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

Abstract Background and purpose To evaluate feasibility and toxicity of Hyperfractionated Accelerated Radiotherapy (HART) 1.24 Gy 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 3–15 years (median 7) with metastatic MB (M1–9; M2–3, M3–22) received HART with a craniospinal radiotherapy (CSRT) dose of 39.68 Gy followed by 22.32 Gy boost to the whole posterior fossa and 9.92 Gy metastatic boosts. The 8th and subsequent patients received vincristine (VCR) 1.5 mg/m 2 weekly × 8 doses over 8 weeks starting during the 1st week of RT. Maintenance chemotherapy comprised 8 six-weekly cycles of VCR 1.5 mg/m 2 weekly × 3, CCNU 75 mg/m 2 and cisplatin 70 mg/m 2 . Results Median duration of HART was 34 days (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.