High-precision radiotherapy of motor deficits due to metastatic spinal cord compression (PRE-MODE): a multicenter phase 2 study.

Abstract

BACKGROUND:

For metastatic spinal cord compression (MSCC), conventional radiotherapy with 10 × 3 Gy in 2 weeks results in better local progression-free survival (LPFS) than 5 × 4 Gy in 1 week. Since patients with MSCC are often significantly impaired, an overall treatment time of 1 week would be preferable if resulting in similar outcomes as longer programs. This may be achieved with 5 × 5 Gy in 1 week, since the biologically effective dose is similar to 10 × 3 Gy. It can be expected that 5 × 5 Gy (like 10 × 3) Gy results in better LPFS than 5 × 4 Gy in 1 week.

METHODS/DESIGN:

This phase 2 study investigates LPFS after high-precision RT with 5 × 5 Gy in 1 week. LPFS is defined as freedom from both progression of motor deficits during RT and new or progressive motor deficits dur to an in-field recurrence of MSCC following RT. Considering the tolerance dose of the spinal cord, 5 × 5 Gy can be safely administered with high-precision radiotherapy such as volumetric modulated arc therapy (VMAT) or stereotactic body radiotherapy (SBRT). Maximum dose to the spinal cord should not exceed 101.5% of the prescribed dose to keep the risk of radiation myelopathy below 0.03%. Primary endpoint is LPFS at 6 months following radiotherapy; secondary endpoints include motor function/ability to walk, sensory function, sphincter dysfunction, LPFS directly and 1 and 3 months following radiotherapy, overall survival, pain relief, quality of life and toxicity. Follow-up visits will be performed directly and at 1, 3 and 6 months following radiotherapy. After completion of this phase 2 study, patients will be compared to a historical control group receiving conventional radiotherapy with 5 × 4 Gy in 1 week. Forty-four patients will be included assuming 5 × 5 Gy will provide the same benefit in LPFS when compared to 5 × 4 Gy as reported for 10 × 3 Gy.

DISCUSSION:

If superiority regarding LPFS is shown for high-precision radiotherapy with 5 × 5 Gy when compared to conventional radiotherapy with 5 × 4 Gy, patients with MSCC would benefit from 5 × 5 Gy, since high LPFS rates could be achieved with 1 week of radiotherapy instead of 2 weeks (10 × 3 Gy).

TRIAL REGISTRATION:

clinicaltrials.gov NCT03070431 . Registered 27 February 2017.

• Authors: Dirk Rades, Jon Cacicedo, Antonio J Conde-Moreno, Claudia Doemer, Jürgen Dunst, Darejan Lomidze, Barbara Segedin, Denise Olbrich, Niels Henrik Holländer
• Journal: BMC cancer (BMC Cancer) Vol. 17 Issue 1 Pg. 818 (Dec 04 2017) ISSN: 1471-2407 [Electronic] England
• PMID: 29202720 (Publication Type: Journal Article)

Topics

• Clinical Trials, Phase II as Topic
• Disease-Free Survival
• Dose Fractionation, Radiation
• Humans
• Motor Disorders (etiology, therapy)
• Multicenter Studies as Topic
• Radiotherapy Planning, Computer-Assisted
• Spinal Cord Compression (complications, radiotherapy)
• Spinal Neoplasms (radiotherapy, secondary)