Prognosis

Survival

Five-year progression-free survival for average-risk patients is approximately 71% to 83%, but only 50% to 66% for high-risk patients.[21][60]​​[75][76][77][78][79]​​ Reducing the radiation boost volume in average-risk patients was found to be safe and did not compromise survival, but reducing the craniospinal irradiation (CSI) dose in those with average-risk disease resulted in inferior outcomes, possibly in a subgroup-dependent manner, but was associated with better neurocognitive outcome.[79]​ Improvement in 5-year event-free survival by 19% was reported for high-risk group 3 patients in a randomized phase 3 trial adding carboplatin concurrently with CSI.[60]​ One study looking at the long-term outcomes of 1311 survivors of medulloblastoma, who were treated between 1970 and 1999, showed that the changes in treatment reduced all-cause late mortality and recurrence-related mortality but increased the risk of subsequent neoplasms (malignant or benign; not including recurrence of the original medulloblastoma).[80] For infants, historic data suggests 5-year progression-free survival in the range of 20% to 40%; however, infants with desmoplastic subtype have a clearly improved outcome.[44][45][46]​​ Some studies lend optimism that survival in infants may be improved by the use of intraventricular methotrexate or the addition of high-dose chemotherapy with stem cell rescue. Caution should be taken in interpreting these trials, as the sample sizes are small, the follow-up interval short, and (in some cases) the study population skewed with a larger than expected number of subjects with favorable prognostic features.[47][49][50]​ One study has reported a benefit compared to historical data with the addition of systemic high-dose methotrexate to the induction chemotherapy backbone prior to high-dose chemotherapy and stem cell rescue in high-risk infants. The study documented a 5-year overall survival of 100% in those with sonic hedgehog (SHH) tumors, with or without metastatic disease, and 80% overall survival in those with group 3 tumors.[81]​

Prognostic factors

Poor prognostic factors include age <3 years, the presence of metastases, and at least 1.5 cm² of residual tumor after surgery.[82] The large-cell/diffuse anaplastic histology represents a poor-risk characteristic, although it remains unclear whether this alone in the absence of concurrent high-risk molecular alterations remains prognostic.[82] There is strong evidence that amplification of the MYC or MYCN oncogenes, and deletions of chromosome 17p, are associated with poor outcome.[18][19][20]​​ SHH tumors that harbor TP53 mutations also convey a poor prognosis and are deemed high-risk.[83][84] Amplification of Gli2 or chromosome 14q loss may also be high-risk molecular alterations in SHH tumors.[83]​​​​ Wnt/Wg pathway activation as demonstrated by nuclear beta-catenin status in wingless tumors is associated with distinctively favorable clinical behavior.[21][85]​​ It is unclear whether time to diagnosis is a prognostic factor, although one study suggested no significant association between the prediagnostic symptom interval and the risk of metastatic disease and survival.[86]

Recurrence

Recurrent medulloblastoma in patients who have already had radiation therapy has a very poor outcome with a salvage rate of <10%, irrespective of the treatment modality used. Multiple chemotherapy regimens have been used, but durable responses are rare.[87][88][89]​​​​​ Some patients with nondisseminated relapse may be salvaged with a multimodal therapy, including surgery and focal reirradiation or CSI, if not previously administered or if more than a 2 year interval has elapsed since initial CSI treatment.

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