WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas
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 ( ) mutation has recently been questioned. We stud...
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| Published in | Frontiers in oncology Vol. 11; p. 803975 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
Frontiers Media S.A
10.01.2022
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2234-943X 2234-943X |
| DOI | 10.3389/fonc.2021.803975 |
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| Abstract | 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
(
) 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.
A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed.
mutations, codeletion of chromosomal arms 1p/19q, and
deletions were analyzed.
There was no survival benefit for patients with WHO grade 2 over grade 3
-mut dLGG after exclusion of tumors with known
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
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).
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
-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in
-mut astrocytomas only. The age cutoffs for determining high risk in patients with
-mut dLGG from the pre-molecular era are not supported by our results. |
|---|---|
| AbstractList | 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. 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.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.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).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. BackgroundWhile 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 MethodsA 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.ResultsThere 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).ConclusionOur 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. 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.BACKGROUNDWhile 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.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.MATERIAL AND METHODSA 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.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).RESULTSThere 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).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.CONCLUSIONOur 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. 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 ( ) 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. A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. mutations, codeletion of chromosomal arms 1p/19q, and deletions were analyzed. There was no survival benefit for patients with WHO grade 2 over grade 3 -mut dLGG after exclusion of tumors with known 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 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). 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 -mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in -mut astrocytomas only. The age cutoffs for determining high risk in patients with -mut dLGG from the pre-molecular era are not supported by our results. |
| Author | Dénes, Anna Jakola, Asgeir Store Barchéus, Hanna Bontell, Thomas Olsson Sjögren, Helene Carstam, Louise Ferreyra Vega, Sandra Carén, Helena Corell, Alba Smits, Anja Modin, Klara |
| AuthorAffiliation | 3 Department of Neurology, Sahlgrenska University Hospital , Gothenburg , Sweden 1 Department of Neurosurgery, Sahlgrenska University Hospital , Gothenburg , Sweden 7 Department of Neurosurgery, St. Olavs University Hospital , Trondheim , Norway 4 Clinical Genetics and Genomics, Sahlgrenska University Hospital , Gothenburg , Sweden 5 Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden 2 Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden 6 Department of Clinical Pathology and Cytology, Sahlgrenska University Hospital , Gothenburg , Sweden |
| AuthorAffiliation_xml | – name: 5 Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden – name: 7 Department of Neurosurgery, St. Olavs University Hospital , Trondheim , Norway – name: 2 Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden – name: 3 Department of Neurology, Sahlgrenska University Hospital , Gothenburg , Sweden – name: 6 Department of Clinical Pathology and Cytology, Sahlgrenska University Hospital , Gothenburg , Sweden – name: 4 Clinical Genetics and Genomics, Sahlgrenska University Hospital , Gothenburg , Sweden – name: 1 Department of Neurosurgery, Sahlgrenska University Hospital , Gothenburg , Sweden |
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| Copyright | Copyright © 2022 Carstam, Corell, Smits, Dénes, Barchéus, Modin, Sjögren, Ferreyra Vega, Bontell, Carén and Jakola. Copyright © 2022 Carstam, Corell, Smits, Dénes, Barchéus, Modin, Sjögren, Ferreyra Vega, Bontell, Carén and Jakola 2022 Carstam, Corell, Smits, Dénes, Barchéus, Modin, Sjögren, Ferreyra Vega, Bontell, Carén and Jakola |
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| Keywords | IDH-mut oligodendroglioma astrocytoma extent of resection lower-grade glioma prognostic factors WHO grade CDKN2A/B deletion |
| Language | English |
| License | Copyright © 2022 Carstam, Corell, Smits, Dénes, Barchéus, Modin, Sjögren, Ferreyra Vega, Bontell, Carén and Jakola. 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. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Giuseppe Minniti, University of Pittsburgh Medical Center, United States Reviewed by: Maarten Wijnenga, Erasmus Medical Center, Netherlands; Makoto Ohno, National Cancer Center Hospital, Japan This article was submitted to Neuro-Oncology and Neurosurgical Oncology, a section of the journal Frontiers in Oncology |
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| Snippet | While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come... Background: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic... BackgroundWhile molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic... |
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| SubjectTerms | astrocytoma Cancer and Oncology Cancer och onkologi CDKN2A/B deletion extent of resection IDH-mut Kirurgi lower-grade glioma Neurologi Neurology oligodendroglioma Oncology prognostic factors Surgery WHO grade |
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| Title | WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas |
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