2635 - Radiation Dose Fractionations for Malignant Spinal Cord Compression in Patients Not Eligible for Surgery: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

H. C. Y. Wong¹, M. D. C. Santos², S. Leung¹, K. N. E. Wong¹, S. Chan¹, S. Caini³, P. Hoskin^4,5, E. Maranzano⁶, D. Dearnaley⁷, S. F. Lee⁸, A. W. Chan⁹, G. N. Marta², I. J. Choi¹⁰, C. B. Simone II¹⁰, S. Raman¹¹, E. Oldenburger¹², A. Rembielak^5,13, L. Khan¹⁴, E. Chow⁹, and D. Rades¹⁵; ¹Department of Oncology, Princess Margaret Hospital, Kwai Chung, Hong Kong, ²Department of Radiation Oncology, Hospital Sírio-Libanês, Sao Paulo, Brazil, ³Institute for Cancer Research, Prevention, and Clinical Network (ISPRO), Florence, Italy, ⁴Mount Vernon Cancer Centre, Middlesex, United Kingdom, ⁵Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom, ⁶University of Perugia, Perugia, Italy, ⁷The Institute of Cancer Research and Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, ⁸Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore, ⁹Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, ¹⁰New York Proton Center, New York, NY, ¹¹Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada, ¹²Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium, ¹³The Christie NHS Foundation Trust, Manchester, United Kingdom, ¹⁴Department of Radiation Oncology, Trillium Health Partners, The Credit Valley Hospital, Mississauga, ON, Canada, ¹⁵Department of Radiation Oncology, University of Lübeck, Lübeck, Germany

Purpose/Objective(s): Randomised controlled trials (RCTs) have compared different radiotherapy (RT) fractionation regimens for the treatment of malignant spinal cord compression (MSCC). This systematic review and network meta-analysis aim to evaluate the comparative efficacy and safety of single fraction RT (SF-RT), short-course RT (SC-RT, = 1 week) and long-course RT (LC-RT, = 2 weeks). Materials/Methods: We systematically searched Medline, EMBASE, and Cochrane CENTRAL from January 2003 to February 2024 for RCTs comparing two or more RT fractionation schedules in MSCC patients ineligible for surgery. The primary endpoint was ambulatory response at 1 month, defined as becoming ambulatory from being non-ambulatory or maintenance of ambulation post-treatment. Secondary endpoints included urinary function improvement, pain relief, in-field failure and/or re-treatment for MSCC, 6-month overall survival (OS) and = grade 3 toxicities. We assessed study quality using the Cochrane Risk of Bias tool (v.2.0) and graded evidence certainty via the Confidence in Network Meta-Analysis (CINeMA) framework. Summary odds ratios were estimated using network meta-analysis with random effects.

Results: Six RCTs involving 1,913 patients met the inclusion criteria. The median survival of patients ranged from 3.0 to 4.0 months. The RT regimens evaluated were SF-RT (8Gy/ Fx, 10Gy/ Fx), SC-RT (16 Gy/ 2 Fx, 20 Gy/ 5 Fx) and LC-RT (30 Gy/10 Fx, 15Gy /3 Fx then 15Gy/ Fx, 40 Gy/20 Fx). SC-RT and LC-RT were not significantly different in ambulatory response compared to SF-RT (SC-RT: OR = 0.92; p=0.55; LC-RT [2 weeks]: OR = 0.84; p=0.43; LC-RT [4 weeks]: OR = 0.92.; p=0.82). SC-RT was similar in ambulatory response compared to the LC-RT schedules. No significant heterogeneity was observed (I 2 = 0%, [0.0%; 79.2%]; Q test = 2.17, p=0.70). The ranking of RT schedules from most to least effective in ambulatory response according to P-scores was: SF-RT (0.699), LC-RT (4 weeks) (0.498), SC-RT (0.487) and LC-RT (2 weeks) (0.316). No significant differences were observed across the RT schedules in the secondary efficacy outcomes. However, there was substantial heterogeneity for in-field failure and/or re-treatment for MSCC (I 2 = 53%, [0.0%; 86.5%]; Q test = 4.26, p=0.11) and 6-month OS (I 2 = 54%, [0.0%; 86.9%]; Q test = 4.37, p=0.11). Incidences of grade 3 or above diarrhea, esophagitis, nausea, and vomiting were rare and comparable across all RT schedules.

Conclusion: SF-RT, SC-RT and LC-RT were similar in terms of efficacy and safety. SF-RT should be recommended in MSCC patients with a limited life expectancy for better patient convenience and lower healthcare costs. An individual patient-level meta-analysis including tumour type and validated survival scores may identify patients who benefit from dose escalation for better local control.