Hyperfractionated Accelerated Radiotherapy (HART) with maintenance chemotherapy for metastatic (M1-3) Medulloblastoma--a safety/feasibility study

BACKGROUND AND PURPOSE: To evaluate feasibility and toxicity of Hyperfractionated Accelerated Radiotherapy (HART) 1.24Gy b.i.d. followed by chemotherapy for M1-3 Medulloblastoma (MB). The aim of HART was to use hyperfractionation to improve therapeutic ratio combined with acceleration to minimise tumour cell repopulation during radiotherapy (RT).

MATERIALS AND METHODS: Between February 2002 and May 2008, 34 eligible patients (22 male, 12 female) aged 3-15years (median 7) with metastatic MB (M1-9; M2-3, M3-22) received HART with a craniospinal radiotherapy (CSRT) dose of 39.68Gy followed by 22.32Gy boost to the whole posterior fossa and 9.92Gy metastatic boosts. The 8th and subsequent patients received vincristine (VCR) 1.5mg/m(2) weekly×8 doses over 8weeks starting during the 1st week of RT. Maintenance chemotherapy comprised 8 six-weekly cycles of VCR 1.5mg/m(2) weekly×3, CCNU 75mg/m(2) and cisplatin 70mg/m(2).

RESULTS: Median duration of HART was 34days (range 31-38). Grade 3-4 toxicities included mucositis (8), nausea (10), anaemia (5), thrombocytopaenia (2), leucopaenia (24). With 4.5-year median follow-up, 3-year EFS and OS were 59% and 71%, respectively. Of 10 relapses, 1 was outside the central nervous system (CNS), 1 posterior fossa alone and 8 leptomeningeal with 3 also associated with posterior fossa.

CONCLUSION: HART with or without VCR was well tolerated and may have a place in the multi-modality management of high-risk MB.