Dosimetric and Clinical Prognostic Factors in Single-Isocenter Linac-Based Stereotactic Radiotherapy for Brain Metastases

Simple Summary Although some of the novel systemic treatments, especially the group of tyrosine kinase inhibitors, have shown a durable central nervous system response, ionizing radiation remains the mainstay in the management of brain metastases (BM). Recent technological advancements have enabled the replacement of whole-brain radiotherapy with localized stereotactic radiotherapy (SRT) for treating up to 10 BM, either as a primary or combined treatment, reducing neurotoxicity and improving local control (LC). The delivered target dose and patient selection play a crucial role in enhancing treatment efficacy. However, there is still limited evidence supporting which factors most affect LC and which patients derive the greatest benefit from SRT. This retrospective single-institutional study evaluated treatment outcomes in a heterogeneous patient population treated with Linac-based SRT, with the aim of identifying potential dosimetric and clinical prognostic factors to better inform the decision-making process.Abstract Background/Objectives: To report on predictive factors in Linac-based SRT for single and multiple BM. Methods: Consecutive patients receiving either one or three fractions of single-isocenter coplanar VMAT SRT were retrospectively included. The GTV-PTV margin was 1-2 mm. The delivered target dose was estimated by recalculating the original plans on roto-translated CT according to errors recorded by post-treatment CBCT. The Kaplan-Meier method estimated local progression-free survival (LPFS), intracranial progression-free survival (IPFS), and overall survival (OS). Log-rank and Wilcoxon-Mann-Whitney tests evaluated inter-group differences, whereas Cox regression analysis assessed prognostic factors. Results: Fifty females and fifty males, with a median age of 69 years, received 107 SRTs. A total of 213 BM (range, 1-10 per treatment) with a median volume of 0.22 cc were irradiated with a median minimum BED of 59.5 Gy. The median delivered GTV D95 reduction was -0.3%. The median follow-up was 11 months. Nineteen LP events and a 1-year LC rate of 90.1% were observed. The GTV coverage did not correlate with LC, while the GTV volume was a risk factor for LP, with the 1-year rate dropping to 73% for volumes >= 0.88 cc. The median LPFS, IPFS, and OS were 6, 5, and 7 months, respectively. Multivariate analysis showed that patients with melanoma histology and those receiving a second or subsequent systemic therapy line had the worst outcomes, whereas patients with adenocarcinoma histology and mutations showed better results. Conclusions: The accuracy and efficacy of the Linac-based SRT approach for BM were confirmed, but the dose distribution alone failed to predict the treatment response, suggesting that other factors must be considered to maximize SRT outcomes.