OS03.4 Gammaknife versus Linac based (EDGE) radiosurgery (SRS) for patients with limited brain metastases (BMS) from different solid tumor: a phase III randomized trial.
Authors: M. Scorsetti, P. Navarria, A. Ascolese, E. Clerici, P. Mancosu, P. Picozzi, G. Pecchioli, C. Franzese, G. Reggiori, S. Tomatis
Journal: Neuro-Oncology (2017)

Introduction: Radiosurgery is an emerging terapeutich approach for the treatment of brain metastases (BMs), considering the effective local control obtained without neurological impairment. Different technological modalities have been used: Gammaknife, Cybernife, or Linac with comparable results and different incidence of symptomatic radionecrosis. To date no comparative randomized studies have been published on this matter. We draw this randomized phase III trial with the aim to evaluate incidence of symptomatic radionecrosis using gamma knife radiosurgery versus linac based (EDGE) radiosurgery. Local control (LC) rate and patients overall survival (OS) were assessed as well. Materials: Patients with limited BMs (up to 4) from different solid tumors, except SCLC or hematologic malignancies, were enrolled. Inclusion criteria were a histopatological diagnosis of malignant primary tumor, a KPS ≥70, RPA class I-II, and BMs with maximum diameter ≤3 cm and/or with a total tumor volume <30 cm3. The total dose prescribed was 24 Gy for BMs ≤ 20 mm or 4.2 cm3, and 20 Gy for BMs 21–30 mm or volume <14.1 cm3 as suggested by RTOG guidelines. Clinical outcome was evaluated by neurological examination and MRI at 2 months after SRS and then every 3 months. The radionecrosis was considered the presence of central hypodensity and peripheral enhancement on T1-weighted post-contrast imaging, with edema on T2-weighted sequences and a clear lack of perfusion without any nodular highly vascularized area within the contrast enhanced lesion on perfusion MRI. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume on serial MR imaging, and distant failure by the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Results: From October 2014 to December 2015, 101 consecutives patients of the expected 250, for 167 BMs treated, were evaluated. The most common primary cancer was NSCLC (55.4%). The majority of patients have a KPS of 90–100 (53.5%) and were in RPA class II (85%). Symptomatic radionecrosis was observed in a total of 12 (11.9%) cases of the entire cohort evaluated. In the gammaknife ARM Grade II radionecrosis was recorded in 5 cases and Grade III in 2 cases. In the EDGE ARM only grade II radionecrosis occurred in 5 cases treated. No local progression in site of SRS occurred. At a median time of 11 months (range 9–12 months) 42 (41.5%) patients had new distant brain metastases, and 59 (58%) had extracranial progression at a median time of 8 months (range 7–11 months). The 6 months and 1 year OS were 81% and 70%, comparable in both arms. On univariate analysis the KPS was the only factor recorded as statistically impacting on OS. Conclusions: Gamma-knife and LINAC based SRS for BMs were comparable in terms of LC. In this evaluation the risk of symptomatic radionecrosis was greater in the gammaknife arm. This trial is supported by Varian.