DecisionDx-G-CIMP

Product Information

The World Health Organization (WHO) classification system for central nervous system tumors is used to guide treatment and establish prognosis. Grades range from Grade 1 to Grade 4; the higher the grade, the more advanced and aggressive the tumor, which usually means a poorer prognosis.

Studies Show Significant Inter-Observer and Intra-Observer Grading Variances in Glioma
Study # patients Reviewers Variance
Bruner ’97 (retrospective) 500 4 neuropath 43%
Aldape ‘00 (retrospective) 457 academic vs community 23%
Coons ‘97 (prospective) 244/315 4 neuropath 48%
Hillebrand ’08 (prospective) 193 Local vs central path 53% not confirmed by central path
van den Bent ‘06 (prospective) 314 Local vs central path 74% not confirmed by central path

Standard of care treatment plans are different for patients diagnosed with WHO grade 2, 3, or 4 gliomas (van den Bent, 2010).

Tumor type Standard of care
Oligodendroglial tumors Initial mngt with upfront chemotx widely accepted, regardless of grade
Low grade gliomas RT 45-55 Gy, higher dosages of RT correlate with toxicity, unproven role for upfront chemotx alone
Grade III tumors RT 60 Gy, value of adjuvant chemotx and of combined chemotx-RT unproven
GBM Combined chemotx-RT (60 Gy) with TMZ

The Need for DecisionDx-G-CIMP

It is well-recognized that there is clinically significant inter-observer and intra-observer variability in the diagnosis and grading of gliomas. For example, one study evaluated a systematic series on a cohort of 500 brain tumor patients and found some degree of disagreement in 43% of cases (Bruner, et al). A prospective study on 244 cases reviewed by 4 neuro-pathologists reported a diagnostic inter-observer variability rate of 48% with the first review (Coons, et al).

Because the grade of glioma (among other factors) establishes prognosis and treatment planning, this variability has a direct impact on patient care decisions. For example, patients with tumor biology similar to a grade 3 tumor may receive a grade 2 histopathologic designation. This difference would likely result in under-treatment for that patient's glioma. Likewise, a patient with grade 2 tumor biology who was diagnosed with a histopathologic grade 3 would likely be relatively in over-treated (van den Bent).

While it remains a clinical issue, inter-observer variability is less with grade 4 tumors. However, there is a subset of approximately 5% of grade 4 tumors that are secondary tumors. That is, these grade 4 gliomas are believed to have progressed to grade 4 from grade 2 or 3. These tumors exhibit longer survival times than patients with primary grade 4 gliomas.

Knowing that histology does not necessarily reflect biology, it would be advantageous to incorporate molecular profiling data along with the histopathologic diagnosis to assemble a more complete and accurate picture of expected tumor behavior and prognosis. This information in turn provides foundation for the most appropriate individual treatment plan.

What is DecisionDx-G-CIMP?

The DecisionDx-G-CIMP CIMP profile test is a robust, proprietary multi-methylation test that determines the glioma-CpG island methylator phenotype (G-CIMP) of grade 2, 3 or 4 gliomas.

The DecisionDx-G-CIMP CIMP profile was discovered using 272 glioma samples from The Cancer Genome Altas project (TCGA). The TCGA is an initiative of the National Cancer Institute (NCI). The profile was then validated on more than 486 grade 2, 3, and 4 glioma samples. More recently, the DecisionDx-G-CIMP test has been prospectively validated as a secondary endpoint in the multi-center Radiation Therapy Oncology Group 0525 study (RTOG-0525). The DecisionDx-G-CIMP test has achieved the National Comprehensive Cancer Network (NCCN) Level of Evidence “2B”. The DecisionDx-G-CIMP test is intended to be used in conjunction with WHO grade and other clinical factors in determining the appropriate treatment plan for an individual patient.

The DecisionDx-G-CIMP molecular profile is also called CIMP glioma. The CIMP glioma profile (CIMP+ or CIMP-) is robustly associated with prognosis in glioma patients with a histopathology grade of 2, 3, or 4. Patients with a CIMP+ glioma show a favorable prognosis. This favorable prognostic profile cannot be detected with histopathology alone. The DecisionDx-G-CIMP CIMP glioma profile is an independent predictor of survival, even after adjustment for grade and age (p<0.0003).

The DecisionDx-G-CIMP test is intended to be used in conjunction with WHO grade and other clinical factors in determining the appropriate treatment plan for an individual patient.

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