Abstract

Following surgical resection of brain metastases (BMs), adjuvant stereotactic radiosurgery (SRS) has become the standard of care post-operative cavity irradiation. Recent studies, however, have demonstrated that with the current sequence of surgery and radiation, risk of leptomeningeal disease (LMD) and radiation necrosis (RN) remains high. Pre-operative, or neoadjuvant, SRS (nSRS) has been proposed as an alternative treatment strategy which not only minimizes local recurrence (LR) but also LMD and RN. It is thought that nSRS sterilizes the tumor, allowing for minimal spillage of viable tumor cells during resection, creating less favorable conditions for LMD. Furthermore, nSRS allows for easier contouring and decreased margin irradiation during planning and treatment, respectively, diminishing the risk of symptomatic RN. While nSRS has already been adopted for treating other extra-cranial tumors, its role in treating BMs is yet to be defined. We aim to summarize recent studies in nSRS usage for BMs and the rationale of this treatment strategy. We performed a search for articles regarding nSRS for BMs published in PubMed from 2018 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized a total of 14 retrospective reviews, case series, dose/timing studies, and ongoing Phase II & III clinical trials. In this review, we describe the findings of current studies and identify prospective clinical trials with the aim of understanding the efficacy of nSRS over current treatment standards. Herein, we also discuss the theoretical advantages and limitations of nSRS (both biologic and clinical) to help guide future clinical investigations.

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