PROTOCOL FOR A PROSPECTIVE, SINGLE-ARM, PHASE II CLINICAL TRIAL EVALUATING THE EFFICACY AND SAFETY OF NEO-ADJUVANT STEREOTACTIC RADIOSURGERY PRIOR TO SURGICAL RESECTION OF A DOMINANT BRAIN METASTASIS

Abstract

AIMS: Surgery alone for brain metastases can lead to high rates of local recurrence and focal leptomeningeal disease (fLMD). Adjuvant stereotactic radiosurgery (SRS) does not lower leptomeningeal rates and is associated with high radionecrosis rates. SRS prior to surgery has been proposed as a way to mitigate these risks. Here we present our protocol for an upcoming prospective, single-arm, phase II clinical trial evaluating the efficacy and safety of neo-adjuvant SRS prior to surgical resection of a dominant brain metastasis. The primary objective is local event-free survival (LEFS), a composite outcome of local failure, symptomatic radionecrosis and fLMD. METHOD(S): This prospective, single-arm phase II trial is open to multiple centres offering SRS services, and will collect data on clinical, radiological, pathological and quality of life outcomes. Patients with radiologically confirmed solid tumour brain metastases, with a maximum of 10 metastases, and suitable for surgical resection and SRS will be included. Neo-adjuvant SRS will be delivered with a prescribed peripheral dose in a single fraction. The total follow-up period will be two years. RESULT(S): The primary endpoint is time to LEFS, defined as the interval from randomisation to the first occurrence of either local failure, symptomatic radionecrosis or fLMD. Secondary endpoints include overall survival, time to local failure, time to symptomatic radionecrosis, time to focal and classical LMD, time to distant in-brain failure, and patient-reported quality of life. Analysis of acute histopathological changes in resected tissue will also be performed as an optional outcome. CONCLUSION(S): This phase II trial will provide valuable preliminary data on the safety and efficacy of neo-adjuvant SRS in the treatment of brain metastases. The results will inform the design of a larger, randomised phase III controlled trial to definitively establish the role of this approach in improving outcomes for patients with brain metastases.