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Annals of Surgical Oncology

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Epirubicin and Ifosfamide with Preoperative Radiation for High-Risk Soft Tissue Sarcomas

Eric Lu MD, Kelly S. Perlewitz MD, James B. Hayden MD, PhD, Arthur Y. Hung MD, Yee-Cheen Doung MD, Lara E. Davis MD, Atiya Mansoor MD, John T. Vetto MD, Kevin G. Billingsley MD, Andy Kaempf MS, Byung Park PhD, Christopher W. Ryan MD
Bone and Soft Tissue Sarcomas
Volume 25, Issue 4 / April , 2018



The optimal treatment of high-risk soft tissue sarcomas (STS) of the extremities remains controversial. We report follow-up from a phase II study of dose-intense chemotherapy with preoperative hypofractionated radiation in this population supplemented with subsequent data from an extensive institutional experience using this regimen.


Patients with localized, intermediate- or high-grade STS of the extremity or body wall measuring > 5 cm were treated with epirubicin 30 mg/m2/day and ifosfamide 2.5 g/m2/day on days 1–4 every 21 days for 3 preoperative and 3 postoperative cycles. During cycle 2 of preoperative therapy, epirubicin was omitted, and a total of 28 Gy of radiation (8 fractions) was delivered. Twenty-five patients were treated on the phase II study (2002–2005). Fifty-one additional patients were identified from a retrospective chart review (2005–2014).


The 5-year rates for overall survival, distant disease-free survival, and freedom from local regional failure were 70.4% (95% CI 59.2–83.7%), 55.9% (95% CI 44.5–70.2%), and 87.2% (95% CI 77.9–96.5%) respectively. Thirty-eight percent of tumors (29/76) demonstrated ≥ 90% pathologic response. Wound complications occurred in 32% (24/76) of patients.


Treatment with preoperative radiation and pre- and post-operative epirubicin and ifosfamide was associated with favorable clinical outcomes. Survival and recurrence rates were comparable to those reported with other preoperative chemotherapy regimens in high-risk extremity sarcomas. Use of trimodality therapy should be considered for appropriate high-risk STS patients.

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