In Case 2 with H3K27M-mutated DMG (and BRAFV600E and SMARCB1 alterations), and Case 3 with gliomatosis cerebri (EGFR overexpression and CDKN2A deletion) in reduced clinical condition, local re-irradiation and targeted therapy (with or without chemotherapy and/or immunotherapy) were proposed. The gene discussed is SMARCB1; the disease is gliomatosis cerebri.