Repeated HyperArc Radiosurgery for Recurrent Intracranial Metastases and Dosimetric Analysis of Recurrence Pattern to Account for Diffuse Dose Effect on Microscopical Disease

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2 -8) HyperArc courses in case of exclusive intracranial progression. Primary end -point was the overall survival (OS), secondary end -points were intracranial progression -free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole -brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1 -year OS was 70 %, and the median was 20.8 months (17 -36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non -melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1 -year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0 -7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2 -year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non -melanoma histology were significant predictors of higher LC. The 2 -year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV . Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.