The Emerging Paradigm of Preoperative Stereotactic Radiosurgery for Resectable Brain Metastases

Abstract

In the treatment of metastatic brain disease, the efficacy of stereotactic radiosurgery (SRS) as an effective cognition-sparing alternative to whole-brain radiotherapy (WBRT) has been well-established, largely in part to the level 1 evidence provided by Chang et al 1 that supports the initial treatment of brain metastases with the combination of SRS and close monitoring rather than with WBRT. For metastatic brain disease that is amenable to operative resection (1-4 brain metastases total with at least 1 lesion producing a significant mass effect and/or ≥2 cm in maximum diameter), Mahajan et al 2 provided level 1 evidence that SRS (performed in this trial as singlefraction gamma knife SRS) is associated with reduced 1-year resection cavity local recurrence from 57% to 28% for patients with 1 to 3 resected brain metastases. Brown et al 3 provided level 1 evidence that suggested that for patients with 1 resected brain metastasis and a resection cavity less than 5 cm, SRS is significantly less toxic than WBRT to cognition, with this reduced toxic effect not compromising overall survival.Because operative resection may carry the risk of leptomeningeal seeding of disease, preoperative sterilization of the lesion with SRS has increased in popularity with the goal of improving on the 28% risk of leptomeningeal disease (LMD) at 12 months post-SRS (as established by Mahajan et al), 2 as it allows for radiation delivery before potential dissemination of the tumor by operative resection. Data on the comparative risk of radionecrosis and local control are also areas of particular interest for investigating the future role of preoperative SRS.The article in this issue of JAMA Oncology by Prabhu et al 4 retrospectively combined the data from 8 centers to create a 416-lesion cohort study (from 404 patients) to evaluate the risk factors for progression and morbidity following preoperative SRS for brain metastases. Stereotactic radiosurgery was performed via either gamma knife or linear accelerator and administered to a single-fraction range of 14 to 17 Gy (median, 15 Gy) or a 3-fraction range of 24 to 26 Gy (median, 24 Gy) to a median gross tumor volume of 10 cc (approximately equivalent to a maximum diameter of 2.7 cm), with a median interval of 2 days between preoperative SRS and resection. The 1-year incidence of resection cavity local recurrence was 11.9%, 2 with an encouragingly low 13.7% 2-year cavity local recurrence rate.The authors found that single-fraction SRS provided worse local control than multifraction SRS, although the tumor size criteria between patients receiving single-fraction vs multifraction SRS was not clearly stated. For single-fraction preoperative SRS, it is likely that the 15-Gy dose the authors used was simply not sufficient to optimally sterilize lesions smaller than 3 cm. For instance, RTOG 90-05 recommendations indicated