Citations

e16598 Background: Brain metastases occur in a substantial proportion of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. Stereotactic radiosurgery (SRS) is frequently used for intracranial disease control; however, contemporary real-world survival outcomes and the influence of systemic therapy exposure and metastatic burden remain incompletely characterized. Methods: We conducted a retrospective observational study using the TriNetX global federated health research network. Adult patients (≥18 years) with RCC and documented brain metastases who underwent stereotactic radiosurgery between January 2013 and December 2023 were identified. The index date was defined as the date of first SRS. Baseline demographics, comorbidities, and prior systemic therapy exposure including immune checkpoint inhibitors and VEGF-targeted therapies within 6 months before SRS were assessed. Metastatic burden was approximated using the number of distinct extracranial metastatic organ sites (single-organ vs multi-organ involvement). Overall survival (OS) was evaluated using Kaplan–Meier methods. Results: A total of 232 patients with RCC and brain metastases treated with SRS were included. Mean age was 61.2 ± 10.6 years, and 72% were male. Common comorbidities included hypertension (53%), diabetes mellitus (30%), chronic kidney disease (28%), and cerebrovascular disease (26%). Prior to SRS, 78% of patients received systemic therapy, including immune checkpoint inhibitors (49%) and VEGF-targeted therapies (46%). Using organ-site count as a proxy for disease burden, 59% demonstrated single-organ extracranial metastatic involvement. During follow-up, 95 patients (40.9%) experienced all-cause mortality. Median overall survival was 967 days (31.8 months). Estimated long-term survival probability at maximum follow-up was 21.2%. Kaplan–Meier analysis demonstrated early survival attrition followed by prolonged survival in a subset of patients. Patients receiving immunotherapy and those with limited extracranial metastatic burden demonstrated more favorable survival patterns. Conclusions: In this large contemporary real-world cohort of RCC patients with brain metastases treated with stereotactic radiosurgery, median overall survival exceeded 2.5 years, providing important modern survival benchmarks. Favorable outcomes were observed among patients receiving systemic immunotherapy and those with limited metastatic burden, supporting the continued role of SRS within multidisciplinary management strategies for selected patients with metastatic RCC.

e16469 Background: Pancreatic cancer remains among the most lethal malignancies worldwide, with limited improvement in survival despite therapeutic advances. Contemporary real-world data characterizing recent diagnosis acceleration, demographic disparities, and future burden remain limited. We evaluated national trends in pancreatic cancer burden using a large federated electronic health record (EHR) network. Methods: We conducted a retrospective multicenter real-world cohort analysis using the TriNetX Research Network. Adult patients (≥18 years) with pancreatic cancer were identified using ICD-10-CM code C25. Annual newly recorded diagnosis proportions, prevalence, and incidence rates were calculated for calendar years 2020–2024 and stratified by age, sex, race, and ethnicity. New diagnoses were defined as first recorded pancreatic cancer encounters within each calendar year. Exploratory future burden projections were generated through 2028 using autoregressive integrated moving average (ARIMA) time-series modeling. Results: Between 2020 and 2024, newly recorded pancreatic cancer diagnoses increased from 0.032% (21,118 cases) to 0.046% (23,660 cases), representing a descriptive relative increase exceeding 40%. Prevalence increased from 0.101% (65,971 cases) to 0.145% (74,139 cases), reflecting rapid expansion of disease burden. Diagnosis burden increased markedly with advancing age, with the highest burden observed among individuals aged ≥65 years. Males consistently demonstrated higher diagnosis proportions compared with females. Racial stratification demonstrated higher recorded diagnosis proportions among White and Asian populations, while substantial prevalence burden persisted across all racial groups, potentially reflecting differences in healthcare utilization and access. Non-Hispanic individuals exhibited higher diagnosis and prevalence proportions compared with Hispanic individuals. Exploratory ARIMA forecasting projected continued growth in pancreatic cancer burden through 2028, with widening uncertainty intervals over time, indicating escalating long-term healthcare demand. Conclusions: Pancreatic cancer burden in the United States is rapidly increasing, with disproportionate impact among older adults and males and persistent demographic disparities. Exploratory projection modeling suggests continued expansion of disease burden in the near term. These findings highlight the urgent need for earlier detection initiatives, risk-adapted screening strategies, and healthcare system preparedness to address the growing national impact of pancreatic cancer.

e16322 Background: Small intestine neuroendocrine carcinoma (NEC) is a rare, aggressive malignancy comprising less than 0.1% of gastrointestinal cancers. Population-level data remain limited, restricting understanding of long-term survival patterns, demographic disparities, and evolving disease burden. We evaluated survival outcomes, demographic predictors, and incidence trends of small intestine NEC in the United States. Methods: We conducted a retrospective population-based cohort study using SEER Research Data (17 registries, November 2024 submission). Patients diagnosed with malignant small intestine NEC (ICD-O-3 morphology code 9.3.3.1.2) between 2000 and 2022 were identified using SEER*Stat (v9.0.4.2). Variables including age group, sex, race, year of diagnosis, survival time, and vital status were analyzed in R (v4.5.1). Overall survival (OS) was estimated using Kaplan–Meier methods and compared using log-rank testing. Cox proportional hazards models identified independent predictors of OS. Annual case counts were modeled using time-series forecasting to project future incidence. Results: A total of 506 patients were included. Estimated OS was 94.4% (95% CI 92.4–96.4) at 1 year, 88.1% (85.3–91.0) at 3 years, and 82.4% (79.0–85.9) at 5 years, with a subset demonstrating survival beyond 15 years. Increasing age was associated with worse survival (log-rank p = 0.058). Significant racial differences in OS were observed (log-rank p < 0.0001). In multivariable analysis, race remained independently associated with OS. Incidence forecasting projected a modest increase in annual case burden over the next decade. Conclusions: Small intestine NEC demonstrates heterogeneous survival outcomes, significant demographic disparities, and projected growth in disease burden. These findings highlight the need for improved risk stratification, equitable access to care, and integration of molecular and treatment-level data to optimize management of this rare malignancy

e16246 Background: First line systemic therapy for advanced hepatocellular carcinoma (HCC) includes immune checkpoint inhibitor (ICI) combination therapy, with tyrosine kinase inhibitors (TKIs), lenvatinib or cabozantinib, commonly used as second line therapy. However, there is limited data comparing efficacy of TKIs following first line ICI therapy. In the present study, we compared survival and risk of hospitalization in a propensity score matched analysis of patients who received lenvatinib or cabozantinib following progression on first line ICI therapy in patients with advanced HCC. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. We identified adult patients with a history of HCC who received atezolizumab plus bevacizumab (A+B) or durvalumab plus tremelimumab (D+T) as first line treatment. We then stratified patients by use of lenvatinib or cabozantinib in the subsequent line setting. Propensity score matching (PSM) was conducted between those who received lenvatinib and those who received cabozantinib, matching for demographic factors (age, sex, race), clinical characteristics (history of alcohol use, ascites, esophageal varices, or viral hepatitis), and laboratory parameters [platelets, albumin, bilirubin, INR and alpha-1-fetoprotein (AFP)]. Results: We identified 416 patients who were initially treated with either A+B or D+T, with 327 patients receiving A+B and 89 patients receiving D+T. Of these, 336 patients (80.8%) subsequently received lenvatinib and 80 patients (19.2%) received cabozantinib. Baseline characteristics of demographic factors, clinical characteristics, and laboratory parameters were comparable between patients in the lenvatinib arm and cabozantinib arm with all standardized mean differences (SMD) < 0.10. After PSM, 76 patients were included in the analyses, with all variables adequately balanced. There was no significant difference in the risk of hospitalization between those receiving lenvatinib or cabozantinib at 3 months [31.6% vs 34%, odds ratio (OR) 1.13, 95% confidence interval (CI) 0.57-2.2]. There was also no significant difference in mOS between those receiving lenvatinib and cabozantinib [9.5 vs 9.0 months, hazard ratio (HR) 1.03, 95% CI 0.62-1.7]. Conclusions: In patients with HCC who received lenvatinib or cabozantinib as second-line therapy following first-line ICI combination therapy, we found no significant differences in rate of hospitalization or survival. These findings suggest that either option may be appropriate, and decisions may be based in side effect profile and patient preferences. Prospective studies will be important to further assess differences in patient outcomes.

e15598 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of gastrointestinal (GI) malignancies. Emerging evidence suggests that gut microbiome composition plays a critical role in modulating the efficacy of immunotherapy. Antibiotics, by disrupting intestinal microbial diversity, may attenuate antitumor immune responses and compromise ICI outcomes. We evaluated time-dependent clinical outcomes associated with antibiotic exposure using real-world data. Methods: We conducted a retrospective cohort study using a large federated real-world database (2015-2025). Adults (18–89 years) with gastrointestinal or hepatobiliary malignancies (including colorectal, gastric, esophageal, and liver cancers) treated with ICI, receiving systemic antibiotics, were compared with matched controls without antibiotic exposure. Cohorts were balanced using 1:1 Propensity score matching for demographics, comorbidities, and treatment variables. The primary outcome was all-cause mortality at 30 days of ICI initiation; the secondary outcomes were hospitalization secondary to infectious and organ-related complications, overall survival at 1 and 3 years. Pre-specified subgroup analyses were performed in older adults ( > / = 65 years). Effect estimates were reported as risk ratios( RR), hazard ratios (HR), and absolute risk differences. Survival was analyzed using Kaplan–Meier curves and Cox proportional hazards models. Results: Within 30 days, antibiotic exposure was associated with significantly increased risks of Clostridioides difficile infection (RR 2.39), pneumonia (RR 2.93), acute kidney injury (RR 1.40), acute respiratory failure (RR 2.11), and neutropenia (RR 1.18) (all p < 0.05). Absolute risk differences translated to a number needed to harm (NNH) of approximately 38 for pneumonia, 143 for acute kidney injury, and ~140 for C. difficile infection. One-month mortality was modestly higher in the antibiotic group (5.4% vs 4.5%; HR 1.22; p = 0.014). However, no significant differences in mortality were observed at 6 months, 1 year, or 3 years, and survival curves converged over time. In the subgroup analysis of adults ≥65 years, early adverse event patterns were preserved, while long-term mortality remained unchanged. One-year hospital admission rates did not differ significantly between groups. Conclusions: Antibiotic exposure is associated with substantial early infectious and organ-related harm and a small increase in short-term mortality, without improvement in long-term survival, including among older adults. These findings highlight a critical opportunity for risk-adapted antibiotic stewardship and careful reassessment of empiric antibiotic use. Key words: ICI- Immune checkpoint inhibitors, RR- Risk ratio, HR- Hazard Ratio, NNH- Number Needed to Harm.

Objectives To evaluate whether extracellular volume (ECV) fraction derived from contrast‐enhanced computed tomography (CT) is associated with recurrence risk in patients with treatment‐naïve high‐risk non‐muscle‐invasive bladder cancer (HR‐NMIBC) receiving intravesical gemcitabine/docetaxel (Gem/Doce) therapy. Patients and Methods This retrospective cohort study, conducted at a tertiary referral centre, included 103 patients with HR‐NMIBC treated with intravesical Gem/Doce between 2012 and 2024. All patients underwent pre‐resection contrast‐enhanced CT with an equilibrium phase (~3 min post‐injection). Tumour ECV fraction (%) was calculated using the formula: ECV = (ΔHUtumour/ΔHUaorta) × (1 − haematocrit) × 100, where Δ Hounsfield units (HU) represents the change in attenuation between non‐contrast and equilibrium phases. Regions of interest were manually placed in the tumour and abdominal aorta, and haematocrit values obtained within ±10 days were used. Associations between clinical variables, ECV, and recurrence were evaluated using Cox proportional hazards models, with discrimination assessed by Uno's C‐statistic. Results The median (interquartile range) follow‐up was 17 (10–25) months. High‐grade recurrence‐free survival (HG‐RFS) was 76% at 12 months and 69% at 24 months. CT‐derived ECV was the only variable significantly associated with HG‐RFS (hazard ratio 1.05, 95% confidence interval 1.03–1.08), demonstrating strong discrimination (C‐statistic, 0.81; P < 0.01). A 15% threshold offered the best sensitivity–specificity trade‐off (~70% each) for predicting HG‐RFS at 12 and 24 months. Patients with ECV ≤15% had markedly better HG‐RFS than those with ECV >15% at 24 months (88% vs 41%). Conclusions The CT‐derived ECV is a practical, first‐of‐its‐kind imaging biomarker associated with recurrence risk and useful for risk stratification in patients with HR‐NMIBC treated with intravesical Gem/Doce, a regimen increasingly used in the setting of global Bacillus Calmette‐Guérin shortages and intolerance. ECV can be rapidly quantified from routine contrast‐enhanced CT using standard picture archiving and communication system (PACS) tools, without additional imaging or proprietary software, making it a feasible metric for integration into risk‐adapted management pending large‐scale validation with extended follow‐up.

9525 Background: Melanocortin-1 receptor (MC1R) is a novel target for radiopharmaceutical therapy and is highly expressed on melanoma tumor cells. VMT01 is an MC1R-targeted peptide. 203 Pb is used for patient selection via SPECT imaging. Peptide radiolabeling with 212 Pb delivers alpha-particle therapy. Here, we present data on the treatment of adult patients with MC1R-positive metastatic melanoma receiving [ 212 Pb]VMT01 either as a monotherapy or in combination with the programmed death-1 (PD-1) checkpoint inhibitor, nivolumab. Methods: This is an ongoing phase I/IIa, first-in-human, prospective, multicenter, open-label, radioactive dose-finding and dose-expansion trial. The objectives are to investigate safety, pharmacokinetics, dosimetry, and efficacy. Participants receive up to 3 treatment cycles with either [ 212 Pb]VMT01 3 mCi, 5 mCi, or 1.5 mCi monotherapy, or combination therapy with [ 212 Pb]VMT01 (1.5 mCi) + nivolumab (480 mg, Q4W) or [ 212 Pb]VMT01 (3 mCi) + nivolumab. Participants are evaluated for any DLTs for the first 6 weeks after cycle 1. Efficacy is assessed by RECIST v1.1 criteria by the investigator. Results: As of 24 December 2025, 26 participants (53.8% male; median age: 68 years [range: 27-81]) with MC1R-positive metastatic melanoma were enrolled. The median prior systemic therapies was 4. All 26 enrolled participants received ≥1 dose of [²¹²Pb]VMT01. No DLTs were reported. All SAEs (including one grade 5 SAE) were attributed to disease progression. Most TEAEs were grade 1 (19.2%) and grade 2 (34.6%). Grade 3 TEAEs occurred in 8 participants (30.8%), 5 on monotherapy and 3 on combination therapy (3 mCi + nivolumab). Of the 22 evaluable participants, 1 PR, 9 SD, and 12 PD were reported. Four participants had progression-free survival of ≥6 months. Conclusions: [ 212 Pb]VMT01 as a monotherapy and in combination with nivolumab was generally safe and well-tolerated in 26 enrolled participants, with antitumor activity observed at the 3 mCi dose level. These data may be supplemented with a more complete follow-up at the time of the meeting. Clinical trial information: NCT05655312 .

9535 Background: MUM carries a poor prognosis with few effective treatments, especially for HLA-A*02:01-negative pts. While a subset of MUM pts responds to immune checkpoint inhibitors, the comparative efficacy of IPI+PD1 versus PD1 monotherapy is unclear. This study compares objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety between these regimens in MUM. Methods: MUM pts treated with PD1 or IPI+PD1 at 15 major melanoma centres (from Australia, Europe, United States and Israel) were included. Demographics, patient and disease characteristics, and clinical outcomes were examined. Univariate and multivariate (MVA) analyses were performed to identify clinical predictors of response and survival. Results: Of 412 MUM pts treated, 150 (36%) had PD1 and 262 (64%) received PD1+IPI. Compared to the PD1 group, PD1+IPI-treated pts were younger (64 vs. 70 years; p<0.001), had higher rate of elevated LDH (44% vs. 31%; p=0.037), and more frequently had prior treatment with tebentafusp (6.5% vs. 1.3%; p=0.031). Median follow-up from commencement of PD1+/-IPI was 4.9 years (95% CI 4.7 – 6.1). ORR was higher in IPI+PD1 group (18%) vs. PD1 (9%) (p=0.008), particularly in males (p=0.009), patients with liver metastases (p=0.018) and with lung metastases (p=0.011), with elevated LDH (p=0.047) and with no prior treatment with tebentafusp (p=0.007). PFS and OS at 1 and 2 years were numerically higher with IPI+PD1 (1- and 2-year PFS: 23% and 15%; 1- and 2-year OS: 63% and 39%) vs. PD1 (1- and 2-year PFS: 17% and 11%; 1- and 2-year OS: 54% and 36%), but these differences were not statistically significant (p>0.05). On MVA, adjusting for predefined variables (age, gender, ECOG PS, LDH, presence/absence of liver/lung metastases, prior treatment with tebentafusp), IPI+PD1 was associated with higher ORR (OR 2.71, 1.30 – 6.05; p=0.01) but not with PFS or OS compared to PD1. Presence of liver metastases (ORR [OR 0.28; 95% CI 0.13 - 0.64], PFS [HR 1.61; 95% CI 1.11 - 2.34], OS [HR 2.02; 95% CI 1.32 - 3.10]), ECOG PS≥2 (PFS [HR 1.82; 95% CI 1.07 - 3.10], OS [HR 2.24; 95% CI 1.25-4.01]), elevated LDH (PFS [HR 1.66; 95% CI 1.30 - 2.11], OS [HR 2.39; 95% CI 1.84-3.10]) and prior tebentafusp treatment (OS [HR 2.36; 95% CI 1.21-4.59]) were also independent predictors of response and/or survival. A higher percentage of pts experienced grade ≥3 immune-related adverse events (irAEs) in the IPI+PD1 group compared to the PD1 group (34% vs 13%, p<0.0001). Most pts ceased treatment due to progression (234, 57%), and more pts stopped due to toxicity in the IPI+PD1 vs. PD1 group (25% vs. 9%, p<0.0001). Conclusions: In pts with MUM, IPI+PD1 demonstrated a higher ORR but did not improve survival compared with PD1 alone. IPI+PD1 was more toxic, leading to early treatment discontinuation in one-quarter of pts. These findings may help guide treatment selection in MUM.

9007 Background: Since transition to virtual interviews, application and interview inflation have increased the work burden of GME recruitment. In 2021, AAMC ERAS implemented a process that allows applicants to assign signals to top programs of interest. There is a paucity of guidance on optimal use of ERAS signals (ES), resulting in apprehension and uncertainty amongst applicants and program directors (PD). For the 2026 ERAS cycle, Hematology/Oncology programs (HOP) had the option to participate in ES, in which applicants are provided 5 gold (G) signals and 15 silver (S) signals. First-hand knowledge on how ES was utilized by HOP, as well as PD perceptions about ES, may guide best practices on ES. Methods: During the ASCO Oncology Training Program Leadership Retreat in November 2025, an anonymous survey, assessing HOP utilization and perception of ES, and the impact of ES on recruitment practices, was launched. One PD from each HOP was invited to complete the survey while onsite. Results: 88 HOP (46% of ACGME HOP) are represented. 97% (n=85) utilized ES. Of HOP who used ES, 74% are academic. 32% are small (1-9 fellows), 43% medium (10-19 fellows), and 25% large (20+ fellows). 79% received 400+ applications. 69% reviewed applications without signals but gave higher consideration to signaled applicants. 25% only reviewed applications with signals. 28% used ES when creating rank list; 45% think ES utilization is appropriate during ranking. 85% reported ES did not alter their approach to applicants requiring visa sponsorship. 78% felt ES made the interview selection process easier. 66% were more satisfied with this year’s recruitment process compared to years without ES. The most requested change to ES was reduction of allowed signals, especially silver. 98% will use ES next year. Conclusions: Despite limited knowledge on ES impact on recruitment, nearly all surveyed HOP participated in ES this past year and will continue. Most HOP view ES positively though many desire changes, particularly with the number of signals. Most HOP consider all applications regardless of ES. However, some HOP with larger applicant pool are using ES as inclusion criteria for interview consideration. Signals are a strong predictor for interview invitation when internal selection criteria are met. The “borderline” applicant may be the greatest benefactor from ES, viewed similarly to the non-signaled applicant who meets internal selection criteria. Sharing PD perspectives and real-life data from this year’s ES process breeds opportunities for further improvement and increased confidence with ES. Likelihood HOP offer interview invitation based on quality of application and signals (%, n=85). Internal Selection Criteria Signal Extremely Likely Likely Neutral Unlikely Extremely Unlikely Met G 73 22 5 0 0 S 42 47 8 2 1 None 8 27 24 22 19 Nearly met G 4 35 39 19 3 S 0 9 52 28 11 Not met G 0 2 12 41 45 S 1 1 6 30 62

8001 Background: The ALCHEMIST clinical trial platform, launched by the National Clinical Trials Network (NCTN) in 2014, screened patients with resected non-small cell lung cancer (NSCLC) for molecular markers and tailored post-operative adjuvant therapy trials. A081105 evaluated whether adjuvant erlotinib improved overall survival (OS) following complete resection in patients with early stage EGFR mutated lung adenocarcinoma. Methods: A081105 was a randomized phase III trial enrolling patients with completely resected stage IB (≥4 cm), II, or IIIA non-squamous NSCLC (per the 7 th TNM staging classification) harboring EGFR exon 19 deletion or L858R mutations. Patients were randomized 1:1 to erlotinib 150 mg daily for up to 2 years or placebo/observation, stratified by stage, prior chemotherapy, EGFR mutation subtype, and ECOG performance status. The primary endpoint was OS in the per-protocol (PP) population with centrally confirmed EGFR mutations, designed to detect a hazard ratio (HR) of 0.67 in favor of erlotinib with a power of 86% and one sided type I error rate of 5%. Secondary endpoints included OS and disease free survival (DFS) in a modified intent-to-treat (mITT) population with local or centrally confirmed EGFR mutations, and safety. A prespecified backstop analysis was conducted after a minimum of 5 years of follow-up on all patients. Results: Trial enrollment was discontinued when 390 of the intended 450 patients had been enrolled due to the proven benefit of adjuvant osimertinib. Among 390 enrolled patients, the arms were balanced for age (median: 67.0 years), sex (70% female), race (70% white), stage (II: 51%, IIIA: 37%), prior chemotherapy (82%), ECOG PS 0 (60%), and exon 19 deletion (57%). Adjuvant erlotinib did not significantly improve OS compared with placebo/observation in the overall PP population (364 patients, 108 events, HR 0.89; 95% CI, 0.59–1.34; 1-sided P = 0.29) or within exon 19 deletion (HR: 0.94) or L858R mutation (HR: 0.82) subgroups. Five-year OS rates were 78.6% versus 77.9%, respectively. Results were consistent in the mITT analysis (379 patients, 113 events, HR 0.86; 95% CI, 0.58–1.28). Erlotinib improved DFS (mITT: 181 events, median: 68 vs 50 months, HR 0.74; 95% CI, 0.55–1.01). Across both arms, 11% of patients started non-protocol treatment (Osimertinib: 9%) prior to disease progression, and 9% withdrew consent for all follow-up prior to recurrence. In the erlotinib arm, 3 deaths on study were reported; grade 3 or higher adverse events were reported on 39% of patients. Median duration of treatment on Erlotinib arm was 16 months; only 37% of patients completed the planned treatment. Conclusions: In resected EGFR -mutant NSCLC, adjuvant erlotinib did not improve overall survival but improved DFS. Additional studies are exploring efficacy in selected subsets of patients using genomics and proteomic analyses. Clinical trial information: NCT02193282 .