Neoadjuvant chemotherapy and radiotherapy for large soft tissue sarcomas

Purpose: The treatment of soft tissue sarcomas of the extremity with radiation therapy and limb sparing surgery results in local control rates of greater than 90%. Because of these excellent results, interest is now focused on reducing the incidence of distant failure. We have begun a phase II trial evaluating The efficacy of preoperative chemotherapy with Mesna, Adriamycin, Ifosfamide and Dacarbazine (MAID) and radiation, followed by resection and postoperative radiotherapy and chemotherapy. Materials and Methods: Adult patients with AJCC stage IIB or IIIB extremity soft tissue sarcomas, ≥ 8 cm were treated with three cycles of MAID chemotherapy combined with 44 Gy. After a three week rest surgical resection was performed. If surgical margins were positive, an additional 16 Gy boost was delivered. All patients received an additional three cycles of MAID. Results: A total of 26 patients who were clinically M0 at entry have completed protocol therapy. The median follow-up time for this group of patients is 13 months (range 3-76 months). Pathologic response rates have varied from 10 to 100% with mean and median values of 84% and 96%. In general, radiographic volume change did not correlate with pathologic response rates and therefore was not a good predictor of treatment response. For example, patients with ≥ 95% necrosis had only a 16% decrease in tumor volume compared to 34% for patients 50-<95% necrosis. The local control, disease-free survival and overall survival of these patients has been compared to a control group of 32 matched historically for tumor size, grade, age and era of treatment. The actuarial five-year local control, disease-free survival rate and overall survival rates for MAID patients is 100, 84 and 93%, respectively. For the control group these rates are 97, 45 and 60%, respectively. Conclusion: Following a course of aggressive of chemotherapy and radiation therapy 85% of patients with high risk soft tissue sarcoma are free of disease at five years compared to 45% of patients treated without chemotherapy. Despite a short follow-up time, these results are encouraging. Currently the Radiation Therapy Oncology Group is planning a multi institutional phase II trial based on the results of this pilot study