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CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data

Homozygous CDKN2A/B deletion has been associated with an increased risk of recurrence in meningiomas. However, the evidence is confined to a limited number of studies, and the importance of heterozygous CDKN2A/B deletions remains insufficiently investigated. Hence, the present meta-analysis reconstr...

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Autores principales: Wach, Johannes, Basaran, Alim Emre, Arlt, Felix, Vychopen, Martin, Seidel, Clemens, Barrantes-Freer, Alonso, Müller, Wolf, Gaunitz, Frank, Güresir, Erdem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685484/
https://www.ncbi.nlm.nih.gov/pubmed/38017560
http://dx.doi.org/10.1186/s40478-023-01690-y
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author Wach, Johannes
Basaran, Alim Emre
Arlt, Felix
Vychopen, Martin
Seidel, Clemens
Barrantes-Freer, Alonso
Müller, Wolf
Gaunitz, Frank
Güresir, Erdem
author_facet Wach, Johannes
Basaran, Alim Emre
Arlt, Felix
Vychopen, Martin
Seidel, Clemens
Barrantes-Freer, Alonso
Müller, Wolf
Gaunitz, Frank
Güresir, Erdem
author_sort Wach, Johannes
collection PubMed
description Homozygous CDKN2A/B deletion has been associated with an increased risk of recurrence in meningiomas. However, the evidence is confined to a limited number of studies, and the importance of heterozygous CDKN2A/B deletions remains insufficiently investigated. Hence, the present meta-analysis reconstructs individual patient data (IPD) and reconstructs the probabilities of progression-free survival (PFS) stratified by CDKN2A/B status. IPD of PFS rates were extracted from published Kaplan–Meier plots using the R package IPDfromKM in R studio (RStudio, Boston, MA, USA). Reconstructed Kaplan–Meier Plots of the pooled IPD data were created. One-stage and two-stage meta-analyses were performed. Hazard ratios (HR) were used as effective measures. Of 181 records screened, four articles with 2521 participants were included. The prevalence of homozygous CDKN2A/B deletions in the included studies was 0.049 (95% CI 0.040–0.057), with higher tumor grades associated with a significantly greater proportion of CDKN2A/B deletions. The reconstructed PFS curves for the pooled cohort showed that the median PFS time of patients with a CDKN2A/B wild-type status, heterozygous or homozygous CDKN2A/B deletion was 180.0 (95% CI 145.7–214.3), 26.1 (95% CI 23.3–29.0), and 11.00 (95% CI 8.6–13.3) months, respectively (p < 0.0001). Both hetero- or homozygous CDKN2A/B deletions were significantly associated with shortened time to meningioma progression. One-stage meta-analysis showed that hetero- (HR: 5.5, 95% CI 4.0–7.6, p < 0.00001) and homozygous CDKN2A/B deletions (HR: 8.4, 95% CI 6.4–11.0, p < 0.00001) are significantly associated with shortened time to meningioma progression. Multivariable Cox regression analysis of progression in a subgroup with available covariates (age, sex, WHO grade, and TERT status) and also two-stage meta-analysis confirmed and validated the results of the one-stage analysis that both heterozygous and homozygous CDKN2A/B deletions are of prognostic importance. Further large-scale studies of WHO grade 2 and 3 meningiomas are needed to validate the importance of heterozygous CDKN2A/B deletions with consideration of established factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01690-y.
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spelling pubmed-106854842023-11-30 CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data Wach, Johannes Basaran, Alim Emre Arlt, Felix Vychopen, Martin Seidel, Clemens Barrantes-Freer, Alonso Müller, Wolf Gaunitz, Frank Güresir, Erdem Acta Neuropathol Commun Review Homozygous CDKN2A/B deletion has been associated with an increased risk of recurrence in meningiomas. However, the evidence is confined to a limited number of studies, and the importance of heterozygous CDKN2A/B deletions remains insufficiently investigated. Hence, the present meta-analysis reconstructs individual patient data (IPD) and reconstructs the probabilities of progression-free survival (PFS) stratified by CDKN2A/B status. IPD of PFS rates were extracted from published Kaplan–Meier plots using the R package IPDfromKM in R studio (RStudio, Boston, MA, USA). Reconstructed Kaplan–Meier Plots of the pooled IPD data were created. One-stage and two-stage meta-analyses were performed. Hazard ratios (HR) were used as effective measures. Of 181 records screened, four articles with 2521 participants were included. The prevalence of homozygous CDKN2A/B deletions in the included studies was 0.049 (95% CI 0.040–0.057), with higher tumor grades associated with a significantly greater proportion of CDKN2A/B deletions. The reconstructed PFS curves for the pooled cohort showed that the median PFS time of patients with a CDKN2A/B wild-type status, heterozygous or homozygous CDKN2A/B deletion was 180.0 (95% CI 145.7–214.3), 26.1 (95% CI 23.3–29.0), and 11.00 (95% CI 8.6–13.3) months, respectively (p < 0.0001). Both hetero- or homozygous CDKN2A/B deletions were significantly associated with shortened time to meningioma progression. One-stage meta-analysis showed that hetero- (HR: 5.5, 95% CI 4.0–7.6, p < 0.00001) and homozygous CDKN2A/B deletions (HR: 8.4, 95% CI 6.4–11.0, p < 0.00001) are significantly associated with shortened time to meningioma progression. Multivariable Cox regression analysis of progression in a subgroup with available covariates (age, sex, WHO grade, and TERT status) and also two-stage meta-analysis confirmed and validated the results of the one-stage analysis that both heterozygous and homozygous CDKN2A/B deletions are of prognostic importance. Further large-scale studies of WHO grade 2 and 3 meningiomas are needed to validate the importance of heterozygous CDKN2A/B deletions with consideration of established factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01690-y. BioMed Central 2023-11-28 /pmc/articles/PMC10685484/ /pubmed/38017560 http://dx.doi.org/10.1186/s40478-023-01690-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Wach, Johannes
Basaran, Alim Emre
Arlt, Felix
Vychopen, Martin
Seidel, Clemens
Barrantes-Freer, Alonso
Müller, Wolf
Gaunitz, Frank
Güresir, Erdem
CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data
title CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data
title_full CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data
title_fullStr CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data
title_full_unstemmed CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data
title_short CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data
title_sort cdkn2a/b deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685484/
https://www.ncbi.nlm.nih.gov/pubmed/38017560
http://dx.doi.org/10.1186/s40478-023-01690-y
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