bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early and long-term outcome data on 2,298 patients with pseudomyxoma peritonei of appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Authors: Chua Terence C. , Moran Brendan J. , Sugarbaker Paul H. , Levine Edward Allen , Glehen Olivier , Gilly Francois N. , Elias Dominique , Baratti Dario , Deraco Marcello , Sardi Armando , Morris David L. ,   Peritoneal Surface Oncology Group International
Published: February 2017

532 Background: Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of this study was to evaluate the outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an International Registry study. Methods: A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International (PSOGI). Results: 2298 patients from 16 specialized units underwent CRS for PMP. Treatment related mortality was 2% and major operative complication was 24%. The median survival was 196 months (16.3 years) and the median progression-free survival was 98 months (8.2 years) with a 10- and 15-year survival rate of 63% and 59% respectively. Multivariate analysis identified prior chemotherapy treatment (P<0.001), PMCA histopathological subtype (P<0.001), major postoperative complication (P=0.008), high PCI (P=0.013), debulking surgery (CCR2/3) (P<0.001), not using HIPEC (P=0.030) as independent predictors for a poorer progression-free survival. Older age (P=0.006), major postoperative complication (P<0.001), debulking surgery (CCR2/3) (P<0.001), prior chemotherapy treatment (P=0.001) and PMCA histopathological subtype (P<0.001) were independent predictors of a poorer overall survival. Conclusions: The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10-years. Minimizing non-definitive operative and systemic chemotherapy treatments prior to definitive cytoreduction may facilitate the feasibility and outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.
Predictive value of the antiangiogenic VEGF splice variant expression for bevacizumab efficacy in the phase III trial of bevacizumab and FOLFOX4 versus FOLFOX4 in previously treated patients with advanced colorectal cancer (ECOG E3200T2).
Authors: Bates David O. , Catalano Paul J. , Symonds Kirsty E. , Varey Alexander H. R. , Ramani Pramila , O'Dwyer Peter James , Giantonio Bruce J. , Meropol Neal J. , Benson Al Bowen , Harper Steven J. 
Published: February 2017

545 Background: Treatment of metastatic colorectal cancer (CRC) with bevacizumab (anti-VEGF) in combination with chemotherapy increases survival in a proportion of patients, but it is not possible a priori to predict which patients will receive benefit. The VEGF-A gene is alternatively spliced into two families by alternative splice site usage in exon 8. The pro-angiogenic (e.g. VEGF165) isoforms are generated by proximal splice site selection, and the anti-angiogenic (e.g. VEGF165b) by distal splice site selection. The relative levels of the isoforms vary in CRC. VEGF165b over-expression in mice inhibits bevacizumab treatment.We tested the hypothesis that survival would be better in patients with low VEGF165b levels on bevacizumab than placebo. Methods: To determine whether survival was better in patietns with low VEGF165b when treated with FOLFOX4+bevacizumab (Arm A) than FOLFOX4 + placebo (Arm B), 108 coded patient samples from the E3200 trial of FOLFOX4±bevacizumab (NCT NCT00897754 ) were successfully stained for VEGF-A165b and scored in well differentiated tissue relative to normal tissue blind to outcome. The VEGF165b expression relative to normal tissue was calculated. 108 cases were analysed for VEGF165b/Normal, 48 in arm A, 60 in Arm B. Results: Adjusted Cox Binary analysis of VEGF165b/Normal comparing staining ratio in bevacizumab versus placebo treated patients demonstrated significantly better survival for the less than median ratios (HR=0.28, p=0.0031, median progression free survival, 8.4 versus 5.1 months in placebo), whereas in the higher than median VEGF165b/Normal group there was no effect of bevacizumab (HR=0.96, median PFS, 11.9 compared with 11.0months). Results held after adjustment for other clinical and demographic features in proportional hazards regression modelling. Conclusions: In conclusion, these results indicate that low VEGF165b levels in well-differentiated tumours may predict response to bevacizumab.
Influence of age on chemoradiotherapy outcome in patients with rectal cancer: Exploratory analysis from the phase III study ACCORD 12/0405 PRODIGE 2.
Authors: Francois Eric , Azria David , Gourgou-Bourgade Sophie , Martel-Lafay Isabelle , Hennequin Christophe , Etienne Pierre-Luc , Vendrely Veronique , Seitz Jean Francois , Conroy Thierry , Juzyna Beata , Gerard Jean-Pierce 
Published: February 2017

550 Background: Preoperative radiochemotherapy (RCT) is the standard of care for patients (pts) with locally advanced rectal adenocarcinoma. However elderly pts may have an increased risk of adverse events after combined modality treatment. The randomized trial ACCORD 12/0405 PRODIGE 2 compared 5 weeks of treatment with radiotherapy 45 Gy/25 fractions (f) with concurrent capecitabine 800 mg/m² twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 f with capecitabine 800 mg/m2 twice daily, 5 days per week and oxaliplatin 50 mg/m2 once weekly (Capox 50), results of efficacy (complete pathologic response) were not different between the two arms. We analyzed the results of RCT according to pts age. Methods: All eligible pts (n=584) were included in this exploratory analysis. Pts were divided in 2 groups: <70 y and ≥70 y. Toxicity and tumor regression scores were compared between the 2 groups. Results: 442 pts were <70 y and 142 were ≥70 y. Pts characteristics were well balanced between groups (gender, ECOG performance status, primary tumor, histology). Tolerance was worse in pts ≥70 y as shown in the table. Surgical procedures were not different between the 2 groups. Results on histological response were similar between the 2 groups: complete pathologic response was 16.9% (95% CI 13.1 to 20.2%) for pts <70 y and 14.7% (95% CI 9.2 to 21.8%) for pts ≥70 y, (p=0.55) and rates of R0 surgery for pts < 70 y and pts ≥ 70 y were respectively: 90.6% and 88.2%, (p=0.54). Conclusions: As tolerance of elderly pts treated with preoperative RTCT is worse than in younger pts, appropriate therapeutic schedule are warranted for these pts. [Table: see text]
Ten-year results of the Lyon R96-2 randomized trial in distal rectal cancer: Radiation dose escalation to increase organ preservation.
Authors: Gérard Jean-Pierre , Ortholan Cecile , Chapet Olivier , Romestaing Pascale 
Published: February 2017

556 Background: This trial was designed to test the role of a radiation dose escalation to increase conservative treatment in distal rectal cancer. The early results showed a significant increase of sphincter saving surgery (Gerard JP et al. J Clin Oncol. 2004;22:2404-2409). We present here clinical results with a 10 years follow up. Methods: Between 199- and 2001, 88 patients were included. Inclusion criteria were: adenocarcinoma of the distal rectal, T2-3 N0 M0 less not exceeding half circumference. Treatment allocation was betweeen 1) external beam radiotherapy(EBRT) (39 Gy/13 fractions/17 days) followed 6 weeks later by surgery. 2) same EBRT with Contact X-Ray 50 Kv boost (CXRT) (90 Gy /3fr/4 weeks). A careful evaluation of the clinical response was performed with digital examination and rigid rectoscopy one week before surgery. Type of surgery was left to the surgeon decision. Results: Median follow-up was 132 months. At 10 years there was no difference between both groups for overall survival and local recurrence but significantly less colostomy in the CXRT group (table). In patient with cCR the cumulated rate of colostomy was 17 % vs 42 % with cPR and 77 % with no response (p=0.014) out of 11 pts in cCR with EBRT + CXRT, 9 were treated with organ preservation (RT alone : 6, transanal local excision 3). Anorectal function was good or excellent in all these 9 patients. Conclusions: After 10 years follow up increased preservation of the anal sphincter due to CXRT has no detrimental effect on local control and survival. These results stress the importance to achieve a clinical complete response (cCR) in order to modify the surgeon decision and to increase the chance of organ preservation with a well preserved function. [Table: see text]
Macroscopic tumor size as an independent prognostic factor for patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1.
Authors: Aoyama Toru , Yoshikawa Takaki , Hayashi Tsutomu , Kuwabara Hiroshi , Mikayama Yo , Ogata Takashi , Cho Haruhiko , Tsuburaya Akira 
Published: February 2017

56 Background: In patients with stage II/III gastric cancer, tumors often recur even after curative D2 gastrectomy followed by adjuvant S-1 chemotherapy. The objective of this retrospective study was to clarify the prognostic factors in these patients that might be useful for future patients. Methods: Overall survival was examined in 82 gastric cancer patients who underwent curative D2 surgery, were diagnosed with stage IIA, II B, IIIA, IIIB, or IIIC pathologically, and received adjuvant S-1 after surgery between June of 2002 and March of 2010. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter and the depth of tumor invasion. A macroscopic tumor diameter greater than 70mm was regarded as a critical point of classification considering the survival. Uni- and muliti-variate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 64.9% in patients with a macroscopic tumor diameter <70mm, and 33.1% in patients with a macroscopic tumor diameter ≥70mm (P=0.022). Conclusions: The macroscopic tumor diameter was the most important prognostic factor for survival in patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant S-1 chemotherapy. Prognostic factors can be affected by adjuvant chemotherapy.
Systemic therapy for advanced appendiceal adenocarcinoma: An analysis from the National Comprehensive Cancer Network (NCCN) database.
Authors: Tejani Mohamedtaki Abdulaziz , ter Veer Anna , Milne Dana , Ottsesen Rebecca , Bekaii-Saab Tanios S. , Benson Al Bowen , Schrag Deborah , Shibata Stephen , Skibber John Michael , Weiser Martin R. , Wilkinson Neal W. , Cohen Steven J. 
Published: February 2017

562 Background: Appendiceal neoplasms are rare and represent 1% of intestinal tumors in the United States. The role and efficacy of modern systemic therapy in advanced appendiceal adenocarcinoma has not been established. Methods: Patients with recurrent or metastatic appendiceal adenocarcinoma in the NCCN Colorectal Database (2005-2010) were analyzed. Study objectives were to describe and evaluate the efficacy of systemic therapy and investigate relationships with clinicopathologic features. Cox regression analysis was performed to identify predictors of PFS and OS. The hazard ratio and 95% CI from Cox models and median PFS and OS from Kaplan-Meier curves were reported. Results: Of 177 patients with advanced appendiceal carcinoma, 81 (46%) received systemic therapy for measurable disease and are the focus of this report (patients undergoing IP chemotherapy excluded). Patient/tumor characteristics: median age 50 (range 20-82), ECOG PS 0/1 (67%/22%), mucinous/non-mucinous (44 %/ 51%), 91% peritoneal and 15% liver metastases. 70% of patients had primary surgical debulking. Common chemotherapy regimens included FOLFOX with or without bevacizumab (n=30 and n=28), FOLFIRI (n=11), and single-agent fluoropyrimidine (n=7). Among 70 patients with a recorded best response, the response rate (RR) was 46% with 31% stable disease. Median PFS was 1.0 year (95% CI: 0.7-1.9) and OS was 2.1 years (95% CI: 1.7-2.6). Patients with non-mucinous histology, high grade tumors and non-debulking surgery had worse PFS and OS (Table). Conclusions: Treatment of advanced appendiceal adenocarcinoma at NCCN centers commonly incorporates agents utilized for colorectal cancer. RR, PFS and OS are comparable to those achieved in the treatment of metastatic CRC and support routine use of these regimens in clinical practice. Poor prognostic factors include non-mucinous histology, high grade and not undergoing debulking surgery. [Table: see text]
Use of bevacizumab to reduce the rate of oxaliplatin-induced thrombocytopenia and splenomegaly.
Authors: Overman Michael J. , George Binsah , Kalil Karime , Ferrarotto Renata , Eng Cathy , Garrett Chris R. , Loyer Evelyn , Hoff Paulo Marcelo , Charnsangavej Chusilp , Kopetz Scott 
Published: February 2017

564 Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. In the NSABP C-08 study a reduced rate of thrombocytopenia (1.4% vs 3.4%, P <0.01) was seen in the bevacizumab arm. Evidence suggests that bevacizumab may protect against HSI, though the clinical impact of this has not been well examined. Methods: A retrospective review of metastatic colorectal cancer patients treated at MD Anderson Cancer Center from 1/2003 to 1/2010 with ≥3 months of frontline fluoropyrimidine and oxaliplatin (FOLFOX) with or without bevacizumab was conducted. Presence of known liver disease, prior liver surgery, absence of spleen, or adjuvant oxaliplatin were exclusion criteria. Splenic volumes pre, during, and post FOLFOX treatment were determined from CT scans and correlated with platelet counts and treatment. Results: 184 pts (138 FOLFOX/Bev; 46 FOLFOX) were identified. The median number of cycles (9 for each cohort) and the total oxaliplatin dose (P = 0.78) did not differ between the two cohorts. The development of splenomegaly (spleen volume increase of ≥30%) was more common in the non-Bev cohort, 48% vs 32%, P=0.013. The median time to splenomegaly was longer in the Bev cohort, 7.6 vs 5.5 months, P=0.023. When comparing patients with and without splenomegaly, the presence of splenomegaly correlated with thrombocytopenia (<150 platelet count) at 3 months (40% vs. 16%, P=0.0005) and beyond (lower mean platelet counts during 3 to 6 months of treatment, P <0.0001 by Two-way ANOVA). A correlation with thrombocytopenia was also seen in the non-Bev vs. Bev cohort at both 3 months (43% vs 24%, P = 0.006) and beyond (P = 0.003). Conclusions: The addition of bevacizumab to oxaliplatin chemotherapy reduces the frequency of splenic enlargement, which directly correlates with a reduced rate of thrombocytopenia. Further study to understand the hepato-protective mechanism of anti-VEGF therapy is needed.
Dose-painted intensity-modulated radiation therapy (DP-IMRT) for anal cancer: No differences in treatment toxicity and early outcomes between human immunodeficiency virus (HIV) positive and negative patients.
Authors: Romesser Paul B. , Mancias Joseph D. , Qureshi Muhammad M. , Hartshorn Kevan L. , Willins John D. , Hong Theodore S. , Kachnic Lisa A. 
Published: February 2017

565 Background: HIV-infected patients are reported to experience increased treatment toxicity with standard concurrent chemoradiation (CRT) protocols for anal cancer. IMRT is a novel radiation (RT) delivery technique that allows the oncologist to conform or “dose paint (DP)” the RT dose to the tumor while sparing surrounding normal organs. We report our multi-institutional experience with DP-IMRT in regards to acute toxicities and treatment outcomes in HIV positive (HIV+) patients on highly active antiretroviral therapy (HAART). Methods: From August 2005 to December 2010, 63 patients, (10 HIV+), were treated with CRT for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. HIV+ and HIV- patients received a median DP-IMRT dose of 50.4 Gy over 43.5 and 42.0 days, respectively. Acute toxicities were graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Two year actuarial control and survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up was 29.3 and 24.3 months for HIV+ and HIV- patients, respectively. No significant differences were noted in acute grade 3+ toxicity in HIV+ versus HIV- patients: dermatologic 10.0% vs. 13.21%, p=1.0; genitourinary 10.0% vs. 3.77%, p=0.410; gastrointestinal 20.0% vs. 15.09%, p=0.653; and hematologic 80.0% vs. 64.15%, p=0.474. Multivariate analysis confirmed that HIV infection was not predictive of acute grade 3/4 toxicity. No significant differences were noted in 2-year local control (90.0% vs. 95.0%), distant control (90.0% vs. 89.7%), overall survival (90.0% vs. 89.2%), and colostomy-free survival (90.0% vs. 83.7%) rates among HIV+ vs. HIV- patients. Conclusions: HIV+ patients on HAART receiving concurrent chemotherapy with DP-IMRT for anal canal cancer showed similar two-year outcomes and no significant differences in acute toxicity compared to HIV- patients. As such, HIV+ patients with anal cancer should be considered eligible for all national trials in which IMRT is employed.
Preplanned initial safety analysis of ACTS-CC 02 trial: A large randomized phase III trial of SOX versus UFT/LV as adjuvant chemotherapy for high-risk stage III colon cancer.
Authors: Takiuchi Hiroya , Tomita Naohiro , Boku Narikazu , Watanabe Toshiaki , Kotake Kenjiro , Itabashi Michio , Takahashi Keiichi , Baba Hideo , Morita Satoshi , Sugihara Kenichi 
Published: February 2017

572 Background: The ACTS-CC 02 trial is designed to verify the superiority of postoperative adjuvant chemotherapy of S-1/Oxaliplatin (SOX) for patients with anyT, N2 colon cancer compared with UFT/Leucovorin (UFT/LV), which is one of standard adjuvant chemotherapies in Japan. To date, there have been no reported phase III trials evaluating SOX as postoperative adjuvant chemotherapy. This report presents initial safety data obtained from 50 patients who received SOX in the trial. Methods: Patients who underwent curative resection for anyT, N2 colon cancer were randomly assigned to receive either SOX (100 mg/m2 of oxaliplatin on day1, and 80 to 120 mg/day according to body surface area (BSA) of S-1 on days 1-14, every 21 days, 8 courses) or UFT/LV (300 to 600 mg/day according to BSA of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 courses). Data were collected from initial consecutive 50 patients assigned to the SOX group and analyzed when they were considered evaluable for safety as planned in the protocol. This ongoing trial is designed to accrue 1200 patients. As of September 15, 2011, 319 patients have been accrued. Results: Of 50 patients assigned to receive SOX, 48 were evaluable for safety. The median number of treatment courses was 5 (range: 1-8). The relative dose intensity of S-1 was 83.8% and that of oxaliplatin was 86.6%. Grade 3 adverse events were neutropenia (14.6%), thrombocytopenia (2.1%), ALT elevation (2.1%), diarrhea (8.3%), fatigue (2.1%), and peripheral sensory neuropathy (2.1%). Grade 4 adverse effects were not observed. Conclusions: In this initial safety analysis, the incidence and severity of adverse events with SOX were acceptable in patients with high risk stage III colon cancer after curative resection. Enrollment of patients is ongoing.
Validating the prognostic relevance of initial change in tumor size using a series of therapeutic regimens for patients with metastatic colorectal cancer (mCRC).
Authors: Mansmann Ulrich Robert , Laubender Ruediger P. , Giessen Clemens Albrecht , Sartorius Ute , Heinemann Volker 
Published: February 2017

580 Background: Piessevaux et al. (ESMO 2010, Abstr. #596P) proposed a decrease in tumor size of 20% at week 8 following 1st-line therapy for mCRC as a predictor of clinical outcome (PFS and OS). Based on the results of a single study Suzuki et al. (Ann. Oncol. 2011) also claimed that change in tumor size at the first follow-up CT scan was strongly prognostic for PFS and OS in mCRC. It is of interest to validate these findings in different treatment regimens. Methods: Based on data from 4 randomized trials (FIRE-1, n = 479; CIOX, n = 185; OPUS, n = 337; CRYSTAL, n = 1198) a total of 6 treatment regimens were studied (mIROX/FUFIRI, CAPIRI/CAPOX + cetuximab, FOLFOX4 + cetuximab, FOLFOX4, FOLFIRI + cetuximab, FOLFIRI). A joint model was used to quantify the non-linear, J-shaped individual relationships between time and largest diameter (LD) and incorporate them into the formal risk calculation for PFS and OS. The first radiological tumor assessment was performed weeks 7-9 after the start of treatment and relative tumor shrinkage compared to baseline evaluated. Results: All 6 groups showed a consistent pattern for PFS and OS. Distinctive shrinkage week 8 (weeks 7-9) was associated with an improved individual prognosis (p<0.0001 in each group). This was even more pronounced for larger sized tumors (LD >100 mm) at baseline (p<0.01 in each group). Distinctive individual shrinkage for a corresponding treatment was defined as shrinkage exceeding the 8 week shrinkage of its mean tumor kinetics. Distinctive shrinkage for the 3 combination chemotherapy regimens was observed with individual shrinkage above 16%, 23%, or 26%. For the 3 combination chemotherapy regimens + cetuximab distinctive shrinkage was reached if individual shrinkage was greater than 21%, 24%, and 29% respectively, independent of KRAS status. Predictivity has not yet been examined. Conclusions: Our results validate the prognostic relevance of the 20% cut-off for shrinkage at week 8. Early tumor shrinkage is a promising surrogate for PFS and OS using a variety of therapeutic regimens for mCRC. These data may serve as a basis for modifying the widely adopted RECIST criteria in favor of modified response evaluation criteria.