Innovative Treatments

We have a great deal of experience using the latest therapies to treat all stages and types of neuroblastoma, including the most advanced and aggressive forms.

Low-risk and Intermediate-risk Neuroblastoma

Low-risk neuroblastomas include all cancers classified as Stage 1, Stage 2, and Stage 4S. Intermediate-risk groups include Stage 4 in babies, Stage 4S with large liver metastasis, and some patients with large tumors that have not spread. Between 80 to 95 percent of these tumors are curable. Surgery is usually done if it will not damage important near-by organs.

Taking out a kidney along with the neuroblastoma should be avoided. Observation alone, including no surgery or biopsy, might be enough for suspected neuroblastomas found by chance in a pregnant mother (from the use of prenatal ultrasound) or in the first few months of life.

For patients with low-risk neuroblastoma, it has been our practice since the late 1980s to avoid the use of chemotherapy or radiation therapy. For patients with intermediate-risk neuroblastoma, chemotherapy and radiation are used cautiously, and individualized as needed. Babies with Stage 4 neuroblastoma are now generally treated with a short course of chemotherapy only.

High-risk Neuroblastoma

Stage 4 metastatic neuroblastoma diagnosed after 18 months of age is considered high risk. In addition, tumors with a genetic marker known as MYCN amplification, irrespective of age or stage, are generally regarded as high risk. Memorial Sloan-Kettering's investigators are actively developing new treatments to fight the worst kinds of neuroblastoma.

While chemotherapy has been generally effective for controlling disease, more tumor-selective and more effective forms of therapy are urgently needed for cure. Special antibodies to bring liquid radiation selectively to tumor cells are currently being tested. Tumor vaccines to arm patients against neuroblastoma are being evaluated. Here at Memorial Sloan-Kettering, our physicians are taking advantage of new classes of drugs that push tumor cells to become normal, to stop growing, or to die. It is believed that combining these new approaches with the standard kinds of therapy will lead to more effective and gentler treatments for children with metastatic neuroblastoma. Building on lessons from past treatment programs (N6, N7, and N8) for patients with the worst kinds of neuroblastoma, our physicians recognize four major problems:

1. Current chemotherapy fails to achieve complete remission in at least 20 percent of patients.
2. In 20 to 50 percent of patients, a very small number of neuroblastoma cells are not killed by treatment and are the reason for relapse.
3. Chemotherapy itself causes leukemia (cancer of the blood) in 5 to 10 percent of patients, and leukemia is very hard to cure.
4. Relapse in the brain or spine (central nervous system) occurs in 5 to 10 percent of patients and is very hard to cure.

Induction Regimen

At Memorial Sloan-Kettering, our doctors have decreased the number of cycles of chemotherapy from six or seven to only five. Treatment results have proven to be just as good, and the chance of chemotherapy-induced leukemia has been significantly reduced. Immunotherapy with the 3F8 monoclonal antibody helps kill neuroblastoma cells that were not killed by the chemotherapy. Other treatments to kill the neuroblastoma cells include the use of antibodies or a particular kind of iodine known as metaiodobenzylguanidine (MIBG) to deliver liquid radiation combined with agents or drugs that can make radiation more effective, including, for example, medicines that stop the formation of tumor blood vessels (a process known as antiangiogenesis).

Treatment of Central Nervous System (CNS) Relapse

Central nervous system (CNS) relapse is very hard to cure. The type of radiation treatment that is normally used to treat primary neuroblastomas has not been successful against CNS relapse. At Memorial Sloan-Kettering, we are exploring the use of monoclonal antibodies (3F8 or 8H9) to deliver liquid radiation. When attached to radioactive iodine-131 (131I-3F8 and 131I-8H9), monoclonal antibodies can be safely injected into the cerebrospinal fluid, which bathes the central nervous system. This treatment is well tolerated even in young children, with no serious side effects. When combined with the usual kind of radiation therapy, longer periods of remission appear possible. Furthermore, we are studying risk factors that may predict central nervous system relapse. The hope is that these markers can help us pick out which patients should get the special treatment before the relapse happens.

Systemic Relapse from Minimal Residual Disease (MRD)

Although high-dose transplant therapy may prolong survival, cure rates around the world have not improved as much as was hoped. At Memorial Sloan-Kettering, about 80 percent of patients have no signs of neuroblastoma after five cycles of chemotherapy. However, minimum residual disease (MRD) has been and continues to be a challenge. We have developed highly sensitive methods to monitor MRD because it is believed that its transition to cure is a far easier task than starting with symptomatic gross disease. Investigators here have shown that immunotherapy using the monoclonal antibody 3F8 plus GM-CSF (a naturally-produced protein of the immune system that stimulates the production of white blood cells) is active against neuroblastoma. But some patients do not benefit from these treatments, possibly because of their genetic makeup. Ways to improve the activity of 3F8 include the use of immune system-stimulating carbohydrates known as oral glucans. New tumor vaccines are also being developed to strengthen the body's immune defense against MRD. Aside from exploring the use of isotretinoin (also known as Accutane and cis-retinoic acid) to differentiate neuroblastoma, we are testing promising agents that target signaling pathways in neuroblastoma (including epidermal growth factor receptor, histone deacetylase, heat shock protein, hypoxia inducing factor, and tubulins). Many of these agents have shown promise in human cancers and are currently in early clinical trials.