Sept. 29, 2010 -- An aggressive new treatment offers new hope to kids with high-risk neuroblastoma, while kids at somewhat lower risk benefit from less intense therapy.
The findings come from two breakthrough studies that already are changing treatment for children with this deadly cancer.
"To improve two-year survival by 20% is just amazing in cancer," study researcher Katherine Matthay, MD, tells WebMD. Matthay, a leading expert in childhood cancer, is chief of pediatric hematology and oncology at the University of California, San Francisco Medical Center.
The second study shows that for kids with intermediate-risk neuroblastoma -- and certain favorable tumor characteristics -- less intensive chemotherapy is just as effective as standard treatment with far fewer short- and long-term side effects.
"There are some tumors where it does not pay to be aggressive, where we need to back off and think of the lifetime to come," Matthay says.
Neuroblastoma is a cancer of the nerves outside the brain. It usually starts in the adrenal glands, located just above each kidney, although the cancer often begins in the nerve centers near the spinal cord.
It's a deadly cancer. Although there are only about 650 to 700 cases a year in the U.S., neuroblastoma accounts for 12% of childhood cancer deaths. About 90% of cases occur in children under age 10; some 60% occur before age 2. It's the most common cancer of newborns.
About half of kids with neuroblastoma have tumors with what doctors call an "unfavorable biology." This means the cancer is very aggressive, carries extra copies of the MYCN cancer gene, and spreads rapidly. Only about 30% to 40% of these children survive.
"The other group of patients have more favorable neuroblastoma, and their tumors are either localized and can be taken out without chemo, or cover a larger area and are invasive but have a favorable biology," Matthay says. "Even with metastases, if it happens before age 1 year, some of these tumors are more favorable and can be cured with chemo and without bone-marrow transplant."
All patients with neuroblastoma usually undergo surgery to take a biopsy of the tumor and to remove as much of the cancer as possible.
Intermediate-Risk Neuroblastoma: Less Treatment, Better Results
Patients with intermediate-risk neuroblastoma usually get nine or 10 months of intensive chemotherapy. It's a tough treatment that can damage the kidneys, cause hearing loss, or even cause other cancers to develop. But over 90% of these cancers can be cured.
Is all this risk really necessary? Matthay and colleagues thought not. They identified subsets of patients based on the biology of their cancers. Those with more favorable biology got only three months of chemotherapy, given in the clinic on an outpatient basis.
The kids still lost their hair and suffered side effects. But the treatment was much less brutal. And nearly all the kids -- 96% -- survived.
"We were very happy with this," Matthay says. "And in our new study, we're trying to give some patients only two cycles of chemo. And in the future, will decrease the number of patients who actually have surgery."
New Treatment for High-Risk Neuroblastoma
Patients with high-risk neuroblastoma usually undergo intensive chemotherapy followed by surgery. If this is successful, the patient then undergoes a bone-marrow transplant, using the patient's own stem cells to reconstitute the bone marrow. This is followed by six months of treatment with retinoic acid to wipe out any remaining cancer cells.
Even after this intensive treatment, more than half of patients eventually relapse and die.
University of California, San Diego researcher Alice L. Yu, MD, PhD, and colleagues tested a new approach in 226 patients with high-risk neuroblastoma.
After successful bone-marrow transplant, Yu and colleagues treated half the patients with standard therapy and half with a new monoclonal antibody developed at the National Cancer Institute. The antibody attaches to a marker on the outside of neuroblastoma cells and targets them for destruction by the immune system. At the same time, patients receive two treatments that boost immune responses.
The results were dramatic. Two-year survival free of cancer recurrence, death, or secondary cancer was 46% in the standard treatment group and 66% in the group getting the new treatment.
"This made a huge difference in overall survival and in event-free survival," Matthay says.
Even so, a third of patients still relapse -- an event that is almost always fatal.
"This is a very tough disease. It is hard to see a 2-year-old progress and die despite all these treatments," Matthay says. "We still have a ways to go. But someday we will get close to curing everyone."
Matthay says parents should know that kids with neuroblastoma need treatment at major cancer centers, where state-of-the-art care greatly improves their chances of survival.
Both studies appear in the Sept. 30 issue of the New England Journal of Medicine.