Treating Neuroblastoma

Children with low-risk neuroblastoma often do not need very intensive treatment to be cured. In fact, some infants with small tumors might not need to be treated at all because some of these neuroblastomas will go away on their own.

For many patients with low-risk neuroblastoma, surgery might be the only treatment needed. Even if some neuroblastoma is left behind after surgery, the child may be watched carefully without further treatment because the remaining tumor could mature or go away on its own.

If much of the tumor cannot be removed, the tumor gets bigger after surgery, or the tumor is causing symptoms, chemotherapy (chemo) can be given. A common chemo regimen is a combination of carboplatin, cyclophosphamide, doxorubicin, and etoposide. But other combinations may be used.

For those few low-risk children who have symptoms related to their tumor that prevent the safe removal of the tumor by surgery, a short course of chemo might be given first. For example, if the tumor is pressing on the spinal cord or affecting breathing, chemo may be used to shrink the tumor and control the symptoms. A short course of radiation therapy might be used if the symptoms are not getting better with chemo, are life-threatening, or are causing spinal cord compression.

Infants with stage 4S (MS) 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, chemo may be used to shrink the tumor. Radiation therapy is used in rare cases when chemo does not shrink the liver right away.

Surgery is an important part of treatment for children with intermediate-risk neuroblastoma. However, chemotherapy is generally also needed to cure these children.

Children often get 2 to 8 cycles (about 6 to 24 weeks) of chemotherapy as part of their treatment plan. The chemo drugs used usually include carboplatin, cyclophosphamide, doxorubicin, and etoposide. Surgery may be done before or after chemo. If the neuroblastoma responds well to chemotherapy, surgery may not be needed in some cases.

Radiation therapy is used only when the tumor is not responding well to chemo or if a child's symptoms from the tumor require emergent treatment.

Intermediate-risk neuroblastoma is monitored closely to watch response after every 2 cycles (6 to 8 weeks). The total number of cycles given depends on how well the chemo shrinks the tumor. Doctors hope that treating based on response can allow children who have tumors that respond quickly to get less chemo and have fewer side effects.

High-risk neuroblastoma requires more aggressive treatment, which often includes chemotherapy, surgery, radiation, stem cell transplant, immunotherapy, and retinoid therapy. Treatment is often done in 3 phases.

Induction

The goal of this phase is to get cancer into remission by destroying or removing as much of it as possible. Treatment usually starts with multiple cycles of intense chemo using several drugs (in the United States, typically cisplatin, etoposide, vincristine, cyclophosphamide, doxorubicin, and topotecan).

Doctors are also studying the use of other treatments in this phase, such as targeted drugs for tumors with ALK gene mutations, anti-GD2 immunotherapy, and MIBG radiotherapy for tumors that take up MIBG.

Surgery is usually done after several cycles of induction chemo, when the tumor is smaller.

Consolidation

This phase uses more intensive treatment to try to get rid of any remaining cancer cells in the body. High-dose chemotherapy is given, followed by stem cell transplant either once or twice depending on the treatment plan. Some research has suggested that giving two stem cell transplants back-to-back (tandem stem cell transplants) may lead to better outcomes than giving one stem cell transplant. This is now being studied further in clinical trials.

Radiation is often given to the primary tumor site after a stem cell transplant (even if the tumor was removed by surgery) and to any other parts of the body that might still have cancer, based on MIBG scan results.

Post-consolidation

The goal of this phase of treatment is to try to lower the chance that the cancer will come back. Treatment is typically given for about 6 months after consolidation has been completed and includes the retinoid drug 13-cis-retinoic acid (isotretinoin), as well as immunotherapy with a monoclonal antibody such as dinutuximab (Unituxin) and an immune-activating cytokine (GM-CSF).

In some cases, the drug eflornithine might be given after post-consolidation immunotherapy for up to 2 years as well.

If neuroblastoma comes back after initial treatment, it is known as a recurrence or relapse. Treatment of recurrent neuroblastoma depends 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 high-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). Good responses have been seen with chemo and anti-GD2 antibody. Other options might include chemo drugs that were not used during the initial treatment or treatment with other antibodies like naxitamab (Danyelza).

Because these cancers can be hard to treat, clinical trials of newer treatments, such as other monoclonal antibodies, CAR T-cell therapy, or other new anticancer drugs, might be another reasonable option.