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St. Jude investigators have shown that children under 3 years old who have a brain tumor called diffuse pontine glioma (DPG) appear to have a better outcome than older children with the same cancer.
Results of the study, which appear in the advance, online publication of the journal Cancer, are important because clinicians have long believed that DPG was universally fatal. Moreover, it was assumed that clinicians had simply misdiagnosed the disease in children who responded to treatment and survived.
“Our findings show that children under 3 years with DPG can potentially respond better to treatment than older children,” said the paper’s first author, Alberto Broniscer, MD, Oncology. “Unlike other previous studies in young children where the diagnosis of DPG was based on either CT scans or magnetic resonance imaging (MRI), the diagnosis of all our patients was based on MRI only. CT scans are not able to differentiate between DPG—a tumor that occurs in the brainstem—and other tumors, which originate in the same area with a better prognosis.”
The researchers reviewed the medical records of 10 patients with DPG who were under 3 years of age. The median age of these patients was 2.2 years, and the median time between symptom development and actual diagnosis was 2.5 months. All children had the diagnosis of DPG based on radiological review of their MRIs at diagnosis.
All of the children received treatment—two with radiation, six with radiation plus chemotherapy, and two with chemotherapy only. Four of the children died, but six have survived for at least two years following this therapy, which is ineffective in older children with similar tumors. Based on these findings, the St. Jude team calculates that 45 percent of children under age 3 treated for DPG will survive for at least three years without experiencing tumor growth, and 69 percent of such children will survive.
From these results, the investigators concluded that distinct biological characteristics of DPG in children under 3 years compared to older children might account for their better response to radiation and chemotherapy. The researchers point to a similar finding with a type of glioma that originates in the cerebrum: Young children with high-grade gliomas originating in that area seem to have better prognoses than older children. Different biological properties also seem to play a role in the latter case.
Brainstem gliomas account for 10 to 15 percent of all brain tumors in children, and DPGs account for 80 percent of brainstem tumors in childhood. Although MRI revolutionized the diagnosis of DPG, no significant improvements have occurred in its treatment in children during the past 20 years. The long-term survival of children with DPG has remained less than 10 percent, despite treatment with radiation and chemotherapy.
The St. Jude team is now collecting tumor samples and performing extensive molecular analyses in order to gain a better understanding of the biology of DPGs in children.
“We believe that the more we learn about DPGs, the more likely we will be able to design more effective treatments for children of all ages with this tumor,” Broniscer said.
Other authors of the paper include Fred Laningham, MD, Radiological Sciences; Larry Kun, MD, Radiological Sciences chair; David Ellison, MD, PhD, Pathology; Amar Gajjar, Oncology co-chair; and Robert Sanders, MD, formerly of St. Jude.
This work was supported by a Cancer Center Support CORE grant from the National Institutes of Health, Musicians Against Childhood Cancer, the Noyes Brain Tumor Foundation, the Ryan McGhee Foundation and ALSAC.