Pérez García, Victor M.. Pérez Beteta, Julián. Ocaña Tienda, Beatriz. 

Background: Stereotactic radiotherapy is the preferred treatment for managing patients with fewer than five brain metastases (BMs). However, some lesions recur after irradiation. The purpose of this study was to identify patients who are at a higher risk of failure, which can help in adjusting treatments and preventing recurrence. Methods: In this retrospective multicenter study, we analyzed the predictive significance of a set of interpretable morphological features derived from contrast-enhanced (CE) T1-weighted MR images as imaging biomarkers using Kaplan-Meier analysis. The feature sets studied included the total and necrotic volumes, the surface regularity and the CE rim width. Additionally, we evaluated other nonmorphological variables and performed multivariate Cox analysis. Results: A total of 183 lesions in 128 patients were included (median age 61 [31-95], 64 men and 64 women) treated with stereotactic radiotherapy (57% single fraction, 43% fractionated radiotherapy). None of the studied variables measured at diagnosis were found to have prognostic value. However, the total and necrotic volumes and the CE rim width measured at the first follow-up after treatment and the change in volume due to irradiation can be used as imaging biomarkers for recurrence. The optimal classification was achieved by combining the changes in tumor volume before and after treatment with the presence or absence of necrosis (p < < 0.001). Conclusion: This study demonstrated the prognostic significance of interpretable morphological features extracted from routine clinical MR images following irradiation in brain metastases, offering valuable insights for personalized treatment strategies.