No abstract

BACKGROUND. The authors studied a dose‐intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high‐risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis. METHODS. Twenty‐five patients with intermediate‐grade or high‐grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). RESULTS. Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty‐one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide‐induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of ≥95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21–59%). Estimates of 2‐year overall and disease‐free survival were 84% (95% CI, 66–100%) and 62% (95% CI, 37–86%), respectively. CONCLUSIONS. A high rate of ≥95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity. Cancer 2008. ©2008 American Cancer Society.

Clear cell sarcoma (CCS) is a rare but highly malignant tumor of soft tissues often appearing as a small tender mass in the deep tissues of the distal extremities. We have studied 17 patients with such lesions treated since 1986 and have a high incidence of local recurrence and metastasis with a survival rate of only 47% despite surgery and for many of the patients, adjuvant therapy. The purpose of this article is to warn the readers of the dangers related to treating this seemingly benign lesion and urge them to perform wide surgery and utilize adjuvant therapy.

Purpose We performed a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma (STS) undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess response to treatment. Experimental Design Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg BID) initiated 14 days prior to 3 preoperative and 3 postoperative cycles of epirubicin/ifosfamide. 28 Gy of radiation was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was performed at baseline, after 2 weeks of sorafenib, and prior to surgery. The imaging data were subjected to quantitative pharmacokinetic analyses. Results 18 subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3–4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔKtrans after 2 weeks sorafenib correlated with histologic response (R2=0.67, p = 0.012) at surgery. Conclusion The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally-invasive tool for rapid assessment of drug effect in STS.