bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of age with acute toxicities in NRG oncology combined modality lower GI cancer trials.
Authors: VanderWalde Noam Avraham , Moughan Jennifer , Lichtman Stuart M. , Jagsi Reshma , Ballo Matthew T. , Vanderwalde Ari M. , Mohiuddin Mohammed , Meropol Neal J. , Kachnic Lisa A. , Garofalo Michael C. , Ajani Jaffer A. , Beart Robert W. , Anne Rani , Evans Lisa Smith , Arora Amit , Meyer Joshua E. , Lee James J. , Keech John A. , Soori Gamini S. , Crane Christopher H. 
Published: January 2019

649 Background: This study sought to compare adverse events (AEs) of older and younger adults with lower gastrointestinal (GI) malignancies treated on NRG studies. Methods: Data from six NRG trials (RTOG 9811/0012/0247/0529/0822 & NSABP R-04), testing combined modality therapy (radiation and chemotherapy) in patients with anal or rectal cancer, were collected to test the hypothesis that older age was associated with increase in acute ( ≤ 90 days from treatment start) AEs. AEs were defined as GI, Genitourinary (GU), hematologic, or skin. AEs and compliance with protocol-directed therapy were compared between patients aged ≥ 70 years and < 70 years. Categorical variables were compared across age groups using the chi-square test. The association of age on AEs was evaluated using a covariate-adjusted logistic regression model, with odds ratio (OR) reported. To adjust for multiple comparisons, a p-value < 0.01 was considered statistically significant. Results: Data from 2525 patients were collected (43% female, 72% rectal cancer). There were 380 patients ≥ 70 years old (15%). Older patients were more likely to have worse baseline performance status (PS 1 or 2) (23% vs. 16%, p <0.01), but otherwise baseline characteristics were similar. Older patients were less likely to have completed their chemotherapy (78% vs. 87%, p < 0.01), but had similar median RT duration. On univariate analysis, patients ≥ 70 were more likely to experience grade ≥ 3 GI AEs (36% vs. 23%, OR 1.82, p < 0.001), and less likely to experience ≥ 3 skin AEs (8% vs. 14%, OR 0.56, p = 0.002). There was no difference between GU or hematologic AEs. On multivariable analysis, age ≥ 70 was associated with grade ≥ 3 GI AE (OR 1.80, 95% CI: 1.40, 2.31; p < 0.001) after adjusting for gender, PS, T stage, disease site, RT duration, and chemotherapy completion. Conclusions: Older patients with curable lower GI cancers who underwent combined-modality therapy were less likely to complete chemotherapy and were more likely to experience serious GI toxicity, whereas younger patients had higher rates of serious skin AEs.
Potentially avoidable acute care use among patients receiving oxaliplatin.
Authors: Roeland Eric , LeBlanc Thomas William , Ruddy Kathryn Jean , Clark-Snow Rebecca Anne , Binder Gary , Bailey William L. , Potluri Ravi C. , Schmerold Luke M. , Papademetriou Eros , Navari Rudolph M. 
Published: January 2019

651 Background: Oxaliplatin (OX), used primarily in gastrointestinal cancers, is considered moderately emetogenic while multiple guidelines classify carboplatin and cisplatin as highly emetogenic chemotherapy (HEC). The new oncology outcome measure (OP-35) from the US Centers for Medicare and Medicaid Services (CMS) deems 30-day post-chemotherapy inpatient (IP) and emergency room (ED) events “potentially avoidable” if involving nausea or emesis (NV) or any of eight other toxicities. We lack data comparing avoidable IP/ED and NV events for OX relative to platinums classified as HEC. Methods: We assessed OX, cisplatin, and carboplatin courses of therapy from 4Q 2012 to 1Q 2018 using the IBM Watson Explorys database. We identified IP/ED and OP-35 toxicities (anemia, dehydration, diarrhea, fever, NV, neutropenia, pain, pneumonia, or sepsis) by diagnosis and procedure codes, and stratified results by sex and age < 70 (median age at diagnosis for colorectal cancer). An IP/ED event could involve ≥ 1 OP-35 toxicity. We also evaluated a FOLFIRINOX subgroup (receiving irinotecan ≤ 3 days after OX). Results: In sum, we identified 4,231 OX courses (382 FOLFIRINOX) (Table). OP-35 toxicities occurred in 75% of IP/ED events; of these, 34% OX and 42% FOLFIRINOX involved NV. Rates of IP/ED, IP/ED OP-35-defined toxicity, and NV after OX were consistent with cisplatin and carboplatin. Among patients receiving OX, women age < 70 (n = 1388) had higher NV rates vs. others (p < 0.001). Conclusions: Roughly one-third of patients receiving OX experienced IP/ED events ≤ 30 days post chemotherapy. Most involved ≥ 1 of 10 OP-35 toxicities, meeting CMS’ criteria as potentially avoidable acute care. OX IP/ED rates and NV rates were similar to other platinums and were worse among women age < 70, suggesting more aggressive antiemetic prophylaxis should be evaluated. [Table: see text]
The impact of psychosocial distress on survival in patients diagnosed with gastrointestinal (GI) malignancies.
Authors: Al-Hashami Zamzam Salam , Ho Cheryl , Moore Sara , Leung Bonnie , Lim Howard John , Bates Alan 
Published: January 2019

654 Background: A cancer diagnosis can cause psychological distress that adversely affects patients’ emotional, social, spiritual and physical capabilities. The aim of this study is to identify factors associated with increased risk for psychosocial distress and to evaluate the influence of anxiety and depression on survival of GI cancer patients. Methods: All patients with GI cancer referred to BC Cancer from 2011-2015 who completed a prospective Psychosocial Screen for Cancer – Revised within 6 months of cancer diagnosis were included in the study. Baseline characteristics were collected from the BC Cancer registry. Patient groups were compared using the Chi-squared Fisher’s exact test. OS was calculated using the Kaplan Meier method, compared using the log rank test and Cox proportional hazards model. Results: 8722 patients were included in the analysis. Baseline characteristic: median age 67, male 60% , metastatic disease 29%. Colorectal/anal cancers (60%) were the most common followed by pancreatic cancer (11%). Patients with anxiety and depression were more likely to be younger (aged 64 and less), female and have metastatic disease. Patients with anxiety were more likely to get chemotherapy. Depression was associated with less chemotherapy use. Anxiety and depression were associated with increased psychosocial needs including emotional, informational, physical, spiritual, social/family concerns (p < 0.001). Psychological distress was not influenced by the patient’s geographic location or socioeconomic status. Median OS for patients with anxiety was 20 m vs no symptoms 27 m (p < 0.001) and depression 17 m vs no symptoms 27m (p < 0.001). The impact on OS remained significant for anxiety and depression in a multivariate model that included age, sex, metastatic status and chemotherapy use. Conclusions: Patients with GI malignancies who are female, younger than 64 and have metastatic disease are at risk for psychological distress. Anxiety and depression were associated with poorer survival outcomes even when controlling for age, sex, metastatic status and chemotherapy. Mobilizing resources to meet patients’ needs is important and should be implemented as part of patients’ comprehensive care.
A prospective study of robotic rectal surgery for carcinoma rectum assessing the functional and oncological outcomes: Hype or hope?
Authors: Somashekhar S.P. , C Rohit Kumar , Rajgopal Ashwin K , Zaveri Shabber , Rauthan Amit , Yethadka Ramya 
Published: January 2019

661 Background: Robotic surgical systems have dramatically changed minimally invasive surgery as they could potentially address limitations of laparoscopic rectal surgery. This prospective observational study is conducted to evaluate the safety, technique, and outcomes (operative, postoperative,functional and oncological long term) of robotic-assisted rectal surgery for carcinoma rectum in the Indian set up. Methods: This was a prospective observational study conducted between 2010 and 2018, including 135 patients, diagnosed of rectal carcinoma. Patients underwent robotic rectal cancer surgery in form of either low anterior resection (LAR) or abdominoperineal resection (APR). Intraoperative, postoperative data were analysed. Results: Out of 135 patients, 67.5% were male, aged between 34-80 years, 85% had ECOG 0. All patients had adenocarcinoma rectum, with 15% mid rectum and 55% in lower rectum. 85% had stage III disease. 77.5% had received neoadjuvant chemoradiation. 82.5% had LAR and 17.5% APR. Average operative time including docking time and surgery time was 226.32 min (170-300 min), mean blood loss was 146.76 ml (120-200 ml), there were 3 conversion to open surgery. Bowel sounds appeared on average on 3rd day. All margins were negative in all patients, mesorectal grade was complete in 95% and near complete in 5%. Mean number of lymph nodes harvested is 9.5 (2-32). Complete pathological response rate was 39%. 2 patients had anastomotic dehiscence after 1 month. Minor complications were noticed in 10% patients. All had acceptable quality of life and well retained bladder function, with 18% sexual dysfunction. Five year DFS was 85% and OS was 94%. Local recurrence was 2.1%. Conclusions: This is one of the largest single center Indian data available. In conclusion, robotic rectal surgery has several benefits in the treatment and should be part of the armamentarium of the experienced surgeon dealing with rectal cancer. We conclude that the robotic-assisted rectal cancer surgery is safe and an oncologically feasible technique with well retained functional outcomes and has lived up to its hope.
Simultaneous resection of colorectal cancer with synchronous liver metastases: A survey-based analysis.
Authors: Griffiths Christopher , Bogach Jessica , Simunovic Marko , Ruo Leyo , Hallet Julie I. , Serrano Aybar Pablo Emilio 
Published: January 2019

662 Background: Decision to proceed with simultaneous or staged resection in synchronous colorectal cancer liver metastases (CRLM) varies and is usually left to the individual surgeon. We examined practice intentions and barriers to performing simultaneous resection. Methods: We developed and pilot-tested a tailored questionnaire. Members of the Society of Surgical Oncology and the College of Physicians and Surgeons of Ontario operating colorectal cancer were surveyed electronically. Four clinical scenarios of synchronous CRLM determined practice intentions for varying degrees of complexity. Perceived barriers were assessed on a 7-point Likert scale. We compared general and hepatobiliary surgeons’ responses with Mann-Whitney U test for continuous variables and Chi-square test for categorical variables. Results: There were 184/1,335 surgeons (14% response rate), including 50 general and 134 hepatobiliary surgeons. Both were supportive of simultaneous resection, though hepatobiliary surgeons were more so; for minor liver and low complexity colorectal resections (Likert ≥5-7: 83% vs. 98% p<0.001), or for complex colorectal resections (57% vs. 73% p=0.042). Both groups were less supportive of simultaneous resection for complex liver with low complexity (Likert ≥5-7: 26% vs. 24% respectively, p=0.858) or high complexity colorectal resections (11% vs. 7.0% respectively, p=0.436). All perceived that simultaneous resection increases post-operative morbidity (63%), but not mortality (69%). Among hepatobiliary surgeons, the most common barriers for simultaneous resections were comorbidities and extrahepatic disease, whereas general surgeons were more concerned about transfer to another facility. Conclusions: While general and hepatobiliary surgeons are supportive of simultaneous resection, especially for less complex liver resections; support is significantly lower among general surgeons. In addition to complexity of procedures and perceived morbidity, the need for transfer of care appears as a barrier to simultaneous resections. The practice intentions and barriers described are important to identify knowledge gaps, guide future trials, and establish disease care pathways.
Simultaneous versus staged resection for synchronous colorectal cancer liver metastases: A population-based cohort study.
Authors: Bogach Jessica , Wang Julian , Parpia Sameer , Simunovic Marko , Hallet Julie I. , Serrano Aybar Pablo Emilio 
Published: January 2019

665 Background: While considered safe, simultaneous resection of colorectal cancer primary and liver metastases is not performed routinely. We aimed to identify practice patterns, short and long-term outcomes of simultaneous vs. staged resections for synchronous colorectal cancer liver metastases. Methods: We conducted a population-based cohort study of patients undergoing resection for synchronous colorectal cancer liver metastases from 2006-2015 by linking administrative healthcare datasets in Ontario, Canada. Resection of the primary colorectal cancer and liver metastases within six months was considered synchronous disease. Simultaneous (same hospital admission) and staged resections were compared. Outcomes were 90-day post-operative mortality, total length of hospital stay, overall survival and healthcare costs. Survival for the staged group was measured from the last surgical resection to death and estimated using Kaplan Meier. Cost analysis was undertaken from the perspective of a third-party payer and compared using t test. Results: Of 2,738 patients undergoing colorectal and liver resection for colorectal cancer, 1,168 were synchronous, of which, 442 underwent simultaneous resection. The rate of simultaneous resections increased on average by 3% per year (p = 0.02). Median total length of stay was shorter (8 vs. 11 days); 90-day post-operative mortality was higher for simultaneous resections (3.4% vs 1.2%). Median overall survival was worse with simultaneous resection (40 months, 95%CI 35-46 vs. 78 months, 95%CI 59-86), with a 5-year overall survival of 37% (simultaneous) and 55% (staged). Mean overall costs were lower for simultaneous resections ($12,722 CAD vs. $16,455 CAD. Conclusions: Simultaneous resection compared to staged resection for patients with synchronous colorectal cancer liver metastases is associated with higher 90-day postoperative mortality and worse survival. It was associated with shorter length of hospital stay and lower costs for the health cares system. Considering selection bias, randomized studies would be necessary to determine the role of simultaneous resection for synchronous disease colorectal cancer liver metastases.
Real-world experience of trifluridine/tipiracil in patients with metastatic colorectal cancer: A multicenter United Kingdom study.
Authors: Stavraka Chara , Pouptsis Athanasios , Kabuubi Paul , Angelis Vasileios , Synowiec Alicja , Baxter Mark , Barrie Ainsley , Andres Costa Amparo , Nizam Alia , De Naurois Julien , Mikropoulos Christos , Hill Mark , Graham Janet Shirley , Harris Victoria , Bridgewater John A. , Ross Paul J. 
Published: January 2019

668 Background: TAS-102 is an orally administered combination of the thymidine-based nucleic acid analogue, trifluridine and the thymidine phosphorylase inhibitor, tipiracil hydrochloride. Following the phase III RECOURSE study, it received approval as third line treatment for metastatic colorectal cancer showing significant improvement in overall and progression free survival and an acceptable toxicity profile. Methods: We performed a multicenter retrospective observational study of patients with metastatic colorectal cancer receiving TAS-102 as third line treatment between 2016 and 2018 in Cancer centers across the UK. Results: A total of 143 patients were included (94 men, 49 women). Median age was 68 years (35-82). All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 90% of patients had ECOG ≥ 1. Median duration of treatment was 2.9 months (0.5-22.9), with a response rate of 1.6% and stable disease achieved in 24%. Median OS was 7 months (95% CI 5.84-8.15) and median PFS 2.6 months (95% CI 2.2-3.36). A dose reduction was required in 28% of patients, while 8% discontinued treatment due to toxicity. AEs reported included fatigue 81.3% (G3 16.8%), nausea 34.5% (G3 4.5%) and diarrhoea 25.5% (G3 1.8%). Neutropenia was common 50.4%, (≥ G3: 25.4%) with 4.2% cases of neutropenic fever while thrombocytopenia was less frequent 8.7% (≥ G3 1.8%). Conclusions: The OS, PFS and ORR observed in our real-world experience were consistent with the RECOURSE trial, though we noted a lower disease control rate. Overall, TAS-102 was well tolerated and the most prevalent adverse events seen in our patients were in keeping with those reported in the trial. Although severe toxicities were less frequent than the trial, we experienced higher rates of toxicity induced dose reductions and treatment cessations, which could reflect the differences between trial and real world populations. Further validation is warranted.
Safety and clinical activity of durvalumab monotherapy in patients with microsatellite instability–high (MSI-H) tumors.
Authors: Segal Neil Howard , Wainberg Zev A. , Overman Michael J. , Ascierto Paolo Antonio , Arkenau Hendrik-Tobias , Butler Marcus O. , Eder Joseph Paul , Keilholz Ulrich , Kim Dong-Wan , Cunningham David , Khleif Samir N. , Doucet Ludovic , Lee Jong-Seok , Nemunaitis John J. , Vaishampayan Ulka N. , Weiss Jared , Gao Chen , Abdullah Shaad Essa , Hollebecque Antoine 
Published: January 2019

670 Background: MSI-H tumors have shown to be responsive to PD-1 inhibitor therapy. We evaluated the anti-PD-L1 mAb durvalumab in patients with MSI-H tumors, in two ongoing studies: a phase 1/2, multicenter, open-label study in patients with advanced solid tumors, and a phase 2 single-center study in patients with advanced colorectal cancer (CRC). Methods: Patients with MSI-H tumors (determined locally by immunohistochemistry or sequencing) received durvalumab 10 mg/kg IV every 2 weeks for 12 months or until confirmed progressive disease, whichever was first. Objectives were to evaluate safety and antitumor activity (per investigator-assessed RECIST v1.1). Results: As of Oct 16, 2017, 62 MSI-H patients (97% with prior anti-cancer therapy) received treatment in the multicenter study; median duration of follow-up was 29 months. Treatment-related adverse events (TRAEs) occurred in 37 patients (60%), most commonly diarrhea (15%), asthenia (11%), fatigue (11%), nausea (10%), and hypothyroidism (10%). Grade 3/4 TRAEs occurred in 2 patients (3%). There were no deaths or treatment discontinuations due to TRAEs. Objective response rates (ORR) were 23% for the total population and 22% for patients with CRC; 9 of 14 responders were ongoing at data cutoff. As of Sep 13, 2018, 11 patients with MSI-H CRC were treated in the single-center study; median duration of follow-up was 30 months. One patient discontinued treatment due to treatment-related aseptic meningitis (resolved with steroids); response rate and survival were similar to the multicenter study (Table). Conclusions: Durvalumab had a tolerable safety profile, and showed promising antitumor activity and overall survival in patients with MSI-H tumors. Clinical trial information: NCT01693562 and NCT02227667. [Table: see text]
Surgery versus surgery with adjuvant radiotherapy for T4 colon cancer.
Authors: Sebastian Nikhil , Miller Eric David , Diaz Pardo Dayssy Alexandra 
Published: January 2019

673 Background: There is no randomized prospective evidence to clarify the role of adjuvant radiotherapy in localized colon cancer. Despite this, national consensus guidelines recommend that adjuvant radiotherapy be considered for patients with T4 disease. Given the lack of prospective data, the aim of this study was to evaluate the role of adjuvant radiation therapy (RT) in colon cancer using two large national databases to help to guide treatment decisions. Methods: We evaluated the association of receipt of adjuvant RT with overall survival (OS), using the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER), as well as with disease-specific survival (DSS) using SEER. We analyzed cohorts of patients with histologically confirmed locally advanced T4 adenocarcinoma of the colon, who underwent oncologic surgery with or without adjuvant radiation and had at least 5 years of follow up. For the NCDB cohort, we restricted RT patients to those who received a dose of 45-60 Gy and those who received treatment within 3 months after surgery. We used nearest-neighbor propensity score matching on the basis of age, race, sex, year of diagnosis, grade, N-stage, receipt of chemotherapy, anatomical subsite, margin status, and comorbidity score. To validate our findings, using SEER, we used propensity matching using the same covariates (except comorbidity). Results: After matching of the NCDB cohort, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=1.08; 95% CI 0.89 - 1.30; p=0.448). Using SEER, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=0.9; 95% CI 0.50 - 1.63; p=0.731) or DSS (HR=0.84; 0.54 – 1.33; p=0.46). Conclusions: In summary, after comprehensively adjusting for covariates using two independent national databases, we found no statistically significant association of adjuvant RT with overall- or disease-specific survival for T4 colon cancer. These findings are limited by the retrospective nature of the data and should be tested in a prospective fashion.
Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside in prevention of oxaliplatin-induced neurotoxicity in stage II/III colorectal cancer patients.
Authors: Li Yu-hong , Wang De-Shen , Wang Zhiqiang , Peng Jie-wen , Wang Wei , Feng Fen , Deng Yanhong , Zhang Jianwei , Wang Fenghua , Ren Chao , Wang Feng , Jin Ying , Xie Chuanbo , Tan Qiong , Chen Gong , Xu Rui-hua 
Published: January 2019

674 Background: Monosialotetrahexosylganglioside (GM1) is a glycosphingolipid, which has antioxidant and neuroprotective properties. Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy. This study was designed to assess the efficacy of GM1 for preventing oxaliplatin-induced neurotoxicity in colorectal cancer (CRC) patients. Methods: A total of 186 patients with stage II/III CRC undergoing adjuvant chemotherapy with modified FOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to intravenous GM1 80mg per day or placebo from day 0 to day 4 during chemotherapy. The primary end point was the rate of grade 2 or worse cumulative neurotoxicity, measured by investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. The secondary end point were the chronic cumulative neurotoxicity measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity by using the NCI-CTCAE or the oxaliplatin-specific neuropathy scale, the rates of acute neurotoxicity measured by a numerical analog scale ranging from 0 to 10, and the rates of dose reduction or withdrawal of both arms. Results: There were no statistically significant differences in the rate of NCI-CTCAE grade 2 or worse neurotoxicity between the study arms (GM1: 33.7% vs. placebo: 31.6%; P= 0.76). Similarly, there were no significant differences measured by EORTC QLQ-CIPN20 neuropathy scale ( P= 0.89) or additional measures of neuropathy, including measurement of the time to grade 2 neurotoxicity by using the NCI-CTCAE ( P= 0.99) or an oxaliplatin-specific neuropathy scale ( P= 0.98). In addition, GM1 did not substantially decrease oxaliplatin-induced acute neuropathy. The rates of dose reduction or withdrawal of both arms were not significantly different (GM1: 64.6% vs. placebo: 54.6%, P= 0.15). Conclusions: This study does not support using GM1 to prevent oxaliplatin-induced neurotoxicity. (NCT02251977) Clinical trial information: NCT02251977.