Deleted Genes Help Predict Outcome in a Children's Cancer

A new study reports that a loss of genes on chromosome 1 or chromosome 11 raises the risk of death from the children’s cancer neuroblastoma, even when other indicators seem to point to a lower-risk form of the disease. This research finding will help guide physicians to the most appropriate treatment for the cancer, which strikes the peripheral nervous system. The approach used may also be applied to customizing care for other cancers.

"Identifying more accurate risk levels of this cancer allows doctors to treat aggressive types of the cancer appropriately, while not subjecting children with lower-risk cancer to overtreatment," said study leader John Maris, M.D., of The Children's Hospital of Philadelphia. The study from the Children's Oncology Group, a cooperative research organization of pediatric cancer centers, appears in the November 24 New England Journal of Medicine.

The research team analyzed tumor samples from 915 children with neuroblastoma. Neuroblastoma is the most common cancer in infants, accounting for 10 percent of all pediatric cancers, but its course is not easily predictable.

Often occurring as a solid tumor in a child's abdomen or chest, some cases spontaneously resolve even without surgery, while others are particularly aggressive — resisting initial therapy, or causing a relapse. The more accurately physicians can identify a patient's risk level at the initial evaluation, the better they can customize treatment to each child.

Turning the Tide of Pediatric Cancers
Using details of tumor biology to help classify a patient's prognosis – a process called risk stratification – has received a large boost from the flood of genetic data from the National Genome Project. At the same time, researchers are translating knowledge of molecular events and biological processes into experimental cancer treatments.

As with all science, findings such as the current study of chromosome deletions in neuroblastoma are incremental advances. Those advances occur against the backdrop of a remarkable turnaround: in one generation, survival rates for pediatric cancer have risen from roughly 25 percent in the 1970s to nearly 80 percent today.

One major reason for the dramatic progress in pediatric survival rates is the fact that, over the years, high percentages of children with cancer have participated in clinical trials of new treatments. Today, as researchers work to counteract the most refractory and aggressive cancers, the new treatments are often targeted therapies— specific agents that attack cancer cells while sparing healthy cells. One such treatment used at Children's Hospital is a compound called MIBG that selectively concentrates in neuroblastoma cells. When bound to a radioactive isotope of iodine and delivered by an I.V. line, the radioactive package kills cancer cells, with low toxicity to healthy tissue.

"These treatments are not cures, but they are bringing us closer to controlling neuroblastoma," says Dr. Maris. "Our goal is to successfully treat the cases that have learned to resist therapy."