A Prospective Randomised Controlled Trial Of Hyperfractionated Versus Conventionally Fractionated Radiotherapy In Standard Risk Medulloblastoma

OBJECTIVES:

• Compare the event-free survival rate in pediatric patients with standard-risk medulloblastoma treated with conventional vs hyperfractionated radiotherapy and vincristine followed by maintenance with cisplatin, lomustine, and vincristine.
• Compare the overall survival of patients treated with these regimens.
• Compare the pattern of relapse, especially local relapse (tumor bed or posterior fossa outside tumor bed), in patients treated with these regimens.
• Determine the toxicity of surgery and whether there are identifiable factors that correlate with toxicity in these patients.
• Determine the impact of any surgical complications on commencement of adjuvant therapy and event-free survival of these patients.
• Compare late sequelae, in terms of health status, endocrine deficiencies, and hearing loss, in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to country. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Within 28-40 days after surgical resection, patients undergo conventional fractionated radiotherapy once daily, 5 days a week, for 6-7 weeks. Patients also receive vincristine IV once weekly for 8 weeks.
• Arm II: Beginning as in arm I, patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, for 6-7 weeks. Patients also receive vincristine as in arm I.
• Maintenance chemotherapy:Six weeks after completion of radiotherapy, all patients receive cisplatin IV over 6 hours and oral lomustine on day 1 and vincristine IV on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 courses.

Patients are followed at least every 6 months for 3 years.