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Hopes For Better Survival And Quality Of Life For Kids With Neuroblastoma

Two new studies published in a leading journal this week suggest new ways to improve survival and quality of life for children with high and medium risk neuroblastoma, an aggressive childhood cancer that attacks the sympathetic nervous system, the nerves that respond to stress.

You can read about the two studies in the 30 September issue of the New England Journal of Medicine.

One study led by researchers at the The Children’s Hospital of Philadelphia found that a new type of immunotherapy, where biologic agents are used to stimulate the body’s own immunity to fight disease, improved two-year survival in children with high-risk neuroblastoma by 20 per cent compared to standard care, the first substantial increase in cure rates in this group for over a decade.

The other study, an eight-year clinical trial involving intermediate-risk neuroblastoma patients, conducted at the University of California, San Francisco, found it was possible to achieve a 96 per cent survival rate by using less chemotherapy than previously believed, thus avoiding harmful side effects caused by cancer drugs.

The immunotherapy study was funded by the National Institutes of Health and the Food and Drug Administration (FDA), and the reduced chemotherapy trial was funded by the National Cancer Institute, all in the US.

Speaking of the immunotherapy trial, co-author Dr. John M. Maris, director of the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia, said in a statement that:

“We expect these findings will change clinical practice, setting a new gold standard of treatment for this often-deadly disease.”

Maris also chairs the neuroblastoma committee of the Children’s Oncology Group (COG), the cooperative multicenter research organization behind the two studies, so he is also a co-author on the reduced chemotherapy study, which also shares other co-authors with the immunotherapy one.

Neuroblastoma accounts for 7 per cent of all childhood cancers, but because it is often aggressive, it causes 15 per cent of childhood cancer deaths. It affects about 650 children a year in the US.

The cancer affects the sympathetic nervous system, attacking the network of cells that control the body’s response to stress, and usually appears as a solid tumor in the chest or abdomen.

For children with the high-risk form, the disease often returns after initial treatment, and for these patients the prognosis is usually poor.

In the immunotherapy study, the researchers recruited 226 high-risk patients attending several cancer centers and assigned them to have either standard chemotherapy treatment (with isotretinoin) or this plus immunotherapy comprising three biological agents: the monoclonal antibody ch14.18, and two cytokines: GM-CSF and interleukin-2. (GM-CSF stands for granulocyte-macrophage colony-stimulating factor.)

Monoclonal antibodies are engineered to target and kill cancer cells by homing in on a particular substance in those cells. Cytokines are naturally occurring proteins that carry signals that control the immune system.

The results showed that within two years of follow-up, 54 per cent of the standard chemo patients relapsed while only 34 per cent patients on the chemo plus new immunotherapy did so, resulting in a much higher cure rate because relapse is almost always fatal.

There was a drawback: the immunotherapy group had more pain and toxic side effects, but nonetheless, the clear benefits in terms of survival caused the researchers to stop the trial earlier than planned.

Since the early trial results were reported in June last year, the Children’s Hospital of Philadelphia’s cancer center has been using this immunotherapy as part of standard treatment for high-risk neuroblastoma kids arriving from all over the world.

The reduced chemotherapy study was a phase 3 clinical trial that focused on reducing the amount of chemotherapy needed to treat intermediate-risk neuroblastoma. It involved 479 patients, the largest trial of its kind.

Corresponding author Dr. Katherine K. Matthay, of the University of California, San Francisco (UCSF), and colleagues found it was possible to substantially reduce the dose and duration of chemotherapy for treating neuroblastoma and still achieve a 98 per cent survival rate among patients.

Lower doses of chemo mean that children, whose developing bodies are very sensitive to the toxic effects of the drugs, experience better quality of life, and reduced long term risk of diseases unrelated to the initial cancer. Another obvious benefit is reduced cost.

Matthay, who is chief of pediatric oncology at UCSF Benioff Children’s Hospital, said in a statement:

“This trial will lead to permanent treatment reductions in our protocol for treating this disease and will have a significant impact on the hundreds of children who are diagnosed with neuroblastoma each year.”

“It is my hope that we will be able to continue reducing the amount of chemotherapy we give to certain groups of neuroblastoma patients, so we can improve the long-term quality of life for these children and not have to worry about them having any secondary cancers,” she added.

Matthay also commented on how good it was to see “our patients many years after they have undergone treatment, when they are on their way to have kids of their own”.

Maris said that together the two studies “report important advances in care for children with this challenging cancer”.

“We will continue to investigate treatments to further refine the standard of care,” he added.



One Response to “Hopes For Better Survival And Quality Of Life For Kids With Neuroblastoma”

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