tbuckley/cabot-search huggingface dataset:
Comparison of screening outcomes associated with advanced precancerous lesion versus colorectal cancer sensitivity for a blood-based test: A simulation study.
Authors: Vahab Vahdat, John B. Kisiel, Derek W. Ebner, Michael Dore, Chris Estes, A. Mark Fendrick, Paul J. Limburg
Journal: Journal of Clinical Oncology (2025)

89 Background: With estimates of over 150,000 incident and 50,000 fatal colorectal cancer (CRC) cases in 2024, efforts are ongoing to improve the national screening performance and engagement in the US. The Centers for Medicare &amp; Medicaid Services (CMS) have established criteria for covering new blood-based CRC screening tests if minimum CRC sensitivity and specificity thresholds are met. However, the current blood-based tests are challenged by their relative inability to detect advanced precancerous lesions (APLs). At present, the importance of APL versus CRC sensitivity on screening outcomes remains undetermined. To address this knowledge gap, we conducted a simulation study to compare the screening effectiveness and outcomes of a hypothetical blood-based test across a range of sensitivities for CRC and APL detection. Methods: Outcomes were simulated using the CRC-AIM microsimulation model, which has been previously calibrated and validated. Predicted outcomes were calculated for average-risk individuals screened triennially with a blood-based test between ages 45-75 years, assuming perfect adherence. Base-case screening sensitivity and specificity inputs were based on CMS minimum thresholds (74% CRC sensitivity, 90% specificity) with assumed 10% APL sensitivity. Additional scenarios considered an increase in either APL or CRC sensitivity. Outcomes of interest included life years-gained (LYG), CRC incidence, and mortality reductions. Results: Compared to the CMS minimum performance (Table), increasing APL sensitivity by 1% (from 10% to 11%) resulted in a similar increase in LYG as compared to increasing CRC sensitivity by 11% (from 74% to 85%). Additionally, increasing APL sensitivity by 1% resulted in greater reductions in CRC cases and deaths (3% decrease) as compared to increasing CRC sensitivity by 11% (0% and 1% reductions, respectively). Conclusions: Data from this study show that increased APL sensitivity is a key determinant of screening-related outcomes, such as LYG, derived from a blood-based strategy, and that similar results would require much larger increases in CRC sensitivity. With the current CMS minimum performance threshold, blood-based tests that are designed to have high APL sensitivity can outperform tests with higher CRC sensitivity and little to no APL sensitivity. Comparison of CRC screening health outcomes with CMS proposed minimum threshold blood-test versus hypothetical tests with either increased APL and CRC sensitivity. APL Sensitivity CRC Sensitivity CRC Specificity Follow-up Colonoscopies CRC Cases (% reduction) CRC Deaths (% reduction) Life-Years Gained (LYG) (% increase) 10% 74% 90% 809 50 (ref) 18 (ref) 220 (ref) 11% 74% 90% 813 48 (-3%) 17 (-3%) 226 (3%) 10% 85% 90% 809 50 (0%) 18 (-1%) 227 (3%) APL: Advanced precancerous lesions; CRC: Colorectal cancer.
Safety and biomarker assessment of ST316, a novel peptide antagonist of ß-catenin, in patients with advanced solid tumors.
Authors: Anthony B. El-Khoueiry, Nehal J. Lakhani, Jason Timothy Henry, Steven Francis Powell, Niharika B. Mettu, Joyce Gakuria, Franco Abbate, Paolo Nuciforo, Jim Rotolo, Abi Vainstein Haras
Journal: Journal of Clinical Oncology (2025)

286 Background: Constitutive activation of ß-catenin, resulting in its nuclear accumulation and deregulated transcriptional activity, is a key event in colorectal cancer (CRC). Additionally, pathway mutations correlate with immune exclusion in CRC and across different tumor types. Disruption of the interaction of ß-catenin and its co-activator BCL9 is sufficient to suppress oncogenic ß-catenin transcriptional activity, without impacting its homeostatic functions in normal tissue. ST316 is a first-in-class, cell-penetrating peptide antagonist of the ß-catenin and BCL9 interaction. Preclinical evaluation revealed significant bioavailability and potent activity in CRC models with no impact on ß-catenin homeostatic functions such as intestinal stem cell survival or bone morphology. Methods: A phase 1-2 (P1-2) escalation-expansion study has enrolled patients (pts) with advanced solid tumors likely to harbor abnormalities in the Wnt/ß-catenin pathway, to assess the safety, pharmacokinetics (PK), biomarker and preliminary activity of ST316, and to recommend a P2 dose (RP2D). Paired biopsies were collected when feasible and assessed for drug penetration and pharmacodynamic biomarkers. Peripheral blood (PB) collected pre- and post-treatment was assessed by flow cytometry for polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Results: As of Sep.24, 2024; 23 pts with CRC (N=14), NSCLC (N=4), PDAC (N=2), or Breast and Ovarian cancer (N=1, each), were treated in 6 cohorts (0.5-12mg/kg) with IV ST316, once weekly. Treatment related AEs were observed in 17/23 pts and were mostly low grade, except for 2 G3 AEs that resolved: Fatigue (1) and ALT/AST elevation (1). No dose-limiting toxicities (DLTs) were observed. Single agent ST316 showed disease stabilization in 4 pts. PK analysis showed dose-proportional increases in Cmax and AUC for doses up to 8 mg/kg. IHC analysis showed substantial tumor penetration of ST316 in all analyzed samples and evidence of a treatment-induced redistribution of β-catenin in a subset of pts. PB analysis indicated high baseline levels of the ß-catenin-driven immunosuppressive PMN-MDSCs , followed by a significant decrease after ST316 exposure (p&lt;0.005). The RP2D selected for combination cohorts in CRC is 8mg/kg; additional PD assessments are ongoing. Conclusions: Monotherapy ST316 was well-tolerated with dose-proportional PK and substantial tumor uptake. Pharmacodynamic analyses demonstrate mechanistic evidence of antagonism of ß-catenin signaling, including redistribution of ß-catenin subcellular localization and significant depletion of the ß-catenin-driven immunosuppressive PMN-MDSC population. Based on these data, ST316 advanced into P2 in CRC pts in combination with SoC in 2 nd and 3 rd line. Clinical trial information: NCT05848739 .
Adjuvant therapy with somatostatin analogs for recurrent gastric neuroendocrine tumors type 1.
Authors: Alla Anatolievna Markovich, Yaroslav Zhulikov, Ekaterina Evdokimova, Vera Gorbunova, Galina Emelianova, Kizler Gadzhieva, Olga Malikhova, Ivan Karasev, Vera Delektorskaya, Yuri Kuvshinov, Anna Kuznetsova, Elena Artamonova
Journal: Journal of Clinical Oncology (2025)

665 Background: Neuroendocrine gastric tumors (gNETs) type 1 are associated with chronic autoimmune atrophic gastritis, hypergastrinemia and usually have multifocal lesions and high frequency of recurrence (up to 70% for 2 years). Somatostatin analogs (SA) showed promising data in neoadjuvant setting with 84% of complete responses in a small retrospective trial. The aim of this study was to evaluate the efficacy of adjuvant treatment with SA for recurrent gNETs type 1. Methods: This retrospective, single-center study included patients (pts) with recurrent gNETs who received adjuvant treatment with SA. Recruitment of pts was carried out from 2012 to February 2024. Results: The study included 35 pts, 33 females and 2 males. Endoscopic mucosal resection (EMR) was performed in 34 cases (97.1%), gastric resection in 1 (2.9%). The median of previous EMR was 2 (1-6) procedures. Most of the pts have multifocal lesions – 28 (80%), the median of lesions is 5. The median tumor size – 6 mm, tumor size &gt;10 mm was observed in 2 cases (5.7%), one of them had N+. The median of ki67 was 3,5% (1-10%), grade 1 (G) - 14 (40%) and G2 - 21 (60%). All pts received adjuvant therapy with SA, 33 (94.3%)long-active releasing octreotide30 mg and 2 (5.7%) lanreotide 120 mg every 4 weeks. The time of SA therapy was &lt;12 months in 23 cases (65.7%) and ≥12 months in 12 (34.3%). The median of follow-up was 30.5 months. The median disease-free survival (DFS) was not reached (95% CI, 67-NR). We compared median DFS after previous EMR (DFS1) without adjuvant SA and DFS after EMR with adjuvant SA (DFS2). The DFS2 was significantly higher – median of DFS1 was 8.8 months (95% CI, 2.7-14.9) not reached (95% CI, 67-NR, p&lt;0.01) . Adjuvant treatment with SA ≥12 months was associated with improved DFS compared to &lt;12 months – not reached (95% CI, 58.1-NR) versus 61 months (95% CI, 26.2-96.2, p=0.05). Adjuvant SA reduced gastrin levels after a year of therapy by ≥50% from baseline in 13 cases (37.1%). Conclusions: Adjuvant treatment with SA significantly improved DFS and should be considered for recurrent and multifocal gNETs type 1. Duration of therapy ≥12 months was significantly associated with improvement in DFS compared with shorter duration of therapy.
Racial disparities in receipt of guideline concordant pancreatic cancer care among older adults in the US.
Authors: Joshua Herb, Kai-Ping Eric Liao, Kever Lewis, Matthew H. G. Katz, John Kent Lin, Rebecca A Snyder
Journal: Journal of Clinical Oncology (2025)

679 Background: Patients racialized as Black experience higher incidence and mortality from pancreatic cancer (PC). The aim of this study was to examine differences in receipt of guideline concordant care (GCC) among older adults with PC racialized as Black, White, or Hispanic ethnicity. Methods: Patients 65 years and older with incident PC racialized as White, Black, or Hispanic ethnicity were identified in the SEER-Medicare database from 2004-2019. The primary outcome was receipt of GCC (stage I/II: surgery+chemotherapy+/-radiation; stage III: chemotherapy+/-surgery+/-radiation; stage IV: chemotherapy+/-radiation). Multivariable logistic regression was used to identify factors associated with GCC. Oaxaca-Blinder decomposition was used to examine the contribution of measured and unmeasured variables to racial disparities in receipt of GCC. Results: Of 12,772 patients included, 85.5% of patients racialized as White (n=10,915), 7.8% Black (n=992), and 6.8% Hispanic ethnicity (n=865). Patients racialized as Hispanic ethnicity and Black were more often dual-eligible for Medicare/Medicaid than patients racialized as White (38.6%, 26.9%, and 7.5%, respectively). In total, 56.3% received GCC. On adjusted analysis, patients racialized as Black were less likely to receive GCC for early stage (stage I/II) disease compared to patients racialized as White (OR 0.66; 95% CI 0.53-0.83), but not for stage III (OR 0.65; 95% CI 0.41-1.01) or stage IV (OR 0.87; 95% CI 0.66-1.14) disease. No difference in GCC was observed among patients of Hispanic ethnicity when compared to patients racialized as White. Increased age and dual-eligibility were associated with decreased likelihood of GCC across stages. Differences in receipt of GCC among patients racialized as Black and White remain largely unexplained. Of the measured factors, comorbidities, dual-eligibility, and area level poverty contributed most to the disparity in GCC (Table). Conclusions: Just over half of an insured population with PC receive GCC. Despite an increased focus on equity in cancer care, Black-White racial disparities in receipt of GCC are prevalent, particularly among patients with early-stage disease. Further studies are critical to identify and address the unmeasured factors driving treatment disparities. Contributing factors to racial disparities in guideline concordant care for patients with pancreatic cancer. Stage I/II Stage III Stage IV Difference (White-Black) 11.6% 9.4% 4.1% Explained Age -3.0% -2.0% -1.0% Sex 0.1% 0.8% 0.1% Dual-Eligibility 2.0% 3.1% 0.8% Charlson Comorbidity Index 1.3% 0.2% 0.7% Area Level Poverty 2.2% -0.8% 0.7% Hospital/Practice Volume 1.2% -0.3% -0.03% Region 0.4% 0.9% -0.2% Year of Diagnosis -0.1% 0.5% 0.1% Unexplained 7.5% 7.0% 3.0% Positive values indicate these factors increased the measured disparity, while negative values indicate these decreased the measured disparity.
Matching adjusted indirect comparison (MAIC) of <sup>177</sup> Lu-DOTATATE vs. sunitinib as first-line (1L) treatment for advanced grade 2 (G2) pancreatic neuroendocrine tumors (pNETs).
Authors: Raj Srirajaskanthan, Jaume Capdevila, Emmanuel Deshayes, Shaunak Navalkissoor, Ilya Folitar, Marcos Lovelle, Thomas Delea, Subhajit Gupta, Anup Kumar, Purnima Pathak
Journal: Journal of Clinical Oncology (2025)

664 Background: The phase 3 NETTER-2 trial recently demonstrated a statistically significant improvement in progression-free survival (PFS) with [ 177 Lu]Lu-DOTA-TATE ( 177 Lu-DOTATATE) plus long-acting octreotide (Oct LAR) vs. high-dose Oct LAR in patients with G2/G3 gastroenteropancreatic neuroendocrine tumors in the 1L setting, across tumor grades and origins (including pNETs). However, no head-to-head comparison of 177 Lu-DOTATATE to other treatment options was conducted. Sunitinib is a currently recommended 1L treatment for patients with advanced G2 pNETs. The Raymond 2018 study is the only study that assessed sunitinib in advanced pNETs and provided sub-group data for the 1L setting (80% of the patients had G2 tumors). We aimed to determine the relative efficacy (PFS) of 177 Lu-DOTATATE + Oct LAR vs. sunitinib as 1L treatment for advanced G2 pNETs using MAIC. Methods: An unanchored MAIC (due to absence of a common comparator) of PFS in patients with advanced G2 pNETs treated in 1L with 177 Lu-DOTATATE + Oct LAR vs. sunitinib was conducted using individual patient data from NETTER-2 and aggregated data published in the Raymond 2018 study. Baseline characteristics and PFS data for the sunitinib arm were available for the treatment-naïve subgroup and were considered for the analysis. Baseline characteristics considered in the MAIC included age, sex, race, prior somatostatin analogue use, and number as well as location of involved disease sites. Multiple scenarios with various combinations of covariates were considered with multivariate Cox-regression of NETTER-2 used to identify covariates predictive of PFS. Finally, the combination of covariates with a reasonable effective sample size (ESS) was selected. Results: The final ESS was estimated to be 22 for 177 Lu-DOTATATE + Oct LAR, representing 43% of the original sample size (n=50), whereas sample size for sunitinib arm was 61 patients. After matching and weighting, patient characteristics were well balanced. MAIC analysis showed a statistically significant PFS benefit with 1L 177 Lu-DOTATATE + Oct LAR vs. sunitinib in G2 pNET (PFS hazard ratio: 0.23 [95% CI: 0.12–0.45]). Unadjusted comparison showed similar results (PFS hazard ratio: 0.34 [95% CI: 0.19–0.61]). Results were consistent across various scenarios assessed. Conclusions: Using MAIC to adjust for cross trial differences, PFS comparison favored 177 Lu-DOTATATE + Oct LAR over sunitinib as 1L treatment of patients with G2 pNET.
Characteristics and outcomes of patients with early-onset versus average-onset small bowel neuroendocrine tumors.
Authors: Udhayvir Singh Grewal, Rishi Patel, Jason Semprini, Michael O'Rorke, Joseph S. Dillon, Chandrikha Chandrasekharan
Journal: Journal of Clinical Oncology (2025)

670 Background: The global incidence of early-onset gastrointestinal cancers (GI) is increasing. Although patients with more common early-onset GI cancers, e.g. colorectal cancer, often present with more advanced disease and experience relatively worse outcomes; the characteristics and treatment outcomes for less common early-onset small bowel neuroendocrine tumors (SBNETs) have yet to be explored. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with SBNETs (2004-2021), using ICD-0-3 SEER histology codes (8240/3, 8241/3, 8243/3, 8244/3, 8249/3, 8246/3). Patients with poorly differentiated histology were excluded. We used the chi-square test to compare categorical variables between early-onset SBNETs (EO-SBNETs, aged 30-49 years) and average-onset SBNETs (AO-SBNETs, aged ≥ 50 years) patients. Overall survival was estimated using the Kaplan-Meier method followed by application of the log-rank test to assess for differences in survival. A multivariable Cox regression analysis included early onset of disease, sex, race/ethnicity, marital status, urban/rural residence, prior treatments, and disease extent as covariates. All tests were conducted with a significance threshold of p &lt; 0.05 using RStudio. Results: A total of 3,713 patients were included, of which, 925 (25%) were EO-SBNETs. Compared to AO-SBNETs, EO-SBNETs patients were more likely to be females (51.1% vs 46.7%, p=0.02), non-Hispanic Black (20.8% vs 17.6%, p=0.04), Hispanic (13.6% vs 8.8%, p&lt;0.0001) and less likely to be non-Hispanic White 60.8% vs 69.9%, p&lt;0.0001). There were no differences in stage at diagnosis between the EO-SBNETs and AO-SBNETs, i.e,, localized disease (33.5% vs 31.0%, p=0.15), regional spread (41.9% vs 42.8%, p=0.64) and distant metastatic disease (20.9% vs 21.9%, p=0.50). There were no differences in receipt of surgical resection (90.5% vs 89.1%, p=0.25) or chemotherapy (5% vs 6.3%, p=0.15) comparing EO-SBNETs and AO-SBNETs respectively. In a multivariate cox regression analysis, early onset was associated with a significantly better overall survival (HR=0.49, 95% CI 0.41-0.59, p&lt;0.0001). Conclusions: With this first of its kind analysis, significantly superior overall outcomes among EO-SBNETs despite no differences in stage and receipt of surgery establishes age at diagnosis as a significant prognostic factor for SBNETs. Further studies investigating the role of factors such as differences in tumor biology and patient preferences in receipt of other therapies besides surgery are needed.
Clinical outcomes of stereotactic body radiation therapy to the liver.
Authors: Lauren Kenney, Yu-Hui Chen, Thomas Howard, Mina Bakhtiar, Harvey J. Mamon, Ritchell van Dams
Journal: Journal of Clinical Oncology (2025)

565 Background: Stereotactic body radiation therapy (SBRT) can accurately and effectively target liver lesions with an ablative dose. However, prior studies suggest that SBRT directed at tumors near the central hepatobiliary tract may lead to downstream toxicity including biliary stricture and impaired liver function. This study aims to evaluate clinical outcomes and hepatobiliary toxicities associated with SBRT to the liver. Methods: This retrospective study reviews 177 patients who received CT- or MR-guided SBRT to the liver at Dana-Farber Cancer Institute and Brigham and Women’s Hospital from 2010 to 2024. Patient demographics, treatment characteristics, and clinical outcomes were extracted from electronic medical records. Local control, regional control, and overall survival were assessed using Kaplan-Meier methods. Toxicity was evaluated by tracking the incidence of biliary stricture requiring intervention and Child-Pugh (CP) scores pre- and post-SBRT. Results: Of the 177 patients, 47 (26.6%) had primary disease and 130 (73.4%) had metastatic disease, with a median follow-up of 58.7 months. Among those with primary disease, 9 (19.1%) had post-SBRT local progression (median time to progression not reached, 95% CI: 47.3, NA) and 26 (55.3%) had regional progression (median time to progression of 20.5 months, 95% CI: 6.5, 58.1). Of patients with metastatic disease, 44 (33.8%) had local progression (median time to progression of 40.2 months, 95% CI: 23.0, NA) and 96 (73.8%) had regional progression (median time to progression of 5.9 months, 95% CI: 4.8, 9.3). Median overall survival post-SBRT was 34.6 months for primary disease (95% CI: 20.2, 57.7) and 23.6 months for metastatic disease (95% CI: 19.0, 28.8). 18 patients (10.1%) later developed biliary stricture requiring intervention (12.8% of primary disease and 9.2% of metastatic disease). Of the 119 patients with CP scores available, 59 patients (49.6%) had a maximum post-SBRT CP score increase of 2 or more (55.0% of primary disease, 46.8% of metastatic disease). Conclusions: This study demonstrates that SBRT is an effective treatment option for local control in the liver, with better survival and progression outcomes for primary disease compared to metastatic disease. Among potential post-SBRT toxicities, initial analysis indicates frequent increase in CP score and low incidence of biliary stricture requiring intervention. An ongoing analysis will explore whether the dose to central bile ducts correlates with late strictures and toxicities.
Trends in utilization of colorectal cancer screening modalities among patients with average risk in the United States from 2017 to 2023.
Authors: Brad Stieber, Mallik Greene, Quang Anh Le, Joshua Mou, Lakshya Sakthisivabalan, Danielle Lynch, A Burak Ozbay, Joseph LeMaster, Michael Dore, A. Mark Fendrick, Paul J. Limburg
Journal: Journal of Clinical Oncology (2025)

98 Background: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the US. The national CRC screening rate (58%) is still below 80%, which is the goal set by the National Colorectal Cancer Roundtable. National guidelines recommend multiple strategies for CRC screening including colonoscopy, sigmoidoscopy, CT colonography, fecal occult blood test (FOBT), fecal immunochemical tests (FIT), or multi-target stool DNA (mt-sDNA) test. To provide updated insights regarding proportional utilization of different CRC screening strategies, we analyzed modality-specific CRC screening rates across demographic subgroups between 2017 and 2023. Methods: A retrospective review was conducted using a large national claims database that covers over 165 million lives and is representative of the US population for the study period from 2017 to 2023. Individuals were included if they were aged 45-75 years, at average CRC risk in the baseline period of 1 year before the index date and continuously enrolled in a health plan for at least 1 year after the index date. The index date was defined as date of the first claim for a CRC screening test. CRC screening uptake by modality and newly screened individuals each calendar year were examined among the entire eligible population and across demographic subgroups. Results: Overall rates of CRC screening were relatively stable across the study years (approximately 20%) with the lowest annual proportion of screen eligible patients in 2020 (16.6%) and highest in 2023 (24.4%). For CRC-screened individuals, colonoscopy was the most commonly used screening modality, increasing from 1,943,733 (53%) in 2017 to 2,319,695 (58.7%) in 2023. The mt-sDNA test use increased significantly from 87,769 (2.4%) in 2017 to 807,227 (20.4%) in 2023; while FIT/FOBT use declined from 1,611,730 (44%) in 2017 to 805,150 (20.4%) in 2023. Utilization of colonoscopy and mt-sDNA tests increased notably among the 45–49 age group starting in 2021, while FIT/FOBT use simultaneously declined in this age group. Observed trends were similar to the above findings across additional subgroups defined by gender, race/ethnicity, payer type, and geographic region. Conclusions: Data from this large study of national claims data provides updated results for overall and proportional utilization of guideline-endorsed CRC screening strategies. While colonoscopy usage remained stable , the use of the non-invasive mt-sDNA test has increased significantly as FIT/FOBT usage declined over time, reflecting growing interest in this noninvasive, home-based option.