2570 - Analysis of the Safety Cohort of a Phase II Study of Preoperative Stereotactic Radiosurgery for Brain Metastases
Presenter(s)
L. Burke1,2, R. Diaz3, T. W. Wang1,2, G. Olsson4, J. McMaster4, H. E. Gee1,2, V. Manivasahan1, R. Stensmyr1, V. Gebski1,5, and N. Nahar1; 1Radiation Oncology Network, Western Sydney Local Health District, Sydney, NSW, Australia, 2University of Sydney, Sydney, NSW, Australia, 3Radiation Oncology, GenesisCare, Rockhampton, QLD, Australia, 4Department of Neurosurgery, Westmead Hospital, Western Sydney Local Health District, Sydney, NSW, Australia, 5NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
Purpose/Objective(s): 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. It is hypothesized to be both safe and efficacious in the treatment of brain metastases and potentially lead to improved local control and reduced rates of radionecrosis and leptomeningeal disease. This is the analysis of the safety cohort from the single-center prospective phase 2 trial, pre-operative SRS for resectable brain metastases.
Materials/Methods: This is a single-institution, single-arm, phase 2 pilot study, of patients with histopathologically diagnosed malignancy and MRI-confirmed brain metastases, with at least 1 lesion amenable to pre-operative SRS (<5cm, requiring resection), target accrual 30 patients. Patients were treated with upfront fractionated SRS to all brain metastases, then proceeded to neurosurgery within 72 hours to target lesions. Routine 3 monthly follow-up with clinical review and MRI assessing adverse events according to NCI-CTCAE v5.0, with highest grade per patient reported and causality assigned retrospectively. Primary outcome of symptomatic radiation toxicity, and secondary outcomes including local recurrence, distant brain failure and overall survival.
Results: Characteristics of the safety cohort comprising the first ten patients completing pre-operative hypofractionated SRS followed by neurosurgical resection; 70% female, mean age 57-years (range 33-77), 60% lung and 30% breast histology, with average GPA 1.9 (range 0.5-4). An average of 3 brain metastases receiving SRS (range 1-13), with target lesions treated 80% with 27Gy in 3 fractions, remainder 30Gy in 5 fractions. Mean time to neurosurgery was 1.2 days (range 1-2), hospital stay 5.9 days (range 2-23), with mean follow-up 15 months (range 2.6-25.9). Symptomatic radionecrosis within 12 months occurred in 1 patient, and all treatment related toxicity (=grade 2) within 12 months occurred in 70% of patients, with only 2 patients with persisting grade 2 toxicity at 12 months. There have been no grade 4 or 5 treatment related toxicities. There was one serious adverse event (grade 3 post-operative wound infection) thus stopping criteria of >2 patients with 30-day =grade 3 surgical morbidity (per Clavien-Dindo Classification) was not met. 12-month local control and overall survival is 100% and 60% respectively.
Conclusion: Pre-operative SRS followed by neurosurgical resection for patients with resectable brain metastases was deemed safe with no excess surgical morbidity. The outcomes of the safety cohort support the ongoing investigation of the use of pre-operative SRS in the management of brain metastases, with no excess rates of radionecrosis compared with current literature, and excellent local control.