2894 - First-in-Human Craniospinal Low-Dose Radiation Therapy for Progressive Multiple Sclerosis: A Case Report
Presenter(s)
E. M. Thomas1, M. Bredel2, S. Makar3, E. Chi4, J. D. Palmer5, and N. S. Koneru6; 1The Renaissance Institute of Precision Oncology & Radiosurgery, Winter Park, FL, 2Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 3Charis Neurology, Lake Mary, FL, 4Renaissance Institute of Precision Oncology & Radiosurgery, Winter Park, FL, 5Department of Radiation Oncology, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, 6Loyola University Strich School of Medicine, Cardinal Bernardin Cancer Center, Maywood, IL
Purpose/Objective(s): Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease characterized by demyelination and progressive neurological disability. Low-dose radiation therapy (LDRT) has demonstrated anti-inflammatory effects through modulation of macrophage phenotype, reduction of pro-inflammatory cytokines, and upregulation of transforming growth factor-ß, with emerging evidence in Alzheimer's disease showing reduction of neuroinflammation and cognitive improvement. We report the first application of craniospinal LDRT in a patient with progressive MS.
Materials/Methods: A male patient with ocrelizumab-refractory primary progressive MS (baseline EDSS 5.0) underwent the first-ever craniospinal LDRT treatment after providing informed consent for this experimental intervention. Pre-treatment assessment revealed severely impaired quality of life with MS Quality of Life-54 (MSQOL-54) physical health composite score of 23.03 and mental health composite score of 16.66. The patient completed craniospinal LDRT to a dose of 4.5Gy/10fx. The treatment was delivered with 4-isocenter VMAT in a vertebral body sparing protocol.
Results: Post-treatment evaluation demonstrated rapid and remarkable clinical response. The patient reported dramatic improvements in balance, gait with reduced foot-drop, ability to work on uneven surfaces with improved stability, and complete resolution of severe neuropathic pain. Fatigue was markedly reduced compared to pre-treatment baseline. MSQOL-54 physical health composite improved to 62.34 (170% increase) and mental health composite to 64.94 (290% increase). Objective neurological assessment showed EDSS improvement from 5.0 to 2.0, representing a clinically significant three-point reduction in disability. Treatment was well-tolerated with only one adverse event: a splitting headache after the fourth treatment session, successfully managed with acetaminophen. The patient intends to pursue aHSCT for definitive management given his disease’s medically refractory nature.
Conclusion: This first-in-human application of craniospinal LDRT for progressive MS demonstrates remarkable clinical efficacy with rapid improvement in disability and quality of life measures. The dramatic response, combined with established anti-inflammatory mechanisms of LDRT and emerging evidence in neurodegenerative diseases, provides compelling rationale for systematic investigation through IRB-approved clinical trials, the first of which is underway.