Summarizing the available evidence, prolongation of icPFS from a combined upfront RT/TKI treatment of BM in dm-NSCLC appears to be reproducible, but the potential OS benefit remains controversial and becomes less likely, as more potent EGFR (osimertinib) and ALK inhibitors (alectinib, brigatinib, lorlatinib) enter the first-line setting. The gene discussed is ALK; the disease is non-small cell lung carcinoma.