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Clin Cancer Res. 2019 Jan 11. pii: clincanres.3101.2018. doi: 10.1158/1078-0432.CCR-18-3101. [Epub ahead of print]

The Misclassification of Diffuse Gliomas: Rates and Outcomes.

Author information

1
Pathology, Brigham and Women's Hospital jiorgulescu@bwh.harvard.edu.
2
Pathology, Brigham and Women's Hospital.
3
Neurosurgery, Brigham and Women's Hospital.
4
Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center.
5
Center for Neuro-Oncology, Dana-Farber Cancer Institute.
6
General Medical Sciences-Oncology, Case Western Reserve University.
7
Department of Neurological Surgery, University of California, San Francisco.

Abstract

BACKGROUND:

The integrated histopathological and molecular diagnoses of the 2016 WHO classification of CNS tumors have revolutionized patient care by improving diagnostic accuracy and reproducibility; however, the frequency and consequences of misclassification of histologically-diagnosed diffuse gliomas are unknown.

METHODS:

Patients with newly-diagnosed ICD-O-3 histologically-encoded diffuse gliomas from 2010-2015 were identified from the National Cancer Database-the misclassification rates and overall survival (OS) of which were assessed by WHO grade and 1p/19q status. Additionally, misclassification rates by IDH, ATRX, and p53 statuses were examined in an analogous multi-institutional cohort of registry-encoded diffuse gliomas.

RESULTS:

Of 74,718 diffuse glioma patients, only 74.4% and 78.8% of molecularly-characterized WHO grade II and III oligodendrogliomas were in fact 1p/19q-codeleted. Additionally, 28.9% and 36.8% of histologically-encoded grade II and III "oligoastrocytomas", and 6.3% and 8.8% of grade II and III astrocytomas had 1p/19q-codeletion, thus molecularly representing oligodendrogliomas if also IDH-mutant. OS significantly depended on accurate WHO grading and 1p/19q status.

CONCLUSIONS:

Based on 1p/19q, IDH, ATRX, and p53, the misclassification rates of histologically-encoded oligodendrogliomas, astrocytomas, and glioblastomas are ~21-35%, ~6-9%, and ~9%, respectively; with significant clinical implications. Our findings suggest that when compared to historical histology-only classified data-in national registry, as well as, institutional databases-there is the potential for false-positive results in contemporary trials of molecularly-classified diffuse gliomas, which could contribute to a seemingly positive phase II trial (based on historical comparison) failing at the phase III stage. Critically, findings from diffuse glioma clinical trials and historical cohorts using prior histology-only WHO schemes must be cautiously re-interpreted.

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