Clinical and molecular characterization of a large Brazilian lung cancer cohort: a real-world observational study

Background Driver alterations influence lung cancer management and vary among ethnicities. Patients from Latin America remain underrepresented in genomic studies. We characterized the molecular and ancestry profiles of Brazilian patients with lung cancer using real-world data and evaluated associations with clinicopathological features. Methods We retrospectively analyzed 1131 patients with lung cancer from a referral center, using DNA/RNA-based Next-generation Sequencing (NGS), immunohistochemistry, and ancestry-informative markers to assess molecular profiles and associate them with clinical features. Findings Oncogenic alterations were detected in 988 (88%) of patients, mainly at TP53 (Tumor Protein p53) [656 (58%)], KRAS (K irsten Rat Sarcoma Viral ) [289 (25.6%)], and EGFR (Epidermal Growth Factor Receptor) [228 (20.6%)] genes. TP53 mutations were associated with former smoking (OR: 2.04, 95% CI: 1.43–2.90), current smoking (OR: 3.79, 95% CI: 2.65–5.41), central nervous system (CNS) metastases (OR: 1.75, 95% CI: 1.18–2.58), and higher African ancestry (OR: 1.53, 95% CI: 1.08–2.18). KRAS mutations were associated with former smoking (OR: 6.47, 95% CI: 3.59–11.68) and current smoking (OR: 7.42, 4.13–13.31). EGFR mutations were associated with never smoking (OR: 12.87, 95% CI 7.12–23.2). Worse cancer-specific survival was observed among patients who currently smoke (HR: 1.38, 95% CI: 1.07–1.78), with poor performance status (HR: 1.99, 1.64–2.41), and those with CNS metastases (HR: 6.38, 4.80–8.47). In patients with TP53 mutations, treatment with chemotherapy was associated with longer survival (15.0 vs . 2.0 months; log-rank p < 0.0001). In the subset of patients harboring EGFR mutations and treated with targeted inhibitors, TP53 co-mutations were associated with shorter cancer-specific survival (24.0 vs . 61.0 months; log-rank p=0.003). Interpretation Most Brazilian patients with lung cancer harbor actionable genomic alterations. TP53 status is prognostically relevant, including in the EGFR -mutant disease, and should be routinely incorporated. It provides region-specific evidence to inform equitable access to molecular diagnostics and targeted therapies in Latin America. Funding Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer—15th zone, Campinas, Brazil), PRONON—PRONON/MS (Abordagens móveis e de tecnologia para prevenção primária e secundária de câncer—NUP: 25000.015000/2019-53), and Barretos Cancer Hospital.