bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 pandemic on psychological health of a sample of the health care workers in the western region of Kingdom of Saudi Arabia
Authors: Sultan Sadia , Bashar Abu , Nomani Ibtesam , Tabassum Aisha , Iqbal Mohammad Shahid , Fallata Ebtihaj O. , Sindi Ramya Ahmad , Almasoudi Nouf M. , Rheem Seeqa 
Published: January 2022

Abstract
Background
The coronavirus disease 2019 pandemic has shown a significant impact on the psychological well-being of health care workers. The aim of the study was to evaluate the impact of the COVID-19 pandemic on the psychological health of health care workers in the Kingdom of Saudi Arabia. During the months of November and December, 283 health care workers completed a survey containing measures of depression, anxiety and stress (using Depression Anxiety and Stress-21 scale [DASS-21]) and questions regarding potential predictors such as the role of COVID-19 perception, availability of mental health support and work-related factors. Pearson X2 test revealed factors associated with the presence of significant psychiatric symptoms.

Result
Among the participants, 17.3% screened positive for depression, 26.2% for anxiety and 17.3% for stress. Nurses reported significantly more depression, anxiety and stress than doctors. Those who received mental health support reported significantly lesser depression, anxiety and stress. Those who felt that quality of life was heavily impacted due to COVID-19 reported significantly high depression, anxiety and stress.

Conclusions
Poor psychological well-being was prevalent in health care workers; however, mental health measures have been shown to significantly reduce the mental health burden in health care workers.
Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): Phase 2 results from CheckMate 9X8.
Authors: Lenz Heinz-Josef , Parikh Aparna Raj , Spigel David R. , Cohn Allen Lee , Yoshino Takayuki , Kochenderfer Mark D. , Elez Elena , Shao Spencer H. , Deming Dustin A. , Holdridge Regan C. , Larson Timothy , Chen Eric , Mahipal Amit , Ucar Antonio , Cullen Dana , Baskin-Bey Edwina S , Ledeine Jean-Marie , Hammell Amy , Tabernero Josep 
Published: January 2022

8 Background: Standard 1L therapies for mCRC include a fluoropyrimidine with oxaliplatin and/or irinotecan, and a biologic agent. NIVO may enhance antitumor activity in combination with 1L standard therapies within a subset of patients (pts) with mCRC. CheckMate 9X8 evaluated NIVO + mFOLFOX6/BEV vs mFOLFOX6/BEV in 1L mCRC (NCT03414983). Methods: Adults with previously untreated, unresectable, mCRC were randomized 2:1 to NIVO 240 mg + mFOLFOX6/BEV Q2W (NIVO + standard-of-care [SOC]) or mFOLFOX6/BEV Q2W (SOC). Primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1. Key secondary endpoints included objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), overall survival (OS), and safety. Results: 195 pts were randomized to NIVO + SOC (n = 127) or SOC (n = 68). Median (range) follow-up was 23.7 (0–33.2) months (mo; NIVO + SOC) vs 23.2 (0–32.3) mo (SOC). Median (range) duration of therapy was 9.9 (0.1–31.8+) mo (NIVO + SOC) and 7.7 (0.1–26.7+) mo (SOC). The HR (95% CI) for PFS was 0.81 (0.53–1.23; P = 0.30), which did not meet the prespecified threshold for statistical significance (median PFS, 11.9 mo in both arms; Table). PFS rates after 12 mo were higher with NIVO + SOC vs SOC (Table). ORR was 60% (NIVO + SOC) and 46% (SOC; odds ratio 1.72 [95% CI 0.96–3.10]) and median (95% CI) DOR was 12.9 (9.0–13.1) mo (NIVO + SOC) and 9.3 (7.5–11.3) mo (SOC; Table). Rates of grade 3−4 treatment-related adverse events (TRAEs) were higher with NIVO + SOC; however, no new safety signals were identified (Table). Biomarker analyses, including tumor mutational burden and baseline CD8 levels, will be presented. Conclusions: The primary endpoint of PFS was not met; however, NIVO + SOC showed higher PFS rates after 12 mo, a higher response rate, and more durable responses compared with SOC, along with acceptable safety, in 1L mCRC. Clinical trial information: NCT03414983. [Table: see text]
Medicaid expansion to reduce racial disparity in the incidence of early onset colorectal cancer.
Authors: Rahman Shafia , Patel Riya Jayesh , Liu Jianyou , Acuna-Villaorduna Ana , Kim Mimi , Goel Sanjay 
Published: January 2022

24 Background: Early onset colorectal cancer (EO-CRC, age < 50 years) is an emerging public health crisis, especially in minorities. We evaluated and compared the effects of Medicaid expansion on the incidence of EO-CRC among Hispanics, Blacks, and Whites across the United States. Methods: The National Cancer Data Base was used to collect data on newly diagnosed cases of EO-CRC (40-49 years) among the three races, across all stages, from 2010-2017. Data for 21 expansion states (ES) that expanded Medicaid in 2014, and 16 non-expansion (NES) states was analyzed, excluding the states which expanded after 2014.The yearly state-wise population of all three races was collected from the U.S Census Bureau for 2010-17. A segmented Poisson regression model with generalized estimating equations was used for statistical analysis. Results: Annual incidence (AI) of EO-CRC pre and post expansion, in ES was 6/100,000 and 9/100,000 in Hispanics; 17/100,000 and 21/100,000 in Blacks and 14/100,000 and 18/100,000 for Whites. In NES the AI, pre and post 2014 was 8/100,000 and 10/100,000 among Hispanics, 19/100,00 and 24/100,000 among Blacks and 16/100,000 and 20/100,000 among Whites. Rate of change in AI of EO-CRC among Hispanics was 4.3% per year (2010-14), and 9.8% (2014-17) for ES states; and 6.4% (2010-14), and 1% (2014-17) in NES; among blacks was 3.8 % per year (2010-14), and 1.3% (2014-17) for ES states; and 1.6% (2010-14), and 3.2% (2014-17) in NES. Among Whites, increase in AI was 4.3% per year (2010-14), and 6.3% (2014-17) for ES states; and 4.0% (2010-14), and 5.7% (2014-17) in NES. ES showed greater change in incidence after expansion compared to pre-expansion in the incidence of EO-CRC as compared to NES (p=0.03) in Hispanics, however no significant difference was noted among Blacks (p=0.33) and Whites(p=0.94). Racial groups did significantly differ with respect to the degree of change in pre and post expansion (2014) rates of incidence of EO- CRC in the ES, however, in the NES, there were significant difference between the Hispanics and Whites (p=0.01), but not between Blacks versus Whites. Conclusions: Medicaid expansion reduces racial disparities in detection of EOCRC.[Table: see text]
Correlation of circulating tumor DNA (ctDNA) with clinical outcomes in appendiceal cancers (AC).
Authors: Kothary Vishesh , Eng Oliver , Polite Blase N. , Liao Chih-Yi , Catenacci Daniel V.T. , Dhiman Ankit , Turaga Kiran , Shergill Ardaman 
Published: January 2022

29 Background: Appendiceal Cancers are a heterogenous group of rare tumors with distinct histopathologic and genomic alterations. These often have peritoneal spread that might not be easily detected on current imaging modalities, and conventional tumor markers may not lend diagnostic support. Hence, novel diagnostic techniques are needed. Measurement of ctDNA for recurrence risk prediction, response to therapy and and early diagnosis is a promising technique. However, limited published data exist in AC to validate the role and utility of ctDNA in clinical practice. Here we present a single institution experience of ctDNA analysis in patients with AC. Methods: ctDNA measurements of 37 pts with stage II-IV AC treated between 1/1/2019 and 9/15/2021 were reviewed retrospectively. ctDNA analysis was done using Signatera bespoke mPCR NGS assay. ctDNA results were compared to crossectional imaging, CEA levels, and clinical evaluation. Results: 19/37 patients (51%) had at least one positive ctDNA test result. Of those, 8 had testing done during the surveillance setting (two with grade 3, one with grade 2, two with grade 1, and three with unknown grade). Of those, 5 pts (62.5%) had positive ctDNA detected, while 33.33% had elevated CEA level, 25% had radiographic and 42.9% had clinical evidence of recurrence (Table). 7/14 (50%) pts had high-grade pathology and positive ct-DNA, 3/6 (50%) patients had low-grade (grade 1) pathology and positive ct-DNA findings. 4 patients had longitudinal ct-DNA measurements available which correlated well with their disease course. Median duration to recurrence (radiographic or laparoscopic) was 376 days. Median duration to the first positive ctDNA test was 370 days. Median duration to positive CEA after initial treatment was 475 days. Conclusions: Measurement of ctDNA can be a useful tool to follow disease course and to guide management decision-making in patients with AC. Prospective studies with serial measurements of ctDNA are planned. [Table: see text]
COVID-19 vaccination in gastrointestinal cancer patients receiving chemotherapy: A single institute experience.
Authors: Suenaga Mitsukuni , Yamauchi Shinichi , Masuda Taiki , Hanaoka Marie , Iwata Noriko , Sato Yuya , Tomii Chiharu , Tokunaga Masanori , Kinugasa Yusuke 
Published: January 2022

30 Background: Early approval of COVID-19 vaccine has significant benefits for cancer patients treated under the COVID-19 pandemic worldwide. However, there has been limited reports that investigated the safety and efficacy of vaccination in cancer patients and the optimal timing of vaccination during chemotherapy. We therefore investigated the effects of vaccination on treatment in cancer patients receiving chemotherapy. Methods: Our retrospective observational study included 52 patients with gastrointestinal (GI) cancer receiving chemotherapy at the medical hospital of Tokyo Medical and Dental University in Tokyo who had two doses of mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) between May 2021 and September 2021. All patients had no history of COVID-19 infection. Treatment- and vaccination-related adverse events were recorded by outpatient interviews and self-reports. All adverse events were evaluated using CTCAE v5.0. Results: Characteristics of patients were as follows (N = 52): median age, 70y (range, 49–89); male/female, 30/22; ECOG PS 0, 75%; local/metastatic, 12/40; mean BMI, 23.4±4.1; comorbidities in 36 (cardiovascular in 24, diabetes in 8, kidney disease in 8, liver disease in 6, lung disease in 1); treatment (cytotoxic in 45, biologics in 23, immune checkpoint inhibitor in 4). Of the 52 patients, 45 received chemotherapy prior to vaccination; days from last dose to first vaccination, median 11 (range, 1–70); days from first to second vaccinations, median 21 (range, 21–41); days from first vaccination to chemotherapy, median 10 (range, 2–34). 11 patients (24.4%) changed treatment schedule: 3 for safety reasons, 4 for myelosuppression and 4 for convenience. 4 patients stopped treatment due to disease progression. Following the first vaccination, 37 patients (82.2%) had adverse events (AEs): injection site pain (n = 35), fatigue (n = 6), fever (n = 3), headache (n = 2), gastrointestinal symptoms (n = 2), redness (n = 1), insomnia (n = 1). There was no treatment- and vaccine-related deaths. Conclusions: Our findings suggest that vaccine-related AEs in GI cancer patients receiving chemotherapy are tolerable, and treatment schedule changes could be minimized. Although careful monitoring is required, COVID-19 vaccination is also recommended for cancer patients toward the convergence of the COVID-19 pandemic.
Patient care satisfaction and emergency room utilization among young adult colorectal cancer survivors during the SARS-CoV-2 pandemic.
Authors: Kagramanov Dalia , Miller Kimberly Ann , Gallagher Phuong , Freyer David R. , Milam Joel , Lenz Heinz-Josef , Barzi Afsaneh 
Published: January 2022

34 Background: Survivors of colorectal cancer (CRC) are at risk for late effects of therapy and recurrence of cancer. With recurrence rates ranging between 30-40% (Siegal et al., 2020), consistent, survivor-focused follow-up care is needed for early detection of late effects and recurrence (Jeffery et al., 2019). CRC-related care delivery has been significantly disrupted by the SARS-CoV-2 pandemic, with decreases of 40% in CRC services in the United States between April 2020 and 2019 (Jammu, 2020). Consequentially, survivors may be left with fewer options for care, potentially causing increases in emergency room (ER) utilization. Methods: This cross-sectional study examined the patterns of ER utilization during the SARS-CoV-2 pandemic among young adult CRC survivors and assessed the relationship between self-reported care satisfaction and ER use. Eligible participants were diagnosed with colon or rectal cancer between 18-39 years, between 6-36 months from diagnosis/relapse, English speaking, and based in the United States. Questions on care satisfaction were Consumer Assessment of Healthcare Providers and Systems (CAHPS) questions. A multivariable logistic regression was conducted to assess the association between patient satisfaction and ER utilization, adjusting for factors related to the pandemic. Covariates for this analysis were chosen based on a significance of p < 0.1 at the univariate level, as well as general clinical significance. Results: The overall sample was N = 196, mean age (SD) was 32.1 years (4.5), and 116 survivors (59%) were male. Tumor location was colon or rectal in 42% and 57%, respectively, and the majority (56%) were diagnosed with stage 2 disease; 42.6% reported relapsed disease, and 20% had an ostomy. The majority of survivors (72.5%) had between 1-4 visits to an emergency room in the last 12 months and were categorized as normal users. Approximately 24.7% of the sample had greater than 4 visits to the ER in the last 12 months and were categorized as super-utilizers (Johnson et al., 2015). Colorectal cancer survivors that reported a delay in their follow-up cancer care as a result of the pandemic were two times (OR: 2.05, 95% CI 0.99, 4.24) more likely to be super-utilizers of the ER. Higher self-reported satisfaction with overall care was associated with a 13.7% (OR: 0.86, 95%CI: -0.68, 1.09) lower likelihood of being a super-utilizer. Conclusions: This study found strong associations between delays in care, self-reported care satisfaction, and being a super-utilizer of the ER during the pandemic among young adult CRC survivors off treatment. Increasing patient satisfaction and minimizing care interruptions amongst this vulnerable population may aid in mitigating over-utilization in the ER during an ongoing pandemic.
A real-world comparison of trifluridine/tipiracil and regorafenib in refractory metastatic colorectal cancer in the United States.
Authors: Nevala-Plagemann Christopher Duane , Ying Jian , Sama Shashank , Florou Vaia , Haaland Benjamin , Garrido-Laguna Ignacio 
Published: January 2022

39 Background: For patients with refractory metastatic colorectal cancer (mCRC), both trifluridine/tipiracil (TAS-102) and regorafenib have received approval for use in the United States. The approvals of these agents were based on modest improvements in overall survival (OS) when compared to best supportive care plus a placebo in the RECOURSE and CORRECT trials, respectively. However, TAS-102 and regorafenib have never been directly compared in a prospective clinical trial. This study utilized a large real-world database to compare clinical outcomes with use of these agents. Methods: The nationwide de-identified Flatiron Health EHR-derived database was reviewed for patients diagnosed with mCRC between 2015 and 2020. Patients who received at least two lines of guideline recommended therapy for advanced disease followed by treatment with TAS-102 and/or regorafenib in the third line or greater were included for analysis. Patients who did not have a visit or medication order within 90 days of metastatic diagnosis were excluded to ensure patients were engaged with care at the data-providing institution. Kaplan-Meier and propensity score weighted models were used to compare survival outcomes between groups. Results: The records of 22,078 patients with mCRC were reviewed. Of the 4,407 patients that received at least two lines of standard therapy, 2,072 subsequently received regorafenib and/or TAS-102. Of these, 813 (39.2%) received TAS-102 alone, 275 (13.3%) TAS-102 followed by regorafenib, 736 (35.5%) regorafenib alone, and 248 (12.0%) regorafenib followed by TAS-102. Median OS for patients treated with TAS-102 alone or prior to receiving regorafenib was 6.66 months (95% CI 6.16-7.18) compared to 6.30 months (95% CI 5.80-6.79) for those treated with regorafenib alone or prior to receiving TAS-102 (p = 0.36). A propensity score weighted analysis controlling for age, race, stage at initial diagnosis, performance status at start of therapy, MSI/MMR status, RAS/RAF status, and line in which TAS-102 or regorafenib was received did not demonstrate a significant difference in survival between groups (HR 0.99, 95% CI: 0.90 -1.09, p = 0.82). A subgroup analysis did not identify any significant differences in outcomes stratified by age, performance status, MSI status, or RAS/RAF status. Conclusions: This analysis of real-world data did not identify a significant difference in survival outcomes in mCRC patients who were treated with TAS-102 or regorafenib. Median OS with both agents in a real-world setting was similar to that shown in the clinical trials that led to their approvals. This data should be considered when discussing the risks and benefits of TAS-102 and regorafenib with mCRC patients who are eligible for third line or greater treatment.
Integrated approach to collecting patient reported toxicities in a colorectal cancer trial.
Authors: Gaddy Jacquelyne Janean , Sanoff Hanna Kelly , Deal Allison Mary , Basch Ethan , Wood William Allen 
Published: January 2022

51 Background: Understanding the toxicities experienced by patients treated with advanced CRC is critical when considering appropriate dose modifications, standard drug dosing, and quality of life. A workflow that makes available Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) to clinicians to inform overall toxicity assessment should be easy to use and focus on clinically relevant issues. The value of a system that not only collects PRO-CTCAE but integrates it with clinician grading to inform overall symptomatic adverse event assessment during clinical trials is unclear. Methods: Patients were simultaneously enrolled in a phase II multi-center clinical trial that evaluated a genotype-guided dosing strategy for irinotecan by prospectively analyzing efficacy in 100 mCRC patients receiving FOLFIRI (5-fluorouracil, leucovorin, irinotecan) and bevacizumab. On day 1 and day 15 of each cycle patients provided PRO-CTCAE responses on 13 symptoms (26 questions) which were made available to clinicians at the time of their toxicity assessment. Descriptive statistics were used to summarize patient demographic and clinical characteristics. Concordance was defined as both patient and clinician giving the same response (both positive or both negative). Results: 100 patients participated in the study, of which 48% were female and 83% White. Overall, 96% of both patients and providers completed at least 80% of PRO-CTCAE forms available to them, demonstrating the feasibility of an integrated workflow for patient-clinician toxicity grading. Across all symptoms, concordance was high (73%) for the patient and provider reporting severe symptoms. 39% of patient-provider pairs reported at least 1 severe symptom and 34% of pairs never reported a severe symptom. In 23% of pairs the patient reported a severe symptom and the provider never did, and in 3% of pairs, the provider reported a severe symptom, but the patient never did. On the symptom level, the concordance was highest (>90%) for dysphagia and vomiting, and lowest (74-82%) for abdominal pain, fatigue, and pain. 52 patients required dose decreases, with the first decrease most often due to hematologic toxicity (80%). In 46% of cases the patient reported at least one severe toxicity prior to or on the same day as the dose decrease, compared to 19% of cases where the provider reported at least severe toxicity prior to or on the same day as the dose decrease. Conclusions: A workflow that brings patient-reported toxicity to clinicians at the time of clinical toxicity rating is feasible. Nevertheless, discordance continues to exist between patient-reported and clinician-reported toxicity ratings, consistent with prior research. Further research could formally compare concordance when using an integrated vs a non-integrated toxicity rating workflow and could ascertain the reasons for continued discordance within an integrated workflow.
Can second-generation multitarget stool DNA panels reliably detect colorectal cancer and advanced precancerous lesions?
Authors: Kisiel John B. , Gagrat Zubin D , Krockenberger Martin , Bhattacharya Abhik , Bourne Bridget L , Leduc Christine M , Matter Michael B , Fourrier Keith D , Edwards David , Limburg Paul J. , Domanico Michael J. 
Published: January 2022

63 Background: Population-based colorectal cancer (CRC) screening can reduce mortality by detecting and removing advanced precancerous lesions (APL) and early-stage invasive disease. One guideline-included strategy is the multi-target stool DNA test (mt-sDNA), which combines detection of methylation DNA markers (MDMs), KRAS mutations, and fecal hemoglobin. Since the mt-sDNA pivotal study was conducted, novel biomarkers have been discovered. A panel of highly discriminant MDMs ( LASS4, LRRC4, PPP2R5C, and reference marker ZDHHC1) was identified through a blinded, case-control study of archival specimens. Here, we evaluated the performance of this novel mt-sDNA panel, combined with fecal hemoglobin, in archival stool samples weighted to early-stage CRC and prospectively collected APL, simulating a screening population. Methods: The verification study featured 777 samples—210 cases (112 CRC [49 stage I, 38 stage II, 17 stage III, and 8 stage IV] and 98 APL) and 567 controls (176 non-APL and 391 colonoscopy-negative)—from three trials (NCT01397747, NCT01260168, and NCT02503631). Median APL size was 12 mm (interquartile range: 10 mm to 15 mm), with 86.7% adenomas (n = 85) and 13.3% sessile serrated polyps (SSPs; n = 13). The average age was 65.5 years for cases (57% men) and 63.2 for controls (47% men). Samples were processed through homogenization, targeted MDM capture, bisulfite conversion, and MDM quantitation using Long‐probe Quantitative Amplified Signal (LQAS). Fecal hemoglobin was quantified using enzyme-linked immunosorbent assay (ELISA). Samples were split into stratified 75%/25% training-testing sets and model outcomes were cross-validated 1,000 times. Results: Mean performance from the cross-validation analysis is summarized in the table below. Overall sensitivity was 95.2% for CRC and 57.2% for APL, with specificities of 89.8% (no CRC/APL) and 92.4% (no neoplasia). Subgroup analyses showed high sensitivity for early-stage CRC, with 93.4% at stage I and 94.2% at stage II. By APL subtype, sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSPs. Conclusions: These data support high sensitivity and specificity for a second-generation mt-sDNA panel. A multicenter pivotal trial evaluating the panel is underway (NCT04144738). [Table: see text]