Funding Agency:

Brain Tumor Society

Total Project Period:

6/1/07 - 5/31/09

Total Project Award:

$199,946

Principal Investigator:

Ian F. Pollack, MD

Co-Investigators:

Ronald Hamilton, MD

Project Summary:

Low-grade gliomas are the most common brain tumors in children. Affected patients have a widely variable prognosis. While most children with cerebellar and superficial cerebral lesions are cured with gross total resection, lesions in deep sites, such as the hypothalamus and brainstem, rarely can be removed and carry high risks for recurrence and morbidity. To date, there has been a paucity of data regarding molecular or biological factors associated with outcome and insights regarding therapeutic targets have been lacking. Although some studies have noted that histology, proliferation markers, expression of genetic alterations, and other biological factors are associated with outcome, such results have been controversial and no consistent panel of markers has been identified that facilitates prognostic or therapeutic stratification.

One of the challenges hampering previous studies for these tumors is that most correlative analyses have been comprised mainly of extensively resected cerebellar and cerebral lesions. Such tumors have the most favorable prognosis and, accordingly, may fail to yield meaningful insights regarding prognostic variables and therapeutic targets for the large group of deep-seated, unresectable lesions for which biological material has been more limited. To address this limitation, the current study takes advantage of a sizeable cohort of pediatric low-grade gliomas at our institution for which biological material at diagnosis is available. This group includes more than 400 cases with matched histological material and outcome data extending in some cases for more than 20 years. Although a number of these cases have been analyzed ad hoc for various biological correlates, there have never been available funds to examine this unique resource in a systematic fashion, using the broad panel of genotyping and phenotyping technology that we have extensively applied for pediatric high-grade gliomas, as noted in our preliminary studies. The studies included in this submission are designed to address this issue. We will evaluate 100 “favorable-risk” (e.g., grossly resected) tumors in parallel with 100 “higher-risk” (midline unresectable) lesions. This analysis should have sufficient statistical power to identify meaningful prognostic associations, and would provide new insights into biological correlates of prognosis in pediatric gliomas and therapeutic targets to improve the chances for curing these tumors.