128 - SJPROTON1 Phase IV Trial: Prospective Insights into Musculoskeletal Toxicities after Pencil Beam Scanning (PBS) Proton Therapy (PT)

02:25pm - 02:35pm ET

Room 259

Presenter(s)

Alexis Narvaez Rojas, MD - Maimonides Medical Center, New York, NY

A. R. Narvaez Rojas¹, J. T. Lucas Jr², S. Kaste³, H. Worrall³, J. Becksfort³, T. T. Patni³, V. T. Groben³, E. Burghen³, H. T. Ruleman³, M. Marker³, C. H. Hua³, N. D. Sabin³, O. Ates³, A. J. Boria³, C. C. Chen³, G. T. Armstrong^3,4, M. M. Hudson³, Y. Li³, C. L. Tinkle², M. Krasin³, K. E. Nichols³, and T. E. Merchant³; ¹Maimonides Medical Center, Brooklyn, NY, ²Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, ³St. Jude Children's Research Hospital, Memphis, TN, ⁴Department of Epidemiology and Cancer Control, St. Jude Children's Hospital, Memphis, TN

Purpose/Objective(s): We assessed musculoskeletal (MSK) adverse events in a Phase IV trial, a known risk of pediatric proton therapy. This report details the incidence, patterns, and radiotherapy (RT) attribution of MSK toxicities—specifically fractures, osteoradionecrosis, scoliosis, growth abnormalities, and deformities—following pencil beam scanning proton therapy (PBS-PT) across all disease groups.

Materials/Methods: This Phase IV trial prospectively collected musculoskeletal (MSK) toxicity data, initially graded by CTCAE v4.03 post-therapy and long-term via SJLIFE-modified CTCAE. Events were characterized by grade, site, relation to operative corridors/RT field, symptoms, and need for intervention. The cumulative incidence was determined using the fine-gray model. Attribution was systematically scored (Excluded to Certain). Descriptive statistics summarized incidence and types.

Results:

Of 995 participants, 4.4% (44) had primary musculoskeletal (MSK) irradiated sites, yet MSK toxicities occurred in all disease groups. Over 120 discrete MSK events were identified. The cumulative incidence of MSK events at 5 years was 1.1% (95% CI 0.3-3.0) and 0.9% (95% CI 0.4-2.0) in the solid tumor/lymphoma and CNS/leukemia patient population. Fractures were the most common event (14, 25%), consisting of vertebral compression fractures (10, 17.9%), stress fractures (1, 1.8%), and nondisplaced extremity fractures (1, 1.8%). Most were Grade 1–2 (12,21.4%), though several Grade 3 fractures required surgical stabilization (2,3.6%). Osteoradionecrosis, typically within the RT field, affected multiple sites (mandible, femoral head, distal radius/carpals, tibia), often in patients with prior surgery (10, 17.9%). Spinal deformities (scoliosis, kyphosis) occurred in 5 (8.9%) CNS and 5 (8.9%) solid tumor survivors after spinal irradiation. Contributing factors included laminectomy (2, 20%) and residual disease instability (1, 10%). Younger children who received extremity irradiation experienced growth suppression and limb-length discrepancy (3-5.4%), sometimes needing orthopedic intervention, such as epiphysiodesis (1-1.8%). Most events (58.8%) occurring clearly within the RT field without competing pathology were rated Likely or Certain. However, fractures in metastatic or postsurgical contexts were often rated Plausible or Disease-related (41.2%). MSK events were predominantly low-grade (91%), but 8.9% required procedural or surgical management.

Conclusion: PBS-PT-associated musculoskeletal (MSK) toxicities, while uncommon, were clinically significant, including vertebral compression fractures, osteoradionecrosis, and deformities. Most events were within the irradiated field and likely related to radiation therapy (RT). Continued surveillance, especially for young children and those receiving high-dose spinal or extremity RT, is necessary. Implementing MSK-specific follow-up and dose-response modeling may decrease long-term morbidity.