Neoadjuvant irradiation of extremity soft tissue sarcoma with ions (Extrem‑ion): Interim report of a randomized phase...

This single-center, prospective, randomized phase II trial evaluated the safety and feasibility of neoadjuvant hypofractionated particle therapy for patients with resectable extremity soft tissue sarcoma.

A total of 45 patients were randomized of which three were excluded from the mITT set. The remaining patients (21 per group) received 39 GyRBE in 13 fractions with either protons or carbon ions. The primary endpoint was the incidence of wound healing disorders (CTCAE grade ≥ 3) within 120 days or treatment related discontinuations. Secondary endpoints included local progression-free survival (LPFS), distant progression-free survival (DPFS), and overall survival (OS). An interim analysis was conducted as part of an adaptive two-stage design. All patients were followed for a minimum of 14 months.

Surgical wound complications requiring intervention occurred in 9 (21%) of patients (4 (19%) in the proton and 5 (24%) in the carbon ion group). The two-year LPFS was 88% (94% in the proton and 79% in the carbon ion arm). All recurrences were retrospectively contoured and all patients reviewed using different models for calculation of the RBE-weighted dose. Potential partial underdosing was identified in two of the recurrence cases, while no correlation was seen in the others. Two-year DPFS was 90% (protons) and 79% (carbon ions). Two patients died of metastatic disease. OS at two years was 97%.

These results confirm the feasibility of neoadjuvant particle therapy, with the ongoing second phase set to further evaluate the trial regimen.