Combined preoperative hypofractionated radiotherapy with doxorubicin-ifosfamide chemotherapy in marginally resectable soft tissue sarcomas: results of a phase II clinical trial.

Abstract Introduction There is no standard treatment for marginally resectable soft tissue sarcomas (STS) of the extremities and trunk wall, and current approaches give unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5x5 Gy hypofractionated radiotherapy may generate a higher ratio of limb-sparing or conservative surgeries with negative microscopic margins (R0) and acceptable treatment toxicity. Materials and Methods We conducted a single-arm prospective clinical trial. Treatment combined one cycle of AI with subsequent 5x5 Gy radiotherapy within one week, followed by two cycles of AI and surgery. The primary endpoint was to assess the number of patients in which en bloc R0 resection was achieved. Results A total of 46 patients met the eligibility criteria. Three patients had resectable lung metastases at baseline. Most patients, 42, received the planned protocol treatment. In two patients, the treatment was prematurely stopped due to the toxicity of chemotherapy. One patient died from septic shock due to severe bone marrow suppression after the second AI cycle; a second death was not related to treatment for STS. Three patients underwent amputation. In 72% of patients in the intention-to-treat analysis, we achieved en bloc R0 resections. Grade 3+ CTCAE 4.03 chemotherapy toxicity requiring dose reduction or treatment interruption occurred in 15 patients. Wound complications occurred in 18 patients, but only six were severe. Conclusion Preoperative AI combined with 5x5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. Further evaluation of this strategy is warranted.