tbuckley/cabot-search huggingface dataset:
Immunotherapy outcomes in dMMR/MSI-H and/or TMB-H metastatic colorectal cancer (CRC) with peritoneal metastases (PM).
Authors: Osama M Mosalem, Ahmed Elhariri, Nathaniel Edward Wiest, Saivaishnavi Kamatham, Nayef Hikmat Abdel-Razeq, Jeremy Clifton Jones, Mohamad B. Sonbol, Zhaohui Jin, Hani M. Babiker, Tanios S. Bekaii-Saab, Umair Majeed, Jason S. Starr
Journal: Journal of Clinical Oncology (2025)

163 Background: CRC with PM has a poor prognosis and limited treatment options. Immunotherapy has shown promise in improving outcomes for patients with microsatellite instability-high (MSI-H), mismatch repair-deficient (dMMR), and high tumor mutational burden (TMB-H) tumors. However the peritoneal niche has a unique microenvironment, which can influence the effectiveness of immune check point inhibitors (ICIs). We assessed the impact of ICI on progression-free survival (PFS) and overall survival (OS) in CRC patients (pts) and PM, considering key clinical and molecular characteristics. Methods: A retrospective review aiming to identify CRC pts with MSI-H/dMMR and PM treated with immunotherapy between 2015 and 2023 was performed. Data collected included pt demographics, tumor characteristics, and treatment details. Responses were evaluated using RECIST v1.1 criteria. Results: 37 pts were included, 9 (24%) had Lynch syndrome. The median age of diagnosis was 61 years and most pts were females (65%). Most pts had MSI-H/dMMR tumors, while one pt was treated based on ultra-hypermutated phenotype (TMB 202) and POLE mutation. Among those with available TMB data, the median TMB was 52 mutations/Mb (0-202). Common mutations were PMS2 (51%), MLH1 (38%), MSH6 (16.2%), and MSH2 (16.2%). Right-sided tumors were in 54%, mucinous histology in 62%, and ascites in 54%. Pts received a median of 11 cycles of ICI (2-52). Pembrolizumab was the most frequently used ICI (78%), while Nivolumab was used either alone (11%) or in combination with Ipilimumab (11%). Median PFS in our cohort was 7.8 months and median OS was 29.9 months. The disease control rate (DCR) was 81%, with an objective response rate (ORR) of 51.3% (9 complete responses, 12 partial responses). At the time of data collection, 30% of pts were off systemic therapy and 5-FU-based chemotherapy combined with a biologic agent was the most common subsequent treatment in 32% who had PD. Univariate analysis showed no significant differences in PFS or OS based on tumor sidedness, isolated PM, liver metastases, mucinous vs. non mucinous histology or BRAF / RAS status (WT vs mutant). Malignant ascites was associated with worse OS(HR 0.3; p= 0.03). Conclusions: Treatment with ICIs in pts with MSI-H/dMMR and/or TMB-H CRC and PM improved disease control in CRC pts with PM, however, as compared to historical controls for patients with MSI-H/d-MMR disease treated with ICI, this group showed less favorable outcomes. Malignant ascites was associated with poorer overall survival. Further research of the immune response and tumor microenvironment in the peritoneal cavity is warranted.
Surufatinib combined with locoregional therapies and immune checkpoint inhibitor (ICI) for treating unresectable or metastatic intrahepatic cholangiocarcinoma.
Authors: Wan Guang Zhang, Zhan Guo Zhang, Jian Ping Zhao, Ze Yang Ding
Journal: Journal of Clinical Oncology (2025)

593 Background: Advanced metastatic ICC, characterized by poor survival and limited therapeutic options, may benefit from the combined use of surufatinib—a selective tyrosine kinase inhibitor targeting VEGFR 1, 2, and 3, FGFR1, and CSF-1R—and ICIs, alongside locoregional treatments like TACE, DEB-TACE, and HAIC. Methods: Eligible pts who were 18 -75 years old with histologically confirmed unresectable or metastatic intrahepatic cholangiocarcinoma were enrolled. Pts received surufatinib (250mg, orally daily), ICI, and locoregional therapies until surgery, disease progression, death, intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), conversion to surgical resection rate and safety. Results: By July 31, 2024, 20 pts were enrolled and 10 pts were evaluated. Median age was 56.4 years (range: 36-69), with a majority being male (70%). 9 pts were pathologically confirmed as adenocarcinoma, 1patient was small bile tract type. Treatment included DEB-TACE (20%), TACE (30%), and HAIC (50%). 50% (5/10) pts achieved partial response (PR), 20% (2/10) pts accepted conversion surgery, 30% (3/10) pts achieved stable disease (SD), and the confirmed ORR was 50%, DCR was 80%. The median PFS (95%Cl: 6.9-NA months) had not yet matured, with no significant differences in survival benefits based on age or gender, though TACE showed potential benefits. The most common AEs of all grades were nausea (30%), dizziness (30%), and headache (10%), No grade ≥ 3 TEAEs or new safety signals occurred. Conclusions: Surufatinib plus immune checkpoint inhibitor, along with locoregional therapies showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of ICC, providing an additional treatment option for pts with ICC. Clinical trial information: NCT05236699 .
Prevalence of extracolonic malignancies in patients with familial adenomatous polyposis.
Authors: Avina Rami, Araceli Garcia-Gonzalez, Julie Moskowitz, Maureen E Mork, Luigi Ricciardiello, Selvi Thirumurthi, Elizabeth G. Grubbs, Y. Nancy You, Eduardo Vilar Sanchez
Journal: Journal of Clinical Oncology (2025)

103 Background: Familial adenomatous polyposis (FAP) is an autosomal-dominant inherited colorectal cancer syndrome resulting from mutations in the adenomatous polyposis coli ( APC ) gene. Patients with FAP have nearly 100% lifetime risk of colorectal cancer, typically managed with prophylactic colectomies. As patient survival has improved, the incidence of extracolonic tumors, including thyroid malignancies and desmoid tumors, has increased. However, limited research exists on the prevalence of extracolonic malignancies in FAP patients. Methods: We prospectively enrolled 219 patients with FAP in the Hereditary Gastrointestinal Cancers Cohort at the MD Anderson Cancer Center between December 2015 and July 2024. Inclusion criteria included either a clinical or molecular diagnosis of FAP. Data on demographics, cancer history (including cancers diagnosed both prior to and during the study period), BMI, tobacco use, medications, endoscopy results, thyroid ultrasound findings, and abdominal/pelvic CT results were collected. Screening for thyroid and desmoid tumors was provider-dependent, with additional screenings as deemed appropriate. Descriptive and inferential statistics were used to identify associations between demographic and clinical factors and the prevalence of extracolonic malignancies. Results: Among 219 patients, 20.5% developed desmoid tumors, 18.7% developed colorectal cancer, and 6.8% developed well-differentiated thyroid cancer (6.4% papillary thyroid cancer, 0.4% follicular thyroid cancer). Prophylactic colorectal surgery was performed in 151 patients (68.9%). Per chart review, benign thyroid disease and hypothyroidism were present in 21% and 11.4% of patients, respectively. Female sex was significantly associated with hypothyroidism (p=0.007) and thyroid cancer (p=0.009). BMI &gt; 30 was also linked to increased thyroid cancer risk (p=0.046). Desmoid tumors were found in 20.5% of patients, most commonly in the abdominal wall. Female sex, BMI &gt; 30, and history of colorectal surgery were significantly associated with desmoid tumor development (p=0.004, 0.0064, 0.0038). Conclusions: FAP patients exhibit a higher prevalence of benign thyroid disease, thyroid cancer, and desmoid tumors compared to the general population. Given these findings, adherence to existing surveillance guidelines, such as those outlined by the National Comprehensive Cancer Network (NCCN), is essential. Our findings further support the importance of these established surveillance strategies in the management of FAP patients.
Association between skeletal muscle morphometrics and overall survival among older adults with gastrointestinal cancers.
Authors: Apoorva Doshi, Omar Saad, Landon Martin, Grant Richard Williams, Smith Giri
Journal: Journal of Clinical Oncology (2025)

808 Background: Older adults with gastrointestinal (GI) cancers face a higher risk of treatment toxicities and adverse survival outcomes. However, the variability in these outcomes remains poorly understood. Age-related changes, including the progressive loss of skeletal muscle and gain in adipose tissue, contribute to this heterogeneity. Recent studies highlight an association between skeletal muscle gauge (SMG) and overall survival (OS) in older cancer patients, but its relevance among those with GI cancers is unclear. Methods: We included adults aged ≥ 60 years with newly diagnosed GI cancers, enrolled in the University of Alabama at Birmingham (UAB) Cancer and Aging Resilience Evaluation (CARE) registry between October 2017 and April 2024. Skeletal muscle index (SMI; skeletal muscle area in m²/height in cm) and skeletal muscle radiodensity (SMD; Hounsfield units) were derived from single-slice computed tomography (CT) staging scans at the third lumbar vertebra (L3) using validated methods. SMG was calculated as the product of SMI and SMD, reported in arbitrary units (AU). Participants were followed until death or the study cutoff date of July 10, 2024. Kaplan-Meier survival analysis was used to estimate OS by SMG status (low: &lt; median; high: ≥ median). Cox proportional hazards models were employed to assess the relationship between SMG and OS, adjusting for age, sex, race/ethnicity, and cancer stage. Results: A total of 568 patients were included in the study, with a median age at diagnosis of 68 years (interquartile range, IQR: 64-74), 55% male, 73% non-Hispanic White, and 43% were diagnosed with Stage IV disease. Colorectal (33%) and pancreatic (27%) cancers were the most common diagnoses. The median SMG was 1,529 AU (IQR: 1,151–1,967). Over a median follow-up of 60 months, 367 patients (64%) died. Median OS was 19 months for those with low SMG and 26 months for those with high SMG (log-rank test, p &lt; .05). After adjustment for confounders, SMG remained independently associated with OS (adjusted Hazard Ratio: 0.678 per IQR increase; 95% CI: 0.57– 0.807; p &lt; .001), indicating that each IQR increase in SMG is associated with a decrease in all-cause mortality risk by 32.2%. Conclusions: Skeletal muscle gauge, an integrated measure of SMI and SMD, is significantly associated with improved survival among older adults with GI cancers. Further research is needed to determine whether SMG has a causal impact on survival in this population.
Hepatocellular carcinoma: A 30-year trend analysis of global burden stratified by risk factors, and socio-demographic indexes.
Authors: Charmi Bhanushali, Kalaivani Babu, Srinishant Rajarajan, Vidhi Bhanushali, Kala Seetharaman
Journal: Journal of Clinical Oncology (2025)

529 Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related morbidity and mortality worldwide, driven primarily by chronic infections with Hepatitis B, Hepatitis C, and alcohol consumption. This study systematically examines global trends of HCC from 1991 to 2021, focusing on age-standardized mortality rates (ASMR) and Disability-Adjusted Life Years (DALYs) according to risk factors across Socio-Demographic Index (SDI) regions. By highlighting these patterns, the study provides insights into the interplay of socio-economic disparities and healthcare advancements on HCC trends. Methods: We utilized data from the Global Burden of Disease database to extract ASMR, and age standardized DALYs for HCC between 1991 and 2021. The data was stratified by etiology (Hepatitis B, Hepatitis C, alcohol consumption) and stratified across five SDI regions: low, low-middle, middle, high-middle, and high SDI. Results: The global HCC ASMR decreased by 4% from 1991 to 2021, with the largest reduction (20.4%) in low SDI regions. Hepatitis B-related HCC ASMR dropped by 16.3%, with reductions across all SDI groups. ASMR of Hepatitis C-related HCC remained stable globally but fell by 15.1% in low SDI regions. Alcohol-related HCC ASMR increased by 10% globally, with the highest rise in high SDI regions (24.5%), and NASH-related HCC ASMR increased by 26.7% globally, with a 42% rise in high SDI regions. Hepatitis B-related HCC DALYs decreased by 22.2%, with the sharpest declines recorded in high (31.4%) and low SDI regions (29%). Hepatitis C-related HCC DALYs saw a 8.8% global reduction, which was consistent across all groups. Alcohol-related HCC DALYs rose by 4.6% globally, with increases of 14.4% in high SDI and 20.5% in low-middle SDI regions. NASH-related HCC DALYs increased by 18.7%, with a 34.7% rise in low-middle SDI regions. Conclusions: The study reveals substantial progress in reducing the global burden of Hepatitis B- and C-related HCC, particularly in low SDI regions. This progress likely reflects advances in vaccination, antiviral treatments, and screening programs. However, the rising mortality and disability associated with alcohol- and NASH-related HCC, especially in high SDI regions, emphasize the growing impact of lifestyle-related risk factors. These findings underscore the need for tailored public health strategies to mitigate the increasing effects of these preventable risk factors on global HCC outcomes.
The role of artificial intelligence in colorectal cancer and polyp detection: A systematic review.
Authors: Sakshi Bai, Bipneet Singh, Jahnavi Ethakota, Oboseh John Ogedegbe, Olanipekun Lanny Ntukidem, Akshit Chitkara, Sindhu Rani, Danesh Kumar, JoAnn Hirth, Devin Birsingh Malik
Journal: Journal of Clinical Oncology (2025)

47 Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Early detection and accurate diagnosis are essential for improving survival rates and optimizing therapeutic strategies. Recently, artificial intelligence (AI) technologies, such as machine learning algorithms, convolutional neural networks (CNNs), and computer-assisted diagnostic (CAD) systems, have significantly enhanced traditional diagnostic tools like colonoscopy and histopathology. This systematic review evaluates the current role of AI in CRC management, focusing on diagnostic improvements, predictive modeling, and outcome prediction. Methods: A comprehensive literature review was conducted using PubMed, Google Scholar, and MEDLINE using MeSH term to identify studies utilizing AI in CRC diagnosis and management, with a focus on diagnostic imaging, histopathological analysis, and predictive modeling. Studies were evaluated for the accuracy of AI-driven diagnostic systems and the predictive performance of AI models in clinical outcomes. Results: Out of 147 studies identified, 37 met the eligibility criteria for this review. AI tools such as CNNs, CAD systems, and EndoBRAIN showed high accuracy in CRC detection and polyp classification. Kudo et al. (2020) reported 98% CRC detection accuracy using EndoBRAIN. Blanes-Vidal et al. (2019) achieved 96.4% accuracy in polyp detection via DCNN. Additionally, Wang et al. (2019, 2020) demonstrated improved Adenoma Detection Rates (ADR) of 34.1% and 29.1%, respectively, using AI over traditional methods. For outcome prediction, AI models, including CNNs, predicted patient prognosis with reasonable accuracy, as highlighted by Skrede et al. (2020) with 76% accuracy in prognosis prediction. Conclusions: The systematic review and analysis of AI-assisted diagnostic modalities in colorectal cancer and polyp detection reveal promising results, with most models demonstrating high sensitivity, specificity, and accuracy. CNN-based models and CAD systems, in particular, show strong potential for improving detection rates and clinical outcomes in CRC screening. The studies included in this review demonstrate that AI can enhance diagnostic precision, particularly in identifying polyps and predicting clinical outcomes, with high validation rates. However, more external validation and long-term clinical studies are needed to fully establish the robustness of these AI tools in routine clinical practice.
Disease-free survival as a surrogate endpoint for overall survival in adults with early-stage pancreatic cancer: A trial-level surrogacy analysis.
Authors: Luís Felipe Leite da Silva, Luiz F. Costa Almeida, Mariana Macambira Noronha, Lucas Diniz da Conceição, Marcos Belotto, Thais Baccili Cury Megid, Renata D'Alpino Peixoto
Journal: Journal of Clinical Oncology (2025)

708 Background: In early-stage cancer, overall survival (OS) is the gold-standard endpoint for assessing therapeutic efficacy. However, long follow-up periods make OS challenging and costly to measure in clinical trials. Disease-free survival (DFS), which captures the time to recurrence or death, has been proposed as a surrogate endpoint for OS in early-stage pancreatic cancer (PC). This surrogacy relationship could allow for a more rapid assessment of treatment benefits, but its validity requires robust analysis across clinical trials. Understanding the trial-level correlation between DFS and OS is crucial to optimizing trial design and grant accelerated drug approval. Methods: We conducted a systematic search of Embase, PubMed, and Cochrane databases through August 2024, identifying randomized controlled trials (RCTs) that evaluated adjuvant or neoadjuvant systemic therapies in adult patients with PC. Included studies reported both OS and DFS outcomes. Hazard ratios for DFS (HR_DFS) were analyzed as surrogate endpoints for OS (HR_OS). Statistical analyses utilized linear regression models, weighted by trial sample sizes, to determine the strength of the correlation. Surrogacy strength was categorized by the coefficient of determination (R²), with R² ≥ 0.7 indicating a strong correlation, 0.69–0.5 a moderate correlation, and values &lt; 0.5 indicating weak correlation. Results: Out of 3,048 studies screened, 30 RCTs met the inclusion criteria, comprising 5,275 patients in adjuvant therapy trials and 557 patients in neoadjuvant therapy trials. The median follow-up duration ranged from 16 to 53.5 months, with 12 phase II trials included. Overall, DFS showed strong surrogacy for OS in adjuvant trials (R² = 0.70; 95% CI, 0.50–0.91). Subgroup analysis indicated strong correlation in phase III trials (R² = 0.71; 95% CI, 0.46–0.96) and moderate correlation in phase II trials (R² = 0.67; 95% CI, 0.21–1.00). The strongest surrogacy was observed in studies incorporating adjuvant radiation therapy (R² = 0.81; 95% CI, 0.52–1.00). In the analysis of neoadjuvant trials, HR-DFS also presented strong correlation with OS (R² = 0.90; 95% CI, 0.56–1.00). Conclusions: There is a strong trial-level correlation between DFS and OS in both adjuvant and neoadjuvant therapy trials for early-stage pancreatic cancer, particularly in phase III studies and trials incorporating adjuvant radiation therapy. However, the strength of this surrogacy varies depending on the treatment setting and trial design.
TYRA-430: First reversible FGFR4/3 inhibitor designed to overcome current challenges in FGF19-driven hepatocellular carcinoma treatment.
Authors: Mohamed A. Ahmed, Jacqueline Starrett, Isaac Hoffman, Kirk Nelson, Melissa Neal, Melissandre Pache, Emily Pettitt, Daniel Bensen, Robert Hudkins, Todd Harris, Ronald Swanson
Journal: Journal of Clinical Oncology (2025)

583 Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy that accounts for approximately 80-90% of all primary liver cancers and is projected to become the third leading cause of cancer-related mortality by 2030. Previous work demonstrated that human Fibroblast Growth Factor 19 (FGF19) was overexpressed in 20-30% of HCC, thereby exerting an oncogenic effect via signaling through its cognate receptors FGFR4, FGFR3, and the co-receptor Klotho b (KLB). Multiple selective covalent FGFR4 inhibitors have been clinically evaluated in FGF19-overexpressing HCC. However, selective inhibition of FGFR4 alone was insufficient and resulted in low response rates and limited duration, likely due to redundant signaling through FGFR3. Here we describe the first report on the preclinical profile of TYRA-430, a first-in-class reversible FGFR4/3 inhibitor. Methods: The preclinical profile of TYRA-430 was assessed in vitro in HCC cellular assays and in vivo in mouse xenograft models. The in vitro potency was assessed by measuring cell viability using Cell Titer-Glo 2.0 Luminescent assay. Percentage of tumor growth inhibition (TGI) was used as a measure to evaluate in vivo efficacy of TYRA-430. Results: TYRA-430 exhibited potency against Ba/F3 cells dependent on wildtype FGFR3 and FGFR4, as well as the known Cys552 and Val550 gatekeeper (GK) resistance mutations in FGFR4. In vitro data showed that TYRA-430 displayed superior potency over the reversible multi-kinase inhibitors sorafenib and lenvatinib, and the covalent FGFR4 inhibitors fisogatinib (BLU-554) and roblitinib (FGF401) in KLB/FGF-19/FGFR3/4 driven models of HCC (Hep3B, HuH-7, and JHH-7 cells). Furthermore, in a human HuH-7 HCC xenograft model in nu/nu mice, TYRA-430 achieved 96% tumor growth inhibition (TGI), compared to 75% TGI for lenvatinib and 86% TGI for FGF401. Additionally, in the GA180 FGF19-driven gastric cancer PDX model, TYRA-430 demonstrated superior efficacy with 93% tumor growth inhibition (TGI), compared to 56% TGI achieved by roblitinib. Conclusions: TYRA-430 was active and potent in multiple KLB/FGF-19/FGFR3/4 models of human hepatocellular carcinoma in vitro and in vivo . Moreover, TYRA-430 displayed potent activity against known FGFR4 resistance mutations compared to covalent FGFR4-specific inhibitors in the clinic. TYRA-430 will be investigated in a Phase 1 clinical trial in hepatocellular carcinoma and other advanced solid tumors.