bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of open colectomy on resection of colorectal liver metastases.
Authors: Robinson Stuart Michael , Arlott Lucas , Sen Gourab , French Jeremy J. , Charnley Richard M. , Manas Derek M. , White Steve A. 
Published: February 2017

783 Background: Laparoscopic liver resection (LLR) is increasingly utilized in the management of patients with metastatic colorectal cancer. The aim of this study was to determine the impact of open vs. colonic resection of the primary tumour on outcomes following LLR. Methods: A prospectively maintained database was searched to identify all patients undergoing laparoscopic resection for colorectal liver metastases (CRLM) between 1/1/2007 and 31/12/2013. Demographic, histological, surgical outcome and survival data were collated retrospectively. Statistical analysis was performed using SPSS. Results: A total of 71 patients (median age 66 yr; 64% male) underwent resection in this study of whom 35 had a laparoscopic colectomy (LC). The presence of a previous open colectomy (OC) surgical morbidity (17% vs. 11%; p=0.53); conversion to open surgery (22% both groups; p=0.95); duration of surgery (240 min vs. 285 min; p=0.28); or length of hospital stay (5 vs. 6 days; p=0.98). Overall survival in this series was 47 months with no difference between groups (p=0.58). Patients who underwent OC appeared to have a poorer recurrence free survival (8 vs. 21 months; p=0.03) although on multivariate analysis the only factor predictive of early recurrence was a node positive primary (OR 3.8; p=0.05). Conclusions: In patients being considered for LLR for metastasic colorectal cancer the surgical approach to colectomy has no bearing on either short term surgical outcomes or longer term disease specific survival.
Association of histologic grade and subtypes of gastric cancer (GC) with chemoradiation response.
Authors: Charalampakis Nikolaos , Nogueras-Gonzalez Graciela M. , Wang Xuemei , Elimova Elena , Shiozaki Hironori , Wadhwa Roopma , Planjery Venkatram , Garris Jeana , Rogers Jane Elizabeth , Hiremath Adarsh , Blum Mariela A. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Estrella Jeannelyn , Matamoros Aurelio , Das Prajnan , Badgwell Brian D. , Ajani Jaffer A. 
Published: February 2017

97 Background: Patients with localized gastric cancer (LGC), when treated with preoperative therapy, tend to have heterogeneous and unpredictable outcomes. Currently, no clinical variables or biomarkers can predict response. Methods: We analyzed 107 LGC patients who were treated with chemoradiation followed by surgery (trimodality therapy; TMT). Tumors were grouped into poorly (G3) or moderately (G2) differentiated and signet ring cell (SRC) or non-SRC histology. Association was made with pathologic complete response (pathCR) or < pathCR. Descriptive statistics and survival analyses were utilized. Results: The majority of the patients were male (60%), had clinical stage III cancer (51%), and received chemotherapy before chemoradiation (94%). All had adenocarcinoma and most had G3 (78%) and SRC histology (58%). PathCR was noted in 18% of patients with G3 and 33% of patients with G2 (p=0.125). Overall survival (OS) was significantly shorter for G3 patients compared to G2 patients (p=0.045). Patients with SRC histology had a lower rate of pathCR than those with non-SRC (8% vs 40%, p<0.001). Patients with SRC histology had a trend towards shorter OS (p=0.063). Surgical pathologic stage was independently associated with OS and recurrence-free survival (RFS) (p<0.001). Conclusions: Our data suggest that histologic grade/ subtypes are associated with response to preoperative chemoradiation. Independent validation and addition of biomarkers could allow individualization of therapy of LGC patients. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI). Dr. Nikolaos Charalampakis has been awarded a scholarship from the Hellenic Society of Medical Oncology.
A phase 3, multicenter, randomized, double-blind, placebo-controlled study of rilotumumab in combination with cisplatin and capecitabine (CX) as first-line therapy for Asian patients (pts) with advanced MET-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The RILOMET-2 trial.
Authors: Doi Toshihiko , Kang Yoon-Koo , Muro Kei , Jiang Yizhou , Jain Rajul K. , Lizambri Richard 
Published: February 2017

TPS226 Background: Rilotumumab is an investigational, fully human monoclonal antibody to hepatocyte growth factor, the only known ligand of the MET receptor. In a phase 2 study, trends toward improved progression-free survival (PFS) and overall survival (OS) were seen with rilotumumab plus epirubicin, cisplatin and capecitabine (ECX) vs ECX alone in pts with G/GEJ cancer; the treatment effect of rilotumumab was enhanced in MET-positive pts (Iveson et al. Lancet Oncol 2014;15:1007). In a phase 1/1b study, rilotumumab plus CX had manageable toxicities and a favorable pharmacokinetic (PK) profile in Japanese pts with MET-positive G/GEJ cancer (Doi et al. J Clin Oncol 2014;32:5s,abstract 4051). Methods: In this phase 3 study, 450 pts from Asian countries are randomized 1:1 to CX (intravenous [IV] cisplatin 80 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 twice daily on days 1−14) plus double-blind rilotumumab 15 mg/kg or placebo IV on day 1 every 3 weeks for up to 6 cycles. After cycle 6, pts will receive capecitabine plus rilotumumab or placebo. Randomization is stratified by disease extent (locally advanced vs metastatic), prior surgery for G/GEJ or esophageal cancer (yes vs no), and country (China vs other). Key eligibility criteria include previously untreated, pathologically confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma, ≥20 years, ECOG score ≤1, MET-positive by centralized immunohistochemistry, HER2-negative, adequate organ function, and ≥6 months since neoadjuvant/adjuvant therapy. The primary endpoints are PFS and OS. A log-rank test stratified by the randomization factors will compare PFS and OS between arms. Key secondary endpoints include 12-month survival rate, time to progression, objective response and disease control rates, duration of/time to response, safety, and PK. Enrollment began in July 2014, and the trial continues to recruit participants. The study is overseen by an independent data monitoring committee. ClinicalTrials.gov: NCT02137343. Sponsor: Amgen Inc. Clinical trial information: NCT02137343.
Phase 3 randomized, double-blind, controlled study of cabozantinib (XL184) versus placebo in subjects with hepatocellular carcinoma who have received prior sorafenib (CELESTIAL; NCT01908426).
Authors: Abou-Alfa Ghassan K. , Cheng Ann-Lii , Meyer Tim , El-Khoueiry Anthony B. , Ikeda Masafumi , Chun Hoo Geun , Furuse Junji , Knox Jennifer J. , Okusaka Takuji , Ping Jerry , Borgman-Hagey Anne E. , Kelley Robin Kate 
Published: February 2017

TPS496 Background: Currently, there are no approved systemic therapies for patients with advanced hepatocellular carcinoma (HCC) who fail sorafenib. Cabozantinib is an oral receptor tyrosine kinase inhibitor (TKI) with activity against tyrosine kinases including MET, RET and VEGFRs. MET and VEGFR signaling have been implicated in tumor neo-angiogenesis and invasion. MET is overexpressed in HCC compared with non-tumor liver tissue, with higher MET expression linked to poor prognosis. Cabozantinib prolonged survival in a MET-driven transgenic mouse model of HCC, and has demonstrated clinical activity in multiple solid tumor types, including 41 subjects with advanced HCC treated in a phase 2 randomized discontinuation study. Methods: This phase 3, randomized, double-blind study evaluates the efficacy and safety of cabozantinib compared with placebo in subjects with advanced HCC previously treated with sorafenib and have progressed following 1-2 prior systemic treatments for HCC. Subjects must be ≥ 18 year old, have Child-Pugh Score of A and ECOG PS ≤ 1. Subjects are randomized 2:1 to receive either cabozantinib or placebo. Stratification factors are etiology of disease, geographic region and the presence of extrahepatic spread of disease and/or macrovascular invasion. The primary endpoint is overall survival. Secondary endpoints are progression-free survival and objective response rate by RECIST 1.1. Additional endpoints include safety, tolerability, circulating tumor cells, serum bone markers and plasma biomarkers, effects on bony disease assessed by bone scan and health-related quality of life (HRQoL) using the EuroQol Health questionnaire (EQ-5D-5L). Enrollment was initiated in September 2013. Target recruitment is 760 subjects. A total of 621 events planned with 2 interim analyses (at 311 and 466 events) would provide 90% power to detect a 31.6% increase in OS (HR=0.76). Clinical trial information: NCT01908426.
A phase II trial of regorafenib as a single agent in patients with advanced and metastatic biliary tract carcinoma and first-line chemotherapy failure.
Authors: Patel Anuj Kishor , Stoller Ronald G. , Rhee John C. , Lembersky Barry C. , Ohr James , Lee James J. , Bahary Nathan , Chu Edward , Sun Weijing 
Published: February 2017

TPS498 Background: Biliary tract cancers (including cholangiocarcinomas) are rare but aggressive malignancies with limited options for treatment. Currently, the combination of gemcitabine and cisplatin is considered the upfront systemic chemotherapy for patients with advanced and metastatic diseases. There is no ‘standard’ for second-line treatment. Several signaling pathways have been identified that might play a role in the development of biliary tract cancer and that may represent targets for directed therapies. Overexpression of VEGF and alterations of the Ras/Raf pathway have been identified in the majority of cholangiocarcinoma; some studies have shown these mutations to be associated with metastasis and poorer prognosis. Regorafenib is an oral multikinase inhibitor of multiple angiogenic and oncogenic kinases (VEGFR1-3, TIE2, PDGFR-β, FGFR1, KIT, RET, RAF) which has shown efficacy as a single agent in multiple solid tumors. This study evaluates the efficacy of regorafenib in patients with advanced/metastatic biliary tract cancer following the failure of first-line chemotherapy. Methods: Enrollment in this phase II, single-arm trial is ongoing. Eligible patients have unresectable advanced or metastatic biliary tract adenocarcinoma, and have failed first-line systemic chemotherapy. Patients receive regorafenib 120 mg orally daily in a 21 days on, 7 days off cycle. Tumor measurements take place every 3 cycles by CT or MRI imaging. Patients continue on therapy until disease progression or unacceptable toxicities. The primary end point of this study is median progression-free survival (PFS). To evaluate for evidence of activity, defined as a median PFS of 3.5 months or greater, with 83% power (one-sided test, α=0.10), target enrollment is 37 patients. Secondary endpoints include safety, overall response rate, disease control rate, median overall survival, and changes in biomarker levels. The correlation of these biomarkers and of tumor mutations with response to treatment is built into the study as well. As of September 2014, 9 patients had been enrolled. ClinicalTrials.gov Identifier: NCT02053376. Clinical trial information: NCT02053376.
The MIRACLE trial: A randomized, controlled trial comparing green tea extract versus placebo for the prevention of metachronous colon adenomas in a screening population.
Authors: Ettrich Thomas Jens , Stingl Julia , Muche Rainer , Claus Katrin , Reiser Baerbel , Seufferlein Thomas 
Published: February 2017

TPS786 Background: Prevention of colorectal cancer is a major health care issue. After polypectomy there is an increased risk of polyp recurrence and various means of chemoprevention have been tried to prevent this. NSAIDs have been shown to be effective but confer side effects such as gastrointestinal bleeding. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and some clinical trials. However, their value in preventing colorectal polyps has not been demonstrated in a large, randomized trial. The beneficial safety profile of decaffeinated green tea extract and accumulating evidence of its cancer preventive potential justify and require, in our view, a validation of this compound for the nutriprevention of colorectal adenoma. Good accessibility and low costs might render this neutraceutical a top candidate for wider use as nutritional supplement in colon cancer prevention. Methods: Randomized, double blinded, placebo-controlled, multicenter trial. After a one month run-in period with verum, 918 patients (age: 50-80 years) who have undergone polypectomy within the last 6 months will be randomized to receive either decaffeinated green tea extract (containing 150 mg epigallocatechin gallate (EGCG) two times daily) or placebo over a period of three years. Primary outcome: Incidence of metachronous colorectal adenomas (tubulovillous, tubular, villous, serrated lesions) at the 3 year follow-up colonoscopy. Secondary outcomes: Occurrences, number, localization, size and histological subtypes of adenomas, frequency of colorectal carcinoma. In addition, genetic and biochemical biomarkers in blood samples and genetic alterations (Ras, B-raf, microRNAs) in tissue samples of adenomas will be analyzed (biobanking subprojects). Additionally, nutrikinetics and nutrigenetics of EGCG and other catechins will be assessed in healthy volunteers. Patient recruitment has started in November 2011. At September 2014, 785 patients were recruited and 651 patients were randomized. We expect the last patient out in Spring 2018. (Trial identifier NCT01360320) Clinical trial information: NCT01360320.
Phase III study of regorafenib versus placebo as maintenance therapy in RAS wild type metastatic colorectal cancer (RAVELLO trial).
Authors: Martinelli Erika , Troiani Teresa , Venturini Filippo , Cervantes Andres , Douillard Jean Yves , Falcone Alfredo , Folprecht Gunnar , Köhne Claus-Henning , Taïeb Julien , Tabernero Josep , Cardone Claudia , Sforza Vincenzo , Martini Giulia , Napolitano Stefania , Capuano Annalisa , Auricchio Fabiana , Ciardiello Fortunato 
Published: February 2017

TPS789 Background: Treatment of metastatic colorectal cancer (mCRC) has improved due to the introduction of more active chemotherapies (CT) and novel targeted agents that have significantly increased response rate (RR), progression free survival (PFS) and overall survival (OS). Recently, CORRECT and CONCUR trials have demonstrated both activity and efficacy of regorafenib, a small multi-kinase inhibitor, as monotherapy in pretreated mCRC. The wide range of action of regorafenib makes it an ideal candidate for monotherapy in earlier disease treatment lines in which different pathways could be involved in the acquisition of resistance. To improve long term efficacy of first line therapy several therapeutic approaches of maintenance treatment have been explored in mCRC. Methods: RAVELLO is an academic randomized, double-blind, placebo-controlled, multi-center, phase III study designed to evaluate efficacy and safety of regorafenib as maintenance treatment after first line therapy. Eligible patients: pathologically confirmed mCRC RAS wild type (KRAS and NRAS genes) treated with a first line fluoropyrimidine-based CT in combination with an anti-EGFR (epidermal growth factor receptor) monoclonal antibody for a minimum of 4 to a maximum of 8 months, with a stratification by response to the first line treatment (complete response/partial response or stable disease). 480 patients will be enrolled and randomly assigned in a 1:1 ratio to receive 160 mg regorafenib or placebo per os, every day for 3 weeks of every 4 weeks cycle, until disease progression or unacceptable toxicity. Primary endpoint is PFS. With a two-tailed alpha error of 0.05, the study will have 90% power to detect a 3-month prolongation of median PFS from randomization (corresponding to a hazard ratio of progression of 0.67 with 6-month median PFS expected in the control arm). Secondary endopoint are OS, safety, and biomarker correlative studies. Currently, one patient has been enrolled and is on treatment. EudraCT number: 2013-005428-41. Clinical trial information: 2013-005428-41.
Randomized phase II studies comparing pathological responses observed on colorectal cancer metastases resected after preoperative treatment combining bevacizumab or cetuximab with FOLFOX or FOLFIRI.
Authors: Van Den Eynde Marc , Castella Marie-Laure , Machiels Jean-Pascal H. , Humblet Yves , Canon Jean-Luc Re , Houbiers Ghislain , Demolin Gauthier , D'Hondt Lionel A. , Coche Jean-Charles , Van Daele Daniel , Delaunoit Thierry , Goeminne Jean Charles. , Beniuga Gabriella , Pairet Geraldine , Sempoux Christine , Jouret-Mourin Anne , Van Maanen Aline , Carrasco Javier 
Published: February 2017

TPS795 Background: Even if the use of targeted therapies combined with chemotherapy has demonstrated increase response rate and survival benefit in non resectable metastatic colorectal cancer (mCRC), the administration of these combinations in frontline resectable disease is source of debate and optimal association is still unclear. Based on a retrospective analysis, we previously reported thatthe chemotherapy partner combined with VEGF or EGFR inhibitors influenced pathological responses (pR) on the resected colorectal cancer metastases (CRCM) with a significant advantage for oxaliplatin with anti-VEGF or irinotecan with anti-EGFR combinations. We aimed to design 2 parallel studies (BEV-ONCO, CET-ONCO) to prospectively precise optimal combination between oxaliplatin and irinotecan with bevacizumab or cetuximab before CRCM resection. Methods: The 2 studies are open label randomized multi-centric trials and concern mCRC patients with resectable disease in whom a preoperative treatment is considered. The primary objective is to assess the CRCM pR rate according the Tumor Regression Grade classification (Rubbia-Brandt) after allocated preoperative treatment (bevacizumab combined with FOLFOX vs. FOLFIRI without consideration of RAS/BRAF for BEV-ONCO trial (EUDRACT 2012-005376-34) and cetuximab associated with FOLFOX or FOLFIRI only for RAS/BRAF wild type tumor for CET-ONCO trial (EUDRACT 2012-005249-19)). According investigator’s choice, patient will received 3 to 6 treatment cycles before CRCM resection. Patient’s survival, safety, surgical complications and treatment associated liver-toxicity are secondary end-points. Up to 60 patients (30 per treatment group) will be randomised in each study (power: 80%, type I error of 5% to detect a difference in proportion of pR rate between FOLFOX or FOLFIRI association of 0.40). Formal comparison will not be done across studies. Translational research projects are ongoing (CRCM immune response, tumour specific genetic rearrangements as new specific biomarkers). Clinical trial information: NCT01858649 (BEV-ONCO); NCT01858662 (CET-ONCO). Clinical trial information: NCT01858649 (BEVONCO) NCT01858662 (CETONCO).
FGFR1, a new FISH biomarker, to predict recurrence of prostate cancer after prostatectomy.
Authors: Zhang Ying , Du Jing , Liu Ping , Buckingham Lela , Colpitts Tracey , Pestova Ekaterina 
Published: February 2017

100 Background: To identify prostate cancer (CaP) with high recurrence risk after Radical Prostatectomy (RP) is a challenge. FGFR1 (Fibroblast Growth Factor Receptor 1) plays a critical role in prostate development and tumorigenesis. In this study, we explored the possibility of using FGFR1 fluorescence in situ hybridization (FISH) to predict recurrence after RP in the Formalin fixed paraffin embedded (FFPE) tissue from CaP patients. Methods: FFPE histological specimens from 52 RP cases were evaluated with FGFR1 (8p12) / CEP 8 probe mix. While 32 of the 52 patients recurred within 5 years (PSA progression or death of disease), and 20 remained disease-free with 8 to 15 years. Median age of patients was 62 with Gleason Score range from 4 to 9. Percent of FGFR1 gain and FGFR1 loss per specimen, as well as mean number of FGFR1 signals per specimen were calculated. CEP8 was used as a control to assess hybridization quality. Statistical analysis (Cox Proportional Hazards model) was conducted using SAS 9.2. Results: Survival analysis demonstrated that percent FGFR1 loss in a specimen could identify recurrent CaP with the Harzard Ratio (HR) of 3.34 (p=0.0011), which indicated that the risk of recurrence for FGFR1 loss-positive group is 3.34 times than that for FGFR1 loss-negative group. On the other hand, survival analysis of the percent FGFR1 gain showed that FGFR1 gain (amplification) is favorable for survival with HR of 0.36 (p=0.0043), which indicated that the risk of recurrence for FGFR1 gain-positive group is 0.36 times than that for FGFR1 gain-negative group. By using mean FGFR1 signals per specimen in the Kaplan-Meier analysis, the patient specimens stratified into three distinct groups (overall logrank p=0.0011): normal for FGFR1, FGFR1 gain (more favorable outcome), and FGFR1 loss (highest risk of recurrence). Conclusions: This study shows the utility of FGFR1 copy number abnormalities in CaP. Our results indicate that gain and loss of FGFR1 may have a different effect on disease recurrence. Therefore, FGFR1 FISH may provide predictive value for CaP recurrence in post RP patients, either by itself, or as an adjunct to the currently clinical prognostic indicators.
Intermediate-risk prostate cancer: A Medicare-based cost comparison of five radiotherapy regimens.
Authors: Nichols Romaine Charles , McIntyre Kathy , Gifford Juana , Ritz Steve K. , Klein Stuart , Bryant Curtis , Henderson Randal H. , Mendenhall William M. , Mendenhall Nancy Price , Hoppe Bradford S. 
Published: February 2017

108 Background: Patients with intermediate risk prostate cancer choosing radiotherapy may be treated with a number of regimens. The current study compares the direct treatment cost for five therapeutic options based on Fiscal Year 2014 Medicare allowable reimbursements. Methods: Hypothetical charge sheets were generated along with the expected Medicare allowable reimbursements (based on global billing where applicable) for the following regimens: 1.) Image Guided Intensity Modulated Radiotherapy (IGIMRT) to a dose of 78Gy in 39 fractions with one field reduction (IGIMRT); 2.) Dose escalated IGIMRT to 84.60Gy in 47 fractions with one field reduction (MSKCC-IGIMRT); 3.)IGIMRT to a dose of 45Gy in 25 fractions followed by a 90 seed I125 prostate implant (IGIMRT-BTX); 4.) Image Guided Proton Therapy to a dose of 78Gy(RBE) in 39 fractions with one field reduction (SFPT); 5.) Image Guided Hypofractionated Proton Therapy to a dose of 72.50Gy(RBE) in 29 fractions with one field reduction (HFPT). Results: Based on Fiscal Year 2014 Medicare allowable reimbursements, the direct cost for each of these interventions including professional fees, technical fees, isotope costs and facility fees is shown in the Table. Conclusions: This data presents a framework for evaluating the cost effectiveness of proton therapy as compared to competing therapeutic options. Under current Medicare allowable reimbursements, the cost of proton therapy relative to the cost of other therapeutic options is highly dependent on the number of radiotherapy fractions delivered. The feasibility of delivering hypofractionated proton therapy for patients with localized prostate cancer is being investigated at a number of institutions as well as within the framework of a multicenter protocol. Ultimately the cost of proton therapy will need to be weighed against tumor control probabilities as well as the economic and quality of life benefits associated with reduced normal tissue exposure. [Table: see text]