Comparing Fractionated and Single-Fraction Gamma Knife Radiosurgery for Brain Metastases From Non-Small-Cell Lung Cancer With a Focus on Driver Alterations

Background As the overall survival in non-small-cell lung cancer has increased, safer, long-term treatments for brain metastases are increasingly needed. This study aimed to analyze the outcomes of fractionated and single-fraction gamma knife radiosurgery for brain metastases from non-small-cell lung cancer, focusing on driver alteration status. Methodology Patients who underwent gamma knife radiosurgery as their first local treatment for brain metastases from non-small-cell lung cancer between May 2018 and December 2021 at our institution were retrospectively enrolled. Results Among the 98 patients (287 lesions), 45 (130 lesions) harbored driver alterations, including epidermal growth factor receptor mutations in 35 patients and anaplastic lymphoma kinase or ROS1 rearrangement in 10 patients. Overall, 64 and 34 patients underwent single-fraction and fractionated radiosurgery (3-15 fractions), respectively. Large tumor size was a risk factor for recurrence, while fractionated radiosurgery (subdistribution hazard ratio (sHR) = 16.47; confidence interval (CI) = 3.58-75.77; p < 0.001) and small tumor size (sHR = 1.15; CI = 1.04-1.28; p = 0.008) independently protected against radiation necrosis. In the case-matched analyses, the cumulative radiation necrosis rates were significantly lower in the fractionated group than in the single-fraction group among all lesions (p = 0.017) and among those with driver alterations (p = 0.046), whereas no significant difference was confirmed among wild-type lesions (p = 0.382). Conclusions Fractionated gamma knife radiosurgery may be an alternative therapeutic approach for reducing the risk of radiation necrosis, particularly for patients with driver alterations, even when the tumors are small. Further research is necessary to determine the optimal indications for fractionated gamma knife radiosurgery and fractionation methods.