Markers Could Improve Treatment Stratification for Pediatric Medulloblastoma

The use of an intensified treatment regimen to treat metastatic medulloblastoma in children and adolescents conferred an overall favorable survival, according to the results of a recent study. However, patients within varying subgroups and with certain biologic parameters did not have uniform outcomes.

Patients in the study were aged between 4 and 21 and diagnosed between 2001 and 2007. All were treated with induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy.

“With this prospective cohort, we newly confirm previous results obtained from retrospective series with heterogeneously treated patients,” wrote researchers led by Andre O. von Bueren, of University Medical Center Hamburg-Eppendorf, Germany, in the Journal of Clinical Oncology. “We demonstrate that stratification of patients can be improved by subgroup status and other biologic factors into low-, intermediate-, high-, or very high–risk groups.”

Results were taken from 123 eligible patients with a median age of 8.2 years. Among these patients, the 5-year event-free survival was 62% and the overall survival was 74%. Looking at different disease types, survival results were:

• Desmoplastic/nodular: event-free survival, 89%; overall survival, 89%;

• Classic: event-free survival, 61%; overall survival, 75%;

• Large-cell/anaplastic: event-free survival, 20%; overall survival 40%.

The researchers identified two independent risk factors for event-free survival: non-response to first chemotherapy cycle (hazard ratio [HR], 1.97) and histology (desmoplastic/nodular HR, 0.19; large-cell/anaplastic HR, 45.97).

“Our study provides evidence of how this large group, for which so far no proposal for substratification is available, may be further substratified for risk-adapted therapy: Nonresponse to the first cycle of induction chemotherapy has been identified as an independent negative prognostic factor for event-free survival, and this prognostic factor has also been shown to have an impact on event-free survival and overall survival in the intermediate-risk group (characterized by WNT-, MYCC/MYCN-, and LC/A-negative tumors),” the researchers wrote. “Patients achieving only stable disease after 8 weeks of induction chemotherapy may benefit from earlier use of radiotherapy.”

Tumor material was available for 81 patients in the study. Among these patients the 5-year event-free survival and overall survival differed. Patients with low-risk disease (wingless [WNT]) had 100% survival for both. Patients with high-risk disease (MYCC/MYCN amplification) had 20% survival for both. Finally, patients with intermediate-risk disease had 63% 5-year event-free survival and 73% overall survival.

The researchers also examined outcomes according to molecular subgrouping (WNT, n = 4; sonic hedgehog, n = 4; group 3, n = 20; group 4, n = 41), but found no overall difference among the groups for event-free or overall survival.

“The strength of our study is that we report on an improved patient prognostication in the context of homogeneous clinical therapy,” the researchers wrote. “In contrast, the value of our study is limited as a result of the sample size with known molecular subgroups and genetic factors. Thus, the numbers were too small to perform a meaningful multivariable analysis. To optimize progress from upcoming medulloblastoma trials for metastatic disease and also to prevent a potential bias, all tumors of the patients should be assessed and profiled in future prospective trials.”