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

Richard Drexler; Ulrich Schueller; Alicia EckhardtKatharina FilipskiTabea I. HartungPatrick N. HarterIris DiveMarie-Therese ForsterMarcus CzabankaClaudius JelgersmaJulia OnkenPeter VajkoczyDavid CapperChristin SiewertThomas SauvignyKatrin LamszusManfred WestphalLasse DuehrsenFranz L. Ricklefs

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

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

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Background. DNA rnethylation-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.

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《Neuro-oncology》 |2023年第2期|315-325|共11页
作者
Richard Drexler; Ulrich Schueller; Alicia EckhardtKatharina FilipskiTabea I. HartungPatrick N. HarterIris DiveMarie-Therese ForsterMarcus CzabankaClaudius JelgersmaJulia OnkenPeter VajkoczyDavid CapperChristin SiewertThomas SauvignyKatrin LamszusManfred WestphalLasse DuehrsenFranz L. Ricklefs;
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Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

Department of Neuropathology, Charite- Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Chariteplatz 7, 70777 Berlin, Germany, German Cancer Consortium (DKTK), Partner Site Berlin, German Canc;

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany , Department of Pediatric Hematology and Oncology, Research Institute Children's Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, GermanDepartment of Pediatric Hematology and Oncology, Research Institute Children's Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Department of Radiation Hematology and Oncology, University Medical Center Hamburg-EppendoNeurological Institute (Edinger Institute), University Hospital, Frankfurt am Main, Germany, German Cancer Consortium (DKTK), Heidelberg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany, Frankfurt Cancer Institute (FCI), Frankfurt amNeurological Institute (Edinger Institute), University Hospital, Frankfurt am Main, GermanyDr. Senckenberg Institute of Neurooncology, University Hospital, Frankfurt am Main, GermanyDepartment of Neurosurgery, University Hospital, Frankfurt am Main, GermanyDepartment of Neurosurgery, Charite - Universitaetsmedizin Berlin, Berlin, Germany;

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DNA methylation; extent of resection; gbm; glioblastoma; glioma; subgroup;

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

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