Chitkara, Akshit

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

58 Background: Skeletal-related events (SREs) are a common cause of morbidity and mortality in metastatic castration-resistant prostate cancer (mCRPC). These complications are managed using bone-modifying agents (BMAs), radiation therapy, and surgery, and lead to diminished quality of life irrespective of their castration status. We sought to evaluate the mortality trends for patients with PC and SREs in patients of >65 years from 1999 to 2023 using the CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) database. Methods: The database was searched from January 1, 1999, to December 31, 2023. Mortality trends were assessed by identifying prostate cancer international classification of diseases-10th revision code (ICD-10 code C61) as the underlying cause of death in individuals aged >65 years, and (SREs) as contributing causes using the following ICD-10 codes: S02, S12, S22, S32, S42, S52, S62, S82, S92, T02, T08, T10, T12, T14.2, Y93.2, E55, M80, M81, M84.4. Joinpoint 5.0 software was used to analyze mortality trends. Results: From 1999 to 2023, a total of 3,231 deaths were reported. Trend analysis revealed a decline in overall mortality from 1999 to 2014, with an annual percentage change (APC) of -1.60 (CI: -2.6, -0.5; p = 0.005), followed by a significant increase in mortality from 2015 to 2023, with an APC of 5.30 (p = 0.0001). When stratified by age, individuals aged 65-69 showed an insignificant decline in mortality over the entire study period. For those aged 70-74, mortality significantly decreased from 1999 to 2014 (APC: -3.02, CI: -5.0, -0.9; p = 0.008), but experienced an exponential increase from 2014 to 2023 (APC: 14.07, CI: 8.7, 19.6; p = 0.00005). In the 75-79 age group, mortality significantly decreased from 1999 to 2011 (APC: -5.6, CI: -9.5, -1.6; p = 0.0091), followed by a robust increase from 2011 to 2023 (APC: 7.06, CI: 2.7, 11.5; p = 0.002). For individuals aged >80 years, the trend showed an insignificant decline in mortality from 1999 to 2023 (APC: -0.260, CI: -0.8, 0.3; p = 0.380). Conclusions: Our study revealed significant trends in prostate cancer mortality attributable to SREs, contributing to a sharp increase from 2015 to 2023. Age-stratified analysis revealed that substantial mortality is reported in patients aged 70-79, with the most pronounced rise occurring after 2014. These findings emphasize the growing burden of SREs in older prostate cancer patients, underscoring the need for targeted interventions along with a focus on patient-reported outcomes to improve survival and quality of life.

402 Background: Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody-drug conjugate (ADC) with a cytotoxic payload. TDXd was approved in 2021 to be used in advanced gastric or GEJ cancers. Although given the recent approval, real-world evidence on efficacy and safety is limited. We sought to evaluate the efficacy and safety of T-DXd through a combined meta-analysis of clinical trials and real-world studies. Methods: A comprehensive search was conducted across PubMed, Embase, Scopus, and Clinicaltrials.gov databases. The original studies evaluating T-DXd in patients with metastatic/recurrent gastric/gastroesophageal junction (GEJ) cancers were included in the analysis. The pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and the incidence of adverse events (AEs) were analyzed. A random-effects model was used for meta-analysis, and the heterogeneity of the data was evaluated by Chi-sq Q test and the I 2 statistic using OpenMeta [Analyst] (Tufts Medical Center, Boston, MA, USA). Results: This meta-analysis incorporated 8 studies (3 phase II clinical trials, 5 retrospective studies) comprising 915 patients with advanced HER2-positive gastric/GEJ cancer. The median patient age was 66.5 years (range: 27–89), with 75.4% males, 70.4% Asian, and 29.0% Caucasians. 77.9% had an ECOG performance status of 0–1, while 21.8% had ECOG ≥2. Histologically, 53.6% had intestinal and 22.9% diffuse-type adenocarcinoma. HER2 overexpression (IHC3+) was observed in 75.8% of evaluable cases, and 22.4% were IHC2+/FISH positive. 77.6% had primary gastric and 22.4% GEJ tumors. The median line of therapy was 3 (range: 2–11), with prior immune checkpoint inhibitor use in 31.8% and prior surgery in 44.5% .The pooled ORR was 47.7% (95% CI 43.0-52.4%) and DCR was 82.50% (79.40%–85.72%); PFS and OS were 4.92 and 9.86 months, respectively. Safety analysis revealed grade ≥3 AEs in 48.2% of patients, neutropenia (24.5%) being the most common. Treatment discontinuation due to adverse events occurred in 12.2%, and dose reductions were required in 21.5%. Patient-reported outcomes were not assessed in any of the studies. Conclusions: Our meta-analysis, encompassing both clinical trials and real-world data, confirms the encouraging efficacy of T-DXd in gastric/GEJ cancers, with a pooled ORR of 47.7% and a median PFS of 4.92 months, and supports its use as an early-line treatment in this challenging disease landscape. This analysis also highlights the significant incidence of grade ≥3 AEs, particularly neutropenia, which necessitates vigilant monitoring and proactive management. Future research should focus on optimizing patient selection, exploring combination therapies, and refining dosing strategies to maximize clinical benefit while mitigating toxicity.