A feasibility trial of delayed resection for brain metastases following pre-operative stereotactic radiosurgery

Pre-operative stereotactic radiosurgery (SRS) for brain metastases (BrM), an emerging alternative to post-operative SRS, is typically performed 1-2 days before resection. However, a longer period of the irradiated tumour in situ may confer anti-tumour immunological benefits. We conducted the first clinical trial to evaluate the feasibility of planned delayed resection after pre-operative SRS.

In this single-arm trial, patients with suspected BrM suitable for pre-operative SRS and surgery were eligible. The primary endpoint was feasibility of resection 7-21 days after SRS, with a pre-defined feasibility threshold of 66% receiving this. Secondary endpoints included 6-month adverse events (AE) and local control (LC) rates. Tumour volume change was assessed from SRS- and neurosurgery-planning MRI's.

78 patients were screened and the target accrual of 15 patients was met. Common reasons for pre-operative SRS ineligibility were lack of existing cancer diagnosis (44%) and tumour size/peri-tumoural oedema (18%). Two patients declined resection after SRS. The median SRS-to-surgery interval was 8 days (range 0-15). Nine tumours in 8 patients (56%) received delayed resection. Reasons for earlier resection were predominantly non-medical. There were no Grade > 2 AE. The 6-month BrM LC was 100%. At a median follow-up of 13.8 months, the only BrM local failure after SRS and resection occurred with a 0-day SRS-to-surgery interval. No histopathological diagnosis issues were encountered with delayed resection. An increased SRS-to-surgery interval correlated with greater tumour shrinkage.

The pre-defined feasibility threshold for delayed resection was not met, but more than half of patients received delayed resection without safety concerns.

ACTRN12622001372774 (Registered 26/10/2022).