LRA0401/ LRB0402 protocols for newly diagnosed patients with low-risk embryonal rhabdomyosarcoma based on the central pathological review system: The first report from the Japan Rhabdomyosarcoma Study Group

Abstract

Abstract Background A retrospective study of pediatric rhabdomyosarcoma patients treated between 1991 and 2002 in Japan revealed that among the two major subtypes, embryonal rhabdomyosarcoma (ERMS), was more prevalent than alveolar rhabdomyosarcoma (ARMS), differing from a United States (US)-based report. Moreover, the survival rate of low-risk ERMS was worse in Japan than in the US. We hypothesized that some patients with ARMS having a poorer prognosis were misdiagnosed and undertreated in Japan. We explored this hypothesis using a nationwide group study, by risk-adopted therapy based upon a central pathological review system to improve the prognosis of patients with “low-risk” rhabdomyosarcoma in Japan. Methods Using the first nationwide Japan Rhabdomyosarcoma Study Group established in 2004, we classified patients into low-risk subgroup A, including ERMS with orbital, grossly resectable, favorable site, and small unfavorable site tumors, who were eligible for JRS-I LRA0401; and low-risk subgroup B, including ERMS with residual, favorable site and grossly resectable, large, unfavorable site tumors, eligible for JRS-I LRB0402. Results ERMS cases decreased from 78–51% before and after the central pathological review. Fusion genes were not detected in ERMS. The overall survival rate was significantly better (p = 0.0015) in ERMS (84.8 ± 4.0%) than in ARMS (57.7 ± 6.1%). The 3-year overall survival rates of low-risk patients in subgroups A and B improved from 86–100% and from 81–94%, respectively. Conclusion By implementing a central pathological review system in Japan and adopting fusion gene analyses for diagnosis, the number of patients with ERMS decreased and their outcomes improved significantly.