New Therapy Boosts Neuroblastoma Two-Year Cure Rate

Published on in CHOP News

May 24, 2011 — Using immunotherapy — biologic agents that stimulate the body’s immune system — pediatric oncologists have achieved the first substantial increase in cure rates for the childhood cancer neuroblastoma in more than a decade. A newly released study shows that the new treatment improved two-year survival rates by 20 percentage points, compared to standard treatment for an aggressive form of neuroblastoma, a cancer of the nervous system.

The study appears in the Sept. 30 issue of the New England Journal of Medicine, along with a separate COG study on intermediate-risk neuroblastoma. The corresponding author of the immunotherapy study is Alice L. Yu, MD, PhD, of the University of California, San Diego.

Findings promise to set a new standard for treating neuroblastoma

“We expect these findings will change clinical practice, setting a new gold standard of treatment for this often-deadly disease,” said John M. Maris, MD, a co-author of the study and director of the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia. Maris is the chair of the neuroblastoma committee of the Children’s Oncology Group (COG), the cooperative multicenter research organization that sponsored the study.

Neuroblastoma, a cancer of the peripheral nervous system, usually appears as a solid tumor in the chest or abdomen. It accounts for 7 percent of all childhood cancers, but because it frequently occurs in an aggressive form, it causes 15 percent of all childhood cancer deaths. While low-risk forms of neuroblastoma may spontaneously disappear, in high-risk forms, the cancer tends to return after initial treatment, usually with lethal results.  

How the neuroblastoma study was conducted

In the current study, researchers assigned 226 high-risk patients at multiple cancer centers to receive one of two treatments:

  • Standard therapy (the chemotherapy drug isotretinoin)
  • Immunotherapy (three biological agents in combination with isotretinoin).

Immunotherapy consisted of:

  • Monoclonal antibody ch14.18
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine
  • Interleukin-2, a cytokine

Monoclonal antibodies are molecular “guided missiles” engineered to kill cancer cells by targeting a substance appearing on those cells. Cytokines are naturally occurring signaling proteins that regulate immune responses. 


  • Within two years of follow up, approximately 54 percent of the neuroblastoma patients receiving standard treatment suffered a disease relapse, which is almost uniformly fatal
  • Only 34 percent of patients receiving the experimental immunotherapy regimen had their disease return, reflecting a much higher cure rate
  • The immunotherapy group of patients experienced pain and other toxic side effects at a higher rate than the standard treatment group, however, the evidence of clear benefits from immunotherapy allowed the researchers to halt the trial earlier than expected.

Translational research brings benefits to CHOP cancer patients sooner

The Cancer Center at The Children’s Hospital of Philadelphia has been using this immunotherapy regimen as part of standard treatment for children with high-risk neuroblastoma for more than a year, since preliminary trial results were reported in June 2009. Children have arrived from around the world to receive this treatment at Children’s Hospital, which has a long-established research and clinical program in neuroblastoma. 

Other CHOP neuroblastoma research highlights

Dr. Maris is internationally prominent as a neuroblastoma expert. Some highlights of his neuroblastoma research efforts include:

  • Leading the first study that identified the gene location in which neuroblastoma originates (2008).
  • Being selected by the New England Journal of Medicine to write a review article describing the current state of the science (Recent Advances in Neuroblastoma, 2010).
  • Co-authoring a study reporting on a separate COG phase 3 clinical trial of intermediate-risk neuroblastoma (see study below)

“Together, these studies report important advances in care for children with this challenging cancer,” said Maris. “We will continue to investigate treatments to further refine the standard of care.”  

About the related Children's Oncology Group study reported in the Sept. 30 issue of NEJM

This study, Outcome after Reduced Chemotherapy for Intermediate Risk Neuroblastoma, found that physicians could substantially reduce the dose and duration of chemotherapy used for neuroblastoma and still achieve very high survival rates of 98 percent among children receiving the treatment. The benefits of lower doses include:

  • Better quality of life
  • Reduced costs
  • An expected reduction in late effects of chemotherapy, which may occur years after treatment.

The corresponding author of this study was Katherine K. Matthay, MD, of the University of California, San Francisco.  

About the study funding

Grants from the National Institutes of Health and the Food and Drug Administration supported the immunotherapy study. Grants from the National Cancer Institute, part of the National Institutes of Health, supported the study of intermediate-risk neuroblastoma. Both studies were conducted through the Children’s Oncology Group. 

More information

  • Anti-GD2 Antibody with GM-CSF, Interleukin-2 and Isotretinoin for Neuroblastoma, New England Journal of Medicine, Sept. 30, 2010.
  • Outcome after Reduced Chemotherapy for Intermediate Risk Neuroblastoma, New England Journal of Medicine, Sept. 30, 2010.