626 Background: The incidence of early-onset gastroenteropancreatic neuroendocrine tumors (EO GEP-NETs), defined as diagnosis before age 50, is on the rise. Given their heterogeneous disease course, we aimed to identify clinical and demographic factors associated with overall survival (OS) in this population. Methods: We conducted a multicenter retrospective study using the TriNetX research platform, a federated network of de-identified electronic medical records. Adults diagnosed with EO GEP-NETs between January 1 st 2010 and January 1 st 2025 were identified, and effect of covariates on OS was evaluated using Cox proportional hazards model. Covariates included age at index, sex, race, marital status, obesity, type 2 diabetes mellitus, nicotine and alcohol dependence, depression, and metastatic sites (liver, bone, peritoneum, brain, lymph nodes, lung, retroperitoneum). Results: A total of 17,476 patients with EO GEP-NETs were identified; 42.3% were female and 65.3% were white. Factors associated with worse prognosis and increased mortality included male sex [HR 1.35, 95% CI 1.24–1.46; p<0.0001], nicotine dependence [HR 1.35, 95% CI 1.19–1.54; p<0.0001], type 2 diabetes mellitus [HR 1.21, 95% CI 1.05–1.39; p=0.008], and older age at diagnosis [HR 1.02 per year, 95% CI 1.02–1.03; p<0.0001]. Metastatic sites significantly associated with worse OS included liver [HR 2.53, 95% CI 2.18–2.93; p<0.0001], bone [HR 2.41, 95% CI 1.95–2.97; p<0.0001], peritoneum [HR 2.27, 95% CI 1.81–2.84; p<0.0001], brain [HR 2.23, 95% CI 1.69–2.94; p<0.0001], lymph nodes [HR 2.05, 95% CI 1.74–2.41; p<0.0001], and lung [HR 1.68, 95% CI 1.33–2.11; p<0.0001]. Protective factors included obesity [HR 0.84, 95% CI 0.74–0.96; p=0.01] and "married" status [HR 0.73, 95% CI 0.66–0.81; p<0.0001]. Race, alcohol dependence, and depression were not significantly associated with OS. Conclusions: Among patients with EO GEP-NETs, adverse prognostic factors include male sex, nicotine dependence, type 2 diabetes, older age at diagnosis, and metastatic involvement of the liver, bone, peritoneum, brain, lymph nodes, or lung. In contrast, marital status and obesity were associated with improved survival. These findings highlight prognostic heterogeneity in EO GEP-NETs and may help inform risk stratification and patient counseling. Cox proportional hazard model for overall survival. Covariate Hazard ratio P value 95% confidence interval Male 1.345 <0.0001 (1.238, 1.462) Alcohol dependence 1.033 0.862 (0.718, 1.486) Nicotine dependence 1.354 <0.0001 (1.189, 1.541) Overweight and obesity 0.843 0.010 (0.740, 0.961) Married 0.731 <0.0001 (0.660, 0.809) Depression, unspecified 0.838 0.118 (0.671, 1.046) Type 2 diabetes mellitus 1.209 0.008 (1.052, 1.389) Age at Index 1.021 <0.0001 (1.015, 1.026)

Background: The optimal first-line biologic therapy for refractory ulcerative proctitis (UP) remains uncertain, largely because patients with UP are frequently excluded from biologic clinical trials, limiting evidence to guide treatment selection. This study evaluated outcomes among patients with UP treated with first-line TNF inhibitors or vedolizumab. Methods: We performed a retrospective cohort study using the TriNetX database between 1995 and 2023. Propensity score matching was applied to balance demographics, laboratory parameters, and baseline medications. Primary outcomes included corticosteroid use, all-cause emergency room (ER) visits and hospitalizations, and colectomy, assessed at 6, 12, and 24 months after initiation of TNF inhibitors or vedolizumab. Secondary outcomes described real-world biologic usage patterns in UP. Results: Among 641 patients with UP receiving advanced therapy, the most commonly used biologics were adalimumab (39%), infliximab (27%), and vedolizumab (26%). Ustekinumab was used in 12% of patients. In matched analyses, TNF inhibitor therapy was associated with reduced ER visits and hospitalizations at 6 and 12 months compared with vedolizumab (6 months: 14.3% vs. 25%, aOR 0.50, p-value 0.03; 12 months: 16.1% vs. 35.2%, aOR 0.35, p-value 0.01). By 24 months, no significant differences were observed. Corticosteroid use and colectomy rates were similar across therapies at all time points. In a subgroup comparison between adalimumab and vedolizumab, results were consistent with the primary analysis, with lower short-term ER visits and/or hospitalizations among patients receiving adalimumab. Conclusions: In this propensity-matched analysis, TNFi therapy was associated with lower short-term healthcare utilization, with no significant differences observed in corticosteroid use. These findings should be interpreted cautiously given nonspecific outcomes and potential residual confounding from unmeasured disease variables such as endoscopic activity.

e20674 Background: Dato-DXd is an antibody-drug conjugate with a TROP2-directed monoclonal antibody. Recent trials have demonstrated promising efficacy for Dato-DXd in pre-treated advanced NSCLC compared to 2nd line chemotherapy. Methods: A systematic search using terms encompassing Dato-DXd and NSCLC was conducted in PubMed, Embase, Cochrane and Scopus. A total of 2866 records were identified and imported into Rayyan. These were screened independently by two reviewers, and a third independent reviewer resolved conflicts. 56 studies were included for full text screening subsequent to which 5 studies were included for final analysis. All 5 studies were randomized controlled trials that studied Dato-DXd. 3 were full text articles, and 2 were abstracts. Binary Random-effects (RE) model pooled proportions (PP) using DerSimonian-Laird method was performed using OpenMeta. Results: A total of 756 patients were included from 5 studies. All studies included patients with advanced stage NSCLC who had received 1-5 prior lines of therapy. 4 studies used a standard Dato-DXd dose of 6mg/kg every 3 weeks while one study divided patients into 4mg/kg, 6mg/kg and 8mg/kg every 3-weeks groups. Disease Control Rate (DCR) ie CR+PR+SD was seen in 77.1% [(74.2-80.1) I2=0%]. Overall Response Rate (ORR) ie CR+PR was seen in 30.8% [(26.8-34.9) I2=24.4%]. Mortality rate was 62.8% [(49.7-76.0) I2=89.3%]. Pooled mean OS was 12.1 months (8.4-15.3), PFS was 5.5 (3.4-7.2). Pooled mean for median time to response was 1.4 months (1.2-9.7), median duration of response (DOR) was 9.6 (4.6-18.2). Stomatitis was seen in 55.5% [(50.0-60.9) I2=50.7%]. Pneumonitis was seen in 5.4% [(2.2-8.6) I2=78.8%]. Drug discontinuation due to adverse effects occurred in 11.5% [(6.7-16.2) I2=70.6%]. Rest of analytic statistics shown in Table 1. Conclusions: Pooled data for Dato-DXd in the subsequent line setting demonstrated a robust overall response rate and disease control rate.In comparison DCR for docetaxel and ramucirumab in the REVEL study was 67%. Based on this, Dato-DXD could be a subsequent line treatment option in metastatic NSCLC. While meta-analysis results can be confounded by heterogeneity between studies, results of ongoing clinical studies on Dato-Dxd that may result in the near future may help better answer this question. Pooled proportion metrics for Dato-DXd in pretreated advanced NSCLC. Dato-DXd in pretreated NSCLC % (95% CI) I 2 Partial Response (PR) 27.7% (22.4-32.9) 48% Complete Response (CR) 1.4% (0.5-2.3) 0% Stable Disease (SD) 47.2% (42.2-52.2) 27.5% Progressive Disease (PD) 14.3% (11.5-17.0) 0% Overall response rate (ORR) 30.8% (26.8-34.9) 24.4% Disease Control rate (DCR) 77.1% (74.2-80.1) 0% Grade 3 or worse adverse effects (AE) 38.8% (28.3-49.4) 88.9% Pneumonitis 5.4% (2.2-8.6) 78.8% Stomatitis 55.5% (50.0-60.9) 50.7%

Introduction Frailty remains an important risk factor for increased morbidity and mortality in patients undergoing various surgical interventions. The impact of frailty on clinical outcomes in patients undergoing Peroral Endoscopic Myotomy (POEM) is not well established. We aim to determine the association between frailty and clinical outcomes in patients hospitalized for POEM procedure. Methods We conducted a cohort study using data from the National Inpatient Sample (NIS) for the years 2017 to 2019. Adult patients who underwent POEM following hospitalization were identified using International Classification of Diseases (ICD) diagnostic codes. The Hospital Frailty Risk Score (HFRS) was used to classify patients as Frail or Non-Frail. Multivariate logistic regression analysis was performed to compare outcomes between study groups. Discharge weights were applied to provide national estimates for total hospital expenses. Results Among 1,735 POEM patients, 220 (12.68%) patients were frail. Frail patients had higher Charlson Comorbidity Index (CCI) compared to non-frail patients. In terms of systemic adverse events, frail patients had more cardiovascular (2.27% vs 0.00%, p < .01), thoracic (13.64% vs 2.97%, p < .01), and infectious (18.18% vs 2.64%, p < 0.01) adverse events compared to non-frail patients. The number of patients requiring TPN was higher in frail (13.64 vs 1.32, p < 0.01) compared to non-fail patients. After adjusting for confounders, frail patients were more likely to require TPN [OR 13.49 (95% CI 2.00-91.25)], had higher incidence of infectious [OR 17.38 (95% CI 5.22–57.91)] and thoracic [OR 5.75 (95% CI 1.75–18.92)] adverse events as well as increased LOS [OR 6.56 (95% CI 3.64–9.47)] when compared to non-frail patients. Conclusion Frailty in patients undergoing POEM is associated with a higher risk of systemic adverse events, need for TPN, longer hospital stays, higher healthcare cost, and increased in-hospital mortality. These findings emphasize the importance of frailty assessments in clinical decision-making for patients undergoing POEM.

Abstract Characterization of a patient’s tumor microenvironment is fundamental to advancing translational strategies in immuno-oncology. Histopathological evaluation of tissue slides from patients can provide this invaluable information, informing disease heterogeneity, tumor contexture, and target expression - all important to identifying patients more likely to benefit from therapy. However, availability of sufficient tissue is often a challenge to produce such a comprehensive tumor characterization. Measurement of target expression using an H&E slide could greatly reduce the usage of tissue for IHC making sections available for other investigative purposes. Here, an AI-driven predictive model was developed on H&E digital slides to simulate the expression of a tumor specific biomarker and CD3 across 4 different tumor types. Four epithelial tumor types (TNBC, NSCLC, ovarian, and cervical cancer) consisted of 400 H&E slides, 400 CD3 slides and 400 tumor specific biomarker IHC slides (100 cases per tumor) were used for this study. The Bio-AI Predict-X platform was utilized for the optimization of separate tumor models using pathology annotations as basis for development. The network output included tumor tiles as well as the tiles from adjacent stromal/normal tissue. Models were optimized until an AUC > 0.8 was achieved and prediction results were approved by the combined pathology teams. Predict-X was used for IHC marker quantification on a tile basis for both CD3 and the tumor specific biomarker slides with significant correlation to manual counts (p<0.001, r>0.8). Images from each case were co-registered so that ground truth for each tile with the IHC count was used in the predictive model. Tiles from tumor and corresponding adjacent stroma/normal tissue from all cases were subdivided into 3 groups for predictive model development. A training, validation, and test set were used, the latter of which was not used for development, only as a final assessment of model performance. A pan-tumor predictive model was developed for CD3 IHC on TNBC, cervical and ovarian cancers. The test set AUC values on cases from all 4 tumors were >0.7. Since the tumor specific biomarker stain was specific to tumor morphology, 4 separate predictive models were developed - one for each of the indications used with a test AUC >0.86. These findings suggest that deep learning can be used as a complementary method to prescreen H&E-stained images to enhance the detection rate of the tumor specific biomarker and CD3 positivity in patient tumors. Additional work will involve the optimization of these models for implementation in a clinical setting. Citation Format: Alan Jerusalmi, Krishna Bairavi, Ayushi Shah, Tom Chittenden, Mike Bonham, Chung-Wein Lee, Brandon Higgs, Anantharaman Muthuswamy. Development of predictive models for expression of a tumor specific biomarker and CD3 on H&E digital slides [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B092.

This study investigated how post-operative ustekinumab levels relate to surgery type, endoscopic, biochemical, and clinical outcomes in patients with Crohn’s Disease. A retrospective study of patients with Crohn’s Disease with a disease-related operation between 2016 and 2022 assessed outcomes based on ustekinumab levels. Patients were included if they had an ustekinumab trough level within two years post-operatively. Patients were separated into groups based on whether their ustekinumab trough levels were adequate, defined as ≥ 4 μg/mL, or suboptimal < 4 μg/mL. A subset of patients with ustekinumab levels taken within two years both before and after surgery was compared to non-surgical treatment-escalated controls outside the initial patient set. Harvey-Bradshaw index was used to evaluate clinical disease activity. Rutgeert’s and Simple Endoscopic Score for Crohn’s Disease was used to evaluate endoscopic disease activity. C-reactive protein and fecal calprotectin values were collected to evaluate the molecular inflammatory disease state. CBC data were used to evaluate anemia. Forty-four patients were identified, which had ustekinumab levels after Crohn’s Disease-related surgery. Twelve of these patients had pre-operative levels and were compared to 26 non-surgical treatment-escalated controls. No relationship between ustekinumab levels and endoscopic or clinical disease activity post-operatively was found. This also held true when looking at different surgery types. Adequate levels of ustekinumab post-operatively yielded lower risk of anemia. Surgery itself did not have an impact on ustekinumab levels. This study provided new insights into how post-operative ustekinumab levels impact several factors in patients having undergone Crohn’s disease-related surgery.