Background:
Pre-operative stereotactic radiosurgery (SRS) has potential advantages over post-operative SRS including certainty of volume delineation, reduced PTV margins limiting healthy brain irradiated, simultaneous treatment of metastases and preventing treatment delays.1,2,3
Aims:
This is a planned interim toxicity analysis of prospective phase 2 trial, pre-operative SRS for resectable brain metastases, with stopping criteria of >2 patients with 30-day grade ≥3 surgical morbidity (per Clavien-Dindo Classification).4
Methods:
Single-institution, single-arm, phase 2 pilot study, target accrual 30 patients, histopathologically diagnosed malignancy and MRI-confirmed brain metastases, at least 1 lesion amenable to pre-operative SRS (<5cm, requiring resection). Patients treated with upfront fractionated SRS to all brain metastases, then proceed to neurosurgery within 72 hours to targeted lesions. Primary outcome of symptomatic radiation toxicity (≥ Grade 2) within 12-months, secondary outcomes; local recurrence, distant brain failure and overall survival. Adverse events graded according to NCI-CTCAE v5.0, with highest grade per patient reported.
Results:
Safety cohort comprises ten patients who completed protocol treatment, 60% female, mean age 57-years (range 33-77), 60% lung, 30% breast cancer with average GPA 1.9 (range 0.5-4). Average 3 brain metastases receiving SRS (range 1-13), 80% with 27Gy in 3 fractions, remainder 30Gy in 5, time to neurosurgery 1.2 days (range 1-2), hospital stay 5.9 days (range 2-23). At mean follow-up 11.7 months (range 1.0-24.3) local control 100%, 70% overall survival, 1 event of radionecrosis (10%). There was only one serious adverse event (grade 3 post-operative wound infection) thus stopping criteria was not met. One patient had grade 3 toxicity (seizure, cerebral oedema) and 14 grade 2 toxicities were deemed possibly/probably/definitely related to protocol treatment. Three patients died during follow-up; one extracranial disease progression, two non-treatment related causes.
Conclusion:
Pre-operative SRS followed by neurosurgical resection for patients with resectable brain metastases was deemed safe and trial stopping criteria was not met.