J Neurooncol in press

Fractionated pre-operative stereotactic radiotherapy for
patients with brain metastases: a multi-institutional analysis.

Palmer JD, Perlow HK, Matsui JK, Ho C, Prasad RN, Liu K, Upadhyay R, Klamer B, Wang J, Damante M, Ghose J, Blakaj DM, Beyer S, Grecula J, Arnett A, Thomas E, Chakravarti A, Lonser R, Hardesty D, Prevedello D, Prabhu R, Elder JB, Raval RR

BACKGROUND : The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD.

METHODS : A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN.

RESULTS : 53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24-25 Gy in 3-5 fractions. There were 0 LFs, 3 Grade 2-3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate.

CONCLUSIONS : In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49-60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.