The Journal of Bone and Joint Surgery (American). 2005;87:315-319.
doi:10.2106/JBJS.C.01714
© 2005 The Journal of Bone and Joint Surgery, Inc.
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Fractures Following Radiotherapy and Limb-Salvage Surgery for Lower Extremity Soft-Tissue Sarcomas

A Comparison of High-Dose and Low-Dose Radiotherapy

Ginger E. Holt, MD1, Anthony M. Griffin, BS2, Melania Pintilie, MSc3, Jay S. Wunder, MD, FRCSC2, Charles Catton, MD, FRCRC3, Brian O'Sullivan, MD, FRCRC3 and Robert S. Bell, MD, FRCSC2

1 Department of Orthopaedic Surgery, Vanderbilt Medical Center, 1161 21st Avenue South, D4216 MCN, Nashville, TN 37232-2550. E-mail address: ginger.e.holt{at}vanderbilt.edu
2 Musculoskeletal Oncology Unit, Mount Sinai Hospital, 600 University Avenue, Suite 476E, Toronto, ON, M5G 1X5 Canada
3 Departments of Biostatistics (M.P.) and Radiation Oncology (C.C. and B.O'S.), Princess Margaret Hospital, 610 University Avenue, Toronto, ON M5G 2M9, Canada

Investigation performed at the Departments of Radiation Oncology and Biostatistics, Princess Margaret Hospital; the Musculoskeletal Oncology Unit, Mount Sinai Hospital; and the Departments of Radiation Oncology and Surgery, University of Toronto, Toronto, Ontario, Canada

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from the Canadian Institutes of Health Research. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.


Background: The purpose of the present retrospective study was to determine the correlation between radiation therapy and the risk of postradiation fracture following combined therapy for the treatment of soft-tissue sarcomas of the lower extremity.

Methods: Three hundred and sixty-four patients with lower extremity sarcomas that had been treated with combined external beam radiation therapy and limb-salvage surgery were evaluated on the basis of a combined chart and data-base review. For the purposes of analysis, high-dose radiation was defined as 60 or 66 Gy and low-dose radiation was defined as 50 Gy. The timing of irradiation was defined as preoperative, postoperative, or preoperative followed by a postoperative boost. Univariate and multivariate analyses were used to determine which factors were associated with fracture risk.

Results: Twenty-seven fractures occurred in twenty-three patients. Twenty-four fractures occurred in twenty patients who had been managed with high-dose radiation. Seventeen of these patients had received postoperative radiation (with fifteen patients receiving 66 Gy and two receiving 60 Gy), and three had received preoperative radiation with a postoperative boost (total dose, 66 Gy). Three fractures occurred in three patients who had received preoperative, low-dose radiation (50 Gy). Of the twenty-three patients who sustained a pathologic fracture, eighteen were female and five were male. The crude median time to fracture was forty-three months. Most fractures occurred in the femoral shaft (thirteen) or the femoral neck (eight). High-dose radiation was associated with a greater risk of fracture when compared with low-dose radiation (p = 0.007).

Conclusions: Women more than fifty-five years of age who are managed with removal of a thigh sarcoma combined with radiation therapy have a higher risk of pathologic fracture. The frequency of pathologic fractures associated with higher doses (60 or 66 Gy) of radiation is significantly higher than that associated with lower doses (50 Gy).

Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.


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