Abstract
PurposeFor 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 methodsA 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 (TDRs,p) was calculated for various p and s based on treatment log files and in-house software.ResultsTDR60min,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. TDR60min,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., TDR60min,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).ConclusionsLarge 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.
Highlights
Stereotactic radiosurgery (SRS) is considered standard therapy for oligo (1–3) brain metastases (OBM) [1,2,3]
The median TDRs,p decreased from 0.34 Gy/min (0.19–0.91 Gy/min) for TDR20min,98% to 0.17 Gy/min (0.11–0.86 Gy/min) for TDR120min,98%, while the difference between median TDRs,50% and TDRs,98% was reduced from 0.09 Gy/min for TDR20min,p to 0.03 Gy/min for TDR120min,p
They noticed slight linear mean increases of 0.03 Gy/min per prescribed Gray (Fig. 2a, R2 = 0.95), TDR60min,98% was not affected by maximum dose (Fig. 2b, R2 = 0.02 and ρ = –0.037 with p = 0.636)
Summary
Stereotactic radiosurgery (SRS) is considered standard therapy for oligo (1–3) brain metastases (OBM) [1,2,3]. Technical challenges for MBM-SRS remain which include dose delivery over time to all tumor cells and simultaneous minimization of healthy brain dose. The treatment complexity will automatically increase treatment time, which in turn will decrease the dose delivered to certain tumor cells within certain time spans. This phenomenon is called tumor-dose-rate (TDR) effects, which are loco-regional effects derived from dose-accumulation differences during treatment. For the dose delivered in, e.g., half the treatment time the situation may be different when some cells may have already received the planned dose while other cells may have not even reached the dose by far
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