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Neuroblastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of High-Risk Neuroblastoma

Table 8. Children's Oncology Group (COG) Neuroblastoma High-Risk Group Assignment Schema Used for COG-P9641 and COG-A3961 Studiesa continued...

Outcomes for patients with high-risk neuroblastoma remain poor despite recent improvements in survival in randomized trials.

The standard treatment option for high-risk neuroblastoma is the following:

  1. A regimen of chemotherapy, surgery, stem cell transplant (SCT), and radiation therapy, cis-retinoic acid, anti-GD2 antibody ch14.18, and interleukin-2/granulocyte-macrophage colony-stimulating factor (GM-CSF).

Chemotherapy, surgery, SCT, radiation therapy,cis -retinoic acid, anti-GD2 antibody ch14.18, and interleukin-2/GM-CSF

Treatment for patients with high-risk disease is generally divided into the following three phases:

  • Induction (includes chemotherapy and surgical resection).
  • Consolidation (hematopoietic stem cell rescue/transplantation [HSCT]).
  • Maintenance (immunotherapy and retinoid).

Induction phase

The backbone of the most commonly used induction therapy includes dose-intensive cycles of cisplatin and etoposide alternating with vincristine, cyclophosphamide, and doxorubicin.[5] Topotecan was added to this regimen based on the anti-neuroblastoma activity seen in relapsed patients.[6] Response to therapy at the end of induction chemotherapy correlates with EFS at the completion of high-risk therapy.[7] After a response to chemotherapy, resection of the primary tumor is usually attempted.

Consolidation phase

The consolidation phase of high-risk regimens involves myeloablative chemotherapy and HSCT, which attempts to eradicate minimal residual disease using lethal doses of chemotherapy and autologous stem cells collected during induction chemotherapy to repopulate the bone marrow. Several large randomized controlled studies have shown an improvement in 3-year EFS for HSCT (31% to 47%) versus conventional chemotherapy (22% to 31%).[8,9,10] Previously, total-body irradiation had been used in HSCT conditioning regimens. Most current protocols use either carboplatin/etoposide/melphalan or busulfan/melphalan as conditioning for HSCT. Two or more sequential cycles of myeloablative chemotherapy and stem cell rescue given in a tandem fashion has been shown to be feasible for patients with high-risk neuroblastoma.[11,12]

A randomized clinical study (COG-ANBL0532) testing the efficacy of two cycles versus one cycle of myeloablative chemotherapy with stem cell rescue has been completed. (Refer to the Autologous Hematopoietic Cell Transplantation section in the PDQ summary on Childhood Hematopoietic Cell Transplantation for more information about transplantation.)

Radiation to the primary tumor site (whether or not a complete excision was obtained) and persistently metaiodobenzylguanidine-positive bony metastatic sites is often performed before, during, or after myeloablative therapy. The optimal dose of radiation therapy has not been determined. Radiation of metastatic disease sites is determined on an individual case basis.

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