Preoperative radiosurgery for brain metastases (PREOP-1): A feasibility trial

Abstract

Purpose: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1).

Methods: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers.

Results: Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm³ (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed.

Conclusion: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

Keywords: Brain; Feasibility; Metastases; Preoperative; Radiosurgery; Trial.

Fig. 1

Preoperative SRS workflow.

Fig. 2

Kaplan-Meier estimate of the probability of Fig. 1a: leptomeningeal disease-free survival (100%), Fig. 1b: local control (80%) and Fig, 1c; overall survival following preoperative SRS. a. There were no cases of leptomeningeal disease (nodular or classical) after preoperative radiosurgery. b. The cavity local control rate was 80% after preoperative radiosurgery. c. Overall survival after preoperative radiosurgery.

Fig. 2

Kaplan-Meier estimate of the probability of Fig. 1a: leptomeningeal disease-free survival (100%), Fig. 1b: local control (80%) and Fig, 1c; overall survival following preoperative SRS. a. There were no cases of leptomeningeal disease (nodular or classical) after preoperative radiosurgery. b. The cavity local control rate was 80% after preoperative radiosurgery. c. Overall survival after preoperative radiosurgery.

Fig. 2

Kaplan-Meier estimate of the probability of Fig. 1a: leptomeningeal disease-free survival (100%), Fig. 1b: local control (80%) and Fig, 1c; overall survival following preoperative SRS. a. There were no cases of leptomeningeal disease (nodular or classical) after preoperative radiosurgery. b. The cavity local control rate was 80% after preoperative radiosurgery. c. Overall survival after preoperative radiosurgery.

Fig. 3

Depiction of the relative difference (percentage change in counts per 10 low power fields) of tumour-infiltrating lymphocytes (CD3, 4 and 8) and markers of proliferation (Ki67) and necrosis in 7 patients with matched tissue from the primary tumour and a preoperatively irradiated metastasis. Six patients had sufficient tissue available for the assessment of all markers.