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WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas
BACKGROUND: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutatio...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785215/ https://www.ncbi.nlm.nih.gov/pubmed/35083156 http://dx.doi.org/10.3389/fonc.2021.803975 |
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author | Carstam, Louise Corell, Alba Smits, Anja Dénes, Anna Barchéus, Hanna Modin, Klara Sjögren, Helene Ferreyra Vega, Sandra Bontell, Thomas Olsson Carén, Helena Jakola, Asgeir Store |
author_facet | Carstam, Louise Corell, Alba Smits, Anja Dénes, Anna Barchéus, Hanna Modin, Klara Sjögren, Helene Ferreyra Vega, Sandra Bontell, Thomas Olsson Carén, Helena Jakola, Asgeir Store |
author_sort | Carstam, Louise |
collection | PubMed |
description | BACKGROUND: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting. MATERIAL AND METHODS: A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed. RESULTS: There was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01–1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00–1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00–1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01–1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08). CONCLUSION: Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results. |
format | Online Article Text |
id | pubmed-8785215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87852152022-01-25 WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas Carstam, Louise Corell, Alba Smits, Anja Dénes, Anna Barchéus, Hanna Modin, Klara Sjögren, Helene Ferreyra Vega, Sandra Bontell, Thomas Olsson Carén, Helena Jakola, Asgeir Store Front Oncol Oncology BACKGROUND: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting. MATERIAL AND METHODS: A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed. RESULTS: There was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01–1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00–1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00–1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01–1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08). CONCLUSION: Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results. Frontiers Media S.A. 2022-01-10 /pmc/articles/PMC8785215/ /pubmed/35083156 http://dx.doi.org/10.3389/fonc.2021.803975 Text en Copyright © 2022 Carstam, Corell, Smits, Dénes, Barchéus, Modin, Sjögren, Ferreyra Vega, Bontell, Carén and Jakola https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Carstam, Louise Corell, Alba Smits, Anja Dénes, Anna Barchéus, Hanna Modin, Klara Sjögren, Helene Ferreyra Vega, Sandra Bontell, Thomas Olsson Carén, Helena Jakola, Asgeir Store WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas |
title | WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas |
title_full | WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas |
title_fullStr | WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas |
title_full_unstemmed | WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas |
title_short | WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas |
title_sort | who grade loses its prognostic value in molecularly defined diffuse lower-grade gliomas |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785215/ https://www.ncbi.nlm.nih.gov/pubmed/35083156 http://dx.doi.org/10.3389/fonc.2021.803975 |
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