Utilizing genomic signatures from diagnostic tumor samples to forecast clinical behavior and response to therapy has long been a goal, and we are now poised to further refine how we can identify the relatively rare patients with aggres sive neuroblastoma masquerading as patients with a more benign form of the disease. In this issue of Clinical Cancer Research, Oberthuer and colleagues report a new gene expression classifier that has the potential to reliably identify children currently assigned as having low- or intermediate-risk neuroblastoma with a significantly increased risk of death (1). Conversely, the authors also demonstrate the classifier's ability to reliably identify low- or intermediate-risk neuroblastoma that will be cured with current treatment guidelines of surgery alone or relatively minimal amounts of adjuvant chemotherapy. They propose that this classifier is ready to be validated in a prospective clinical trial. Until cancer therapy is tailored to the individual patient, risk stratification will remain an important tool in clinical oncology, allowing groups of patients with better or worse outcomes to receive an appropriate treatment plan (as illustrated in Fig. 1). This is especially true for children with neuroblastoma where about 25% of children have disease that spontaneously regresses and/or differentiates; whereas about 50% have metastatic disease that is often refractory to even the most intensive treatment regimens (2). To this end, genomic markers have been used for over 30 years to stratify children with neuroblastoma as having either a low, intermediate, or high risk of relapse (and death).
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