Tumor-dose-rate variations during robotic radiosurgery of oligo and multiple brain metastases

PURPOSE: For step-and-shoot robotic stereotactic radiosurgery (SRS) the dose delivered over time, called local tumor-dose-rate (TDR), may strongly vary during treatment of multiple lesions. The authors sought to evaluate technical parameters influencing TDR and correlate TDR to clinical outcome. MATERIAL AND METHODS: A total of 23 patients with 162 oligo (1–3) and multiple (>3) brain metastases (OBM/MBM) treated in 33 SRS sessions were retrospectively analyzed. Median PTV were 0.11 cc (0.01–6.36 cc) and 0.50 cc (0.12–3.68 cc) for OBM and MBM, respectively. Prescription dose ranged from 16 to 20 Gy prescribed to the median 70% isodose line. The maximum dose-rate for planning target volume (PTV) percentage p in time span s during treatment (TDR(s,p)) was calculated for various p and s based on treatment log files and in-house software. RESULTS: TDR(60min,98%) was 0.30 Gy/min (0.23–0.87 Gy/min) for OBM and 0.22 Gy/min (0.12–0.63 Gy/min) for MBM, respectively, and increased by 0.03 Gy/min per prescribed Gy. TDR(60min,98%) strongly correlated with treatment time (ρ = −0.717, p < 0.001), monitor units (MU) (ρ = −0.767, p < 0.001), number of beams (ρ = −0.755, p < 0.001) and beam directions (ρ = −0.685, p < 0.001) as well as lesions treated per collimator (ρ = −0.708, P < 0.001). Median overall survival (OS) was 20 months and 1‑ and 2‑year local control (LC) was 98.8% and 90.3%, respectively. LC did not correlate with any TDR, but tumor response (partial response [PR] or complete response [CR]) correlated with all TDR in univariate analysis (e.g., TDR(60min,98%): hazard ration [HR] = 0.974, confidence interval [CI] = 0.952–0.996, p = 0.019). In multivariate analysis only concomitant targeted therapy or immunotherapy and breast cancer tumor histology remained a significant factor for tumor response. Local grade ≥2 radiation-induced tissue reactions were noted in 26.3% (OBM) and 5.2% (MBM), respectively, mainly influenced by tumor volume (p < 0.001). CONCLUSIONS: Large TDR variations are noted during MBM-SRS which mainly arise from prolonged treatment times. Clinically, low TDR corresponded with decreased local tumor responses, although the main influencing factor was concomitant medication.