bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colorectal Cancer Alliance: Promoting prevention and early detection with screening navigation and a personalized recommendation via a digital screening quiz tool for colorectal cancer.
Authors: Newcomer Kim , Guevara Alex , Pearson Marianne , Hall Lisa 
Published: January 2024

71 Background: Evaluating the effectiveness of a Colorectal Cancer screening navigation model delivered in a digital platform offered by a patient advocacy organization. Designed as a digital screening quiz tool and live navigation to promote CRC screening, the Colorectal Cancer Alliance’s Screening Quiz is a risk stratification tool that connects respondents to live certified cancer care navigators delivering evidence-based interventions to increase CRC screening, education and patient and family support. The framework utilizes small and mass media, one-on-one education and patient navigation services to help address and reduce barriers to care. Critical interventions which research shows that on-time screening for CRC leads to better outcomes. Methods: The Screening Quiz has been promoted through social sharing, community outreach, media, including influencer campaigns to increase outreach to at-risk communities. Questions assess personal and family history, hereditary syndromes, and demographics to provide a CRC screening recommendation based on current USPSTF guidelines. Respondents overdue for screening who opt in, are triaged to the Alliance’s patient navigation team for follow-up. This interaction includes phone calls and emails for symptomatic individuals or at high risk for CRC, telephonic and email for average-risk uninsured, and emails for average-risk insured. At-risk individuals are connected to resources, such as financial assistance, free at-home screening tests, and colonoscopy scheduling services. Results: July 2022 to August 2023, the Screening Quiz provided over 30,000 screening recommendations. The median age of respondents was 48; 33% of the respondents were between the ages of 45 to 64. Of the respondents, 29% were male and 71% were female. Most were White (74.3%), but nearly half of those who opted into navigation identified as BIPOC, including 14.4% Black/AA, 17.8% Hispanic or Latino, 7.7% Asian, and 2.5% AI/AN. Most respondents were symptomatic (65.5%) but 7.3% were asymptomatic high-risk. These two groups represented 88% of 1,851 respondents triaged to patient navigation. Conclusions: This digital screening tool and live navigation framework may serve as a key solution in driving CRC screening compared to other interventions. Providing access to live navigation, educational resources, and support services for CRC screening and diagnosis.The Alliance is uniquely positioned with its national network of volunteers, partners, and community presence to effectively reach at-risk communities. Aligning with the science of evidence-based interventions, the Alliance will continue to leverage the Screening Quiz in partnership with healthcare and community stakeholders to close Colorectal Cancer screening gaps.
Multicenter clinical validation of GutSeer: A cost-effective, blood-based assay for early detection and localization of major gastrointestinal cancers.
Authors: Chen Wanqing , Xia Changfa , Ma Chengcheng , Liu Yiying , Xu Minjie , Li Wei , Sun Jin , Gong Chengxiang , He Qiye , Zhang Yunzhi , Su Zhixi , Liu Rui 
Published: January 2024

739 Background: Gastrointestinal (GI) cancers account for over one-third of cancer-related deaths. We have previously developed GutSeer, a non-invasive assay utilizing cell-free DNA (cfDNA) methylation and fragmentation signatures, to cost-effectively detect and localize five major GI cancers, including colorectal (CC), gastric (GC), liver (LC), esophageal (EC), and pancreatic cancer (PC). Methods: GutSeer was initially developed and validated in a large retrospective cohort of 1844 plasma samples, demonstrating excellent performance with specificity, sensitivity, and tissue of origin (TOO) accuracy at 96.7%, 86.2%, and 82%, respectively. In this study, we conducted a blind, multi-center clinical test for further validation. Participants were recruited from two centers, Beijing (BJ) and Shanghai (SH). Cohort BJ included 42 participants (20 healthy, 22 cancer), and Cohort SH comprised 403 participants (105 healthy, 123 benign, 175 cancer). Over half of the cancer samples in Cohort SH were in early-stage disease (TNM stages I and II). Results: In Cohort BJ, GutSeer showed 100% specificity, 68.2% sensitivity, and 86.7% TOO accuracy. Individual cancer type sensitivities within Cohort BJ were 100% for CC, 57.1% for EC, 75% for GC, 40% for PC, and 100% for LC. In Cohort SH, GutSeer exhibited 94.6% specificity for healthy samples and 86.2% for benign conditions. For cancer samples in Cohort SH, the overall sensitivity achieved 78.9%, with specific sensitivities of 92.3% for CC, 81.0% for EC, 78.4% for GC, 52.9% for PC, and 86.4% for LC. Moreover, GutSeer also efficiently detected early-stage cancers, with stage-wise sensitivities ranging from 64.7% (stage I) to 96.3% (stage IV). TOO accuracy in Cohort SH was 79.0%, with individual cancer types achieving accuracies from 71.7% to 94.7% (72.2% for CC, 71.7% for EC/GC, 94.7% for LC, and 77.8% for PC). Conclusions: GutSeer demonstrates promising potential as a cost-effective, non-invasive test for early detection and localization of major GI cancers. Its consistently high performance in both retrospective and multi-center blind clinical tests implies its potential to revolutionize the screening and diagnosis paradigm for GI cancers.
A review of comprehensive genomic profiling testing in a Japanese single institution.
Authors: Funatsu Nozomi , Takao Misato , Kanemasa Yusuke , Horiguchi Shinichiro , Sadato Daichi , Harada Yuka , Kawai Kazushige , Yamaguchi Tatsuro 
Published: January 2024

740 Background: In Japan, comprehensive genomic profiling (CGP) testing, including OncoGuide and FoundationOne CDx (F-1), were approved in June 2019 for patients with advanced solid tumors. Here, we report the landscape of CGP testing in our hospital. Methods: This study was conducted with a retrospective design to evaluate the clinico-genomic characteristics of patients who underwent CGP testing. OncoGuide is a panel using matched tumor tissue and blood sample, containing 124 genes, developed by the National Cancer Center. F1 is a tumor-only panel, containing 324 genes, developed by Foundation Medicine Industry. Results: Of the 460 patients enrolled in this study, 376 and 84 underwent F-1 and OncoGuide, respectively. The most common primary tumor was colorectal cancer (93 pts), followed by malignant melanoma (33 pts) and pancreatic cancer (33 pts). Actionable gene alteration was detected in 304 patients (66.1%). The detected actionable genes were TP53 (55.9%), APC (27.8%), KRAS (22.6%), and BRAF (8.5%) in colorectal cancer, BRAF (10.1%), CDKN2A (30.2%), CDKN2B (9.4%), and TERT (33.3%) in malignant melanoma, and KRAS (18.8%), TP53 (54.3%), and CDKN2A (21.8%) in pancreatic cancer. The mean time from sample shipment to result receipt was 42.5 days. As a result of CGP testing, candidate anticancer drugs were found in 304 patients: however, 108 patients were not treated due to poor general condition, complications, or age, which limited access to clinical trials. In germline findings, a pathogenic germline variant of BRCA2 was detected in one patient in OncoGuide, and presumed germline pathogenic variants of MLH1, BRCA2, and PTEN were detected in 1, 13, 26 patients in F-1. Conclusions: In Japan, CGP testing found candidate anticancer drugs, however it requires a significant amount of time to receive treatment because of limiting access to ongoing clinical trials and being typically performed after standard chemotherapy. Therefore, improving access to clinical trials, including determining the timing of testing and selecting appropriate cases, was critical.
Immune-related adverse events in patients with gastrointestinal cancer undergoing pembrolizumab monotherapy: A systematic review of clinical trials.
Authors: Naleid Nikolas , Mears Veronica , Kakish Hanna , Mahipal Amit , Chakrabarti Sakti 
Published: January 2024

744 Background: Pembrolizumab, an immune checkpoint inhibitor targeting programmed death 1 (PD-1), is widely employed in the treatment of various gastrointestinal (GI) cancers. This systematic review aims to assess the spectrum and incidence of immune-related adverse events (irAEs) associated with pembrolizumab monotherapy in GI cancer patients. Methods: A comprehensive search of PubMed/MEDLINE was conducted to identify full-text articles of clinical trials investigating pembrolizumab monotherapy in GI cancer patients. Two independent authors reviewed the articles and extracted data, with discrepancies resolved by consensus. Primary endpoints included the incidence of grade 3 or higher irAEs and the treatment discontinuation rate due to irAEs. Secondary endpoints encompassed the incidence of any-grade irAEs and specific irAEs such as pneumonitis, colitis, hepatitis, myositis, myocarditis, nephritis, pancreatitis, peripheral neuropathy, skin toxicity, endocrine toxicity, infusion reactions, and deaths. Results: After excluding duplicates and articles not meeting inclusion criteria, data extraction and analysis were performed on 25 selected articles. Common reasons for exclusion included concomitant use of chemotherapy or targeted therapy and trials involving non-GI cancer patients. The analysis included 2866 patients with a median age of 62 years, of which 29% were female. Tumor types included colorectal (13%), esophagogastric (46%), hepatocellular carcinoma (25%), and others (16%). The aggregate incidence of grade 3 or higher irAEs was 8.7%, with reported rates ranging from 3% to 41% across different trials. The incidence of any grade irAEs varied from 39% to 98%. The treatment discontinuation rate due to irAEs was 6.8%. The most common grade 3 or higher irAEs were hepatitis (3.6%), pneumonitis (0.8%), and colitis (0.7%). irAE-related deaths were infrequent (0.9%). Detailed irAE data are summarized in the Table. Conclusions: In GI cancer patients receiving pembrolizumab monotherapy, severe irAEs are rare. Treatment discontinuation and deaths attributed to pembrolizumab-related irAEs are infrequent, underscoring the safety profile of this therapy in patients with GI cancer. [Table: see text]
Efficacy of biomarker-matched therapy in clinical trials for advanced gastrointestinal cancers: A pooled analysis of SCRUM-Japan studies.
Authors: Hashimoto Tadayoshi , Fujisawa Takao , Machida Nozomu , Makiyama Akitaka , Boku Shogen , Kadowaki Shigenori , Takahashi Naoki , Oki Eiji , Morizane Chigusa , Sunakawa Yu , Komatsu Yoshito , Okano Naohiro , Esaki Taito , Ohta Takashi , Kato Takeshi , Ozaki Hiroshi , Iida Naoko , Nakamura Yoshiaki , Bando Hideaki , Yoshino Takayuki 
Published: January 2024

753 Background: We conduct the SCRUM-Japan MONSTAR-SCREEN, a nationwide molecular profiling project to facilitate the enrollment of patients with advanced solid tumors into matched clinical trials based on identified biomarkers. Here, we investigated clinical outcomes of patients with gastrointestinal cancers in this project. Methods: The SCRUM-Japan GI-SCREEN was launched for gastrointestinal cancers in 2015, followed by GOZILA, MONSTAR-SCREEN-1, and MONSTAR-SCREEN-2 for advanced solid tumors. The used profiling assay for genomic alterations was Oncomine Comprehensive Assay for tumor tissue in GI-SCREEN, Guardant360 for plasma in GOZILA, FoundationOne CDx for tissue and FoundationOne Liquid CDx for plasma in MONSTAR-SCREEN-1, and CARIS MI Profile for tissue in MONSTAR-SCREEN-2. Patients were treated in clinical trials or practice based on identified biomarkers. We analyzed data from patients with gastrointestinal cancers in this project. Results: Of 11,408 patients enrolled in our project as of May 22, 2023, 555 (5.0%) were enrolled in matched clinical trials based on identified biomarkers. The major cancer types that had matched clinical trials included colorectal (63.2%), biliary tract (12.4%), gastric (n=9.2%), esophageal (n=6.5%), and pancreatic cancer (n=4.7%). The objective response rate (ORR), median progression-free survival, and median overall survival (OS) for patients in matched trials were 27.8% (95% CI, 24.0% to 31.9%), 3.0 months (95% CI, 2.8 to 3.7 months), and 14.4 months (95% CI, 13.0 to 16.1). The major treatment lines in which investigational drugs were administered were third (24.6%) and fourth (16.0%) line. Evaluating by each drug target given to at least 20 patients, therapies targeting HER2 had the highest ORR of 46%, followed by PD-1/PD-L1 (33%), BRAF (30%), and MEK (28%). Antibody-drug conjugates demonstrated the highest ORR with 48.8%, followed by monoclonal antibodies at 37.7% and small molecule inhibitors at 23.0%. Overall, patients who received matched therapy in clinical trials or practice had significantly longer OS than those who did not (hazard ratio, 0.76; 95% CI 0.69 to 0.84; P <0.01). Conclusions: Our nationwide molecular profiling project has facilitated the enrollment of patients with advanced gastrointestinal cancers in clinical trials. Furthermore, it demonstrated a survival benefit by providing patients matching targeted therapy.
Role of circulating tumor DNA in metastatic appendiceal neoplasms: A systematic review.
Authors: Shahzad Moazzam , Dineen Sean P. , Ahmed Mamoon , Basharat Ahmad , Khalid Muhammad Fareed , Noor Jawad , Amin Muhammad Kashif , Imanirad Iman 
Published: January 2024

757 Background: Circulating tumor DNA (ctDNA), tumor DNA fragments detected in blood sourced from primary malignancy, is an emerging non-invasive tool in oncology for screening, diagnosis, and surveillance. Here, we analyze its utility in patients with metastatic appendiceal neoplasms. Methods: Following PRISMA guidelines, PubMed, Cochrane, and Clinicaltrials.gov were searched for ‘Appendiceal Neoplasms’ AND ‘Circulating Tumor DNA’. Four original studies reporting the role of ctDNA in appendiceal cancer were included after screening 195 articles. Results: A total of 196 patients were included in the review. (Table) The total number of collected samples was 209 and 41% were tested positive for ctDNA. Singh et al. 2023 reported eight stage IV appendiceal cancer patients with the median age of 64.5 (45-75) years. 37.5% were tested positive for ctDNA while 37.5% had undetectable ctDNA despite having residual peritoneal disease and 25% had insufficient DNA from tumor specimen. López-Rojo et al. 2020 reported 50% ctDNA positive rate. All included patients had KRAS mutation and received hyperthermic intraperitoneal chemotherapy (HIPEC). On 36.5 months follow-up all the patients were alive but one out of two ctDNA positive patients had a relapse at 39 months follow-up. Kothary et al. 2022 reported 51% ctDNA positivity and 11% had longitudinal ctDNA measurements available which correlated well with their disease course. Zeineddine et al. 2023 collected 160 blood samples from 147 patients. Of 75% with radiographically metastatic disease, 38% had positive ctDNA while out of 25% with no radiographically metastatic disease, 38% had positive ctDNA. The overall survival and progression free survival for ctDNA positive patients was 46.2 months and 60 months, respectively, versus not reached for ctDNA negative patients. When stratified according to tumor grade, the ctDNA detection rate was 22% for well-differentiated, 39% for moderately differentiated, and 49% for poorly differentiated tumors. Conclusions: The use of ctDNA in metastatic appendiceal tumor is not widespread and detection rates are heterogenous. It was observed more in poorly differentiated appendiceal cancers but further studies are needed to evaluate its utility in clinical practice. [Table: see text]
Perceptions of cancer prevention options for Lynch syndrome (LS) in a multi-national convenience sample.
Authors: Hall Michael J. , Singhal Sachi , Osorio Nadine , Chavez Juan Pablo , Riggs Emma D. , Chertock Yana , Daly Mary Beryl 
Published: January 2024

77 Background: LS is among the most common cancer (CA) syndromes affecting 1:280 individuals and portends high lifetime CA risk. Clinical trials are currently evaluating whether frameshift peptide vaccination (FSPVAX) could reduce LS CA risk. FSPVAX enhances immune response to diverse FSP neoantigens in MSI-H tumors and has shown promising results in an MSH2-mutant mouse model and metastatic MSI-H CRC. However, negative public attitudes towards vaccination and evidence suggesting low uptake of ASA chemoprevention (CP) among patients with LS could undermine success of this novel therapy. Here, we benchmark attitudes towards FSPVAX for CA prevention against colonoscopy (COLO) and aspirin or NSAID chemoprevention (CP). Methods: The PREVENTLynchII survey (IRB 20-8014) was distributed electronically to 1) participants in the Fox Chase Cancer Center (FCCC) Risk Registry and 2) members of two online LS support groups. Patients were invited to complete the one-time survey after providing informed consent. Demographic and personal CA history were collected. Attitudes were measured on 9-point scales indicating low vs high agreement with belief statements: e.g. “Colonoscopy is a convenient way to lower my risk of LS-related CA.” Results: Overall 296 participants at FCCC, nationally, and internationally completed the survey. Median age was 52.6 years [23-78], 84% female, and 95% White. Affected genes included MLH1 (20.3%), MSH2/EPCAM (35.5%), MSH6 (28.7%), and PMS2 (15.5%). Use of CP was uncommon (32.1% and 5.1% respectively). Stratified analyses of COLO perceptions by sex, age, and personal history of CA showed no differences. Interestingly, US pts viewed ASA as more convenient than non-US, and with lower risk of side effects (p=0.007), but were no more likely to use or recommend CP. Compared to COLO, FSPVAX was overall viewed as more convenient, but side effect concerns were higher, and perceptions of efficacy were lower (all p<0.001), while compared to CP, FSPVAX was less convenient and fostered greater concerns about side effects, but was viewed as having higher potential preventive efficacy (all p<0.001). FSPVAX perceptions showed high variability: pts >50 (p=0.003) and CA pts (p=0.01) saw FSP as more convenient (p=0.003) than younger and unaffected pts. CA pts reported higher reassurance than unaffected (p=0.04), while those >50 were more likely to participate in an FSPVAX study (p=0.04). US pts perceived more side effect risk of FSPVAX than non-US (p=0.003). Conclusions: Concerns about ASA CP and FSPVAX convenience, side effects, and efficacy are common among US and international patients with LS. [Table: see text]
Retrospective review of compliance with guideline-directed germline testing in microsatellite instability-high colorectal cancer treated at the Veterans Health Administration.
Authors: Williams Silva Karly , Cohen Stacey A. , Frias Kletecka M. Carmen , Ioannou George , Aslan Deniz , Becker Daniel Jacob , Kenny Avi , Montgomery Robert Bruce 
Published: January 2024

86 Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome that confers an increased risk of colorectal cancer (CRC). As clinical and history features under-recognize LS cases (3-5% of CRC), universal screening of CRCs for LS is recommended. Patients whose CRCs are mismatch repair protein deficient (dMMR) and/or microsatellite instability high (MSI-H) are recommended to have subsequent genetics evaluation to screen for germline mutations. Confirmed LS changes cancer surveillance recommendations for affected patients and their relatives. Within Veterans Health Administration (VHA), GT is ordered by genetic counselors at genomic medicine telehealth centers (GMTC), after initial consultation. We aim to quantify rates at which CRC patients treated at the VHA complete germline testing (GT) when indicated. Methods: The electronic health records (EHRs) of VHA patients with known dMMR/MSI-H CRC were reviewed. Cases were extracted from both Veterans Affairs (VA) Puget Sound and referral VA MSI testing laboratories. Surgical pathology reports and clinical documentation were reviewed in Joint Longitudinal Viewer (JLV) to determine if GT was indicated and reason for non-testing, if not performed. Patients with known LS prior to development of CRC were excluded, and patients with dMMR in MLH1 or MSI-H with concurrent BRAFV600 mutation and/or MLH1 hypermethylation were considered to have sporadic CRC. Results: Of 110 patients with abnormal tumor LS screening; 39 (36%) patients’ tumor tissue underwent IHC for dMMR, 16 (14%) underwent PCR for MSI, and 55 (50%) had both. 45 (41%) patients were classified as somatic MSI-H. 65 (59%) patients met criteria for referral for GMTC and GT. Of these 65, 49 ultimately did not undergo GT and 16 did, which confirmed 4 cases of LS and revealed 1 variant of uncertain significance in the MLH1 gene. Reasons for non-testing were: 7 (14%) declined all cancer testing and treatment after CRC diagnosis or were lost to follow-up/declined establishment of cancer care, 3 (6%) declined referral to GMTC, 14 (29%) accepted referral to GMTC but never had consultation, 7 (14%) accepted referral to GMTC but declined GT when offered, and 18 (37%) were never offered GMTC referral or GT. Conclusions: A majority of dMMR/MSI-H cases with an indication for GT were referred for genetic counseling, but only a small subset completed testing. This analysis identified multiple areas for improvement, including a lack of recognition by providers for the need for GT, and lack of completion of testing by patients at multiple levels. Further evaluation of VHA-specific barriers is needed to improve the quality of delivered care.