3-D irradiation of brain cancer in children spares IQ, memory, other cognitive functions

Encouraging results of Phase II conformal radiation trial for ependymoma could resolve the dilemma on whether to withhold therapeutic radiation from children to preserve their cognitive development

A radiation therapy technique that kills brain tumors in children while sparing normal tissue allows young patients to enjoy normal development of memory, reasoning, problem-solving and other cognitive functions, according to investigators at St. Jude Children’s Research Hospital. The results of a Phase II clinical trial of this technique, called conformal radiation therapy (CRT), hold promise for sparing cognitive development even in children younger than three years.

This research is published in the August issue of the Journal of Clinical Oncology. The St. Jude study found that about 75 percent of the children treated for ependymoma with CRT did not experience progression of their cancer after three years, and their cognitive development was not significantly impaired by radiation therapy.

Ependymoma is a malignant brain tumor that occurs predominately in children. About 150 cases occur in the United States each year among people younger than 14 years.

The study’s findings could offer an answer to a long-standing dilemma facing physicians treating children who have brain tumors, according to Thomas Merchant, D.O., Ph.D., chief of Radiation Oncology at St. Jude. Following surgery to remove as much of the tumor as possible, radiation treatment is more effective than chemotherapy at eradicating the remaining cancer. However, despite its lower rate of treatment success, chemotherapy has been used in the past for young children because of fear among physicians and parents of radiation-related treatment effects.

Merchant is the principal investigator and lead author of the JCO report.

“The long-term problems with cognitive development caused by traditional radiation therapy make this treatment unpopular among both physicians and parents,” Merchant said. “However, the improved outcomes we have seen in both disease control and intellectual development using CRT suggest that it might be possible to reintroduce the routine use of radiation therapy as a treatment option even for very young children.”

Merchant is currently principal investigator for a national trial of CRT for ependymoma based on the study’s findings. The trial is conducted by the Children’s Oncology Group.

CRT combines CAT scans and MRI to create pictures of the cancer that a computer then turns into three-dimensional images of the tumor exactly as it appears in the brain. These images are combined with computer-controlled radiation beams and meticulous positioning of the treatment table on which the patient lies. Radiation hits the tumor at precisely calculated angles and depths matching the 3-D image of the tumor, obliterating the cancer and sparing healthy tissue.

The median age of the 88 patients in the St. Jude study was 2.85 years, and 48 patients were younger than three years. According to Merchant, the inclusion of children younger than 3 years at the time of irradiation was unique, since children in this age group are at greatest risk of the effects of irradiation.

Before CRT, all patients underwent surgery to remove as much tumor as possible. Patients underwent testing of their cognitive abilities before CRT and again at six, 12, 24, 36, 48 and 60 months after start of radiation therapy. The tests varied according to age and included assessments of IQ, verbal memory and recall, academic achievement and other developmental skills that could be disrupted by radiation damage to the brain.

Merchant attributes the encouraging results of the study to three factors: 1) the large number of patients that underwent extensive surgery to remove most of the tumor before irradiation therapy; 2) the use of CRT to target tumors; and 3) the relatively high dose of radiation that could be used with CRT without jeopardizing healthy brain tissue.