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A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy

PURPOSE: Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As mo...

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Autores principales: Steidl, Eike, Filipski, Katharina, Zeiner, Pia S., Wagner, Marlies, Fokas, Emmanouil, Forster, Marie-Therese, Ronellenfitsch, Michael W., Divé, Iris, Steinbach, Joachim P., Harter, Patrick N., Bähr, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236451/
https://www.ncbi.nlm.nih.gov/pubmed/33538917
http://dx.doi.org/10.1007/s00432-021-03511-y
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author Steidl, Eike
Filipski, Katharina
Zeiner, Pia S.
Wagner, Marlies
Fokas, Emmanouil
Forster, Marie-Therese
Ronellenfitsch, Michael W.
Divé, Iris
Steinbach, Joachim P.
Harter, Patrick N.
Bähr, Oliver
author_facet Steidl, Eike
Filipski, Katharina
Zeiner, Pia S.
Wagner, Marlies
Fokas, Emmanouil
Forster, Marie-Therese
Ronellenfitsch, Michael W.
Divé, Iris
Steinbach, Joachim P.
Harter, Patrick N.
Bähr, Oliver
author_sort Steidl, Eike
collection PubMed
description PURPOSE: Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study. METHODS: We identified 343 patients (1995–2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS. RESULTS: IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p < 0.01) but not for oligodendroglioma (p = 0.27). Chemotherapy (and temozolomide in particular) showed inferior OS compared to radiotherapy in astrocytomas (median 6.1/12.1 years; p = 0.03) and oligodendrogliomas (median 13.2/not reached (n.r.) years; p = 0.03). While radiochemotherapy improved TTF in oligodendroglioma (median radiochemotherapy n.r./chemotherapy 3.8/radiotherapy 7.3 years; p < 0.001/ = 0.06; OS data immature) the effect, mainly in combination with temozolomide, was weaker in astrocytomas (median radiochemotherapy 6.7/chemotherapy 2.3/radiotherapy 2.0 years; p < 0.001/ = 0.11) and did not translate to improved OS (median 8.4 years). CONCLUSION: This is one of the largest retrospective, real-life datasets reporting treatment and outcome in low-grade gliomas incorporating molecular markers. Current histologic grading features remain prognostic in astrocytomas while being insignificant in oligodendroglioma with interfering treatment effects. Chemotherapy (temozolomide) was less effective than radiotherapy in both astrocytomas and oligodendrogliomas while radiochemotherapy showed the highest TTF in oligodendrogliomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-021-03511-y.
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spelling pubmed-82364512021-07-09 A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy Steidl, Eike Filipski, Katharina Zeiner, Pia S. Wagner, Marlies Fokas, Emmanouil Forster, Marie-Therese Ronellenfitsch, Michael W. Divé, Iris Steinbach, Joachim P. Harter, Patrick N. Bähr, Oliver J Cancer Res Clin Oncol Original Article – Clinical Oncology PURPOSE: Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study. METHODS: We identified 343 patients (1995–2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS. RESULTS: IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p < 0.01) but not for oligodendroglioma (p = 0.27). Chemotherapy (and temozolomide in particular) showed inferior OS compared to radiotherapy in astrocytomas (median 6.1/12.1 years; p = 0.03) and oligodendrogliomas (median 13.2/not reached (n.r.) years; p = 0.03). While radiochemotherapy improved TTF in oligodendroglioma (median radiochemotherapy n.r./chemotherapy 3.8/radiotherapy 7.3 years; p < 0.001/ = 0.06; OS data immature) the effect, mainly in combination with temozolomide, was weaker in astrocytomas (median radiochemotherapy 6.7/chemotherapy 2.3/radiotherapy 2.0 years; p < 0.001/ = 0.11) and did not translate to improved OS (median 8.4 years). CONCLUSION: This is one of the largest retrospective, real-life datasets reporting treatment and outcome in low-grade gliomas incorporating molecular markers. Current histologic grading features remain prognostic in astrocytomas while being insignificant in oligodendroglioma with interfering treatment effects. Chemotherapy (temozolomide) was less effective than radiotherapy in both astrocytomas and oligodendrogliomas while radiochemotherapy showed the highest TTF in oligodendrogliomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-021-03511-y. Springer Berlin Heidelberg 2021-02-04 2021 /pmc/articles/PMC8236451/ /pubmed/33538917 http://dx.doi.org/10.1007/s00432-021-03511-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article – Clinical Oncology
Steidl, Eike
Filipski, Katharina
Zeiner, Pia S.
Wagner, Marlies
Fokas, Emmanouil
Forster, Marie-Therese
Ronellenfitsch, Michael W.
Divé, Iris
Steinbach, Joachim P.
Harter, Patrick N.
Bähr, Oliver
A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy
title A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy
title_full A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy
title_fullStr A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy
title_full_unstemmed A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy
title_short A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy
title_sort 25-year retrospective, single center analysis of 343 who grade ii/iii glioma patients: implications for grading and temozolomide therapy
topic Original Article – Clinical Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236451/
https://www.ncbi.nlm.nih.gov/pubmed/33538917
http://dx.doi.org/10.1007/s00432-021-03511-y
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