Reduction of Bone Fracture After Radiation Therapy in Lower Extremity Soft Tissue Sarcoma After Implementing Bone Avoidance Objectives for Radiation Therapy Planning.

PURPOSE: We evaluate the effectiveness of radiation therapy (RT) dose constraints on bone in reducing the incidence of radiation-associated fractures in patients with LE-STS treated with image guided RT and modern treatment planning techniques. We had established these constraints as bone avoidance objectives for RT planning in 2005 after observing a 4.5% rate of bone fracture in patients. The ultimate goal is to improve functional outcome following external beam radiation therapy (RT) combined with limb salvage surgery for lower extremity soft tissue sarcomas (LE-STS) which can be associated with significant long-term complications, such as bone fractures, which can lead to multiple surgeries or amputation.

METHODS AND MATERIALS: We retrospectively analyzed a prospectively maintained database of all patients with LE-STS who received curative-intent RT that was planned using evidence-based bone avoidance objectives between January 2005 and December 2020 at our institution. Using a standard bone volume contoured 2 cm above and below the planning target volume, the following RT planning objectives were extracted for patients with and without a fracture: mean dose to bone, RT treatment volume, maximum dose to 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 RT 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 χ2 test was used to analyze categorical variables, a Student ttest 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-associated fracture. Two of these patients developed a fracture after reirradiation of the extremity and 2 of the remaining 8 patients did not meet the radiation dose bone constraints. Of the full cohort, 14 patients (2%) had an intramedullary nail and there was only one fracture in this subgroup. Twenty 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.

CONCLUSIONS

The overall fracture risk after RT is reduced with modern planning techniques using the radiation dose constraints to a bone volume contoured 2 cm above and below the planning target volume. RT 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 may help prevent radiation-associated fractures.