It is estimated that approximately 22,000 Americans will be diagnosed with tumor of the brain or nervous system in 2010. Among primary brain tumors, approximately 60% are gliomas, the most common and most malignant of which is glioblastoma multiforme (GBM).The DecisionDx-GBM test is a multigene expression assay that is designed to predict which patients are likely to experience long-term (> 2 years) progression-free survival.
In 2010, approximately 22,000 Americans will be diagnosed with a tumor of the brain or nervous system . Glioblastoma multiforme (GBM) are the most common primary brain tumors. GBMs are aggressive tumors and despite improvements in treatment regimens, which include surgical resection, radiation, and chemotherapy, prognosis is poor with a median survival of 14.6 months  Research has indicated that the genomes of GBMs have multiple changes including deletion of tumor suppressor genes and amplification or over-expression of tyrosine kinase receptors leading to both survival advantage and apoptosis resistance in tumor cells. Consequently, it has been suggested that any successful targeted therapy must take into account multiple genomic changes simultaneously  . The DecisionDx-GBM test is a multigene expression assay that is designed to predict which patients are likely to experience long-term (> 2 years) progression-free survival  .
The DecisionDx-GBM test uses formalin-fixed, paraffin-embedded (FFPE) tumor tissue. RNA is extracted from this specimen and used to measure the expression of 9 genes reported to be associated with survival including 7 genes correlated with decreased survival (aquaporin 1 [ AQP1 ], chitinase 3-like 1 [ CHI3L1 ], epithelial membrane protein 3 [ EMP-3 ], glycoprotein NMB [GPNMB], insulin-like growth factor-binding protein 2 [ IGFBP2 ], galectin 3 [ LGALS3 ] and podoplanin [ PDPN ]) and 2 genes associated with improved survival (oligodendrocyte lineage transcription factor 2 [ OLIG2 ] and reticulon 1 [ RTN1 ]) as well as 3 control genes (eukaryotic translation elongation factor 1, alpha-1 [ EEF1A1 ]; beta-glucoronidase [ GUSB ]; and ribosomal protein S27 [ RPS27 ])  . A proprietary algorithm is used to convert expression levels to a DecisionDx-GBM score, which is then compared to an underlying clinical database. Results are reported as both a DecisionDx-GBM score and a quintile rank compared to other patients in the database. The likelihood of 2-year survival is provided, along with the expected median survival and median progression-free survival    .
Public Health Importance
Although standard histo-pathological methods can accurately diagnosis GBM, no information on patient prognosis is provided. Having prognostic information may lead to a change in patient management such that more aggressive treatments are used earlier in patients with a poorer predicted prognosis. However, it is important to note that there have been no demonstrations that the use of a gene expression assay such as DecisionDx-GBM to guide management of patients with GBM results in improved patient outcomes.
Published Reviews, Recommendations and Guidelines
Systematic evidence reviews
Recommendations by independent group
Guidelines by professional groups
Analytic Validity : Test accuracy and reliability in measuring expression of 9 survival and 3 control genes (analytic sensitivity and specificity).
Clinical Validity : Test accuracy and reliability in accurately predicting patient prognosis (predictive value).
Clinical Utility : Net benefit of test in improving health outcomes
- Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma (NCT00884741)
- Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma (NCT00304031)
There is currently only a single peer-reviewed publication on the derivation and validation of this assay. No information is provided on the analytical validity of the assay. No studies on the clinical utility of this test in the care of patients with GBM have been published. Therefore, there is currently insufficient evidence to recommend adoption of this test for routine use in the care of patients with GBM.
Last updated:October 8, 2010
The authors would like to acknowledge the contributions of the members of the Hayes Genetic Test Evaluation team, particularly Lisa Spock, Linnie Wieselquist and Charlotte Kuo-Benitez.
Funding for the Health Technology Assessment that informed this work was provided by Hayes, Incorporated. Funding to create this Knol was provided by the Centers for Disease Control and Prevention under Contract No. 200-2009-F-32675.This funding was provided through the Genetic Alliance.
The authors are employees at Hayes, Inc., an independent health technology research and consulting company. None of the employees at this company has any financial or personal interest in any of the technologies reviewed by Hayes, Inc.. No input on report content or conclusions is permitted by manufacturers. Although the CDC funded the work to produce this article, the content is based entirely on Hayes, Inc.’s own analysis and there was no input from the CDC.
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