Treatment of Neuroblastoma by Risk Group

Treatment for neuroblastoma is largely based on which risk group a child is in. Generally older children, children with tumors that have spread throughout the body (high stage), or have unfavorable tumor features or extra copies of the MYCN gene will be considered high risk. Some infants with neuroblastoma that has spread throughout the body can still be considered low risk, especially if their tumor does not have extra copies of MYCN or other unfavorable features. 

Low risk

Children at low risk usually don’t need very intensive treatment to cure the neuroblastoma. In fact, some children might not need to be treated at all because some of these neuroblastomas will mature or go away on their own. If a child is low risk and the tumor can easily be removed, surgery can often be their only treatment. Even if 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. 

If much of the tumor can’t be removed, the tumor gets bigger after a surgery, or if a tumor is causing symptoms, chemotherapy (chemo) is typically given. A common chemo 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 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 to control the symptoms. A short course of radiation therapy usually is only used if the symptoms are not getting better with chemo, are life threatening, or are causing spinal cord compression.

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, chemo that is less intense may be used to shrink the tumor. Radiation therapy may be used if chemo doesn't shrink the liver right away.

Recent research has also shown that infants younger than 6 months with small adrenal tumors (which are assumed to be neuroblastomas) can often be watched closely without needing surgery or other treatments. Many of these tumors will mature or go away on their own, but if a tumor keeps growing or is causing symptoms, surgery or chemo might be used.

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 chemo drugs used usually include carboplatin, cyclophosphamide, doxorubicin, and etoposide. If chemo is used first, surgery may then be done to remove any remaining tumor. Radiation therapy usually is only used if the tumor is not responding well to chemo or if a child's symptoms from the tumor require emergency treatment.

Doctors are looking at the possibility of observing infants and young babies with no symptoms and favorable tumor features instead of treatment with surgery and/or chemotherapy. In this approach, doctors watch the tumor closely using imaging tests to make sure the tumor goes away or does not get bigger. If the tumor does gets bigger or a child has symptoms, then treatment with chemotherapy will be started. Some studies have shown promising results using this approach, and more studies are being done now. 

Children at intermediate risk who need chemotherapy are monitored closely to see how they respond after every 2 cycles (6 to 8 weeks). The total number of cycles depends on how well chemotherapy shrinks the tumor. Doctors hope that treating with chemotherapy based on a child's results can help children who have tumors that respond quickly get less chemotherapy..

High risk

Children at high risk require 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 the cancer into remission by destroying or removing as much of it as possible. Treatment usually starts with chemotherapy, using alternating regimens of several drugs (typically cisplatin, etoposide, vincristine, cyclophosphamide, doxorubicin, and topotecan) given at higher doses than what is used for other risk groups. Surgery is usually done after induction 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, followed by one or two stem cell transplants. A recent study showed that giving two stem cell transplants back to back (tandem stem cell transplant) was better than giving one stem cell transplant. Even though long-term results of this study are still being looked at, the short-term results were promising enough that some centers may give two stem cell transplants, followed by immunotherapy. Radiation is often given to the primary tumor site after stem cell transplant (even if the tumor was removed by surgery) and to any other parts of the body that might have active disease, based on MIBG scan results.
  • Maintenance: The goal of this phase of treatment is 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 dinutuximab (Unituxin), along with immune-activating cytokines (GM-CSF and IL-2), is often given as well.

Recurrent neuroblastoma

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). Chemotherapy might include drugs that weren’t used during the initial treatment. Intensive treatment with high-dose chemotherapy followed by a stem cell transplant might be another option. Because these cancers can be hard to treat, clinical trials of newer treatments, such as monoclonal antibodies or new anti-cancer drugs, might be another reasonable option. See What’s New in Neuroblastoma Research?

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Baker D, Schmidt M, Cohn S, et al. Outcome after reduced therapy for intermediate-risk neuroblastoma.  N Engl J Med.  2010; 363;1313-1323.

Brodeur GM, Hogarty MD, Bagatell R, Mosse YP, Maris JM. Neuroblastoma. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 7th ed. Philadelphia Pa: Lippincott Williams & Wilkins; 2016:772–792.

National Cancer Institute. Physician Data Query (PDQ). Neuroblastoma Treatment. 2017. Accessed at www.cancer.gov/cancertopics/pdq/treatment/neuroblastoma/healthprofessional on October 12, 2017.

Nuchtern JG, London WB, Barnewolt CE, et al. A prospective study of expectant observation as primary therapy for neuroblastoma in young infants: A Children’s Oncology Group study. Ann Surg. 2012;256:573–580.

Pappo AS, Navid F, Brennan RC, et al. Solid tumors of childhood: Neuroblastoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2015:
1465-1562

Park JR, Kriessman SG, London WB, et al. A phase III randomized clinical trial of tandem myeloablative autologous stem cell transplant using peripheral blood stem cell as consolidation therapy for high risk neuroblastoma: A Children’s Oncology Group study. J Clin Oncol. 2016: 34;18_suppl, LBA3-LBA3

Pinto NR, Applebaum MA, Volchenboum SL, et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol. 2015: 30;3008-3017.

Speleman F, Park JR, Henderson TO.  Neuroblastoma: a tough nut to crack. Am Soc Clin Oncol Educ Book. 2016; 35:e548-557.  Accessed at https://meetinglibrary.asco.org/record/50740/edbook#fulltext on October 15, 2017.

Last Medical Review: March 19, 2018 Last Revised: March 19, 2018

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.