Christopoulos P, Kirchner M, Roeper J, et al. - For the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC), panel-based next-generation sequencing (NGS) is increasingly used. Researchers here examined if NGS could improve risk assessment in combination with clinical parameters. In this retrospective analysis, they examined the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR + NSCLC patients with validation of results in an independent cohort (n = 130). In EGFR + NSCLC, EGFR variant, TP53 status and brain metastases were predictive of TKI effectiveness and survival irrespective of other currently available parameters (EGFR + NSCLC risk Score, "ENS"). In combination, they represent a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR + NSCLC.