Precision reirradiation in recurrent CNS tumors integrating biology techniques and multimodal care

Reirradiation has re-emerged as a viable salvage modality for recurrent central nervous system (CNS) tumors in the modern era of precision radiotherapy. Advances in image guidance, biological understanding of normal-tissue repair, and integration of targeted systemic agents have expanded its therapeutic window. The 2025 ISRS meta-analysis (62 studies; n = 2640) established a median overall survival (OS) of ~ 10.2 months after re-irradiation (re-RT) of recurrent HGG, confirming that focal single-fraction SRS (16 Gy × 1) or hypofractionated SRS (25 Gy/5 fx) achieves optimal tumor control with acceptable neurologic toxicity (7% vs 4%). EQD₂ > 120-130 Gy markedly increases radionecrosis risk (p = 0.003). Integration of DNA-damage-repair (DDR) inhibitors, VEGF blockade, and tumor-treating fields (TTFields) is under active investigation. Re-RT in ependymoma, meningioma, and spinal tumors is also gaining renewed interest with proton and MR-guided adaptive techniques.