Medulloblastomas: New directions in risk stratification

Abstract

Medulloblastomas (MBs) are the most common malignant brain tumors in children. Current therapeutic approaches combine surgery, radiotherapy, and chemotherapy. Although, there has been significant improvement in long-term survival rates, the tumor remains incurable in about a third of patients while cognitive deficits and other sequelae of therapy are common among long-term survivors. Hence a major challenge remains to differentiate high-from low-risk patients and to tailor therapy based on the degree of biological aggressiveness. A clinical risk-stratification system has been widely used in MBs based on age, extent of resection and the Chang staging system. However, recent reports indicate that these clinical variables are inadequate methods of defining disease risk. This has prompted search for new markers for MB stratification. Recent studies indicate that the classification of MBs according to profiles of histopathology and molecular abnormalities possibly help better risk-stratification of patients, thereby rationalizing approaches to therapy, increasing cure rate, reducing long-term side effects and developing novel therapeutic strategies. The most accurate outcome prediction till date has been obtained through microarray gene expression profiling. In this article, the current histopathological classification and the recent advances in molecular genetics of MBs are reviewed. Global efforts to translate this knowledge of disease biology into clinical practice especially as outcome predictors are highlighted.