How is high-risk pediatric neuroblastoma treated?

Updated: Oct 09, 2017
  • Author: Norman J Lacayo, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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This group of patients seem to require treatment with multiagent chemotherapy, surgery, and radiotherapy, followed by consolidation with high-dose chemotherapy and peripheral blood stem cell rescue.

Current therapeutic protocols involve 4 phases of therapy, including induction, local control, consolidation and treatment of minimal residual disease. The 3-year EFS for patients in the high-risk group who are treated without such high-intensity therapy is less than 20%, compared with an EFS of 38% in patients treated with a single bone marrow transplant and cis-retinoic acid after transplant.

Induction therapy currently involves multiagent chemotherapy with non–cross-resistant profiles, including alkylating agents, platinum, and anthracyclines and topoisomerase II inhibitors. Current studies are ongoing to look at addition of topoisomerase I inhibitors as part of an upfront therapy during induction. Topotecan does display activity against relapsed neuroblastoma.

Local control involves surgical resection of primary tumor site as well as radiation to primary tumor site. Primary tumors are often more amenable to surgical resection after receiving upfront induction chemotherapy. Neuroblastoma is a very radiosensitive tumor, and chemotherapy plays an important role in control of disease in the high-risk setting.

Myeloablative consolidation therapy has shown to improve EFS for patients with high-risk neuroblastoma. Current data from trials in the United States and Europe support improved outcomes for patients receiving myeloablative consolidation therapy with etoposide, carboplatin, and melphalan. Recently, a single-arm study of tandem stem cell transplantation reported an EFS of 58%. A randomized study of tandem stem cell transplant against a single transplant is currently ongoing in the Children’s Oncology Group. [8] Because of significant improvements in time to recovery and a lower risk of tumor cell contamination, most centers now recommend the use of peripheral blood stem cell support over bone marrow for consolidation therapy.

Control of minimal residual disease with biologic agents has also been shown to improve survival. The most experience is with 13-cis -retinoic acid in a maintenance phase of therapy. This agent has been shown to cause differentiation in neuroblastoma cell lines. CCG-3891 showed a significant survival advantage with 3-year EFS of 38% for those patients receiving maintenance therapy with 13-cis -RA compared with 18% for those who did not receive this therapy. Recent data have showed improved survival in patients receiving 13-cis -RA in combination with immunomodulatory therapy with interleukin (IL)-2, granulocyte macrophage colony-stimulating factor (GM-CSF), and the chimeric anti-GD2 (gangliosidase) antibody when compared with 13-cis -RA alone.

On March 10, 2015 the US Food and Drug Administration (FDA) approved dinutuximab, which is a monoclonal antibody against GD2, for use in the treatment of high-risk neuroblastoma. It was approved as part of a multimodality regimen, including surgery, chemotherapy, and radiation therapy, for patients who have achieved at least a partial response to prior first-line multiagent. It is indicated in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) for pediatric patients with high-risk neuroblastoma.

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