The cumulative risk of fracture at 5 years was 6.7% (95% CI 2.8–16.0%) ( Fig. The sixth patient started developing symptoms and signs of avascular necrosis of the femoral head 4 years after IMRT, ultimately leading to planned hip replacement 3 years later (7 years after IMRT). In 5 patients (83.3%), the fracture was an acute event requiring open reduction and internal fixation. Of the 6 patients experiencing Grade 3 fractures, 5 patients (83.3%) were treated to a dose of >60 Gy and had a tumor >10 cm, 4 patients (66.7%) were female, 2 patients (33.3%) underwent significant bone manipulation (both with >20 cm of periosteal stripping), and 2 patients (33.3%) received adjuvant chemotherapy as part of initial definitive treatment. All 6 patients with Grade 3 fractures were > 50 years of age when treated for primary STS (median age of 61 years) and all had tumors located in the anterior compartment of the thigh. The median time to fracture was 23 months (range 6.9–88.6 months). There were 6 (6.5%) Grade 3 femoral fractures. Neoadjuvant or adjuvant chemotherapy was administered in 33 (36%) patients. Preoperative IMRT to 50 Gy was delivered in 13 (14%) patients, and postoperative IMRT was delivered in 79 (86%) patients to a median dose of 63 Gy (range 59.4–66.6 Gy). Periosteal stripping was performed in 20 (22%) patients the extent of periosteal stripping was 20 cm in 7 patients (one patient had a partial cortical resection). The median tumor maximum dimension was 11.1 cm (range 2.5–31 cm), and 56 tumors (61%) were >10 cm in size. Thigh compartment was anterior in 43 (47%) patients, posterior in 28 (30%), medial in 17 (18%), and groin in 4 (4%). The average age was 58 years (range, 19–88). Of the patients treated, 36 (39%) were female. Patient characteristics are provided in Table 1. Median follow-up was 73 months (106 months in surviving patients). The IMRT cohort was limited to patients whose median follow-up (surviving patients) exceeded 8 years.īetween February 2002 and December 2010, 92 consecutive eligible patients were treated with limb-sparing surgery and IMRT. Using this nomogram rather than simply comparing fracture rates with other reports in the literature accounts for the influence of various factors and thus allows for more accurate estimation of the true impact of IMRT on fracture rate. 11 Here, we sought to examine the impact of IMRT on fracture risk by comparing the observed risk of femoral fracture in primary STS treated with limb-sparing surgery and IMRT to the expected risk using the PMH nomogram. Investigators from Princess Margaret Hospital (PMH) incorporated the above risk factors for femur fracture into a predictive nomogram. 2, 3 Second, these radiation-related fractures tend to manifest long after treatment, with a median time to fracture of close to 40 months. First, several factors, apart from radiation techniques, influence the risk of fracture, such as patient age, gender, tumor size, location, and the extent of periosteal stripping. 8 Determining the true impact of IMRT on the rate of fracture, however, is challenging. 7 In a previous report from Memorial Sloan Kettering Cancer Center (MSKCC), the rate of bone fracture using adjuvant IMRT for primary STS of the extremity was 4.8%. One potential means of reducing fracture risk in STS is intensity-modulated radiation therapy (IMRT), which can spare at least a portion of the circumference of a long bone from receiving the full dose of radiation. 3, 5 The dose of radiation also influence the rate of femoral fracture, with 9% rate being reported for lower extremity STS treated to > 60Gy compared to 1% for those treated to 50 Gy. 4 Even within the thigh, there is a higher rate of fracture in anterior compartment tumors compared to medial or posterior compartments. 1– 3 Most of these fractures occur in patients with lower extremity lesions, particularly the thigh. The overall rate of radiation-associated bone fracture in soft tissue sarcoma (STS) of the extremity is about 4–6%.
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