Treatment-related fractures after combined modality therapy for soft tissue sarcomas of the proximal lower extremity: Can the risk be mitigated?

Abstract

The purpose of this study was to investigate the incidence of and risk factors associated with femur fracture after combined modality therapy for soft tissue sarcomas (STS) of the proximal lower extremity. We reviewed the records of 596 patients with STS of the proximal lower extremity consecutively treated with surgery and radiation therapy (RT) from 1966 to 2012. One hundred ninety-seven patients (33%) received 50 Gy to the entire femur circumference (n = 197, 33%); 265 patients (45%) received perioperative chemotherapy, and during surgery, 155 patients (26%) had bone exposure, whereas 82 patients (14%) had the periosteum stripped. The Kaplan-Meier method was used to estimate actuarial outcome rates, and both Cox regression modeling and competing risk analyses using the method of Fine and Gray were performed. Median follow-up time was 110 months (range, 6-470 months). The actuarial 10-year local control and overall survival rates were 88% (95% confidence interval [CI], 84%-90%) and 62% (95% CI, 57%-66%). Twelve patients had pathologic fractures, which were associated with 50 Gy to the entire bone circumference (P < .001), bone exposure (P < .001), and periosteal stripping during surgery (P < .001) and use of perioperative chemotherapy (P = .04). Using a competing risk model, bone exposure (P = .001; sub-hazard ratio [SHR], 9.13; 95% CI, 2.5-33.0), periosteal stripping (P < .001; SHR, 13.03; 95% CI, 4.0-43.0), and perioperative chemotherapy (P = .03; SHR, 4.03; 95% CI, 1.1-14.4) were significantly associated with fracture. The actuarial 10-year fracture rate was 2% (95% CI, 1%-3%) when the 50-Gy isodose line encompassed the entire bone circumference without the other risk factors, whereas it increased to 37% (95% CI, 12%-45%) when all 4 treatment-related factors were present. Although femur fractures are rare, a component from each of the 3 therapeutic modalities contributes to the overall risk, and a multidisciplinary approach to mitigating fracture risk is needed. Although avoiding circumferential bone coverage with the 50-Gy isodose line may be a valuable dosimetric parameter, more rigorous dosimetric studies are required.