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Lung cancer continues to be the leading cause of morbidity and mortality associated with malignancies. Identifying prognostic factors is vital for improving survival outcomes. This study assessed the impact of clinical, demographic, and genetic factors on overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). A prospective cohort of 70 NSCLC patients was analyzed. Demographic and clinical data, including epidermal growth factor receptor (EGFR) mutation status and clinical response by RECIST 1.1 criteria, were assessed. Survival outcomes were estimated using the Kaplan-Meier method with log-rank test. The median PFS and OS were 15 and 24 months, respectively. EGFR-positive patients showed significantly longer survival than EGFR-negative patients (PFS: 17 vs. 11 months, OS: not reached [NA] vs. 24 months). Brain metastases indicated poor OS (OS: 15 months vs. NA) but did not affect PFS. Patients with a partial response after one year exhibited improved overall survival (24-month OS probability of 77.8%). EGFR mutation status, brain metastases, and clinical response are key predictors of survival in NSCLC patients. Integrating genetic screening, timely management of brain metastases, and early assessment may enhance personalized treatment and improve prognosis.