Rhabdomyosarcoma: New Windows of Opportunity

Learning Objectives After completing this course, the reader will be able to: Interpret the histologic findings of rhabdomyosarcoma and differentiate rhabdomyosarcoma from other small round cell neoplasms. Define the extent of disease using the Intergroup Rhabdomyosarcoma Study stage and group systems and apply these systems to predict prognosis. Discuss the multidisciplinary nature of therapy for rhabdomyosarcoma. Evaluate the most appropriate risk‐based therapy alternatives for rhabdomyosarcoma. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com Rhabdomyosarcoma is a highly malignant, small blue cell tumor characterized by muscle differentiation. With modern treatment, more than 70% of children and adolescents with this disease are cured. Adequate biopsy to obtain sufficient tissue for accurate diagnosis and molecular characterization is critical. Patients must be assessed for tumor extent; the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and Staging system is universally applied in North America. Multidisciplinary therapy is necessary to maximize cure rates. Local control relies on complete surgical excision when possible; those whose tumors are not completely excised and those with alveolar histology tumors require local irradiation to maximize local control. In North America, vincristine (Oncovin®; Eli Lilly and Company, Indianapolis, http://www.lilly.com), dactinomycin (Cosmegen®; Merck & Co., Inc., Whitehouse Station, NJ, http://www.merck.com), and cyclophosphamide are the standard chemotherapy agents. The IRS has used therapeutic window studies to confirm the predictive nature of preclinical xenograft models and to identify several new single agents and combinations of agents with activity in high‐risk patient groups. Despite these efforts, the outcome for these high‐risk patients remains poor. The next generation of Children's Oncology Group studies will evaluate the efficacy of topoisomerase‐I inhibitors and dose‐compression therapy approaches. New advances in molecular characterization of tumors, including gene‐expression analysis, may identify new therapeutic targets that can be exploited by expanded preclinical drug discovery efforts, and hold the promise of revolutionizing risk‐based therapies.