13. Radiotherapy and local hyperthermia plus androgen suppression in locally advanced prostate cancer

    International Nuclear Information System (INIS)

    Maluta, S.; Marciai, N.; Gabbani, M.; Palazzi, M.; Dall'Oglio, S.; Grandinetti, A.

    2005-01-01

    Full text: In advanced prostatic cancer, hyperthermia may be useful in order to enhance irradiation efficacy so to avoid delivering of too high dose of radiotherapy which increases acute and late sequelae. A multi-centric phase II study is warranted to give hyperthermia a level 3 evidence in prostate cancer treatment. A randomized phase III study to demonstrate efficacy of hyperthermia is not available because of the optimal results obtained by using radiotherapy combined with androgen suppression. To evaluate hyperthermia gain, LHT should be combined with radiotherapy alone in patients refusing androgen suppression or affected by hormone refractory prostate carcinoma (HRPC). Patients with HRPC have multiple possibilities of treatment improving performance status and median survival, as chemotherapy regimens, and new agents. All these treatments modalities need to be confirmed by phase III trials. Also hyperthermia may be considered among these promising approaches. (author)

  14. Phase II study of capecitabine (Xeloda (registered) ) and concomitant boost radiotherapy in patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Krishnan, Sunil; Janjan, Nora A.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Wolff, Robert A.; Das, Prajnan; Delclos, Marc E.; Chang, George J.; Hoff, Paulo M.; Eng, Cathy; Brown, Thomas D.; Crane, Christopher H.; Feig, Barry W.; Morris, Jeffrey; Vadhan-Raj, Saroj; Hamilton, Stanley R.; Lin, Edward H.

    2006-01-01

    Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda (registered) ), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC). Methods and Materials: We conducted a phase II study of capecitabine (825 mg/m 2 orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative ≥T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters. Results: Of the 54 patients (median age, 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (<10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor ≤5 cm from the anal verge was 67% (18/27). Conclusion: This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC

  15. Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Botrel, Tobias Engel Ayer; Clark, Luciana Gontijo de Oliveira; Paladini, Luciano; Clark, Otávio Augusto C.

    2016-01-01

    Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher

  16. Chemotherapy and intensity modulated conformational radiotherapy for locally advanced pancreas cancers

    International Nuclear Information System (INIS)

    Huguet, F.; Wu, A.; Zhang, Z.; Winston, C.; Reidy, D.; Ho, A.; Allen, P.; Karyn, G.

    2011-01-01

    The authors report a retrospective study of the tolerance and survival of 48 patients who have been treated by a chemotherapy followed by a chemotherapy concomitant with an intensity-modulated radiotherapy for a locally advanced pancreas cancer. Results are discussed in terms of toxicity, cancer response, operability, survival rate. Tolerance is good. Local control rates, global survival rates and secondary resection rates are promising. Short communication

  17. Cervical cancer stem cells and correlation with radiation response in locally advanced cervical cancer

    International Nuclear Information System (INIS)

    Chopra, Supriya; Goda, Jayant Sastri; Deodhar, Kedar

    2016-01-01

    While tumour-initiating cells (TIC) have been reported across solid tumours, there is dearth of data regarding TICs and radiation response in cervical cancer. From October, 2013- July, 2015 patients with locally advanced cervical cancer were included. Pretreatment biopsy was obtained. IHC was performed for SOX-2,OCT-4, Nanog (ESC), CD44 and Podoplanin (TIC). Semiquantitative scoring was used for IHC. All patients received uniform concurrent chemoradiation and brachytherapy. On follow up, local control and distant relapse was recorded

  18. Autoantibodies May Predict Immune-Related Toxicity: Results from a Phase I Study of Intralesional Bacillus Calmette–Guérin followed by Ipilimumab in Patients with Advanced Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Jessica Da Gama Duarte

    2018-03-01

    Full Text Available Immune checkpoint inhibitors (ICIs have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4; however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL bacillus Calmette–Guérin (BCG, a living attenuated strain of Mycobacterium bovis, was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection. We evaluated these two immune stimulants in combination with melanoma with the aim of developing a more effective immunotherapy and to assess toxicity. In this phase I study, patients with histologically confirmed stage III/IV metastatic melanoma received IL BCG injection followed by up to four cycles of intravenous ipilimumab (anti-CTLA-4 (ClinicalTrials.gov number NCT01838200. The trial was discontinued following treatment of the first five patients as the two patients receiving the escalation dose of BCG developed high-grade immune-related adverse events (irAEs typical of ipilimumab monotherapy. These irAEs were characterized in both patients by profound increases in the repertoire of autoantibodies directed against both self- and cancer antigens. Interestingly, the induced autoantibodies were detected at time points that preceded the development of symptomatic toxicity. There was no overlap in the antigen specificity between patients and no evidence of clinical responses. Efforts to increase response rates through the use of novel immunotherapeutic combinations may be associated with higher rates of irAEs, thus the imperative to identify biomarkers of toxicity remains strong. While the small patient numbers in this trial do not allow for any conclusive evidence of predictive biomarkers, the observed changes warrant further examination of autoantibody repertoires in larger patient cohorts at risk of developing irAEs during their

  19. The prognostic values of CYP2B6 genetic polymorphisms and metastatic sites for advanced breast cancer patients treated with docetaxel and thiotepa.

    Science.gov (United States)

    Song, Qingkun; Zhou, Xinna; Yu, Jing; Dong, Ningning; Wang, Xiaoli; Yang, Huabing; Ren, Jun; Lyerly, H Kim

    2015-11-25

    This study investigated interactive effects of CYP2B6 genotypes and liver metastasis on the prognosis of metastatic breast cancer patients who received combined chemotherapy of docetaxel and thiotepa. Totally 153 patients were retrospectively genotyped rs8192719 (c.1294 + 53C > T) and rs2279343 (c.785A > G). Kaplan-Meier method and Cox Proportional Hazard Regression model were used to estimate the survival. Patients with liver metastasis had worsen prognosis, conferring a 2.26-fold high risk of progression and 1.93-fold high risk of death (p T) and AG genotype of rs2279343 (c.785A > G) prolonged survival (p G) was associated with a 47% reduced risk of death and a 6-month-longer overall survival (p T) were 0.45 for progression and 0.40 for death; and the corresponding survival was improved by 6 months and 16 months, respectively (p < 0.05). Genotypes of CYP2B6 had an interaction with clinical efficacy of docetaxel and thiotepa on metastatic breast cancer patients; and metastatic sites also affected clinical responses. Further therapies should take into account of chemotherapy regimen, genotypes of metabolizing enzymes and metastatic sites for the particular subpopulation.

  20. Nivolumab-induced new-onset seronegative rheumatoid arthritis in a patient with advanced metastatic melanoma: A case report and literature review.

    Science.gov (United States)

    Haikal, Ammar; Borba, E; Khaja, Taqui; Doolittle, Gary; Schmidt, Paul

    2018-01-01

    Immune-related adverse events have been reported in patients treated with anti-programmed death-1 receptor drugs such as nivolumab. We present a case of a new-onset seronegative rheumatoid arthritis in a patient with metastatic melanoma treated with nivolumab.

  1. Women with inoperable or locally advanced breast cancer -- what characterizes them?

    DEFF Research Database (Denmark)

    El-Charnoubi, Waseem Asim Ghulam; Svendsen, Jesper Brink; Tange, Ulla Brix

    2012-01-01

    Breast cancer is the most common cancer among Danish women. Locally advanced breast cancer occurs in a relatively large proportion of all new primary breast cancer diagnoses and for unexplained reasons 20-30% of women with breast cancer wait more than eight weeks from the initial breast cancer...

  2. Acute toxicity after a diverting stoma and spacer prior to chemoradiation in locally advanced rectal cancer

    NARCIS (Netherlands)

    Van Der Voort Van Zyp, Jochem R N; Ceha, Heleen M.; Niehe, Valerie; Marinelli, Andreas W K S; Putter, Hein; Marijnen, Corrie A M

    2015-01-01

    Abstract Background and purpose Chemoradiotherapy (CRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC). For grade ≥3 acute diarrhea there is a relationship between dose and irradiated small bowel volume. The aim of this study was to evaluate whether combined

  3. Individualised 3D printed vaginal template for MRI guided brachytherapy in locally advanced cervical cancer

    DEFF Research Database (Denmark)

    Lindegaard, Jacob Christian; Lænsø Madsen, Mads; Hansen, Anders Traberg

    2016-01-01

    Intracavitary–interstitial applicators for MRI guided brachytherapy are becoming increasingly important in locally advanced cervical cancer. The 3D printing technology enables a versatile method for obtaining a high degree of individualisation of the implant. Our clinical workflow is presented...

  4. Case Report: Down-staging locally advanced head and neck cancer ...

    African Journals Online (AJOL)

    Case Report: Down-staging locally advanced head and neck cancer in an HIV infected patient in a limited resource setting. L Masamba, D Nkosi, D Kumiponjera. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals ...

  5. Feasibility of stereotactic body radiotherapy for locally-advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Katrina Woodford

    2017-10-01

    Full Text Available SBRT was feasible for approximately half of the locally-advanced NSCLC patients we assessed and for these patients has the potential to reduce a 30 fraction course to 12 fractions. Using SBRT in this setting requires compromises in techniques and further compromises may allow SBRT in a greater proportion of patients.

  6. Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Ploen, John; Vuong, Té

    2012-01-01

    PURPOSE: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation...

  7. Computed tomography findings after radiofrequency ablation in locally advanced pancreatic cancer

    NARCIS (Netherlands)

    Rombouts, Steffi J. E.; Derksen, Tyche C.; Nio, Chung Y.; van Hillegersberg, Richard; van Santvoort, Hjalmar C.; Walma, Marieke S.; Molenaar, Izaak Q.; van Leeuwen, Maarten S.

    2018-01-01

    The purpose of the study was to provide a systematic evaluation of the computed tomography(CT) findings after radiofrequency ablation (RFA) in locally advanced pancreatic cancer(LAPC). Eighteen patients with intra-operative RFA-treated LAPC were included in a prospective case series. All CT-scans

  8. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    Science.gov (United States)

    2018-03-28

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  9. Clinical implementation of coverage probability planning for nodal boosting in locally advanced cervical cancer

    DEFF Research Database (Denmark)

    Ramlov, Anne; Assenholt, Marianne S; Jensen, Maria F

    2017-01-01

    PURPOSE: To implement coverage probability (CovP) for dose planning of simultaneous integrated boost (SIB) of pathologic lymph nodes in locally advanced cervical cancer (LACC). MATERIAL AND METHODS: CovP constraints for SIB of the pathological nodal target (PTV-N) with a central dose peak...

  10. Liquid fiducial marker performance during radiotherapy of locally advanced non small cell lung cancer

    DEFF Research Database (Denmark)

    Rydhög, Jonas Scherman; Mortensen, Steen Riisgaard; Larsen, Klaus Richter

    2016-01-01

    We analysed the positional and structural stability of a long-term biodegradable liquid fiducial marker (BioXmark) for radiotherapy in patients with locally advanced lung cancer. Markers were injected via endoscopic- or endobronchial ultrasound in lymph nodes and reachable primary tumours. Marker...

  11. Radical prostatectomy in the 21st century - the gold standard for localized and locally advanced prostate cancer.

    Science.gov (United States)

    Schostak, M; Miller, K; Schrader, M

    2008-01-01

    Radical prostatectomy for treatment of prostate cancer is a technically sophisticated operation. Simpler therapies have therefore been developed in the course of decades. The decisive advantage of a radical operation is the chance of a cure with minimal collateral damage. It is the only approach that enables precise tumor staging. The 10-year progression-free survival probability is approximately 85% for a localized tumor with negative resection margins. This high cure rate is unsurpassed by competitive treatment modalities. Nowadays, experienced surgeons achieve excellent functional results (for example, recovery of continence and erectile function) with minimum morbidity. Even in the locally advanced stage, results are very good compared to those obtained with other treatment modalities. Pathological staging enables stratified adjuvant therapy based on concrete information. The overall prognosis can thus be significantly improved.

  12. A comparison of tumor motion characteristics between early stage and locally advanced stage lung cancers

    International Nuclear Information System (INIS)

    Yu, Z. Henry; Lin, Steven H.; Balter, Peter; Zhang Lifei; Dong Lei

    2012-01-01

    Purpose: With the increasing use of conformal radiation therapy methods for non-small cell lung cancer (NSCLC), it is necessary to accurately determine respiratory-induced tumor motion. The purpose of this study is to analyze and compare the motion characteristics of early and locally advanced stage NSCLC tumors in a large population and correlate tumor motion with position, volume, and diaphragm motion. Methods and materials: A total of 191 (94 early stage, 97 locally advanced) non-small cell lung tumors were analyzed for this study. Each patient received a four-dimensional CT scan prior to receiving radiation treatment. A soft-tissue-based rigid registration algorithm was used to track the tumor motion. Tumor volumes were determined based on the gross tumor volume delineated by physicians in the end of expiration phase. Tumor motion characteristics were correlated with their standardized tumor locations, lobe location, and clinical staging. Diaphragm motion was calculated by subtracting the diaphragm location between the expiration and the inspiration phases. Results: Median, max, and 95th percentile of tumor motion for early stage tumors were 5.9 mm, 31.0 mm, and 20.0 mm, which were 1.2 mm, 12 mm, and 7 mm more than those in locally advanced NSCLC, respectively. The range of motion at 95th percentile is more than 50% larger in early stage lung cancer group than in the locally advanced lung cancer group. Early stage tumors in the lower lobe showed the largest motion with a median motion of 9.2 mm, while upper/mid-lobe tumors exhibited a median motion of 3.3 mm. Tumor volumes were not correlated with motion. Conclusion: The range of tumor motion differs depending on tumor location and staging of NSCLC. Early stage tumors are more mobile than locally advanced stage NSCLC. These factors should be considered for general motion management strategies when 4D simulation is not performed on individual basis.

  13. First case report of locally advanced malignant nodular hidradenoma of the scrotum.

    Science.gov (United States)

    Shah, Binay K; Qamruzzaman, Yusuf; Serban, Karina; Hire, Ervin; Ying, Shan-Ching

    2010-01-01

    Malignant nodular hidradenoma (MNH) is a malignant tumor of the eccrine glands, and most commonly involves the head, trunk, and extremities. To the best of our knowledge, MNH of the scrotum has not yet been described in the English literature. Despite the use of surgery, chemotherapy, radiotherapy, and hormonal therapy, optimal treatment of MNH is unclear. We describe the case of a 30-year-old African American man who was diagnosed with locally advanced MNH of the scrotum and treated with surgery. More than 2 years after surgery, the patient is without evidence of disease. This is the first case report of MNH of the scrotum. Surgery alone may be sufficient for the treatment of localized or locally advanced MNH. Copyright © 2010 S. Karger AG, Basel.

  14. The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Christopher R; Khandelwal, Shiv R; Schmidt-Ullrich, Rupert K; Ravalese, Joseph; Wazer, David E

    1995-06-15

    Purpose: Current methods to clinically define head and neck tumor bulk are qualitative and imprecise. Although the American Joint Committee on Cancer (AJCC) staging system is important for this purpose, limitations exist. This study will investigate the prognostic value of computed tomography (CT) derived tumor volume measurements in comparison to AJCC stage and other significant variables. Materials and Methods: Seventy-six patients with advanced head and neck squamous cell carcinoma were treated with concomitant boost accelerated superfractionated irradiation. Doses ranged from 68.4-73.8 Gy (median 70.2 Gy). Good quality pretherapy CT scans were available in 51 patients. Total tumor volume (TTV) estimates were derived from these scans using digital integration of primary tumor and metastatic lymphadenopathy. Actuarial and multivariate statistical techniques were applied to analyze local control. Results: Thirty-six-month local control was 63%. TTV ranged from 5-196 cm{sup 3} (median 35 cm{sup 3}) for all cases, 5-142 cm{sup 3} (median 17 cm{sup 3}) for those controlled, and 16-196 cm{sup 3} (median 47 cm{sup 3}) for local failures. There was a significant increase in failures above 35 cm{sup 3}. Univariate analysis found that TTV, T-stage, N-stage, and primary site were each significant prognostic variables. Local control for TTV {<=}35 cm{sup 3} was 92% at 36 months vs. 34% for TTV >35 cm{sup 3} (p = 0.0001). Multivariate analysis, however, found that TTV, primary site, and sex were important as independent variables; T and N stage were not independently significant unless TTV was removed from the model. Conclusions: This study demonstrates the prognostic significance of TTV in advanced carcinoma of the head and neck. This variable appears to be a more predictive than AJCC clinical stage. Quantitative tumor volume measurements may prove to be a useful parameter in future analyses of head and neck cancer.

  15. Combined modality treatment including intraoperative radiotherapy in locally advanced and recurrent rectal cancer

    International Nuclear Information System (INIS)

    Tveit, Kjell Maque; Wiig, Johan N.; Olsen, Dag Rune; Storaas, Andreas; Poulsen, Jan Peter; Giercksky, Karl-Erik

    1997-01-01

    Background: Treatment of locally advanced and recurrent rectal cancer usually has a high local recurrence rate and poor survival. Promising results have been reported by combined external radiotherapy, extensive surgery and intraoperative radiotherapy (IORT). Methods: One hundred fifteen patients with locally advanced rectal cancers fixed to the pelvic wall or locally recurrent rectal cancers underwent preoperative external radiotherapy with 46-50 Gy. Six to 8 weeks later radical pelvic surgery was attempted, and was combined with intraoperative electron beam radiotherapy (15-20 Gy) in 66 patients. The patients were followed closely to evaluate complication rate, local and distant recurrence rate and survival. Results: Surgery with no macroscopic tumour remaining was obtained in 65% of the patients with no postoperative deaths. Pelvic infection was the major complication (21%). Although the observation time is short (3-60 months), the local recurrence rate seems low (22%) and survival seems promising (about 60% at 4 years) in patients with complete tumour resection, in contrast to patients with residual tumour (none living at 4 years). Conclusions: The combined modality treatment with preoperative external radiotherapy and extensive pelvic surgery with IORT is sufficiently promising to start a randomized trial on the clinical value of IORT as a boost treatment in the multidisciplinary approach to this disease

  16. Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

    Science.gov (United States)

    2017-07-15

    Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

  17. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma

    International Nuclear Information System (INIS)

    Hoyer, Morten; Roed, Henrik; Sengelov, Lisa; Traberg, Anders; Ohlhuis, Lars; Pedersen, Jorgen; Nellemann, Hanne; Kiil Berthelsen, Anne; Eberholst, Frey; Engelholm, Svend Aage; Maase, Hans von der

    2005-01-01

    Background and purpose: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. Patients and methods: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. Results: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. Conclusions: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma

  18. Association between obesity and local control of advanced rectal cancer after combined surgery and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Seon; Park, Sung Kwang; Cho, Heung Lae; Ahn, Ki Jung [Dept. of Radiation Oncology, (Korea, Republic of); Lee, Yun Han [Dept. of Molecular Medicine, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2016-06-15

    The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2–3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ≥25 kg/m{sup 2}) in local control was evaluated. The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of 25.6 kg/m{sup 2} as a cutoff value. Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted.

  19. Association between obesity and local control of advanced rectal cancer after combined surgery and radiotherapy

    International Nuclear Information System (INIS)

    Choi, Yun Seon; Park, Sung Kwang; Cho, Heung Lae; Ahn, Ki Jung; Lee, Yun Han

    2016-01-01

    The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2–3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ≥25 kg/m 2 ) in local control was evaluated. The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of 25.6 kg/m 2 as a cutoff value. Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted

  20. Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

    Science.gov (United States)

    Li, Duo-Jie; Li, Hong-Wei; He, Bin; Wang, Geng-Ming; Cai, Han-Fei; Duan, Shi-Miao; Liu, Jing-Jing; Zhang, Ya-Jun; Cui, Zhen; Jiang, Hao

    2016-01-01

    To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

  1. Irreversible electroporation of locally advanced solid pseudopapillary carcinoma of the pancreas: A case report

    Directory of Open Access Journals (Sweden)

    Luciano Tarantino

    2018-04-01

    Full Text Available Introduction: Solid pseudopapillary Carcinoma (SPC is a rare pancreatic Tumor with variable, usually low, malignancy potential. Howewer, several SPC are associated with aggressive behavior, local vascular infiltration, organ invasion, distant metastasis, and can be unresectable. Irreversible Electroporation (IRE is an emerging non-thermal ablation technique for the treatment of locally advanced pancreatic carcinoma. We report the results of four year disease-free follow-up in a case of locally advanced unresectable SPC treated with IRE. Presentation of case: A 24-year female patient with SPC of the pancreas underwent IRE during laparotomy under general anesthesia with intubation. Computed Tomography (CT showed complete tumor thrombosis of splenic vein, encasement of celiac artery and mesenteric vein. Six insertions of 3–4 electrodes per insertion were performed. One month-CT-control showed shrinkage of the tumor. 6 months-post-treatment imaging showed complete regression of the mass, patent Splenic/mesenteric veins, absence of local recurrence or distant metastasis. Post treatment CTs at 12-18-24-30-36-42-48 months follow-up confirmed absence of local or distant recurrence. Discussion: Surgery is the first choice curative treatment of SPC. Howewer aggressive surgery (duodeno-pancreasectomy in unresectable cases, may have a high risk of recurrences, morbidities and death, and bring concerns about endocrine and exocrine insufficiency in a young patient. In these cases, IRE could be a safe and effective alternative treatment and could realize, in selected cases, the condition for a radical surgery, and a bridge to R-0 resection. Conclusions: IRE could represent an effective alternative therapy to surgery in local advanced, unresectable SPC. Keywords: Pancreatic neoplasm, Solid papillary carcinoma, Intraoperative ultrasound, Irreversible electroporation, Case report

  2. Local Institutional Development and Organizational Change for Advancing Sustainable Urban Water Futures

    Science.gov (United States)

    Brown, Rebekah R.

    2008-02-01

    This paper presents the local institutional and organizational development insights from a five-year ongoing interdisciplinary research project focused on advancing the implementation of sustainable urban water management. While it is broadly acknowledged that the inertia associated with administrative systems is possibly the most significant obstacle to advancing sustainable urban water management, contemporary research still largely prioritizes investigations at the technological level. This research is explicitly concerned with critically informing the design of methodologies for mobilizing and overcoming the administrative inertia of traditional urban water management practice. The results of fourteen in-depth case studies of local government organizations across Metropolitan Sydney primarily reveal that (i) the political institutionalization of environmental concern and (ii) the commitment to local leadership and organizational learning are key corporate attributes for enabling sustainable management. A typology of five organizational development phases has been proposed as both a heuristic and capacity benchmarking tool for urban water strategists, policy makers, and decision makers that are focused on improving the level of local implementation of sustainable urban water management activity. While this investigation has focused on local government, these findings do provide guideposts for assessing the development needs of future capacity building programs across a range of different institutional contexts.

  3. Locally advanced leiomyosarcoma of the spleen. A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Recchia Franco

    2007-11-01

    Full Text Available Abstract Background Leiomyosarcomas are rare tumours, predominantly localized in the stomach, small intestine and retroperitoneum. Only one case of primary leiomyosarcoma of the spleen is described in human beings in literature. Case presentation We report a case of locally advanced primary leiomyosarcoma of the spleen in a 54 year-old woman, diagnosed only after splenectomy, performed with the suspicion of splenic haematoma. Conclusion Due to the lack of cases, no specific chemotherapy regimen has been tested to provide a longer survival.

  4. Long-term results of preoperative intra-arterial doxorubicin combined with neoadjuvant radiotherapy, followed by extensive surgical resection for locally advanced soft tissue sarcomas of the extremities

    International Nuclear Information System (INIS)

    Nijhuis, P.H.A.; Pras, E.; Sleijfer, D.T.; Molenaar, W.M.; Schraffordt Koops, H.; Hoekstra, H.J.

    1999-01-01

    Background and purpose: In the 1980s a combined modality therapy of intraarterial doxorubicin, neoadjuvant radiotherapy and surgery was initiated at the Groningen University Hospital as a limb-saving treatment for locally advanced, primarily irresectable high-grade soft tissue sarcomas (STS) of the extremities. This study presents the short- and long-term results.Patients and methods: Between 1983 and 1987, 11 patients were treated with intraarterial doxorubicin, preoperative radiotherapy (10x3.5 Gy) and surgical resection. Non-radical resections received additional postoperative radiotherapy of 20-30 Gy.Results: The limb-salvage rate was 91%, without local recurrences during a median hollow-up of 84 months. Six patients died (55%); five from metastatic disease (45%). There were five long-term survivors with a median follow-up of 10 years. Three patients (60%) suffered serious late complications, resulting in disabilitating limb function. Conclusion: Although this approach is feasible as a limb-saving treatment for these unfavorable STS, long-term morbidity is high. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years

    DEFF Research Database (Denmark)

    Iversen, Peter; Johansson, Jan-Erik; Lodding, Pär

    2006-01-01

    The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostat...

  6. Comprehensive clinical study of concurrent chemotherapy breathing IMRT middle part of locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    Jung, Jae Hong; Moon, Seong Kwon; Kim, Seung Chul

    2015-01-01

    The standard treatment of locally advanced type of mid-esophageal cancer is concurrent chemoradiation therapy (CRT). We evaluated the feasibility of chemotherapy with adding docetaxel to the classical basic regimens of cisplatin plus 5-fluorouracil (5-FU) and radiotherapy up to 70.2 Gy using dose escalations for esophageal cancer. It was possible to escalate radiation treatment dose up to 70.2 Gy by the respiratory-gated intensity- modulated radiotherapy (gated-IMRT) based on the 4DCT-simulation, with improving target coverage and normal tissue (ex., lung, heart, and spinal cord) sparing. This study suggested that the definitive chemo-radiotherapy with docetaxel, cisplatin, and 5-fluorouracil (i.e., DCF-R) and gating IMRT is tolerable and active in patients with locally advanced mid-esophageal cancer (AEC)

  7. Locally Advanced Oncocytic Carcinoma of the Nasal Cavity Treated With Surgery and Intensity-modulated Radiotherapy

    Directory of Open Access Journals (Sweden)

    Yu-Wen Hu

    2010-03-01

    Full Text Available Oncocytic carcinomas of the nasal cavity are extremely rare. We report 1 patient whose primary tumor and neck lymphadenopathies were under control nearly 2 years after combined surgery and radiotherapy. An 80-year-old man with a history of nasal oncocytoma had received excision twice previously. Computed tomography demonstrated locally advanced recurrent tumor invading the paranasal sinuses and orbit with lymphadenopathies in the right neck. Skull base surgery was performed. Pathological examination revealed oncocytic carcinoma. Positron emission tomography showed hypermetabolic lesions in the surgical bed and right neck. The patient subsequently received intensity-modulated radiotherapy to the primary site and the whole neck. Follow-up computed tomography 4 months later showed marked shrinkage of the neck lymphadenopathies. There was no progression after nearly 2 years. Although these tumors have historically been regarded as radioresistant, the combined treatment of surgery followed by radiotherapy may offer the best chance for control of locally advanced disease.

  8. Is adjuvant hysterectomy an option after radio-chemotherapy for locally advanced cervical cancer? A review

    OpenAIRE

    Cornelia Nitipir; Cristina Orlov; Ana-Maria Popa; Iulian Slavu; Adrian Tulin

    2018-01-01

    Objective. The purpose of this paper is to review the current concepts in the literature regarding the beneficial effects of adjuvant surgery after concurrent radio-chemotherapy for locally advanced cervical cancer. Method. Research of the literature was performed using PubMed databases in order to find articles relevant to the central topic. The PICOS criteria were used to filter the results. The paper was then structured according to the PRISMA guideline. Results. 50 individual papers...

  9. Breast Conserving Surgery and Sentinel Lymph Node Biopsy in Locally Advanced Breast Cancer: Single Center Experience

    Directory of Open Access Journals (Sweden)

    Atakan Sezer

    2011-06-01

    Full Text Available Objective: Patients with locally advanced breast cancer may undergo breast conserving surgery after neoadjuvant chemotherapy. The aim of the study is to evaluate the results of locally advanced breast cancer patients who underwent breast conserving surgery, axillary dissection and sentinel lymph node biopsy in a single center. Material and Methods: 12 patients with locally advanced breast cancer stage IIIA/IIIB were included in the study between 2002-2009. The patients were given anthracycline-based regimen before surgery. Patients underwent breast conserving surgery, axillary dissection, and sentinel lymph node biopsy followed by radiotherapy. Results: There were five patients in stage IIIA, six in stage IIIB, and one in stage IIIC. Patients had received 3-6 regimen of FAC/FEC. Eight had partial and four had complete response. Five positive axilla were detected. The median value of the lymph nodes was 12 (n:8-19. Five patients underwent sentinel lymph node biopsy. The biopsy has failed in one patient and the median value of dissected sentinel node was 3.5 (n:3-4. Locoregional recurrence was not observed in any patients. The mean follow-up of the patients was 29.8 months and median time was 16 (n:2-80 months.Of the 12 patients 10 are alive and 2 were deceased. Conclusion: In selected locally advanced patients, breast conserving surgery and sentinel lymph node biopsy may be applied by a multidisciplinary approach, and excellent success may be achieved in those patients as in early breast cancer patients.

  10. Geometric uncertainties in voluntary deep inspiration breath hold radiotherapy for locally advanced lung cancer

    DEFF Research Database (Denmark)

    Josipovic, Mirjana; Persson, G F; Dueck, Jenny

    2016-01-01

    BACKGROUND AND PURPOSE: Deep inspiration breath hold (DIBH) increases lung volume and can potentially reduce treatment-related toxicity in locally advanced lung cancer. We estimated geometric uncertainties in visually guided voluntary DIBH and derived the appropriate treatment margins for different...... image-guidance strategies. MATERIAL AND METHODS: Seventeen patients were included prospectively. An optical marker-based respiratory monitoring with visual guidance enabled comfortable DIBHs, adjusted to each patient's performance. All patients had three consecutive DIBH CTs at each of the treatment...

  11. Contemporary management of locally advanced rectal cancer: Resolving issues, controversies and shifting paradigms.

    Science.gov (United States)

    Nacion, Aeris Jane D; Park, Youn Young; Kim, Nam Kyu

    2018-02-01

    Advancements in rectal cancer treatment have resulted in improvement only in locoregional control and have failed to address distant relapse, which is the predominant mode of treatment failure in rectal cancer. As the efficacy of conventional chemoradiotherapy (CRT) followed by total mesorectal excision (TME) reaches a plateau, the need for alternative strategies in locally advanced rectal cancer (LARC) has grown in relevance. Several novel strategies have been conceptualized to address this issue, including: 1) neoadjuvant induction and consolidation chemotherapy before CRT; 2) neoadjuvant chemotherapy alone to avoid the sequelae of radiation; and 3) nonoperative management for patients who achieved pathological or clinical complete response after CRT. This article explores the issues, recent advances and paradigm shifts in the management of LARC and emphasizes the need for a personalized treatment plan for each patient based on tumor stage, location, gene expression and quality of life.

  12. Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

    Science.gov (United States)

    Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

    2010-09-01

    This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

  13. [Perioperative changes of coagulation functions in the local advanced liver cancer patients receiving liver transplantation].

    Science.gov (United States)

    Wang, Hao-Yuan; Zhao, Qing-Yu; Yuan, Yun-Fei

    2008-07-01

    Liver transplantation is widely accepted as an effective therapy of hepatoma. Perioperative dynamic observation of coagulation function is important for graft-receivers. This study was to explore perioperative changes of coagulation functions in the local advanced liver cancer patients who received liver transplantation. Clinical data of 31 local advanced liver cancer patients, underwent liver transplantation from Sep. 2003 to Jan. 2007, were analyzed. Platelet (PLT) counting, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) and international normalized ratio (INR) before operation, at anhepatic phase and the first week after operation were analyzed to evaluate congulation function. The coagulation functions of most patients were normal before operation. The six parameters varied significantly at anhepatic phase and on most days of the first week after operation when compared with the preoperative levels (Pfunctions of local advanced liver cancer patients shift from hypocoagulatory to hypercoagulatory or normal in perioperative period, therefore, prevention of bleeding should be focused on at anhepatic phase and on 1-2 days after operation while prevention of thrombosis should be focused on after the first week after operation. The degree of liver cirrhosis and Child-Pugh level could help to evaluate postoperative coagulation disorder.

  14. Radical Prostatectomy for Locally Advanced Prostate Cancers-Review of Literature.

    Science.gov (United States)

    Srivatsa, N; Nagaraja, H; Shweta, S; Raghunath, S K

    2017-06-01

    Twenty-five to thirty percent of patients with prostate cancer present with locally advanced disease. While risk stratification remains the same with high incidence of upstaging of disease on imaging and histopathological evaluation; there have been progressive refinements in surgical therapy. With availability of reasonably robust data, radical prostatectomy in men with locally advanced prostate cancers seems to effect improvement in both cancer specific and overall survival rates in comparison to the current standard of care of radiation with androgen deprivation therapy. Studies using radical prostatectomy as a part of multimodality approach have also shown promising results. There is an imminent need for well-designed prospective studies of benefits of radical prostatectomy over radiation and androgen deprivation as well as benefits of multimodality therapy over monotherapy. Surgery for patients with locally advanced prostate cancer is technically challenging. Surgical outcomes are comparable to those of organ-confined disease when performed in high-volume centers. Neoadjuvant therapies prior to radical prostatectomy might improve surgical outcomes, but whether they will translate into a better cancer specific and overall survival are yet to be ascertained.

  15. Prognostic factors in the treatment of locally advanced hepatocellular carcinoma with radiotherapy and arterial infusion

    International Nuclear Information System (INIS)

    Wang, Y.; Jin, Y.; Zhang, Z.

    2000-01-01

    Prognostic factors in the treatment of local advanced hepatocellular carcinoma with radiotherapy, transcatheter arterial embolization and arterial infusion. The treatment effects of radiotherapy and combination modality therapy for the local advanced hepatocellular carcinoma (HCC) were retrospectively reviewed. Three hundred and fifty-six patients of HCC (187 recurrent cases after surgical resection) were treated by: radiotherapy only ; bi-therapeutic method: hepatic artery ligation (HAL) and/or hepatic artery embolization (HAE) plus radiotherapy; and tri-therapeutic method (bi-therapeutic method plus hepatic artery infusion) from 1975 to 1996. Kaplan-Meier method has been used to evaluate the survival rates. There were no significant differences among these three treatment groups in the symptom relied rate, but the mean relief time period was much shorter in radiotherapy alone group (2.5 vs 44 months, P 0.05). There were evident differences in five-year survivals among these three treatment groups: 0 % for radiotherapy alone, 22.8 % for bi-therapeutic method and 38.8 % for tri-therapeutic method (P < 0.01). The prognosis was influenced by Okuda classification. Non-resectable local advanced HCC can be treated by the combination modality therapy, including radiotherapy, with a quite high cure rate. Radiotherapy alone can relief the symptoms. (authors)

  16. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    Energy Technology Data Exchange (ETDEWEB)

    Trip, Anouk K. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Poppema, Boelo J. [Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Siemerink, Ester [Department of Internal Medicine, Ziekenhuisgroep Twente, Hengelo (Netherlands); Beukema, Jannet C. [Department of Radiation Oncology, University Medical Centre Groningen (Netherlands); Verheij, Marcel [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Plukker, John T.M. [Department of Surgical Oncology, University Medical Centre Groningen (Netherlands); Richel, Dick J. [Department of Medical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Hulshof, Maarten C.C.M. [Department of Radiation Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Sandick, Johanna W. van [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Cats, Annemieke [Department of Gastroenterology and Hepatology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Jansen, Edwin P.M. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Hospers, Geke A.P., E-mail: g.a.p.hospers@umcg.nl [Department of Medical Oncology, University Medical Centre Groningen (Netherlands)

    2014-08-15

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates.

  17. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    International Nuclear Information System (INIS)

    Trip, Anouk K.; Poppema, Boelo J.; Berge Henegouwen, Mark I. van; Siemerink, Ester; Beukema, Jannet C.; Verheij, Marcel; Plukker, John T.M.; Richel, Dick J.; Hulshof, Maarten C.C.M.; Sandick, Johanna W. van; Cats, Annemieke; Jansen, Edwin P.M.; Hospers, Geke A.P.

    2014-01-01

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates

  18. Dosimetric evaluation of tomography and four-box field conformal radiotherapy in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Yu, Mina; Lee, Hyo Chun; Chung, Mi Joo; Kim, Sung Hwan; Lee, Jong Hoon; Jang, Hong Seok; Jeon, Dong Min; Cheon, Geum Seong

    2013-01-01

    To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer. Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, Vn Gy, Dmin, Dmax, radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose. Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p 0.001). But, V26.25 Gy and V27.5 Gywere not significantly different between the two modalities. Tomotherapy showed higher Dmax and lower Dmin. The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT. In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.

  19. Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.

    Science.gov (United States)

    Supaadirek, Chunsri; Pesee, Montien; Thamronganantasakul, Komsan; Thalangsri, Pimsiree; Krusun, Srichai; Supakalin, Narudom

    2016-01-01

    To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (prectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

  20. Dosimetric evaluation of tomography and four-box field conformal radiotherapy in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Mina; Lee, Hyo Chun; Chung, Mi Joo; Kim, Sung Hwan; Lee, Jong Hoon [Dept. of Radiation Oncology, St. Vincent' s Hospital, The Catholic University of Korea College of Medicine, Suwon (Korea, Republic of); Jang, Hong Seok; Jeon, Dong Min; Cheon, Geum Seong [Dept. of Radiation Oncology, Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer. Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, Vn Gy, Dmin, Dmax, radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose. Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p 0.001). But, V26.25 Gy and V27.5 Gywere not significantly different between the two modalities. Tomotherapy showed higher Dmax and lower Dmin. The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT. In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.

  1. Locally advanced oral cavity squamous cell carcinoma: Barriers related to effective treatment

    Directory of Open Access Journals (Sweden)

    K C Lakshmaiah

    2015-01-01

    Full Text Available Background: Oral cavity cancer is a significant health problem in India. Majority of patients present with locally advanced disease requiring multimodality treatment. Compliance to recommended treatment is an important factor affecting outcome. Aims: The aim was to evaluate the outcome of locally advanced oral cavity cancer patients with regards to treatment adherence and to assess reasons of noncompliance. Materials and Methods: This was a prospective observational study. We included patients referred to Department of Medical Oncology for induction chemotherapy in view of locally advanced oral cavity cancer. Results: Only 15 (26% patients completed planned treatment schedule. Their 1 year overall survival was 93%. The remaining 43 patients who received inadequate treatment had a dismal 21% 1 year overall survival. Illiteracy, poverty, long waiting list for surgery, prolonged delay for health scheme treatment plan approval and dissatisfaction with attitude of hospital staffs are major barriers related to effective treatment of these patients. Conclusions: A detailed discussion with patient and their relatives regarding recommended treatment, proper implementation of health schemes, increasing trained manpower to avoid long waiting list for surgery, provision of additional financial support for family member accompanying the patient and a sympathetic approach toward patients are needed to help these patients overcome the battle.

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

    Science.gov (United States)

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

    2013-04-01

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

  3. 6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru; Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation); Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru; Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation)

    2016-08-02

    The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

  4. En bloc urinary bladder resection for locally advanced colorectal cancer: a 17-year experience.

    Science.gov (United States)

    Li, Jimmy C M; Chong, Charing C N; Ng, Simon S M; Yiu, Raymond Y C; Lee, Janet F Y; Leung, Ka Lau

    2011-09-01

    En bloc bladder resection is often required for treating colorectal cancer with suspected urinary bladder invasion. Our aim was to review our institutional experience in en bloc resection of locally advanced colorectal cancer involving the urinary bladder over a period of 17 years. The hospital records of 72 patients with locally advanced colorectal cancer who underwent en bloc urinary bladder resection at our institution between July 1987 and December 2004 were retrospectively reviewed. Clinical and oncologic outcomes were evaluated. The mean duration of follow-up was 64.3 months. Genuine tumor invasion into the urinary bladder was confirmed in 34 patients (47%) by histopathology. Forty patients (56%) underwent primary closure of the urinary bladder, while 32 patients (44%) required various kinds of urologic reconstructive procedures. Operative mortality occurred in four patients (6%). The overall postoperative morbidity rate was significantly higher in patients undergoing urologic reconstruction (81% vs. 45%, p = 0.002) when compared to that in patients undergoing primary closure. This was mostly attributable to significantly higher rates of urinary anastomotic leak (21.9% vs. 0%, p = 0.002) and urinary tract infection (50% vs. 18%, p = 0.003) in the urologic reconstruction group. For the 57 patients (79%) who underwent curative resection, the 5-year overall survival rate was 59%, and the local recurrence at 5 years was 15%. Both parameters were not significantly affected by the presence of pathologic bladder invasion or the extent of surgical procedures. En bloc bladder resection for locally advanced colorectal cancer involving the urinary bladder can produce reasonable long-term local control and patient survival.

  5. Stable and high expression of Galectin-8 tightly controls metastatic progression of prostate cancer

    Science.gov (United States)

    Gentilini, Lucas Daniel; Pérez, Ignacio González; Kotler, Monica Lidia; Chauchereau, Anne; Laderach, Diego Jose; Compagno, Daniel

    2017-01-01

    Two decades ago, Galectin-8 was described as a prostate carcinoma biomarker since it is only expressed in the neoplastic prostate, but not in the healthy tissue. To date, no biological function has been attributed to Galectin-8 that could explain this differential expression. In this study we silenced Galectin-8 in two human prostate cancer cell lines, PC3 and IGR-CaP1, and designed a pre-clinical experimental model that allows monitoring the pathology from its early steps to the long-term metastatic stages. We show for the first time that the natural and conserved expression of Gal-8 in tumour cells is responsible for the metastatic evolution of prostate cancer. In fact, Gal-8 controls the rearrangement of the cytoskeleton and E-Cadherin expression, with a major impact on anoikis and homotypic aggregation of tumour cells, both being essential processes for the survival of circulating tumour cells during metastasis. While localized prostate cancer can be cured, metastatic and advanced disease remains a significant therapeutic challenge, urging for the identification of prognostic markers of the metastatic process. Collectively, our results highlight Galectin-8 as a potential target for anti-metastatic therapy against prostate cancer. PMID:28591719

  6. Concurrent chemoradiotherapy for locally advanced lung carcinoma: present results and future prospects

    International Nuclear Information System (INIS)

    Reboul, F.; Vincent, P.; Brewer, Y.; Taulelle, M.

    1997-01-01

    The prognosis of locally advanced lung cancer is reportedly poor in all histologic types. In non-small cell lung cancer, radiation therapy alone results in disappointing long-term survival. Three recent randomized trials, however, have shown a limited but significant improvement of survival with induction chemotherapy, though local control remained poor in these studies as well as in small-cell lung cancer treated with chemotherapy and late radiotherapy. Tow randomized trials focusing on small-cell lung cancer have recently shown significant benefit due to the combination of early concurrent mediastinal irradiation and chemotherapy, with major improvement in local control and a more than 40% 2-year survival rate. The concept of concurrent chemoradiotherapy has also been studied in non-small cell carcinoma with several pilot studies leading to both encouraging results and improved survival rate (up to 40% at 2 years). Ongoing phase III trials are comparing sequential versus concurrent chemoradiotherapy and will define the role of radical surgery after chemoradiotherapy in locally advanced non-small cell lung cancer. (authors)

  7. Hit by waves-living with local advanced or localized prostate cancer treated with endocrine therapy or under active surveillance.

    Science.gov (United States)

    Ervik, Bente; Nordøy, Tone; Asplund, Kenneth

    2010-01-01

    Previous studies of living with prostate cancer have shown that the illness and the treatment cause physical as well as psychosocial problems. The aim of this study was to illuminate men's experiences living with localized or local advanced prostate cancer when curative treatment such as surgery or radiation therapy is not an option at the time of diagnosis. The study was conducted via qualitative interviews, using a phenomenological hermeneutic approach. Ten men treated with endocrine therapy or under active surveillance were interviewed. Being diagnosed with prostate cancer was described as a shock, with different aspects of the illness revealed gradually. The limited amount of time available for meeting with health care providers contributed to patients' feelings of being left alone with difficulty getting information and help. Sexual and urinary problems were perceived as a threat to their manhood. The spouses provided the closest everyday support. The life situation of these patients can be understood as living in a "state of readiness," expecting something to happen regarding their illness, and not always knowing where to get help. The results confirm existing knowledge of patient's experiences in living with prostate cancer regarding the initial shock perceived by the patients, the bodily alterations, and the important role of their spouses. Nurses, as well as general practitioners, must play a more active role in follow-up to ensure that the men and their spouses receive better help and support.

  8. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  9. Therapeutic Results of Concurrent Chemoradiation in Locally Advanced Uterine Cervical Cancer

    International Nuclear Information System (INIS)

    Kang, Seung Hee; Suh, Hyun Suk; Yang, Kwang Mo; Lee, Eung Soo; Park, Sung Kwon

    1995-01-01

    Purpose : Despite a development for therapeutic machines and advance in modern radiation therapy techniques, locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate. Combination of chemotherapy and radiotherapy demonstrated benefit in improving local control and possibly the overall survival. Our study was performed to evaluate effect of concurrent chemoradiation on locally advanced uterine cervical cancer. Methods and Materials : Twenty six patients with locally advanced stage(FIGO stage IIB with ≥ 5 cm in diameter, III, IVA) were treated with combination of radiation therapy and concurrent cisplatinum between May of 1988 and September of 1993 at our hospital. Radiation therapy consisted of external irradiation and 1-2 sessions of intracavitary irradiation, Cisplatinum was administered in bolus injection of 25mg/m 2 at weekly intervals during the course of external radiation therapy. Results : Of the 26 patients, twenty-five patients were evaluable for estimation of response. Median follow-up period was 25 months with ranges from 3 to 73 months. Stage IIB, III, and IVA were 16, 5,4 patients, respectively. Twenty patients were squamous cell carcinoma. Response was noted in all 25 patients: complete response(CR) in 17/25(68%), partial response(PR) in 8/25(32%). Of the 24 patients except one who died of sepsis at 3 months follow-up, seventeen patients(70.8%) maintained local control in the pelvis: 16/17(94.1%) in CR, 1/17(14.3%) in PR. Fourteen of the 17 patients with CR are alive disease free on the completion of follow-up. Median survival is 28 months for CR and 15 months for PR. Analysis of 5-year survival by stage shows 11/16(59.8) in IIB, 3/5(60.6%) in III, and 1/4(25.0%) in IVA. Overall 5-year survival rate was 55.2%. Ten Patients recurred: 4 at locoregional, 3 in distant metastasis and 3 with locoregional and distant site. Toxicity by addition of cisplatinum was not excessive. Conclusion : Although the result of this

  10. Use of 6-[18F]-fluorodopamine positron emission tomography (PET) as first-line investigation for the diagnosis and localization of non-metastatic and metastatic phaeochromocytoma (PHEO).

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Eisenhofer, G.; Carrasquillo, J.A.; Chen, C.C.; Whatley, M.; Ling, A.; Adams, K.T.; Pacak, K.

    2009-01-01

    OBJECTIVE: Imaging modalities available for the localization of phaeochromocytoma (PHEO) include computed tomography (CT), magnetic resonance imaging (MRI), [(123)I]- or [(131)I]-labelled metaiodobenzylguanidine ((123/131)I-MIBG) scintigraphy and 6-[(18)F]-fluorodopamine ((18)F-FDA) positron

  11. A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer.

    Science.gov (United States)

    Gupta, Arunima; Roy, Somnath; Majumdar, Anup; Hazra, Avijit; Mallik, Chandrani

    2014-01-01

    Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m(-2) intravenously on day 1 and 5-fluorouracil (1000 mg m(-2) continuous intravenous infusion on days 1-4 starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions.

  12. Weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Hu Wei; Ding Weijun; Yang Haihua; Shao Minghai; Wang Biyun; Wang Jianhua; Wu Sufang; Wu Shixiu; Jin Lihui; Ma, Charlie C.-M.

    2009-01-01

    Purpose: To evaluate the efficacy and toxicity of weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy (AC) in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods and materials: Between 2004 and 2007, 54 patients with locally advanced NPC were included in this protocol. Patient characteristics: median age 48; 69% male; 52% World Health Organization (WHO) III; 50% stage III, 50% stage IV. The patients underwent a course of definitive conventional radiotherapy (70 Gy in 7 weeks with 2 Gy/fraction), with concurrent weekly paclitaxel 35 mg/m 2 from the first to the sixth week of radiation. AC was started 4 weeks after the end of the radiotherapy (RT), paclitaxel 135 mg/m 2 on day 1 and cisplatin 30 mg/m 2 on days 1-3 were administered every 4 weeks for two cycles. Results: Median follow-up was 32 months. Eighty-five percentage of complete response and 15% partial response were achieved at the time of one month after AC. The 3-year actuarial rate of local regional control was 86%; distant metastases-free survival, progression-free survival and overall survival at 3 years were 81%, 69% and 76%, respectively. Forty-nine (91%) patients completed six courses of concurrent chemotherapy with weekly paclitaxel, and 4 (7%) patients delayed at the second cycle of AC. No patient developed severe acute toxicities. Conclusions: Weekly paclitaxel with concurrent RT followed by AC is a potentially effective and toxicity tolerable method for locally advanced NPC. Further studies are needed to identify the optimal dose of weekly paclitaxel in this strategy.

  13. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Dianliang; Zheng, Hongmei; Zhou, Yanbing [Department of General Surgery, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003 (China); Tang, Xingming; Yu, Baojun; Li, Jieshou [Research Institute of General Surgery, Jinlin Hospital, Nanjing University, Nanjing 210093 (China)

    2007-03-14

    IL-1beta has been implicated in inflammatory episode. In view of the inflammatory nature of cancer cachexia, we determined the predictive value of IL-1B-31 T/C, -511 C/T, +3954 C/T and IL-1RN VNTR gene polymorphisms on the occurrence of cachexia associated with locally advanced gastric cancer. The study included 214 patients and 230 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of polymerase chain reaction products. The overall frequencies of IL-1B-31 T, -511 T, +3954 T and IL-1RN VNTR alleles in patients with locally advanced gastric cancer were all comparable with those in controls. No significant differences were found in the distribution of IL-1B-31 T, -511 T and IL-1RN VNTR between patients with cachexia and without. Patients with cachexia showed a significantly higher prevalence of IL-1B+3954 T allele than those without (P = 0.018). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the IL-1B+3954 CT genotype was associated with an odds ratio of 2.512 (95% CI, 1.180 – 5.347) for cachexia. The IL-1B+3954 T allele is a major risk for cachexia from locally gastric cancer. Genetic factors studied are not likely to play an important role in the determination of susceptibility to locally advanced gastric cancer.

  14. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer

    International Nuclear Information System (INIS)

    Zhang, Dianliang; Zheng, Hongmei; Zhou, Yanbing; Tang, Xingming; Yu, Baojun; Li, Jieshou

    2007-01-01

    IL-1beta has been implicated in inflammatory episode. In view of the inflammatory nature of cancer cachexia, we determined the predictive value of IL-1B-31 T/C, -511 C/T, +3954 C/T and IL-1RN VNTR gene polymorphisms on the occurrence of cachexia associated with locally advanced gastric cancer. The study included 214 patients and 230 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of polymerase chain reaction products. The overall frequencies of IL-1B-31 T, -511 T, +3954 T and IL-1RN VNTR alleles in patients with locally advanced gastric cancer were all comparable with those in controls. No significant differences were found in the distribution of IL-1B-31 T, -511 T and IL-1RN VNTR between patients with cachexia and without. Patients with cachexia showed a significantly higher prevalence of IL-1B+3954 T allele than those without (P = 0.018). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the IL-1B+3954 CT genotype was associated with an odds ratio of 2.512 (95% CI, 1.180 – 5.347) for cachexia. The IL-1B+3954 T allele is a major risk for cachexia from locally gastric cancer. Genetic factors studied are not likely to play an important role in the determination of susceptibility to locally advanced gastric cancer

  15. Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jochen Greiner

    2010-01-01

    Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

  16. The results of postoperative irradiation for locally advanced carcinoma of the larynx

    International Nuclear Information System (INIS)

    Wieczorek, A.; Fijuth, J.; Michalski, W.

    2002-01-01

    The aim of the study was to conduct a retrospective analysis of advanced laryngeal cancer patients treated with postoperative radiotherapy in order to assess the clinical outcome and identify prognostic factors which may alter their prognosis. We retrospectively reviewed the medical records of 165 patients with advanced laryngeal carcinoma treated with postoperative radiotherapy between 1984 and 1996. Initially all patients underwent total laryngectomy combined, in 91 cases, with unilateral or bilateral neck dissection. Postoperative irradiation was initiated within 15 to 162 days after surgery (mean - 53 days). The total dose varied between 50-70 Gy with the fraction size of 2.0 Gy. The analysis of overall survival and local control was performed using the actuarial method according to Kaplan and Meier. Sex, age, performance status, T, N stages, primary tumor site, hemoglobin level, histological grade, involvement of lymph nodes, extracapsular lymph node extension, surgical margin status, presence of extension of the primary beyond larynx and/or thyroid cartilage invasion and/or subglottic extension and time from operation to start of radiotherapy were studied in multivariate analysis for the prognostic significance for both overall survival and local control. The actuarial survival for the entire group of postoperatively irradiated patients was 0.70, 0.56 and 0.43 at two, five and ten years respectively. The actuarial local control for the entire group of patients was 0.86, 0.78 and 0.75 at one, two and three years respectively and remained stable thereafter. For the overall survival - sex, positive lymph nodes and time interval between surgery and radiotherapy were found to be the significant prognostic factors. For the local control the extracapsular lymph node extension was found to be the only significant prognostic factor. Combined surgery and postoperative radiotherapy is an effective treatment modality in the management of locally advanced laryngeal cancer

  17. Three dimensional-conformal radiotherapy combined with capecitabine chemotherapy for locally advanced (unresectable) rectal cancer

    International Nuclear Information System (INIS)

    Zhu Yaqun; Tian Ye; Zhang Junning; Wang Bin

    2010-01-01

    Objective: To evaluate the compliance and efficacy of chemoradiotherapy for locally advanced (unresectable) rectal cancer. Methods: Thirty eight patients with locally advanced (T4 or recurred) rectal cancer received three dimensional-conformal radiotherapy (for 46 ∼ 50Gy/5 weeks and was boosted to the tumor 16 ∼ 18Gy/2 weeks, 2Gy/fraction, 5 days/week) in combination with capecitabine 1 650mg · m -2 · d -1 , day 1-14, every 3 weeks. Results: The overall response rate was 57.9%, with CR 5 (13.2%), PR 17(44.7%), SD 10 (26.3%), PD 6 (15.8%), median survival time, the 1-year overall survival rate and the 2-year overall survival rate were 18 months, 64.43%, 18.78%, respectively. The remission rate of pain and improvement rate of performance status were 100% and 52.8%. Treatment-related toxicity mainly showed at diarrhea, neutrocytopenia and hand-foot syndrome, the incidence of grade 3 toxicity were 15.8%, 15.8%, 7.9%, respectively. there were no grade 4 toxicity and treatment-related death. Conclusion: Combination of three dimensional-conformal radiotherapy with capecitabine is active in advanced rectal cancer, It is a well-tolerated regimen. (authors)

  18. Multimodality approach to surgical management of locally advanced epidermoid carcinoma of the anorectum

    International Nuclear Information System (INIS)

    Wanebo, H.J.; Futrell, W.; Constable, W.

    1981-01-01

    Seven patients (five female, two male) had locally advanced epidermoid carcinoma of the anal canal. Three patients had recurrent or persistent disease previously treated and four had advanced primary cancer. Five patients had groin node metastasis. The treatment protocol consisted of chemotherapy with continuous 5-day infusion of 5-fluorouracil, 750 mg/m2, and mitomycin C, 15 mg/m2, by bolus injection and radiation 3000 rads. All patients received one or two cycles of chemotherapy pre-operatively and four (not previously irradiated) received radiation. Tumor regression greater than 50% occurred in five patients, minor regression (25-50%) occurred in one patient and one patient showed no regression (on chemotherapy alone). All patients had total resection of all gross tumor with microscopic clear margins and five had groin dissection. One patient had no residual cancer in specimen and one patient had a microscopic focus only. Four of five patients had residual nodal metastases at groin dissection. Currently three patients are free of disease at 24, 24, and 26 months. Two patients died with disease at 6 months and 34 months, and two patients died of other causes while still free of disease, at 4 and 5 months after resection. Multimodality therapy of locally advanced epidermoid cancer of anal canal can provide effective control and palliation of many of these tumors and, in some, possibly effect cure

  19. Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Schellenberg, Devin; Goodman, Karyn A.; Lee, Florence; Chang, Stephanie; Kuo, Timothy; Ford, James M.; Fisher, George A.; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Greco, Ralph; Yang, George P.; Koong, Albert C.

    2008-01-01

    Purpose: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. Methods and Materials: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). Conclusion: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant

  20. Prospective single-arm study of intraoperative radiotherapy for locally advanced or recurrent rectal cancer

    International Nuclear Information System (INIS)

    Tan, Jennifer; Hui, Andrew C; Heriot, Alexander G.; Mackay, Jack; Lynch, A. Craig; Van Dyk, Sylvia; Bressel, Mathias; Fox, Chris D.; Leong, Trevor; Ngan, Samuel Y.

    2013-01-01

    This study aims to evaluate the feasibility and outcomes of intraoperative radiotherapy (IORT) using high-dose-rate (HDR) brachytherapy for locally advanced or recurrent rectal cancers. Despite preoperative chemoradiation, patients with locally advanced or recurrent rectal cancers undergoing surgery remain at high risk of local recurrence. Intensification of radiation with IORT may improve local control. This is a prospective non-randomised study. Eligible patients were those with T4 rectal cancer or pelvic recurrence, deemed suitable for radical surgery but at high risk of positive resection margins, without evidence of metastasis. Chemoradiation was followed by radical surgery. Ten gray (Gy) was delivered to tumour bed via an IORT applicator at time of surgery. There were 15% primary and 85% recurrent cancers. The 71% received preoperative chemoradiation. R0, R1 and R2 resections were 70%, 22% and 7%, respectively. IORT was successfully delivered in 27 of 30 registered patients (90% (95% confidence interval (CI)=73–98)) at a median reported time of 12 weeks (interquartile range (IQR)=10–16) after chemoradiation. Mean IORT procedure and delivery times were 63 minutes (range 22–105 minutes). Ten patients (37% (95% CI=19–58)) experienced grade 3 or 4 toxicities (three wound, four abscesses, three soft tissue, three bowel obstructions, three ureteric obstructions and two sensory neuropathies). Local recurrence-free, failure-free and overall survival rates at 2.5 years were 68% (95% CI=52–89), 37% (95% CI=23–61) and 82% (95% CI=68–98), respectively. The addition of IORT to radical surgery for T4 or recurrent rectal cancer is feasible. It can be delivered safely with low morbidity and good tumour outcomes.

  1. Locally advanced cervix cancer: chemotherapy prior to definitive surgery or radiotherapy. A single institutional experience

    International Nuclear Information System (INIS)

    MacLeod, C.; O'Donnell, A.; Tattersall, M.H.N.; Dalrymple, C.; Firth, I.

    2001-01-01

    Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer. It can down stage a cancer and allow definitive local therapy to be technically possible (surgery), or potentially more effective (radiotherapy). It can also eradicate subclinical systemic metastases. This report reviews a single institution's experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13-year period. One hundred and six patients were treated with this intent. The patients were analysed for their response to chemotherapy, treatment received, survival, relapse and toxicity. The chemotherapy was feasible and the majority of patients had a complete or partial response (58.5%). Eight patients did not proceed to local treatment. Forty-six patients had definitive surgery and 52 had definitive radiotherapy. The 5-year overall survival was 27% and the majority of patients died with disease. The first site of relapse was usually in the pelvis (46.2%). Late complications that required ongoing medical therapy (n = 6) or surgical intervention (n = 2) were recorded in eight patients (7.5%). On univariate analysis stage (P= 0.04), tumour size (P = 0.01), lymph node status (P=0.003), response to chemotherapy (P = 0.045) and treatment (P = 0.003) were all significant predictors of survival. On multivariate analysis, tumour size (P < 0.0001) and nodal status (P = 0.02) were significant predictors of survival. Despite the impressive responses to chemotherapy of advanced cervix cancer, there is evidence from randomized trials that it does not improve or compromise survival prior to radiotherapy. As its role prior to surgery remains unclear, it should not be used in this setting outside a prospective randomized trial. Copyright (2001) Blackwell Science Pty Ltd

  2. Surgical resection of locally advanced primary transverse colon cancer--not a worse outcome in stage II tumor.

    Science.gov (United States)

    Hung, Hsin-Yuan; Yeh, Chien-Yuh; Changchien, Chung-Rong; Chen, Jinn-Shiun; Fan, Chung-Wei; Tang, Reiping; Hsieh, Pao-Shiu; Tasi, Wen-Sy; You, Yau-Tong; You, Jeng-Fu; Wang, Jeng-Yi; Chiang, Jy-Ming

    2011-07-01

    In locally advanced primary transverse colon cancer, a tumor may cause perforation or invade adjacent organs. Extensive resection is the best choice of treatment, but such procedures must be weighed against the potential survival benefits. This study was performed to identify the clinicopathological features and treatment outcomes of such tumors. We retrospectively reviewed the database of the Colorectal Cancer Registry of Chang Gung Memorial Hospital between February 1995 and December 2005. Patients with colon cancer sited between the hepatic and splenic flexure that involved an adjacent organ without distant metastasis were defined as having locally advanced transverse colon cancer. A total of 827 patients who underwent surgery for transverse primary colon cancer were enrolled in the study. Stage II and stage III colon cancer were diagnosed in 548 patients. Thirty-two (5.8%) patients were diagnosed with locally advanced tumors. Multivariate analysis revealed that stage III, preoperative carcinoembryonic antigen ≥5 ng/mL, a tumor with perforation or obstruction, and the presence of a locally advanced tumor were significant prognostic factors for both overall and cancer-specific survival. Postoperative morbidity rates differed significantly between the locally advanced and non-locally advanced tumor groups (22.7% vs. 12.3%, P transverse colon tumors (P = 0.21). Surgical resection of locally advanced transverse colon tumors resulted in a higher morbidity and mortality than that of non-locally advanced tumors, but the benefit of extensive surgery in the case of locally advanced tumors cannot be underestimated. Furthermore, this benefit is more pronounced in the case of stage II tumors.

  3. Morbidity and outcome of pelvic exenteration in locally advanced pelvic malignancies.

    Science.gov (United States)

    Ramamurthy, Rajaraman; Duraipandian, Amudhan

    2012-09-01

    Pelvic exenteration is a technically demanding surgical procedure performed for locally advanced cancers in the pelvis. Aim of the present study was to analyze morbidity, failure pattern and survival after pelvic exenteration during a period of 15 years in a dedicated cancer centre in South India. Retrospective analysis of case records of 50 patients who underwent pelvic exenteration from 1996 to 2011 in the Department of Surgical Oncology, Government Royapettah Hospital Chennai. Forty-six patients were females and 4 were males with a mean age of 48.3 years (range 21-72). Twenty six patients had cervical cancer,14 had rectal cancer, 3 had bladder cancer,2 had endometrial cancer, 2 had vaginal cancer, 1 had uterine sarcoma, 1 had anal cancer and 1 had ovarian cancer. The postoperative morbidity was 50%. 7 patients (14%) developed recurrence of which 5 had local and 2 had distant recurrence. The estimated 5 year overall survival for all patients in our series was 53.5% and for the patients with Ca rectum and Ca cervix was 60.6% and 40.1% respectively. Adjacent organ invasion had a significant impact over survival. Pelvic exenteration provides a curative form of treatment for carefully selected locally advanced cancer in the pelvis and it can be done safely with acceptable complications in centers experienced in multivisceral resections.

  4. Prognostic value of pathological response to chemo radiotherapy of locally advanced low rectal cancer

    International Nuclear Information System (INIS)

    Bannura C, Guillermo; Vargas N, Claudio; Barrera E, Alejandro; Melo L, Carlos; Illanes F, Felipe

    2013-01-01

    Background: Preoperative chemo radiotherapy improves the prognosis of locally advanced low rectal cancer and induces a pathological response in the tumor, which may have prognostic value. Aim: To assess the results of rectal cancer treatment according to the degree of pathological response of the tumor after chemo radiotherapy. Patients and Methods: All patients with a locally advanced rectal cancer located within 11 cm of the rectal margin, subjected to preoperative chemo radiotherapy followed by surgical treatment in a period of 13 years, were included. Pathological response was classified as complete, intermediate and poor. The tumor was staged according to TNM 2002 classification. Survival was analyzed with Kaplan Meier curves and Cox regression. Results: Patients were followed for a mean of 50 months (range 18-156). Exclusive and global local relapse was observed in 3 and 9.6% of patients, respectively. Pathological response was complete in 13 patients (none died), intermediate in 23 (three died) and poor in 68 (22 died). Global five years survival was 74%. There was a concordance of 0.64 between survival and pathological response. The concordance between survival and TNM classification was 0.69. Conclusions: The pathological response of the tumor to chemo radiotherapy has a good concordance with prognosis, although it is not superior to the final pathological status

  5. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    International Nuclear Information System (INIS)

    Valentini, Anna Lia; Gui, Benedetta; D’Agostino, Giuseppe Roberto; Mattiucci, Giancarlo; Clementi, Valeria; Di Molfetta, Ippolita Valentina; Bonomo, Pierluigi; Mantini, Giovanna

    2012-01-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio 1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value 2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  6. National Trends and Predictors of Locally Advanced Penile Cancer in the United States (1998-2012).

    Science.gov (United States)

    Chipollini, Juan; Chaing, Sharon; Peyton, Charles C; Sharma, Pranav; Kidd, Laura C; Giuliano, Anna R; Johnstone, Peter A; Spiess, Philippe E

    2017-08-12

    We analyzed the trends in presentation of squamous cell carcinoma (SCC) of the penis and determined the socioeconomic predictors for locally advanced (cT3-cT4) disease in the United States. The National Cancer Database was queried for patients with clinically nonmetastatic penile SCC and staging available from 1998 to 2012. Temporal trends per tumor stage were evaluated, and a multivariable logistic regression model was used to identify predictors for advanced presentation during the study period. A total of 5767 patients with stage ≤ T1-T2 (n = 5423) and T3-T4 (n = 344) disease were identified. Increasing trends were noted in all stages of penile SCC with a greater proportion of advanced cases over time (P = .001). Significant predictors of advanced presentation were age > 55 years, the presence of comorbidities, and Medicaid or no insurance (P guide targeted interventions in vulnerable populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [The necessary perseverance of surgery for the treatment of locally advanced colorectal cancer].

    Science.gov (United States)

    Gu, Jin

    2018-03-25

    Colorectal cancer, a malignant tumor arising from the colon or rectum, is a common cancer in China, with most patients diagnosed at the advanced stage or locally advanced stage. Large tumor size results in the invasion of adjacent organs and the multiple organ involvement, which poses certain challenges for clinical treatment. When facing advanced stage colorectal cancer, some surgeons do not consider surgery, a reasonable option. However, in fact, multi-disciplinary treatment can achieve relatively good treatment outcomes in patients with advanced stage or locally advanced stage colorectal cancer. Therefore, reasonable surgery should not be hastily abandoned. For patients with large tumors without distant metastases but with multiple organ involvement, directly surgical resection is difficult, therefore, preoperative adjuvant therapy can be considered. The basic principle of surgical treatment is to accomplish maximum protection of organ functions and to perform reasonable regional lymph node dissection on the basis of achieving R0 resection. Common surgical procedures for locally advanced colorectal cancer are as follows: (1)Right-sided colon cancer with duodenal invasion: first, the colon must be freed from three directions, namely the right posterior surface of the colon, the left side of the tumor, and the upper side of the tumor inferior to the pylorus, so as to expose and assess the spatial relationship between the tumor and the duodenum; the actual tumor invasion depth in the duodenum may be shallow. (2) Splenic flexure colon cancer with invasion of the cauda pancreatis and hilum lienis: multivisceral resection must be performed without separating the attachment between the tumor and spleen. The tumor border can be found more easily through manipulations starting from the descending colon. (3) Giant sigmoid colorectal cancer with bladder invasion: invasion usually occurs at the bladder fundus. Therefore, during surgery, the attachment between the rectum and

  8. Complex surgery for locally advanced bone and soft tissue sarcomas of the shoulder girdle.

    Science.gov (United States)

    Lesenský, Jan; Mavrogenis, Andreas F; Igoumenou, Vasilios G; Matejovsky, Zdenek; Nemec, Karel; Papagelopoulos, Panayiotis J; Fabbri, Nicola

    2017-08-01

    Surgical management of primary musculoskeletal tumors of the shoulder girdle is cognitively and technically demanding. Over the last decades, advances in the medical treatments, imaging and surgical techniques have fostered limb salvage surgery and reduced the need for amputation. Despite well-accepted general principles, an individualized approach is often necessary to accommodate tumor extension, anatomical challenges and patient characteristics. A combination of techniques is often required to achieve optimal oncologic and durable functional outcome. Goal of this article is to review approach and management of patients with locally advanced sarcomas of the shoulder girdle requiring major tumor surgery, to illustrate principles of surgical strategy, outcome and complications, and to provide useful guidelines for the treating physicians.

  9. Multiple urinary bladder masses from metastatic prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Richard Choo

    2010-12-01

    Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

  10. Locally advanced cancer of the tongue base: new method of surgical treatment

    Directory of Open Access Journals (Sweden)

    I. A. Zaderenko

    2018-01-01

    Full Text Available Introduction. Patients are characterized by locally advanced tumors in 70–80 % of cases at presentation, so possibility of cure and surgical treatment is limited. Total glossectomy, tongue base resection is associated with severe and permanent disability. Such surgical procedures lead to severe dysphagia, alalia and social maladjustment. Enumerated issues motivated us to develop new method of surgical treatment  of locally advanced base of tongue cancer.Objective is to introduce new opportunities of surgical treatment of locally advanced cancer of the tongue base.Materials and methods. Glossectomy is accomplished in 5 patients suffering from tongue cancer and admitted to N.N. Blokhin National Medical Research Center of Oncology. Swallowing and speech is preserved in all 5 cases.Results. The main advantage of the proposed method is that the cut out muscle flap has a different innervation from different cranial nerves involved in the rate of swallowing, so there is not just a mechanical movement of the epiglottis, but also the control of swallowing by the central nervous system. The reduction of injury and operation time in the proposed method is due to the fact that tissues directly contacting with the defect are used to preserve swallowing and speech. The proposed muscle flap has various sources of blood supply, which improves its nutrition and reduces the risk of complications, and healing occurs in a shorter time in comparison with the prototype. All of the above reduces the duration of hospitalization for an average of 7–9 days.Conclusion. The developed surgical technique allows to achieve early rehabilitation; patients are able to breathe effortlessly, swallow and speak. There is no need in permanent tracheostoma and percutaneous endoscopic gastrostomy tube. All patients remains socially active. 

  11. Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

    2009-01-01

    Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m 2 /wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m 2 ) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p 2 /wk vs. 296 ± 15 mg/m 2 /wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP

  12. A single centre experience with sequential and concomitant chemoradiotherapy in locally advanced stage IV tonsillar cancer

    Directory of Open Access Journals (Sweden)

    Coyle Catherine

    2010-12-01

    Full Text Available Abstract Background Chemo-radiotherapy offers an alternative to primary surgery and adjuvant therapy for the management of locally advanced stage IV squamous cell carcinomas of the tonsil. Methods A retrospective analysis was performed of the outcomes of 41 patients with locoregionally advanced squamous cell carcinoma of the tonsil treated non-surgically at the Yorkshire Cancer Centre between January 2004 and December 2005. Due to long radiotherapy waiting times, patients received induction chemotherapy with cisplatin and 5-fluorouracil followed by either cisplatin concurrent chemoradiotherapy or radiotherapy alone. Results Median age was 55 years (range 34-76 years and 28 (68% patients were male. 35/41 patients (85% received 2 or more cycles of induction chemotherapy. Following induction chemotherapy, 32/41 patients (78% had a clinical response. Concomitant chemotherapy was given to 30/41 (73%. All patients received the planned radiotherapy dose with no delays. There were no treatment related deaths. Six (15% patients had gastrostomy tubes placed before treatment, and 22 (54% required nasogastric tube placement during or after treatment for nutritional support. 17 patients required unplanned admissions during treatment for supportive care. At 4 months post treatment assessment 35 out of 41 (85% patients achieved complete clinical and radiographic response. Median follow-up is 38 months (8-61 months. Local and regional control rate in complete responders at 3 years was 91%. Distant metastases have been found in 4 (9.8% patients. Three year progression-free survival rate in all patients is 75%. The 3-year cause specific survival and overall survival are 75% and 66% respectively. Conclusion Cisplatin-based induction and concurrent chemoradiotherapy provides excellent tumour control with acceptable toxicity for patients with locally advanced tonsillar cancer.

  13. A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas.

    Science.gov (United States)

    Ansari, M; Omidvari, S; Mosalaei, A; Ahmadloo, N; Mosleh-Shirazi, M A; Mohammadianpanah, M

    2011-03-01

    The combination of cisplatin and 5-fluorouracil (PF) is currently considered a standard and effective regimen for the treatment of advanced head and neck carcinomas. The aim of this study was to evaluate the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with unresectable head and neck carcinomas. Forty-six patients with previously untreated non-metastatic stage IV head and neck carcinomas were enrolled. All patients received three cycles of induction chemotherapy with docetaxel (75 mg/m(2)), cisplatin (40 mg/m(2)) (days 1-2), and 5-FU (500 mg/m(2), days 1-3), repeated every 21 days. Following induction chemotherapy, all patients underwent concurrent chemoradiotherapy using weekly cisplatin (30 mg/m(2)) and a median total dose of 70 Gy was delivered. Clinical response rate and toxicity were the primary and secondary end-points of the study. There were 31 men and 15 women. All patients had non-metastatic stage IV (T2-3N2-3 or T4N0-3) of disease. Overall and complete response rates were 74% and 24% respectively. Advanced T4 classification was associated with poorer response rate (p value=0.042). The major (grade 3-4) treatment-related toxicities were myelosuppression (78%), anorexia (13%), diarrhea (7%), emesis (11%) and stomatitis/pharyngitis (24%). In comparison with the data of historical published trials of the PF regimen, the TPF regimen was more effective. However, the TPF regimen appears to be associated with a higher incidence of major toxicities. Therefore, our limited findings support the TPF regimen as an alternative chemotherapeutic regimen for advanced head and neck carcinomas.

  14. On the treatment of nonlinear local feedbacks within advanced nodal generalized perturbation theory

    International Nuclear Information System (INIS)

    Maldonado, G.I.; Turinsky, P.J.; Kropaczek, D.J.

    1993-01-01

    Recent efforts to upgrade the underlying neutronics formulations within the in-core nuclear fuel management optimization code FORMOSA (Ref. 1) have produced two important developments; first, a computationally efficient and second-order-accurate advanced nodal generalized perturbation theory (GPT) model [derived from the nonlinear iterative nodal expansion method (NEM)] for evaluating core attributes (i.e., k eff and power distribution versus cycle burnup), and second, an equally efficient and accurate treatment of local thermal-hydraulic and fission product feedbacks embedded within NEM GPT. The latter development is the focus of this paper

  15. Advanced materials for improving biosensing performances of propagating and localized plasmonic transducers

    Science.gov (United States)

    Manera, M. G.; Colombelli, A.; Convertino, A.; Rella, S.; De Lorenzis, E.; Taurino, A.; Malitesta, C.; Rella, R.

    2015-05-01

    Among all transduction methodologies reported in the field of solid state optical chemical sensors, the attention has been focused onto the optical sensing characterization by using propagating and localized surface plasmon resonance (SPR) techniques. The research in this field is always oriented in the improvement of the sensing features in terms of sensitivity and limits of detection. To this purpose different strategies have been proposed to realize advanced materials for high sensitive plasmonic devices. In this work nanostructured silica nanowires decorated by gold nanoparticles and active magneto-plasmonic transductors are considered as new biosensing transductors useful to increase the performance of sensitive devices.

  16. Nutritional variations during chemotherapy for patients suffering from a locally advanced oesophagus cancer

    International Nuclear Information System (INIS)

    Duclos, A.; Blondin, V.; Quiesse, M.; Iwanicki-Caron, I.; Lecleire, S.; Michel, P.; Di Fiore, F.; Dubray, B.; Di Fiore, F.

    2010-01-01

    As de-nutrition is frequently noticed for patients suffering from a locally advanced oesophagus cancer, the authors report a study of the variations of nutritional parameters during chemotherapy and of their impacts of the treatment process and efficiency. Thus, different parameters have been studied at the beginning, during and at the end of the treatment: weight, albumin range, body weight index, calorie survey, and the nutritional support type. The authors observe very important variations with a significant impact on treatment tolerance and efficiency. Short communication

  17. Single nucleotide polymorphisms in the HIF-1α gene and chemoradiotherapy of locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Ploen, John

    2012-01-01

    The aim of this study was to investigate the predictive impact of polymorphisms in the HIF-1α gene on the response to chemoradiotherapy (CRT) in rectal cancer. This study included two cohorts of patients with locally advanced rectal cancer receiving long-course CRT. The HIF-1α C1772T (rs11549465...... tumour response (P=0.03) in the validation cohort. In conclusion, these results suggest that HIF-1α polymorphisms have no value as predictors of response to neoadjuvant CRT in rectal cancer. The results of the HIF-1α c(*)191T>C in two cohorts differ and emphasise the importance of biomarker validation....

  18. Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

    Science.gov (United States)

    Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

    2017-08-01

    This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

  19. Risk Factors for Pelvic Insufficiency Fractures in Locally Advanced Cervical Cancer Following Intensity Modulated Radiation Therapy

    DEFF Research Database (Denmark)

    Ramlov, Anne; Pedersen, Erik Morre; Røhl, Lisbeth

    2017-01-01

    and underwent external beam radiation therapy with 45 Gy in 25 fractions (node-negative patients) or 50 Gy in 25 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions (node-positive patients). Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition......PURPOSE: To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: We analyzed 101 patients with LACC treated from 2008-2014. Patients received weekly cisplatin...

  20. Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

    DEFF Research Database (Denmark)

    Bjerregaard, Jon K; Mortensen, Michael B; Jensen, Helle A

    2009-01-01

    BACKGROUND: Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior...... underwent resection, leading to a resection rate of 17%, and a median survival of 46 (23-nr) months. All 11 patients had a R0 resection. Median survival for the patients not resected was 8.8 (8-12) months. CONCLUSION: CRT with 50 Gy combined with UFT, is a well-tolerated and effective treatment for patients...

  1. Characteristics of edge-localized modes in the experimental advanced superconducting tokamak (EAST)

    DEFF Research Database (Denmark)

    Jiang, M.; Xu, G.S.; Xiao, C.

    2012-01-01

    Edge-localized modes (ELMs) are the focus of tokamak edge physics studies because the large heat loads associated with ELMs have great impact on the divertor design of future reactor-grade tokamaks such as ITER. In the experimental advanced superconducting tokamak (EAST), the first ELMy high...... confinement modes (H-modes) were obtained with 1 MW lower hybrid wave power in conjunction with wall conditioning by lithium (Li) evaporation and real-time Li powder injection. The ELMs in EAST at this heating power are mostly type-III ELMs. They were observed close to the H-mode threshold power and produced...

  2. Preliminary experience with external hemipelvectomy for locally advanced and recurrent pelvic carcinoma

    DEFF Research Database (Denmark)

    Nielsen, Mette Bak; Rasmussen, Peter Chr.; Keller, Johnny Østergaard

    2012-01-01

    was found. With agreement by the multidisciplinary team, surgery was performed by a colorectal surgeon and an orthopaedic sarcoma surgeon and, if needed, by an urologist and vascular surgeon. Patients were reconstructed with either a femoral or a gluteal musculocutaneous flap. Results Of the eight women...... [median age 54.5 (40– 68) years], two had primary carcinoma and six local recurrence of a previously treated carcinoma. R0 was possible in six patients and R1 resection in two. The median duration of hospital stay was 29.5 (17– 102) days. The median follow up was 8.3 (4.7– 52.8) months. Three patients...... for a highly selected group of patients with locally advanced carcinoma or recurrence involving the lumbosacral neural plexus....

  3. Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shinoto, Makoto, E-mail: shinoto@saga-himat.jp [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu (Japan); Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yamada, Shigeru [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Terashima, Kotaro [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yasuda, Shigeo [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Shioyama, Yoshiyuki [Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Kamada, Tadashi; Tsujii, Hirohiko [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Saisho, Hiromitsu [Department of Internal Medicine and Clinical Oncology, Kaken Hospital, Chemotherapy Research Institute, Chiba (Japan); Asano, Takehide; Yamaguchi, Taketo; Amano, Hodaka; Ishihara, Takeshi; Otsuka, Masayuki; Matsuda, Masamichi; Kainuma, Osamu; Funakoshi, Akihiro; Furuse, Junji; Nakagori, Toshio; Okusaka, Takuji; and others

    2016-05-01

    Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.

  4. Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer.

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    Murphy, James D; Chang, Daniel T; Abelson, Jon; Daly, Megan E; Yeung, Heidi N; Nelson, Lorene M; Koong, Albert C

    2012-02-15

    Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost-effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer. A Markov decision-analytic model was constructed to compare the cost-effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity-modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity. SBRT increased life expectancy by 0.20 quality-adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost-effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost-effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost-effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT. The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost-effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by

  5. 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.)

  6. Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Kato, Shingo; Ohno, Tatsuya; Tsujii, Hirohiko; Nakano, Takashi; Mizoe, Jun-etsu; Kamada, Tadashi; Miyamoto, Tadaaki; Tsuji, Hiroshi; Kato, Hirotoshi; Yamada, Shigeru; Kandatsu, Susumu; Yoshikawa, Kyosan; Ezawa, Hidefumi; Suzuki, Michiya

    2006-01-01

    Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose, 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were ≥60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rate for patients in the first and second studies was 45% and 79%, respectively. When treated with ≥62.4 GyE, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors ≥6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to <60 GyE to avoid major complications. Although the number of patients in this study was small, the results support continued investigation to confirm therapeutic efficacy

  7. The specific localization of advanced glycation end-products (AGEs) in rat pancreatic islets.

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    Morioka, Yuta; Teshigawara, Kiyoshi; Tomono, Yasuko; Wang, Dengli; Izushi, Yasuhisa; Wake, Hidenori; Liu, Keyue; Takahashi, Hideo Kohka; Mori, Shuji; Nishibori, Masahiro

    2017-08-01

    Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies. We found that Glycer-AGEs and methylglyoxal-derived AGEs (MGO-AGEs) were present in pancreatic islets of healthy rats, distinguished clearly into the pancreatic α and β cells, respectively. Although streptozotocin-induced diabetic rats suffered from remarkable impairment of pancreatic islets, the localization and deposit levels of the Glycer- and MGO-AGEs were not altered in the remaining α and β cells. Remarkably, the MGO-AGEs in pancreatic β cells were localized into the insulin-secretory granules. These results suggest that the cell-specific localization of AGEs-modified proteins are presence generally in healthy peripheral tissues, involved in physiological intracellular roles, such as a post-translational modulator contributing to the secretory and/or maturational functions of insulin. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  8. Combined modality therapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Recine, D.; Rowland, K.; Reddy, S.; Lee, M.S.; Bonomi, P.; Taylor, S.; Faber, L.P.; Warren, W.; Kittle, C.F.; Hendrickson, F.R.

    1990-01-01

    Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting

  9. Risk factors for early complications after laparoscopic total mesorectal excision for locally advanced rectal cancer: A single center experience

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    Liye Liu

    2016-01-01

    Conclusions: Aged patients, large tumor, lower tumor location and conversion were risk factors in performing laparoscopic TME for locally advanced rectal cancer. Patients with these characteristics should be carefully considered before undergoing laparoscopic total mesorectal excision.

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

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    Xun He

    2015-01-01

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

  11. Curative resection for locally advanced sigmoid colon cancer using neoadjuvant chemotherapy with FOLFOX plus panitumumab: A case report

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    Kenji Tomizawa

    2017-01-01

    Conclusion: To our knowledge, this is the first report of a successful curative resection in a patient with initially unresectable, locally advanced colorectal cancer who was treated with FOLFOX4 combined with panitumumab.

  12. Radiofrequency assisted pancreaticoduodenectomy for palliative surgical resection of locally advanced pancreatic adenocarcinoma.

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    Kumar, Jayant; Reccia, Isabella; Sodergren, Mikael H; Kusano, Tomokazu; Zanellato, Artur; Pai, Madhava; Spalding, Duncan; Zacharoulis, Dimitris; Habib, Nagy

    2018-03-20

    Despite careful patient selection and preoperative investigations curative resection rate (R0) in pancreaticoduodenectomy ranges from 15% to 87%. Here we describe a new palliative approach for pancreaticoduodenectomy using a radiofrequency energy device to ablate tumor in situ in patients undergoing R1/R2 resections for locally advanced pancreatic ductal adenocarcinoma where vascular reconstruction was not feasible. There was neither postoperative mortality nor significant morbidity. Each time the ablation lasted less than 15 minutes. Following radiofrequency ablation it was observed that the tumor remnant attached to the vessel had shrunk significantly. In four patients this allowed easier separation and dissection of the ablated tumor from the adherent vessel leading to R1 resection. In the other two patients, the ablated tumor did not separate from vessel due to true tumor invasion and patients had an R2 resection. The ablated remnant part of the tumor was left in situ. Whenever pancreaticoduodenectomy with R0 resection cannot be achieved, this new palliative procedure could be considered in order to facilitate resection and enable maximum destruction in remnant tumors. Six patients with suspected tumor infiltration and where vascular reconstruction was not warranted underwent radiofrequency-assisted pancreaticoduodenectomy for locally advanced pancreatic ductal adenocarcinoma. Radiofrequency was applied across the tumor vertically 5-10 mm from the edge of the mesenteric and portal veins. Following ablation, the duodenum and the head of pancreas were removed after knife excision along the ablated line. The remaining ablated tissue was left in situ attached to the vessel.

  13. Identification of the sentinel lymph node using hemosiderin in locally advanced breast cancer

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    PAULO HENRIQUE WALTER DE AGUIAR

    Full Text Available ABSTRACT Objective: to verify the agreement rate in the identification of sentinel lymph node using an autologous marker rich in hemosiderin and 99 Technetium (Tc99 in patients with locally advanced breast cancer. Methods: clinical trial phase 1, prospective, non-randomized, of 18 patients with breast cancer and clinically negative axilla stages T2=4cm, T3 and T4. Patients were submitted to sub-areolar injection of hemosiderin 48 hours prior to sentinel biopsy surgery, and the identification rate was compared at intraoperative period to the gold standard marker Tc99. Agreement between methods was determined by Kappa index. Results: identification rate of sentinel lymph node was 88.9%, with a medium of two sentinel lymph nodes per patients. The study identified sentinel lymph nodes stained by hemosiderin in 83.3% patients (n=15, and, compared to Tc99 identification, the agreement rate was 94.4%. Conclusion: autologous marker rich in hemosiderin was effective to identify sentinel lymph nodes in locally advanced breast cancer patients.

  14. Retrospective Analysis of Locally Advanced Noninflammatory Breast Cancer From Chennai, South India, 1990-1999

    International Nuclear Information System (INIS)

    Shanta, Viswanathan; Swaminathan, Rajaraman; Rama, Ranganathan M.Sc.; Radhika, Ramachandran M.S.

    2008-01-01

    Purpose: This was a retrospective observational study to elicit the outcome of the therapeutic strategy of concurrent neoadjuvant chemoradiotherapy protocol for locally advanced breast cancer. Methods and Materials: A large series of 1,117 consecutive cases of locally advanced breast cancer treated at the Cancer Institute (WIA), in Chennai, South India, between 1990 and 1999 and followed through 2004 formed the basis for this study. Disease-free survival was the main outcome, and nodal and tumor downstaging were the intermediate outcome measures studied. Results: Primary tumor downstaging was observed in 45% and nodal downstaging in 57.5%. The disease-free survival rate of nodal downstaged patients at 5, 10, and 15 years was 75%, 65%, and 58%, respectively. The corresponding rates for pre- and postoperative node-negative patients were 70%, 60%, and 59%. The best survival was seen among those who were tumor and node negative postoperatively. Nodal downstaging halved the risk of disease recurrence and death compared with node positivity, irrespective of tumor sterility. Conclusions: A randomized trial using cyclophosphamide, methotrexate, and 5-fluorouracil vs. an anthracycline-based regimen in the setting of concurrent chemoradiotherapy appears indicated. Additional preoperative chemotherapy to maximize nodal and tumor downstaging should be investigated. A change in postoperative chemotherapy according to nodal status could also be explored

  15. Locally advanced female urethral adenocarcinoma of enteric origin: The role of adjuvant chemoradiation and brief review

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    Ling-Ping Chen

    2011-04-01

    Full Text Available Primary female urethral adenocarcinoma (FUA is rare and has a poor prognosis. The common manifestations include urethrorrhagia, urinary frequency, dysuria, urethral obstructions, focal tenderness, and urinary tract infection. These symptoms are neither diagnostic nor pathognomonic; therefore, a delay in diagnosis and even a misdiagnosis is hardly uncommon. The histogenesis of FUAs may have derived from urethritis glandularis, Mullerian ducts, Skene’s glands, or mixed origins. Tumors of different embryologic origins displayed heterogeneous pathological morphology and immunohistochemistical phenotypes. Because of its rarity and the lack of large-scale studies, there is no current consensus on the optimal treatment of urethral adenocarcinomas. Here, we report two cases of locally advanced FUA of enteric origin. They manifested as slightest warning symptoms of urinary tract infection and stress urinary incontinence, respectively. One patient died of disease progression 2 months after curative operation. The other patient underwent surgery followed by adjuvant irinotecan-containing chemoradiation, and the effect was at least modest. Hence, we recommend adjuvant chemoradiation in locally advanced FUA. Individualizing cancer care of chemoregimens in accordance with the tumor origins may probably be beneficial in FUAs.

  16. Chemotherapy related toxicity in locally advanced non-small cell lung cancer

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    Bahl Amit

    2006-01-01

    Full Text Available Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0 Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients. Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

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

    International Nuclear Information System (INIS)

    Inoue, Tatsushi; Suto, Hiromasa; Kashiwagi, Hirotaka

    2010-01-01

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

  18. Is adjuvant hysterectomy an option after radio-chemotherapy for locally advanced cervical cancer? A review

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    Cornelia Nitipir

    2018-05-01

    Full Text Available Objective. The purpose of this paper is to review the current concepts in the literature regarding the beneficial effects of adjuvant surgery after concurrent radio-chemotherapy for locally advanced cervical cancer. Method. Research of the literature was performed using PubMed databases in order to find articles relevant to the central topic. The PICOS criteria were used to filter the results. The paper was then structured according to the PRISMA guideline. Results. 50 individual papers were analyzed and sorted according to their relevance for the topic. 18 were classified as relevant. There was little agreement as to how beneficial adjuvant hysterectomy is in locally advanced cervical cancer after chemoradiotherapy. Some articles concluded that patients with a total clinical response after initial treatment might have superior progression-free survival and overall survival after surgery. 2 articles underlined the importance of accurate restaging after primary treatment. The lack of benefit for surgery in patients with bulky disease or persistent adenopathies was agreed upon in all cases. Conclusions. The decision for adjuvant hysterectomy with or without lymphadenectomy is a controversial one and has to be personalized and taken in a multidisciplinary team.

  19. [Two Cases of Curative Resection of Locally Advanced Rectal Cancer after Preoperative Chemotherapy].

    Science.gov (United States)

    Mitsuhashi, Noboru; Shimizu, Yoshiaki; Kuboki, Satoshi; Yoshitomi, Hideyuki; Kato, Atsushi; Ohtsuka, Masayuki; Shimizu, Hiroaki; Miyazaki, Masaru

    2015-11-01

    Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46-year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub-intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case.

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

    Science.gov (United States)

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

    2016-02-01

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

  1. Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

    International Nuclear Information System (INIS)

    Hsieh, Chen-Hsi; Shueng, Pei-Wei; Wei, Ming-Chow; Lee, Hsing-Yi; Hsiao, Sheng-Mou; Chen, Chien-An; Wang, Li-Ying; Hsieh, Yen-Ping; Tsai, Tung-Hu; Chen, Yu-Jen

    2009-01-01

    To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer. Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m 2 intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully. HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted

  2. THORACO - ABDOMINAL FLAP FOR RESURFACING LARGE POST MASTECTOMY DEFECTS IN LOCALLY ADVANCED CA. BREAST

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    Srinivasa Rao

    2015-02-01

    Full Text Available Covering of large wounds after mastectomy in locally advanced Ca breast with skin that can withstand radiotherapy is a challenge to the surgeon. Here this study we used a local advancement flap from the adjacent area called Thoraco - A bdominal F la p (TA flap for such giant defects. This is based on superficial and lumbar arteries and is thick to with stand consequent RT . MATERIALS AND METHODS: Of the total 107 cases of LABC 32 had post mastectomy defects of larger than 12 cm and could not be closed by simple approximation. Among the 32 cases 17 cases are covered by split thickness skin grafting. 15 cases are covered by TA flap. These cases are assessed for mean operating time, mean blood loss, post - operative stay, flap necrosis and viability of the f lap after radiotherapy. RESULTS: There is minimal extra time or blood loss in these cases . All the flaps healed well except for small edge necrosis in 4 cases. In all the patients we could start radiotherapy in the fourth week of surgery and all the flaps withstood RT well. After further evaluation probably this can be recommended as procedure for giant post mastectomy defects particularly for those who require RT early

  3. Hemoglobin as an important prognostic factor in concurrent chemoradiotherapy for locally advanced carcinoma of the cervix

    International Nuclear Information System (INIS)

    Toma, Takashi; Nagai, Yutaka; Moromizato, Hidehiko; Toita, Takafumi; Murayama, Sadayuki; Kanazawa, Koji

    2005-01-01

    The objective of this study was to examine a possible association of hemoglobin with clinical outcome in patients with locally advanced squamous cell carcinoma of the cervix who were treated with concurrent chemoradiotherapy (CCRT). Seventy-five patients with Stage IB to IVA disease who were treated with CCRT were reviewed retrospectively. The mean age was 49.8 years. In the treatment, standard radiotherapy was performed accompanied by concomitant chemotherapy using cisplatin. Pre-treatment hemoglobin was defined as the earliest hemoglobin level prior to the initiation of treatment. Weekly nadir hemoglobin levels throughout treatment were averaged and used as average weekly nadir hemoglobin during treatment (AWNHg). The mean follow-up time was 28.6 months. The mean pre-treatment hemoglobin of 11.6 g/dL was significantly reduced to the mean AWNHg of 9.9 g/dL. The levels of pre-treatment hemoglobin and AWNHg were significantly associated with tumor response to treatment. The 5-year cumulative disease-free survival and overall survival rates for all 75 patients were 67.8% and 75.3%, respectively. Multivariate statistical analysis revealed that AWNHg (≥9.0 versus <9.0 g/dL) was an independent prognostic factor for overall survival (p=0.038), but pre-treatment hemoglobin was not a significant factor. AWNHg was one of the most powerful independent predictors of overall survival in patients undergoing CCRT for locally advanced squamous cell carcinoma of the cervix. (author)

  4. Retrospective analysis of role of interstitial brachytherapy using template (MUPIT in locally advanced gynecological malignancies

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    Nandwani Pooja

    2007-01-01

    Full Text Available Aim : The aim of this retrospective study was to assess treatment outcomes for patients with locally advanced gynecological malignancies being treated with interstitial brachytherapy using Martinez universal perineal interstitial template (MUPIT and to study the acute and late sequelae and survival after treatment by this technique. Materials and Methods : Ninety seven patients untreated with histopathological confirmation of carcinoma of cervix (37 vault (40 and vagina (20 were treated by combination of external beam RT (EBRT using megavoltage irradiation to pelvis to dose of 4000-5000 cGy followed by interstitial brachytherapy using MUPIT between September 2001 to March 2005. Median age was 46 years. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitatory radiotherapy was found to be unlikely to encompass a proper dose distribution were treated by interstitial template brachytherapy using MUPIT application and were enrolled in this study. The dose of MUPIT was 1600-2400 cGy in 4-6# with 400 cGy /# and two fractions a day with minimum gap of six hours in between two fractions on micro-HDR. Criteria for inclusion of patients were as follows: Hb minimum 10 gm/dl, performance status - 70% or more (Karnofsy scale, histopathological confirmation FIGO stage IIB-IIIB (excluding frozen pelvis. Results : Among the 97 patients studied, 12 patients lost to follow-up and hence they were excluded from the study. Follow-up of rest of the patients was then done up to September 2006. The duration of follow-up was in the range of 20-60 months. Parameters studied were local control rate, complication rate, mortality rate and number of patients developing systemic metastasis. Local control was achieved in 56/85 (64.7% and complication rate was 15/85 (17.6%. Local control was better for nonbulky tumors compared bulky tumors irrespective of stage of disease. Local control was better in patients with good regression of

  5. A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

    OpenAIRE

    Chitapanarux, Imjai; Chomprasert, Kittisak; Nobnaop, Wannapa; Wanwilairat, Somsak; Tharavichitkul, Ekasit; Jakrabhandu, Somvilai; Onchan, Wimrak; Traisathit, Patrinee; Van Gestel, Dirk

    2015-01-01

    The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan w...

  6. KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Young; Shim, Eun Kyung [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Yeo, Hyun Yang [Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Tae Won [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jee Hyun [Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Im, Seock-Ah [Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Kyung Hae [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Chang, Hee Jin, E-mail: heejincmd@yahoo.com [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2013-01-01

    Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with

  7. KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

    International Nuclear Information System (INIS)

    Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang; Baek, Ji Yeon; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seock-Ah; Jung, Kyung Hae; Chang, Hee Jin

    2013-01-01

    Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m 2 weekly and 1650 mg/m 2 /day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m 2 on 1 week before radiation, and 250 mg/m 2 weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus

  8. [A Case of Effective Chemoradiotherapy Using mFOLFOX6 for Locally Advanced Rectal Cancer].

    Science.gov (United States)

    Kuga, Yoshio; Kitamura, Shosuke; Mouri, Teruo; Miwata, Tomohiro; Hirata, Yuzoh; Ishizaki, Yasuyo; Hashimoto, Yasutoshi

    2017-05-01

    We report a case of locally advanced rectal cancer, treated effectively with chemotherapy consisting of mFOLFOX6 combined with radiotherapy. A 63-year-old man was admitted to our hospital in March 2012 for diarrhea and anal and perineal pain. Advanced rectal cancer with invasion ofthe right perineum was diagnosed based on computer tomography(CT) findings. Surgery was performed; however, the rectal cancer was unresectable. A sigmoid colostomy was performed, and a central venous port was implanted. In April 2012, the patient was treated with chemotherapy using 3 courses ofmFOLFOX6 and concurrent radiotherapy. Radiotherapy at 2 Gy/day was administered 25 times(total dose, 50 Gy). After chemoradiotherapy, the patient underwent 3 courses ofmFOLFOX6 as an additional therapy. By June 2012, CT showed resolution ofthe tumor in the right perineum and a marked decrease in the size ofthe primary rectal cancer. Because the patient refused surgery, we started treatment with combination chemotherapy using oral S-1 and intravenous CPT-11 in August 2012. After 18 courses, the treatment was changed to oral administration ofS -1 alone, which was continued for 1 year. The patient remained well without recurrence for 54 months since the original diagnosis. Therefore, chemoradiotherapy with mFOLFOX6 is a possible option for the management of advanced rectal cancer.

  9. Quantitative ultrasound characterization of locally advanced breast cancer by estimation of its scatterer properties

    Energy Technology Data Exchange (ETDEWEB)

    Tadayyon, Hadi [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Sadeghi-Naini, Ali; Czarnota, Gregory, E-mail: Gregory.Czarnota@sunnybrook.ca [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5T 1P5 (Canada); Wirtzfeld, Lauren [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Wright, Frances C. [Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada)

    2014-01-15

    Purpose: Tumor grading is an important part of breast cancer diagnosis and currently requires biopsy as its standard. Here, the authors investigate quantitative ultrasound parameters in locally advanced breast cancers that can potentially separate tumors from normal breast tissue and differentiate tumor grades. Methods: Ultrasound images and radiofrequency data from 42 locally advanced breast cancer patients were acquired and analyzed. Parameters related to the linear regression of the power spectrum—midband fit, slope, and 0-MHz-intercept—were determined from breast tumors and normal breast tissues. Mean scatterer spacing was estimated from the spectral autocorrelation, and the effective scatterer diameter and effective acoustic concentration were estimated from the Gaussian form factor. Parametric maps of each quantitative ultrasound parameter were constructed from the gated radiofrequency segments in tumor and normal tissue regions of interest. In addition to the mean values of the parametric maps, higher order statistical features, computed from gray-level co-occurrence matrices were also determined and used for characterization. Finally, linear and quadratic discriminant analyses were performed using combinations of quantitative ultrasound parameters to classify breast tissues. Results: Quantitative ultrasound parameters were found to be statistically different between tumor and normal tissue (p < 0.05). The combination of effective acoustic concentration and mean scatterer spacing could separate tumor from normal tissue with 82% accuracy, while the addition of effective scatterer diameter to the combination did not provide significant improvement (83% accuracy). Furthermore, the two advanced parameters, including effective scatterer diameter and mean scatterer spacing, were found to be statistically differentiating among grade I, II, and III tumors (p = 0.014 for scatterer spacing, p = 0.035 for effective scatterer diameter). The separation of the tumor

  10. Quantitative ultrasound characterization of locally advanced breast cancer by estimation of its scatterer properties

    International Nuclear Information System (INIS)

    Tadayyon, Hadi; Sadeghi-Naini, Ali; Czarnota, Gregory; Wirtzfeld, Lauren; Wright, Frances C.

    2014-01-01

    Purpose: Tumor grading is an important part of breast cancer diagnosis and currently requires biopsy as its standard. Here, the authors investigate quantitative ultrasound parameter