bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model of comparative effectiveness research (CER): The impact of biologic agents in a cohort of patients from ethnic minorities with metastatic colorectal cancer (mCRC).
Authors: Shah Umang , Khot Ashish Abhay , Goyal Dharmendra , Guo Shuang , Kaubisch Andreas , Rajdev Lakshmi , Goel Sanjay , Aparo Santiago 
Published: February 2017

591 Background: The role of biologic agents in the treatment of mCRC has been studied in clinical trials. These studies included ≥ 90% patients (pts) of white race. Hispanics and blacks were largely underrepresented. CER allows exploration of the impact of biologic agents in a cohort composed largely of pts from minorities. We present the results of a cohort of pts served by Montefiore Einstein Cancer Center (MECC) in Bronx, NY. Methods: Pts diagnosed and treated for mCRC from January 2000 to December 2011 were identified using data from the MECC Cancer Registry. Pts demographic and clinical characteristics were extracted from pts medical records. A Cox proportional–hazard model was used to assess survival differences between pts treated with chemotherapy alone vs. pts treated with chemotherapy plus biologics. Results: A total of 293 pts where identified; 45% were black, 27% were Hispanic, and 28% were white. Of the pts receiving biologics, 90% received bevacizumab and 50% received cetuximab or panitumumab. The median overall survival was 15.2 months in the chemotherapy alone group and 25.6 months chemotherapy + biologics group (p=0.003). Univariate analysis showed that 1 metastatic site vs. ≥ 2, CEA <40 ng/mL, receiving ≥ 2 lines of chemotherapy and exposure to biologics were independently associated with longer survival. Multivariate analysis of the whole cohort (n=290), which included all ethnic groups, showed that exposure to biologics offered a survival benefit (HR of 0.70, 95%CI 0.52–0.93, p=0.02), after adjusting for gender, age, CEA, number of metastatic sites and lines of chemotherapy received. Subgroup analysis based on ethnicity showed survival benefit for Whites (HR of 0.38, 95%CI 0.22–0.66, P=0.001) but not for Hispanics (HR of 0.65, 95%CI 0.35–01.23, p=0.18) nor Blacks (HR of 1.04, 95%CI 0.63–1.70, p=0.87). Conclusions: In this cohort weighted heavily towards ethnic minorities, the addition of biologics to chemotherapy was associated with longer survival, an effect mainly driven by whites. Hispanics and blacks did not seem to benefit from exposure to biologics. An effort should be made to include minority pts in ongoing clinical trials.
Treatment and outcomes of neuroendocrine malignancies (NEMs) of the rectum.
Authors: Tsang Erica , Speers Caroline , Kennecke Hagen F. 
Published: February 2017

594 Background: NEMs of the rectum are rare and standard therapy is not well defined. We sought to characterize the clinicopathologic features, locoregional, and systemic management of a series of rectal NEMs and correlated these with outcomes. Methods: Patients referred to the BC Cancer Agency with rectal NEMs between 2005-2011 were included. Well-differentiated tumors with a Ki67 ≤20% and/or mitotic count ≤ 20 per high power field were classified as neuroendocrine tumors (NETs) while poorly differentiated tumors with higher Ki67 and/or mitotic count were classified as neuroendocrine carcinomas (NECs). Results: Of 28 NEMs, 18 (64%) NETs, and 9 (36%) NECs were identified with a median age of 56 and 59, respectively. Of 15 patients with stage I-III NETs, 13 underwent local excision, 2 had a surgical resection and none received pelvic radiation. Univariate analysis demonstrated an association between tumor size (< 1cm, 1-2 cm, > 2cm) and T stage (χ2 = 10.7, p = 0.03). One of 15 NETs developed distant relapse 8.9 months after surgical resection of a T1bN1 tumor. Of 9 NECs, only 2 presented with stage I-III tumors and were treated with radiation (1) or surgery (1). One patient developed distant relapse 4.8 months after radiation. Among all NEMs, liver was the most common site of metastasis (n = 10) followed by bone (n = 3). Median overall survival was 46.5 and 4.8 months for NETs and NECs (p < 0.01), respectively. Conclusions: Rectal NEMs comprise a rare subgroup of rectal tumors and may be classified as NETs or NECs. NETs generally present with early stage disease and are associated with good outcomes with local excision and without pelvic radiation. Rectal NECs frequently present with advanced disease and are associated with poor outcomes.
The efficacy and safety outcomes of bevacizumab and systemic therapy in metastatic colorectal cancer patients with peritoneal disease in the AGITG MAX clinical trial and in nontrial patients in two cancer centers.
Authors: Roohullah Aflah , Sjoquist Katrin Marie , Gebski Val , Ng Weng , Chua Wei , Price Timothy Jay , Tebbutt Niall C. , Chantrill Lorraine A. 
Published: February 2017

595 Background: Metastatic colorectal cancer with peritoneal disease (PmCRC) represents a phenotype that may derive a greater clinical benefit from bevacizumab (BEV) due to the effect of VEGF on peritoneal spread and ascites production. However, there is concern of greater adverse events, in particular GI perforations. We investigated the clinical benefit and safety of adding BEV to chemotherapy in PmCRC in clinical trial and nontrial populations. Methods: We compared PFS and OS in PmCRC patients receiving first-line chemotherapy with and without BEV in: (1) the AGITG MAX trial (capecitabine [CAP] vs CAP/BEV +/- mitomycin C) and (2) two cancer centers in New South Wales between Jan 2005 and Dec 2012 (any regimen +/- BEV). Secondary endpoints included chemotherapy duration and GI adverse events. Time to event outcomes were estimated using the method of Kaplan-Meier and comparisons made using the logrank test. Proportional hazards models were used to obtain hazard ratios for regression analysis. Results: See Table. 84 MAX and 69 nontrial pts had PmCRC and there was a 37% reduction in the risk of progression in those receiving BEV, which is similar when compared to the nonperitoneal disease pts (HR= 0.63 95% CI 0.52-0.79 p value < 0.001). OS in the PmCRC group was significantly worse than the nonperitoneal group (14.3 months vs 18.8 months p value = 0.02). Chemotherapy duration was similar across the groups. The rate of notable GI adverse events, including GI perforation was not increased in the PmCRC group receiving BEV in either cohort. One pt had a GI perforation after receiving CAP+BEV. Conclusions: Pts with mCRC and peritoneal disease receiving first-line therapy in trial and nontrial populations appear to derive a similar proportional benefit when BEV is added to systemic therapy without an increase in GI adverse events. However, this subgroup of patients continues to have a worse prognosis. [Table: see text]
Association of the prognostic role of FGFR4 Gly388Arg polymorphism with treatment outcomes after chemoradiotherapy in esophageal cancer.
Authors: Cho Sanghee , Shin Min-Ho , Hwang Jun-Eul , Shim Hyung-jung , Kim Min-Jee , Chung Ik-Joo 
Published: February 2017

60 Background: Fibroblast growth factor receptor 4 (FGFR4) has been associated with increased risk, staging, and metastasis in several type of cancer. The purpose of this study was to evaluate the prognostic role of FGFR4 Gly388Arg polymorphism in esophageal cancer after chemoradiotherapy. Methods: Peripheral blood samples from 250 patients who were treated with chemoradiotherapy were used for this study. Patients were diagnosed as a stage of I in 12 (5%), II in 54 (21%), III in 115 (46%) and IV in 69 (28) patients. All of the patients were received chemotherapy using cisplatin and fluorouracil or docetaxel. Results: The overall response was 85%, with 21% complete response and 64% partial response. The overall survival (stage II, 34months; stage III, 23.3 months; stage IV, 19.3 months, p=0.005) and progression survival (stage II, 23.8 months; stage III, 12.8 months; stage IV, 9 months, p=0.001) was significantly improved according to stage. In FGFR4 genotypic analysis, 96 patients (38.6%) were homozygous for Gly388 allele, with 113 heterozygous (45.4%) and 40 (16.0) homozygous for Arg388 allele. There was no significant association between FGFR4 genotype and stage. However, Gly388 allele patients show better overall response rate (90.6%) than Arg388 carriers (82.4%, p=0.050). In early stage (I, II, n=66), Gly388 allele patients tendted to have a better OS (p=0.898) or PFS (p=0.597) than Arg388 carriers. However, in advanced stage (III, IV), the survival outcomes was similar between genotypes. Conclusions: Present study shows that FGFR4 Gly388 allele has a prognostic role in response after chemoradiotherapy in esophageal cancer. Especially in early stage of esophageal cancer, FGFR4 might have an important role in disease progression and survival outcomes. It suggests that the possibility of new therapeutic target for esophageal cancer treatment.
Work satisfaction at a multidisciplinary gastrointestinal oncology fast-track outpatient clinic.
Authors: Basta Yara , Vogel Jantien A. , Molenaar J. , Tytgat Kristien M. A. J. , Klinkenbijl Jean H. G. 
Published: February 2017

605 Background: Physician and nurse satisfaction is positively correlated with patient satisfaction. In our university centre we have established the Gastrointestinal Oncology Clinic Amsterdam (GIOCA), a patient centred multidisciplinary one day diagnostics and fast track treatment planning outpatient clinic for gastrointestinal malignancies. The GIOCA team consists of dedicated surgeons, gastroenterologists, medical oncologists, radiation oncologists, radiologists, nuclear radiologists, pathologists, and specialized nurses. We have measured a high patient satisfaction. However to our knowledge there are no studies that focus on the satisfaction of physicians and nurses working within a multidisciplinary team. Our aim was to evaluate the experience and work satisfaction of the physicians and nurses at GIOCA. Methods: A qualitative observational study was performed to compose a questionnaire. This questionnaire was then sent to every physician (specialist, fellow, and resident) and nurse (n=77) working at the outpatient clinic. Answers were given on a 5-point Likert scale. Data were analysed using non-parametric tests. Results: The questionnaire was answered by 73 respondents, of whom 8.2% were nurses and 91.8% were physicians (95% overall response rate). Overall satisfaction with the fast track outpatient clinic was high for all groups (4; 3-5). The workload was experienced as average by physicians and high by nurses (p<0.001). The highest emotional strain was reported by nurses and residents. The emotional strain reported by residents was significantly higher compared to the level of emotional strain reported by specialists (p=0.034). The quality of the multidisciplinary meeting was rated high by both physicians and nurses. The importance of a multidisciplinary one day diagnostics outpatient clinic was invariably rated high to very high by all physicians and nurses. Conclusions: The overall work satisfaction at GIOCA is high. A patient centred one day diagnostics and fast track treatment outpatient clinic for gastrointestinal malignancies is indispensible according to the physicians and nurses. This may have contributed to a high patient satisfaction and a high overall work satisfaction.
Retrospective cohort study of patients with anal cancer treated over a 12-year period at a large Canadian cancer center.
Authors: Abunassar Michael J. , Reinders Jordan , Jonker Derek J. , Asmis Timothy 
Published: February 2017

606 Background: While optimal management of anal cancer has become better defined in light of recent clinical trials including selected patients, the outcomes in an unselected population are less well defined. We reviewed the outcomes of anal cancer patients in a population referred to a sole-provider regional cancer program at the Ottawa Hospital over a 12 year period (2000 to 2011). Methods: Patient data was collected from hospital records, including demographic, treatment and outcome. Outcomes of interest included overall and recurrence free survival, as well as colostomy free survival. Results: Patients were 72% (n = 130) female and 28% (n = 50) male, 6.6% (n = 12 males) HIV positive, 60% (n = 108) ever smokers, mean age 62 [range 35-90] years. Most frequent presenting symptoms were blood per rectum (87%) and anal pain (80%). Treatment intent was curative in 87%. Treatment included radiotherapy (94%), brachytherapy (26%), chemotherapy (73%). Combined chemoradiotherapy was received by 71%, including MMC-5FU (n = 87) and cisplatin+5FU (n = 41). Among patients treated with curative-intent, 72% had a complete response, 31% local/regional recurrence, 16% required salvage surgery and 21% had distant recurrence. Colostomy rate was 23%. 5 year overall survival (OS) was not significantly different for patients by HIV status; 52 vs. 60% for HIV positive vs negative, respectively, HR 1.36, p = 0.47. Survival was superior if MMC+5FU was used first vs. Cisplatin+5FU; 5yOS 73 vs 46% respectively, [HR 0.45 (95%CI 0.25 – 0.83), log rank p = 0.013]. Conclusions: The outcomes of patients in this large retrospective cohort study are similar to the outcomes of patients in highly selective clinical trials. Five year overall survival and colostomy free survival are encouraging. MMC +5FU was found to be superior to Cisplatin +5FU. Further study is required to improve outcomes for patients with metastatic disease.
Preoperative radiotherapy combined with simultaneous chemotherapy with capecitabine plus oxaliplatin versus surgery alone: A single-centered, phase II study in patients with mid/low rectal cancer.
Authors: Wang Fulong , Lu Zhen-Hai , PAN Zhizhong , Gao Yuan-Hong , Chen Gong , Wu Xiaojun , Ding Pei-Rong , Zeng Zhi-Fan , Wan Desen 
Published: February 2017

609 Background: Though total mesorectal excision (TME) has proved to effectively decrease local recurrence rate of mid/low rectal cancer, the efficacy of preoperative radiotherapy in Asian patients remains unclear. The present study aimed to compare the efficacy of TME alone versus TME after preoperative radiotherapy and simultaneous chemotherapy with capecitabine plus oxaliplatin in Chinese patients with stage II and III mid/low rectal adenocarcinoma. Methods: Patients (n=192) aged between 18 and 70 years enrolled from March 23, 2008 to August 2, 2012 were randomly divided into two groups. Group A (n=97) received preoperative radiotherapy and simultaneous chemotherapy [46-50 GY/23-25 with oxaliplatin 100 mg/m2 (D1) and capecitabine 1,000 mg/m2 (bid, D1-15), repeated since D22], which was followed by TME; while patients in group B (n=95) underwent TME alone. While disease free survival (DFS) was the primary endpoint; the following were evaluated as secondary endpoints: pathological response rate, pathologic complete response (PCR) rate, anal preservation rate, local recurrence rate, distant metastasis rate, acute toxic effects, and late toxic effects. Results: Excluding the drop outs, 90 and 94 patients were analyzed in group A and B, respectively. The median follow-up time was 29 (range: 0 to 59) months. PCR was achieved for 32 patients (35.6%). The median survival time and overall survival (OS) rate in group A were 24 months and 92.5% (95% CI: 88.3-96.7), respectively; while the same were 34 months and 88.7% (95% CI: 84.8-92.6) in group B. The median DFS time was 22 and 31 months in group A and B, respectively; and the overall DFS was 86.1% (95% CI: 81.6-90.6%) and 80.6% (95% CI: 74.8-85.4%) in both groups. No significant differences were observed between groups in OS rate (p=0.323), overall DFS, (p=0.612), and anal preservation rate (p=0.849). Conclusions: Preoperative radiotherapy combined with chemotherapy of capecitabine plus oxaliplatin could result in higher PCR rate. However, studies with long follow up and large sample are recommended to demonstrate the efficacy of this treatment strategy over TME alone. Clinical trial information: ChiCTR-TRC-00000122.
A phase II study of cetuximab (cet) and mFOLFOX6 in metastatic colorectal cancer (mCRC) (JACCRO CC-05).
Authors: Yamaguchi Tatsuro , Tsuji Akihito , Sunakawa Yu , Nakamura Masato , Kochi Mitsugu , Denda Tadamichi , Shimada Ken , Tani Satoshi , Takagane Akinori , Kotaka Masahito , Kuramochi Hidekazu , Koike Junichi , Furushima Kaoru , Yonemura Yutaka , Negoro Yuji , Takinishi Yasutaka , Takeuchi Masahiro , Ichikawa Wataru , Fujii Masashi , Nakajima Toshifusa 
Published: February 2017

611 Background: FOLFOX4 combined with cet for mCRC patients (pts) with KRAS wild tumor demonstrated the prolonged progression-free survival (PFS) with higher response rate (RR) in the OPUS study. To evaluate the clinical efficacy and safety of the cet plus mFOLFOX6, we conducted a multi-center phase II study of Japanese pts. Methods: In this trial, pts with KRAS wild type tumor and receiving no prior chemotherapy for mCRC were treated with cet (initial dose 400, and 250 mg/m2 weekly) followed by mFOLFOX6 (oxaliplatin 85mg/m2, l-leucovorin 200 mg/m2, fluorouracil, as 400mg/m2 intravenous bolus then 2,400mg/m246-hour continuous infusion). The treatment was repeated every 2 weeks. The primary endpoint was RR evaluated by the external review board according to RECIST v1.1. Secondary endpoints included PFS, OS, % chronological change at the base line and safety. Results: A total of 57 pts were enrolled from August 2010 to September 2011. The median age was 60 years, 65% of pts were male, and ECOG PS 0 was observed in 91% of pts. All pts had EGFR-expressing disease. The median treatment courses were 21 (cet) and 10 (FOLFOX). The RR was 66.7% (95%CI, 53.4 to 77.7). Complete remission was observed in 5 cases (9.3%). The median PFS was 11.1 months (95%CI, 8.0 to 14.7). The early tumor shrinkage (ETS; over 20% regression at 8 weeks) was observed in 80% of pts, and the PFS for pts with ETS was statistically significantly prolonged as compared with pts without ETS (median PFS, 11.5 vs. 3.7 months, respectively; p = 0.0002). The OS was not reached at the time of median follow-up (19.2 months). Grade 3 or worse adverse events were neutropenia (48.2%), leucopenia (22.2%), rash acneform (20.4%), and peripheral neuropathy (18.5%). Conclusions: The first-line cet+mFOLFOX6 has an acceptable safety profile and demonstrates advantages in response rate for pts with KRAS wild tumor. The first-line cet+mFOLFOX6 should be considered as one of the recommended treatment regimens for pts with KRAS wild tumor. Update survival data will be presented. Clinical trial information: UMIN000004197.
Surgical management of synchronous colorectal liver metastases: Simultaneous versus staged resections.
Authors: Shchepotin Igor , Lukashenko Andrii , Kolesnik Olena , Burlaka Anton 
Published: February 2017

616 Background: Surgical treatment of metastatic colorectal cancer remains the only method that improves overall 5-year survival. This study aimed to compare the surgical outcome and survival benefit between synchronous and staged resection of liver metastases from colorectal cancer. Methods: Clinicopathologic data, treatments, and postoperative outcomes from 110 patients who underwent simultaneous (48 patients, group A) or staged (62 patients, group B) colorectal and hepatic resections at clinic of National cancer institute in period of 2008-2013 were reviewed. Results: Postoperative complications in patients with simultaneous resections (group A) were observed in 13 cases (27.1%), including 5, 1, 4, 2, 0, and 1 of grades I, II, IIIa, IIIb, IV, and V, respectively. Similar results have been reported in group B after staged resections, where overall postoperative complications registered in 16 patients (25.8 %), including 4, 3, 6, 3, 0 of grades I, II, IIIa, IIIb, and IV respectively. Overall level of post-operative complications in the groups A and B after surgical stages finishing did not differ statistically (p=0.96). Shorter operative intervention duration was registered in the group A – (311±10.1) min, whereas in the group B it was (496.6±16.2) min (р<0.001). Patients after staged resection stayed in clinic for a longer time – 23.9±0.8 bed-days, when simultaneous resections provided with shorter recovery terms in post-operative period – 9.8±0.5 bed-days (p<0.001). Overall 3-year survival in the group of patients with simultaneous resections (group А) was 42 % and in the group B 55 % (р=0.22). Conclusions: Analysis of our research indicated necessity of the development of differentiated approach in management of synchronous colorectal liver metastatic cancer. Simultaneous resections of colorectal cancer primary lesions and hepatic metastases were safe and could serve as a primary option for selected patients. Subsequent research should be directed towards study of prognosis factors and criteria for patients’ selection for surgical treatment groups, assessment of economic effect, and patients life quality.
Combination of 5FU-based chemoradiation with EGFR inhibitor cetuximab and effect on PCR rate in patients undergoing neoadjuvant treatment in advanced rectal cancer.
Authors: Semrau Robert , Kocher Martin , Vallbohmer Daniel , Hoelscher Arnulf 
Published: February 2017

623 Background: Neoadjuvant chemoradiation is a standard treatment for advanced rectal cancer patients. Here, we investigate whether treatment combined with the EGFR inhibitor cetuximab could enhance prognosis. Safety and efficacy (pathohistological regression rate, pCR) of chemoradiation in combination with cetuximab were evaluated. Methods: In a single-center phase I/II study patients with adenocarcinoma of the rectum (up to 16 cm above the anal verge) in stage cT3-4, cN0-1, were treated with cetuximab (weekly 250mg/m2, loading dose 400mg/m2) combined with radiotherapy (50,4Gy in 28 fractions) and 5-FU. Maximal tolerated dose of 5FU in combination with cetuximab and radiotherapy was determined in a phase I part (3+3 design; dose level 1: 750 mg/m2 5FU days 1-5 and 29-33; dose level 2: 1000 mg/m2 5FU days 1-5 and 29-33. Surgery was performed between 4 to 6 weeks after combined treatment. pCR rate of tumor cells was determined after surgery. Results: 20 patients were included into the trial, 19 patients received treatment: In the phase I part 2 out of 6 patients in level 2 experienced dose limiting toxicities (thrombocytopenia and diarrhea grade 3). Therefore, dose level 1 was considered safe for further enrollment. All 19 patients received the complete course of radiotherapy (50,4Gy). 15 patients received the complete cetuximab schedule, one patient discontinued after an allergic reaction at the first infusion, 3 patients missed 1 cycle of cetuximab in week 3 or 6. 18 patients continued to surgery. Sphincter preservation surgery was performed in 12 patients (63.2%), R0-resection rate was 100%. pCR grade IV (pCR) was documented in 1 patient (5,5%), grade III in 4 patients and grade I and II in 13 patients. So far no local recurrences occurred, 4 patients died (3 patients due to metastatic disease progression). Conclusions: The MTD of 5FU in combination with radiotherapy and cetuximab was 750mg/m2. Treatment was well tolerated and did not alter surgical management. However, pCR-rate was not elevated compared to standard 5FU-based preoperative chemoradiation. Whether the addition of cetuximab improves prognosis in this group of patient remains unclear. Clinical trial information: 2005-004139-23.