Revised: June 2014
Medulloblastomas or posterior fossa primitive neuroectodermal tumours are aggressive tumours characterized histologically by small dark cells with scanty cytoplasm. They constitute 20 – 25% of all pediatric brain tumours but are rare in adults. In the BCCA, only 22 cases were identified between 1978 & 1995(1). Because of their rarity, management has been mainly guided by knowledge derived from pediatric medulloblastomas.
Presentation & Investigations
With its posterior fossa location, symptoms of a medulloblastoma are those of increased intracranial pressure and those related to the cerebellar tracts and brainstem long tracts. Medulloblastomas are well known for their propensity for spread through the craniospinal axis. In the series from B.C., 5 out of the 13 patients who were worked up for craniospinal axis disease had positive CSF dissemination (1). Metastasis outside of the CNS is possible but rare at presentation. All patients diagnosed with medulloblastomas should have an MRI of the craniospinal axis +/- CSF cytology to rule out CSF dissemination.
Recent molecular diagnostic studies have elucidated several different prognostic subtypes of medulloblastoma. Most adult medulloblastomas are of an intermediate prognosis subtype showing upregulation of Sonic Hedgehog pathways (2). While testing for these molecular subtypes is not standard at this time, therapies targeting these pathways are being developed and may lead to subtype specific therapies.
Treatment
Medulloblastomas are treated with surgical resection, followed by craniospinal radiation with or without chemotherapy.
An attempt should be made to excise as much as possible the gross tumour. Although data in adults are rare, pediatric series have consistently shown significantly better survival in patients with minimal postoperative disease compared to those with gross residual disease (3,4).
Because of the propensity of metastasis through the spinal axis, postoperative radiotherapy to the entire craniospinal axis is the standard treatment in patients with medulloblastomas. Hair loss and general fatigue are common during craniospinal radiation. In addition, patients may have hematological toxicity, particularly lymphopenia, during the 5 – 6 weeks of treatment. Their blood picture will be monitored and prophylactic antibiotics started as indicated.
The role of chemotherapy is not well defined for adult medulloblastomas. Whether chemotherapy can improve the cure rate after optimal surgery and craniospinal radiation is not clear because of the rarity of the disease. Nevertheless, chemotherapy is often given for high risk patients based on the results of adjuvant chemotherapy in the pediatric age group. Patients considered high risk for recurrence are those with gross residual disease and evidence of intracranial or spinal axis dissemination. This definition of high risk group is again an extrapolation from the pediatric literature (5). Many combination therapies have been tried with no superiority of one protocol over another. Commonly used agents include nitrosoureas, platinum-based agents, cyclophosphamide, etoposide and vincristine. The toxicity of these regimens in adults is not insignificant. If chemotherapy is given, it is usually started after surgery and radiation is completed.
Outcome of Treatment
Older series of adult medulloblastoma patients from the Royal Marsden Hospital (6) and the Princess Margaret Hospital (7) included about 50 patients each treated over a 30-year period from the 1950's to the 1980's. The 5-year survival is about 50 – 60% and 10-year survival is about 40%. More recently Padovani et al (8) studied 253 adults between 1975 and 2004 showing 5 and 10 year survivals of 72% and 55%, respectively. The 22 patients treated in BCCA from 1978 – 1995 did slightly better, with a 5 year disease specific survival of over 80%. Even among patients with proven spinal dissemination, only 1 out of 5 failed (1). The reason for this better outcome may just reflect the different time periods in which patients are treated.
After relapse, there is no standard of care for salvage therapy and outcomes are generally poor. Patients treated with high dose myeloablative regimens have not had a significant higher cure rate over less intensive protocols (9,10)
References:
Kwan W, Agranovich A, Rheaume D et al: Adult medulloblastomas, the B.C. experience. Unpublished data, presented at the 8th Biennial Canadian Neuro-Oncology Meeting, Niagara-on-the-Lake. May 1998.
Kool M, Korshunov A, Remke M, et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3 and group 4 medulloblastomas. Acta Neuropathol 123:473, 2012.
Bourne JP, Geyer R, Berger M et al: The prognostic significance of post-operative residual contrast enhancement on CT scan in paediatric patients with medulloblastoma. J Neuro-Oncology 14: 263-270, 1992.
Jenkin D, Goddard K, Armstrong D, et al: Posterior fossa medulloblastoma in childhood: Treatment results and a proposal for a new staging system. Int J Radiation Oncology Biol Phys 19: 265-274, 1990.
Chang CH, Housepain EM, Herbert C. Radiology 93:1351, 1969.
Bloom HJG, Bessell EM: Medulloblastoma in adults: a review of 47 patients treated between 1952 and 1981. Int J Radiation Oncology Biol Phys 18: 763-772, 1990.
Frost PJ, Laperriere NJ, Wong CS et al: Medulloblastoma in adults. Int J Radiation Oncology Biol Phys 32: 951-957, 1995.
Padovani L, Sunyach MP, Perol D, et al. Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults. Int J Radiat Oncol Biol Phys 68(2):433-40, 2007.
Massomino M, Gandola L, Spreafico F, et al. No salvage using high dose chemotherapy plus/minus re-irradiation for relapsing previously irradiated medulloblastoma. Int J Radiat Oncol Biol Phys 73:1358-63, 2009.
Gajjar A, Pizer B. Role of high dose chemotherapy for recurrent medulloblastoma and other CNS primitive neuroectodermal tumors. Pediatr Blood Cancer 54:649-51, 2010.
