Repeated Stereotactic Radiotherapy for Local Brain Metastases Failure or Distant Brain Recurrent: A Retrospective Study of 184 Patients

SIMPLE SUMMARY: Brain metastases are the most common intracranial malignant neoplasms in adults. Stereotactic radiotherapy (SRT) is one of the most widely used therapeutic modalities to treat BMs. The main benefit of SRT is to delay whole-brain radiotherapy, which causes cognitive impairment. About 20–40% of patients will require salvage treatment after an initial SRT session because of local failure or due to distant failure. The aim of this retrospective monocentric study was to evaluate the factors affecting overall survival (OS) and neurological death-free survival (NDFS). Patients receiving multiple repeated SRT for locally recurrent brain metastases or distant brain failure have better OS and NDFS than those receiving only two SRT sessions. The patients who would benefit most from repeat SRT are those treated for kidney or breast cancer, those in good general condition, those who did not receive systemic treatment and without extracerebral metastases and those with a low brain metastasis velocity. ABSTRACT: Background: The main advantages of stereotactic radiotherapy (SRT) are to delay whole-brain radiotherapy (WBRT) and to deliver ablative doses. Despite this efficacy, the risk of distant brain metastases (BM) one year after SRT ranges from 26% to 77% and 20 to 40% of patients required salvage treatment. The role and consequences of reirradiation remain unclear, particularly in terms of survival. The objective was to study overall survival (OS) and neurological death-free survival (NDFS) and to specify the prognostic factors of long-term survival. Methods: we retrospectively reviewed the data of patients treated between 2010 and 2020 with at least two courses of SRT without previous WBRT. Results: In total, 184 patients were treated for 915 BMs with two-to-six SRT sessions. Additional SRT sessions were provided for local (5.6%) or distant (94.4%) BM recurrence. The median number of BMs treated per SRT was one with a median of four BMs in total. The mean time between the two SRT sessions was 8.9 months (95%CI 7.7–10.1) and there was no significant difference in the delay between the two sessions. The 6-, 12- and 24-month NDFS rates were 97%, 82% and 52%, respectively. The 6-, 12- and 24-month OS rates were 91%, 70% and 38%, respectively. OS was statistically related to the number of SRT sessions (HR = 0.48; p < 0.01), recursive partitioning analysis (HR = 1.84; p = 0.01), salvage WBRT (HR = 0.48; p = 0.01) and brain metastasis velocity (high: HR = 13.83; p < 0.01; intermediate: HR = 4.93; p < 0.01). Conclusions: Lung cancer and melanoma were associated with a lower NDFS compared to breast cancer. A low KPS, a low number of SRT sessions, synchronous extracerebral metastases, synchronous BMs, extracerebral progression at SRT1, a high BMV grade, no WBRT and local recurrence were also associated with a lower NDFS. A high KPS at SRT1 and low BMV grade are prognostic factors for better OS, regardless of the number of BM recurrence events.