Femoral Fracture in Primary Soft-Tissue Sarcoma of the Thigh and Groin Treated with Intensity-Modulated Radiation Therapy: Observed versus Expected Risk

Abstract

Purpose.-To compare the observed risk of femoral fracture in primary soft-tissue sarcoma (STS) of the thigh/groin treated with IMRT to expected risk calculated using the Princess Margaret Hospital (PMH) nomogram. Methods.-Expected femoral fracture risk was calculated using the PMH nomogram. Cumulative risk of fracture was estimated using Kaplan-Meier statistics. Prognostic factors were assessed with univariate and multivariate analysis using Cox's stepwise regression. Results.-Between February 2002 and December 2010, 92 consecutive eligible patients were assessed. Median follow-up was 73 months (106 months in surviving patients). IMRT was delivered preoperatively (50 Gy) in 13 (14%) patients, and postoperatively in 79 (86%) patients (median dose of 63 Gy, range 59.4-66.6 Gy). The observed crude risk of fractures was 6.5% compared to 25.6% expected risk from the nomogram; the cumulative risk of fracture using IMRT at 5 years was 6.7% (95% CI 2.8-16.0%). The median time to fracture was 23 months (range 6.9-88.6). Significant predictors of fracture on univariate analysis were age ≥ 60 years (p = 0.03), tumor location in the anterior thigh (p = 0.008), and periosteal stripping to > 20 cm (p < 0.0001). On multivariate analysis, age ≥ 60 years and periosteal stripping > 20 cm retained significance (p = 0.04 and p = 0.009, respectively). Conclusions.-In this study, the cumulative risk of femur fracture in patients treated with IMRT (6.7%) is less than the expected risk using the PMH nomogram (25.6%). Established predictors of femur fracture such as gender, tumor size, and dose of RT seem to have less impact on fracture risk when using IMRT.

Radiation Therapy in Adult Soft Tissue Sarcoma—Current Knowledge and Future Directions: A Review and Expert Opinion

“…Folkert et al [12] observed a significant reduction of the local failure rate (8% vs. 15%) paralleled by a reduction of side effects in a large retrospective series comparing IMRT with 3D-conformal RT. In a follow-up study, they found a clear reduction in observed fractures after IMRT compared with the anticipated rate from a validated nomogram based on 3D-conformally treated patients [13]. O'Sullivan et al [14] further showed in a phase II trial, that preoperative IMRT with sparing of anticipating skin regions of wound closure during surgery might result in less perioperative wound complications.…”

Neoadjuvant Radiotherapy-Related Wound Morbidity in Soft Tissue Sarcoma: Perspectives for Radioprotective Agents

“…Though there has never been a prospective trial randomizing patients to IMRT vs. either 3D-CRT or BT, IMRT has been associated with lower rates of wound complications compared with historical 3D-CRT results (30.5 vs. 43%, respectively) [11,30], but higher rates compared with BT (19% IMRT vs. 11% BT) [24] though neither of these results were statistically significant. IMRT has some evidence of lower rates of femoral fracture [62].…”

“…An additional mid-to long-term complication that can substantially impact the quality-of-life of sarcoma survivors is a radiation-associated fracture. The most recent estimates place the risk of femur fracture at 7%, after treatment with 50-66 Gy, with a median time to fracture of 2 years [62]. Radiation treatment can alter the mechanical strength of the bone [133], making it more prone to fracture after a subclinical force or progress to a complete fracture after the development of a stress reaction.…”

Adjuvant radiotherapy treatment for soft tissue sarcoma of extremities and trunk. A retrospective mono-institutional analysis

“…Furthermore, thanks to possibility of achieving better dose conformality, IMRT is expected to lower the toxicity rate of 3D-CRT. This hypothesis is currently supported by two retrospective works, showing a reduction in the observed risk of femoral fracture [27] and woundrelated morbidities [28]. Furthermore, two recently-published series have shown that volumetric arc therapy (VMAT) is an alternative promising technique [29,30] with one work showing its ability to outperform IMRT in sparing dose to normal-tissue-corridor and, subsequently, the risk of lymphedema [30].…”