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Neuroblastoma is the second most common pediatric solid tumor, comprising
8-10% of all pediatric malignancies.  This neoplasm is one of the most deadly pediatric cancers  today and accounts for approximately 15% of all pediatric oncology deaths.  There are approximately 600 new cases of neuroblastoma in the United States each year.  The median age at diagnosis is 22 months of age with one-third of patients diagnosed in the first year of life and 90% of children diagnosed before 5 years of age.  Occasional patients can be diagnosed in adolescence and young adulthood and have an indolent course with poor overall survival.

High-risk Disease

Treatment of children with high-risk disease remains one of the greatest challenges for pediatric oncologists.  In recent years, modest improvement is survival has been seen, but cure rates remain dismal.  The modest improvement is thought to be due to intensification of induction chemotherapy, megatherapy consolidation with stem cell transplant, maintenance therapy with the differentiation agent 13-cis retinoic acid, and improved supportive care.  Cisplatin, etoposide, cyclophosphamide, and doxorubicin are the backbone of high-risk neuroblastoma chemotherapy.  The superiority of using myeloablative therapy and autologous bone marrow transplant over conventional dose chemotherapy has been demonstrated in a randomized study conducted by the Children’s Cancer Group.  However, even with stem cell transplant, 3-year event-free survival was only 34% + 4% in that study.

More Effective and Less Toxic Therapy is Needed

To ultimately improve survival for high-risk patients, a better understanding of the biological pathways responsible for neuroblastoma initiation and progression is needed.   Angiogenesis, or the development of new blood vessels that supply nutrients to the tumor, has been shown to be critical for cancer growth.  Clinical studies in adults with cancer have shown that survival is prolonged with agents that block angiogenesis.  Laboratory studies suggest that this treatment strategy may also be effective in neuroblastoma.  Recent genomic studies have led to the discovery of a number of putative molecular targets, including ALK.  Epigenetic changes (or abnormal gene methylation) have also been demonstrated in neuroblastoma tumors.  Agents that are capable of reversing epigenetic changes have been shown to have promising activity in a number of different types of cancers and may also be effective in neuroblastoma.  Although significant progress has been made in understanding neuroblastoma biology, more work still needs to be done.  Defining the events that drive aggressive neuroblastoma tumor growth will provide the insight needed for the development of more effective therapeutic strategies.