The Impact of Radiation Therapy on Metastatic Rhabdomyosarcoma: Results From the EpSSG MTS 2008 Study

Purpose: Radiation oncologists use radiation variably for children with metastatic rhabdomyosarcoma (RMS). Data from the European paediatric Soft tissue sarcoma Study Group (EpSSG) MTS 2008 study were retrospectively analyzed to validate the previous observation that the use of radiation is associated with improved outcomes and guide future recommendations on radiation use in this patient group. Methods and Materials: The radiation delivered to 216 patients aged 0 to 21 years with metastatic RMS was retrospectively reviewed and classified as radical (all sites of disease irradiated within the protocol parameters), partial (some sites irradiated within the protocol parameters), and none (no radiation or delivered outside the protocol parameters). Landmark analysis excluded those with an event before day 221. Overall survival (OS) and progression-free survival were modeled using the Kaplan-Meier method to investigate the impact of radiation. The joint effect of treatment and known prognostic factors was examined using the Cox regression model. Results: Overall, 56 patients received radical, 104 partial, and 56 no radiation therapy per protocol. Owing to nonrandomized data, the groups were heterogeneous, particularly fewer sites of metatatic disease and less with bone metatases in those receiving radical radiation. The 3-year progression-free survival was 62.0% (95% CI, 47.9-73.4), 39.5% (95% CI, 29.8-49.1), 30.1% (95% CI, 18.7-42.3) for radical, partial, and no radiation therapy groups (P =.002), respectively, and the 3-year OS was 70.1% (95% CI, 55.8-80.6), 53.1% (95% CI, 42.6-62.5), and 52.3% (95% CI, 38.3-64.5; P =.019), respectively. Multivariable analysis confirmed incremental improvement in OS with additional radiation, with hazard ratio of 1, 1.8, and 2.4 (P =.022) for radical, partial, and no radiation therapy per protocol, respectively. Conclusions: Radiation to all sites of disease seems to improve outcomes for children with metastatic RMS and should be considered when feasible. If not feasible, radiation is still recommended to the primary site and involved regional lymphadenopathy. Randomized clinical trials are required to confirm these findings, given the heterogeneity between the groups and potential confounding factors in this analysis.