bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between naldemedine administration and the maximum dose of oral opioids.
Authors: Kajiura Shinya , Chikaoka Shingo , Kadota Ayaka , Fukai Sakie , Matsushita Takako , Hayashi Naomi , Ryu Nobukazu , Yagi Yuta , Takaki Akiyoshi , Horikawa Hideyo , Takemura Yoshinori , Sakamoto Kazunori , Furuichi Astushi , Shima Tomoko , Motoo Iori , Ando Takayuki , Yasuda Ichiro , Hayashi Ryuji 
Published: February 2020

818 Background: Opioid-induced constipation (OIC) is the most common side effect of opioid therapy. Laxatives are usually used as a first-line treatment for OIC. Treatment options for OIC are switching to other opioids associated with less frequent OIC, such as Fentanyl. Naldemedine is an orally active peripherally acting µ-opioid receptor antagonists that was approved in Japan from 2017 for management of cancer-related OIC. The aim of this study is to investigate the relationship between Naldemedine administration and the maximum dose of oral Oxycodone which is the most frequently used oral opioids at our hospital. Methods: During June 2017 and December 2018, a total of 217 patients with cancer-related pain received Oxycodone at our institution. The first group of the patients concurrently received Naldemedine 0.2 mg daily (group A, n = 101), and the second group didn’t receive it (group B, n = 116) for cancer-related OIC reduction. We compared the maximum Oxycodone dose between two groups by medical record retrospectively. Results: The median age of group A was 69 y.o. (range 20-87 y.o.), and the median age of group B was 67 y.o. (range 27-88y.o.). There was no significant difference in common patient background between group A and B. The median dose of maximum Oxycodone dose of group A was 40 mg/day (range 10-480 mg/day), and that of group B was 20 mg/day (range 10-320 mg/day). There was a significant difference in the median dose of maximum Oxycodone between group A and B (Mann-Whitney U test, P < 0.0001). In Group A, the administration was started in 31 patient Naldemedine and Oxycodone at the same time. As for 70 remaining patients, the administration was started when they had constipation after oxycodone was administrated. In those patients, the median days was 19 days from the Oxycodone administration starting date to the Naldemedine administration starting date. Conclusions: Naldemedine administration in patients with cancer-related OIC may increase the maximum dose of oral Oxycodone.
Stereotactic radiotherapy in oligometastatic (OM) gastrointestinal (GI) tumors: A single institution retrospective analysis.
Authors: Figueiredo Renata Reis , Palhares Daniel Moore Freitas , Fernandes Gustavo Dos Santos , Pereira Allan Andresson Lima , Marchetti Katia Regina , Gumz Brenda Pires , Faria Luiza Dib , Alves Teixeira Marcela , Gadia Rafael 
Published: February 2020

825 Background: Metastatic GI cancers are mainly treated with systemic treatment (ST), in selected patients (pts), surgery is considered depending on pts characteristics and institutional preferences. Stereotactic Radiotherapy (SRT) is a growing treatment option in such landscape aiming to improve local disease control and maximize ST results for oligometastatic pts. Methods: This is a single center retrospective study. Data were collected from sequential pts with GI tumors who underwent SRT for OM-GI cancers from May 2014 to July 2019. Information was collected on pts characteristics, primary site, clinical staging at diagnosis, sites undergoing SRT, whether there was progression after the first SRT, time between the first SRT and progression and the last follow-up date. Results: 381 pts underwent SRT in our center, of these, 75 pts had OM-GI tumors and underwent 120 courses of SRT. 50,7% were women, the median age at diagnosis was 60 years and the median follow-up was 36 months. 76% had colorectal cancer (CRC) being 26% from the right, 26% from the left colon and 30% were from the rectum, in 18% of the patients we could not determine sidedness. 35% already had metastatic disease at diagnosis. The lung was the site with largest number of lesions treated with SRT (50), followed by central nervous system (CNS) (42), bones (32), liver (29) and lymph nodes (16). After a median follow up of 15.3 months, 11% of patients were progression-free and only 24% had progressed on treated lesions. The median progression free survival following SRT was 4.5 months (0.6-45.8 range) for distant metastasis and was not achieved for treated sites. Conclusions: This retrospective study adds to the previous body of evidence supporting the use of SRT to improve GI cancer management. Detailed information on pts characteristics, pathology, toxicity and previous treatments will be presented.
Clinical outcome for gastrointestinal cancers with polymerase epsilon mutations treated with immunotherapy.
Authors: Zhu Limin , Meric-Bernstam Funda , Holla Vijaykumar , Kim Taebeom , Shaw Kenna Rael , Chen Ken , Routbort Mark , Kopetz Scott , Overman Michael J. 
Published: February 2020

828 Background: Predictive factors for immunotherapy benefit across gastrointestinal (GI) cancers are limited to those with deficient mismatch repair (dMMR). Mutations in DNA polymerase E (POLE) can cause a hypermutated phenotype irrespective of MMR status and may serve as a predictor factor for immunotherapy. Methods: All POLE-mutant GI cancers with tumor mutation burden (TMB) measured at MD Anderson Cancer Center were identified (N = 58) from 2014 to 2019 and those that had received immunotherapy (N = 18) were studied. TMB was measured by genomic profiling assays FoundationOne or STGA 2018. Samples were analyzed using Kaplan-Meier method and compared using log rank test, with a predefined high TMB threshold of 20 muts/mb. Results: Of the 58 POLE-mutant GI tumors a high TMB was present in 50% of the cases. 18 patients (median age 64, female gender 16.7%, median prior lines of therapy 2) with locally advanced (N = 4) or metastatic (N = 14) POLE-mutant GI cancers (13 colorectal, 1 small intestine, 1 esophageal, 1 pancreatic, and 2 gallbladder) were identified. Immunotherapy agents were PD-1/PD-L1 based in 17 and CTLA-4 based in 1. High TMB was present in 11 patients. dMMR was present in 7 patients, all with high TMB. Treatment response was seen in 3 patients (2 CR and 1 PR), all TMB high and dMMR. Progression-free survival (PFS) was significantly longer in those with high TMB (median: 10.1 months vs. 3 months, p = 0.048). Of the 11 pMMR patients median PFS was 9.3 months in high TMB and 3 months in low TMB (p = 0.246). Conclusions: POLE mutations in GI cancers were associated with a high TMB ( > 20muts/mb) in 50% of patients. Within POLE mutant GI cancers a high TMB may identify patients who benefit from immunotherapy irrespective of mismatch repair status.
Platinum-based therapy of patients with gastrointestinal cancers that harbor homologous recombination DNA damage response (HR-DDR) mutations: A single institutional retrospective analysis.
Authors: Singh Bhavana Pendurthi , Ballman Madison , Drake Evan , Khanchandani Ashish , Prins Petra , Weinberg Benjamin Adam 
Published: February 2020

836 Background: HR-DDR deficiencies have been described across cancer types and associated with response to specific therapies, including platinum (Pt)-based drugs and poly ADP-ribose polymerase (PARP) inhibitors. We sought to estimate the frequency of HR-DDR gene mutations in gastrointestinal (GI) cancers and determine if these patients (pts) benefit from Pt-based therapy. Methods: A retrospective chart review was performed on 421 pts with GI cancers treated at our institution. Tumors were categorized as colorectal (CRC), gastroesophageal (GE), pancreatic (PDA), hepatobiliary (HB), or other. All had next-generation sequencing with mutations in one or more of the following HR-DDR genes: BRCA1, BRCA2, PALB2, CHEK2, ATM, ARID1A, MRE11A, NBN, BARD1, and BL M. Overall survival (OS) of pts was analyzed using Log-rank test. Results: Of those analyzed, 127 pts (84 women and 43 men) met the inclusion criteria. Forty-eight percent had primary CRC tumors, and the remainder had primary GE (17%), PDA (14%), HB (10%), and other GI (11%) tumors. Fifty-four percent had stage IV disease. Sixty-five percent received Pt-based therapy at some point during their disease course. HR-DDR analysis revealed the following mutation rates: 34% ARID1A; 16% ATM; 19% BRCA2; and 9% BRCA1. OS analysis showed no significant survival advantage based on stage or mutation type for any of the disease-specific cohorts. There was no significant OS benefit in pts who received Pt-based therapy vs. those who did not, although pts with ARID1A-mutated tumors did show a trend towards improved OS (P = 0.09). Conclusions: Despite our limited cohort, our data suggest that pts with GI tumors harboring certain HR-DDR gene mutations might benefit from Pt-based therapy, supporting the development of mutation-specific Pt-based clinical trials.
Travel distance and time to adjuvant chemotherapy in veterans with colorectal cancer.
Authors: Martin Richard Lewis , Edwards Gretchen C. , Samuels Lauren R. , Roumie Christianne L. 
Published: February 2020

84 Background: Patients from rural areas have well described disparities in quality cancer care. We hypothesized that longer travel distance is associated with less chemotherapy acceptance and less timely treatment. Methods: We reviewed 705 electronic medical records of patients with colorectal surgeries from January 1, 2000 to December 31, 2015 at the Veterans Health Administration Tennessee Valley Healthcare System. Two trained abstractors reviewed standard elements (k = 0.79 – 0.92). The study sample included patients with pathological stage high risk II or III CRC and excluded those with metastatic disease or documented National Comprehensive Cancer Network (NCCN) defined medical exclusions from chemotherapy. Primary exposure was distance to care calculated from central zip code of residence to Nashville infusion center. Primary outcomes were receipt of any chemotherapy, and days from surgery to first treatment (truncated at 120 days). We analyzed 2 populations; chemotherapy received and a second sensitivity population who were eligible for, but did not receive, chemotherapy (no documentation of NCCN ineligibility or declined). Results: Of 705 colorectal resections, we excluded 262 for non-cancer, 220 for stage I or low risk stage II, and 46 for NCCN exclusion criteria, yielding 177 cases: 120 colon and 57 rectal. Most patients were male (98%) and white (85%); median age was 64 [Interquartile Range 60, 70]. Distribution by travel distance was 60/177 [33.9%] < 50 miles, 61/177 [34.5%] 50-99 miles, and 56/177 [31.6%] > 100 miles. Of all eligible patients, 123/177 [69.5%] patients received chemotherapy and 54/177 [30.5%] did not receive chemotherapy. Among receivers, median times to treatment were 52 days [40, 61] < 50 miles; 48.5 [40,61] 50-99 miles; and 54 [43,77] > 100 miles, p = 0.3. Patients not receiving chemotherapy varied by distance: 15/60 (25%) < 50 miles; 18/61 (30%) 50-99 miles; 21/56 (38%) > 100 miles, p = 0.3. Including non-receivers, median times to treatment were 58 days [43, 120] < 50 miles; 58.5 [46.5, 120] 50-99 miles; and 80 [48.5, 120] > 100 miles, p = 0.1. Conclusions: Distance to care may influence acceptability of chemotherapy. Understanding patient/provider reasons for omission merits exploration.
Racial disparity of stage III rectal cancer among young adults: A combined NCDB/SEER analysis.
Authors: Quinn Thomas J. , Kabolizadeh Peyman 
Published: February 2020

85 Background: With the advent of screening colonoscopy in 1997, there has been an overall decreasing incidence in rectal cancer. Recently, the ACS updated guidelines to started screening patients at 45 years old. The purpose of this study was to further investigate incidence and overall survival trends for rectal cancer among young white and African-American (AA) patients using the SEER and NCDB databases. Methods: Rectal cancer incidence trends in SEER-9/SEER-18 were analyzed for patients < 50 years old. Treatment and survival outcomes were also evaluated using the NCDB (2004-2014). White and AA patients were matched using propensity score analysis and inverse probability of treatment weighting (IPTW). Baseline characteristics were compared with Pearson Chi Square, before and after matching. Univariate and multivariable analyses were performed with Kaplan-Meier and Cox proportional hazard modeling, incorporating the IPTW-adjusted population. Results: 6,144 (SEER) and 17,819 (NCDB) young, white or AA patients were identified. There was an overall increase in incidence of stage III (APC 5.57, P < 0.05) and IV (APC 4.66, P < 0.05) rectal cancer among young white patients. For the entire population, there was improved overall survival for white patients compared to AA patients, even after adjusting for confounding factors. Subset analysis of both the SEER and NCDB databases revealed that the largest disparity was between AAn and white rectal cancer patients, is among the Stage III subset with HR of 1.6 (P < 0.001) and HR of 1.4 (P < 0.001), respectively. Conclusions: There is an alarming increase in younger patients being diagnosed with rectal cancer. Specifically, there appears to be more locally advanced rectal cancer among younger patients and a racial disparity favoring whites for survival outcomes was identified. This research further supports the utility of earlier screening and to identify the factors involved in this rise in rectal cancer incidence.
Evaluation of adjuvant chemotherapy-associated steatosis in colorectal cancer.
Authors: Lee Michelle (Chae Min) , Taqi Ayesha , Malik Aftab , Dzulynsky Raissa , Di Tomaso Amy , Brezden-Masley Christine 
Published: February 2020

94 Background: Chemotherapy-associated steatosis (CAS) is poorly understood in context of colorectal cancer (CRC). It has been anecdotally observed that CRC patients undergoing chemotherapy appeared to develop steatosis at a higher rate than expected, and that statin therapy may have protective effects against CAS. Here, we sought to evaluate 1) the frequency of CAS in Stage II-III CRC patients; and 2) whether patients on statins throughout adjuvant chemotherapy develop CAS at a lower frequency. Methods: This study retrospectively examined medical records of 267 Stage II-III CRC patients who received adjuvant chemotherapy and were followed up at St. Michael’s Hospital, Toronto, Canada between January 1, 2006 and January 1, 2017. Patient information, relevant co-morbid conditions, statin use, and adjuvant chemotherapy were collected. Baseline and incident steatosis for up to one year from chemotherapy start date was assessed based on imaging reports (CT, ultrasound, MR). Results: Of 267 patients, 78 (29.2%) had steatosis at baseline radiology, prior to treatment with adjuvant chemotherapy. Of the remaining 189 cases, the incidence of steatosis within one year of adjuvant chemotherapy start date was significantly greater in patients who received adjuvant treatment (n = 132) compared to those who did not (n = 57), (39% vs. 23%, p = 0.03). Among patients who underwent chemotherapy, statin use for preexisting hyperlipidemia, a known risk factor for steatosis (n = 39), was associated with a lower incidence of steatosis compared to no statin administration (n = 93), although this result was not significant (31% vs. 42%, p = 0.243). Among statin users, 42.9% of patients treated using oxaliplatin-containing FOLFOX regimen (n = 21) developed steatosis, compared to 20% in patients on a capecitabine regimen (n = 15). There was a trend towards significance, with p = 0.151. Conclusions: Chemotherapeutic treatment of Stage II-III CRC is associated with an increased incidence of steatosis. Statins may protect against acute development of CAS within one year following chemotherapy, particularly with single agent capecitabine. Prospective clinical trials should be considered to assess protective use of statin in this curative patient population.
A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer (PANDORA).
Authors: Tamberi Stefano , Grassi Elisa , Barbera Maria aurelia , Corbelli Jody , Papiani Giorgio , Montroni Isacco , Di Bartolomeo Maria , Cascinu Stefano , Marzola Marina , Bonetti Andrea , Frassineti Giovanni , Pinto Carmine , Zingaretti Chiara , Nanni Oriana , Carli Moretti Chiara , Panzini Ilaria , Rossi Giulio , Ugolini Giampaolo 
Published: February 2020

TPS259 Background: The standard treatment for cT3-4 N0-1 rectal cancer is preoperative chemo-radiation therapy (CT/RT). The combination of capecitabine plus long course radiotherapy (RT) is standard therapy in this setting. Pathologic Complete remission (pCR) can be considered as surrogate end point of efficacy of treatment in terms of disease free survival (DFS). Clinical complete remission (cCR) is an important endpoint for “wait and see” strategy. In the PACIFIC trial in non-small cell lung cancer the patients were treated with durvalumab maintenance after CT/RT with advantage in progression free survival. Preclinical data points heavily toward a strong synergy between RT and immune treatments. Furthermore, a systemic effect of RT is possible when enhanced by targeted immune treatments. Methods: This is a prospective phase II, open label, single arm, multi-centre study to evaluate the activity of an innovative sequence in operable rectal cancer: standard concomitant CT/RT therapy with 825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks followed by 1500 mg Q4W durvalumab for 3 administration. After 9-10 weeks from neoadjuvant therapy will be performed re-staging with CT and MRI scan. Surgery will be performed at week 10-12 from the end of CT/RT. Primary Objective: pCR rate, defined as a TRG 3-4 according to DWORAK criteria. Secondary Objectives: Safety of treatment with durvalumab; cCR rate after durvalumab treatment before surgery and DFS. cCR will be evaluated with clinical, endoscopic and radiological assessment to look for evidence of residual disease. DFS will be evaluated during a follow up of 5 years. Exploratory Objective: Biological translational analysis of tumor biomarkers will be performed on the endoscopy biopsy done at the diagnosis and on the biopsy performed after the CT/RT prior to treatment with durvavalumab. We hypothesize that the addition of durvalumab after standard CT/RT for the treatment of locally advanced rectal cancer may improve the pathological response rate and we have planned to enlist 60 patients in 7 centers with an enrollment period of 12 months, already underway. Clinical trial information: NCT04083365.
NRG-GI005 (COBRA): Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer.
Authors: Morris Van K. , Yothers Greg , Kopetz Scott , Jacobs Samuel A. , Lucas Peter C. , Iqbal Atif , Boland Patrick McKay , Deming Dustin A. , Scott Aaron James , Lim Howard John , Wolmark Norman , George Thomas J. 
Published: February 2020

TPS261 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. Trial accrual is anticipated across all US and Canadian cooperative groups.NCT#: 04068103. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: 04068103.
NSABP FR-2: Phase II study of durvalumab following neoadjuvant chemoRT in stage II-IV rectal cancer.
Authors: George Thomas J. , Yothers Greg , Jacobs Samuel A. , Finley Gene Grant , Parekh Hiral D. , Moore Timothy David , Maalouf Bassam Nabih , Krauss John C. , Deutsch Melvin , Lee James J. , Allegra Carmen Joseph , Wolmark Norman 
Published: February 2020

TPS264 Background: Clinical improvements for locally advanced rectal cancer have been relatively static over the past few decades. While immunotherapy shows no benefit in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitor use. Using a “window-of-opportunity” study design, this prospective phase II trial will determine the safety and activity of this approach with the anti-PD-L1 agent durvalumab (MEDI4736). Methods: This multi-center phase II trial is currently enrolling patients (pts) with rectal cancer who are undergoing standard NCCN guideline-compliant neoadjuvant chemoradiotherapy (CRT). Eligibility includes pts with MSS stage II-IV rectal cancer with adequate organ function and pre-treatment diagnostic tumor available for profiling with intent to proceed to surgical resection after CRT. Stage IV disease must be limited such that the primary pelvic tumor requires definitive management. Standard ineligibility criteria include active infections, systemic steroid use, or other conditions making immunotherapy use unsafe. Treatment includes durvalumab (750mg IV infusion once every 2 wks) for 4 total doses beginning within 3-7 days after CRT completion. Surgery must be within 8-12 wks of the final CRT dose. Primary endpoint is a demonstrated improvement in Neoadjuvant Rectal Cancer (NAR) score compared to historical controls targeting a 20% relative risk reduction in DFS and 3-4% absolute OS improvement. Secondary endpoints include OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, off-target “abscopal” effects for the subset of stage IV pts, and exploratory assessments of tumor infiltrating lymphocytes, tumor Immunoscore, circulating immunologic profiles, and molecular predictors of response. A safety run-in phase has completed as a precedent to full enrollment. Enrollment now continues to 47 total pts to achieve 41 surgically evaluable pts. Support: AstraZeneca-Medimmune, NSABP Foundation. Clinical trial information: NCT03102047.