Financially Effective Test-Algorithm to Identify an Aggressive, EGFR-amplified Variant of IDH-Wildtype, Lower-Grade Diffuse Glioma.

Financially Effective Test-Algorithm to Identify an Aggressive, EGFR-amplified Variant of IDH-Wildtype, Lower-Grade Diffuse Glioma.

Neuro Oncol. 2018 Nov 28;:

Authors: Bale TA, Jordan JT, Rapalino O, Ramamurthy N, Jessop N, DeWitt JC, Nardi V, Martinez-Lage Alvarez M, Frosch M, Batchelor TT, Louis DN, Iafrate AJ, Cahill DP, Lennerz JK

Abstract
Background: cIMPACT-NOW update 3 recognizes amplification of EGFR as one important aberration in diffuse gliomas (WHO grade II/III). While these recommendations endorse testing, a cost-effective, clinically relevant testing paradigm is currently lacking. Here, we use real-world clinical data to propose a financially effective diagnostic test-algorithm in the context of new guidelines.
Methods: To determine the prevalence, distribution, neuro-radiographic (VASARI) features, and prognostic relevance of EGFR amplification in lower-grade gliomas, we assembled a consecutive series of diffuse gliomas. For validation we included publicly available data from The Cancer Genome Atlas (TCGA) and for a cost-utility analysis we compared: combined EGFR and IDH testing, EGFR testing based on IDH results, and no EGFR testing.
Results: In n=71 WHO grade II/III gliomas, we identified EGFR amplification in 28.2%. With one exception, all EGFR amplifications occurred in IDH-wildtype gliomas. Comparison of overall survival showed EGFR amplification denotes a significantly more aggressive subset of tumors (P<0.0001, log-rank). The radiologic phenotype in the EGFR amplified tumors includes diffusion restriction (15%, P=0.02), >5% tumor contrast enhancement (75%, P=0.016), and mild (not avid) enhancement (P=0.016).. The proposed testing algorithm reserves EGFR fluorescent in situ hybridization (FISH) testing to IDH wildtype cases. Implementation would result in ~37.9% cost reduction at our institution or ~1.3-4 Million USD nationally.
Conclusion: EGFR amplified diffuse gliomas are 'glioblastoma-like' in their behavior and may represent under-sampled glioblastomas, or subsets of IDH-wildtype diffuse gliomas with inherently aggressive biology. EGFR FISH after IDH testing is a financially effective and clinically relevant test-algorithm for routine clinical practice.

PMID: 30496526 [PubMed - as supplied by publisher]

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