250 - Reduction of Bone Fracture after Radiotherapy in Lower Extremity Soft Tissue Sarcoma after Implementing Bone Avoidance Objectives for Radiotherapy Planning

H. M. Othman^1,2, A. Griffin^2,3, A. Parent^1,4, B. OSullivan^1,2, C. Catton^1,2, P. Chung^1,2, P. Wong^1,2, D. B. Shultz^1,2, C. I. Dickie^1,4, N. Wattakiyanon^1,2, K. Tsoi^2,3, P. Ferguson^2,3, J. Wunder^2,3, and D. G. Kirsch^1,2; ¹Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, ²University of Toronto, Toronto, ON, Canada, ³Division of Orthopaedic Surgery, University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, ON, Canada, ⁴Departments of Medical Biophysics and Radiation Oncology, University Health Network, Toronto, ON, Canada

Purpose/Objective(s): External beam radiation therapy combined with limb salvage surgery for lower extremity soft tissue sarcomas (LE-STS) can be associated with significant long-term complications, such as bone fractures, which can lead to multiple surgeries or amputation. After observing a 4.5% rate of bone fracture in patients with LE-STS treated with radiotherapy and surgery, we established bone avoidance objectives for radiotherapy planning with the goal of reducing the incidence of fracture. Here, we evaluate the effectiveness of the radiation dose constraints on bone on the incidence of radiation-induced fractures in LE-STS patients treated with image-guided radiotherapy and modern treatment planning techniques. Materials/

Methods: We retrospectively analyzed a prospective data base of all patients with LE-STS who received curative-intent radiotherapy that was planned using evidence-based bone avoidance objectives between January 2005 and December 2020 at our institution. The following radiotherapy (RT) planning objectives were extracted for patients with and without a fracture: Mean dose to bone, RT treatment volume, maximum dose to a 2cc volume of bone, and volume of bone irradiated to =40 Gy (V40). Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the radiotherapy plan with isodose distribution. Patient and tumor factors, treatment details, and patient survival were extracted from medical records and compared between the fracture and non-fracture patient cohorts. The Chi-square test was used to analyze categorical variables, a student T-test was used to analyze continuous variables and T-test was used to compare means. Survival was estimated using the method of Kaplan-Meier.
Results: Between January 2005 and December 2020, 700 eligible patients were assessed, 594 patients (84.9%) received preoperative RT, 103 (14.7%) received postop RT, and 3 (0.4%) both. At a median follow-up of 55 months, 10 patients (1.4%) developed radiation-induced fracture. Two of these patients developed a fracture after re-irradiation of the extremity and 2 of the remaining 8 patients did not meet the bone constraints. Of the full cohort, 15 patients (2.1%) had an intramedullary nail and there was only one fracture in this subgroup. 20 patients (2.8%) in the entire cohort required bone resection necessitating replacement with a prosthesis or an allograft. The mean time to fracture was 41.7 months. Fracture management varied from conservative treatment to amputation. Local recurrence occurred in 44 patients (6.3%) and 248 patients (35.4%) developed metastasis
Conclusion: The overall fracture risk after RT is reduced with modern planning techniques using our radiation dose constraints. Radiotherapy treatment planning for LE-STS should include a focus on limiting radiation dose to the bone to minimize the risk of fracture. For high risk patients prophylactic intramedullary nailing of the femur can help prevent radiation-associated fractures.