Control freak.

Top Line: Does dose escalation improve local control in the definitive treatment of Ewing sarcoma?

The Study: Treatment of Ewing sarcoma typically consists of induction chemotherapy, local therapy, and consolidation chemotherapy. Radiation is the primary local therapy for unresectable disease. The standard dose for definitive treatment of unresectable EWS is 55.8 Gy. This single institution, randomized phase III trial from Tata Memorial Centre explored the potential benefit of dose escalation for unresectable EWS. Ninety-five patients with EWS or primitive neuroectodermal tumor (PNET) deemed unresectable after induction chemotherapy (VAC/VIE) were randomized to standard dose (55.8 Gy in 31 fractions) or dose escalated radiation (70.2 Gy in 39 fractions). Most patients had pelvic tumors (63%). The latter consisted of standard dose treatment followed by a 14.4 Gy boost to the post-chemo GTV plus a 5mm PTV margin with 95% of the prescribed dose covering 95% of the PTV. The goal was to detect a 17% improvement in local control. At 5 years, local control was significantly better with dose escalation (76.4% v 49.4%). Though the primary endpoints, the improvement in local control did not translate into significantly higher 5-year DFS (31.8% v 46.7%) or OS (58.8% v 45.4%). That’s because the primary pattern of failure was distant (47.9% in the dose escalation arm). As expected, grade 2+ skin toxicity was higher with dose escalation (10.4% v 2.1%), but late toxicity was similar. There were no second malignancies in either arm at this point in follow-up.

TBL: Dose escalation improves local control for unresectable Ewing sarcoma with a minimal increase in acute toxicity. | Laskar, Int J Radiat Oncol Biol Phys 2022