tbuckley/cabot-search huggingface dataset:
A comprehensive molecular and clinical study of patients with young-onset CRC.
Authors: Elham Nasrollahi, Shuaichao Wang, Rami Yanes, Cyndi Gonzalez, Tara Magge, Abigail E. Overacre-Delgoffe, Ronan Wenhan Hsieh, Ashley Mcfarquhar, Aatur D. Singhi, Anwaar Saeed, Curtis Tatsuoka, Ibrahim Halil Sahin
Journal: Journal of Clinical Oncology (2025)

235 Background: Young-onset colorectal cancer (YO-CRC), defined as colorectal cancer diagnosed in individuals under 50 years of age, has emerged as a distinct clinical entity, often presenting at advanced stages. Despite the increasing incidence, molecular and clinical underpinnings of YO-CRC remain underexplored. This study aims to characterize the clinical and molecular features of YO-CRC and to evaluate their impact on OS. Methods: We retrospectively reviewed 110 patients diagnosed with YO-CRCfrom our institution’s molecular database. All patients underwent next-generation sequencing. Demographic, clinical, and molecular data, including age, gender, race, tumor location, cancer stage, and mutation status (KRAS, NRAS, BRAF, POLE, ERBB-2/HER2, microsatellite status), were collected by reviewing electronic medical records. For OS analysis, we focused on patients diagnosed with de novo Stage 4. Cox proportional hazards regression and Kaplan-Meier survival analysis were utilized to assess the association of these factors with OS, with statistical significance determined by a p-value threshold of &lt;0.05. Results: Among 110 patients, N=44 (40%) presented with local disease (stage 1-3), while N=66 (60%) patients presented with de novo metastatic disease at the time of diagnosis. The median age at diagnosis was 44.5 years. The cohort consisted of 64% males and 36% females, with 84% of patients identified as White. Most tumors were left-sided (77%), including the distal colon/sigmoid (44%) and rectum (33%). KRAS and BRAF mutations were present 36% and 5.5%, respectively. ERBB-2/HER2 amplification and microsatellite instability were observed in 4.5% and 6.4% respectively. Tumor mutation burden (TMB) was &lt;10 in 57% of patients, with 14% having TMB &gt;20. CNV analysis revealed that 14% of patients had copy gains, 12% had concurrent gains/losses, and 31% had copy losses. Among the 66 Stage 4 patients, 44% had died by the time of analysis, with a median overall survival (OS) of 43.6 months (95% CI, 28.7 - not reached). KRAS mutation was found to be significantly associated with worse survival outcomes. Cox regression analysis reveals the prognostic significance of KRAS status, with a hazard ratio (HR) of 3.52 (95% CI: 1.59-7.76, P = 0.002 &lt; 0.05), indicating a significantly higher risk of death for KRAS-mutant YO-CRC patients. Conclusions: KRAS mutations are a key prognostic factor in YO-CRC, highlighting the need for therapeutic need to improve outcomes in this high-risk group.
Performance of a blood-based screening test for the early detection of colorectal cancer.
Authors: Yoshiaki Nakamura, Johannes Reiter, Joshua Babiarz, Preethi Srinivasan, Ehsan Haghshenas, Tzu-Chun Chen, Nathan Liang, Jayashree Joshi, Hsiao-Yun Huang, Misagh Kordi, Boris Gutman, Wen-Ching Chan, Ilker Tunc, Prashanthi Natarajan, Adham A Jurdi, Matthew Rabinowitz, Bree Mitchell, Trupti Kawli, Alexey Aleshin, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2025)

232 Background: While the clinical benefit of highly sensitive screening tools for colorectal cancer (CRC) has been established, adherence rates remain low. The convenience and familiarity of blood-based testing may reduce disease burden through greater access and compliance to regular and recommended asymptomatic screening. We report on preliminary findings from a minimally invasive blood-based early cancer detection (ECD) screening test for CRC. Methods: Plasma samples from healthy individuals and CRC patients sourced from biobanks were included. A targeted panel composed of differentially methylated genomic regions was developed. Using an independent cohort of plasma samples, a machine-learning model was trained to classify patient samples into cancer-free and CRC based on observed differential methylation patterns in circulating cell-free DNA (cfDNA). The assay performance was calculated based on concordance with clinical diagnosis (CRC, cancer-free). Results: The test set included 440 individuals: 127 with a confirmed CRC diagnosis (47% stage I/II, mean age 65±12 years, male 46%) and 313 without cancer (mean age 56±10 years, male 41%). Overall sensitivity was 95% (95% CI: 88-100%), and specificity was 91% (95% CI: 84-98%). Among patients with stage I disease, sensitivity was 92% overall, and 88% in screen-detected individuals. Sensitivity was 100% (n=14/14) in microsatellite-high tumors and 95% (n=107/113) in microsatellite-stable tumors. Multivariate analysis demonstrated associations between methylation signal and tumor size, cancer stage, and sex. Compared with a tumor-informed, variant-based circulating tumor DNA (ctDNA) test (Signatera), we observed a PPA (positive percent agreement) of 100%. Moreover, the differentially methylated allele fraction (DMAF) across target regions strongly correlated with variant allele frequencies (VAFs) from the tumor-informed test (Spearman’s correlation coefficient, 0.85). Conclusions: Using epigenetic markers specific for CRC, we developed a sensitive and specific blood-based test to detect cfDNA from early-stage and asymptomatic disease. The methylation signal strongly correlated with ctDNA VAFs from a clinically validated tumor-informed test and increased with cancer stage and disease burden. This test could serve as a means to increase patient adherence rates for CRC screening, thereby improving patient outcomes.
Real-world insights into immune-related adverse events (irAE) in gastrointestinal (GI) malignancies.
Authors: Ashish Manne, Samuel Paul, Eric Min, Pannaga Malalur
Journal: Journal of Clinical Oncology (2025)

545 Background: This retrospective review aimed to examine the incidence and baseline characteristics (BLC) that irAE risk in patients with gastrointestinal (GI) cancers undergoing immune checkpoint inhibitor (ICI) therapy at our institution. Methods: GI cancer patients who received at least one dose ICI-only between 1/1/2017 and 7/31/2021 at the Ohio State University were included in the study. The BLC including hematological and chemistry labs were extracted with immune-related adverse events (irAE) details. Statistical analyses included descriptive statistics, chi-square test, logistic regression, and matched pairs t-tests were performed. Results: Our analysis included 198 patients (14 anal (Al), 65 hepatobiliary (HPB), 46 lower (LGI) and 74 upper (UGI)) with irAEs reported in 37 patients (19%). Median age of irAE-group was 67 years (range: 26 to 88) with 54% males and 86% Caucasians. Most of them (n=36) in had single agent ICI. Pneumonitis was most frequently (n=7) noted followed by dermatitis (n=), colitis (n=5), hypophysitis (n=5), and hepatitis (n=4). Relatively rare ones were hypothyroidism (n=3), nephritis (n=2), encephalitis (n=2), diabetes mellitus (n=1), neutropenia (n=1), and myasthenia gravis (n=1). In irAE-group, 18 (49%) required hospitalization (≥ grade 3) and 5 (14%) had irAE-related deaths. Complete recovery from irAEs was reported in 20 patients (54%), with 13 patients (35%) restarting ICI therapy. The irAE incidence in HPB group was significantly higher than other GI malignancies (HPB vs. LGI vs. Al vs. UGI = 46% vs. 24% vs. 16% vs. 14%, p=0.004). History of asthma (41% vs. 16% (p=0.004) and female gender (26% vs. 15%, p=0.04) increased irAE-risk; presence of liver (9 % 22%, p=0.04) and &gt; 3 lung (8 vs. 21%, p=0.04) metastasis reduced the risk. Compared to non-irAE group, the irAE-group had significantly lower baseline (mean) whole blood cell count (WBC: 6.3 vs. 7.6 K/uL, p=0.02), neutrophil count (NC: 4.2 vs. 6.8 K/uL, p=0.04), and neutrophil-lymphocyte-count (NLR: 5.1 vs. 9.3, p=0.03), and lower albumin (3.7 vs. 3.5 mg/dL, p=0.02). A significant rise in NC (2.1 K/uL, p=0.0008), NLR (by 2.5, p=0.004), WBC (by 2.1 K/uL, p=0.002) from baseline was noted at irAE-incidence. Heterogeneity in the primary tumors and treatments received is a notable limitation of this analysis. Conclusions: Overall, the risk of irAEs in patients with GI cancers is relatively low, and certain BLC can predict their incidence.
Use of gene expression profiling to examine association between MUC1 and claudin 18 in gastrointestinal cancers: Implications for targeted therapies.
Authors: Aditya V. Shreenivas, Andrew M. Gaya, Muzammil Shaikh, Amish Vora, Shivam Shingla, Shriniwas Subhash Kulkarni, Ramin Ajami, Dadasaheb B Akolkar, Stefan Schuster, Vineet Datta, Darshana Patil, Sachin Apurwa, Rajan Datar, Sewanti Atul Limaye
Journal: Journal of Clinical Oncology (2025)

838 Background: Gastrointestinal tract cancers exhibit considerable molecular heterogeneity, which requires a detailed understanding of their distinct genetic profiles. Understanding the gene expression of other genes along with Claudin 18 (CLDN18) could provide insights into their interactions. Methods: We conducted a retrospective analysis of NGS profiling on 1,043 GI cancer tissue samples from three cohorts: Upper and Lower Gastrointestinal Cancer Cohort (GICC; n=651), Pancreaticobiliary Cancer Cohort (PBCC; n=316), and Hepatocellular Carcinoma Cohort (HCC; n=76). Immunohistochemistry data for PD-L1, Her2 and MMR proteins, NGS based Tumor mutation burden (TMB) and gene expression profiling (GEP) of 20,802 genes including CLDN18 was examined in a subset by targeted transcriptome profiling. We explored associations of these biomarkers with expression of CLDN18. Results: In GICC, frequent mutations were seen in TP53 (68%; 442), APC (33.5%; 218) and KRAS (33.3%; 217). PBCC, showed mutations in TP53 (62%; 197), KRAS (47%; 149) and CDKN2A (16%; 51). HCC showed mutations in TP53 (42%; 32), ARID1A (18%; 14) and KRAS (9%; 7). Amplifications were predominantly observed in MYC (13%; 120), ERBB2 (5%; 49) and CCND1 (5%; 44). Fusions were infrequent. All MSI-H cases (11/462; 2.4%) were observed in GICC. High TMB (≥10 muts/mb) was seen in 23% (111/481), stratified as 28% (90/318) in GICC, 13% (18/139) in PBCC and 10% (3/30) in HCC. Out of 321 samples analyzed for gene expression profiling, CLDN18 was significantly upregulated in 65 (20%) samples. The expression of CLDN18 did not show statistically significant correlation with Her2 (n=184), PD-L1 (n=231), TMB (n=228), or MSI (n=229); (p&gt;0.05). In subset where both CLDN18 and MUC1 expression were analyzed (n=118), all the CLDN18 positive tumors showed overexpression of MUC1. This finding was statistically significant (p&lt;0.05). Increased expression of MUC1 promotes cancer cell mobility promoting metastases. Expression of MUC1 can play an important role in the development of resistance to chemotherapy. MUC1 expression in cancer cells is associated with avoidance of immune defenses. Thus, this finding of CLDN18 and MUC1 association is especially relevant as the CLDN18 targeted therapies may be the potential avenue for the aggressive and chemo-resistant MUC1 expressing tumors. Conclusions: This study identifies potential association between MUC1 and CLDN18. GEP could enhance biomarker detection and support personalized treatment approaches. Future research should integrate these findings with clinical data to improve precision in GI cancer care.
Financial toxicity in patients with newly diagnosed hepatocellular carcinoma.
Authors: Seohyuk Lee, Esteban Garita, Santiago Sucre, Juan Jose Juarez, Mary Linton Bounetheau Peters, Andrea J. Bullock
Journal: Journal of Clinical Oncology (2025)

538 Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths and has been associated with significant patient (pt) financial liability, however no study has yet examined pt-reported measures of financial toxicity (FT) in this population. We sought to assess pt-reported FT in newly diagnosed HCC and to identify pt-, disease-, and treatment-related factors associated with FT. Methods: Pts with HCC were recruited prior to treatment initiation during their initial visit at a multidisciplinary liver cancer clinic at a tertiary care center between January 2023-May 2024. The Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT), a validated survey for assessing financial distress in pts with cancer (range, 0-44; lower scores reflect worse financial wellness), was completed by participants during their initial visit. Sociodemographic (age, sex, race, ethnicity, primary language, insurance status, employment status, marital status, highest education completed, household income, living arrangement, home zip code), clinical (Barcelona Clinic Liver Cancer stage, performance status, age-adjusted Charlson comorbidity index, albumin-bilirubin score, presence and etiology of chronic liver disease, Child-Pugh grade, MELD-Na score), and planned treatment (surgery, liver-directed therapy, systemic therapy, clinical trial enrollment) characteristics were evaluated by questionnaires or medical record review. The EORTC QLQ-HCC18 was used to assess pt-reported quality of life (QOL). Area Deprivation Indices were calculated using pts’ home zip codes. Mean COST-FACIT scores were compared using two-sided t test for binary variables and one-way ANOVA for non-binary variables. Results: Among 47 pts enrolled, 35 (74%) completed the COST-FACIT survey. Younger age (&lt;65 vs ≥65 yrs; mean, 20.3 vs 27.8; p=0.05), non-English primary language (non-English vs English; mean, 16.2 vs 26.7; p=0.04), less completed education (high school or earlier vs college or beyond; mean, 23.3 vs 32.0; p=0.02), and worse self-reported QOL (EORTC QLQ-HCC18 score ≥cohort median vs &lt;cohort median; mean, 21.4 vs 29.2; p=0.02) were significantly associated with worse FT. Although not statistically significant, Hispanic ethnicity (Hispanic vs not Hispanic; mean, 16.1 vs 26.4; p=0.07), lack of employment (not employed vs retired vs employed; mean, 15.5 vs 29.4 vs 24.3; p=0.07), and no plan for liver-directed therapy (no vs yes; mean, 17.9 vs 26.7; p=0.07) trended towards worse pt-reported FT. Conclusions: Among pts with newly diagnosed HCC, significantly higher pt-reported FT is associated with younger age, non-English primary language, less completed education, and worse QOL. Efforts are underway to longitudinally follow our study cohort to assess the course of self-reported FT over 1-year follow-up as well as its associations with treatment response and survival.
A global comparative study on MDT practices in the management of hepatocellular carcinoma in high-income countries (HICs) and low- and middle-income countries (LMICs).
Authors: Huang Zhiyong, Eduard Jonas, Lianxin Liu, Martin Smith, Hossam El-Deen Mohamed Soliman, Jiaping Li, Jizhou Wang, Wenzhe Fan, Ahmed Elsayed Esmaal Zeid, John Devar, Erlei Zhang, Qian Chen, Bichai Yin, Poka Yingjing Cui, Yufang Dong, Zoe (Zheng) Su, Pablo Azcue, Lucy Turner, Maria Teresa Campos Partera, Xiaoping Chen
Journal: Journal of Clinical Oncology (2025)

562 Background: As the sixth most common malignancy worldwide, hepatocellular carcinoma (HCC) accounted for 4.7% of all new cancer diagnoses in 2022. Low- and middle-income countries seem to bear a disproportionate burden of the disease, with over 50% of new HCC cases estimated to occur in China and Africa. Research on multidisciplinary team (MDT) practices in these regions is limited. The objective of this study is to compare MDT practices in the management of HCC in HICs and LMICs. Methods: Data on MDT practices from hospitals that manage HCC in Italy, Spain, Switzerland, Germany, Denmark, Canada and the USA, representing HICs, and in China, South Africa and Egypt, representing LMICs were collected through virtual semi-structured interviews and workshops. Results: Ten key areas of differences were identified (Table 1) that could be categorized as organizational/regulatory or clinical. In HIC institutions, the focus currently is on optimizing MDTs as standard of care approach accessible to all patients with HCC; MDT principles are often integrated into national policies. In LMICs, emphasis is on establishing MDTs and expanding their capacity; patient access to MDT care is not a mandatory requirement, nor regulated in national policy. Of note, LMICs are seeking early technology adoption to overcome some potential barriers to MDT interactions; online formats are more often explored to facilitate participation and AI-assisted diagnostic tools are explored to compensate for absence of radiologists. Absence of screening and surveillance for early detection in HCC is more common in LMICs, and therefore likely that patients more often present with advanced stage disease. Also, with limited diagnostic modalities, diagnostic work-up and staging may be sub-optimal. Conclusions: Significant variation exists in HCC MDT practices between HICs and LMICs. The ultimate goal of this study is to develop a format for clinical MDTs that will facilitate interaction between HICs and LMICs. Consideration for the differences highlighted above is crucial for the development of this concept. 10 key areas highlighting differences identified between HICs and LMICs. MDT development direction: Standard of Care for all patients vs. specific session for complex cases National/regional regulatory requirements Institutionalizing MDT principles MDT composition (specialists) Use of digital tools Reimbursement Access to therapeutic options Stage presentation of HCC patients Use of clinical staging Patient follow-up after MDT discussion
Prognostic implication of body composition changes in patients with borderline resectable/locally advanced pancreatic adenocarcinoma (PDAC) treated with mFOLFIRINOX.
Authors: Jong Hyuk Lee, Hyehyun Jeong, Yousun Ko, Kyung Won Kim, Hyunseok Yoon, Kyu-Pyo Kim, Changhoon Yoo, Tae Won Kim, Sun Young Kim
Journal: Journal of Clinical Oncology (2025)

783 Background: Although cachexia is a known prognostic factor in patients with advanced cancer, individual body composition changes during chemotherapy and their association with survival in PDAC warrant further investigation. We aimed to analyze the prognostic implication of comprehensive body composition, including areas and attenuation of muscle mass, body fat area and its distribution, and body mass index (BMI) during mFOLFIRINOX in patients with PDAC. Methods: Patients with borderline resectable or locally advanced PDAC, who were not able to undergo curative surgery and received first-line mFOLFIRINOX between January 2017 and December 2020 from Asan Medical Center, Seoul, Korea, were included in this retrospective study if they had paired CT scans of the abdomen at baseline and after 12 weeks of mFOLFIRINOX. Body composition was measured using artificial intelligence software (AID-UTM, iAID Inc.) from the CT images, and their association with overall survival (OS) were analyzed. Results: A total of 377 patients were included. Median age was 63 (range, 56–69) and 214 patients (56.8%) were males and 163 patients (43.2%) were females. During the first 12 weeks, significant changes in the body composition occurred as follows (median changes and interquartile range): skeletal muscle area, -5.8% [-11.1%–0.6%]; normal attenuation muscle area/total attenuation muscle area, -2.8% [-8.7%–3.2%]; visceral fat area (VFA), -6.1% [-23.7%–18.6%]; skeletal fat area (SFA), -12.2% [-27.8%–77.1%]; and BMI, -2.2% [-6.8%–1.5%]. Furthermore, changes in the VFA and BMI was associated with tumor response (Kruskal-Wallis test, p = 0.012 for VFA; p = 0.054 for BMI). There was no significant relationship between body composition abnormalities including sarcopenia, myosteatosis, or obesity at baseline and OS. However, patients who experienced the greatest decrease in SFA and BMI after 12 weeks of mFOLFIRINOX had poorer OS (tertile 1 [greatest decrease] vs 3 [smallest decrease]: HR 0.67 [95% CI, 0.52–0.87] for SFA, p = 0.003; 0.68 [95% CI, 0.49–0.83] for BMI, p = 0.001). Conclusions: In patients with borderline resectable/locally advanced PDAC, body composition significantly changes during the first 12 weeks. Decrease in the body fat and BMI from baseline were associated with poorer tumor response and OS.
Short- and long-term outcomes of conversion surgery for initially unresectable advanced gastric cancer: A Japanese multicenter retrospective cohort study.
Authors: Itaru Yasufuku, Masanori Terashima, Naoki Takahashi, Narikazu Boku, Yukinori Kurokawa, Seito Fujibayashi, Nobuhisa Matsuhashi, Takeshi Omori, Yuichi Ito, Michihiro Ishida, Yukinori Yamagata, Takanobu Yamada, Takuro Saito, Atsushi Takeno, Sho Sato, Keijiro Sugimura, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2025)

402 Background: The efficacy of conversion surgery in patients with unresectable advanced gastric cancer at the initial diagnosis who converted to be resectable due to remarkable response to chemotherapy is unclear. To evaluate short- and long-term outcomes of conversion surgery for initially unresectable cStage IVB/pStage IV gastric cancer as the basic data for the JCOG2301 trial, which is a randomized controlled trial comparing conversion surgery with continuation of chemotherapy, a multicenter retrospective cohort study was conducted in the Stomach Cancer Study Group of the Japan Clinical Oncology Group. Methods: Inclusion criteria were as follows; (1)gastric cancer with at least one of following distant metastasis at the initial diagnosis; (i) peritoneal metastasis (PER) diagnosed by imaging examination or P1b or P1c disease diagnosed by laparoscopy or laparotomy, (ii) multiple liver metastasis (HEP) more than three lesions, and (iii) distant lymph node metastasis (LYM) beyond paraaortic lymph node station 16a2/b1, (2) conversion to be resectable after systemic chemotherapy, (3) surgery aiming at an R0 resection of the primary and remaining lesions between April 2010 and September 2017. Clinical data were retrospectively obtained from electronic patient records of 58 institutions. Results: Atotal of 241 patients were included to the study. Initial unresectable factors were PER, HEP, and LYM in 132(55%), 37(15%), and 63(26%) patients, respectively, and 9(4%) patients had two or more factors. Conversion to be resectable obtained during the first and second/later line chemotherapy was in 209 (87%) patients and 32 (13%), respectively. 182(76%), 29(12%), and 30(12%) patients underwent R0, R1, and R2 resection, respectively. The incidence of postoperative complication of Clavien-Dindo Grade II or higher was 24% and no surgery-related death was observed. The median overall survival (mOS) from surgery was 45.4 (95%CI 30.9-61.4) months in R0 resection, 16.6 (11.5-18.5) months in R1, and 20.9 (11.3-35.6) months in R2. In case of R0 resection, the mOS from surgery was 34.4 (95%CI 26.5-59.2) months in PER, 55.9 (21.8-96.7) months in HEP, 54.6 (30.9-98.3) months in LYM, and not reached (19.7-NA) in two or more factors. Conclusions: Conversion surgery appears to be safe and a promising treatment strategy for patients who have initially unresectable advanced gastric cancer and presented remarkable response to systemic chemotherapy.