bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early detection and localization of multiple cancers using a blood-based methylation assay (ELSA-seq).
Authors: Gao Qiang , Li Bingsi , Cai Shangli , Xu Jiayue , Wang Chenyang , Su Jing , Fang Shuai , Qiu Fujun , Wen Xiaofang , Zhang Yuzi , Wang Guoqiang , Liu Hao , Zhang Zhihong 
Published: January 2021

459 Background: Early detection of cancer can potentially offer clinical benefits, particularly for those without effective screening methods. The PREDICT study (pan-cancer early detection project, NCT 04383353) is a prospective, multi-center, longitudinal study that aims to identify multiple cancers non-invasively before symptoms become apparent. As a pilot project, the THUNDER (the unintrusive detection of early-stage cancer) study is designed for development and validation of ELSA-seq, a sensitive targeted methylation sequencing assay that interrogates epigenetic alterations from circulating cell-free DNA (cfDNA). Herein we report results from the second THUNDER sub study (THUNDER-II), which focused on malignancies developed in liver, colon/rectum, esophagus, pancreas, lung and ovary, of which four are gastrointestinal (GI) cancer types. Methods: THUNDER-II comprises four independent steps: marker discovery, model training, validation, and single-blind test. The marker discovery work was conducted by profiling 5.5 million CpG sites in 247 tissue samples (116 cancer, 131 normal/benign, 6 cancer types) using a SeqCap Epi CpGiant system (Roche). By combining data generated in-house and from public sources, a custom hybridization capture panel was designed to target 161,984 CpG sites. For cfDNA applications, 625 patients and 483 non-cancer controls were enrolled and divided into a training set (274 cancer and 195 non-cancer) and an independent validation set (351 cancer and 288 non-cancer). Results: The cancer patients and non-cancer controls were generally comparable with respect to age, gender, and smoking status. Various stages were represented in the cancer group, and 79.5% patients were diagnosed at early stages (I-III). At 99.5% training specificity (95%CI: 96.7-100%), the cross-validated sensitivity was 79.9% (95%CI: 74.6-84.4%). The results were consistent in the validation set, with 98.3% specificity (95%CI: 95.8-99.4%) and 80.6% (76.0-84.6%) sensitivity across stages and cancer types. In terms of tracking diseased organ(s), the classifier returned a tissue-of-origin (TOO) result in 98.6% cases, and 81.0% (95%CI: 77.2-84.3%) of these predictions were correct. Conclusions: Results from the THUNDER-II study demonstrated that early cancer signals could be identified by ELSA-seq with high specificity. This method also enabled accurate prediction of TOO, offering guidance for subsequent diagnostic work-up. Together these findings highlight the potential implementation of this sensitive and robust assay as a multi-cancer detection test.
Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer.
Authors: Zuckerman Jesse , Coburn Natalie G. , Callum Jeannie , Mahar Alyson , Acuña Sergio A , Guttman Matthew P , Zuk Victoria , Turgeon Alexis F. , Martel Guillaume , Hallet Julie 
Published: January 2021

464 Background: Perioperative anemia and red blood cell (RBC) transfusions are common in patients undergoing gastrointestinal cancer surgery. To adequately balance the risks and benefits of transfusion, clinicians must understand the potential effect of transfusions on long-term outcomes. Methodologic issues have limited previous studies exploring the association between RBC transfusion and survival in this specific patient population. Our objective was to determine, among patients who have undergone gastrointestinal cancer resection, if perioperative RBC transfusions are associated with higher risk of all-cause and cancer-specific death. Methods: In this population-based retrospective cohort study, we used administrative datasets containing routinely collected data from Ontario, Canada. Patients who underwent gastrointestinal cancer resection between January 1, 2007 and March 31, 2019 and survived at least 90 days postoperatively were eligible for inclusion. All-cause death from the ninetieth post-operative day was compared between groups using Kaplan-Meier methods and Cox proportional hazards models. Cancer-specific death was compared using competing risk methods. Regression adjusted for potential confounders. Sensitivity analyses, including the E-value, evaluated the robustness of estimates. Results: We identified 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) who underwent resection for gastrointestinal cancer and survived at least 90 days after surgery. Over a median follow-up of 4.1 years (interquartile range 1.9-5.0 years), patients who received RBC transfusions demonstrated increased hazards of all-cause and cancer-specific death relative to patients who were not transfused (hazard ratio: 1.39, 95% confidence interval 1.34 to 1.44; cause-specific hazards ratio: 1.36, 1.30 to 1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months post-operatively) but remained elevated in each subsequent interval over 5 years. Conclusions: RBC transfusion among patients with gastrointestinal cancer is associated with increased all-cause death; this persisted over time suggesting a long-term effect of perioperative transfusion. These findings should help clinicians balance the risks and benefits of transfusion and highlight the need for well-designed, multicenter randomized trials to determine if aggressive transfusion avoidance protocols could improve patient survival after gastrointestinal cancer surgery.
Feasibility of using a computerized food frequency questionnaire (FFQ) to assess dietary patterns in patients with advanced gastrointestinal (GI) malignancies.
Authors: Jain Rishi , Denlinger Crystal S. , Handorf Elizabeth A. , George Roshan , Lewis Bianca , Hunt Alexandra , Stromberg Kara , Astsaturov Igor A. , Dotan Efrat , Hall Michael J. , Vijayvergia Namrata , Fang Carolyn Y 
Published: January 2021

465 Background: Identification of poor dietary patterns is important for the optimal management of patients with metastatic GI malignancies who suffer from high rates of malnutrition and sarcopenia which are associated with increased rates of treatment-related toxicity and worsened survival. Dietary records or recall methods and FFQs are available but have high patient burden and are seldom utilized in oncology settings outside of formal nutritional consultations. Thus, we evaluated the feasibility of conducting serial assessments of dietary patterns using a novel computerized FFQ technology. Methods: Assessments of diet using the computerized FFQ, nutritional status (NUTRISCORE), QOL and anorexia/cachexia burden (FAACT), anxiety/depression (HADS) and taste burden were done at the time of initiation of first-line chemotherapy (baseline) and 3 months later. The FFQ was done independently either at home on personal computer after visit or via iPad in infusion room. Dietary quality was defined by the Healthy Eating Index 2010 (HEI) score, which was automatically calculated by the computerized FFQ software. Feasibility was defined as at least 70% of patients completing baseline and 3-month assessments. Spearman’s correlations were used to determine associations between measures. Results: 29 patients with advanced (metastatic or unresectable) GI cancers were enrolled and 23 completed the baseline FFQ (8 colorectal, 5 pancreas, 5 gastroesophageal, 5 other). Median age was 58 (20-78) with M:F ratio of 10:13. The overall completion rate of baseline and 3-month assessments was 81.8%, meeting the pre-defined feasibility criteria. The mean baseline HEI score was 65 (range 38-88). Of patients who completed both baseline and 3-month assessments, the mean HEI score remained stable at 58 with changes in specific HEI components including a 20% decline in the seafood and plant protein score and a 13% decline in the whole grain score and small improvements in other areas (e.g. empty calories, dairy). There were no significant correlations between baseline HEI score and other assessments. Conclusions: It is feasible to use a computerized FFQ to assess for longitudinal changes in eating patterns and dietary quality in patients with advanced GI cancers, particularly when patients can complete the assessments during chemotherapy infusions. Preliminary findings also suggest that the FFQ can be helpful for highlighting areas in which diet quality could be improved. Additional analysis of other computerized FFQ data (e.g. macro/micronutrient consumption) is ongoing.
Incidence, mortality and hospital resource utilization in patients with gastrointestinal cancer and malnutrition: A nationwide analysis.
Authors: Katiyar Vatsala , Vohra Ishaan , Lingamaneni Prasanth , Baral Binav , Kumar Rohit 
Published: January 2021

466 Background: Malignancies are associated with a high prevalence of cachexia, protein energy malnutrition (PEM) and failure to thrive. We analyzed the National inpatient Sample database (NIS) to understand the temporal trends and differences between gastrointestinal cancers (GIC) patients with and without malnutrition. Methods: All adults admitted with GIC including esophageal, gastric, pancreatic, hepatic, gall bladder, small and large intestine and anal cancers from 2012-2016 were identified from the NIS using the ICD 9 and ICD 10 codes. We analyzed the temporal trends of mortality and resource utilization. Multivariable logistic regression was used to evaluate the risk factors for malnutrition in patients with GIC. Results: There were 2,645,285 GIC inpatient admissions between 2012-2016, out of which 6.1% patients died. 11.1% (±0.22) patients had PEM and three most common GIC associated with PEM were Esophageal (19.7±0.24%), gastric (16.5±0.22%) and small intestine (15.2±0.41%). On multivariate analysis, PEM was more common in male gender (OR: 1.07, 95% CI:1.05-1.08, P<0.01), African- American race (OR:1.14, 95% CI: 1.10-1.17, P<0.01) and Charlson comorbidity index >=2(OR:1.5, 95% 1.42-1.51, P<0.01). Malnourished patients were often terminally ill (48.8% vs 39.8%), in intensive care unit (7.89% vs 3.75%), were more likely to be seen by palliative care team (17.6 % vs 9.8%) and were more likely to die (9.6% vs 5.70%, OR-1.76; p <0.01). The incidence, mortality, and total charge of PEM in patients with GIC significantly increased from 2012 to 2016 as shown in the table below. Conclusions: Malnourished patients with GIC tend to have more advanced disease and have an increased mortality as compared to patients with adequate nutritional status. Optimization of their nutritional status can greatly improve outcomes and curb healthcare costs. [Table: see text]
Beyond BRCA? clinical utility of homologous recombination deficiency in gastrointestinal cancers.
Authors: Tsang Erica S , Csizmok Veronika , Williamson Laura , Pleasance Erin D. , Topham James T. , Karasinska Joanna , Titmuss Emma , Schrader Kasmintan A , Cafferty Fergus , Yip Stephen , Tessier-Cloutier Basile , Mungall Karen , Sun Sophie , Lim Howard John , Loree Jonathan M. , Laskin Janessa J. , Marra Marco A. , Jones Steven J. M. , Schaeffer David F. , Renouf Daniel John 
Published: January 2021

472 Background: There is emerging evidence about the predictive role of homologous recombination deficiency (HRD) in multiple cancers. The clinical utility of HRD is less well defined in gastrointestinal (GI) malignancies. Methods: We reviewed the whole genome (WGS) and transcriptomic (RNA-Seq) data of patients with advanced GI cancers between 2012-2018 in the Personalized Oncogenomics trial (NCT02155621). Scores were calculated as the sum of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions scores. HRD was defined as a score ≥34. Mutational analysis was performed to determine the presence of mutational signature 3, which is usually strongly associated with BRCA status. Retrospective chart review was conducted to extract treatment and survival outcomes. Overall survival (OS) from initiation of first-line systemic therapy and time to progression on platinum therapy (TTPp) were calculated. Linear and multivariable regression analyses were conducted. Results: Of 154 patients with GI primaries, 56% were male and 105 (68%) were exposed to a platinum agent in the metastatic setting. Primary sites included upper GI (N=20, 9%), pancreas (N=35, 16%), colorectal (N=74, 33%), and other GI primary (N=25, 11%). Ten patients (6%) had a BRCA1/2 mutation, 20 (13%) had a high HRD score, and 11 (7%) had a high signature 3 score (>0.05). Six patients had both high HRD and high signature 3 scores (Table). On linear regression, high HRD scores and mutational signature 3 were independently associated with longer TTPp (β=4.17, 95% CI 0.15-8.19, p=0.04; β=8.03, 95% CI 2.87-13.18, p<0.05, respectively). On multivariable linear regression, after adjusting for HRD score, BRCA1/2 status, and tumor site, only cases with a mutational signature 3 retained significance ( p<0.05). HRD status was not prognostic for OS (HR 1.02, 95% CI 0.65-1.62, p=0.92). Conclusions: Within a cohort of patients with GI malignancies characterized by WGS and RNA-Seq, mutational signature 3 was more strongly associated with TTPp compared to HRD score. These data highlight potential predictive implications of Signature 3 to complement HRD and BRCA status in identifying patients who may benefit from exposure to platinum therapy. [Table: see text]
The impact of immunotherapy education on GI cancers.
Authors: Parikh Kinjal , Lucero Katie , Warren Charlotte , Van Laar Emily Sherene , Kugel Patrick , Kadkhoda Haleh 
Published: January 2021

479 Background: Gastrointestinal (GI) cancers are a heterogeneous group of cancers with varying underlying pathophysiology and distinct treatment paradigms. Immunotherapy (IO) is unique in each of the subtypes and biomarkers utility varies. With the expansion of IO in each cancer subtypes, education remains essential to optimize patient outcomes through integration of the latest evidence-based data at point of care. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, 2 educational activities were designed to increase the knowledge and competence of oncologists surrounding the role of IO in patients with advanced GI cancers. Methods: The 2 educational activities included a text based online activity with 3 chapters focused on gastroesophageal cancers, colorectal cancers, and hepatocellular carcinoma (HCC) and a 30-minute online, video discussion with 3 faculty and synchronized slides on HCC. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. A chi-square test was used to identify statistical significance in proportion of correct responses. The first activity launched 11/27/2019 and the second activity launched on 5/8/20. Data were collected and reported through 8/25/2020. Results: A total of 8433 learners, including 1543 oncologists, participated from 11/2019 through 8/2020. Participation in education resulted in significant relative improvements among oncologist learners on IO in GI cancers in (n = 641): 110%: role or eligibility of immune checkpoint inhibitors (ICIs) (p < .001) 38%: clinical trial data of ICIs (p < .001) Subsequent education on unresectable HCC demonstrated a significant relative improvement in both knowledge and competence for oncologist learners (n = 902): 19%: regarding clinical trial data in unresectable HCC (p = .073) 19%; competence identifying role of ICIs in unresectable HCC (p < .05) 59%: competence managing irAEs in unresectable HCC (p < .001). Conclusions: These 2 online CME-certified educational activities resulted in statistically significant gains in oncologist knowledge surrounding the use of IO in advanced GI cancers Follow-up education on HCC demonstrated the value and benefit of multi-modal and sequential activities on improving competence among oncologists caring for patients with unresectable HCC There remains a need for continuous education as more oncologists utilize IO in their practice while the understanding and availability of clinical data continues to expand and evolve in the varying GI cancer subtypes. More than 50% of learners continued to demonstrate a need in understanding the clinical trial data or role of IO in metastatic GI cancers with more than 40% of the learners demonstrating continued need on clinical trial data or role of IO in HCC specifically.
Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in Uruguay: A population-based study.
Authors: Fontes Santiago , Marín-Jiménez Ana , Berry Megan , Cuello Mauricio , Sánchez Juan Carlos , Reyes Graciela , Krygier Gabriel David 
Published: January 2021

53 Background: Despite surgery, the 5-year risk of systemic recurrence of colorectal cancer (CRC) in the absence of any further therapy is approximately 50 % for those with lymph node involvement and 20 ─ 30 % if the lymph nodes are negative. Adjuvant chemotherapy contributes to improved disease-free and overall survival for node-positive (stage III) or high-risk node negative (stage IIB) colon cancer. Similar benefits are observed for adjuvant chemoradiotherapy in rectal cancer. Previous research shows varied rates of adherence to published adjuvant chemotherapy Clinical Practice Guidelines (CPGs) for CRC, although population-based data is scarce. Purpose: The aim of this analysis was to assess adherence rates to adjuvant chemotherapy prescription within 16 weeks of surgery according to local and international CPGs for CRC patients treated with curative intent between 2008 and 2019 at the Uruguayan National Cancer Institute. Data regarding factors associated with chemotherapy receipt beyond 16 weeks from surgery and chemotherapy non receipt was also retrieved and analysed. Methods: We retrospectively reviewed medical and pathology reports of 833 patients diagnosed with CRC at our institution. Patients with stages IIB or III CRC who underwent curative-intent surgery were identified and included in the present analysis. A 16-week benchmark timeline for treatment initiation from date of surgery was considered. Fisher’s exact test was used to determine factors independently associated with receipt of chemotherapy and meeting the 16-week benchmark (p 0.05). Results: A total of 400 patients were identified of which 72% had peritoneal colorectal tumors and 28% had sub-peritoneal rectal tumors. Approximately 70% of the latter group received neoadjuvant chemo-radiotherapy. Considering the total cohort, 61% received adjuvant chemotherapy. Factors predicting chemotherapy receipt in the peritoneal colorectal group were age ≤ 70 and stage III disease. In the sub-peritoneal rectal group no significant effect was found. The 16-week benchmark was met in 72% (175) of those receiving chemotherapy and 70.6% (167) completed 6 months of systemic adjuvant treatment. A total of 156 patients (39%) did not receive adjuvant chemotherapy. The factors predicting chemotherapy non receipt were age > 70 and stage IIB in the peritoneal colorectal group. Conclusions: This analysis of adherence to CPGs identified several factors associated with chemotherapy non receipt and chemotherapy receipt outside of timeline benchmarks from date of curative-intent surgery in Montevideo, Uruguay. The two main factors significantly associated with chemotherapy non receipt were advanced age and lower disease stage. To our knowledge, our data is the first to elucidate these specific factors in the Uruguayan CRC patient population.
Clinician perspectives on preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies.
Authors: Lau-Min Kelsey S. , Varughese Lisa A. , Nelson Maria N. , Cambareri Christine , Reddy Nandi J. , Oyer Randall A. , Teitelbaum Ursina R. , Tuteja Sony 
Published: January 2021

54 Background: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Methods: We conducted a multi-site mixed-methods study to understand clinician attitudes toward PGx testing and to identify facilitators and barriers to using preemptive testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a demographic survey and semi-structured interview informed by the Consolidated Framework for Implementation Research. Interviews were analyzed using a modified grounded theory approach. Results: A total of 16 medical oncologists and 9 oncology pharmacists from one academic medical center and two community hospitals participated. Fifteen (60%) participants reported feeling comfortable or very comfortable with interpreting PGx test results. While clinicians expressed generally favorable attitudes toward PGx testing, many were hesitant to use it to preemptively guide chemotherapy dosing due to a perceived lack of evidence for this practice. They cited a lack of consensus chemotherapy dosing recommendations in response to PGx test results, as well as concerns about decreased drug efficacy, especially in patients treated with curative intent. Additional barriers included 1) a low prevalence of actionable PGx variants; 2) lengthy PGx test turnaround time; 3) concerns about testing costs and lack of insurance coverage; and 4) burdensome integration of PGx testing into clinical workflows. The electronic health record emerged as a potential tool for the unobtrusive integration of PGx testing into clinical practice–suggested applications included default PGx test orders for eligible patients, discrete reporting of PGx variant results, and clinical decision support to guide subsequent chemotherapy dosing. Conclusions: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multi-level effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study. The electronic health record should be explored as a tool to integrate PGx testing into routine practice.