bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of educational YouTube videos related to pancreatic cancer: Analysis of patient-focused and NCI-designated cancer center videos.
Authors: Didier Alexander , Fang Lauren , Stiene Jennifer , Ud Din Shabab , Spencer Caleb , Hamouda Danae M. 
Published: January 2023

756 Background: The incidence of pancreatic cancer among young adults has sharply risen over the past decade. Young adults often utilize online educational media, such as YouTube videos, for information about their disease. These may be subject to a high degree of bias and misinformation; previous analyses have demonstrated low quality of other cancer-related YouTube videos. Thus, we sought to determine if patients can rely on YouTube videos for accurate information about pancreatic cancer, and we compared relevant YouTube videos with those published by NCI-designated cancer centers (CCs). Methods: We designed a novel search query and inclusion/exclusion criteria based on published studies evaluating YouTube user tendencies. These criteria were used to identify videos most likely watched by patients, which composed our “Patient-Focused” (PF) group. We compared PF videos with those uploaded by CCs by manually searching each CC’s affiliated YouTube and applying the same inclusion/exclusion criteria. Data were summarized by descriptive statistics. Videos were evaluated based on two well-known criteria, the DISCERN and JAMA tools, as well as a tool published by Sahin et al to analyze the contents of colorectal cancer videos. A score of ≥ 6 on the Sahin scale correlated with high quality information. We used t-test and Chi-squared test to analyze differences between groups. Results: 39 videos met inclusion criteria within the PF sample and 19 videos within the CC sample, total sample of 58 videos. The PF sample had mean Sahin scores of 4.24 ± 2.21, DISCERN scores of 2.15 ± 0.47, and JAMA scores of 1.77 ± 0.60. CC videos had mean Sahin scores of 3.84 ± 2.70, DISCERN scores of 2.25 ± 0.63, and JAMA scores of 2.00 ± 0.0. Perceived speakers’ ethnicity was 75% White (n=77), 21% Asian (n=21), and 4% Hispanic (n=4). There were no Black speakers. Most videos uploaded were fair or poor quality. 16.4% (n=27) were of average or high quality by the Sahin criteria, with 1 video receiving a perfect score. 9.6% (n=5) and 90.4% (n=47) were average or high quality by DISCERN and JAMA criteria, respectively. 8.6% (n=5) of videos discussed palliative care and 10.3% (n=6) discussed staging. Independent samples t-test revealed no significant differences between PF and CC videos for the Sahin criteria (p=0.429) and DISCERN criteria (p=0.387). The mean JAMA score was higher for CCs (2.0 ± 0.0) than the PF group (1.8 ± 0.6) (p=0.001). Chi-squared test revealed that CC and PF videos had similar speaker ethnic diversity (p=0.381). Conclusions: Educational pancreatic cancer YouTube videos demonstrate low to moderate quality information with limited speaker ethnic diversity. Given ongoing trends in the spread of misinformation through social media, CCs and other patient educators should be mindful of their role in producing high quality, comprehensive information for patients and their caregivers.
Metachronous colorectal cancers in Icelandic MSH6 and PMS2 Lynch syndrome carriers in 1955-2017: A population-based study.
Authors: Haraldsdottir Sigurdis , Andresdottir Arna Kristin , Einarsson Haukur , Jonsdottir Hildur , Snaebjornsson Petur , Bjornsson Einar Stefan , Jonasson Jon G. 
Published: January 2023

76 Background: The prevalence of Lynch syndrome in Iceland is the highest described so far or 1:226 with three founder mutations, one in MSH6 and two in PMS2, and was first reported in 2017. Lynch syndrome predisposes carriers to colorectal cancer and metachronous primaries. Most data on metachronous colorectal cancer reflects on MLH1 and MSH2 carriers and is not well described in MSH6 and PMS2 carriers. The purpose of this study was to examine the cumulative incidence of metachronous colorectal cancer in Icelandic Lynch syndrome carriers diagnosed with colorectal cancer from 1955-2017. Methods: This retrospective study included all individuals with pathogenic variants in mismatch repair genes identified in a nationwide genotype database and a colorectal cancer diagnosis in the Icelandic Cancer Registry from 1955-2017. DeCODE genetics has collected extensive genotypic information on the Icelandic population sequencing the whole genomes of 49,708 Icelanders and imputing genotypes into 116,573 Icelanders whose DNA had been genotyped with SNP chips. Cancer information was obtained from patient charts and cause of death obtained from the Cause of Death Register. All polyp pathology was accessed in the pathology registry and reassessed by two pathologists. Results: A total of 65 individuals developed colorectal cancer during the study period with 34 (52.3%) PMS2 carriers and 25 (38.5%) MSH6 carriers. The cumulative incidence of metachronous colorectal cancer was low or one case (1.5%) in an MSH2 carrier with a median follow-up time of 58 months (Q1 8.0, Q3 167.0, range 0-365 months) in the cohort. Only two (3.1%) individuals, one with MSH2 and one with MSH6 pathogenic variants, underwent a total colectomy. Median age at first colorectal cancer diagnosis was 63 years (Q1 54.0, Q3 72.5, range 28-94). Thirty-one (47.7%) individuals had polyps resected during the study period with adenomas (67.1%) being the most common. Significantly more MSH6 carriers had a history of advanced adenomas as compared to PMS2 carriers (36.0 % vs 11.8%, p = 0.026). Five-year colorectal cancer survival was 81.4% for PMS2 carriers and 71.5% for MSH6 carriers. Conclusions: The incidence of metachronous colorectal cancer was zero in Lynch syndrome carriers with MSH6 or PMS2 pathogenic variants from 1955-2017 despite these individuals not undergoing rigorous Lynch syndrome screening. This would support performing segmental colectomies and following European screening guidelines for MSH6 and PMS2 carriers in Iceland.
Demographic and regional trends of gastrointestinal (GI) cancer mortality in adolescents and young adults (AYA) in the US, 1999-2019.
Authors: Hussaini S. M. Qasim , Blackford Amanda L. , Sedhom Ramy , Gupta Arjun 
Published: January 2023

786 Background: There is an alarming rise in incidence of GI cancers in AYAs that face unique social challenges in navigating their healthcare and receiving guideline-concordant care. There is limited data on mortality trends in this understudied group. We investigated age-adjusted mortality rates (AAMRs) in young adults with GI cancer. Methods: We utilized the CDC WONDER database to analyze deaths among young adults aged 15 to 44 years from GI cancer (ICD 15-26) from 1999 to 2019. We calculated AAMRs per 100,000 and stratified by sex, race/ethnicity, census, and urban metro (population >1,00,000), medium/small (50,000 – 999,999) or rural area (<50,000) per NCHS Classification Scheme. We used Joinpoint regression software (v4.9) to establish annual percentage change (APC) trends. Results: Between 1999 and 2019, there were 73,954 deaths from GI cancer in young adults (39% female, 16% Hispanic, 20% non-Hispanic Black, 16% rural, 42% Southern-located, 52% colorectal, and 17% each pancreatic, hepatobiliary, and gastric cancers). Overall AAMR over study period was 3.3. Among subgroups, the AAMR was higher in men (3.9), non-Hispanic Black adults (4.6), and rural areas (3.7). Time analysis by year showed overall stability or slight decrease in AAMRs between 1999-2009, followed by an increase from 2009-2019. This was especially notable in Hispanic individuals. Earlier increases in AAMR were noted in rural (since 2004) and Midwestern (since 2001) locations. Highest AAMRs were noted in Southern states (Mississippi, Kentucky, West Virginia, and Alabama). Compared to our younger cohort, older adults (45+) had expectedly higher but recorded significantly better AAMR improvements during study period. Conclusions: Mortality rates for AYAs with GI cancers remained relatively stable from 1999 to 2009, but have since risen, with significant sociodemographic and regional variation. These data highlight the need to better understand risk factors (diet, environmental, and other), screening trends, and variation in receipt of guideline-concordant care to ensure appropriate and equitable risk reduction and cancer management in AYAs.[Table: see text]
Continuous maintenance (Maint) capecitabine (Cape) dosing for colorectal (CRC) and pancreatic cancers (PC): A single-institution, retrospective, real-world study.
Authors: Mukherji Reetu , Yin Chao , Weinberg Benjamin Adam , Alqahtani Ali , Hameed Rumaisa , Barcellos Anna , Connole Maegan , Perelgut Chelsea , Fortuin Josephine , Marshall John 
Published: January 2023

789 Background: Cape is an oral fluoropyrimidine (FP) used as maint therapy in CRC and PC. While the standard FDA dosing is 1250 mg/m2 twice daily (BID) for 14 days followed by 7 days off in a 21-day cycle, there are variations across institutions as to the preferred schedule. To improve tolerability and convenience, our institution adopted a “continuous” dosing schedule where cape is taken BID Monday-Friday (M-F) with a treatment break on Saturday and Sunday. Here, we describe our institution’s experience with continuous maint dosing in advanced CRC and PC patients (pts) and explore real-world outcomes. Methods: Pts ≥ 18 years of age treated with continuous maint cape (+/- bevacizumab) after any line of therapy for stage 4 CRC/PC or locally advanced PC between 1/2016-12/2020 were identified in the COTA real-world database. The final study population included 35 PC and 85 CRC pts. Pt characteristics were analyzed descriptively and progression-free survival (PFS) was calculated using Kaplan Meier methods. Results: Among the 35 PC pts, the median age was 66 years (IQR: 61-73), 57.1% were females, and 65.7% were Caucasian. Among the 85 CRC pts, the median age was 54 years (IQR: 47-66), 47.1% were females, and 55.3% were Caucasian. Most PC (71.4%) and CRC (57.7%) pts were initially prescribed a total daily cape dose of 2 g (range 0.5-4 g). Dose adjustments, including dosage/schedule changes, occurred 11 times amongst PC and 36 times amongst CRC pts, and the leading cause was toxicity (72.7% in PC, 55.6% in CRC). Among PC pts, 14.3% had a dose reduction, 3% had a dose increase, and 11.4% switched to an alternative dosing schedule. Among CRC pts, these rates were 32.9%, 12.9%, and 9.4%, respectively. The leading cause of maint discontinuation was progression of disease (POD) (55.6% in PC, 59.3% in CRC). Additional outcomes are summarized in the table. Conclusions: Although maint FP is an established standard of care, it is often underutilized due to inherent inconveniences and toxicities associated with FDA cape dosing or intravenous FP therapy. The PFS reported here using a continuous cape dosing (predominantly starting at 2 g daily dosing) was in range with those previously reported in PC/CRC 1st-line maint studies using FDA cape dosing or intravenous FP. The rates of cape discontinuation attributed to toxicity we report may be confounded by not controlling for the treatment setting. We argue fixed cape dosing (1 g BID) M-F should be considered a standard maint regimen based on efficacy, convenience, tolerability, and feasibility of dose adjustments.[Table: see text]
Prevalence of UGT1A1 polymorphisms in gastrointestinal cancer: A single-institutional retrospective study.
Authors: Jiang Bei , Daboul Nour , Hafez Maria , Wen Sijin , Heise Crystal , Safi Danish , Abonofal Abdulrahman , Uchida Emma , Malla Midhun 
Published: January 2023

797 Background: UGT1A1 gene polymorphisms are heterogeneously distributed among ethnicities and varying geographical regions. Patients with UGT1A1*6 and UGT1A1*28 polymorphisms have an increased risk of grade 3-4 neutropenia and diarrhea from irinotecan due to poor metabolism. This study evaluated the prevalence of UGT1A1 polymorphisms in the cancer patients in a large tertiary cancer center in the Appalachian region, in order to develop individualized institutional guidelines on the utility of UGT1A1 testing in chemotherapy dose management. Methods: This retrospective study evaluated all patients with gastrointestinal (GI) malignancies who underwent UGT1A1 testing prior to chemotherapy initiation between 1/1/2020 and 6/30/2022 at West Virginia University. All patients within this disease sub-specialty who were eligible for chemotherapy were tested for UGT1A1 *6 and UTG1A1*28 polymorphism via PCR based pharmacogenomic evaluation using OneOme RightMed comprehensive testing. Patients were excluded if they were tested for genetic alterations specifically due to previous treatment intolerances. Prevalence of the alterations along with demographic characteristics of patients are reported. Results: UGT1A1 genotyping was performed in 278 patients prior to initiating chemotherapy and 12 patients were excluded due to insufficient sample. A total of 266 patients met the inclusion criteria. The median age was 66 years (IQR: 26-92). Males constituted a higher proportion of the population compared to females (M: F = 147: 119). Colon (n-81; 30.5%) and pancreatic (n-80; 30%) cancers were the predominant GI malignancies. Fifty five percentage of patients (n-146) had metastatic disease. The distribution of the UGT1A1 variant genotype is showed in the table below. Conclusions: The prevalence of heterozygous and homozygous of UGT1A1*28 polymorphism in GI cancer patients in the Appalachian region is 51.5%, consistent with the reported literature. Homozygous and heterozygous UGT1A1 *28 alterations constituted 13.2 and 38.3% respectively. Data collection for pre-emptive chemotherapy dosage adjustments and adverse events is ongoing to integrate testing for UGT1A1 polymorphism routinely for all GI malignancies cancer patients starting irinotecan chemotherapy.[Table: see text]
The efficacy and safety of ripretinib in Chinese patients with advanced gastrointestinal stromal tumors: A multicenter, retrospective study.
Authors: Yang Weili , Qian Haoran , Yang Litao , Wang Pengfei , Qian Hailong , Chu Binbin , Liu Zhuo , Sun Jingyu , Wu Dan , Sun Lifeng , Zhou Wenqiang , Hu Jingwei , Chen Xiaolei , Shou Chunhui , Ruan Lingxiang , Yu Jiren 
Published: January 2023

800 Background: Ripretinib is a switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits KIT and platelet-derived growth factor receptor α (PDGFRA) kinase signaling. Ripretinib demonstrated favorable therapeutic efficacy and safety in clinical trial settings and was approved for advanced GIST who have received prior treatment with three or more TKIs. Here, we report the efficacy and safety of ripretinib in Chinese patients with advanced GIST in a multicenter, retrospective study. Methods: Patients with advanced GIST who received ripretinib in ZheJiang province were included and analyzed. The primary endpoint was progression-free survival (PFS) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 GIST-Specific Standard. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of therapy (DOT), safety and overall survival (OS). Exploratory endpoint was the predominant genotype for ripretinib treatment. Results: 23 patients were enrolled, while 21 patients were included in the study. The median number of prior lines of therapy was 3 (range, 0-4). The site of primary tumor was predominantly the small intestine (52.38%) and 47.62% of patients with ECOG performance status≥2. Median PFS was 7.1 months (95% CI, 4.9-NA), the ORR and DCR were 9.52% and 85.71%, respectively. Median duration of therapy was 7.3 months (range, 1.8-12). For patients on ≥fourth-line therapy, the median PFS was 9.2 months (95% CI, 4.6-NA), the ORR and DCR were 7.14% and 100%, respectively. Shorter interval between the end of the latest TKI and ripretinib therapy was correlated with longer median PFS and OS (P = 0.021 and P = 0.009, respectively). In univariate analysis, patients with KIT exon 9 mutation had a shorter PFS than patients without KIT exon 9 mutation (hazard ratio, 3.692; 95% CI, 1.109 to 12.294; P = 0.033). Patients with KIT exon 17/18 mutation had a longer PFS (hazard ratio, 0.097; 95% CI, 0.011 to 0.871; P = 0.037). Ripretinib was associated with a favorable safety profile, grade 3 treatment-emergent adverse events (TEAEs) were recorded in 5 patients. No grade 4 or 5 TEAEs were recorded. Conclusions: The ECOG performance status of the patients that received ripretinib in this study is poor. Ripretinib can provide clinical benefit in advanced GIST in real-world China with a favorable safety profile. Immediately switch from the latest TKI to ripretinib after progression will prolong the survival of the patients.
Prevalence and genomic landscape of BRAF alterations across gastrointestinal cancers.
Authors: Driscoll David , Wang Min , Alyaqoub Fadel S. , Udhane Sameer S. , Szelinger Szabolcs , Jalkanen Aimee , Hall David W. , Hoag Jess R , LoBello Janine R. , Baehner Frederick L. , Thakkar Snehal Govind , Basu Gargi D. 
Published: January 2023

806 Background: BRAF V600E mutations can lead to activation of the MEK/ERK pathway. The combination of dabrafenib plus trametinib was recently FDA-approved for use in these BRAF V600E altered unresectable or metastatic cancers. BRAF non-V600 alterations also increase phosphorylation of MEK and ERK and are potential candidates for MEK/ERK inhibitors. Here we examine the frequency of BRAF mutations and their genomic background across GI cancers. Methods: The Oncomap ExTra genomic profiling assay utilizes tumor-normal, whole-exome, whole-transcriptome DNA and RNA sequencing to identify somatic alterations in tumors. The assay detects single-nucleotide substitutions, indels, copy number alterations, alternative transcripts, and gene fusions. Tumor mutational burden (TMB) and microsatellite instability (MSI) are also assessed. The frequency of BRAF and other gene alterations were identified across all GI cancers. Reported BRAF alterations were limited to those linked to an FDA approved therapy, clinical trial eligibility, and those deemed significant from review of the literature. Results: A total of 1927 patients with GI cancers were assayed between April 2018 to July 2022. The BRAF gene was mutated in 85 (4.4%) patients, which included 53 (2.8%) that were V600E and 32 (1.5%) that were non-V600, representing 37.6% of BRAF mutations. Colorectal and small bowel cancers had the highest frequencies of BRAF mutations at 7.6% and 7.1% respectively, and the frequency was lower in other GI cancers (0-2.3%). In addition to BRAF V600E, other mutations occurred across the kinase domain, including D594 (0.6%), K601E (0.3%), G466 (0.3%) and G469 (0.2%). BRAF fusions were found in 1 CRC and 2 pancreatic cancer cases. BRAF mutational status (altered versus not) was significantly associated with mutations in several other genes. In addition, BRAF status was significantly associated with TMB-high and MSI-high. Conclusions: Analysis of whole-exome and whole transcriptome sequencing data found actionable BRAF mutations in 4.4% of GI cancer patients, 37.6% of whom had BRAF mutations not at V600. Several biomarkers were significantly associated with BRAF alterations. Assays that are limited to DNA sequencing, or to targeted gene panels, may not detect mutations and fusions that could aid in therapy selection and prognosis. [Table: see text]
The Wnt signaling pathway in gastrointestinal cancers.
Authors: Gatalica Zoran , Dogruluk Turgut W , Noel Pawan , Dombrowski Susan M. , Hong Lenny , Barbi Michelle , Chandrasekaran Thiruppavai , Basu Gargi D. , Hall David W. , Hoag Jess R , Kundranda Madappa N. 
Published: January 2023

807 Background: Activation of the Wnt signaling pathway leads to increases in β-catenin levels, which subsequently increases transcription of various genes, including those involved in cell proliferation. Dysregulation of the Wnt signaling pathway has been observed in numerous gastrointestinal (GI) cancers. Here we examine Wnt pathway activation across all GI cancers by investigating alterations in certain genes of the Wnt pathway, which may identify patients eligible for clinical trials. Methods: The Oncomap ExTra genomic profiling assay utilizes tumor-normal, whole-exome, whole-transcriptome DNA and RNA sequencing to identify somatic alterations in tumors. The assay detects single-nucleotide substitutions, indels, copy number alterations, alternative transcripts, and gene fusions. Alterations in genes that activate Wnt signaling and their frequency across all GI cancers was determined. Results: A total of 1928 patients assayed April 2018 to July 2022 were included. The Wnt signaling pathway was activated in 922 (47.8%) patients. Wnt pathway activation varied substantially across GI cancers, from 81.1% in colorectal cancer (CRC) to 3.4% in anal cancer. APC was the most commonly altered gene in CRC, small bowel and biliary carcinomas. CTNNB1 was predominant in liver (41.2%), MEN1 in neuroendocrine (14.6%), and RNF43 in gastric (9.4%) cancer. Of 921 patients with alterations in the Wnt pathway, 5.2% had a co-mutation in another Wnt pathway-related gene. RSPO2/3 fusions were found in 4 CRC, 1 stomach, 1 biliary, and 1 small bowel cancer and were mutually exclusive with other alterations in the Wnt pathway. Conclusions: Wnt signaling is activated in about half of all GI cancers, and APC alterations are the most frequently observed. Whole transcriptome profiling allowed us to identify RSPO2/3 fusions, which also contribute to activation of the Wnt pathway. Wnt activation appears to be a particularly important in CRC, with 81.1% of CRC having a Wnt pathway alteration. Our results highlight the therapeutic potential of targeting the abnormal Wnt/β-catenin signaling pathway in GI malignancies. [Table: see text]
Factors associated with weekend emergency department visits in patients with GI cancer.
Authors: Parekh Jay , Lee Victor , Yerlikaya Aslihan , Abraham Soniya , Park Henry Soo-Min , Stein Stacey , Jairam Vikram 
Published: January 2023

813 Background: Gastrointestinal (GI) cancers account for highest ED revisits among cancer patients. Weekend ED visits are also associated with higher mortality. We aimed to analyze factors associated with weekend ED visits among GI cancer patients. Methods: Nationwide Emergency Department Sample (NEDS) database was queried from 2009 to 2017 for ED visits with GI primary tumor. ED visits were characterized by demographic, socioeconomic factors, hospital characteristics and primary cancer. Univariate and multivariate logistic regression were performed. Data was analyzed using Stata. Results: From 2009 to 2017, 6,862,077 ED visits associated with GI cancer were analyzed and 1,811,111(26.4%) visits were on weekend. Weekend visits were associated with increased in-hospital mortality (odds ratio [OR] 1.06; 95% Confidence Interval [CI] 1.04-1.). Weekday mortality was 3.8%, while weekend was 3.9%. Weekend visits were negatively associated with presentation in 2013-2017 as compared to 2009-2012 (OR 0.96; 0.95-0.97), Northeast hospitals (OR 0.89; 0.88-0.91) compared to Midwest, teaching hospital status (OR 0.96; 0.95-0.97) compared to non-teaching and metastatic cancer (OR 0.96; 0.95-0.97) compared to non-metastatic cancers. Compared to colon, weekend admissions were also negatively associated with anorectal (OR 0.96; 0.95-0.98) and hepatobiliary cancers (OR 0.96; 0.95-0.98). Conclusions: Presentation between 2013 to 2017, teaching hospital status, Northeast hospitals and metastatic stage were associated with fewer weekend ED visits. These findings could be potentially explained by increased and primary care utilization. There was a statistically significant association between mortality and weekend admissions, however the absolute difference was only 0.1%. Possible explanations include potential differences in staffing, interventions and procedures over the weekends compared to weekdays. In comparison to colon, anorectal and hepatobiliary cancer patients are less likely to have weekend ED visits while pancreatic cancer patients are more likely to have weekend ED visits. Our findings may help GI oncologists identify patients at risk of weekend ED visits.[Table: see text]