tbuckley/cabot-search huggingface dataset:
Incidence and survival trends in small bowel adenocarcinoma (SBA) from 2000-2019 in the United States.
Authors: James Jerod Sears, Yifei Xu, Jingxia Liu, Mark Aaron Fiala, Robert R. McWilliams, Michael J. Overman, Katrina Sophia Pedersen
Journal: Journal of Clinical Oncology (2025)

801 Background: SBA is a rare, poorly understood gastrointestinal malignancy. Adenocarcinomas are often grouped with other small bowel cancer histologies in epidemiologic and outcomes reports, which limits the ability to detect SBA-specific trends. Recent studies in European populations show increasing SBA incidence, but there are limited published data in American cohorts. Identifying trends in SBA can improve understanding of the population most at risk for developing SBA. This study describes U.S. trends in SBA incidence and outcomes from 2000 to 2019. Methods: Using the 2022 SEER research-limited dataset, we identified SBA cases and measured the incidence change from 2000-2019. We built linear regression models to evaluate changes in annual incidence by groups, including sex, race, and age of diagnosis, separately. We then compared the overall incidence and trends between subgroups. We investigated overall survival (OS) through the SEER research case listings for SBA patients diagnosed during the study period. Results: An average of 0.67 cases/100,000 SBA cases were reported annually from 2000-2019, with a median diagnosis age of 69 years. SBA incidence has increased annually by 0.3% per year from 2000-2019 (p=0.05). From 2000-2019, men were at a higher risk for SBA compared to women (p=0.02). In men, SBA cases increased at a rate of 0.004 cases/100,000/year from 2000-2019 (p=0.01) and a nonsignificant decrease in women of 0.00012 cases/100,000/year. There were no statistically significant differences in incidence or the change in incidence of SBA by race. The age-adjusted incidence was significantly higher each year between 2000 and 2019 in the &gt; 70 cohort compared to the &lt;70 cohort (p=0.02). Cases of SBA increased at a rate of 0.02 cases/100,000/year in adults &gt;70 years (p=0.02). There were no differences in incidence rates in patients &lt;70 years. There was no significant difference in OS for patients diagnosed with SBA in 2000, 2005, 2010, 2015, and 2019 (p=0.21). Conclusions: The overall annual incidence of SBA is increasing in the U.S. population. The most significant rate increases are in men and adults older than 70. In the SEER population, trends in SBA contrast with the recent rise of colorectal cancer in the young adult population, highlighting the unique nature of SBA compared to other gastrointestinal malignancies. Additionally, survival outcomes in patients diagnosed with SBA have remained stable over the past 20 years, while other malignancies have shown improvement in the same period. The small cohort size and the lack of a universal U.S. cancer registry limited this evaluation. Improved reporting of SBA cases and further research to identify risk factors are urgently needed to reduce the growing impact of SBA.
Association between visceral adipose tissue radiodensity and overall survival among older adults with colorectal carcinoma.
Authors: Apoorva Doshi, Omar Saad, Landon Martin, Grant Richard Williams, Smith Giri
Journal: Journal of Clinical Oncology (2025)

43 Background: Central obesity is a known risk factor for colorectal carcinoma (CRC); however, the association between visceral adipose tissue (VAT) and survival outcomes remains unclear. This study aims to investigate the relationship between VAT and overall survival (OS) among older adults with CRC. Methods: We analyzed data from the Cancer and Aging Resilience Evaluation registry, including adults aged ≥ 60 years with newly diagnosed CRC who were seen at the University of Alabama at Birmingham for initial consultation between October 2017 and April 2024. Using single-slice computed tomography staging scans, we calculated visceral adipose tissue radiodensity (VATD; in Hounsfield units, HU) at the third lumbar vertebra (L3) using validated methods. A lower VATD (more negative score) indicates higher visceral adipose tissue. Participants were followed until death or the study cutoff date of July 10, 2024. Kaplan-Meier survival analysis was performed to estimate OS for those with low VAT (VATD ≥ median VATD) versus high VAT (VATD &lt; median VATD). Additionally, Cox proportional hazards models were utilized to evaluate the association between VATD and OS, adjusting for age at diagnosis, sex, race/ethnicity, skeletal muscle index (SMI), skeletal muscle density (SMD), and cancer stage. Results: A total of 190 patients were included, with a median age at diagnosis of 68 years (IQR: 64-75), 56% male, 72% non-Hispanic White, and 40% diagnosed with Stage IV disease. The median SMI and SMD were 42.06 (IQR: 33.81 - 49.52) cm 2 /m 2 and 38.68 HU (IQR: 31.38 - 44.89) respectively. The median VATD was -86.14 HU (IQR: -93.78 – -76.39). Over a median follow-up of 60 months, 96 patients (51%) died. Median OS was 27 months for patients with low VAT and 62 months for those with high VAT (log-rank test, p &lt; .001). After adjusting for confounders, VATD remained independently associated with OS (adjusted Hazard Ratio: 1.41 per IQR decrease; 95% CI: 1.06 – 1.86; p ≤ .05), indicating that each IQR decrease in VATD scores (implying an increase in VAT) is associated with a 41% increased risk of all-cause mortality. Conclusions: Our findings demonstrate that increased visceral adipose tissue, indicated by more negative VATD scores, is significantly associated with poorer survival outcomes among older adults with CRC. These results underscore the importance of dietary and weight loss interventions to improve outcomes in this population.
Mortality trends and racial disparities in hepatocellular carcinoma associated with metabolic syndrome in the United States and Texas: A 21-year analysis (1999-2020) using CDC WONDER database.
Authors: Sidra Naz, Abdullah Shaikh, Mazen Alasadi, Hao Chi Zhang
Journal: Journal of Clinical Oncology (2025)

525 Background: The prevalence of hepatocellular carcinoma(HCC) and metabolic syndrome (MetS) is increasing globally. This study aims to examine annual trends of mortality in MetS-associated HCC in the United States and its state of Texas, from 1999 to 2020, to evaluate public health initiatives and identify socioeconomic factors. Methods: Mortality trends for adults aged ≥25 years with MetS-associated HCC were analyzed using CDC WONDER database, identifying deaths through ICD-10 codes C22.9 “Liver Malignant neoplasms” and E88.9 “Metabolic Syndrome”. Crude and age-adjusted mortality rates (AAMRs) per 100,000 people were extracted. Annual percent changes (APCs) in AAMRs, with 95% confidence intervals, were determined across various demographic (sex, race/ethnicity, age) and geographic (state, urban-rural, regional) subgroups. Results: Between 1999 and 2020, 271,046 documented deaths were attributed to HCC due to metabolic syndrome. The AAMR for MetS-related HCC mortality increased in the US from an adjusted rate (AR) (3.7) in 1999 to (4.5) in 2009 (APC:2.10%; 95% CI: -0.13% to 3.10%), after which it increased to (7.6) in 2018 (APC:5.83%; 95% CI:4.25% to 6.99%) and increased to 9.9 in 2020 (APC:13.19%; 95% CI:8.78% to 15.7%). In Texas, AAMR for MetS-related HCC mortality increased from AR (4.9) in 1999 to (8.9) in 2015 (APC:3.95%; 95% CI:3.11% to 4.69%) after which it increased to (15.3) in 2020 (APC:10.64%; 95% CI:8.18% to 17.33%). Men had consistently higher AAMRs than women (12.4 vs. 8). The AAMR in U.S. men increased from (5.1) in 1999 to (12.4) in 2020. The AAMR in U.S. women increased from (2.7) in 1999 to (8) in 2020. The non-Hispanic (NH) American Indian or Alaska Native population has the greatest AAMR (13.4), followed by the NH Black or African American(AA) (12.7) and the Hispanic or Latino population with AAMR (10.9). The low-risk population was NH White with AAMR (9.6) and NH Asian or Pacific Islander (6.6). The AAMR also varied by region (South:11.5; Midwest:9.9; West:9.4; Northeast:7.4) and non-metropolitan areas had higher AAMR (small metro:12.1; non-core areas:11; micropolitan areas:11.7) than metropolitan areas (large central metropolitan: 8.8; large fringe areas: 8.7). The states in the upper 90th percentile of MetS-related HCC AAMRs were Texas, Louisiana, Arkansas, Michigan, Nevada exhibited an approximately two-fold increase in AAMRs, compared to states falling in the lower 10th percentile Nebraska, Wisconsin, Washington, Maine. Conclusions: Mortality rates from hepatocellular carcinoma associated with metabolic syndrome have risen in the United States and Texas over the past two decades. However, significant demographic and geographic disparities in MetS-related HCC mortality continue, emphasizing the need for further investigation and the development of targeted treatment strategies.
Frequency of surveillance CT scan ordering in patients with stage II/III colorectal cancer.
Authors: William Silverstein, Samuel Murray, Michael J. Raphael, Adina S Weinerman
Journal: Journal of Clinical Oncology (2025)

106 Background: Patients with stage II/III colorectal cancer (CRC) undergo surveillance CT scans to detect early asymptomatic oligometastatic spread, which can be treated with curative intent. However, randomized clinical trials show no difference in 5-year mortality in those that undergo low intensity surveillance (annual) compared a higher intensity strategy (every 6 months). In Ontario, the Program in Evidence-Based Care (PEBC), Ontario Health (Cancer Care Ontario) guidelines recommend surveillance CT scan for patients with stage II/III CRC every 12 months. We aimed to determine the frequency at which clinicians in our Ontario-based hospital system ordered surveillance CT scans for patients with stage II/III CRC. Methods: This single centre retrospective cohort study included all patients that underwent surgical resection for CRC from April 1, 2018 – March 31, 2019 at our academic tertiary care centre in Ontario, Canada. We excluded patients that were followed at an outside hospital, had stage IV disease, had disease recurrence, had a concurrent neoplasm, or did not have CRC. The primary outcome was the proportion of surveillance CT scans completed 10+ months after the previous scan. We also described sociodemographic and medical characteristics of included patients. Follow-up was until August 2023. Results: We included 200 patients. The median age was 62 years (IQR: 52-70), 48% (N=96) were female, the rectum was the most commonly involved disease site (43%, N=86), 38% (N=76) had stage III disease, and 54% (N=107) received adjuvant chemotherapy. A total of 1286 scans were ordered during the study period. Of these, 67% (N=860) were ordered as surveillance. Of these, 18% (n=155) were completed 10 months or longer from the previous scan. The median time interval between surveillance scans was 6.6 months (IQR: 5.9-7.9). Approximately 20% (n=137 of 630) of surveillance scans ordered by general surgeons were completed 10 months or longer from the previous scan, whereas only 9% (n=18 of 205) of scans ordered by medical oncologists were completed 10 months or longer from the previous scan. Less than 1% of surveillance scans (n=3) identified new metastatic disease. Conclusions: The minority of surveillance CT scans ordered in patients with stage II/III CRC in our hospital were timed in concordance with Ontario-based guidelines. Future studies should seek to standardize ordering habits such that they align with best practices.
Combining low-dose regorafenib with pembrolizumab for patients with MSI-H colorectal cancer: REGPEM-CRC-01.
Authors: Ibrahim Halil Sahin, Ronan Wenhan Hsieh, Vikram Gorantla, Stacey A. Cohen, John C. Rhee, Rachael A. Safyan, Curtis Tatsuoka, E. Gabriela Chiorean, Mohamedtaki Abdulaziz Tejani, Al B. Benson, Patrick M Boland, Richard D. Kim, Anwaar Saeed
Journal: Journal of Clinical Oncology (2025)

TPS313 Background: Currently, pembrolizumab is one of the front-line therapies for patients with MSI-H CRC. However, approximately 40% of patients who received pembrolizumab experienced disease progression early in the course of disease (KEYNOTE 177). Therefore, there is still an unmet need to enhance the efficacy of checkpoint inhibitors in MSI-H CRC. MSI-H CRC has a higher level of expression of VEGF in blood compared to patients compared to its MSS counterpart (Hansen et al. Colorectal Dis. 2011). Consistently, exploratory analysis of CALBG-80405 and PARADIGM trial showed that patients with MSI-H CRC were more likely to benefit from anti-VEGF therapy than anti-EGFR therapy regardless of the side of the tumor. NSABP C-08 also suggested that anti-VEGF therapy may have biological activity even in as adjuvant therapy for patients with MSI-H colon cancer. Regorafenib is a potent VEGF inhibitor, with preclinical evidence showing its immune modulatory effect in the tumor microenvironment. In this trial, we hypothesize that adding low-dose regorafenib to pembrolizumab may induce synergistic activity beyond their independent clinical efficacy and create deep and durable responses for patients with MSI-H CRC. Methods: In the lead arm of this prospective randomized study, 22 patients will be enrolled through Hoosier Cancer Research Network (HCRN-GI23-643). Patients with treatment naïve MSI-H CRC will be enrolled in this front-line trial. One cycle of pembrolizumab and up to 3 cycles of chemotherapy prior to determination of MMR-D/MSI-H is allowed. Patients will receive regorafenib 60 mg daily in combination with pembrolizumab 200mg IV in cycle 1, followed by regorafenib 90mg in subsequent cycles to improve treatment tolerance. The primary outcome that will be measured is ORR, defined as the percentage of partial or complete response to the treatment within 12 months. ORR will be measured using RECIST 1.1. criteria. A formal one-sided hypothesis test will be conducted for futility, assuming that we will reject the null hypothesis of a target ORR only if we have strong evidence. In this study, we assume a null hypothesis that ORR is 0.60, which would reflect significant clinical improvement over the current standard of ORR = 0.43 from KEYNOTE 177. The alternative hypothesis is that ORR is less than 0.60. For the lead-in phase of the study, the emphasis is on controlling Type I error to be small, approximately 0.05. The test statistic will be the number of ORRs in the 22 patients, which we assume to follow a binomial distribution. Clinical trial information: NCT06006923 .
A phase 2, multicenter, open-label study of AlloStim combined with anti-PD-L1immunotherapy as 4L therapy in patients with MSS/pMMR metastatic colorectal cancer.
Authors: Wirote Lausoontornsiri, Wirote Lausoontornsiri
Journal: Journal of Clinical Oncology (2025)

TPS318 Background: Microsatellite stable (MSS)/mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) are immunologically 'cold' tumors that do not respond to immunotherapy. Cold tumors represent a formidable hurdle for checkpoint blockade immunotherapy approaches. Therefore, there is a need for novel strategies that could reprogram mCRC cold tumors to become inflamed hot tumors in a manner that might potentially convert low tumor mutational burden (TMB) tumors into checkpoint blockade responsive tumors. AlloStim is an experimental allogeneic, non-genetically manipulated, Th1-like activated living cell immunotherapy derived from healthy unrelated blood donors. The mechanism of action is designed to convert immunologically cold tumors into inflamed hot tumors. A case study of a single 3L MSS/pMMR mCRC patient primed with AlloStim followed by combination anti-PD-1/anti-CTLA4 checkpoint blockade resulted in a rare objective tumor response (Hirschfeld, et al, Translational Medicine Communications (2024) 9:15). The AlloStim priming results in an abundance of infiltrating interferon-gamma producing Th1 cells. Interferon-gamma has been shown to increase expression of PD-L1 in the TME. Therefore, it is hypothesized that the combination of AlloStim with an anti-PD-L1 checkpoint inhibitor might optimally evoke anti-tumor immune responses in this immunotherapy-refractory MSS/pMMR mCRC population. Methods: The study is a phase 2, multicenter, single-arm clinical trial of MSS/pMMR mCRC subjects in 4L that have been previously treated with an oxaliplatin-containing and irinotecan-containing chemotherapy regimen, anti-EGFR (RAS wt and left-sided), anti-VEGF and have progressed on 3L TAS-102 +/- bevacizumab or regorafenib or fruquinitinib. The study is evaluating weekly AlloStim priming from day 0 to day 49 followed by combination of AlloStim IV infusion (q2w) followed a week later by anti-PD-L1 (avelumab 800mg/q2w) from days 63 to day 98. Objective tumor response and disease control rate are the primary end-points. Overall survival is the secondary end-point. Clinically stable patients at day 112 can continue in an expansion phase with another round of combination AlloStim and avelumab from day 119 to day 154. CT scans are conducted at baseline, day 56 after AlloStim priming, day 112 after combination of alternating q2w infusions of AlloStim and avelumab and day 168 in all patients. CT scans will be analyzed by independent central readers using RECIST 1.1. Up to 50 patients will be enrolled with an interim analysis performed to assess efficacy after 20 patients become evaluable. The study is open and has not yet enrolled any patients at time of submission. Clinical trial information: NCT06557278 .
Landscape of metastatic colorectal cancer (CRC) using comprehensive circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in India: Expanding beyond RAS and RAF.
Authors: Viraj Kiran Lavingia, Amit Rauthan, Nitesh Rohatgi, Ankur Bahl, Aparna Dhar, Atul Sharma, Bhuvan Chugh, Rejiv Rajendranath, Shekar Patil, Prabrajya Narayan Mohapatra, Rohit Bharat, Nippun Sandhir, Nisarg Joshi, Vikas S. Ostwal
Journal: Journal of Clinical Oncology (2025)

49 Background: Traditional testing in mCRC primarily focuses on RAS and RAF mutations. However, a broader range of emerging biomarkers, collectively termed the "Pressing panel" (PP), identifies patients with RAS/RAF wild-type (wt) tumors who may particularly benefit from anti-EGFR therapy. Comprehensive liquid biopsies provide a non-invasive method for identifying traditional and emerging biomarkers. Limited genomic data, including the prevalence of PP alterations (alts), is available for mCRC patients in India tested by ctDNA NGS. Methods: We reviewed the results of Guardant360 (Guardant Health, Inc.) ordered for patients with mCRC as part of routine clinical practice in India through July 2024. NGS analyzed plasma samples at a CLIA-certified, CAP-accredited central laboratory. Guardant360 analyzes ctDNA for mutations (mts), insertions and deletions, amplifications (amps), and fusions in up to 83 genes, including PP genes, i.e., KRAS, NRAS, BRAF, ERBB2, PIK3CA, PTEN, AKT1, ALK, ROS1, NTRK, RET, and MSI status. The Indian cohort's prevalence of PP mts was compared to that from other countries in Asia and Middle East (AME). Timing of testing relative to line of therapy was unknown. Results: Among 145 samples from India, ctDNA was detected in 92% (n=134). Median age was 59 years, with women comprising 40%. The median turnaround time from blood collection to result was 7 days. The mean mts count per sample was 5, and the median variant allele frequency was 1.5%. Frequent mts were in APC (53%), KRAS (56%), and SMAD4 (13%), while amps of EGFR (16%) and FGFR1 (9%) were common. Clinically relevant fusions were observed in 3% of patients. KRAS, NRAS, and/or BRAF V600E alterations were found in 63% of both India and AME samples. PP alts were identified in 24% and 27% of Indian and AME patients, respectively. Most frequent PP alts included PIK3CA (15%), PTEN (3%), and MET amp (2%). The prevalence of most of the PP alts was similar between the Indian and AME cohorts (Table), with minor differences observed in PIK3CA (15% vs 18%) and MSI-High (3% vs 1%). In patients with RAS/RAF wild-type lacking EGFR-amp, 9.5% (India) and 18% (AME) harbored at least one PP alt. Conclusions: This study highlights the role of liquid CGP for characterizing the mutational landscape and identifying PP mts for patients from India with advanced CRC. Pressing panel alterations. PP Alteration INDIA % (n=134) AME % (n=720) ERBB2 Amp 1% 2% MET Amp 2% 3% ALK Fusion 0% 0% ROS1 Fusion 0% 0% NTRK1 Fusion 1% 0% RET Fusion 0% 1% ERBB2 Mut 1% 2% PIK3CA Mut 15% 18% PTEN Mut 3% 3% AKT1 Mut 0% 1% MSI-High 3% 1%
Trastuzumab emtansine as second-line therapy in HER2 positive advanced biliary tract cancers: Single arm prospective phase II clinical trial (TAB-3 trial).
Authors: Vikas S. Ostwal, Prabhat Ghanshyam Bhargava, Rajiv Kumar Kaushal, Subhash Yadav, Gauri Wagh, Deepali Naughane, Tejashree Garkal, Sarika Mandavkar, Deepali Chaugule, Anant Ramaswamy
Journal: Journal of Clinical Oncology (2025)

584 Background: HER2 overexpression or amplification is a therapeutic target of interest in advanced BTC, especially gallbladder cancers (GBC). Limited studies evaluate the role of T-DM1 in these groups of cancers. Methods: This study was an investigator-initiated, open-label, single-arm, phase II trial in patients (pts) aged 18 years or older with HER2-positive (defined as IHC 3+ or IHC 2+, and FISH positive), advanced BTCs who had previously received systemic therapy (irrespective of prior additional HER2 targeted therapy). Pts received T-DM1 at 3.6mg/kg q 3 -weekly till disease progression (PD), unacceptable toxicities, or patient choice. The primary end-point of the study was an improvement in 3-month progression-free survival (PFS) from 50% (historical cohort) to 70% in the study arm. Secondary endpoints included overall response rates (ORR), disease control rate (DCR), overall survival (OS), and incidence of grade 3 and 4 treatment-related adverse events (TRAE). Results: From July 2023 to July 2024, ‘52’ pts with HER2-positive BTC were screened, and 40 enrolled in the study. A majority of patients had GBC (95%) and most commonly received combination chemotherapy with gemcitabine-cisplatin, with or without nab-Paclitaxel (78%). Six patients (15%) had previously received trastuzumab in combination with chemotherapy. A majority of patients (n=24; 60%) had rapid progression (within 3 months) on prior systemic therapy. With a median follow-up of 7.1 months [95% confidence interval (CI): 5.1-9.1] , 24 patients had disease progression with a 3-month PFS of 51.2% (95% CI: 33.4 - 69) and median PFS of 3.1 months (95% CI: 2.3-3.8); median OS was 7.1 months (95% CI: 5.1-9.1). Partial responses (PR) were seen in 5 patients (12.5 %) and 8 had stable disease (20 %) for a disease control rate of 32.5 %. Patients without rapid disease progression on prior therapy (n=16; 40%) had a 3-month PFS of 70% (95% CI: 44.8 - 95.2) and median PFS of 4.9 months (95% CI: 2.9-6.9). Grade 3 and grade 4 TRAE in the overall cohort were noted in 11 patients (28%), with the commonest being grade 2 fatigue in 6 patients and grade 3 thrombocytopenia in 2 patients. Conclusions: T-DM1 was well tolerated in pre-treated HER2 positive advanced BTCs, but did not statistically improve PFS in comparison to historical data. Patients who did not have rapid progression on prior systemic therapy appeared to have a more favorable survival in comparison to rapid progressors and the role of T-DM1 in such favorable cohorts can be explored in larger studies. Clinical trial information: CTRI/2023/07/055785.