Abstract 4108: Association between age and clinico-molecular features in lung adenocarcinoma: Data from the AACR GENIE database

Abstract Background: Although lung adenocarcinoma (LUAD) is mostly diagnosed at older age, its incidence declines with age >75 years. Furthermore, patients with younger onset (YO) LUAD often exhibit distinct clinico-molecular features. The aim of this study is to explore the relationships between age and clinico-molecular features in LUAD, with focus on YO (<55 years) and older onset (OO, >75 years). Methods: Data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) v.18 and GENIE Biopharma Collaborative (BPC) NSCLC v.2 databases were queried for clinico-genomic characteristics and survival analyses, respectively. The age at time of sequencing was stratified into reference onset (RO, 55-75 years), YO, and OO group. The cBioPortal was employed to analyze data of LUAD patients, with one sample, and to examine differences between age groups. Results: This study included 9,269 patients from GENIE cohort, who underwent genomic testing. RO, YO, and OO group represented 66.5%, 12.2%, and 21.2%, respectively. Comparison with the RO indicated that OO was more associated with male sex (40.6% vs 36.3%), while YO was more associated with Asian (13.5% vs 6.9%) and black (8.4% vs 5.2%) race. Regarding genomic alterations, OO exhibited lower fraction genome altered (mean: 0.13 vs 0.15), whereas lower mutation count was observed in YO (mean: 8.87 vs 10.4). RBM10 mutation (16.3% vs 11.5%), MET mutation (8% vs 4.9%) and fusion (1.3% vs 0.4%), and MDM2 amplification (8% vs 4.9%) were more frequent among OO, while TP53 mutation was less frequent (39.3% vs 47.7%). On the other hand, ALK (9.8% vs 2.7%), EML4 (8.9% vs 2.7%), ROS1 (3.8% vs 1.1%), CD74 (2.8% vs 0.4%), and RET (3.2% vs 1.4%) fusions were more frequent in YO, with low occurrence of KRAS (22.1% vs 35.3%), STK11 (11.8% vs 16.9%), and RBM10 (3.1% vs 11.5%) mutations (q<0.05). In GENIE BPC NSCLC with 1395 LUAD patients, a statistically significant difference in overall survival (OS) was observed among patients with metastatic stage (n=610). The median OS in RO, YO, and OO was 26 (CI95%: 22.2-29.9), 37.2 (29.3-46.9), and 13.8 (9.5-24.1) months, respectively (p<0.05). Conclusion: These findings suggest that age influences on clinico-molecular properties of LUAD. Besides the distinct features related to younger age, oldest patients exhibit specific clinico-molecular patterns with potential implications for prognosis and precision treatment. Citation Format: Mohamed Lahmadi, . Association between age and clinico-molecular features in lung adenocarcinoma: Data from the AACR GENIE database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4108.