bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pattern of recurrence after curative resection of stage I-III duodenal adenocarcinoma.
Authors: Colina Andreina , Raghav Kanwal Pratap Singh , Katz Matthew H. G. , Das Prajnan , Ikoma Naruhiko , Koay Eugene Jon , Thomas Jane V , Tzeng Ching-Wei David , Wolff Robert A. , Overman Michael J. 
Published: February 2020

794 Background: Duodenal adenocarcinoma (DA) is a rare cancer with limited data regarding the pattern of disease recurrence following resection. Methods: A retrospective review of 115 patients with Stage I-III DA from 3/1994 to 6/2018, at a single high-volume cancer center was conducted. Only patients (pts) who underwent a potentially curative surgical resection (R0/R1 margins) and had a postoperative follow-up radiographic evaluation were included. Periampullary adenocarcinomas were excluded. Clinicopathologic features and patterns of recurrence were compared across cohorts. Results: Of 76 patients who met inclusion criteria, 7 (9%) were stage I, 25 (33%) stage II, and 44 (57%) stage III. Histologic grade was moderate in 58% and poor in 38%. Median age was 63 years (range, 29-84), 38% were female, and R0 resection was 97%. Neoadjuvant therapy was given to 14% and adjuvant therapy to 61%. Radiation therapy (XRT) as either adjuvant/neoadjuvant therapy was used in 27%. Median follow-up was 44 (6-293) months. Median time to recurrence was 11mo, with 84% of recurrences occurring within 2 years. Median time to local recurrence (LR) vs. distant recurrence (DR) was 11mo vs. 12mo, respectively, p = 0.42. Stage impacted recurrence rate: 0% in stage 1 vs. 50% stage 2 vs. 71% stage 3 (p = 0.002). Median time to recurrence was 16mo for stage II and 11mo for stage III (p = 0.04). In total, 4 (5%) pts had LR only, 8 (10%) had LR concurrent with DR, and 32 (42%) had DR only. Recurrence distribution was similar across stage II (LR 8%, LR+DR 15%, DR 77%) and stage III (LR 10%, LR+DR 19%, DR 71%). LR was similar in patients that received XRT (10%) compared to those who did not (9%). Most common sites of DR were peritoneal (38%), liver (33%), distant lymph nodes (12%), and lung (10%). Conclusions: The recurrence pattern for resected DA is predominantly distant metastatic disease with the majority of recurrences occurring within the first two years. Future therapies should focus on improved systemic therapy, and surveillance should be most intensive in the first two years.
Pilot study to test safety and efficacy of avelumab in small bowel adenocarcinoma (SBA).
Authors: Cardin Dana Backlund , Whisenant Jennifer , Ayers G. Dan , Gilbert Jill , Dahlman Kimberly Brown , Shi Chanjuan , Berlin Jordan 
Published: February 2020

797 Background: SBA is rare and often grouped with, and treated like, large intestinal adenocarcinomas. However, SBA has a very different microenvironment and could respond differently to the same therapies, potentially lowering efficacy. Also no standard treatments exist due to the lack of prospective randomized trials. We presented data at GI ASCO 2016 that suggested SBAs might benefit from targeting the PD-1/PD-L1 axis based on strong PD-L1 staining in ~50% of SBAs tested. Thus, we designed a pilot phase 2 trial to study safety and efficacy of avelumab in SBA. Methods: Patients (pts) with advanced (not amenable to surgery) or metastatic disease were eligible; ampullary tumors were considered part of the duodenum and allowed. Pts with prior PD-1/PD-L1 were excluded. Avelumab (10 mg/kg) was given every 2 weeks in 14-day cycles, and imaging was performed every 8 weeks. Primary endpoint was response rate (RR). Enrollment of 25 pts were planned, and avelumab would be considered active if ≥4 responses (RR≥16%) were observed (80% power, a = 5%). Secondary endpoints included disease-control rate (DCR) and progression-free survival (PFS). Results: Eight SBA pts (5 small intestine; 3 ampullary) were enrolled, with a majority (88%) being male and a median age of 61 years. Median time on treatment was 3.4 months; 1 patient is still on study with an ongoing partial response (PR). Of 7 efficacy-evaluable patients, 2 had a PR for a RR of 29%; DCR was 71% (5/7). Median PFS was 8.0 months. Most frequent, related adverse events were fatigue (38%), elevated alkaline phosphatase (25%), and infusion related reaction (25%), all ≤G2; a G3 (not serious) hypokalemia and a G4 (serious) diabetic ketoacidosis occurred in 1 pt each. Conclusions: Avelumab was considered safe, and antitumor activity was observed as evidenced by a 29% RR and 71% DCR. Despite this benefit, accrual was slower than expected and the study was closed early due to feasibility. A general clinical observation is that more pts are receiving immunotherapy off-label as the availability of these agents increases. This was a likely contributor to slow accrual, in addition to disease rarity. Analysis of PD-L1 expression, MSI status, and other immune cell markers is planned and will be compared to response. Clinical trial information: NCT03000179 .
Clinical outcomes of patient migration in locally advanced rectal cancer from community cancer centers: An analysis of the National Cancer Database.
Authors: Kumar Rohit , Bhandari Shruti , Ngo Phuong , Singh Sunny R K , Malapati Sindhu Janarthanam , Rojan Adam 
Published: February 2020

81 Background: With cancer care changing at a rapid pace, patients are becoming increasingly involved with their management and oftentimes migrating to a different facility to seek better care. Our study evaluated the characteristics of such patients who were initially diagnosed at a community cancer center (CCC) and how this affects clinical outcomes. Methods: The National Cancer Database identified 11,977 patients with stage II/III rectal cancer initially diagnosed at a CCC between 2005 and 2015. Clinical characteristics and outcomes between patients who received all of their treatments at the CCC versus those who received part or all of their treatments elsewhere were compared using rank-sum and X2 tests where appropriate. Cox model was used for survival analysis. Results: Of the total population, 51% were stage II and 49% were stage III. Gender and ethnic distributions were similar between the groups. Approximately 44 % of patients received all their treatment at the CCC and 56% had part or all of their care elsewhere. Patients who migrated were younger (63 vs 65 years, p<0.001) and had govt insurance (43.5 vs 35.8%, p<0.001). On multivariate analysis, age <65 years (OR 1.12, 95% CI 1.02-1.24), govt insurance (OR 1.17, 95% CI 1.06-1.29), Charlson/Deyo comorbid score <2 (OR 1.29, 95% CI 1.11-1.49), higher income (OR 1.21, 95% CI 1.16-1.27) and Stage III (OR 1.15, 95% CI 1.07-1.24) were associated with higher probability of migration. The treatment characteristics and outcomes are shown in Table. The 5y-OS rate was better in patients who received part or all of their treatment at other institutions (adjusted HR 0.80, 95% CI 0.74-0.86, p<0.001). Conclusions: Further studies are needed to provide direction for future strategies to reduce the apparent survival disparities in patients who migrate from CCC. [Table: see text]
Survivorship care engagement with American Indian and Alaska Native survivors of gastrointestinal (GI) cancers.
Authors: Hill-Kayser Christine E. , Vachani Carolyn , Amaniera Isabella , Bach Christina , Arnold-Korzeniowski Karen , Hampshire Margaret K. , Metz James M. 
Published: February 2020

814 Background: American Indian and Alaska Native (AI/AN) survivors are at significant risk for GI cancers, and also represent an underserved medical population. Gastrointestinal cancers represent the third most commonly diagnosed cancers in the AI/AN population and are a leading cause of death. Survivorship resources tailored for the AI/AN population are sparse and patterns of survivorship care poorly understood. Methods: The OncoLife survivorship care plan has been through the OncoLink website since 2007. The tool is free and publically available. It asks survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. All research is IRB approved. Results: Over the past 12 years, the OncoLife tool has been utilized by >85,000 persons, with survivors of GI cancer representing 10-12% of users each year. Most users are women (75%) and Caucasian (80%). American Indian and Alaska Native survivors represent <1% of users since the launch of the tool. Of 519 AI/AN users, median age was 54 years, and 76% identified as female. Of plans created for AI/AN survivors, 13% were for survivors of GI cancers, with the most common GI diagnosis being colorectal cancer (74%), followed by pancreas (11%) and anal (6%). Most plans (73%) were created by HCP, with the remainder by survivors themselves; 20% of AI/ AN users completing plans requested information on smoking cessation as part of their care plan. Conclusions: American Indian and Alaska Native survivors represent a very small minority of survivors utilizing this free Internet-based tool, with most plans for this population being created by healthcare providers and not by survivors themselves. Future efforts should be directed at supporting this underserved population with survivorship information, particularly given high risk of morbidity and mortality related to GI cancers.
Comprehensive genomic profiling for chemotherapy-naïve advanced gastrointestinal malignancies.
Authors: Kondo Tomohiro , Pham Nguyen Quy , Matsubara Junichi , Fukuyama Keita , Nomura Motoo , Funakoshi Taro , Funakoshi Mari , Sakamoto Hitomi , Ashida Kanami , Mukai Kumi , Uemoto Shinji , Sakai Yoshiharu , Seno Hiroshi , Minamiguchi Sachiko , Haga Hironori , Kosugi Shinji , Kanai Masashi , Matsumoto Shigemi , Muto Manabu 
Published: February 2020

832 Background: From June, 2019, two comprehensive genomic profiling (CGP) assays, "FoundationOne CDx" and “OncoGuide NCC Oncopanel”, were reimbursed by the national insurance system in Japan for patients who were refractory to standard chemotherapy. However, their clinical utility for chemotherapy-naïve cancer patients is unknown. Methods: We conducted a single institutional prospective observational study to evaluate the clinical utility of FoundationOne CDx assay (Cambridge, MA, USA) for the patients with chemotherapy-naïve advanced gastrointestinal malignancies. Patients with adequate H.E. sample were registered in this study. Primary outcome was the detection rate of at least one actionable/druggable cancer genomic alterations. The evidence levels were classified according to clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (Edition 1.0) (Sunami K. Cancer Sci. 2018). Results: From October 2018 to June 2019, a total of 238 patients were screened and the following 158 patients were registered: colorectal cancer (n = 60), gastric cancer (n = 19), esophageal cancer (n = 23), pancreatic cancer (n = 30), biliary tract cancer (n = 11), rare gastrointestinal malignancies (n = 15). The CGP data were obtained for 113 patients . Median turn-around time was 14 days (range 10-247 days). Actionable/druggable cancer genomic alterations were observed in 113 patients (100%)/ 65 patients (57.5%), respectively. Clinically relevant biomarkers and genomic alterations were identified in 22 patients (19.5%); BRCA2 (n = 4), ERBB2 (n = 4) , BRAF (n = 3) , EGFR (n = 3), FGFR2 (n = 2), MET (n = 2), NTRK (n = 2) , MSI-H (n = 2 ), TMB-high (n = 2), ALK (n = 1) , KIT (n = 1) and ROS1 (n = 1). Of note, novel biomarkers such as ROS1- GOPC fusion and PALB2 rearrangement were obtained in the patients with esophageal squamous cell carcinoma. Conclusions: This is the first study to evaluate the clinical utility of CGP in patient with chemotherapy-naïve advanced gastrointestinal malignancies. Our result indicated that CGP might provide a chance of potentially effective drugs as a novel approach in precision cancer medicine. Clinical trial information: UMIN000034830.
Understanding the expanding armamentarium for GIST: Engaged learning outcomes.
Authors: Worst Michelle Arielle , Van Laar Emily Sherene , Tanzola Mindy , Heinrich Michael C. , Villalobos Victor Manuel 
Published: February 2020

837 Background: Gastrointestinal stromal tumors (GIST) are rare soft-tissue sarcomas that harbor specific genomic alterations, making GIST an ideal model for targeted therapy. Common oncogenic drivers include mutations in the KIT and PDGFR tyrosine kinase. Due to varying resistance patterns to existing TKIs, clinicians are challenged to stay current with new data and how best to integrate new agents into treatment paradigms. The objective of this study was to assess the changes in oncologists’ and gastroenterologists’ knowledge, competence, and confidence through participation in education regarding optimal GIST treatment. Methods: The educational activity consisted of a 30-minute online, 2 faculty, video discussion with synchronized slides. Educational effect was assessed with a repeated pairs pre-/post-assessment study with a 3-item, multiple choice, knowledge/competence questionnaire and one confidence assessment question. For all questions, each participant served as his/her own control. Pre- and post-assessment scores were compared to determine the relative changes in the proportion of correct responses. A chi-square test assessed statistical significance at the P < 0.05 level. The activity launched 25th June 2019; data were collected until 19th August 2019. Results: Overall significant improvements were seen after education for oncologists (N=52, P < 0.001) and gastroenterologists (N=127, P < 0.01). The relative improvement was 79% for oncologists and 44% for gastroenterologists (pre-/post-assessment average correct response rates were 24%/43% and 23%/33%, respectively). Following the activity, 44% of oncologists and 37% of gastroenterologists were more confident in their ability to select appropriate therapy for patients with metastatic GIST. Conclusions: Participation in an online, 30-minute video discussion CME intervention resulted in statistically significant improvements in knowledge, competence, and confidence of oncologists and gastroenterologists, that may lead to improvements in clinical care. As new data and agents emerge, new educational activities are necessary to reinforce knowledge, close persistent gaps, and increase oncologists’ confidence in this clinical setting.
New response evaluation criteria using early morphological change in imatinib treatment for patients with gastrointestinal stromal tumor.
Authors: Ishida Tomo , Takahashi Tsuyoshi , Saito Takuro , Kurokawa Yukinori , Yamashita Kotaro , Tanaka Koji , Makino Tomoki , Yamasaki Makoto , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro 
Published: February 2020

838 Background: While the introduction of molecularly targeted drugs, including imatinib, has greatly improved the prognosis of gastrointestinal tumor (GIST), the response evaluation criteria have not been optimized. Early morphological change (EMC) was previously reported as a predictive marker for molecularly targeted drugs in metastatic colorectal cancer. The purpose of the present study was to verify the efficacy of EMC in predicting the outcome in patients with GIST receiving imatinib. Methods: We retrospectively reviewed 55 patients. EMC in computed tomography (CT) image was evaluated, and the patients were categorized into two groups; active MR (morphologic response) (+) group and active MR (-) group, judging from the morphological features including the sharpness of the outline and the attenuation of target lesion. We investigated the association between the presence of active MR and clinical outcomes. Similarly, clinical outcomes classified by response evaluated by RECIST and Choi criteria were analyzed respectively. Results: Thirty-two patients had active MR (+). The median Progression-free survival(PFS) was 7 months vs 31 months (active MR(-) vs active MR(+), P = 0.013) and the median overall survival (OS) was 58 months vs 91 months ( P = 0.086), respectively. Although PFS of RECIST PD (progression disease) or Choi PD patients was shorter than that for PR (partial response) or SD(stable disease) patients ( P = 0.0037 for RECIST, P = 0.0058 for Choi), the number of PD patients was very small (N = 3, both in RECIST and Choi). Conclusions: The evaluation criteria based on EMC could be a sensitive method to predict the clinical outcome of imatinib treatment for patients with inoperative GIST.
Comparing FOLFOXIRI plus bevacizumab with doublet chemotherapy plus anti-EGFR antibody: A systemic review and network meta-analysis.
Authors: Zhang Jianwei , Li Jianxia , Xie Xiaoyu , Cai Yue , Wu Zehua , Hu Huabin , Ding Miaomiao , Deng Yanhong 
Published: February 2020

97 Background: FOLFOXIRI plus bevacizumab (Triplet+Bev) improved survival benefit when comparing with doublet chemotherapy plus Bev (doublet+Bev) as initial treatment in metastatic colorectal cancer (mCRC). Several trials also compared the efficacy of doublet plus EGFR antibody (doublet+EGFRi) with doublet+Bev. However, little is known about triplet+Bev comparing with doublet +EGFRi in mCRC. Methods: We did a systematic review and network meta-analysis with a systematic literature search on PubMed, EMbase, Web of Science, and international oncology conferences. We included phase 2 and 3 randomized controlled trials investigating FOLFOXIRI+Bev versus doublet+Bev or doublet+EGFRi versus doublet+Bev as first-line treatments in mCRC. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for PFS and OS in overall population, Ras wild type population, left or right side patients, left or right-side Ras wild-type population. And to compare relative risk (RR) for objective response rates. Results: Eight trials involving 3980 patients were included. In direct comparison, Triplet+Bev was superior to doublet+EGFRi both in OS (HR 0.83 0.72-0.97), PFS (HR 0.73, 0.65-0.83)and ORR (RR 1.5, 1.2-2.0). Doublet+EGFRi was beneficial in OS (HR 1.2, 1.1-1.5) and ORR (RR 0.74, 0.52-0.97) than doublet+Bev, but not PFS. In indirect comparison, Triplet+Bev showed no difference to doublet+EGFRi in OS (HR 1.0, 0.84-1.4) and ORR (RR 1.1, 0.73-1.6) in all population, and improved PFS (HR 0.71, 0.60-0.86). In left side RAS wild-type subgroup, Triplet+Bev showed similar efficacy in OS (HR 1.2, 0.6-2.5), PFS (HR 1.6, 0.59-4.3), and ORR (RR 0.63, 0.22-15). But in Right-side subgroup, Triplet+Bev was beneficial both in OS (HR 0.41, 0.18-0.93) and PFS (HR 0.55, 0.34-0.92). In right-side RAS wild-type subgroup, Triplet+Bev also showed trend of longer OS (HR 0.37, 0.12-1.1) and PFS (HR 0.43, 0.18-1.1) than doublet+EGFRi. Conclusions: In left-side RAS wild-type mCRC, FOLFOXIRI+Bev showed similar efficacy to doublet+EGFRi. While in right-side subgroup or right-side RAS wild-type population, Triplet+Bev is preferable as initial treatment for mCRC, in the meanwhile, in cautious of AE.
A phase III randomized controlled trial comparing surgery plus adjuvant chemotherapy with or without preoperative chemoradiotherapy for locally recurrent rectal cancer: A Japan Clinical Oncology Group study (JCOG1801).
Authors: Tsukada Yuichiro , Ito Masaaki , Nakamura Naoki , Ito Yoshinori , Bando Hideaki , Ando Masahiko , Onaya Hiroaki , Ikeda Masataka , Sekimoto Mitsugu , Kadota Tomohiro , Katayama Hiroshi , Mizusawa Junki , Fukuda Haruhiko , Kanemitsu Yukihide 
Published: February 2020

TPS263 Background: Local recurrence is one of the most common forms of recurrence after curative resection for primary rectal cancer. Surgical resection is recommended for locally recurrent rectal cancer (LRRC) to achieve radical cure if the tumor is judged as resectable with negative margins. However, a high local re-recurrent risk after surgery is a major problem due to the difficulty of re-resection and the serious symptoms, such as pain or fistula, resulting from re-recurrence. Preoperative chemoradiotherapy (preCRT) is expected to improve local control after radical surgery for radiation naïve LRRC; however, high frequency of surgical complications after preCRT cannot be ignored. Due to the refractory nature and rarity of LRRC, the true impact of preCRT on oncological and surgical outcomes has not been clarified by clinical trials. The purpose of this study is to confirm the superiority of preCRT followed by surgery plus adjuvant chemotherapy over surgery plus adjuvant chemotherapy alone, in terms of local relapse-free survival for resectable LRRC. Methods: Eligibility criteria include resectable LRRC without distant metastasis, no prior pelvic irradiation, no prior surgery for LRRC, aged 20-80 years, and sufficient organ function. Eligible patients are randomized into the surgery and adjuvant chemotherapy (arm A) or preCRT followed by surgery and adjuvant chemotherapy (arm B). PreCRT consists of the standard dose of capecitabine and radiotherapy (50.4Gy). Adjuvant chemotherapy consists of mFOLFOX6, CAPOX, capecitabine, or 5FU+l-LV. The primary endpoint is local relapse-free survival (LRFS), and the secondary endpoints include overall survival, relapse-free survival, %R0 resection, incidence of adverse events, and quality of life after surgery. The 3-year LRFS of arm A is assumed to be 60% with a 13% increase expected in arm B. The sample size was calculated as 106 (53 per arm) with a one-sided alpha of 10%, power of 70%, and accrual period of 6 years. This trial was initiated on 19 August 2019. Clinical trial information: jRCTs031190076.
A phase II study of trifluridine/tipiracil, irinotecan, and bevacizumab in pretreated metastatic colorectal cancer (TABAsCO).
Authors: Gupta Medhavi , Fountzilas Christos , Vijayvergia Namrata , Attwood Kristopher , Hochster Howard S. , Mukherjee Sarbajit , Iyer Renuka V. , Boland Patrick McKay 
Published: February 2020

TPS275 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in US. The majority of US patients (pts) receive first-line therapy (Rx) with FOLFOX [Folinic acid (FA), 5-fluorouracil (5-FU) and oxaliplatin (Ox)] + a biologic, making FOLFIRI [FA+ 5-FU+ irinotecan (Iri)] + bevacizumab (Bev) a common second-line Rx. This regimen has a median progression-free survival (PFS) of approximately 6 months (mo) and overall survival (OS) of 12 mo. Further gains are desperately needed. Trifluridine/tipiracil (FTD/TPI) is an oral combination Rx of a thymidine-based nucleoside analogue, FTD, and a phosphorylase inhibitor, TPI. FTD/TPI has a distinct mechanism of action from 5-FU and in preclinical models can overcome 5-FU resistance via DNA incorporation, base excision repair pathway and glycosylation responses to DNA damage. Further, there is an additive effect in combination with Iri. FTD/TPI was FDA approved for use in refractory metastatic CRC (mCRC) based on phase III RECOURSE trial. Phase I data showed combination of FTD/TPI, Iri and Bev to be safe, and an efficacy signal was seen in dose-expansion cohort (NCT01916447). A 12.5% response rate, 83.4 % disease control rate and PFS of 7.9 mo was achieved. As this study largely assessed refractory pts, one might expect a greater efficacy in Iri naïve pts. To test this hypothesis, we are conducting a multi-center phase II study of FTD/TPI, Iri and Bev as second-line Rx in mCRC pts. Methods: Eligible pts have mCRC and received first-line Ox based Rx. Rx to be given in 28-day cycles: Iri (180 mg/m2) and Bev (5 mg/kg) on D1 & 15, and FTD/TPI (25 mg/m2) twice daily on D2-6 & 16-20. Response assessment via CT/MRI to be done q8 wks (RECIST 1.1). Rx to continue until disease progression or unacceptable toxicity. The primary objective is to estimate PFS. Secondary objectives include ORR, OS, and safety. Final analysis to be done either 12 mo after enrollment of the final pt or once all pts have progression, whichever occurs earlier. A total of 40 pts to be accrued, and enrollment to start in January 2020. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Taiho Oncology, Inc.