bluuebunny/crossref_metadata_2025_split huggingface dataset:
An investigation of the role of irinotecan and oxaliplatin in liver toxicity during first-line neoadjuvant chemotherapy.
Authors: Desjardin Marie , Bonhomme Benjamin , Soubeyran Isabelle , Vara Jeremy , Fonck Marianne , Becouarn Yves , Desolneux Gregoire , Brouste Veronique , Evrard Serge , Bechade Dominique 
Published: February 2017

689 Background: Neoadjuvant chemotherapy (CT) have been associated with an increased risk of surgery for colorectal liver metastases (CRLM). Irinotecan (IRI) is claimed to induce CT-associated steatohepatitis (CASH) and oxaliplatin (OX) to induce sinusoidal obstruction (SOS). Imputability is sometimes difficult to establish and the impact on postoperative complications is unclear. The objective of this study is to investigate the impact of IRI and OX on induced liver toxicity, and to study the effects of toxicity on surgical outcomes. Methods: Patients (Pts) who received only one line of CT before resection of CRLM were retrospectively included. CASH and SOS were described according to Kleiner and Rubbia-Brandt classifications respectively. Associations were sought between CASH or SOS and various patient and treatment factors, and between patient and treatment factors and the occurrence of post-operative complications grade 3 or over. Results: Among 379 pts operated on for CRLM from 2003 to 2013, 223 were eligible for inclusion; 57 were excluded as there was no healthy hepatic parenchyma to be analyzed. Median age was 64 y [34-88], BMI ≥25 kg/m² for 52%, 8% had diabetes, and 28% had a dyslipidemia. CRLM were synchronous in 76.5%. 65 (39.2%) received Folfox, 95 (57.2%) Folfiri and 6 (3.6%) Folfirinox. Bevacizumab, cetuximab and panitumumab were given in 71 (42.8%), 30 (17.5%), 4 (2.4%) respectively. Extra-hepatic resections were performed in 78 pts (47%). 90-day mortality was 1.8% and 31 pts encountered complications more severe than 3A. Histological hepatoxicity was established for 82 pts (49%) including 33 (19.9%) with grade 2 or 3 SOS and 22 (13%) with CASH. No significant associations were identified between SOS and OX, nor CASH and IRI. BMI ≥ 25 kg/m² was correlated with an increased risk of CASH. Only septic extra-hepatic surgeries were correlated with the prediction of postoperative complications. Conclusions: In this selected series, preoperative CT was not associated to liver toxicity. The presence of histological lesions did not worsen post-operative outcomes. BMI and extra-hepatic surgery were the only co-factors correlated with CASH and post-operative complications respectively.
Lower rates of acute gastrointestinal toxicity with pencil beam proton therapy relative to IMRT in neoadjuvant chemoradiation for rectal cancer.
Authors: Batra Sonny , Comisar Lauren , Lukens John Nicholas , Kirk Maura , Both Stefan , McDonough James , Mahmoud Najjia N. , Giantonio Bruce J. , Ben-Josef Edgar , Metz James M. , Plastaras John Peter 
Published: February 2017

696 Background: Preoperative chemoradiotherapy (CRT) is standard treatment for locally advanced rectal cancer (LARC). GI toxicity leading to ED visits, hospitalization, and need for IV hydration remains a management challenge. Previous studies have established volume of bowel receiving low dose radiation (V15) as the strongest predictor of GI toxicity. We have previously shown pencil beam scanned proton therapy (PBSPT) is dosimetrically superior to IMRT in LARC with respect to low dose to the bowel. This studycompares the toxicity of patients treated with PBSPT and IMRT in neoadjuvant treatment of LARC. Methods: A retrospective review was conducted of patients treated at the University of Pennsylvania with neoadjuvant 5-FU or capecitabine CRT. Patient and tumor characteristics, treatment, and toxicity data were collected. PBSPT (50.4 Gy RBE to standard volumes) was delivered using either two opposed lateral fields or posterior oblique fields with a patient supine or prone. These patients were registered on a prospective registry study. IMRT plans were delivered with 7-9 field IMRT or volumetric arc therapy in the supine or prone position. Statistical analysis was performed using STATA v12.0. Results: Between 3/2009 and 6/2014, 39 patients treated with IMRT and 26 patients treated with PBSPT were studied. Continuous-infusion 5-FU was administered in 31 (79%) IMRT patients and 16 (62%) PBSPT patients (p = 0.162); the remainder received capecitabine. PBSPT patients had significantly lower rates of acute Grade ≥ 2 diarrhea, 12% versus 39% with IMRT (p = 0.022). On multivariable analysis incorporating the type of chemotherapy, use of PBSPT remained a significant predictor of lower rate of Grade ≥ 2 diarrhea (OR = 0.20, 95% CI 0.05 - 0.82, p = 0.025). There was also a borderline significant reduction in Grade ≥ 2 fatigue with the use of PBSPT, occurring in 8% versus 29% of IMRT patients, p = 0.057. Conclusions: These preliminary results indicate PBSPT is associated with significant reduction in acute Grade ≥ 2 diarrhea compared to IMRT. PBSPT may play an important role in the treatment of LARC, a disease with high cure rate where radiation toxicity should be minimized.
The significance of EGFR pathway mutations for the efficacy of first line treatment with bevacizumab in metastatic colonrectal cancer.
Authors: Nakayama Izuma , Shinozaki Eiji , Wakatsuki Takeru , Kumekawa Yosuke , Ogura Mariko , Ichimura Takashi , Takahari Daisuke , Ozaka Masato , Suenaga Mitsukuni , Chin Keisho , Mizunuma Nobuyuki , Yamaguchi Toshiharu 
Published: February 2017

699 Background: After analysis of minor RAS mutations (KRAS exon3, 4/NRAS) in FIRE-3 or PRIME study, so called all RAS mutation would be being regarded as a biomarker for anti-EGFR antibodies. BRAF and PIK3CA mutation would be a candidate of biomarkers for anti EGFR targeted therapies. However it remains unknown whether EGFR pathway mutations affect the efficacy of bevacizumab in Stage.‡W CRC. Methods: Of the 1,001 consecutive patients of CRC in our institute between Nov 2006 and Dec 2013, we examined RAS, PIK3CA and BRAF mutational status, 141 patients received systemic chemotherapy for the first line treatment of Stage.‡W. Among them, 96 patients were administered chemotherapy with bevacizumab. Overall survival (OS), Time to Treatment Failure (TTF) and Objective Response Rate (ORR) were evaluated by mutational status. Results: Baseline characteristics were as follows (n=141): median age, 63; male/female, 80/61; ECOG PS 0-1/2, 135/4; chemotherapy with bevacizumab/chemotherapy with anti-EGFR antibodies/cytotoxic agent alone, 96/22/23;KRAS (codon 12,13) wild-type (WT)/RAS wild-type(WT), 89/80; PIK3CA mutation (exon 9/exon 20)/BRAF mutation, 11(5/6)/13. Median OS and TTF were 32.1 and 8.0 months respectively. In chemotherapy with bevacizumab, ORRs were 46.3% (all cases), 55.3% (KRAS WT), 54.5% (RAS WT) and 60.6% (all WT) respectively. ORR was gradually improved by focusing therapeutic target on all wild population. However, there were no significant differences in TTF and OS among them. PIK3CA mutation had a trend toward shorter TTF of bevacizumab (p=0.056). This trend was observed in PIK3CA mutation on exon 20 but not observed exon 9. BRAF mutation had significantly associated with poor OS not only for bevacizumab cases but also all therapies. Conclusions: In our study, profiling of EGFR pathway mutations may not contribute to enrich patients with benefit from chemotherapy with bevacizumab.
Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003): Detailed analysis of peripheral sensory neuropathy.
Authors: Sogabe Susumu , Yuki Satoshi , Fukushima Hiraku , Takahashi Norihiko , Shichinohe Toshiaki , Kusumi Takaya , Nakamura Fumitaka , Iwanaga Ichiro , Hatanaka Kazuteru , Miyashita Kencho , Konno Jun , Uemura Kazuhito , Nenohi Masaaki , Kina Masaya , Sakamoto Naoya , Taketomi Akinobu , Hirano Satoshi , Amano Toraji , Ito Yoichi M , Komatsu Yoshito 
Published: February 2017

701 Background: Oxaliplatin-containing regimen is a standard adjuvant chemotherapy for resected stage III colon cancer. Oxaliplatin-containing regimens were investigated for their efficacy in patients with resected stage III colon cancer in MOSAIC and XELOXA studies. Since these two international randomized studies were performed outside of Japan, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy in Japanese patients (pts) with resected stage III colon cancer (UMIN ID: 000004590). Methods: This phase II study enrolled patients with resected stage III colon cancer. Patients received 12 biweekly cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was DFS. Secondary endpoints included overall survival (OS) and safety. Results: From September 2010 to March 2013, 273 pts were enrolled at 28 institutions. Safety analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age, 65 (33-84); male/female: 131/134; PS 0/1:258/7; stage IIIA/IIIB/IIIC: 37/197/31; colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), platelet count decreased (2.3%), and allergic reaction (1.5%). The incidence of peripheral sensory neuropathy (PSN) was 41.9% (grade 1), 38.1% (grade 2), and 6.4% (grade 3). PSN tended to be serious depending on the cumulative dose of oxaliplatin (table 1). Median cumulative dose of oxaliplatin at which PSN occurred were as follows: grade 1; 170 mg/m2, ≥ grade 2; 850 mg/m2, ≥ grade 3; (-). The median number of cycles of chemotherapy was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. Clinical trial information: 000004590. [Table: see text]
Characteristics of long- versus short-surviving patients (Pts): An analysis of the ARIES Observational Cohort Study (OCS) of bevacizumab (BV)-treated pts with metastatic colorectal cancer (mCRC).
Authors: Kozloff Mark , Grothey Axel , Bendell Johanna C. , Cohn Allen Lee , Bekaii-Saab Tanios S. , Roach Nancy , Flick Elizabeth Dawn , Mun Yong , Fish Susan Meredith , Laeufle Rita , Sommer Nicolas , Hurwitz Herbert 
Published: February 2017

702 Background: Median overall survival (OS) in mCRC has significantly improved over the past 20 yrs, but the observed range of OS in pts remains wide; a large percentage of pts have OS <1 yr or >4 yrs. ARIES was a prospective OCS conducted from 2006–2012 that evaluated outcomes in pts receiving BV + chemotherapy (CT) for mCRC in general clinical practice. The objective of this analysis is to examine clinical characteristics of pts with long vs short OS. Methods: This analysis included 1,417/1,550 first-line (1L) BV-treated mCRC pts who died or had complete follow-up on study. Long OS was defined as OS within the upper quartile of the analysis population (range 42–67 mos); short OS was defined as OS within the lower quartile (range 0.3–12 mos). Progression-free survival (PFS) was estimated using Kaplan-Meier methods. Pt and disease characteristics and treatment patterns were described using summary statistics. Results: Pt and disease characteristics are shown in the Table. Median PFS was 22.3 mos (95% CI, 19.9–23.3) vs. 4.9 mos (95% CI, 4.6–5.4), in the long-OS vs. short-OS groups. More pts with long OS received any second-line (2L) therapy (71% vs. 46%), and were exposed to 5-fluorouracil, oxaliplatin, and irinotecan throughout the course of their disease (53% vs. 32%) compared with pts with short OS. KRAS/BRAF mutation status was not collected. Conclusions: Pts with long OS had better baseline performance status, primary tumors more likely to have been resected, and were more likely to have received 2L CT. Additional analyses of detailed treatment patterns and safety are ongoing. Clinical trial information: NCT00388206. [Table: see text]
Randomized phase III study of panitumumab (pmab) vs. cetuximab (cmab) in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC): Outcomes by hypomagnesemia (hypomag) in ASPECCT.
Authors: Price Timothy Jay , Peeters Marc , Kim Tae Won , Li Jin , Cascinu Stefano , Ruff Paul , Suresh Attili Venkatasatya , Thomas Anne , Tjulandin Sergei , Zhang Kathy , Sidhu Roger , Murugappan Swaminathan 
Published: February 2017

705 Background: ASPECCT met its primary endpoint of non-inferiority of overall survival (OS) of pmab vs. cmab. We evaluate outcomes by hypomag, an on-treatment, anti-EGFR related adverse event that develops due to the inhibition of EGFR function. Conflicting reports have suggested hypomag is associated with survival. Methods: Patients with previously treated WT KRAS exon 2 mCRC were randomized 1:1 to receive pmab or cmab. The primary endpoint was non-inferiority of OS. Progression-free survival (PFS) and objective response rate (ORR) were secondary endpoints. Patients were categorized ± any grade hypomag during the study and data analyzed by treatment arm. Analysis of Mg supplementation during hypomag was not conducted. Results: 999 patients were randomized and treated: 499 pmab, 500 cmab. Any grade hypomag was 28.8% and grade ≥3 was 7.3% in the pmab arm vs. 18.9% and 2.6% in the cmab arm, respectively. Median time to first hypomag onset was 82 days in the pmab arm and 57 days in the cmab arm. In the pmab arm, 1.0% of patients discontinued treatment and 5% of patients had dose modifications due to hypomag vs. <0.5% and 3% in the cmab arm, respectively. Results are shown (Table). Conclusions: In ASPECCT, rates of hypomag were higher in the pmab vs. the cmab arm. Patients who developed any grade hypomag with pmab or cmab had higher ORR, PFS, and OS compared with those patients who did not. Clinical trial information: NCT00788957. [Table: see text]
A prospective patient (pt) survey on clinical trials.
Authors: Moorcraft Sing Yu , Marriott Cheryl , Peckitt Clare , Cunningham David , Chau Ian , Starling Naureen , Watkins David , Andreyev Jervoise , Rao Sheela 
Published: February 2017

707 Background: Recruitment to clinical trials can be challenging. We conducted a patient survey to improve our understanding of pts’ views and experiences of clinical trials and what aspects could be improved. Methods: Pts who had been approached about participation in any clinical trial in the Gastrointestinal (GI) and Lymphoma Unit at the Royal Marsden were prospectively invited to complete a questionnaire about their views and experiences of cancer research. Results: Between August 2013 and July 2014, 276 pts (90% GI, 10% lymphoma) received 298 clinical trial pt information sheets (PIS) and were asked to complete a questionnaire. 263 respondents (Res) consented to a trial and 249 of these (95%) completed the questionnaire (65 for clinical trials of an investigational medicinal product (CTIMP), 156 for non-CTIMPs and 28 for molecular pre-screening trials). 25 Res declined a trial and 10 of these completed the questionnaire. Of the 249 Res who consented to a trial, 96% were glad to be approached about clinical trials. 90% of Res felt the PIS was easy to understand and rated the verbal explanation of the trial as excellent/good. 10 Res who declined a trial felt the verbal explanation was excellent/good and that the PIS was easy to understand. The mean total PIS length (including sub-studies) was 17 pages (range 3-50 pages). 9% of Res who consented to a trial felt the PIS was too long. Regarding CTIMP trials, 48-50% of Res would have liked more information on trial drugs and any additional research procedures, 28-30% were neutral and 20-24% did not want more information. 75% of Res would consider participating in studies requiring a research biopsy and 78% would donate their tissue for genetic research. 79% of pre-screening trial Res, 66% of non-CTIMP trial Res and 54% of CTIMP trial Res would have been willing to consent to the trial on the day they received the PIS. 75% of Res (including 89% of CTIMP Res) believed pts should be told trial results, even if results are not available for many years. Conclusions: The majority of pts are willing to be approached regarding clinical trials. A high proportion of pts would consider studies involving research biopsies. New strategies for tailoring additional trial information according to the patient and informing pts of trial results should be explored.
Survival impact of adjuvant chemotherapy for resected early-stage rectal adenocarcinoma.
Authors: Tay Rebecca Yin , Jamnagerwalla Murtaza , Steel Malcolm , Wong Hui-Li , McKendrick Joseph James , Faragher Ian , Kosmider Suzanne , Hastie Ian , Desai Jayesh , Gibbs Peter , Wong Rachel 
Published: February 2017

712 Background: Recent data have created uncertainty regarding the benefit of the current standard of care adjuvant fluoropyrimidine-containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer. In particular, patients with a pathologic complete response may derive no benefit from adjuvant chemotherapy. Methods: This is a retrospective analysis of patients with early stage rectal adenocarcinoma, diagnosed between 1 January 2003 and 30 June 2013 at three Melbourne health services (Eastern Health, Royal Melbourne Hospital, and Western Health). Patients were identified from a search of the ACCORD (Australian Comprehensive Cancer Outcomes and Research Database) database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pre-treatment staging, post-operative treatment, recurrence, and survival were analyed. Results: A total of 580 patients with localized rectal cancer were identified, of whom 451 had received neoadjuvant long-course chemoradiation followed by resection of the primary tumor. 369 patients (82%) subsequently received adjuvant 5-fluorouracil. At a median follow-up of 45.9 months, 63 (19%) patients in the adjuvant chemotherapy group and 21 (29%) in the surveillance only group had relapsed. Median relapse-free survival (RFS) has not been reached in either group; 3-year RFS was 81% in the adjuvant chemotherapy group compared to 71% in the surveillance only group (p=0.034). Five-year overall survival was 83% in the adjuvant chemotherapy group compared to 71% in the surveillance only group (p=0.038). The impact of age, surgical complications, treatment-related toxicity, and pathological complete response post-neoadjuvant therapy on the uptake of post-operative chemotherapy and on survival are being evaluated. Conclusions: A high proportion of patients in routine practice receive adjuvant chemotherapy following neoadjuvant treatment and surgery for early stage rectal cancer. Adjuvant chemotherapy was associated with a significant improvement in 3-year relapse-free and 5-year overall survival.
Is panitumumab monotherapy safe in metastatic colorectal cancer patients over 70 years old?
Authors: Martin-Babau Jerome , Douillard Jean-Yves , Dupuis Olivier Jean Marie , Porneuf Marc , Ramée Jean François , Raoul Jean-Luc , Deguiral Philippe , Faroux Roger , Gourlaouen Alain , Miglianico Laurent , Van Hulst Sylvie , El Hannani C. , Bassoulet James , Stampfli Claire , Riche Christian , Marhuenda Fanny , Deniel Lagadec Delphine , Jestin Le Tallec Veronique , Grude Francoise , Metges Jean-Philippe 
Published: February 2017

714 Background: Metastatic Colorectal Cancer (mCRC) often occurs in patients older than 70 years old. Monoclonal antibodies targeting EGFR have improved the outcome of mCRC patients. Panitumumab in monotherapy is indicated in wild-type K-RAS mCRC progressing disease following fluoropyrimidine-, oxaliplatin- and irinotecan-containing chemotherapy regimens. Very few data are available in elderly patients receiving panitumumab. Methods: Based on the cohort of the Observatory of Cancer B PL in France, we studied the efficacy and tolerance of panitumumab. We retrospectively collected data from patients treated between July 2008 and January 2014 and older than age 70 and compared the results between two cohorts: one contained patients ages 70 to 74; the other contained patients age 75 and older. Results: 136 patients were identified. The median age was 77. The median number of course received was 7 infusions. There was no difference in outcomes between the patients of the two cohorts. Median overall survival was 6.16 months. Median PFS was 13 weeks. The older patients received less previous chemotherapy ligns than the younger with a statistical difference (p=0.023). Tolerance was acceptable with a skin toxicity rate of 67% and 11.5% of grade 3-4. No diarrhea or hypomagnesemia were reported. Conclusions: Our study shows that panitumumab is feasible in elderly patients "in the real world" and has comparable efficacy than in younger patients.
Bowel dysfunction-related needs assessment in colorectal cancer survivors.
Authors: Sun Virginia , Smith David D. , Lai Lily L. , Chong Carrie , Grant Marcia 
Published: February 2017

715 Background: Bowel dysfunction is common following treatment for colorectal cancer (CRC), with substantial impact on survivors’ quality of life (QOL). There are few evidence-based protocols to support positive adjustments to bowel function changes. The purpose of this study was to assess CRC survivors’ bowel dysfunction related information needs following surgery. Methods: CRC survivors who were within 1-3 months post-resection (n=37) completed questionnaires on bowel function, fecal incontinence specific QOL, and bowel dysfunction needs. Six randomly selected participants were interviewed to further explore unmet needs. Quantitative data were summarized using descriptive statistics for all subscales and individual items. Qualitative data were interpreted through content analysis methods. Results: The mean number of daily bowel movements was 5.5 (range 2-10). Many survivors reported incomplete bowel evacuation (66%) and increased urgency/frequency (75%). More problems were reported on the impact of diet on function (X=12, SD=3.2) and urgency/soilage (X=13.5, SD=4.5). Lower QOL scores were observed for the impact of dysfunction on lifestyle (X=2.7, SD=1.0) and coping behavior (X=2.7, SD=0.9). Survivors reported unmet information needs for the following: 1) managing bowel dysfunction in an emergency; 2) type of foods that are helpful or not helpful with bowel function; and 3) talking to others who share the same experience. The majority (75%) desired to participate in a rehabilitation program, and preferred to receive content before treatments or discharge from hospital following surgery. Conclusions: CRC survivors report unmet bowel dysfunction related needs, and desire more information and strategies to help with managing changes to their bowel patterns. Evidence-based interventions that are timely and personalized are needed to support long-term, positive adjustments following treatment.