PMID- 30496526 OWN - NLM STAT- MEDLINE DCOM- 20200819 LR - 20200827 IS - 1523-5866 (Electronic) IS - 1522-8517 (Print) IS - 1522-8517 (Linking) VI - 21 IP - 5 DP - 2019 May 6 TI - Financially effective test algorithm to identify an aggressive, EGFR-amplified variant of IDH-wildtype, lower-grade diffuse glioma. PG - 596-605 LID - 10.1093/neuonc/noy201 [doi] AB - BACKGROUND: Update 3 of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recognizes amplification of epidermal growth factor receptor (EGFR) as one important aberration in diffuse gliomas (World Health Organization [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, neuroradiographic features (Visually Accessible REMBRANDT Images [VASARI]), 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. For a cost-utility analysis we compared combined EGFR and isocitrate dehydrogenase (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 that 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 fluorescence in situ hybridization (FISH) testing for IDH-wildtype cases. Implementation would result in ~37.9% cost reduction at our institution, or about $1.3-4 million nationally. CONCLUSION: EGFR-amplified diffuse gliomas are "glioblastoma-like" in their behavior and may represent undersampled 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. CI - (c) The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Bale, Tejus A AU - Bale TA AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. AD - Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Jordan, Justin T AU - Jordan JT AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. AD - Department of Neurology, Boston, Massachusetts. AD - Division of Hematology/Oncology, Boston, Massachusetts. FAU - Rapalino, Otto AU - Rapalino O AD - Department of Radiology, Division of Neuroradiology, Boston, Massachusetts. FAU - Ramamurthy, Nisha AU - Ramamurthy N AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Jessop, Nicholas AU - Jessop N AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - DeWitt, John C AU - DeWitt JC AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Nardi, Valentina AU - Nardi V AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Alvarez, Maria Martinez-Lage AU - Alvarez MM AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Frosch, Matthew AU - Frosch M AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Batchelor, Tracy T AU - Batchelor TT AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. AD - Department of Neurology, Boston, Massachusetts. AD - Division of Hematology/Oncology, Boston, Massachusetts. FAU - Louis, David N AU - Louis DN AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Iafrate, A John AU - Iafrate AJ AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Cahill, Daniel P AU - Cahill DP AD - Department of Neurosurgery, Boston, Massachusetts. AD - Massachusetts General Hospital, Boston, Massachusetts. FAU - Lennerz, Jochen K AU - Lennerz JK AD - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - R01 CA225585/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Neuro Oncol JT - Neuro-oncology JID - 100887420 RN - 0 (Biomarkers, Tumor) RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM CIN - Neuro Oncol. 2019 May 6;21(5):559-561. PMID: 31059570 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - *Algorithms MH - Biomarkers, Tumor/*genetics MH - Brain Neoplasms/economics/genetics/pathology MH - Child MH - Child, Preschool MH - ErbB Receptors/genetics MH - Female MH - Follow-Up Studies MH - Glioma/*economics/genetics/*pathology MH - Humans MH - Isocitrate Dehydrogenase/*genetics MH - Male MH - Middle Aged MH - *Mutation MH - Neoplasm Grading MH - Phenotype MH - Retrospective Studies MH - Young Adult PMC - PMC6502496 OTO - NOTNLM OT - VASARI OT - WHO grade II/III OT - glioblastoma-like glioma EDAT- 2018/11/30 06:00 MHDA- 2020/08/20 06:00 PMCR- 2020/05/06 CRDT- 2018/11/30 06:00 PHST- 2018/11/30 06:00 [pubmed] PHST- 2020/08/20 06:00 [medline] PHST- 2018/11/30 06:00 [entrez] PHST- 2020/05/06 00:00 [pmc-release] AID - 5212363 [pii] AID - noy201 [pii] AID - 10.1093/neuonc/noy201 [doi] PST - ppublish SO - Neuro Oncol. 2019 May 6;21(5):596-605. doi: 10.1093/neuonc/noy201.