Significance of target location relative to the depth from the brain surface and high-dose irradiated volume in the development of brain radionecrosis after micromultileaf collimator-based stereotactic radiosurgery for brain metastases

The objective of this study was to investigate the factors that potentially lead to brain radionecrosis (RN) after micromultileaf collimator-based stereotactic radiosurgery (SRS) for brain metastases. We retrospectively evaluated 131 lesions with a minimum follow-up of 6 months, 43.5% of which received prior whole-brain radiotherapy (WBRT). The three-tiered location grade (LG) was defined, as follows, for each target by considering mainly the depth from the brain surface: grade 1 (superficial), involving the region at a depth of ≤5 mm from the brain surface; grade 2 (deep), located at a depth of >5 mm from the brain surface; and grade 3 (central), located in the brainstem, cerebellar peduncle, diencephalon, or basal ganglion. The predictive factors for RN, including high-dose irradiated isodose volumes (IIDVs) and LG, were evaluated by univariate and multivariate analysis. Symptomatic RN (S-RN) and asymptomatic RN (A-RN) were observed in 8.4% and 6.9% of cases, respectively. Multivariate analysis indicated that the significant factors for both types of RN were LG, V12 Gy, and V22 Gy in all cases; V22 Gy and LG for the non-WBRT cases; and V15 Gy and LG for the WBRT cases. For the non-WBRT cases, the cutoff values of V22 Gy were 2.62 and 2.14 cm³ for S-RN and both RN, respectively. For the WBRT cases, the cutoff values of V15 Gy were 5.61 and 5.20 cm³ for S-RN and both RN, respectively. In addition to the IIDV data, LG helps predict the risk of RN. High-dose IIDV, V22 Gy, was also significantly correlated with RN, particularly for patients treated with SRS alone.