Salvage stereotactic radiotherapy for locally recurrent brain metastases: a systematic review

Stereotactic radiotherapy (SRT), including stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hfSRT), plays a key role in the management of brain metastases (BM). As advances in systemic therapies prolong survival, local recurrence of BM has become more frequent, prompting interest in salvage reirradiation strategies. This systematic review aimed to evaluate the efficacy and safety of a second course of stereotactic radiotherapy (SRT2) for in-field recurrent brain metastases. Data on local control, overall survival, and radionecrosis were extracted and pooled using random-effects models. Eleven retrospective studies published between 2020 and 2025 were included, comprising 914 patients and 2,352 brain metastases, with 389 lesions treated with salvage SRS2/SRT2. Patients who had received prior whole-brain radiotherapy were excluded. The pooled 1-year local failure rate was 24%, and radionecrosis occurred in approximately 13% of cases. Median overall survival after salvage SRS2 was 14 months. Radionecrosis typically occurred within 4–8 months post-treatment and was associated with larger tumor volume and higher prescribed dose. Moderate heterogeneity was observed across studies, and conclusions regarding the impact of multifraction regimens should be interpreted cautiously. Salvage SRS2/SRT2 appears to provide meaningful local control and survival benefit in selected patients with recurrent brain metastases, with an acceptable toxicity profile. These findings support its role as an effective non-surgical salvage option, although prospective studies are needed to better define optimal treatment parameters and patient selection.