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St Jude researchers show that young children respond better to DPG treatment

St. Jude Childrens Research Hospital : 30 May, 2008  (Company News)
St Jude Children's Research Hospital researchers have shown that children under three years old who have a diffuse pontine glioma (DPG) brain tumour 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 three years with DPG can potentially respond better to treatment than older children,' said Alberto Broniscer, MD, assistant member in the St Jude Department of Oncology and the paper's first author. '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 tumour that occurs in the brainstem - and other tumours, which originate in the same area with a better prognosis.'

The researchers reviewed the medical records of 10 patients under three years of age with DPG. 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 tumours. Based on these findings, the St Jude team calculates that 45 percent of children under three years treated for DPG will survive for at least three years without experiencing tumour growth, and 69 percent of such children will survive.

From these results, the investigators concluded that distinct biological characteristics of DPG in children under three 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 the cerebrum seem to have a better prognosis when compared to 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 tumours in children; and DPGs account for 80 percent of brainstem tumors in childhood. Although MRI revolutionised the diagnosis of DPG, no significant improvements have occurred in its treatment in children during the past 20 years, according to St Jude researchers. 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 tumour 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 tumour,' Broniscer said.

Other authors of the paper include Fred H Laningham, Larry E Kun, David W Ellison and Amar Gajjar (St Jude) and Robert P Sanders (formerly of St Jude).

The 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.

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