Koren Smith

Radiation therapy remains a cornerstone in the clinical care of patients with medulloblastoma. Nevertheless, while treatment with radiation improves disease control, it is also associated with potential late effects impacting neurologic and neurocognitive function, pituitary function as well as hearing. The development of secondary, treatment-related malignancies is an uncommon but possible late outcome. In this chapter, we review the role of radiation therapy in medulloblastoma, as well as changes in management that have resulted both from technological therapeutic advancements and enterprising cooperative group clinical trials for this disease. Moreover, with increasing utilization of molecular diagnostics both for prognosis and stratification of treatment, we also endeavor to explore opportunities to further improve the delivery of radiation therapy to patients with varied risk of disease recurrence.

Medulloblastoma is the most common malignant brain tumor in children. Prognosis remains guarded in patients who at diagnosis are very young, have craniospinal metastatic disease, or after resection, have residual disease. Treatment incorporates chemotherapy and radiation therapy. Cancer survivors often have life-altering treatment effects. This chapter reviews clinical trials over the years and the efforts to improve survival and minimize sequelae along with challenges in performing clinical trials. Quality assurance of the radiation therapy provided worldwide monitors compliance. Advances in the risk stratification and targeted treatment based on the genomics and biology of medulloblastoma are highlighted in recent clinical trials. Through chemotherapy aligned with specific biomarkers, sophisticated radiation therapy strategies, and continued quality assurance, the future vision of managing medulloblastoma is presented.

Clinical trials in radiation oncology are the best vehicle to optimize our strengths in therapeutic technology, define progress in our field, and improve patient outcome. Trials advance our knowledge in each disease site and provide us information to improve the radiation dose-volume for both tumor control and therapeutic sequelae to normal tissue. An increasing number of systemic and targeted therapies have been developed and are currently in early phase clinical trial design. Ultimately, these new therapies will need to be tested with standard-of-care therapy including radiation oncology. Therefore, during a study, it is essential that radiation therapy is delivered in a uniform and consistent manner for the credibility of the study. If the radiation therapy component of the study does not have a structure or management for maintaining therapeutic compliance, including a real-time data management strategy, it becomes difficult to trust the study outcome and apply the outcome to daily clinical practice. In this chapter, we review the strategy and process involved in the management of dosimetry in radiation oncology clinical trials and how this can impact clinical trial management, primary study endpoints, and the overall success of the study.