bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel classification of small bowel adenocarcinoma based on a hidden genome classifier: A multi-institutional study.
Authors: Schleimer Lauren E. , Ethun Cecilia Grace , Court Colin , Chou Joanne F. , McIntyre Sarah Margaret Helena , Walch Henry S. , Sigel Carlie S. , Sharib Jeremy , Masoud Sabran , Chen Wei , Aveson Victoria , Wang Huamin , Katz Matthew H. G. , Overman Michael J. , Lidsky Michael , Maithel Shishir K. , Poultsides George A. , Fields Ryan , Gonen Mithat , Jarnagin William R. 
Published: January 2024

724 Background: Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. Data describing the clinical and pathologic characteristics of this disease are sparse, and few studies examine the genetic footprint of SBAs within the continuum of the gastrointestinal tract. Methods: All patients with small bowel adenocarcinoma for whom primary tumor tissue was available from 1993 to 2021 at six institutions were included. A hidden genome classifier (HGC) was developed based on genomic features from 286 gastroesophageal cancers (foregut) and 286 colorectal cancers (hindgut) using targeted tumor sequencing. The SBA samples were run through the HGC to obtain the predicted probability of either foregut or hindgut lineage. For patients submitted to curative intent resection, overall survival (OS) was calculated from 90 days post resection until date of last follow up. Cox regression was used to examine factors associated with OS and to construct the multivariable model. Results: Of a total of 243 patients with SBA, 60% were male. The most common anatomic locations were duodenum (53%), jejunum (28%), and ileum (12%). HGC prediction of foregut lineage was higher for duodenal (55%) and intestinal-type periampullary (64%) tumors, while prediction of hindgut lineage was higher for ileal (68%) and jejunal (54%) tumors. Patients were then divided into three HGC prediction groups based on the lowest-, highest-, and inter-quartile ranges: foregut (n=61), characterized by gene amplification of CDK12, CD3, EGFR, and KRAS and cytoband segmentation of chromosomes 8-p21.1 and 15-q26.3; hindgut (n=61), characterized by APC and KRAS mutations; and mixed-type (n=121) with elements of both. Among those undergoing curative-intent surgery (n=160), median OS was 73 months. On multivariable analysis, HGC prediction group (hindgut vs mixed-type, HR 3.22, 95%CI 1.54-6.73), age (HR 1.03, 95%CI 1.01-1.05) and positive lymph node status (HR 1.96, 95%CI 1.02-3.76) were associated with decreased survival (Table). Neither anatomic site nor the presence of other driver mutations was associated with survival. Conclusions: Small bowel adenocarcinomas display genomic heterogeneity. A novel hidden genome classifier that stratifies SBAs based on homology to foregut or hindgut genomic alterations may be superior to anatomic location for characterizing disease biology. Additional studies are needed to validate and further explore these findings. [Table: see text]
Diversity of patients enrolled in SWOG gastrointestinal cancers therapeutic trials.
Authors: Safyan Rachael A , Colby Sarah , Figueroa-Moseley Colmar , Guthrie Katherine A. , Chiorean E. Gabriela , Philip Philip A. 
Published: January 2024

726 Background: Racial/ethnic minorities, elderly, and rural populations are underrepresented in clinical trials. Globally, gastrointestinal (GI) cancers represent more than a quarter of all cancers, and socioeconomic and lifestyle factors impact their incidence. Additionally, racial/ethnic disparities exist across GI tumor types, including early-onset colorectal cancer, and are associated with survival outcomes. Here we examine the proportion of women and minority participants with GI malignancies enrolled on SWOG Cancer Research Network therapeutic trials. Methods: We analyzed data on participants enrolled to SWOG phase I-III GI cancers treatment trials launched and completed between 2011-2021 according to sex, age (< 70 years vs ≥ 70 years), ethnicity (Hispanic vs not Hispanic), Race (Black vs Asian/Pacific Islander (PI) vs Native American vs White), insurance type (Medicaid or no insurance vs other), and residence types (classified as urban, large rural, small rural, and isolated small rural) using Rural-Urban Commuting Area (RUCA) codes based on zip codes. Participants reporting any category of Black, Asian/PI, Native American, or Hispanic were considered minority. Results: In total, n=1486 participants from 10 trials (S1005, S1115, S1201, S1310, S1313, S1406, S1505, S1513, S1613, S1815) conducted in 5 different GI cancers categories were enrolled, of whom 696 (46.8%) were women and 313 (21.1%) were minority. The five cancer types represented were biliary tract (34.0%), colorectal (10.8%), esophageal (4.8%), gastric/gastroesophageal junction (GEJ) (14.5%), and pancreatic (35.9%). Overall, 696 (46.8%) were female, 94 were Black (6.3%), 83 (5.6%) were Asian/PI, 5 (0.3%) were Native American, 132 were Hispanic (8.9%), 349 (23.5%) were ≥ 70 years, 1263 (85.0%) lived in an urban area, and 155 (10.4%) had Medicaid or no insurance. Minority participants were younger on average than non-minority participants (mean 58.7 vs 63.1, p<0.001), more likely to live in urban settings (92.7% vs. 82.9%, p<0.001) and have Medicaid or no insurance (26.5% vs. 6.1%, p<0.001). Over one-third (37.9%) of Hispanic, 22.3% of Black, and 13.3% Asian/PI participants vs 8.0% of White participants had Medicaid or no insurance. Women’s participation varied according to cancer type, ranging from 8.3% for esophageal to 56.2% for biliary tract, as did minority participation, ranging from 5.6% for esophageal to 36.6% for gastric/GEJ. Conclusions: Our findings suggest that racial/ethnic minorities, the elderly, and those residing in non-urban settings were less likely to enroll in SWOG GI cancers treatment trials than were whites, younger patients, and urban residents. Efforts are needed to enhance diverse enrollment, to break down barriers preventing minority participation, and to improve trial access to minimize disparities.
Utility of gene expression–based cancer classification in diagnosis of malignant peritoneal mesothelioma (MPeM): Filling in the gaps in standard pathologic work-up for a rare cancer.
Authors: Allam Joelle , Ma Li , Estrella Jeannelyn , Willett Anneleis , Beaty Karen A. , Matamoros Aurelio , Lano Elizabeth A , Fournier Keith F. , Treuner Kai , Raghav Kanwal Pratap Singh , Huey Ryan W 
Published: January 2024

728 Background: Malignant peritoneal mesothelioma (MPeM) is a rare cancer (incidence of 0.12 per 100,000) and an arduous diagnostic challenge, requiring skillful evaluation by expert pathologists. Subjective and experiential immunophenotyping coupled with inattention to this rare entity causes delayed or misdiagnosis and leads to suboptimal treatment and outcomes. Gene-expression-based cancer classification offers an objective molecular assessment of the tissue of origin for cancers with uncertain diagnosis and improves diagnostic accuracy for MPeM compared to standard pathology. Methods: We retrospectively evaluated 23 patients (pts) with cancer of unknown primary (CUP) or uncertain diagnoses, with peritoneal/retroperitoneal carcinomatosis and reported as malignant mesothelioma using a 92-gene assay (CancerTYPE ID), a validated classifier for predicting tumor types, between January 2013 to December 2016. Pathology was verified by central review. Clinicopathologic data including immunohistochemistry (IHC) was collected using archived pathology specimens and reports. Results: Pts had a median age of 64 years (range: 39 – 93) at diagnosis, 57% were females and 74% had biopsy from omentum/peritoneum. Original histopathology was reported as poorly differentiated in 81% and as adenocarcinoma, carcinoma and malignant neoplasm in 10 (43%), 7 (30%) and 6 (27%) of cases, respectively. The number of IHC stains performed ranged between 0 and 28 (median: 10). Key IHC stains are shown in the table. Conclusions: In this cohort of CUP or uncertain diagnoses with a molecular cancer classification of malignant mesothelioma, we found huge variability and critical gaps in pathological work-up. Integration of molecular cancer classification using the 92-gene assay helped resolve this diagnostic uncertainty, further supporting its clinical utility to complement standard pathology. The impact of these findings goes beyond just MPeM and may benefit numerous pts with orphan cancers, who account for nearly 20% of all cancers diagnosed globally. [Table: see text]
Comprehensive analysis of differentially methylated regions in colorectal cancer (CRC).
Authors: Solari Omid , Constantin Tudor , Jiang Yuqian , Chan Wengching , Tunc Ilker , Srinivasan Preethi , Kordi Misagh , Santaguida Marianne , Mitchell Breeana L. , Aleshin Alexey , Swenerton Ryan , Babiarz Joshua , Kawli Trupti , Reiter Johannes G. 
Published: January 2024

73 Background: Epigenetic alterations have been shown to govern many disease states, including cancer. A key epigenetic mark is the DNA methylation of CpGs. Large studies, like The Cancer Genome Atlas, have shown that DNA methylation can differentiate between cancer status and type. Here, differentially methylated genomic patterns were defined between patients with CRC and healthy individuals by utilizing patterns of co-methylation of adjacent CpG loci. Methods: Deep, whole genome bisulfite sequencing (WGBS) was conducted on DNA samples from 100 healthy individuals (median effective coverage of 352x±38x) and from 75 patients with CRC (median effective coverage of 48x±18x). The two cohorts were chosen to be balanced in terms of age (CRC: 58±11 years; healthy: 57±8 years) and to represent major ethnicities in the USA, and the CRC cohort was chosen to represent all stages, histologies and morphologies, and microsatellite instability (MSI, 23%). A novel machine learning model was developed to discover differentially methylated regions between the healthy and CRC cohorts as well as between subpopulations within the CRC cohort, including age, sex, stage, histology, and MSI vs microsatellite stability (MSS). Results: In total, we discovered 132,911 differentially methylated regions between healthy and CRC cohorts, spanning more than 1.14 million CpGs. 76% of all discovered regions were hypermethylated (70% CpG islands, 1.3% CpG shelves, 21% CpG shores) and the rest were hypomethylated (7.3% CpG islands, 8.6% CpG shelves, 25% CpG shores). We also discovered 220 hypermethylated regions that were differentially methylated between CRC MSI samples and CRC MSS samples and healthy cfDNA samples. Furthermore, we discovered subtype-specific differentially methylated regions, such as 62 hyper-methylated regions that were differentially methylated between mucinous adenocarcinoma samples and the rest of the cohort. Conclusions: Based on deep WGBS data from heterogeneous cohorts, representative of the US population eligible for CRC screening, we identified many differentially methylated regions as strong biomarker candidates for the early detection of cancer. Compared to recurrently mutated driver genes in CRC, we find that differential methylation profiles of CRC samples are generally much more homogenous and are therefore ideal biomarkers for targeted sequencing panels with the purpose of early cancer detection. Further, analysis of these patterns based on clinicopathologic factors enabled discovery of subtype specific markers, which can be incorporated to ensure equivalent performance for underrepresented subtypes or subpopulations.
A retrospective analysis of the efficacy and safety of imatinib in elderly patients with advanced gastrointestinal stromal tumor.
Authors: Awatsu Takahito , Hirano Hidekazu , Matsuguma Kunihito , Hirose Toshiharu , Okita Natsuko Tsuda , Shoji Hirokazu , Takashima Atsuo , Kato Ken 
Published: January 2024

730 Background: Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor arising from the gastrointestinal tract, characterized by a high predominance of the elderly population. Imatinib is the standard first-line therapy for advanced GIST with a median survival of around 4 years in pivotal clinical trials. However, clinical data for the elderly population is not known well. The aim of this study is to evaluate the efficacy and safety of imatinib for advanced GIST in the elderly population in comparison with the non-elderly population. Methods: We extracted clinical data of patients with advanced GIST treated with imatinib as first-line therapy at our institution between January 2010 and July 2023. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events (AEs) were assessed and compared between the elderly group (age: ≥ 70 years, E group) and the non-elderly group (age: < 70 years, NE group). Multivariable analyses were performed using Cox proportional hazard models to evaluate the prognostic significance of age groups. Results: A total of 91 patients were included in this analysis with 32 patients in the E group and 59 patients in the NE group with a median follow-up duration of 39.8 months. Patient characteristics were as follows (the E group vs. the NE group): median age 76 (70–90) vs. 54 (29–69) years, male: 50% vs. 56%, performance status 0: 19% vs. 63%, disease status (: 47% vs. 44%), stomach primary 44% vs. 34%, KIT mutation (exon 11: 50% vs. 61%), and maximum tumor diameter (≥8cm: 66% vs. 51%). The proportion of patients with a reduced starting dose of imatinib was significantly higher in the E group (34% vs. 2%, p <0.0001). Median PFS in the E group and the NE group were 29.4 months and 60.0 months (HR=2.04, log-rank p=0.035). Median OS in the E group and the NE group were 91.5 months and not reached (HR=2.74, log-rank p=0.02). ORR was 53% in the elderly group and 66% in the non-elderly group (p=0.32). In for OS, age was not an independent prognostic factor (HR=2.09, p=0.14) with a significant independent prognostic factor of disease status (unresectable/initially metastatic vs. recurrent (reference): HR=3.58, p=0.03). The occurrence of ≥ grade 2 non-hematologic AEs was more common in the elderly group compared to the non-elderly group (78% vs. 32%, p<0.001). Conclusions: The elderly population with advanced GIST may achieve a survival period comparable to that observed in pivotal trials with imatinib. Even with reduced doses of imatinib, careful monitoring is necessary because of the high frequency of non-hematologic ≥ grade 2 AEs in the elderly population.
Patient-reported outcomes in patients with gastrointestinal cancer on oral chemotherapy.
Authors: Zhang Kevin Juan , Tehranchi Kian , Academia Emmeline C , Celmen Melis , Doolin Jim W , Hotait Mohamad , Lasoff Arielle , Tong Patricia , Berkowitz Seth J , Bullock Andrea J. , Zerillo Jessica Ann 
Published: January 2024

732 Background: Over the last several years, patient reported outcomes (PROs) have been demonstrated to address patient symptoms, improve outcomes, and reduce health care utilization. We aim to provide an electronic PRO (ePRO) tool for gastrointestinal (GI) oncology patients with the goals of improving adherence, reducing toxicity, and enhancing patient access to the clinical team. Methods: Patients are provided an ePRO tool consisting of a cellphone app integrated into the electronic health record with questions on adherence and 10 questions on symptoms adapted from the NCI PRO-CTCAE for local use. Emails are sent to the clinical team for nonadherence, new or worsening symptoms, or patient requested callback. Outcomes including time to first symptom assessment, emergency department (ED) visit and/or hospitalization at 30 and 90 days from enrollment will be compared with historical controls. Other outcomes including adherence and patient-reported access to the clinic will be assessed. Results: Six patients have been enrolled between May 1, 2023 and September 4, 2023. Five patients were newly starting oral chemotherapy agents and one patient had already been on therapy. Types of cancers included colon cancers (2), rectal cancer (1), pancreatic cancer (1), GIST (1), and cholangiocarcinoma (1). Types of oral chemotherapy included capecitabine (4), olaparib (1), and imatinib (1). Five patients have submitted a total of ten responses. Of the five who completed the ePROs, patients responded a median of one time (range 1-5). Reported symptoms were fatigue (4), pain (2), nausea (1), diarrhea (1), other symptoms (2) and a request callback (1). Seven (70%) responses have prompted emails alerts for clinical symptoms and one (10%) for adherence concerns. All alerts were resolved; average time to alert response 1.6 calendar days (range 1-3). Among historical controls, time to first symptom assessment after a new oral chemotherapy prescription was seven days, 30-day rate for ED and/or hospitalizations was 12%, and 90-day rate of ED visits and/or hospitalizations was 28%. Conclusions: Early data suggests a new process to manage ePROs can provide timely responses to email alerts. Of the responses thus far, 70% prompted email alerts due to clinical symptoms and 10% reported nonadherence, suggesting a high need for ongoing ePRO tools. Results are forthcoming on outcomes including time to symptom assessment/clinical action, ED visit/hospitalization and access.
Real-world data of anlotinib for gastrointestinal tumors with liver metastases in China.
Authors: Zhu Yujia , Zhuo Minglei , Xu Xiaoxian , Qin Yanru , Wang Zhehai 
Published: January 2024

738 Background: Patients with advanced gastrointestinal tumors, such as gastric cancer (GC), colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), biliary tract cancer (BTC) and pancreatic cancer (PC), often develop liver metastases with poor prognosis. Recent clinical studies have implicated that anlotinib (a novel anti-angiogenesis agent) could improve survival outcomes in gastrointestinal tumors with liver metastases, albeit with limited real-world evidence. This study aimed to report the efficacy and safety of anlotinib for gastrointestinal tumors with liver metastases in real-world practice. Methods: Demographic and clinical data of patients treated with anlotinib in any line of treatment for solid tumors with liver metastases (excluding primary liver cancer) was collected retrospectively through 5 large hospitals in China, between Jan, 2016 and Feb, 2023. The primary endpoints were progression-free survival (PFS) and objective overall response (ORR). Secondary endpoints included overall survival (OS), hepatic PFS (hPFS), hepatic ORR (hORR) and safety. In this abstract, we present data from patients with gastrointestinal tumors. PFS, hPFS and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: A total of 475 patients were enrolled in the study and 238 patients with gastrointestinal tumors were analyzed, including 73 (30.7%) GC, 71 (29.8%) CRC, 46 (19.3%) ESCC, 24 (10.1%) PC, and 24 (10.1%) BTC. 75.2% were <75 years old, 82.4% were male, 63.9% had a normal body mass index (BMI) (18.5-24 kg/m2), 87.8% received third-line anlotinib, and 90.3% received anlotinib monotherapy. At data cut-off (Feb 28, 2023), the median PFS was 5.90 months (95% CI: 5.23-6.77), the median hPFS was 6.20 months (95% CI: 5.27-6.77), and the median OS was 9.37 months (95% CI: 8.40-NR). There was no statistically significant difference according to the tumor types in terms of PFS (p=0.66), hPFS (p=0.8) and OS (p=0.72). We also found patients with a BMI < 18.5 kg/m2 had significantly shorter PFS (p=0.005) and hPFS (p=0.01). Adverse events (AEs) were manageable and tolerable, 30 (12.6%) patients had treatment-emergent adverse events (TEAEs) and 3 patients (1.3%) had ≥3 TEAEs. The most common treatment-related adverse events (TRAEs) were leukopenia (5.9%). Conclusions: To our knowledge, this is the first real-world report about anlotinib for gastrointestinal tumors with liver metastases in China, showed the clinical benefit of anlotinib in any line of treatment for gastrointestinal tumors with liver metastases and indicated that anlotinib could be a feasible treatment option in this specific population.
Clinicopathologic characteristics of patients with early-onset colorectal cancer.
Authors: Takagi Maki , Takao Misato , Funatsu Nozomi , Natsume Soichiro , Nakano Daisuke , Kawai Kazushige , Yamaguchi Tatsuro 
Published: January 2024

74 Background: Although the incidence of colorectal cancer has been declining in the United States in recent years, the incidence of young patients under 50 years of age has been reported to be increasing by several percent per year. Various studies have been conducted to characterize early-onset colorectal cancer (EO-CRC); however, it has been unclear whether it is a different entity from late-onset colorectal cancer (LO-CRC). In this study, we evaluated the clinicopathologic characteristics of EO-CRC in Japan. Methods: This study included 1,336 patients who underwent surgical resection for colorectal cancer at Tokyo Metropolitan Komagome Hospital from January 2015 to December 2019. We performed genetic testing for patients with suspected Lynch syndrome after providing genetic counseling and obtaining informed consent. The study protocol was approved by the Institutional Review Board. Results: Of the 1,336 colorectal cancer patients, 117 (8.9%) had EO-CRC with a median age at the diagnosis of 44 (17–49) years. Tumors were located at right-sided colon in 23 patients and left-sided colorectum in 92 patients with EO-CRC, respectively. The clinical stage of the tumor was I in 19, II in 23, III in 50, and IV in 23 patients with EO-CRC, respectively. Histologically, differentiated type, undifferentiated type, and mucinous carcinoma were 106, 5, and 3 patients, respectively. KRAS mutation was detected in 25.0% and BRAF V600E was detected in 4.3% of patients with EO-CRC. In the microsatellite status, MSI-High was detected in 6 (5.1%) patients with EO-CRC, of whom 3 (2.6%) were diagnosed with Lynch syndrome by genetic testing. Causative genes were MLH1 in 2 patients and MSH2 in one patient. In hereditary tumors, 2 patients with familial adenomatous polyposis were included in addition to Lynch syndrome. On the other hand, 1,219 (91.2%) had LO-CRC with 34.5% of KRAS mutation and 6.4% of BRAFV600E. MSI-High was detected in 69(5.7%) patients with LO-CRC，of whom 5 (0.4%) were diagnosed with Lynch syndrome. Lynch syndrome was significantly more common in EO-CRC (p=0.026). Conclusions: The alterations of KRAS and BRAF tended to be more frequent in EO-CRC. The frequency of hereditary CRC was more frequent in EO-CRC than in LO-CRC.