Abstract Background Young patients with non-small cell lung cancer (NSCLC) exhibit distinct clinical and molecular profiles. However, regional evidence is limited. We evaluated the clinicopathological features, survival, and prognostic factors to inform treatment strategies in the Middle East. Methods We conducted a retrospective study from February 2015 to February 2024. Eligible patients were ≤50 years of age with stage IV NSCLC. Baseline demographics, tumor characteristics, treatment details, and clinical status were abstracted from records. Overall survival was measured from the first treatment to death or the last follow-up. Analyses used Kaplan-Meier estimates, log-rank tests, and Cox regression with p 0.05 for significance. Results The cohort included 215 patients with a median age of 46 years, and 66.5% were male. Adenocarcinoma was the predominant histological type (80.5%). First-line therapy consisted of chemotherapy in 48.4%, ALK inhibitors in 14.4%, tyrosine kinase inhibitors in 15.8%, immunotherapy in 9.3%, and chemo-immunotherapy in 12.1%. Brain metastases were observed in 44.2% of patients. Never-smokers had superior overall survival at 1 year compared to smokers (65.2% vs. 47.8%). Patients with ECOG 0-1 showed markedly better outcomes, while those with ECOG ≥2 had no survival beyond 1 year. The absence of brain metastases was associated with higher long-term survival. Multivariate analysis revealed that a poor ECOG performance status independently predicted worse overall survival. Molecular testing identified EGFR mutations in 15.3% of patients and ALK alterations in 14.0% of patients. High PD-L1 expression (≥ 50 %) occurred in 27.4% of patients. Among the treatment groups, ALK inhibitor first-line therapy produced the most favorable survival, with a 1-year overall survival of 83.6% and a 5-year overall survival of 55%. Chemotherapy alone yielded inferior results. Conclusion Young patients with stage IV NSCLC in the Middle East exhibit a high rate of actionable mutations, and survival is strongly influenced by performance status and access to targeted therapy. Comprehensive biomarker testing and timely, targeted treatment are essential. Persistent gaps in molecular diagnostics and access to immunotherapy demand expanded testing capacity, better coverage, and multicenter research to improve outcomes in this underserved population. This abstract is funded by: None
Kharabsheh et al. (Fri,) studied this question.