Significant correlation between gross tumor volume (GTV) D98% and local control in multifraction stereotactic radiotherapy (MF-SRT) for unresected brain metastases.

Abstract

Stereotactic radiotherapy (SRT) should be applied with a biologically effective dose with an α/β of 12 (BED₁₂) ≥ 40 Gy to reach a 1-year local control (LC) ≥ 70%. The aims of this retrospective study were to report a series of 81 unresected large brain metastases treated with Linac-based multifraction SRT according to the ICRU 91 and to identify predictive factors associated with LC. Included in this study were the first 81 brain metastases (BM) consecutively treated with Linac-based volumetric modulated arc therapy (VMAT) multifraction SRT from 2017 to 2019. The prescribed dose was 33 Gy for the GTV and 23.1 Gy (70% isodose line) for the PTV in 3 fractions (3f). Mean BM largest diameter and GTV were 25.1 mm and 7.2 cc respectively. Mean follow-up was 10.2 months. LC was 79.7% and 69.7% at 1 and 2 years respectively. Significant predictive factors of LC were GTV D_98% (HR = 0.84, CI 95% = 0.75-0.95, p = 0.004) and adenocarcinoma as the histological type (HR = 0.29, CI 95% = 0.09-0.96, p = 0.042) in univariate and multivariate analysis. A threshold of 29 Gy for GTV D_98% was significantly correlated to LC (1-year LC = 91.9% for GTV D_98% ≥ 29 Gy vs 69.6% for GTV D_98% < 29 Gy (p = 0.030)), corresponding to a BED₁₂ = 52.4 Gy. No tumor progression was observed for a BED₁₂ ≥ 53.4 Gy, corresponding to a GTV D_98% ≥ 20 Gy /1f and GTV D_98% ≥ 29.4 Gy 3f. Median OS was 15 months. Symptomatic radionecrosis occurred in 4.9% of cases. The GTV D_98% is a strong reproducible significant predictive factor of LC for brain SRT. Dose prescription should lead to a GTV BED_{12 98%} ≥ 52.4-53.4 Gy to significantly improve LC, corresponding to respectively a GTV D_98% ≥ 19.7-20 Gy/1f and 29-29.4 Gy/3f.