Neuroblastoma, a rare cancer of nerve tissue, usually occurs in very young children. About half of the cases are considered high risk. Doctors respond to these aggressive cases with intense therapy. Typically, this includes a combination of surgery, high doses of chemotherapy, antibody treatment, and radiation therapy. These treatments are effective in extending life and, in many instances, curing the disease.
With the success of these treatments, however, a new challenge has emerged. As children with this disease are living longer, the delayed side effects of the intense therapy — notably radiation therapy — have become a growing concern. Because neuroblastoma usually occurs in the abdomen, using radiation to destroy the cancer can also harm the pancreas, kidneys, and bones of the spine. This can raise the risk of diabetes and kidney dysfunction, as well as stunt a child’s growth.
Now a Memorial Sloan Kettering team led by radiation oncologist Suzanne Wolden has shown that it may be possible to lower the radiation dose in the treatment regimen without compromising its effectiveness. Results from a pilot study were presented this week at the annual meeting of the American Society for Radiation Oncology (ASTRO). The findings show that the reduced dose proved effective in 25 children with the high-risk form of the disease.
“This could lead to a much higher quality of life in the long term, with less risk of late complications,” Dr. Wolden says. The next step of the pilot study, set to begin soon, will test whether the dose can be lowered even further.
Maintaining Cancer Control
Radiation dosage is measured in units called grays (Gy). The usual course of treatment for high-risk neuroblastoma has been to give chemotherapy first. Next, the tumor is removed surgically. Finally, a 21 Gy radiation dose is delivered to the area to kill any remaining cancer cells and prevent the disease from returning.
“There has never been a clinical trial that looked at the optimal radiation dose for these patients,” says Dana Casey, a radiation oncology resident who presented the results of the study at the ASTRO meeting. “We wanted to see whether reducing the dose from 21 Gy to 18 Gy would still maintain local control of the cancer and keep the same survival outcomes.”
Earlier research had shown that children have markedly less growth impairment after radiation dosages of 18 Gy, she explains. The hope is that the reduced dose will also prevent the other side effects involving the kidney and pancreas.
In the first phase of the pilot study, 25 children received 18 Gy and were followed for one year after treatment. None had their cancer return in the field of radiation. In the next stage of the study, the researchers will lower the dose to 15 Gy in a new group of 25 children with high-risk neuroblastoma. As a precaution, the research team will screen out children whose tumors have a high expression of a gene called MYCN, which has been linked to an even worse prognosis in this disease.
“Lowering the dose even more, from 18 Gy to 15 Gy, is likely to have even more significant benefits in protecting the bones, kidney, pancreas, and other organs,” Dr. Wolden says.
Most, if not all, of the children in the new group will be treated with proton therapy. This advanced form of radiation therapy uses charged particles called protons rather than x-rays. Proton therapy can further reduce side effects. It is being increasingly used for pediatric cancers due to the high sensitivity of developing tissue.
Dr. Wolden explains that the need to refine the standard neuroblastoma treatment procedure is a reflection of tremendous progress. “In the old days, we didn’t worry about long-term side effects because, sadly, we were not curing those children,” she says. “Now many are surviving long term. The reason we’re doing this is very positive.”