Long‐term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high‐risk, high‐grade, soft tissue sarcomas of the extremities and body wall

BACKGROUND: The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long‐term (≥5 years) follow‐up in patients with high‐grade, high‐risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy. METHODS: Patients with high‐grade soft tissue sarcoma ≥8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine). RESULTS: Sixty‐four of 66 patients were analyzed. After chemotherapy and RT, 61 patients had surgery; 58 had R0 resections (5 amputations), and 3 had R1 resections. Ninety‐seven percent experienced grade 3 or higher toxicity, including 3 deaths. These toxicities were short term. With a median follow‐up of 7.7 years in surviving patients, the 5‐year rates of locoregional failure (including amputation), and distant metastasis were 22.2% (95% confidence interval [CI], 11.8‐32.6) and 28.1% (95% CI, 17.0‐39.2). The most common site of metastasis was lung. Estimated 5‐year rates of disease‐free survival, distant disease‐free survival, and overall survival were 56.1% (95% CI, 43.9‐68.3), 64.1% (95% CI, 52.3‐75.8), and 71.2% (95% CI, 60.0‐82.5), respectively. CONCLUSIONS: Although the toxicity was significant, it was limited in its course and for the most part resolved by 1 year. The long‐term outcome was better than might be expected in such high‐risk tumors. Cancer 2010. © 2010 American Cancer Society.