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

• Published in: BMC cancer 2017-12, Vol.17 (1), p.818-6, Article 818
• Main Authors: Rades, Dirk, Cacicedo, Jon, Conde-Moreno, Antonio J, Doemer, Claudia, Dunst, Jürgen, Lomidze, Darejan, Segedin, Barbara, Olbrich, Denise, Holländer, Niels Henrik
• Format: Article
• Language: English
• Subjects: Cancer metastasis; Care and treatment; Clinical Trials, Phase II as Topic; Disease-Free Survival; Dose Fractionation, Radiation; Humans; Local progression-free survival; Medical research; Metastatic spinal cord compression; Motor Disorders - etiology; Motor Disorders - therapy; Motor function; Multicenter Studies as Topic; Overall survival; Radiotherapy; Radiotherapy Planning, Computer-Assisted; Spinal cord compression; Spinal Cord Compression - complications; Spinal Cord Compression - radiotherapy; Spinal Neoplasms - radiotherapy; Spinal Neoplasms - secondary; Stereotactic body radiotherapy; Study Protocol; Volumetric modulated arc therapy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-017-3844-x

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. 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. 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). clinicaltrials.gov NCT03070431 . Registered 27 February 2017.