Phase 1 study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery in the primary management of patients with inoperable, previously irradiated metastatic epidural spinal cord compression

BACKGROUND: Patients with previously irradiated metastatic epidural spinal cord compression (MESCC) who are not surgical candidates are at high risk of neurologic deterioration due to disease in the setting of limited treatment options. We seek to establish the feasibility of using salvage spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of MESCC in inoperable patients monitoring for radiation related toxicity and radiographic local control (LC). METHODS: Inoperable patients with previously irradiated MESCC were enrolled on this prospective Phase 1 single institution protocol. Single fraction SSRS was delivered to a prescription dose of 18 Gy. Spinal cord constraint relaxation was performed incrementally from an initial allowable Dmax cohort of 8 Gy to 14 Gy in the final planned cohort. Patients were monitored every 3 months with follow-up visits and MRI scans. RESULTS: The trial was closed early due to slow accrual. From 2011 to 2014, 11 patients were enrolled of which 9 patients received SSRS. Five patients were in the 8 Gy cord Dmax cohort and 4 in the 10 Gy cord Dmax cohort. The median overall survival (OS) was 11.9 months (95% CI 7.1, 22 months). Of the 9 patients treated with SSRS, 1 died prior to post-SSRS evaluation. Of the remaining 8 patients, 5 experienced a local failure. Three of the five were treated with surgery while two received systemic therapy. Two of the five failures ultimately resulted in loss of neurologic function. The median LC was 9.1 months (95%CI 4.8, 20.1 months). With a median clinical follow-up of 6.8 months, there were no cases of RM. CONCLUSIONS: Despite the limited life expectancy in this high-risk cohort of patients, strategies to optimize LC are necessary to prevent neurologic deterioration. Larger prospective trials exploring optimal dose/fractionation and cord constraints are required.