Tumor control probability modeling of stereotactic radiosurgery and fractionated stereotactic radiosurgery for patients with brainstem metastases.

Abstract

Evidence supports stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS) for brainstem metastases (BSMs). The optimal dose-fractionation schedule remains undefined. We evaluated tumor control probability (TCP), overall survival (OS), and treatment-related adverse events after SRS and fSRS. We conducted a comprehensive review of studies from the PubMed, Embase, and Cochrane databases and from our institutional cohort. Logistic dose-response models compared TCP and OS using biological effective dose (BED) calculated using the linear-quadratic model and equivalent doses for 1-5 fractions. The α/β ratio was estimated by fitting TCP data using maximum likelihood estimation across three representative radiobiological models. A total of 2,237 patients (2,423 lesions) from 28 articles and our institutional cohort were included in the analysis. The median tumor volume was 0.4 cm³ (range, 0.04-4.2; interquartile range [IQR], 0.19-0.995), and the median follow-up duration was 10 months (range, 3.2-37.7; IQR, 5.8-14.15). Fitting the clinical TCP data from SRS and fSRS consistently yielded α/β ratios of approximately 20 Gy across all three radiobiological models. SRS and fSRS achieved an estimated 1-year TCP of 90% at a BED₂₀ ≈ 36.8 Gy (≈ 18.9 Gy/1 fx, 23.3 Gy/2 fx, 25.7 Gy/3 fx, 27.4 Gy/4 fx, and 28.6 Gy/5 fx) and a 2-year TCP of 90% at a BED₂₀ ≈ 41.4 Gy (≈ 20.5 Gy/1 fx, 25.3 Gy/2 fx, 28.2 Gy/3 fx, 30.1 Gy/4 fx, and 31.5 Gy/5 fx). Estimated 1- and 2-year TCPs of 80%, 85%, and 90% were achieved with single-fraction doses of 15.8, 17.2, and 18.9 Gy as well as 17.4, 18.8, and 20.5 Gy, respectively. A trend toward significance was observed for BED₂₀ and equivalent dose in relation to 1- and 2-year OS following SRS and fSRS. Grade ≥ 3 adverse events were infrequent (3.1%), with only one patient experiencing grade 5 hemorrhage (0.04%). For carefully selected patients with BSMs, SRS or fSRS should be delivered at a BED₂₀ of at least 41.4 Gy, corresponding to 20.5-31.5 Gy in 1-5 fractions, yielding favorable 2-year LC with acceptable incidences of grade ≥ 3 adverse events. These findings are warranting validation through ongoing and planned prospective clinical trials.