Radiation Therapy Dose Escalation Failed to Improve Local Control for Intermediate-Risk Rhabdomyosarcoma on ARST1431: A Report From the Children's Oncology Group.

Purpose: To evaluate local failure (LF) rates for patients with intermediate-risk rhabdomyosarcoma treated on the Children's Oncology Group ARST1431 clinical trial, the first and largest international, phase 3 randomized study to use FOXO1 fusion status for risk stratification. To improve local control, radiation therapy (RT) dose was increased to 59.4 Gy for patients with tumors >5 cm and residual gross disease at the time of RT.

Methods and materials: For the 297 patients included, LF was defined as progression or relapse at the primary site. The rate of LF was calculated 3-years after enrollment.

Results: LF for group 3, FOXO1 fusion-positive patients (n = 58) compared with fusion-negative patients (n = 175) was 10.7% versus 21.5%, respectively (P = .08). The LF rate for patients with tumors >5 cm at diagnosis (n = 180; 24.4%) was higher than that of patients with tumors ≤5 cm at diagnosis (n = 117; 9.8%), P = .002. The risk of LF for patients who received proton (n = 99) versus photon RT (n = 126) was not different (16.1% vs 15.9%, P = .8). For the 75 patients with tumors >5 cm at diagnosis and gross disease at the time of RT, the boost to 59.4 Gy did not improve the 3-year LF rate compared with that of patients who did not receive the boost (29.7% vs 16.1%, P = .6). For patients with group 3/4 disease, those who underwent delayed primary excision (n = 72) had a lower LF rate compared with those who had RT alone (n = 151) (5.8% vs 19.7%, P < .01).

Conclusions: On ARST1431, tumors >5 cm at diagnosis had poor local control despite dose escalation to 59.4 Gy. Proton and photon RT had equivalent local control. For select patients, delayed primary excision significantly improved local control.