Single-fraction versus hypofractionated gamma knife radiosurgery for small metastatic brain tumors

Stereotactic radiosurgery (SRS) has become a standard of care for the treatment of metastatic brain tumors (METs). Although a better balance of tumor control and toxicity of hypofractionated SRS (hfSRS) compared with single-fraction SRS (sfSRS) was demonstrated in large METs, there is no data comparing two approaches for small METs (< 4 cm³). It was aimed to compare clinical outcomes between sfSRS versus hfSRS Gamma Knife radiosurgery (GKRS) in a series of patients with unresected, small METs. Patients (n = 208) treated with sfGKRS or hfGKRS between June 2017 and May 2020 were retrospectively examined in a single center. The co-primary endpoints of local control (LC) and toxicity were estimated by applying the Kaplan-Meier method. Multivariate analysis using Cox proportional hazards (HR) modeling was used to assess the effect of independent variables on the outcomes. The actuarial LC rate was 99.7% at six months and 98.8% at 18 months in the sfGKRS group, and 99.4% and 94.3% in the hfGKRS group (p = 0.089), respectively. In multivariate analysis, MET volume (p = 0.023, HR 2.064) and biologically effective dose (BED₁₀) (p < 0.0001, HR 0.753) was associated with LC. In total, treatment-related toxicity was observed in 13 (8.7%) patients during a median period of 10 weeks (range 1-31). Radiation necrosis was observed in four patients (1.9%), and all patients were in the sfGKRS group (p = 0.042). Only the maximum dose was associated with toxicity (p = 0.032, HR 1.047). Our current results suggest that hfGKRS is advantageous and beneficial also in patients with unresected, small METs.