Citations

e23055 Background: Geographic distance to care has been associated with outcomes in solid tumors, reflecting differences in access, follow-up, and supportive care. However, its relationship with biologic transplant toxicities such as graft-versus-host disease (GVHD) has not been well characterized. Understanding whether access-related factors are associated with immune-mediated complications is important for systems-level optimization of post-transplant care and survivorship. Methods: We conducted a retrospective cohort study of adult patients undergoing allogeneic hematopoietic cell transplantation using the CIBMTR hs1802 publicly available dataset. Distance from patient residence to the transplant center was categorized as less than 20 miles, 20 to 50 miles, 50 to 150 miles, and greater than 150 miles, with less than 20 miles as the reference group. Primary outcomes were acute GVHD and chronic GVHD within one year after transplantation. Secondary outcomes included overall survival. Multivariable Cox proportional hazards models were used to evaluate associations between distance and outcomes, adjusting for age, sex, race and ethnicity, HCT comorbidity index, conditioning intensity, donor type, GVHD prophylaxis, transplant era, disease type, and total body irradiation use. Results: A total of 5,473 patients were included, with a median follow-up of 60.2 months. Crude rates of acute GVHD increased with greater distance from the transplant center, occurring in 40.2 percent of patients living less than 20 miles away and 45.1 percent of those living more than 150 miles away. In adjusted analyses, residence more than 150 miles from the transplant center was associated with a higher risk of acute GVHD compared with less than 20 miles, with an adjusted hazard ratio of 1.15 and a 95 percent confidence interval of 1.00 to 1.31. No significant differences were observed for intermediate distance categories. For chronic GVHD within one year, patients living more than 150 miles away had a lower recorded risk compared with those living less than 20 miles away, with an adjusted hazard ratio of 0.79 and a 95 percent confidence interval of 0.71 to 0.88. Distance to transplant center was not significantly associated with overall survival. Conclusions: Greater geographic distance from transplant centers is associated with a higher risk of severe GVHD after allo-HCT. These findings suggest that access to specialized post-transplant care and close monitoring may influence immune-mediated outcomes. Strategies to improve follow-up care, including enhanced care coordination and telemedicine, may help mitigate GVHD-related disparities and inform health policy efforts aimed at improving access to specialized transplant services, reimbursement for remote monitoring, and regional models of post-transplant care delivery.

e23005 Background: Cardiovascular disease (CVD) is the leading non-cancer cause of death among cancer survivors. Managing this risk increasingly requires a transition from traditional generic therapies (e.g., statins, ACEi) to novel agents (e.g., SGLT2i, GLP-1RA). While these drugs are clinically recommended for survivors comorbidities, their population level economic impact has not been well defined. Methods: We analyzed the 2016–2023 Medical Expenditure Panel Survey (MEPS-HC) to identify U.S. adults with a history of cancer (n=5,165; weighted ~54.3M) and non-cancer controls (n=217,834). We evaluated utilization, total prescription expenditures, and out-of-pocket (OOP) costs across 10 cardioprotective drug classes: statins, ACE inhibitors, ARBs, aspirin, antiplatelets, ezetimibe, GLP-1RA, SGLT2i, PCSK9i, and colchicine. surgery-weighted Pearson chi-square tests and design-based F-statistics accounted for the complex sampling design. Results: Cancer survivors were older (mean age ~68 vs 46 years), with higher prevalence of hypertension (54.5% vs 31.5%), diabetes (18.7% vs 8.1%), and dyslipidemia (56.1% vs 23.1%) than controls (all p<0.001). Survivors more frequently used traditional cardioprotective therapies, including statins (43.7% vs 23.1%) and ACE/ARBs (35.8% vs 18.2%). Aspirin use remained common and stable with negligible expenditures and OOP costs, reflecting its role as a low-cost foundational therapy. Antiplatelet use was higher among survivors and associated with modest but persistent OOP spending. Between 2016 and 2023, mean annual per-patient statin expenditures declined by 65% ($177 to $61). In contrast, expenditures for novel agents increased substantially. Mean per-person SGLT2 inhibitor expenditures rose from $0.36 to $211.55, while GLP-1RA utilization increased from 2.0% to 20.5%. These shifts increased patient cost sharing: survivor OOP costs increased 40-fold for SGLT2 inhibitors ($0.35 to $13.91) and more than four-fold for GLP-1 receptor agonists ($3.69 to $15.83). Socioeconomic disparities were evident, with PCSK9 inhibitor users reporting higher family incomes than non-users ($123,069 vs $85,530), and ezetimibe utilization was higher among Black compared with White survivors (14.8% vs 9.5%; p<0.05). Conclusions: Among U.S. cancer survivors, declining costs of generic cardioprotective therapies have been fully offset by rising expenditures and OOP burdens from newer agents. Access to high-value therapies increasingly reflects socioeconomic disparities more than clinical risk alone. Reducing patient cost sharing will be essential to prevent financial barriers from worsening adherence and long-term cardiovascular outcomes in survivorship.

e22677 Background: Lung cancer without tobacco exposure is a growing and preventable source of global morbidity driven by environmental and occupational exposures, with marked regional variation and unevenly addressed prevention strategies. Methods: Global Burden of Disease (GBD) 2023 estimates were used to quantify lung cancer disability-adjusted life years (DALYs) and age-standardized mortality rates (ASMRs) attributable to ambient particulate matter (PM2.5), household air pollution (HAP), residential radon, and occupational carcinogens across seven GBD super-regions from 1990–2023. Population attributable fractions (PAFs) and temporal trends were assessed, with sex-stratified analyses for radon and occupational exposures. Results: Air pollution accounted for the largest attributable lung cancer DALYs in low and middle-income regions, particularly South Asia, where PM2.5 (PAF 15.9%) and HAP (PAF 16.8%) together accounted for 32.7% of DALYs. In Sub-Saharan Africa, HAP alone accounted for 21.4%. Occupational carcinogens contributed the largest proportion in high-income regions (PAF 21.7%) and were associated with the highest DALY rate (230/100,000) and ASMR (13/100,000). From 1990–2023, HAP-attributable lung cancer burden declined across all regions (40–70%), consistent with transitions away from solid household fuels. In contrast, PM2.5-attributable DALY rates declined by 30–40% in high-income regions but increased by 40–50% in South Asia and the Middle East and North Africa. Radon- and occupational carcinogen–attributable burdens remained largely stable across most regions, although high-income regions experienced declines in radon (18.4%) and occupational carcinogen (32.1%) attributable DALY rates. Radon showed a modest male excess (male-to-female ratios 1.2–1.5), whereas occupational carcinogens demonstrated marked male predominance (often > 4). Conclusions: Despite substantial decrease in HAP related lung cancer burden, other modifiable factors including PM2.5, occupational carcinogen and radon exposure remain major contributors, specially in high-income regions where occupational exposures account for the largest PAF. These patterns suggest that reducing household energy exposure alone is insufficient. We need regional exposure targeted prevention strategies that extend beyond tobacco control and are relevant to oncology practice, survivorship and policy advocacy. Population-attributable fractions of lung cancer burden from environmental and occupational exposures across gbd super-regions. GBD Super-Region Air Pollution (PM2.5 + HAP) Residential Radon Occupational Carcinogens High-income 6.2 4.6 21.7 Central Europe, Eastern Europe & Central Asia 11.3 6.3 10.9 Latin America & Caribbean 12.5 4.1 11.9 North Africa & Middle East 21 3.7 12.7 South Asia 32.7 4.3 10 Sub-Saharan Africa 30.7 4.3 9.4 Southeast Asia, East Asia & Oceania 23.6 3.4 9.8

e22604 Background: Heart, pericardial, and mediastinal tumors are rare neoplasms with potential sex-specific disparities. Despite their clinical significance, long-term temporal trends stratified by sex remain poorly characterized. Methods: We conducted a population-based analysis using data from the Surveillance, Epidemiology, and End Results (SEER) database, evaluating annual case counts from 1975 to 2022, stratified by sex. Temporal trends in total, male, and female cases were assessed using linear regression models. Results: A total of 657 cases were reported over the study period (445 males; 212 females). Total case counts showed a significant upward trend, increasing by 1.25 cases per year (p < 0.001, R² = 0.59). Male cases increased by 0.85 cases/year (p < 0.001), nearly twice the increase observed in females (0.40 cases/year, p < 0.001). Male predominance persisted throughout the study period, with both sexes showing a gradual upward trend, reflecting a consistent sex disparity in these tumors. Conclusions: The occurrence of heart, pericardial, and mediastinal tumors has increased steadily over the past five decades, disproportionately affecting males. These findings highlight persistent sex-based disparities and underscore the need for further sex-specific research to elucidate underlying risk factors and inform targeted surveillance and early detection strategies.

e22593 Background: Pheochromocytoma is a rare neuroendocrine tumor, and population-level data describing long-term temporal trends are limited. Evaluating national patterns over time may improve epidemiologic understanding and clinical awareness. Methods: We performed a retrospective analysis of pheochromocytoma cases recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2022. Annual case counts were examined overall and by race (White, Black, Other, and Unknown). Temporal trends were assessed using Poisson regression, and annual percent change (APC) was calculated to quantify changes over time. Results: A total of 408 pheochromocytoma cases were identified during the study period. Overall case counts increased significantly over time, with Poisson regression demonstrating a consistent upward trend corresponding to an APC of 5.8% per year (p < 0.001). White individuals accounted for the majority of reported cases, while Black and other racial groups had significantly lower case counts compared with the reference population. Visual assessment of decade-level trends suggested a gradual increase from 1975 through approximately 2010, followed by a sharper rise in more recent years. Conclusions: Pheochromocytoma case counts in the United States have increased substantially over the past five decades based on SEER data. These findings suggest evolving epidemiologic patterns in this rare tumor and emphasize the importance of continued surveillance. Observed trends should be interpreted in the context of potential changes in diagnostic practices, imaging utilization, and cancer registry reporting over time.

e22007 Background: Long-term neurocognitive impairment is a major source of disability in survivors of pediatric CNS tumors. Proton radiotherapy may reduce dose to developing brain structures, potentially preserving cognition compared with conventional photon therapy. Methods: We performed a systematic review and meta-analysis of MEDLINE, Embase, PsycINFO, and CENTRAL. Eligible studies included pediatric CNS tumor patients treated with proton or photon radiotherapy reporting neurocognitive outcomes (full-scale IQ, attention, processing speed, executive function) over time. Standardized mean differences (SMD) were pooled using random-effects models, and slope analyses assessed longitudinal IQ change. Subgroups included age at radiotherapy, craniospinal vs focal fields, tumor type, chemotherapy exposure, and follow-up duration. Certainty of evidence was graded using GRADE. Results: Eleven studies encompassing 624 patients were included. Proton therapy was associated with significantly less decline in full-scale IQ compared with photon therapy (SMD 0.43, 95% CI 0.21–0.65, p < 0.001). Domain-specific analyses showed preservation of attention (SMD 0.36, 95% CI 0.10–0.61) and processing speed (SMD 0.41, 95% CI 0.18–0.64). Longitudinal slope analysis indicated an average IQ decline of 0.7 points/year after proton therapy versus 2.4 points/year after photon therapy. Benefits were greatest in younger children (<8 years) and those receiving craniospinal irradiation. Attrition and missing data were similar across groups. Conclusions: Proton radiotherapy in pediatric CNS tumors is associated with clinically meaningful preservation of neurocognitive function compared with photon therapy, particularly in younger patients and those receiving extensive fields. Clinical Takeaway: When available, proton therapy should be considered for children at high risk of cognitive decline to optimize long-term functional outcomes.

e22006 Background: Metastasectomy is recommended for select pediatric patients with osteosarcoma with resectable pulmonary parenchymal metastases. It is unclear whether pulmonary metastasectomy confers the same benefit to patients with hilar or mediastinal lymph node metastases (LNM). This study aims to characterize pediatric patients with osteosarcoma with thoracic LNM and their outcomes compared to those with only pulmonary parenchymal metastasis. Methods: This is a retrospective cohort study of patients aged 0-21 with osteosarcoma metastatic to the lung who underwent pulmonary metastasectomy between 2000-2024. Patients were categorized into groups based on the presence or absence of LNM on imaging reviewed by pediatric surgeons and radiologists. Descriptive statistics and Wilcoxon rank sum, chi-square or Fisher’s exact tests evaluated differences between patients with and without LNM. Kaplan-Meier survival curves with log-rank tests evaluated the relationship between the presence of LNM and outcomes. The primary outcome was overall survival (OS) with secondary outcomes of recurrence-free survival (RFS) and disease-free survival (DFS). Results: 39 patients met inclusion criteria for this study, of which 13 (33%) had LNM (Table). Of the 13 patients with LNM, 8 (62%) had a pulmonary metastasectomy after their LNM diagnosis. Patients with LNM had poorer OS after first metastasectomy (log-rank p = .027), DFS after first metastasectomy (p = .018), and RFS after diagnosis (p = .039) than patients with pulmonary parenchymal metastasis without LNM. Patients who underwent metastasectomy after their LNM diagnosis had improved OS after LNM diagnosis than patients who did not undergo metastasectomy (pairwise log-rank test with Bonferroni correction p = .015). Conclusions: Pediatric patients with osteosarcoma metastatic to the lung with LNM had poorer OS, DFS, and RFS compared to patients without LNM. These results confirm the importance of attention to the presence of nodal involvement in patients with pulmonary metastatic osteosarcoma. Despite their poor prognosis, these results suggest a persistent survival benefit to surgical intervention. Total N = 39 No LMN N = 26 LMNN = 13 p Age 13.7 (9.5, 16.1) 13.9 (9.0, 15.9) 13.7 (10.7, 16.5) .777 Female 15 (38%) 10 (38%) 5 (38%) > .999 Histology Chondroblastic Osteoblastic Telangiectatic 11 (39%)16 (57%)1 (3.6%) 9 (50%)8 (44%)1 (5.6%) 2 (20%)8 (80%)0 (0%) .162 Primary tumor site Chest wall Femur Humerus Pelvis Radius Tibia 2 (5.1%)24 (62%)5 (13%)2 (5.1%)1 (2.6%)5 (13%) 2 (7.7%)14 (54%)3 (12%)2 (7.7%)1 (3.8%)4 (15%) 0 (0%)10 (77%)2 (15%)0 (0%)0 (0%)1 (7.7%) .821 Lung metastases present at time of diagnosis 20 (51%) 13 (50%) 7 (54%) .821 Treatment protocol AOST0331 AOST06P1 CCG 7921 P9754 30 (81%)2 (5.4%)4 (11%)1 (2.7%) 19 (79%)1 (4.2%)3 (13%)1 (4.2%) 11 (85%)1 (7.7%)1 (7.7%)0 (0%) > .999 Lung nodules removed during first metastasectomy 3 (2, 6) 3 (2, 5) 6 (1, 20) .567

e21607 Background: The association between timing of palliative care referral and survival outcomes in patients with melanoma brain metastases (MBM) treated with immune checkpoint inhibitors remains poorly characterized. Methods: We conducted a retrospective cohort study of patients with MBM treated with combination ipilimumab and nivolumab at Mayo 3 sites from 2016 to 2024. Palliative care referral timing relative to MBM diagnosis was categorized as early (≤56 days), late ( > 56 days), or none. Patients without referral documentation were excluded from referral-based analyses. Overall survival (OS) was estimated using Kaplan–Meier methods and compared with log-rank tests. Multivariable Cox proportional hazards models were used to identify factors independently associated with OS, with stepwise selection (entry p < 0.25; stay p < 0.15). Results: Among 147 patients, 139 had referral information: 33 (23.7%) early, 56 (40.3%) late, and 50 (36.0%) no referral. Median OS differed significantly by referral timing (log-rank p < 0.0001): 2.8 months (early), 7.9 months (late), and 47.8 months (no referral). Among patients with ECOG 2–3, a higher proportion had early or late referral (each 42.9%) compared with no referral (14.3%), whereas patients with ECOG 0–1 were more evenly distributed across referral groups (early 21.6%, late 40.0%, none 38.4%). In multivariable analysis of 88 patients with complete covariate data, both early (HR 4.54; p = 0.0016) and late referral (HR 2.86; p = 0.011) were independently associated with worse OS compared with no referral. Progressive disease versus objective response (HR 4.45; p = 0.0002), hemorrhagic metastases (HR 2.79; p = 0.0015), male sex (HR 2.07; p = 0.044), and increasing age (HR 1.02 per year; p = 0.032) were also associated with inferior OS. Treatment with ipilimumab 1 mg/kg plus nivolumab 3 mg/kg showed a trend toward improved OS compared with ipilimumab 3 mg/kg plus nivolumab 1 mg/kg (HR 0.48; p = 0.055). Conclusions: Timing of palliative care referral was strongly associated with overall survival in patients with MBM treated with ipilimumab and nivolumab. Although patients with ECOG 2–3 were more frequently referred early or late, ECOG category overall did not clearly differentiate referral timing groups, suggesting referral may reflect unmeasured clinical factors beyond baseline performance status. Prospective studies incorporating more granular functional and symptom measures are needed to better define the role of palliative care integration in this population. Multivariable cox model for overall survival. Variable Comparison HR P value Referral timing Early vs None 4.54 0.0016 Late vs None 2.86 0.011 Best overall response PD vs ORR 4.45 0.0002 SD vs ORR 2.16 0.098 Hemorrhagic metastases Yes vs No 2.79 0.0015 Sex Male vs Female 2.07 0.044 Age Per year increase 1.02 0.032 Regimen Ipi1+Nivo3 vs Ipi3+Nivo1 0.48 0.055

e21561 Background: Immune checkpoint inhibitors (ICIs) have become the standard first-line systemic therapy for metastatic Merkel cell carcinoma (MCC). Radiotherapy (RT) remains commonly used for local control and palliation, and growing biologic interest suggests that RT may enhance antitumor immune responses when combined with ICIs. However, population-level evidence regarding contemporary patterns of RT use and its association with survival in immunotherapy-treated patients with metastatic MCC is limited. Methods: We conducted a retrospective population-based cohort study using the National Cancer Database (NCDB), including adults diagnosed with metastatic MCC between 2011 and 2022. Temporal trends in treatment utilization were described across the study period. Among patients diagnosed in the immunotherapy era (2017–2022), factors associated with receipt of RT were examined using multivariable logistic regression. To evaluate survival, analyses were restricted to immunotherapy-treated patients, and overall survival was compared between those who received RT and those who did not using propensity score-matched Kaplan-Meier and Cox proportional hazards analyses, with a focus on 2-year overall survival. Results: A total of 1,736 patients with metastatic MCC were included. Following 2017, immunotherapy use increased substantially, while chemotherapy use declined; RT utilization remained relatively stable over time. In multivariable analyses restricted to the immunotherapy era, higher primary tumor stage and lymph node dissection were independently associated with RT receipt. Among immunotherapy-treated patients in the propensity score-matched cohort, RT was not associated with improved 2-year OS (aHR,1.09; 95% CI, 0.84-1.42), and Kaplan-Meier analyses demonstrated no significant survival difference. Conclusions: In the contemporary immunotherapy era, RT continues to be selectively incorporated into the management of metastatic MCC, particularly in patients with greater local or regional disease burden. However, among immunotherapy-treated patients, RT was not associated with improved short-term overall survival at the population level. These findings support a continued role for RT in local disease management while underscoring the need for prospective studies to better define its optimal integration with immunotherapy.

e21533 Background: Clinical decision-making in melanoma is challenged by heterogeneous disease biology, evolving treatment paradigms, and fragmented longitudinal data. Although EMRs contain real-world information, clinicians often lack tools that organize these data around clinically meaningful milestones to support pre-visit decision-making. We developed CODE-M, an AI–enabled framework designed to identify clinically similar patients (“patients like mine”) and surface outcome-relevant insights using real-world data. Methods: CODE-M was developed using data derived from EMRs at a large academic cancer center. Patient data were normalized and aligned to a clinically defined ordinal timeline spanning diagnosis, adjuvant therapy, recurrence, progression, systemic treatment, and outcomes. Similarity modeling incorporated demographics, disease stage, treatment history, longitudinal outcomes, and available molecular and genomic attributes, represented as contextual features within the timeline. AI-based similarity modeling generated retrospective cohorts reflecting shared clinical features of an index patient and supported iterative cohort generation for competing progression-free and overall survival analyses using automated Kaplan–Meier, Cox proportional hazards, and feature association models. A clinician-facing pre-visit summary presents cohort characteristics, outcomes, and relevant clinical trial options prior to patient encounters. Results: The framework reliably aligned heterogeneous longitudinal EMR data to a shared clinical timeline and generated reproducible, clinically coherent patient cohorts reflecting shared disease stage, treatment exposure, and melanoma care patterns. Iterative cohort generation enabled comparative analyses across competing cohorts, resulting in predictable shifts in observed progression-free and overall survival distributions. Pre-visit summaries and analytic outputs were reviewed by clinicians and demonstrated interpretability and relevance for visit preparation. The platform also identified clinical trials based on eligibility criteria, trial availability, and patient geographic proximity, integrating trial matching into the clinical decision workflow. Conclusions: An AI-enabled, ordinal timeline–based approach can structure real-world melanoma data to support pre-visit clinical context through patient similarity analysis and comparative outcome visualization. CODE-M summarizes observed outcomes among clinically similar patients and is intended to support contextual understanding of prior care experiences rather than generate treatment recommendations or patient-specific predictions. This framework supports clinical insight, hypothesis generation, and shared decision-making using longitudinal EMR-derived data, with applicability across oncology disease types.