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Introduction.Neuroblastoma is a solid tumor of childhood that arises in the nervous system outside of the brain. Half of patients have clinical and biologic features at diagnosis that define their tumors as "high-risk neuroblastoma".

This portion of the NANT web site briefly reviews the initial treatment options available for children with high-risk neuroblastoma. We also present some of the new approaches to treating patients with high-risk neuroblastoma whose tumors are recurrent/refractory after frontline therapy.

International Neuroblastoma Staging System (INSS)
(Please click on the diagram thumbnail to load a larger version)

The staging system (by degree of tumor spread) for neuroblastoma is shown above. All patients with metastatic (stage 4) disease diagnosed after 18 months of age are in the high-risk category. In stage 4 disease, the neuroblastoma tumor cells have already spread (metastasized) to other sites in the body such as the bone or bone marrow. Additionally, essentially all patients who have tumors with many copies ("gene amplification") of the MYCN cancer gene also have high-risk disease, even if they do not have evidence of the tumor having spread.

Initial Therapy of High-Risk Neuroblastoma.

Clinical trials results have formed the basis of the current standard therapy for high-risk neuroblastoma. This includes "induction" chemotherapy over about five months followed by "consolidation" with very high dose chemotherapy + stem cell transplant.

The patient's own stem cells are obtained during "induction" from the peripheral blood (peripheral blood stem cells, or PBSC), and are given back after the high-dose chemotherapy to "rescue" the patient from the side effects on the normal blood cells. The primary tumor is surgically resected if possible during induction.

After stem cell transplant, local radiation is given to residual sites of tumor. Patients then receive "maintenance" therapy which includes immunotherapy with five courses of ch14.18 monoclonal antibody or (dinutuximab) given with GM-CSF alternating with IL-2, plus isotretinoin for six courses in an attempt to eliminate any remaining tumor cells. These established principles apply to "frontline" therapy of high-risk neuroblastoma.

For patients whose tumor does not respond, or grows during or after the above therapy, the chance of survival is greatly reduced. Because there are no established effective treatments for such patients, experimental therapies, such as those being developed and studied by investigators of the NANT consortium may be appropriate.

Recurrent or Refractory Neuroblastoma. High-risk neuroblastomas tumors that do not respond, or grow during therapy or return after apparently having gone away almost always are resistant to the "standard" induction, consolidation, or maintenance therapy discussed above. Patients in this condition are encouraged to enroll in phase I or II clinical trials that test new therapeutic strategies. A variety of phase I and II studies are carried out by the NANT, the Children's Oncology Group and other organizations.

These studies almost always are limited to patients with recurrent or refractory neuroblastoma because their side effects and ability to improve survival are not well-defined.

Brief descriptions of the clinical trials being conducted by the NANT are available on this web site under "Clinical Trials". Web sites for the National Cancer Institute and the Children's Oncology Group also provide information on other clinical trials that are available for patients with neuroblastoma.