Kinder gentler cure for childhood cancer

STANFORD -- Most children with early-stage non-Hodgkin's lymphoma can be cured. That's good, but what's even better is the news that the standard chemotherapy regimen for many of these children can be reduced by more than two-thirds -- from eight months to just nine weeks -- with no negative consequences.

A large-scale international study, led by a children's cancer specialist at Stanford University School of Medicine, has shown that it's safe to cut back on chemotherapy for most children with this disease.

The study appears in the Oct. 30 New England Journal of Medicine.

Early-stage non-Hodgkin's lymphoma, a cancer of the lymphatic system, accounts for roughly 5 percent of all childhood cancer cases.

In recent decades, cancer specialists have had great success using radiation therapy and chemotherapy to treat children with non-Hodgkin's lymphoma. The cure rate has risen steadily since the 1970s, when most patients died, to roughly 70 percent cured today, said Dr. Michael P. Link, a Stanford professor of pediatrics, who led the newly published study.

"It's a pediatric oncology success story. And for children with the early-stage form of non-Hodgkin's lymphoma, the survival now exceeds 90 percent," said Link, whos practices at Lucile Packard Children's Hospital at Stanford.

But until the 1990s, those cures came with a cost: Radiation therapy can lead to more cancers and often leaves girls infertile in adulthood, while chemotherapy can cause a host of short-term side effects such as infections, mouth sores and nausea.

"And just going to the hospital for their treatment every week for months and months is a major downer for most kids and their parents," Link said.

In 1990, a multicenter trial directed by Link revealed that radiation therapy was unnecessary for children with early-stage non-Hodgkin's lymphoma. The results of this trial, conducted by the Pediatric Oncology Group (a group of cancer researchers working at medical institutions in Canada, Puerto Rico, Switzerland and the United States), were published in the April 26, 1990 New England Journal of Medicine.

"This was great news," Link said. "We saw that we could eliminate irradiation for children with early-stage non-Hodgkin's lymphoma.

"So then we took the next step and asked, 'How much chemotherapy do these children really need?"

The newly published conclusions of that second trial offer heartening news for children diagnosed with the disease. The trial involved 198 children at about 65 centers in Canada, Puerto Rico, Switzerland and the United States.

"We found that in most cases, children who got just nine weeks of chemotherapy did as well as those who got the full eight months of chemotherapy plus irradiation. So we've gone from eight months of chemotherapy with irradiation to nine weeks of chemotherapy without irradiation -- and the cure rate has stayed the same," Link said.

For one group of children in the study, however, the reduced chemotherapy regimen wasn't enough. The longer regimen worked better than the shorter one for those with lymphoblastic lymphoma, a subtype representing about 15 percent of childhood early-stage non-Hodgkin's lymphoma cases. But even with the longer course of treatment, these children were less likely than the others to remain free of disease.

Link's co-authors on the chemotherapy study were Dr. Sarah Donaldson, professor of radiation oncology at Stanford; Jonathan Shuster, professor of statistics at the University of Florida; Dr. Costan Berard, professor of pathology (retired) at the University of Tennessee, Memphis; and Dr. Sharon Murphy, professor of pediatrics at Northwestern University School of Medicine.

The study was carried out by members of the Pediatric Oncology Group and was funded by the National Cancer Institute.