bluuebunny/crossref_metadata_2025_split huggingface dataset:
Encorafenib plus cetuximab with or without binimetinib for BRAF V600E-mutant metastatic colorectal cancer: Quality-of-life results from a randomized, three-arm, phase III study versus the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC).
Authors: Kopetz Scott , Grothey Axel , Van Cutsem Eric , Yaeger Rona , Wasan Harpreet Singh , Yoshino Takayuki , Desai Jayesh , Ciardiello Fortunato , Loupakis Fotios , Hong Yong Sang , Steeghs Neeltje , Guren Tormod Kyrre , Arkenau Hendrik-Tobias , Garcia-Alfonso Pilar , Gollerkeri Ashwin , Maharry Kati , Christy-Bittel Janna , Keir Christopher Hunt , Pickard Michael D , Tabernero Josep 
Published: February 2020

8 Background: In the BEACON CRC study, the triplet regimen of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) significantly improved overall survival (OS, HR:0.52, P < 0.0001) and objective response rates (ORR, 26% vs 2%, P < 0.0001) in patients (pts) with BRAF V600E metastatic colorectal cancer (mCRC) compared with current standard of care. This analysis focuses on the patient-reported quality of life (QOL) assessments from this study. Methods: The BEACON CRC study was a randomized, open-label, 3-arm, phase 3 global study which evaluated triplet (ENCO+BINI+CETUX) or doublet (ENCO+CETUX) vs. investigator’s choice of irinotecan + CETUX or FOLFIRI + CETUX in pts with BRAFV600E mCRC. QOL assessments (secondary endpoints in the trial) included the EORTC QOL Questionnaire (QLQ C30), Functional Assessment of Cancer Therapy Colon Cancer (FACT C), EuroQol 5D 5L, and Patient Global Impression of Change (PGIC). The primary assessment for the QOL variables was the time to definitive 10% deterioration between arms. Results: 665 pts were randomly assigned to receive either triplet (n = 224), doublet (n = 220), or control (n = 221). Reduction in the risk of QOL deterioration was an estimated 45% (HR 0.55, 95% CI: 0.43, 0.70) and 44% (HR 0.56, 95% CI: 0.44, 0.71) in EORTC QLQ C30 and FACT C assessments, respectively, in favor of the triplet regimen over control. For the doublet vs. control, reduction in risk of QOL deterioration was an estimated 46% (HR 0.54, 95% CI: 0.43, 0.69) and 43% (HR 0.57, 95% CI: 0.45, 0.72) in EORTC QLQ C30 and FACT C, respectively in favor of the doublet. Similar results were observed in EuroQol 5D 5L and PGIC assessments. There were no overall differences in QOL between triplet and doublet across the 4 instruments. Conclusions: In BEACON CRC, triplet and doublet demonstrated substantial improvement in patient-reported QOL assessments over the current standard of care in pts with BRAF V600E-mutant metastatic CRC whose disease had progressed after 1 or 2 prior regimens. Clinical trial information: NCT02928224.
Declining use of red blood cell transfusions for gastrointestinal cancer surgery: A population-based analysis.
Authors: Zuckerman Jesse , Coburn Natalie , Callum Jeannie , Mahar Alyson , Zuk Victoria , Lin Yulia , McLeod Robin , Turgeon Alexis F. , Pearsall Emily , Martel Guillaume , Hallet Julie 
Published: February 2020

802 Background: Perioperative anemia is common in gastrointestinal (GI) cancer surgery patients and is often treated with red blood cell transfusion (RBCT), which carries risks for inferior oncologic outcomes. Despite level-1 evidence for restrictive transfusion strategies, RBCT use is often not consistent with guidelines leading to a high rate of unnecessary transfusions. Understanding of RBCT use at the population-level is necessary to develop system-level efforts to minimize perioperative RBCT for cancer. We sought to evaluate the secular trends of transfusion in a large North American population. Methods: We conducted a population-based retrospective cohort study of patients undergoing GI cancer resection between 2007-2018 using linked administrative health datasets in Ontario, Canada. Primary outcome was administration of any RBCT during the hospitalization. Temporal RBCT trends were analyzed with Cochran-Armittage tests for trend. Modified Poisson regression assessed trends while controlling for potential confounders. Results: Of 79,764 patients undergoing GI cancer resection, median age was 69 (IQR: 60-78) years old and 55.5% were male. The most frequent cancer site was colorectal cancer (n = 63,243), followed by esophago-gastric (n = 7,307), hepato-pancreato-biliary (n = 6,510), and small bowel (n = 2,704). 30% of patients received RBCT. The proportion of patients transfused decreased from 26.5% in 2007 to 18.9% in 2018 (p < 0.001). This trend remained consistent when stratified by sex, age, cancer type, operative approach, procedure setting, and institution teaching status. After adjusting for patient and institution factors, the time period was associated with receipt of RBCT with a relative risk of 0.94 (95% CI 0.91-0.96) for 2011-14 and 0.75 (95% CI 0.73-0.78) for 2015-2018 compared to the period of 2007-10. Conclusions: Over the 11-year study period, we observed a decrease in RBCT for GI cancer resection. These findings may reflect the dissemination of clinical guidelines and implementation of patient blood management programs. An evaluation of institutional variation and the relationship with outcomes is warranted to identify opportunities for further improvement.
The cost of chemotherapy administration: A systematic review and meta-analysis.
Authors: Sohi Gursharan Kaur , Levy Jordan , Delibasic Victoria , Davis Laura , Mahar Alyson , Amirazodi Elmira , Earle Craig , Hallet Julie , Hammad Ahmed , Mittmann Nicole , Coburn Natalie 
Published: February 2020

810 Background: Cancer treatment is a significant driver of healthcare costs worldwide, however, the economic impact of treating patients with anti-neoplastic agents is poorly elucidated. Hence, we conducted a systematic review and meta-analysis to estimate the direct costs associated with administering intravenous chemotherapy in an outpatient setting. Methods: We systematically searched four databases from 2010 to present and extracted hourly administration costs and the respective components of each estimate. Separate analyses were conducted of Canadian and United States (US) studies, respectively, to address a priori hypotheses regarding heterogeneity amongst administration cost estimates. The Drummond checklist was used to assess risk-of-bias. Data were summarized using medians with interquartile ranges and five outliers were identified; costs were presented in 2019 USD. Results: A total of 44 studies were analyzed, including sub-analyses of 19 US and seven Canadian studies. 26/44 studies were of moderate or high quality. When components of administration cost were evaluated, physician costs were reported most frequently (24 studies), followed by lab tests (13) and overhead costs (9). The median cost estimate when outliers were excluded was $142/hour (IQR = $103-166). Sensitivity analyses determined the median administration cost in the US was $149/hour (IQR = $118-158), and was $128/hour (IQR = $102-137) in Canada. Conclusions: There is currently a paucity of literature addressing the costs of chemotherapy administration, and existing studies utilize a patchwork of reporting methodologies which renders direct comparison challenging. Our results demonstrate that the cost of administering chemotherapy is approximately $125-150/hour, globally. This value is dependent upon the region of analysis, inclusiveness of cost subcomponents as well as the methodology used to estimate unit prices, as described here.
First analysis of same-day pegfilgrastim use with concurrent capecitabine-based regimens in pts with GI malignancies.
Authors: Hakim Nausheen , Chi Jeffrey , Rehman Hasan , Goyal Shreya Prasad , Olazagasti Coral , Moriarty Linda , Jose Jyothi , Lamont Carol , Saif Wasif M. 
Published: February 2020

817 Background: Pegfilgastrim is administered 24 hrs after chemotherapy to reduce risks of myelosuppression. This requires an additional clinic visit, which can be difficult for some patients (pts) due to work and transportation issues. In GI malignancies, pts receiving capecitabine-based regimens also require pegfilgastrim to reduce myelotoxicity. Capecitabine is converted to active 5-FU by cytidine deaminase which is present in humans in low levels and generally does not cause severe myelosupression. Therefore, administering pefilgastrim concurrently with chemotherapy may be an option. We present here the first study to analyze safety and efficacy of administering pegfilgrastim on the same day as capecitabine-based regimens in patients with GI malignancies. Methods: We evaluated 157 pts with GI malignancies who received a capecitabine-based chemotherapy regimens, including XELOX, EOX, ECX, XELIRI, MIXE, gemcitabine-capecitabine and same-day pegfilgrastim (6 mg) within 1 hr of completion of systemic agents. As per institutional guidelines, pts were counseled on risks of same-day pegfilgrastim prior to its administration. Pts were followed to determine the degree of neutropenia and toxicity. Results: A total of 914 chemotherapy cycles in 157 pts were analyzed. Median ANC nadir for all cycles was 5634/uL (range: 450-23800). Grade 1 and 2 neutropenia developed in 11 of 914 cycles. Bone pain reported in 9 pts. There was 1 episode of grade >3 neutropenia resulting in infection and antibiotic use. No other pt required dose reductions, chemotherapy delays, or hospitalizations. No increased toxicity of capecitabine was noticed. Conclusions: We believe our study is the first in GI malignancies to report that same-day pegfilgrastim administration with capecitabine-based regimens may be as effective and safe as next-day administration. Additionally, given the absence of CD in human bone marrow, it appears capecitabine can be used concurrently with pegfilgastrim. Prospective studies should be done to further investigate, as this practice can benefit pts clinically, decrease office visits, increase pt satisfaction and reduce healthcare costs.
Glycogen synthase kinase-3 beta (GSK-3β) blockade with 9-ing-41 in gastrointestinal cancers: The 1801 phase Ib/II study.
Authors: Safran Howard , Dhawan Mallika Sachdev , Cavalcante Ludimila , De Souza Andre Luiz , Powell Steven Francis , Billadeau Daniel D. , Giles Francis J. , Munster Pamela N. , Carneiro Benedito A. 
Published: February 2020

827 Background: 9-ING-41 is a selective GSK-3β inhibitor with significant pre-clinical antitumor activity in a broad spectrum of malignancies as a single agent and in combination with cytotoxic agents. GSK-3β is a serine/threonine kinase whose overexpression is associated with advanced stage, aggressive tumor growth, and chemotherapy resistance. We report the preliminary results of patients (pts) with gastrointestinal (GI) malignancies. Methods: Phase 1b/2 study evaluating safety and efficacy of 9-ING-41 as monotherapy and combination therapy in pts with refractory cancers. 9-ING-41 is administered intravenously twice-weekly as a single agent (21-day-cycle) or combined with chemotherapy agents, including gemcitabine (GEM), nab-paclitaxel + GEM, carboplatin, or paclitaxel. Study parts 1 and 2 evaluate the safety, describe dose-limiting toxicities (DLTs), determine the maximum tolerated dose and the recommended phase 2 study dose (RP2D) for 9-ING-41 as monotherapy (Part 1) and as combination therapy (Part 2). Part 3 (Simon 2-Stage Phase 2) assess clinical benefit in pts treated with 9-ING-41-based combinations at the RP2D established in Part 2. Response is assessed by RECIST 1.1 criteria in the evaluable lesions. Results: To date, the study accrued 63 pts. Five dose levels (1, 2, 3.3, 5 and 7 mg/kg) have been completed without DLTs. Part 2 of the study evaluating 9-ING-41-based chemotherapy combinations is ongoing. Five out of nine pts with pancreas cancer (PCa) enrolled had stable disease (SD) as the best response; 2 out of 9 pts had a 40-45% decline of CA 19-9. One pt completed 6 cycles with 9-ING-41, two pts completed 4 cycles with 9-ING-41/GEM. Two active pts are receiving 9-ING-41/GEM with SD after 3 and 4 cycles. Three out of four pts with adenocarcinoma of the appendix enrolled had SD as the best response; two pts in active treatment are receiving cycles 5 and 6. One out of 13 pts with colorectal cancer had SD. 9-ING-41-attributable AE to date are reversible grade 1 transient visual changes (color perception). Conclusions: 9-ING-41 is well-tolerated with encouraging SD among heavily pretreated pts with carcinoma of the pancreas and appendix. Clinical trial information: NCT03678883.
Prospective study for comprehensive genomic profiling (GP) in cancer of unknown primary (CUP): Feasibility, molecular landscape, and clinical utility in current era.
Authors: Raghav Kanwal Pratap Singh , Willett Anneleis , Huey Ryan , Dhillon Nishat , Modha Jignesh , Matamoros Aurelio Aurelio , Estrella Jeannelyn , Sanghavi Kunal , Antov Andrey , Choquette Linda , Statz Cara , Kelly Kevin , Rowe Shannon , Liu Edison T. , Rueter Jens , Kopetz Scott , Overman Michael J. , Varadhachary Gauri Rajani 
Published: February 2020

834 Background: CUP presents a unique niche and challenge for application of GP. Absence of a primary limits consensus regarding site-directed and availability of tissue specific targeted therapy. We evaluated the real time feasibility and clinical utility of GP in CUP. Methods: Treatment eligible CUP pts were prospectively enrolled. A novel next-gen targeted sequencing (NGS) assay (ActionSeq/FusionSeq) was used to find genomic alterations (GAs) (somatic mutations in 212 and fusions in 53 cancer-associated genes). The primary objective was to determine prevalence of GAs and to assess the clinical impact via change in pre-test planned therapy (either referral to biomarker pertinent clinical trial (CT) or off label use of FDA approved drugs). With 54 pts we achieved 80% power (α 0.05) to a treatment change in 10% (5% to 15%) pts. Results: Between 9/2016 and 8/2019, 150 pts were consented. Tissue for GP was available in 59 (39%) pts (for 91 pts, samples had exhausted or insufficient tissue). Test was successfully performed on 54 (92%) pts. Cohort characteristics include: median age: 58 yr, male 43%, ECOG PS ≤1 96%, median IHC 8 (range 2-26), median survival 33 m (95% CI 18-47). Median reporting time was 23 days. Four (7%) pts had no identifiable GAs. A fusion ( PTRPK) was seen in 1 (2%) pt. Among 50 pts, total number of GAs were 487; 123 (26%) were “clinically relevant” (median 2.5/pt, range 1-11) while 364 (76%) were variants of unknown significance. Of the 123 GAs, 94 were mutations and 29 were amplifications. The 5 most common mutations were TP53, KRAS, PIK3CA, ARID1A, and NRAS and amplifications were CCND1, FGFR3, ERBB2, EGFR, and MYC. Planned therapy change post ActionSeq occurred in 13 pts (22%, 95% CI 13-34) (2 received an off-label drug; 9 were CT eligible [2 enrolled, 5 had PS decline, 2 pending]; 2 were lost to follow-up). Responses were seen in 2 of 4 pts who received GP based treatment. Conclusions: Comprehensive GP should be offered early to CUP pts. GP can help identify novel therapy and clinical trial options. Given the high rate of insufficient tissue cases, integrating a tissue sensitive algorithm involving IHC and GP in therapeutic management of CUP is merited.
Characteristics of gastrointestinal stromal tumors incidentally discovered during abdominal surgery.
Authors: Garg Meera , Hitscherich Kyle Joseph , Bennett Joseph J. 
Published: February 2020

835 Background: Gastrointestinal Stromal Tumors (GISTs) are rare sarcomas with 5000 new cases each year. Despite their low incidence, surgeons should be familiar with this pathology since GISTs can be encountered incidentally during abdominal surgery. Methods: A retrospective series was conducted by querying pathology and operative reports from a community cancer center between 2005 and 2019 for all GIST diagnoses. Patients identified to have incidental GISTs discovered intra-operatively while undergoing surgery for another diagnosis were the focus of this study. Patient and tumor characteristics were evaluated. Results: A total of 195 patients had a diagnosis of a resected GIST during our study period. Of these 195, 48 patients were incidentally discovered to have a GIST excised during another index operation. The average age of these patients was 62 years old, 27 were female and 21 male. The primary location of these incidental GISTs in descending frequency was stomach (62.5%, n = 30), small bowel (31.3%, n = 15), colon (4.2%, n = 2) and esophagus (2.1%, n = 1). The average GIST size for the cohort was 1.7cm, with stomach, small bowel, colon and esophagus measured at 1.8cm, 1.7cm, 0.65cm and 0.30cm, respectively. Mitotic rate was < 5 mitosis/50 HPF in 96% of patients. Incidental GISTs were identified during the following surgery: colon (n = 14), bariatric (n = 13), non-bariatric gastric (n = 10), hernia (n = 4), pancreatic (n = 3), esophageal (n = 2) and other (n = 2). Most incidental GISTs were discovered during elective surgery (81.3%, n = 39) compared to emergency surgery (18.8%, n = 9), and for benign disease (n = 33) compared to malignant (n = 15). Conclusions: Approximately one quarter of all GISTs resected at our community cancer center in 15 years were discovered incidentally, and during a wide variety of abdominal surgeries for both benign and malignant disease. Almost all these GISTs were < 2cm, benign, and should be cured with the incidental resection. Abdominal surgeons should be aware of unexpectedly finding small GISTs and should not be apprehensive about resecting since they have indolent characteristics. Larger lesions should trigger expert surgical oncology consultation.
Effect of weight loss in patients with metastatic colorectal cancer treated within the randomized phase III FIRE-3 trial (AIO KRK 0306).
Authors: Liu Lian , Erickson Nicole Tonya , Holch Julian W. , Ricard Ingrid , Gesenhues Alena Britta , Theurich Sebastian , Stintzing Sebastian , Heinemann Volker 
Published: February 2020

87 Background: A subgroup of RAS wild-type metastatic colorectal cancer patients within the FIRE-3 study consisted of 400 patients. Gaining insight into frequency and effects of weight change among patients treated with FOLFIRI plus either cetuximab or bevacizumab was aim of this analysis. Methods: A subgroup of 400 RAS wild-type metastatic colorectal cancer (mCRC) patients of the FIRE-3 trial were evaluated. Linear mixed effect models were fitted to explore the mean evolution of weight over time. The presence of a breakpoint at month 1 was investigated by the addition of an adequate parameter into the model. A linear evolution was supposed from month 1. In this exploratory analysis, patients were grouped into cohorts according to weight change using the cut off ≥ 5%. Kaplan-Meier estimations and median survival times were analyzed using log-rank testing. Hazard ratios and corresponding 95% confidence interval from univariate Cox proportional hazards were followed by a multivariate analysis. Results: Patients lost in average 0.75 kg during the first month of treatment, whereas body weight increased hereafter 0.43 kg per month. Of note, patients older than 65 years lost most body weight at month one (1.35kg) and gained least hereafter (0.20kg per month). Within this population a weight loss of ≥ 5% was observed to be an independent prognostic factor for both PFS after 3 months (HR 1.72, 95% CI 1.26-2.34, P = 0.001) and OS after 3 months (HR 1.754, 95% CI 1.29-2.39, P < 0.001). This remained significant when adjusted for age, sex, ECOG score, primary tumor side and treatment arm. Conclusions: In the overall RAS wild-type population, weight loss is an independent prognostic factor for survival in patients with RAS wild-type metastatic colorectal cancer patients and may predict the frequency of adverse events. Therefore, we assume that early preventative measures targeted at weight maintenance might contribute to improved outcomes among this population.
Feasibility of using fitness tracker to assess activity level and toxicities in colorectal cancer (CRC) patients (Pts).
Authors: Holden Thomas , Hill Maureen , Ward William Harrell , Meeker Caitlin R. , Handorf Elizabeth A. , Hall Michael J. , Sigurdson Elin R. , Astsaturov Igor A. , Denlinger Crystal S. , Reddy Sanjay S. , Meyer Joshua E. , Zibelman Matthew R. , Dotan Efrat , Farma Jeffrey M. , Vijayvergia Namrata 
Published: February 2020

91 Background: Performance status (PS) is used to predict tolerance and morbidity associated with CRC treatment. Monitoring activity level at the start of therapy using a wearable fitness tracker Fitbit (Fb) may provide a more accurate estimate of a pt’s overall PS and help predict treatment related toxicity (T). Methods: With IRB approval, we prospectively enrolled CRC pts undergoing therapy into 2 cohorts, medical undergoing chemotherapy (M) and surgical undergoing definitive surgery (S). Our objective was to assess feasibility of using Fb to track pt activity level and secondarily correlate with T. After documenting baseline ECOG PS, M and S pts wore Fb for 4 days while receiving chemotherapy or prior to surgery, respectively. Pts’ mean steps per day (SPD) were calculated excluding days Fb was worn <12 hours. To stratify prediction of toxicity risk, a cutoff of 5000 SPD was selected and any post-operative complication (S pts) or ≥grade 3 toxicity (M pts) was counted as T. The study met accrual of 80 pts. Results: On final analysis, 80 pts were evaluated for the primary aim. 68 pts had at least 3 days with ≥12 hours of Fb usage, meeting the 75% feasibility endpoint. 76 pts had at least 1 day with ≥12 hours of Fb usage with data for analysis. SPD correlated with PS and the SPD and active minutes (read by device) for PS 0 and PS 1 pts was 6313 steps and 122 min and 2925 steps and 55 min, respectively (p=0.0003). Rate of T was 25% in pts with PS 0 and 33% in pts with PS 1. With SPD, rate of T was numerically lower in pts with >5000 SPD compared to pts with <5000 SPD (21% vs 32%, p = NS). Conclusions: We observed high rates of compliance with Fb in CRC pts. SPD cutoff of 5000 correlated with ECOG PS 0 vs 1. We observed usefulness of SPD as an identifier for toxicities and suggestion that it may be more reliable compared to PS alone in this small sample of pts. These findings provide rationale to study SPD in conjunction with PS for risk stratification of pts undergoing therapy, and can possibly be incorporated into pre-habilitation selection in high risk groups. [Table: see text]