bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between chemotherapy-induced peripheral neuropathy and heart rate variability.
Authors: Jang Aelee , Kim Dong Uk 
Published: February 2020

820 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication related to chemotherapeutic agents and dose accumulation. Initial symptoms are known to be sensory including numbness and pain whereas autonomic symptoms are the latest. Autonomic dysfunction is related to heart rate variability (HRV) change which may precede the symptoms. But, the relationship between CIPN and heart rate variability is not fully evaluated. Therefore, we aimed to evaluate the HRV with CIPN-related questionnaires in patients underwent chemotherapy. Methods: Fifty-five patients with gastrointestinal cancers were enrolled in this cross-sectional cohort study. Patients have received chemotherapeutic agents such as paclitaxel, cisplatin, and oxaliplatin. CIPN was diagnosed using National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI-CTCAE version 4.03). We evaluated the quality of life, CIPN symptom scale, and HRV. Results: Forty-two patients were male (76.4%) and mean age was 63.2 years old. Thirty-nine patients (71.0%) had CIPN of more than grade I according to NCI-CTCAE. Patients with CIPN represented lower physical and role functions. The standard deviation of all normal R-R intervals (SDNN) was decreased in the CIPN group. Parasympathetic tone (high frequency band) were decreased, but sympathetic activity (low frequency band/high frequency band) were increased in CIPN. Conclusions: CIPN affected the quality of life in gastrointestinal cancer patients underwent chemotherapy. HRV was related to CIPN. Further study may be needed to check the feasibility of HRV as early biomarkers for detecting CIPN. [Table: see text]
Feasibility of endoscopic resection in gastric gastrointestinal stromal tumor.
Authors: Kim Yuri , Jung Hwoon-Yong , Kim Do Hoon , Lee Jeong Hoon , Choi Kee Don , Ahn Ji Yong , Na Hee Kyong , Park Young Soo 
Published: February 2020

822 Background: Endoscopic resection (ER) can be applied for small SETs of stomach. GISTs can be diagnosed pathologically after resection. Initially we used ESD. Submucosal tunneling endoscopic resection (STER) was introduced for overcoming limitations of ESD. However, STER was very difficult to apply for gastric lesions. We developed new ER method, clip-assisted surgical endoscopy (CASE, Jung's method). In this study, we evaluate the feasibility of ER for GISTs and compared 3 ER methods. Methods: Medical records of 53 patients who diagnosed GISTs after ER for SETs from 2005 to 2019 were reviewed retrospectively. Average age was 60.0 ± 10.6 years. ESD, STER and CASE were performed for 23, 5, and 25 patients, respectively. Clinical characteristics, procedure times, and outcomes of each endoscopic technique were analyzed. Results: Average pathological size of GIST was 2.1 cm. 94.3% proved to be very low risk of malignant potential. Location of SETs were different; ESD applied mainly for body lesions, STER tried for fundus lesions, CASE also mainly for fundus and high body lesions. Overall R0 and R1 resection rate was 62.3%, and 35.8%. There are 34 patients who had complications after the procedure (21 micro-perforation, 12 macro-perforation, 1 bleeding), but perforation would be a part of ER procedure for SETs. In ESD, some macro-perforations was a reason for surgical conversion. Four patients (2 ESD, 1 STER, 1 CASE) underwent surgical conversion during ER. STER had the longest procedure time (50.3, 95.2 and 40.7 min, P = 0.018). After development of CASE procedure, we can reduce procedure time and on-site surgical conversion. R0 resection rate was highest in CASE. No R1 resected patients were recurrent so far. Conclusions: ER seems to be safe and effective therapeutic options for removing small gastric GISTs. Using CASE (Jung's method), ER would be more comfortable especially in the fundus lesions.
Regorafenib as second-line therapy for imatinib-resistant gastrointestinal stromal tumor (GIST).
Authors: Takahashi Tsuyoshi , Nishida Toshirou , Kudo Toshihiro , Boku Narikazu , Honma Yoshitaka , Komatsu Yoshito , Nakatsumi Hiroshi , Matsumoto Koji , Onoe Takuma , Oki Eiji , Nakamoto Masako , Fukutani Miki , Nomura Shogo , Sato Akihiro , Naito Yoichi , Doi Toshihiko 
Published: February 2020

823 Background: Imatinib is a standard first line treatment for advanced gastrointestinal stromal tumor (GIST); however eventually almost all the GISTs become resistant to imatinib. Secondary mutation in KIT is the most relevant cause of imatinib-resistant, as high as 70% of cases. Sunitinib is standard of care for imatinib-resistant GIST with median progression-free survival (PFS) of 24.6 weeks; however, in a preclinical study sunitinib is not active for approximately half of secondary mutations. Regorafenib is active for some secondary mutations resistant to sunitinib in the preclinical study. Therefore, we conducted a phase II study evaluating regorafenib for imatinib-resistant GIST. Methods: Patients with imatinib-resistant advanced GIST were enrolled. Key eligibility criteria were ECOG PS of 0-1 and adequate organ function. Prior exposure of sunitinib was not allowed. The primary endpoint was PFS rate at 24 weeks. ctDNA for KIT was evaluated prior to regorafenib administration. Results: A total of 38 patients were enrolled as planned. Median age was 64.5 (39 - 80). Twenty-five patients were male. Primary site was stomach in 17, small intestine in 16. Median PFS was 36.3 weeks and PFS rate at 24 weeks was 47.4% (primary endpoint was not met). Best overall response was PR for 6 (16 %), SD for 25 (63 %) and PD for 5 (13 %) patients. Grade 3 or more adverse events (AE) were observed in 25 (66 %) patients. Common grade 3 or more AE were hand-foot-skin reaction (n = 9), hypertension (n = 9), hepatotoxicity (n = 4). ctDNA was evaluated in 32 patients and among them secondary mutations were observed in 15 patients (47%). PFS was shorter (15.6 weeks) in patients with exon 13 mutation than that in patients without second mutation (49.3 weeks, not statistically significant). Conclusions: Regorafenib demonstrated favorable activity in patients with imatinib-resistant GIST as second line therapy with acceptable toxicity. Secondary mutation in KIT might be a predictor of the efficacy of regorafenib. Clinical trial information: UMIN000016115.
Clinical activity of avapritinib in ≥ fourth-line (4L+) and PDGFRA Exon 18 gastrointestinal stromal tumors (GIST).
Authors: Heinrich Michael C. , Jones Robin L. , von Mehren Margaret , Bauer Sebastian , Kang Yoon-Koo , Schoffski Patrick , Eskens Ferry , Mir Olivier , Cassier Philippe , Serrano Cesar , Tap William D. , Trent Jonathan C. , Rutkowski Piotr , Patel Shreyaskumar , Chawla Sant P. , Meiri Eyal , Zhou Teresa , Roche Maria , George Suzanne 
Published: February 2020

826 Background: Targeting oncogenic KIT and PDGFRA mutations revolutionized treatment of patients (pts) with advanced GIST; however, nearly all pts succumb to resistant disease. Avapritinib is a potent and selective kinase inhibitor with broad activity against oncogenic KIT/PDGFRA mutants, including PDGFRA D842V and other primary or secondary resistance mutations. Results from the phase 1 NAVIGATOR (NCT02508532) study of avapritinib in pts with advanced GIST are presented. Methods: Adult pts with unresectable PDGFRA D842V or other mutant GIST who progressed on imatinib and ≥1 other tyrosine kinase inhibitor (TKI) were treated with oral, daily, continuous avapritinib. Adverse events (AE) and response by mRECIST 1.1 per central radiology were assessed. Overall population safety (30-600 mg starting doses) and efficacy in the response-evaluable 4L+ and PDGFRA Exon 18 (Ex 18) populations treated at the MTD (400 mg)/RP2D (300 mg) were analyzed. Results: As of 16 Nov 2018, 237 pts [172 KIT, 62 PDGFRA Ex 18 [56 D842V, 6 non-D842V), 2 PDGFRA N659K, 1 missing] were enrolled including 111 in the 4L+ population (primarily KIT, median 4 prior TKI) and 43 in the Ex 18 population (median 1 prior TKI). The 4L+ ORR was 22% [1 CR, 23 PR (1 pending)], and 52 SD with mDOR of 10.2 months (95% CI: 7.2–NE). The Ex 18 ORR was 86% [3 CR, 34 PR (1 pending)] and 5 SD; mDOR was not reached (95% CI: 11.3–NE). Most AEs were grade 1–2, most commonly nausea (63%), fatigue (58%), anemia (49%), periorbital edema (42%), diarrhea (40%), vomiting (40%), decreased appetite (38%), increased lacrimation (33%), peripheral edema (33%) and memory impairment (most common cognitive AE, 29%). 10% of pts discontinued due to a related AE. Grade 3–4 related AE ≥ 2% were anemia, fatigue, hypophosphatemia, hyperbilirubinemia, neutropenia, and diarrhea. Conclusions: Avapritinib has important clinical activity in pts with advanced GIST who have no effective therapies. The ORR and DOR of avapritinib in 4L+ exceeds that of approved 2nd and 3rd line therapies and shows impressive activity in D842V and other Ex 18 mutant PDGFRA GIST. Results suggest avapritinib has the potential to change the treatment paradigm of pts with advanced GIST. Clinical trial information: NCT02508532.
The role of circulating tumor DNA (ctDNA), tumor markers (TMs), and patient-reported outcomes (PROs) in predicting treatment response in patients with metastatic gastrointestinal (GI) cancer.
Authors: Parikh Aparna Raj , Fish Madeleine , Van Seventer Emily E. , Fosbenner Kathryn , Kanter Katie , Allen Jill N. , Clark Jeffrey William , Giantonio Bruce , Weekes Colin D. , Klempner Samuel J. , Franses Joseph Wang , Roeland Eric , Goyal Lipika , Wo Jennifer Yon-Li , Hong Theodore S. , Fetter Isobel , Siravegna Giulia , Horick Nora K. , Corcoran Ryan Bruce , Nipp Ryan David 
Published: February 2020

833 Background: Changes in ctDNA and serum TMs (CEA and CA19-9) can serve as predictors of response to systemic therapy in GI cancer patients (pts). Similarly, PROs correlate with survival and treatment response. We present a preliminary analysis of ctDNA, TMs, and PROs in predicting treatment response. Methods: We are enrolling 200 pts in a prospective study with metastatic pancreatic (PDAC), colorectal (CRC), gastroesophageal (GE), and biliary cancers. We are collecting ctDNA, TMs (CEA for all tumor types; CA19-9 for PDAC, GE, biliary), and PROs (FACT-G for QOL [higher scores indicate better QOL]; ESAS-r and PRO-CTCAE for symptoms; and PHQ-4 [consists of GAD-2 and PHQ-2 for anxiety and depression]; higher ESAS-r, PRO-CTCAE, and PHQ-4 scores reflect greater symptom burden) at baseline and 4 weeks. ctDNA is benchmarked against somatic tissue alterations, and serially assessed by digital droplet PCR. We correlated median percent change from baseline to 4 weeks for ctDNA, TMs, and PROs with treatment response (clinical benefit [CB], progressive disease [PD]). Results: From April to August 2019, we have enrolled 38/45 (84.4%) eligible pts (median age = 64 years; 36.8% female). Among these 38 pts, tumor types are PDAC (36.8%), CRC (31.6%), GE (28.9%), and biliary (2.6%). 18/38 pts were evaluable for ctDNA. Change in ctDNA was -94.5% in pts with CB (n = 10) and -19.5% in pts with PD (n = 8; p = 0.025). No correlation was observed between CEA and treatment response (p = 0.367). Change in CA19-9 was -1.5% for pts with CB and +47% for pts with PD (p = 0.019). Changes in PRO-CTCAE (p = 0.345), GAD-2 (p = 0.697), and ESAS scores (p = 0.743) did not differ between pts with CB and PD. However, changes in PHQ-2 (CB 0% v. PD +22.5%; p < 0.001), PHQ-4 (CB -8.5% v. PD +5%; p = 0.015), and FACT-G (CB +30% v. PD +5%; p = 0.049) were significant. Conclusions: Preliminary analysis suggests that ctDNA and PROs demonstrate promising utility for early prediction of treatment response, with favorable performance relative to standard TMs. Further analyses of larger pt numbers in this ongoing study may clarify the use and integration of these measures to better predict pt outcomes.
Depression among older adults with gastrointestinal (GI) malignancies: Results from the Cancer and Aging Resilience Evaluation (CARE) registry.
Authors: Godby Richard , Al-Obaidi Mustafa , Smith Crystal Young , Kenzik Kelly , McDonald Andrew Michael , Paluri Ravi Kumar , Gbolahan Olumide B. , Bhatia Smita , Williams Grant Richard 
Published: February 2020

92 Background: Depression among older adults with cancer is often under recognized and under treated. This study characterizes the burden of depression in older adults with GI malignancies and its relationship with geriatric assessment (GA) impairments, health-related quality of life (HRQOL), and healthcare utilization. Methods: Since September 2017, patients ≥60 years in GI oncology clinics at UAB were asked to complete a CARE GA questionnaire. We examined depression using the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression 4 item short form; moderate/severe (mod/sev) depression was defined by a T-score ≥60. GA impairments, HRQOL (PROMIS Global-10), and healthcare utilization were compared between those with and without mod/sev depression using a Chi-squared or t-test. Results: A total of 462 enrolled; mean age was 69 (range 60-96), majority white (72%), males (52%), and with advanced stage (III/IV, 69.1%). Most common cancers were colorectal (36%), pancreatic (23%), or hepatobiliary (15%). Overall, 55 patients reported mild depressive symptoms (12%) and 60 (13%) were found to have mod/sev depression. Depressed participants did not differ in demographics or GI cancer type/stage. Those reporting mod/sev depression were more likely to report falls (44 v 19%, p<.001), impaired performance status (63 v 27%, p<.001), dependence in activities of daily living (ADL; 45 v 14%, p<.001), dependence in instrumental ADL (84 v 45%, p<.001), cognitive dysfunction (40 v 5%, p<.001), financial distress (37 v 23%, p=.03), anxiety (76 v 10%, p<.001), fatigue (88 v 54%, p<.001), and pain (70 v 32%, p<.001). Depressed patients reported lower physical (32 v 45%, p<.001) and mental (36 v 50%, p<.001) HRQOL sub-scores, as well as more emergency room visits (67 v 49%, p=.009), but no difference in hospitalizations. Conclusions: More than one out of eight older adults with a GI malignancy reported mod/sev depression, which was associated with impairment in several geriatric domains and overall quality of life. As depression is a pleiotropic yet treatable comorbidity, oncologists should prioritize its screening and treatment.
Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): Final results of the phase II AVETUX trial (AIO-KRK-0216).
Authors: Stein Alexander , Binder Mascha , Goekkurt Eray , Lorenzen Sylvie , Riera-Knorrenschild Jorge , Depenbusch Reinhard , Ettrich Thomas Jens , Doerfel Steffen , Al-Batran Salah-Eddin , Karthaus Meinolf , Pelzer Uwe , Simnica Donjete , Waberer Lisa , Hinke Axel , Bokemeyer Carsten , Hegewisch-Becker Susanna 
Published: February 2020

96 Background: Single agent PD-1/L1 inhibition is efficacious in MCRC patients (pts) with high microsatellite instability (MSI-H). For the vast majority of MCRC pts with MS stable (MSS) phenotype the role of immunotherapy remains undetermined. Methods: The single arm phase II AVETUX trial combined mFOLFOX6 and cetuximab with avelumab (10mg/kg day 1 from cycle 2 onwards) in RAS/BRAF wildtype (local lab) MCRC pts. Primary endpoint was 12 month progression-free survival rate. Secondary endpoints included overall response rate (ORR), tolerability, overall survival and translational research evaluating tissue including PD-L1 expression (tumour/immune cells) and serial ctDNA. Efficacy analyses were done by intention to treat (ITT). Results: Overall 43 pts were enrolled. Median age was 61 (range 29-82), 14 pts (33%) were female and 39 (91%) left sided. 30 pts (70%) had liver mets and 17 (40%) liver mets only. 2 pts were MSI-H, one MSI-low and 40 MSS. Besides immediate and otherwise unexplained fever in 4 pts treatment was well tolerated and avelumab was not associated with unexpected adverse events to standard FOLFOX/cetuximab. Central tissue review found 4 pts to be ineligible due to low frequent KRAS or BRAF mutation (15-31%). Thus, ITT included 39 pts. The ORR was 79.5%, including 6 complete (CR) and 25 partial responses (PR). Further 5 stable diseases were noted, thus disease control rate was 92.3%; 2 pts had progression and 1 was not evaluable. Early tumor shrinkage (ETS) rate (≥20% after 8 weeks) was 79.5% (1 CR, 27 PR and 3 SD with ≥20% - < 30%). In MSI-H pts 1 PR and 1 SD and in the 3 low RAS mut pts 2 PR were noted. Panel sequencing was feasible with 153 mutations detected, showing an immediate ctDNA drop within 4 weeks of treatment, mirroring the high rate of early tumor response. Notably, the 4 pts with fever had a high T cell infiltration in the tumor. Final data including the primary endpoint and translational data will be presented at the meeting. Conclusions: The AVETUX regimen was feasible producing a high rate of responses in MSS pts mainly occurring within the first 8 weeks. The noted ORR/ETS of 79.5% warrants further evaluation in a randomized trial. Clinical trial information: NCT03174405.
mFOLFOXIRI with or without cetuximab as conversion therapy in patients with RAS/BRAF wild-type unresectable liver metastases colorectal cancer: The FOCULM study.
Authors: Hu Huabin , Wang Kun , Wang Wei , Qiu Meng , Lin Rongbo , Zhang Haibo , Liu GuangJian , Wan Yunle , Kang Liang , Wang Hui , Zhou Zhiyang , Li Fangqian , Huang Yan , Zhang Jianwei , Cai Yue , Wu Zehua , Ling Jiayu , Huang Meijin , Deng Yanhong 
Published: February 2020

99 Background: Conversion therapy for unresectable colorectal liver metastases (LM) can downsize tumours and create a situation where the patient has no evidence of disease (NED). We assessed the effectiveness of cetuximab plus mFOLFOXIRI or mFOLFOXIRI in this setting. Methods: FOCULM was a prospective 2:1 controlled, multicenter, phase II trial. Given no free drugs offered and the patients' affordability for cetuximab, the study design has been amended from randomization to non-randomization since September, 2016. Patients with unresectable LM were assigned to receive cetuximab (500mg/m2) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2800mg/m2 46h infusion, every 2 weeks) (group A) or mFOLFOXIRI (group B). Primary endpoint was the rate of NED achieved, secondary endpoints were ORR, resection rate, the rate of local and ablative treatment (LAT), OS, PFS and DpR. Results: From February 2014 to July 2019, 114 patients were enrolled at 6 centers in China and 101 patients were in the ITT population (67 group A, 34 group B). Treatment groups were generally well balanced, although more patients with ≥5 LM were in group A. The rate of NED achieved was 62.7% in group A and 38.2% in group B (P = 0.020). At a median follow-up of 19.4 months, patients in group A had significantly prolonged the mOS, increased ORR, the rate of LAT and DpR compared with those in group B (Table). Patients with NED achieved yielded a significant survival benefit, whether in group A (Not reached vs. 49.4 months; P = 0.001) or group B (Not reached vs. 25.1 months; P = 0.007). Conclusions: The addition of cetuximab to a mFOLFOXIRI in patients with RAS/BRAF wild-type unresectable LM colorectal cancer significantly improved the rate of NED achieved, ORR and OS. Clinical trial information: NCT02063529. [Table: see text]
AGENT: An open-label phase III study of arfolitixorin versus leucovorin in modified FOLFOX-6 for first-line treatment of metastatic colorectal cancer.
Authors: Lenz Heinz-Josef , Gibbs Peter , Stintzing Sebastian , Prager Gerald W. , Nygren Peter , Papadimitriou Christos A. , Tell Roger , Yoshino Takayuki , Jonker Derek J. , De Gramont Aimery , Tabernero Josep 
Published: February 2020

TPS268 Background: 5-fluorouracil (5FU), in combination with folates, is an established cornerstone of metastatic colorectal cancer (mCRC) treatment. All folates currently approved for mCRC need to be metabolically activated to [6R]-5,10-methylenetetrahydrofolic acid ([6R]-MTHF), the active thymidylate synthase co-substrate that potentiates the effect of 5FU. Arfolitixorin does not require multi-step metabolic activation, and may produce higher, and less inter- and intraindividually variable, concentrations of [6R]-MTHF than leucovorin. Methods: The phase III AGENT trial (NCT03750786) is a randomized, multicenter, parallel-group study comparing the efficacy of arfolitixorin versus leucovorin in mCRC patients treated with first-line 5FU, oxaliplatin, and bevacizumab. Patients are randomized (1:1) to the investigational arm (arfolitixorin + 5FU + oxaliplatin [ARFOX] + bevacizumab) or the comparator arm (leucovorin + 5FU + oxaliplatin [modified FOLFOX-6] + bevacizumab), and treated until disease progression based on RECIST 1.1 criteria. Recruitment is ongoing, and aims to randomize 440 patients in 18 months. Eligibility criteria include non-resectable mCRC; eligibility for 5FU, oxaliplatin, and bevacizumab therapy; ECOG PS 0 or 1. The study will be conducted across approximately 100 sites in Australia, Austria, Canada, France, Germany, Greece, Japan, Spain, Sweden, and USA. The primary endpoint is objective response rate. Key secondary endpoints are progression-free survival and duration of response. Additional secondary endpoints include overall survival, quality of life, safety and tolerability, and number of patients undergoing curative metastasis resection. A translational program will evaluate expression levels of several folate metabolism- and transportation-related genes in mCRC tumor biopsies to determine their relationship to treatment outcome. A broad array of genes will analyzed, including ATP-binding cassette C3 (ABCC3) transporter, methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), proton-coupled folate transporter (PCFT), and serine hydroxymethyltransferase 1 (SHMT1). Interim data are expected in mid 2020. Clinical trial information: NCT03750786.