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 is, which usuallly means a poorer prognosis.
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-LGG
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).
As the grade of glioma establishes prognosis and treatment planning, this variability has a direct impact on patient care decisions. For example, patients with a grade 3 tumor may receive a grade 2 diagnosis. This difference would likely result in under-treatment for that patient's glioma. Likewise, a patient with a grade 3 tumor who was diagnosed with a grade 4 tumor (also known as a glioblastoma) would likely result in over-treatment (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.
It would be advantageous to incorporate molecular profiling data along with the histopathologic diagnosis to provide more accurate data on expected prognosis for more appropriate individual treatment planning.
What is DecisionDx-LGG?
The DecisionDx-LGG CIMP profile assay is a robust, proprietary multi-methylation assay that determines the glioma-CpG island methylator phenotype (G-CIMP) of grade 2, 3 or 4 gliomas.
The DecisionDx-LGG CIMP profile assay was discovered and developed using 272 glioma samples from The Cancer Genome Altas project (TCGA). The TCGA is an initiative of the National Cancer Institute (NCI). The assay was then validated on more than 486 grade 2, 3, and 4 glioma samples.
The DecisionDx-LGG assay identifies a molecular profile called CIMP. The CIMP 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-LGG CIMP profile is an independent predictor of survival, even after adjustment for grade and age (p<0.0003).