bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain among older adults diagnosed with gastrointestinal (GI) malignancies: Results from the cancer and aging resilience evaluation (CARE) registry.
Authors: Al Obaidi Mustafa , Kosmicki Sarah , Harmon Christian , Outlaw Darryl Alan , Gbolahan Olumide B. , Khushman Moh'd M. , Bhatia Smita , Giri Smith , Williams Grant Richard 
Published: January 2022

82 Background: The impact of pain on functional status and neuropsychological disorders among older adults with cancer is relevant, yet poorly understood. We sought to identify the prevalence of pain at diagnosis in older adults with GI malignancies and evaluate the association between pain and functional status limitations, cognition, and mental health issues. Methods: This study included patients diagnosed with cancer at age ≥60 years and enrolled in the CARE Registry at the University of Alabama at Birmingham (UAB). Patients completed a patient-reported geriatric assessment at their initial visit with a medical oncologist. Patients rated pain on a numeric scale from 0-10. We employed the literature-based cut off for moderate-severe pain of ≥4. Logistic regression modeling was used to determine the association between moderate/severe pain and functional status, falls, cognition, and depression/anxiety. We adjusted the models for sex, race, education, race/ethnicity, marital status, cancer type, and cancer stage. Results: Our cohort included 714 older adults. Median age at diagnosis was 70y (range 60-96) and 59% were male. Median time between diagnosis and study participation was 37 days. Most prevalent diagnoses included colorectal (27.9%), pancreatic (18%), hepatobiliary (11.5%) and gastroesophageal (6.4%) cancers. Overall, 53.1% of the participants reported none/mild (0-3) pain, 25.6% reported moderate (4-7) pain, and 21.4% reported severe (8-10) pain. In univariate analyses, Black patients, lower education, disabled employment, and pancreatic cancer was associated with moderate/severe pain. After multivariate adjusting for covariates, participants with moderate/severe pain were more likely to report limitations in instrumental activities of daily living (adjusted Odds Ratio [aOR] 4.3, 95% confidence interval [CI] 3.1-6.1, p <.001), limitations in activities of daily living (aOR 3.2, 95% CI 2.0-5.1, p <.001), falls (aOR 2.4, 95% CI 1.6-3.6, p <.001), cognitive complaints (aOR 2.9, 95% CI 1.4-6.0, p <.004), anxiety (aOR 2.2, 95% CI 1.4-3.4, p < 0.01), and depression (aOR 3.7, 95% CI 2.2-6.5, p <.001). Conclusions: Pain is common amongst older adults with GI cancers and is associated with functional status limitations, falls, cognitive complaints, and depression/anxiety. Strategies to reduce pain and/or minimize its potential impact on function and mental health warrant future research.
Phase 1/1b trial of fruquintinib in patients with advanced solid tumors: Preliminary results of the dose expansion cohorts in refractory metastatic colorectal cancer.
Authors: Dasari Arvind , Hubbard Joleen M. , Eng Cathy , Yeckes-Rodin Heather , Ukrainskyj Stacey M , Yang Zhao , Schelman William R. , Kania Marek K. , Bekaii-Saab Tanios S. 
Published: January 2022

93 Background: Fruquintinib (F) is a highly selective, novel, oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3. The phase (Ph) 3 FRESCO study (NCT02314819) that investigated F (5mg daily, 3 weeks (wks) on 1 wk off) showed improved median overall survival in patients (pts) with metastatic colorectal cancer (mCRC) in third line and beyond when compared to placebo (9.3 vs. 6.6 months); hazard ratio 0.65 (P < 0.001) and led to its approval in China. Methods: This is an ongoing Ph 1/1b open-label, dose escalation/expansion study conducted in the US. Here we present the preliminary safety and antitumor efficacy data from pts with refractory mCRC in Cohort (Coh) B (progressed on all standard therapies including TAS-102 [TAS] and/or regorafenib [R]) and in Coh C (did not receive TAS or R). Results: As of data cutoff on 27 July 2021, 81 mCRC pts had been treated (41 in Coh B and 40 in Coh C); median age of 57 years (range: 34─77), Caucasian (81.5%), female (44.4%), and ECOG PS 1 (59.3%). In Coh B, the median number of prior therapies was 5 (range: 3-9), 8 pts (19.5%) received R, 19 (46.3%) received TAS and 14 (34.1%) received both R and TAS. In Coh C, the median number of prior therapies was 4 (range: 1-10). Five pts remain on treatment; reasons for treatment discontinuation included: 56 pts (69.1%) due to progressive disease or death, 8 pts (9.9%) due to adverse events (AE), and 12 pts (14.8%) due to withdrawal of consent or physician decision. The median duration of F treatment was 4.4 months (range: 0.7– 20.0) in Coh B and 3.7 months (range: 0.02-14.3) in Coh C. The most frequently reported AEs of any grade in Coh B were fatigue (53.7%), proteinuria (51.2%), and hypertension (HTN; 48.8%). In Coh C the most frequently reported AEs of any grade were HTN (75.0%), proteinuria (40.0%), and myalgia (32.5%). Hand-foot syndrome (HFS) was reported in 29.3% of Coh B pts and 22.5% of Coh C pts. The disease control rate [DCR] was 68.3% in Coh B (1 partial response [PR] and 27 stable disease [SD]) and 59.5% for the 37 patients with at least one post-baseline tumor assessment in Coh C (2 PRs and 20 SDs). Conclusions: F is generally well-tolerated in heavily-pretreated pts with refractory mCRC. Evidence of antitumor activity was observed in cohorts B and C. The multi-cohort dose expansion is ongoing. F is being further investigated in refractory mCRC in a global Ph 3 study (NCT04322539). Clinical trial information: NCT03251378.
Oxaliplatin in metastatic colorectal cancer: Does hepatic arterial infusion reduce sensitive neuropathy compared to the intravenous route?
Authors: Valery Marine , Tanguy Marie Laure , Boige Valérie , Smolenschi Cristina , Hollebecque Antoine , Fuerea Alina , Klotz-Prieux Caroline , Benhaim Leonor , Debaere Thierry , Gelli Maximiliano , Tselikas Lambros , Ducreux Michel , Malka David 
Published: January 2022

95 Background: Oxaliplatin, a major drug in metastatic colorectal cancer (MCRC), is responsible for a cumulative and limiting peripheral neuropathy (PN). Hepatic arterial infusion (HAI) chemotherapy, which makes sense in cases of exclusive or predominant liver metastases, increases the intratumor concentration of the administered drug(s) to improve efficacy and limit systemic toxicity. Methods: We compared the frequency and severity of NP in oxaliplatin-naive patients with MCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (CHOICE, OSCAR, and PACHA-01 trials) or by intravenous (IV) route (FFCD 2000-05 trial). The primary endpoint was the occurrence of clinically significant NP (grade 2-4) according to the cumulative dose of oxaliplatin received. The secondary endpoints were the occurence of severe NP (grade 3-4) and time to onset of NP. Results: 342 patients were included (IV oxaliplatin: 300; HAI: 42). 180 patients in the IV group (60%) and 24 patients in the HAI group (57%) developed clinically significant NP, with no significant difference between the 2 groups (p = 0.85). 95 patients in the IV group (32%) and 8 patients in the HAI group (19%) developed severe NP, with no significant difference between the 2 groups (p = 0.082). NP appeared earlier in the HAI group, with more treatment discontinuations for neurotoxicity. Conclusions: The administration of oxaliplatin HAI rather than IV in the treatment of MCRC does not seem to reduce the incidence, precocity and severity of NP.
Nivolumab plus ipilimumab (N+I) in patients (pts) with colorectal cancer (CRC) with high tumor mutational burden (hTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.
Authors: Vaccaro Gina M. , Rothe Michael , Mangat Pam K. , Garrett-Mayer Elizabeth , Hwang Jimmy J. , Alese Olatunji B. , Khalil Maged F. , Hameed Muhammad Khurram , Duvivier Herbert Leon , Cannon Timothy Lewis , Grantham Gina N. , Halabi Susan , Schilsky Richard L. 
Published: January 2022

107 Background: TAPUR is a phase II basket study evaluating the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with hTMB treated with N+I are reported. Methods: Eligible pts had advanced CRC, no available standard treatment options, measurable disease, ECOG performance status (PS) 0-2, adequate organ function and no prior immune checkpoint inhibitor treatment. PDL-1 expression testing was not required. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. hTMB was defined a priori as ≥9 mutations/megabase (Muts/Mb) reported by a FoundationOne test (n=7) or other tests (n=5) if approved by the Molecular Tumor Board. Pts received N 1 mg/kg IV every 3 weeks (wks) for 4 doses in combination with I 3 mg/kg every 3 wks for 4 doses. N was then continued at 240 mg every 2 wks or 480 mg every 4 wks until disease progression. Primary endpoint was disease control (DC), defined as complete (CR) or partial (PR) response, or stable disease at 16+ wks (SD 16+). Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 has DC, 18 more pts are enrolled; otherwise, the study stops for futility. If ≥7 of 28 pts has DC, the null DC rate is rejected. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: 12 pts (9 male) with CRC with hTMB in tissue biopsy were enrolled from February 2018 to May 2020; 2 pts were not evaluable and excluded from efficacy analyses. All pts were evaluated for toxicity. TMB ranged from 9 to 233 Muts/Mb (median 13). Demographics and outcomes are summarized in the table below. Tumor microsatellite (MS) status was reported stable for 11 pts and indeterminate for 1 pt. 1 PR (88.1 wks duration, tumor 11 Muts/Mb, MS stable, PDL-1 expression not reported, KRAS mutant) and 0 pts with SD16+ were observed for a DC and OR rate of 10% (95% CI: 0%, 45%); the null DC rate of 15% was not rejected (p=0.80) and the cohort closed due to futility. 4 pts had at least one grade 3-4 adverse or serious adverse event (AE/SAE) at least possibly related to N+I including myasthenia gravis, diarrhea, glucose intolerance, hyperglycemia, and small intestinal obstruction. Conclusions: Combination therapy with N+I does not have sufficient clinical activity in pts with MS stable, hTMB CRC for further evaluation in this pt population. Other treatments should be considered for these pts, including treatments offered in clinical trials. Clinical trial information: NCT02693535. [Table: see text]
Tumor response of FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: The subgroup-analysis of DEEPER trial (JACCRO CC-13).
Authors: Satake Hironaga , Tsuji Akihito , Tanaka Chihiro , Takahashi Takao , Wakamura Kunihiko , Yoshida Taichi , Murata Kohei , Shindo Yoshiaki , Ishikawa Yasuhide , Konishi Ken , Kochi Mitsugu , Sagawa Tamotsu , Kotaka Masahito , Kubota Yutaro , Sunakawa Yu , Sekikawa Takashi , Nakamura Masato , Takeuchi Masahiro , Ichikawa Wataru , Fujii Masashi 
Published: January 2022

109 Background: Triplet regimen, FOLFOXIRI, combined with bevacizumab (bev) or panitumumab has been shown to be superior in terms of early tumor shrinkage and depth of response (DpR) compared to doublet combinations in patients with RAS wild-type metastatic colorectal cancer (mCRC). We performed a randomized phase II study, DEEPER trial (JACCRO CC-13)[NCT02515734], to investigate the efficacy and safety of cetuximab (cet) vs. bevacizumab (bev) in combination with modified (m)-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, 5-FU 2400 mg/m2) in previously untreated mCRC patients with RAS wild-type tumors (Tsuji A, et al. ASCO 2021). Methods: The primary endpoint was DpR during the entire course. Secondary endpoints included overall response rate (ORR), disease control rate, R0 resection rate, progression-free survival, and overall survival. A post-hoc subgroup analysis by PS, tumor sidedness, age, and location of metastases was performed to evaluate the efficacy of triplet plus cet vs. bev regimen. Results: A total of 359 patients were enrolled between July 2015 and June 2019. For the full analysis set (median age 65y, 64% male, PS0/1: 91%/9%, left/right primary: 83%/17%), 173 and 175 patients were randomly assigned to the cet and bev arms, respectively. Median DpR was 57.4% vs. 46.0% ( p = 0.001), and the ORR was 69.1% vs. 71.7% ( p = 0.60), in cet vs. bev, respectively. The subgroup analysis was present in the table. There was no significant difference in terms of ORR and R0 resection rate between groups according to PS, tumor sidedness, age, and liver metastases (LM). In patients with only LM, the R0 resection rate of cet vs. bev was 25.0% vs. 14.8% ( p = 0.21). Conclusions: The m-FOLFOXIRI plus cet showed to be significantly superior to the m-FOLFOXIRI plus bev in terms of DpR in first-line treatment for RAS wild-type mCRC. The better DpR of m-FOLFOXIRI plus cet was evident for RAS wild-type mCRC patients with left-sided tumors, LM or under 70 years old. Clinical trial information: UMIN000018217.[Table: see text]
Radioembolization with chemotherapy for liver-dominant colorectal cancer: Time to subsequent treatment and quality of life in the EPOCH trial.
Authors: Salem Riad , Mulcahy Mary Frances ,   On behalf of the EPOCH Trial Investigators
Published: January 2022

114 Background: The primary objective of the EPOCH trial evaluated potential benefit of adding second-line transarterial radioembolization (TARE) with yttrium-90 glass microspheres to chemotherapy compared to chemotherapy alone in patients with liver-dominant metastatic colorectal disease (mCRC). Secondary endpoints included time to deterioration of quality of life (TTDQoL). Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter phase 3 trial. TTDQoL was assessed using the Functional Assessment of Cancer Therapy-colorectal (FACT-c) questionnaire and defined as the time from randomization to the change from baseline in FACT-c total score ≤ -7 points or date of death and was estimated using Kaplan-Meier analysis. Time to subsequent therapy was defined as the time from randomization to the start of subsequent therapy and was estimated using Kaplan-Meier analysis. Restricted mean survival time (RMST) analysis was used to estimate the area under Kaplan-Meier curves (AUC) for progression-free survival (PFS), hepatic PFS (hPFS), and TTDQoL, and the difference in AUC estimates between the two arms were assessed. The use of TheraSphere in the USA in the trial was under Investigational Device Exemption from FDA. Results: The EPOCH trial included 428 patients. Both primary endpoints of PFS (HR = 0.69, 95% CI: 0.54, 0.88; 1-sided p=0.0013) and hPFS (HR = 0.59, 95% CI: 0.46, 0.77; 1-sided p<0.0001) were met in the EPOCH study. Median time to subsequent therapy in the TARE plus chemotherapy arm was 21.0 months, compared to 10.1 months in the chemotherapy only arm (HR = 0.49, 95% CI: 0.37, 0.67). TTDQoL before subsequent therapy was reported in 53.5% (115/215) patients in the TARE plus chemotherapy arm, compared to 43.7% of patients in the chemotherapy only arm (93/213). Median TTDQoL was 3.8 months in both the TARE plus chemotherapy arm and the chemotherapy alone arm (1-sided p=0.1513; HR = 0.86, 95% CI: 0.65, 1.14). AUC for PFS until 22.1 months was 9.4 months (95% CI: 8.4, 10.4) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.6, 8.1) for the chemotherapy only arm (1-sided p=0.0008). AUC for hPFS until 22.1 months was 10.3 months (95% CI: 9.2, 11.3) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.7, 8.2) for the chemotherapy only arm (1-sided p<0.0001). AUC for TTDQoL until 18.5 months was 6.6 (95% CI: 5.6, 7.6) for the TARE plus chemotherapy arm, compared to 5.5 (95% CI: 4.4, 6.5) for the chemotherapy only arm (1-sided p=0.0663). Conclusions: These results suggest that the addition of TARE to second-line chemotherapy in patients with liver-dominant mCRC extended PFS, hPFS, and time to subsequent treatment without compromising quality of life. Clinical trial information: NCT01483027.
SONCAR study: A prospective randomized controlled study on optimized neoadjuvant chemotherapy-oxaliplatin plus CRT in patients with locally advanced rectal cancer.
Authors: Zhang Rong-Xin , Zeng Zhifan , Gao Yuan-Hong , Wu Xiao-Jun , Chen Gong , Li Liren , Ding Pei-Rong , Liu Min , Wang Qiaoxuan , Xiao Weiwei , Pan Zhi-Zhong , Wan De-Sen , LU Zhen-Hai 
Published: January 2022

117 Background: The benefit of adding Oxaliplatin to neoadjuvant chemoradiotherapy in Locally Advanced Rectal Cancer (LARC) patients remains controversial. The present study investigated whether induction chemotherapy (CapOX), 2 cycles of CapOX combined with standard radiation (Oxa-CRT) concurrently and consolidation chemotherapy (CapOX) could improve OS compared with standard treatment (nCRT) for locally advanced rectal cancer. Methods: We conducted this randomized, single center, open-label, phase III trial in China. Eligible patients were pathologically confirmed rectal adenocarcinoma, clinical T3-4 with or without regional N + and no sign of distance metastasis determined by pelvic MRI, chest and abdominal CT scan. All patients were randomly allocated to the experimental group: pelvic radiation of 50Gy/25 fractions with 4 cycles of oxaliplatin and capecitabine (1 cycle of CapOX (oxaliplatin: 130mg/m2, cape: 1000mg/m2, bid, Day 1 to Day 14) administrated before radiotherapy as induction chemotherapy, 2 cycles of CapOX (oxaliplatin: 100mg/m2, cape: 1000mg/m2, bid, Day 1 to Day 14) administrated concurrent with RT, and 1 cycle of CapOX (oxaliplatin: 130mg/m2, cape: 1000mg/m2, bid, Day 1 to Day 14) conducted as consolidation chemotherapy); or control group: radiation with capecitabine. The primary end point was OS. This trial was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT02031939). Results: From January 2014 to June 2020, 556 patients enrolled in this study (n=278 in both groups), and 536 patients were evaluable (269 in experimental group and 267 patients in control group). Surgery was performed in 235 patients (84.5%) in experimental group and 242 patients (87.1%) in control group. The pCR rates were 27.8% (75 in 269) and 19.4% in control group (52 in 267) (p = 0.025). 16 and 5 patients achieved clinical complete response (cCR) in experimental and control group, respectively. Grade 3-4 toxicities were recorded in 42 (21.8%) and 6 (5.1%) patients in experimental and control group. The most common grade 3-4 toxicities were leukopenia, thrombocytopenia and neutropenia. The overall surgical complication rate was not significantly different between two groups (12.1% vs. 11.9%). Conclusions: Four cycles of CapOX combined with RT in LARC significantly increased complete tumor response in Chinese patients with acceptable toxicities. Clinical trial information: NCT02031939.
Periop-01: A randomized controlled trial of extended perioperative tinzaparin to improve disease-free survival in patients with resectable colorectal cancer.
Authors: Auer Rebecca Ann C , Karanicolas Paul Jack , Ott Michael , Brackstone Muriel , Ashamalla Shady , Asmis Timothy R. , Boutros Marylise , Caycedo Marulanda Antonio , Jayaraman Shiva , Jonker Derek J. , Moloo Husein , Patel Sunil , Spadafora Silvana , MacLellan Steven , Mallick Ranjeeta , Stotland Peter , Tagalakis Vicky , Trottier Daniel C. , Weaver Joel , Carrier Marc 
Published: January 2022

124 Background: Cancer patients undergoing surgical resection of their tumor are hypercoagulable beyond the period of hospitalization. Preclinical studies demonstrate that the postoperative hypercoagulable state promotes metastases, an effect that is abrogated by administration of perioperative low molecular-weight heparin (LMWH). Methods: We conducted a randomized, open label clinical trial to determine if extended duration thromboprophylaxis using subcutaneous LMWH (tinzaparin 4,500 IU daily), beginning at decision to operate and continuing for 56 days postoperatively, compared to inpatient postoperative thromboprophylaxis only, increased the 3-year disease-free survival (DSF) in patients undergoing resection for colorectal cancer. Secondary outcomes included 5-year overall survival (OS), postoperative bleeding and venous thromboembolism (VTE). Results: Trial recruitment was stopped prematurely after 614 of the planned 1075 patients were registered, following a pre-defined interim analysis for futility. The intention-to-treat analysis included 602 patients with demographics in the table. The 3-year DFS was 78.9% (63/299 recurrences) in the tinzaparin group and 80.5% (59/303 recurrences) in the control group (hazard ratio (HR) 1.09; [95% CI 0.91,1.31; p=0.3]). The 5-year OS was 91.3% in the tinzaparin group and 92.4% in the control group (HR 1.08; [95% CI 0.66,1.79; p=0.1]). The incidence of postoperative VTE was 1.7% and 1.3% in the tinzaparin and control groups, respectively (HR 1.3; [95% CI 0.30,5.69; p=0.7]. The incidence of major bleeding in the first postoperative week was 0.3% and 2% in the tinzaparin and control groups, respectively (HR 0.16; [95% CI 0.02,1.15; p=0.07]. Conclusions: Extended duration perioperative anticoagulation with tinzaparin did not improve DFS or OS in colorectal cancer patients undergoing surgical resection. The incidences of postoperative bleeding and VTE were low. Funded by Canadian Institute of Health Research and Leo Pharma Clinical trial information: NCT01455831. [Table: see text]