{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:50:19Z","timestamp":1768549819314,"version":"3.49.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011176","name":"Peking Union Medical College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011176","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>The aim of this study is to investigate whether the therapeutic efficacy of bevacizumab (BEV) in the treatment of high-grade glioma (HGG) is associated with the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) on the basis of excluding the interference from chemotherapy drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included 57 patients with histologically confirmed HGG who, due to various reasons, were unable to complete the standard chemotherapy protocol and thus received BEV treatment. Patients enrolled in the study were divided into two groups based on their MGMT status: the unmethylated MGMT group and the methylated MGMT group. Depending on whether the numerical variables of the patients satisfied a normal distribution, either the T-test or the rank-sum test was employed. For the comparison of categorical variables, the chi-square test was used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After BEV treatment, both PFS and OS were higher in the methylated MGMT group compared to the unmethylated group. Additionally, the tumor control rate was also higher in the methylated group. Furthermore, in both patient groups, a decrease in steroid dosage was observed following BEV treatment, accompanied by an increase in KPS. Multivariate COX regression analysis revealed that radiotherapy and complete tumor resection were significant factors influencing PFS and OS in HGG patients. Additionally, pathological grade was found to influence PFS in HGG patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on the exclusion of the interference from chemotherapy drugs, our study is the first to confirm the correlation between the methylation status of MGMT and the therapeutic effect of BEV on HGG.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1644934","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T05:33:42Z","timestamp":1756791222000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Correlation between MGMT methylation and the efficacy of bevacizumab in high-grade glioma"],"prefix":"10.3389","volume":"15","author":[{"given":"Chengrui","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuexue","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30874","article-title":"A phase 1 study of mebendazole with bevacizumab and irinotecan in high-grade gliomas","volume":"71","author":"Krystal","year":"2024","journal-title":"Pediatr Blood Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13045-024-01544-7","article-title":"Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives","volume":"17","author":"Lin","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/medsci12010001","article-title":"Novel therapies in glioblastoma treatment: review of glioblastoma; current treatment options; and novel oncolytic viral therapies","volume":"12","author":"Shah","year":"2023","journal-title":"Med Sci (Basel)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"840","DOI":"10.3390\/molecules29040840","article-title":"Synergistic effects of temozolomide and doxorubicin in the treatment of glioblastoma multiforme: enhancing efficacy through combination therapy","volume":"29","author":"Dhungel","year":"2024","journal-title":"Molecules"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.05.001","article-title":"Dose escalated radiation therapy for glioblastoma multiforme: an international systematic review and meta-analysis of 22 prospective trials","volume":"111","author":"Singh","year":"2021","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.155794","article-title":"Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma","volume":"153","author":"Hao","year":"2024","journal-title":"Metabolism"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-023-04513-1","article-title":"A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma","volume":"166","author":"Gately","year":"2024","journal-title":"J Neurooncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3348\/kjr.2019.0898","article-title":"Radiological recurrence patterns after bevacizumab treatment of recurrent high-grade glioma: A systematic review and meta-analysis","volume":"21","author":"Cho","year":"2020","journal-title":"Korean J Radiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-022-03980-2","article-title":"Contrast enhancing pattern on pre-treatment MRI predicts response to anti-angiogenic treatment in recurrent glioblastoma: comparison of bevacizumab and temozolomide treatment","volume":"157","author":"Moon","year":"2022","journal-title":"J Neurooncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.3390\/ijms25052529","article-title":"Glioblastoma therapy: past, present and future","volume":"25","author":"Obrador","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s12885-020-6589-x","article-title":"Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series","volume":"20","author":"Tamura","year":"2020","journal-title":"BMC Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-23-0926","article-title":"Prognostic markers of DNA methylation and next-generation sequencing in progressive glioblastoma from the EORTC-26101 trial","volume":"29","author":"Kessler","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1667\/rade-22-00198","article-title":"Effect of temozolomide combined with intensity modulated radiation therapy on serum factor, immune function and clinical efficacy in postoperative glioma patients","volume":"200","author":"Yuan","year":"2023","journal-title":"Radiat Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-023-04551-9","article-title":"The risk and burden of thromboembolic and hemorrhagic events in patients with Malignant gliomas receiving bevacizumab","volume":"167","author":"Dasgupta","year":"2024","journal-title":"J Neurooncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s11547-021-01381-5","article-title":"Bevacizumab in recurrent high-grade glioma: a single institution retrospective analysis on 92 patients","volume":"126","author":"Detti","year":"2021","journal-title":"Radiol Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1191480","article-title":"Efficacy and safety of pharmacotherapy for recurrent high-grade glioma: a systematic review and network meta-analysis","volume":"14","author":"Xu","year":"2023","journal-title":"Front Pharmacol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.clineuro.2016.07.008","article-title":"Role of mass effect, tumor volume and peritumoral edema volume in the differential diagnosis of primary brain tumor and metastasis","volume":"148","author":"Baris","year":"2016","journal-title":"Clin Neurol Neurosurg"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2015.01.012","article-title":"Bevacizumab: A dose review","volume":"94","author":"Falk","year":"2015","journal-title":"Crit Rev Oncol Hematol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/js.2019-00130","article-title":"Comparison of radiographic approaches to assess treatment response in pituitary adenomas: is RECIST or RANO good enough","volume":"3","author":"Imber","year":"2019","journal-title":"J Endocr Soc"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nor091","article-title":"A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma","volume":"13","author":"Kreisl","year":"2011","journal-title":"Neuro Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.S87258","article-title":"Incidence and risk of hypertension with bevacizumab in non-small-cell lung cancer patients: a meta-analysis of randomized controlled trials","volume":"9","author":"Chen","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3094-7","article-title":"Efficacy and tolerance of frontline bevacizumab-based chemotherapy for advanced non-small cell lung cancer patients: a multicenter, phase IV study of the Hellenic Oncology Research Group (HORG)","volume":"78","author":"Matikas","year":"2016","journal-title":"Cancer Chemother Pharmacol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.21037\/qims-20-1084","article-title":"The relationship between the degree of brain edema regression and changes in cognitive function in patients with recurrent glioma treated with bevacizumab and temozolomide","volume":"11","author":"Wang","year":"2021","journal-title":"Quant Imaging Med Surg"},{"key":"B24","doi-asserted-by":"publisher","first-page":"15990","DOI":"10.1038\/s41598-025-00758-0","article-title":"Predicting the efficacy of bevacizumab on peritumoral edema based on imaging features and machine learning","volume":"15","author":"Bai","year":"2025","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.jocn.2024.01.018","article-title":"Effect of low-dose bevacizumab on health-related quality of life in patients with recurrent high-grade glioma: A retrospective clinical study","volume":"120","author":"Liao","year":"2024","journal-title":"J Clin Neurosci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"166","DOI":"10.3390\/brainsci7120166","article-title":"Advances in brain tumor surgery for glioblastoma in adults","volume":"7","author":"Lara-Velazquez","year":"2017","journal-title":"Brain Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/cncr.33918","article-title":"Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system","volume":"128","author":"Gritsch","year":"2022","journal-title":"Cancer"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-1776793","article-title":"Classification and grading of central nervous system tumors according to the world health organization 5th edition","volume":"43","author":"Yoda","year":"2023","journal-title":"Semin Neurol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1177\/1756285617753597","article-title":"Bevacizumab in temozolomide refractory high-grade gliomas: single-centre experience and review of the literature","volume":"11","author":"Jeck","year":"2018","journal-title":"Ther Adv Neurol Disord"},{"key":"B30","doi-asserted-by":"publisher","first-page":"324","DOI":"10.3390\/biomedicines9030324","article-title":"Current FDA-approved therapies for high-grade Malignant gliomas","volume":"9","author":"Fisher","year":"2021","journal-title":"Biomedicines"},{"key":"B31","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1056\/NEJMoa043331","article-title":"MGMT gene silencing and benefit from temozolomide in glioblastoma","volume":"352","author":"Hegi","year":"2005","journal-title":"N Engl J Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-013-1225-0","article-title":"Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival","volume":"115","author":"Chen","year":"2013","journal-title":"J Neurooncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-019-03245-5","article-title":"Long-term survival in patients with recurrent glioblastoma treated with bevacizumab: a multicentric retrospective study","volume":"144","author":"Morisse","year":"2019","journal-title":"J Neurooncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707358","article-title":"Lomustine and bevacizumab in progressive glioblastoma","volume":"377","author":"Wick","year":"2017","journal-title":"N Engl J Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-15-0776","article-title":"Identification of patients with recurrent glioblastoma who may benefit from combined bevacizumab and CCNU therapy: A report from the BELOB trial","volume":"76","author":"Erdem-Eraslan","year":"2016","journal-title":"Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2011.0037","article-title":"Bevacizumab for recurrent glioblastoma multiforme: a meta-analysis","volume":"9","author":"Wong","year":"2011","journal-title":"J Natl Compr Canc Netw"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.S481289","article-title":"Dose and efficacy of bevacizumab in recurrent high-grade gliomas: A retrospective study","volume":"16","author":"Bai","year":"2024","journal-title":"Cancer Manag Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1644934\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T05:33:42Z","timestamp":1756791222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1644934\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":37,"alternative-id":["10.3389\/fonc.2025.1644934"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1644934","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"article-number":"1644934"}}