Batra, Akshee

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

2028 Background: Patients with EGFR-mutated non–small cell lung cancer (NSCLC) frequently develop BM, and CNS progression is a common mode of failure on earlier-generation EGFR tyrosine kinase inhibitors (TKIs). After TKI failure in the setting of BM, optimal next-line systemic therapy remains uncertain, particularly regarding the comparative effectiveness of targeted escalation, immunotherapy (IO)-based regimens, and chemotherapy. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. We identified EGFR-mutated NSCLC patients treated with first- or second-generation EGFR TKIs who subsequently developed metachronous BM and initiated next-line systemic therapy between 2015 and 2025. Patients with leptomeningeal disease prior to earlier-generation TKI exposure were excluded. Treatment strategies were categorized as targeted escalation with osimertinib, IO-based therapy (immune checkpoint inhibitor with or without chemotherapy), or chemotherapy alone. The index date was defined as initiation of next-line systemic therapy. Propensity score matching was performed for pairwise comparisons. The primary endpoint was overall survival (OS) at 180 days. Restricted mean survival time (RMST) through 181 days was evaluated as a sensitivity analysis. Baseline covariate balance after matching was assessed using standardized mean differences, with values <0.10 indicating adequate balance. Results: After propensity score matching with adequate baseline balance, osimertinib was associated with significantly lower 180-day mortality compared with chemotherapy (24.5% vs 33.2%; hazard ratio [HR] 0.69, 95% CI 0.47–1.00). Comparisons between osimertinib and IO-based therapy showed numerically lower 180-day mortality with osimertinib (26.0% vs 32.6%; HR 0.79, 95% CI 0.54–1.15), but this difference did not reach statistical significance. Similarly, IO-based therapy was not associated with a statistically significant survival advantage compared with chemotherapy alone (31.7% vs 37.5%; HR 0.78, 95% CI 0.58–1.06). RMST analyses for death over 181 days were directionally consistent with hazard ratio–based results, with modest, non-significant differences in mean survival time. Conclusions: In EGFR-mutated NSCLC patients with metachronous brain metastases after earlier-generation TKI failure, targeted escalation with osimertinib was associated with significantly lower 180-day mortality compared with chemotherapy. IO-based approaches demonstrated intermediate, directionally favorable but non-significant outcomes relative to both osimertinib and chemotherapy. These real-world findings support guideline recommendations prioritizing next-generation TKIs and help inform systemic treatment sequencing in a CNS-enriched population where prospective data remain limited.

e13718 Background: Colorectal cancer (CRC) is the third-leading cancer worldwide and racial minorities bear a disproportionate burden of this disease. Methods: We searched the clinicaltrials.gov database for all the completed clinical trials conducted on adult patients until 2023 in the United States. In intervention trials, we manually abstracted data on the racial distribution of enrollees, phases, tumor histology, intervention type, and year of completion. We divided interventions into chemotherapy, radiotherapy, surgery, immunotherapy, behavioral, diagnostic tests, and others. To quantify the racial disparity, we calculated the enrolment ratio (ER) as the observed ratios of racial participation in the study compared to the prevalence in colorectal cancer per the 2009-2019 Surveillance, Epidemiology and End Results (SEER) database. We also conducted subgroup racial enrollment based on clinical trial and type of intervention. Results: We identified 394 studies, of which 252 studies (64%) had racial distribution published, including 138814 participants. Most studies were phase 2 trials (168), followed by phase 1/2 trials (49) and phase 3 studies (43). The racial breakdown included 88677 White participants (63.9%), 23230 were African Americans (16.7%), 9963 were Asians (7.1%), 4398 were of other races (3.2%), and 12546 were of unknown race (9.0%). The frequency of including racial data was 100% in Phase 1 studies, 56.5% in Phase 2, 58.1% in Phase 3, and only 16% in Phase 4. A total of 185 were immunotherapy trials, out of which 63 studied chemotherapies, radiotherapy and/ or surgery along with immunotherapy. Racial enrolment data was reported in 68.6 %, 58% and 59.3% in immunotherapy, chemotherapy, and radiotherapy interventions respectively. The ERs of whites, blacks, and Asians were 0.8, 1.3, and 0.9, respectively (Table). However, ER in subgroups with specific interventions, such as chemotherapy, immunotherapy, and radiotherapy, were 0.5, 0.4, and 0.6, respectively. Conclusions: African Americans are underrepresented in CRC intervention trials. Equal access and tailored strategies for cultural and linguistic differences are needed for fair participation. [Table: see text]