4 - Randomized Trial of Low-Dose Radiotherapy for Knee Osteoarthritis: Patient-Reported, Structural and Long-Term Clinical Endpoints

02:20pm - 02:30pm ET

Grand Ballroom

Presenter(s)

Nagendra (Bobby) Koneru, MD, FASTRO - FHN Memorial Hospital, Freeport, IL

M. Makarova¹, R. E. Shaffer², N. S. Koneru³, D. A. Barron⁴, E. M. Thomas⁵, S. A. Javadinia⁶, H. M. Seegenschmiedt⁷, and M. Y. Valkov¹; ¹Northern State Medical University, Arkhangelsk, Russian Federation, ²Xstrahl, Suwanee, GA, ³Loyola University Strich School of Medicine, Cardinal Bernardin Cancer Center, Maywood, IL, ⁴Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁵The Renaissance Institute of Precision Oncology & Radiosurgery, Winter Park, FL, ⁶Sabzevar University of Medical Sciences, Sabzevar, Iran (Islamic Republic of), ⁷MVZ RON ERGÉA STRAHLENTHERAPIE, AALEN, GERMANY, Germany

Purpose/Objective(s): Previous reports from this randomized trial described patient-reported outcomes, MRI structural findings, and long-term clinical outcomes separately. We now present the first integrated analysis of the complete randomized trial to determine whether the overall pattern of findings supports a disease-modifying effect of low-dose radiotherapy (LDRT) in early knee osteoarthritis (OA).

Materials/Methods:

Between 2012 and 2014, 292 patients with symptomatic Kellgren-Lawrence (KL) grade 0-2 knee OA were randomized 1:1 to symptomatic slow-acting drugs for OA (SYSADOA) alone (n=146) or SYSADOA plus orthovoltage LDRT (4.5 Gy in 10 fractions; n=146). Pain, WOMAC, SF-36, and MRI structural progression (Whole-Organ Magnetic Resonance Imaging Score [WORMS]) were assessed through 36 months. Government-certified disability and total knee arthroplasty (TKA) were evaluated after a median follow-up of 11.9 years using regional health registry linkage. Kaplan-Meier and Cox regression analyses were performed.

Results:

LDRT produced greater and more durable improvements in pain, physical function, and quality of life than SYSADOA alone. MRI demonstrated significantly less structural progression, including reduced overall WORMS progression at 12 months (-0.3 vs +0.9, p=0.02) and 36 months (+0.5 vs +2.3, p=0.01), with less cartilage deterioration and bone marrow edema progression. During long-term follow-up, LDRT reduced disability by 67% (adjusted HR 0.33, 95% CI 0.18-0.59; p<0.001). Overall TKA favored LDRT (HR 0.51, p=0.089). Patients with baseline KL2 disease derived the greatest benefit, with disability reduced from 61.1% to 31.0% (HR 0.37, p=0.005) and TKA from 36.1% to 14.3% (HR 0.32, p=0.021).

Conclusion: This integrated analysis demonstrates concordant benefits of LDRT across patient-reported outcomes, MRI-confirmed structural preservation, and objective long-term clinical endpoints. The consistency of symptomatic, structural, and long-term clinical benefit provides the strongest randomized evidence to date supporting a potential disease-modifying effect of LDRT in early knee OA and establishes the most comprehensive evaluation of LDRT reported to date, supporting definitive multicenter randomized trials.