Treatment

Bone marrow aspiration and biopsy

Diagnosis

The diagnosis of neuroblastoma is based on the clinical signs and symptoms discussed previously.

The child’s urine is sent for HVA and VMA. The primary tumor is usually assessed with CT scan which helps determine the extent of disease, invasion into surrounding structures, and lymph node involvement. In children with a primary abdominal tumor, involvement of the liver with tumor can also be assessed. For patients who present with neurologic symptoms, MRI can be helpful to define involvement of the spinal canal or cord. MIBG scan is a compound resembling norepinephrine that binds to norepinephrine sites and is stored in neural crest cells. When this substance is labeled with ¹²³I or ¹³¹I it can define the tumor or identify metastases even in those few patients with normal catecholamine levels.

To assess for metastases, a bone scan and a plain chest radiograph are obtained.

Some neuroblastomas are easily recognized when looked at by doctors experienced in testing children’s tumor samples. But some cases may be hard to tell apart from other types of children’s cancers. In these situations, special tests such as immunohistochemistry must be done. For this test, a portion of the sample is treated with special proteins (antibodies) that attach to substances in neuroblastoma cells but not in other cancers. Chemicals (stains) are then added so that cells containing these substances change color and can be easily seen under a microscope. This lets the pathologist know that the tumor is a neuroblastoma.

Neuroblastoma often spreads to the bone marrow. If blood or urine levels of catecholamines are increased, then finding cancer cells in a bone marrow sample is enough to diagnose neuroblastoma (without getting a biopsy of the main tumor). If neuroblastoma has already been diagnosed by a biopsy done elsewhere in the body, bone marrow testing is done to help determine the extent of the disease.

A bone marrow aspiration and biopsy are usually done at the same time. In most cases the samples are taken from the back of both of the pelvic (hip) bones.

The diagnosis of neuroblastoma is confirmed by:

1. Biopsy with unequivocal diagnosis of neuroblastoma by light microscopy, or

2. Bone marrow biopsy or aspirate with unequivocal tumor cells and increased serum or urine catecholamines.

The approach to treatment of neuroblastoma depends on the stage of the cancer, the child's age, and other factors such as the prognostic markers mentioned previously.

The types of treatment used may include:

· Surgery

· Chemotherapy

· Retinoid therapy (retinoids are chemicals that are related to vitamin A; retinoids such as 13-cis-retinoic acid (isotretinoin) have reduced the risk of recurrence after treatment in children with high-risk neuroblastoma)

· Radiation therapy

· High-dose chemotherapy/radiation therapy and stem cell transplant

· Immunotherapy (monoclonal antibodies are man-made versions of immune system proteins that can be made to attack a very specific target)

In many cases, more than one type of treatment is needed.

Treatment for neuroblastoma is largely based on which risk group a child falls into.

v Low risk

Children at low risk can often have surgery as their only treatment. Even in cases where some neuroblastoma is left behind after surgery, the child can usually be watched carefully without further treatment because the remaining tumor will often mature or go away on its own.

Chemotherapy is typically given after surgery if much of the tumor can’t be removed or if it has some unfavorable features. A common chemotherapy regimen is a combination of carboplatin, cyclophosphamide, doxorubicin, and etoposide. But other combinations may be used.

For those few children that have symptoms from a low-risk tumor that can’t safely be treated right away with surgery, a short course of chemotherapy might be given first. For example, if the tumor is pressing on the spinal cord or affecting breathing, chemotherapy may be used to shrink the tumor to control the symptoms. Radiation therapy may be needed if chemotherapy doesn't shrink the tumor fast enough.

Infants with stage 4S disease and no symptoms can often be watched carefully with no treatment, because these cancers typically mature or go away on their own. If the tumor causes problems such as an enlarged liver, which can be life-threatening for very young infants, chemotherapy that is less intense may be used to shrink the tumor. Radiation therapy may be used if chemo does not shrink the liver right away.

v Intermediate risk

Surgery is an important part of treatment for children at intermediate risk, but it is rarely enough on its own. Children are typically given 4 to 8 cycles (about 12 to 24 weeks) of chemotherapy before or after surgery. The chemotherapy drugs used are usually the same as for low-risk disease, although the doses may be higher. Radiation therapy may be used if chemotherapy is not effective.

If chemotherapy is used after surgery, a “second look surgery” may be done to see if there is any cancer remaining and, if there is, remove it if possible. This may be followed by radiation therapy, if needed.

v High risk

Children at high risk require more aggressive treatment, which often includes chemotherapy, surgery, and radiation. Treatment is often divided into 3 phases.

Induction: The goal of this phase is to get the cancer into remission by destroying or removing as much of it as possible. Treatment usually starts with chemotherapy, using more drugs and at higher doses than what is used in other risk groups. Surgery may be done after this to try to remove any tumors that are still visible.

Consolidation: This phase uses more intensive treatment to try to get rid of any cancer cells that remain in the body. High-dose chemotherapy is given (often along with radiation therapy), followed by a stem cell transplant.

Maintenance: This phase of treatment is given to try to lower the chance that the cancer will come back. The retinoid drug 13-cis-retinoic acid (isotretinoin) is often given for 6 months after other treatments are completed. Immunotherapy with the monoclonal antibody ch14.18, along with immune-activating cytokines (GM-CSF and IL-2), is often given as well.

v Recurrent neuroblastoma

If neuroblastoma comes back after initial treatment, it is known as a recurrence or relapse. Treatment at this point will depend on many factors, including the initial risk group, where the cancer recurs, and what treatments have been used.

For low- and intermediate-risk neuroblastomas that recur in the same area where they started, surgery with or without chemotherapy may be effective.

For higher-risk cancers or those that recur in distant parts of the body, treatment is usually more intense, and may include a combination of chemotherapy, surgery, and radiation therapy (such as MIBG radiotherapy). Chemotherapy might include drugs that weren't used during the initial treatment. In some relapsed cases, intensive treatment with high-dose chemotherapy/radiation therapy followed by a stem cell transplant may be used. Because these cancers can be hard to treat, clinical trials of experimental treatments, such as monoclonal antibodies or new anti-cancer drugs, may be another reasonable option.