DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients

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DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients. / Drexler, Richard; Schüller, Ulrich; Eckhardt, Alicia; Filipski, Katharina; Hartung, Tabea I; Harter, Patrick N; Divé, Iris; Forster, Marie-Therese; Czabanka, Marcus; Jelgersma, Claudius; Onken, Julia; Vajkoczy, Peter; Capper, David; Siewert, Christin; Sauvigny, Thomas; Lamszus, Katrin; Westphal, Manfred; Dührsen, Lasse; Ricklefs, Franz L.

in: NEURO-ONCOLOGY, Jahrgang 25, Nr. 2, 14.02.2023, S. 315-325.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Drexler, R, Schüller, U, Eckhardt, A, Filipski, K, Hartung, TI, Harter, PN, Divé, I, Forster, M-T, Czabanka, M, Jelgersma, C, Onken, J, Vajkoczy, P, Capper, D, Siewert, C, Sauvigny, T, Lamszus, K, Westphal, M, Dührsen, L & Ricklefs, FL 2023, 'DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients', NEURO-ONCOLOGY, Jg. 25, Nr. 2, S. 315-325. https://doi.org/10.1093/neuonc/noac177

APA

Drexler, R., Schüller, U., Eckhardt, A., Filipski, K., Hartung, T. I., Harter, P. N., Divé, I., Forster, M-T., Czabanka, M., Jelgersma, C., Onken, J., Vajkoczy, P., Capper, D., Siewert, C., Sauvigny, T., Lamszus, K., Westphal, M., Dührsen, L., & Ricklefs, F. L. (2023). DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients. NEURO-ONCOLOGY, 25(2), 315-325. https://doi.org/10.1093/neuonc/noac177

Vancouver

Bibtex

@article{9213571b69cc4b3b9be4f17c730e078f,
title = "DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients",
abstract = "BACKGROUND: DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive.METHODS: Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as a surgical benefit for recurrent glioblastoma.RESULTS: 345 patients (80.2%) fulfilled the inclusion criteria and 305 patients received combined adjuvant therapy. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (RTK I: Ref.; RTK II: HR 0.9 [95% CI, 0.64-1.28]; p = 0.56; MES: 0.69 [0.47-1.02]; p = 0.06). Patients with RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36-6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80-9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68-3.09]; p = 0.33). Therapy response predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19-0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34-0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27-1.02]; p = 0.06). For local recurrence (n = 112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33).CONCLUSION: We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.",
author = "Richard Drexler and Ulrich Sch{\"u}ller and Alicia Eckhardt and Katharina Filipski and Hartung, {Tabea I} and Harter, {Patrick N} and Iris Div{\'e} and Marie-Therese Forster and Marcus Czabanka and Claudius Jelgersma and Julia Onken and Peter Vajkoczy and David Capper and Christin Siewert and Thomas Sauvigny and Katrin Lamszus and Manfred Westphal and Lasse D{\"u}hrsen and Ricklefs, {Franz L}",
note = "{\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2023",
month = feb,
day = "14",
doi = "10.1093/neuonc/noac177",
language = "English",
volume = "25",
pages = "315--325",
journal = "NEURO-ONCOLOGY",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients

AU - Drexler, Richard

AU - Schüller, Ulrich

AU - Eckhardt, Alicia

AU - Filipski, Katharina

AU - Hartung, Tabea I

AU - Harter, Patrick N

AU - Divé, Iris

AU - Forster, Marie-Therese

AU - Czabanka, Marcus

AU - Jelgersma, Claudius

AU - Onken, Julia

AU - Vajkoczy, Peter

AU - Capper, David

AU - Siewert, Christin

AU - Sauvigny, Thomas

AU - Lamszus, Katrin

AU - Westphal, Manfred

AU - Dührsen, Lasse

AU - Ricklefs, Franz L

N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2023/2/14

Y1 - 2023/2/14

N2 - BACKGROUND: DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive.METHODS: Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as a surgical benefit for recurrent glioblastoma.RESULTS: 345 patients (80.2%) fulfilled the inclusion criteria and 305 patients received combined adjuvant therapy. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (RTK I: Ref.; RTK II: HR 0.9 [95% CI, 0.64-1.28]; p = 0.56; MES: 0.69 [0.47-1.02]; p = 0.06). Patients with RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36-6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80-9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68-3.09]; p = 0.33). Therapy response predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19-0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34-0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27-1.02]; p = 0.06). For local recurrence (n = 112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33).CONCLUSION: We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.

AB - BACKGROUND: DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive.METHODS: Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as a surgical benefit for recurrent glioblastoma.RESULTS: 345 patients (80.2%) fulfilled the inclusion criteria and 305 patients received combined adjuvant therapy. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (RTK I: Ref.; RTK II: HR 0.9 [95% CI, 0.64-1.28]; p = 0.56; MES: 0.69 [0.47-1.02]; p = 0.06). Patients with RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36-6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80-9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68-3.09]; p = 0.33). Therapy response predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19-0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34-0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27-1.02]; p = 0.06). For local recurrence (n = 112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33).CONCLUSION: We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.

U2 - 10.1093/neuonc/noac177

DO - 10.1093/neuonc/noac177

M3 - SCORING: Journal article

C2 - 35868257

VL - 25

SP - 315

EP - 325

JO - NEURO-ONCOLOGY

JF - NEURO-ONCOLOGY

SN - 1522-8517

IS - 2

ER -