Staged Stereotactic Radiosurgery as a Novel Adaptive Approach to Salvage Previously Irradiated Brain Metastases

Abstract

We report outcomes specific to a novel 3 fraction (frx) staged stereotactic radiosurgery (St-SRS) regimen designed to salvage metastases previously irradiated and considered to be at high risk of radiation necrosis (RN). A total of 24 patients with 55 metastases treated with our 3 frx St-SRS approach were reviewed. Prior to each frx, patients were re-simulated and planned with a new MRI to allow for treatment adaption. The primary endpoint was the cumulative incidence of local failure (LF) and secondary endpoints included tumor dynamics and RN rates. The median follow up was 9.0 months (range: 2.7-40.1 months) and median age was 59-years (range: 32-84). Primary cancers were of breast (44%), lung (33%), melanoma (22%), and gastro-intestinal (1%) origin. Individual metastases treated with St-SRS had initially failed surgery and post-op cavity hypofractionated SRS (HSRS) for 2/55 (4%), SRS alone for 19/55 (34%), whole brain radiation (WBRT) alone for 6/55 (11%), HSRS for 2/55 (4%), and prior SRS and WBRT exposure for 28/55 (51%). 46/55 (84%) were prescribed 8 Gy, 8 Gy, 4 Gy; 8/55 (14%) had 6 Gy, 6 Gy, 4 Gy and 1/55 (2%) had 8 Gy, 8 Gy, 6 Gy. The median number of weeks between frx was 2.6 (range: 1.0-6.8). The median of the mean and maximum target doses were 9.7 Gy (range: 5.4-11.7 Gy) and 12.4 Gy (range, 7.5-16.0 Gy) respectively. The median prescription isodose line was 62% (range: 50-85%). The mean lesion volume and diameter was 3.8cc (range: 0.05-24.8cc) and 1.6cm (range: 0.2-4.4cm), respectively. The mean percent target volume coverage, Paddick Conformality Index and Gradient Index were 100% (range: 97-100%), 0.7 (range: 0.1-0.9), and 3.2 (range: 2.5-6.7), respectively. The mean volume change between staged frxs was -4.2% (range: -69.3 to +63.1%), and based on the first and last St-SRS MRI was -10.8% (range: -86.6% to +68.7%). The crude LF rate was 27%. The median time to LF was 3.4 months (range: 1.2-7.4 months). Amongst those with a LF, 7/15 (46%) were melanoma, 6/15 (40%) HER2 positive breast cancer, 1/15 (7%) gastrointestinal and 1/15 (7%) non-small cell lung carcinoma. 8/15 (53%) had prior WBRT and SRS exposure, 1/16 (7%) surgery and cavity HSRS, 5/15 (33%) SRS alone and 1/15 (7%) WBRT alone. Only asymptomatic RN events were observed in 4/55 (7%). St-SRS is a promising approach to salvage previously irradiated brain metastases, including prior SRS, with a favorable rate of RN. Tumor volume dynamics between stages can be significant warranting adaptive replanning.