Precision Radiation Therapy for Metastatic Spinal Cord Compression: Final Results of the PRE-MODE Trial.

Objective: To investigate precision radiation therapy for metastatic spinal cord compression and compare it to conventional radiation therapy. Methods and Materials: In a multicenter phase 2 study, 40 patients received 5 Gy x 5 fractions of precision radiation therapy (38 volume modulated arc therapy, 2 intensity modulated radiation therapy) for metastatic spinal cord compression and were evaluated for local progression-free survival (LPFS), motor function, ambulatory status, sensory function, sphincter dysfunction, pain, distress, overall survival (OS), and toxicity. Maximum spinal cord dose was 101.5% (myelopathy risk, <0.03%) of the prescription dose. Patients were compared with a historical control group conventionally irradiated with 4 Gy x 5 fractions (propensity score analysis). The equivalent dose in 2 Gy-fractions of 5 Gy x 5 fractions is similar to 3 Gy x 10 fractions, which results in better LPFS than 4 Gy x 5 fractions. It was assumed that 5 Gy x 5 fractions is also superior to 4 Gy x 5 fractions for LPFS. (ClinicalTrials.gov-identifier: NCT03070431) Results: Six-month rates of LPFS and OS were 95.0% and 42.6%, respectively. Improvement of motor function occurred in 24 patients (60%). Thirty-three patients (82.5%) were ambulatory after radiation therapy. Eight of 16 patients (50.0%) with sensory deficits improved. Pain and distress relief were reported by 61.9% and 54.2% of patients 1 month after radiation therapy. Grade 3 toxicities occurred in 1 patient and grade 2 toxicities in another 3 patients. Of the control group, 664 patients qualified for the propensity score analysis; 5 Gy x 5 fractions was significantly superior to 4 Gy x 5 fractions with regard to LPFS (P = .026) but not motor function (P = .51) or OS (P = .82). Conclusions: Precision radiation therapy with 5 Gy x 5 fractions was well tolerated and effective and appeared superior to 4 Gy x 5 fractions in terms of LPFS. The retrospective nature of the historic control group, which might have led to a hidden selection bias, needs to be considered when interpreting the results. (C) 2019 Elsevier Inc. All rights reserved.