Dose selection and clinical decision-making after Gamma Knife surgery for large brain metastases: implications for...

To evaluate dose selection and post-treatment management after Gamma Knife surgery (GKS) for large brain metastases, with a focus on early identification of true progression.

This retrospective single-institution study included 143 patients with large brain metastases (tumor volume ≥ 4 cm³) treated with primary GKS between 2016 and 2024. One dominant lesion per patient was analyzed. Treatment modality (single-session, staged, or hypofractionated) and dose selection were individualized. Radiographic progression was defined as a ≥ 20% increase in longest tumor diameter from nadir. True progression was defined as sustained enlargement or the need for salvage treatment, whereas lesions that stabilized or regressed without intervention were classified as pseudoprogression.

Median overall survival was 15.3 months. During follow-up, 47 lesions showed radiographic progression: 42 true progression, 4 pseudoprogression, and 1 intratumoral hemorrhage. The 6-, 12-, and 24-month cumulative incidences of true progression were 17.4%, 31.5%, and 33.1%, respectively. True progression did not differ by treatment modality or tumor volume. A marginal dose ≥ 57.6 Gy biologically effective dose (BED₁₀) was associated with a lower risk of true progression (subdistribution hazard ratio [SHR], 0.46; p = 0.02). Recurrent peritumoral edema developed earlier in true progression than pseudoprogression (median, 173.5 vs. 564 days; p = 0.001). Lower marginal dose at repeat GKS was associated with subsequent true progression (SHR, 0.82; p = 0.02).

A BED₁₀ ≥ 57.6 Gy improved local control in large brain metastases. Recurrent peritumoral edema accompanying tumor enlargement within 1 year after GKS strongly suggested true progression and should prompt consideration of early salvage intervention.

Clinical trial number: not applicable.