Radiation dose escalation and local control for intermediate-risk rhabdomyosarcoma on ARST1431: A report from the Children’s Oncology Group

Abstract

10007 Background: The objective of this study was to evaluate local failure (LF) rates for patients with intermediate-risk rhabdomyosarcoma (IR-RMS) treated on the Children’s Oncology Group (COG) ARST1431 clinical trial. To improve local control, the radiation therapy (RT) dose was increased to 59.4 Gy for patients with tumors > 5cm at diagnosis and residual gross disease at the time of RT. Methods: The297 patients randomized on ARST1431 were included. LF was defined as progression or relapse at the primary tumor site. Gray’s test was used to compare the cumulative incidence of LF across variables. Results: There was a trend for lower 3-year LF in group III patients with fusion-positive disease (11.1%, 95% confidence interval (CI) 4.5%-21.1%) compared to patients with fusion-negative disease (21.8%, 95% CI 15.8%-28.4%), p = 0.09.There was no difference in the 3-year LF rate for patients who underwent proton RT (16.3%, 95% CI 9.6%-24.7%) compared to photon RT (16.2%, 95% CI 10.2%-23.6%;), p = 0.8. The 3-year LF rate for all patients with tumors > 5cm at diagnosis (24.9%, 95% CI 18.6%-31.7%) was significantly higher than that of patients with tumors ≤5cm at diagnosis (9.9%, 95% CI 5.2%-16.4%), p < 0.01. Of 81 patients with tumors > 5cm and residual gross disease after induction chemotherapy who went on to receive RT, 62 (76.5%) received the protocol-specified boost to 59.4 Gy. Patients who received the boost had a 3-year LF rate of 32.1% (95% CI 20.1%-44%), while patients who did not undergo an RT boost had a 3-year LF rate of 16.1% (95% CI 3.8%-36.2%), p = 0.3. For patients with group III, non-parameningeal disease, those who underwent delayed primary excision (DPE) had a significantly lower LF rate compared to those who did not undergo DPE (3-year rate of 5.6% (95% CI 1.4%-14.0%) vs. 22.0% (95% CI 14.5-30.7%), p < 0.01). Conclusions: On ARST1431, larger tumors ( > 5cm at diagnosis) were associated with increased risk of LF. Dose escalation to 59.4 Gy did not improve local control for patients with tumors > 5cm at diagnosis with residual gross disease at the time of RT. For a select group of non-parameningeal, group III patients who underwent DPE followed by RT, local control was improved. Clinical trial information: NCT02567435 .