Bevacizumab‑associated intracerebral hemorrhage in patients with malignant glioma

Hama,Yuya; Sasaki,Takahiro; Fukai,Junya; Nakao,Naoyuki

doi:10.3892/mco.2025.2852

Bevacizumab‑associated intracerebral hemorrhage in patients with malignant glioma

Authors:
- Yuya Hama
- Takahiro Sasaki
- Junya Fukai
- Naoyuki Nakao
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Affiliations: Department of Neurological Surgery, School of Medicine, Wakayama Medical University, Wakayama 641‑8509, Japan
Published online on: April 17, 2025 https://doi.org/10.3892/mco.2025.2852
Article Number: 57
Copyright: © Hama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intracerebral hemorrhage (ICH) is a serious complication of the use of bevacizumab in patients with malignant glioma; however, the risk factors are unclear. Therefore, the present study retrospectively analyzed a cohort of patients treated with bevacizumab for malignant glioma to investigate the characteristics of those in the cohort who had ICH. Between January 2015 and December 2022, 64 patients with malignant glioma were treated with bevacizumab. Clinical and molecular biological information, treatment details, and information regarding the presence of ICH after bevacizumab administration were extracted from the hospital database. ICH was found to have occurred in seven patients (10.9%) after bevacizumab administration. The mean (standard deviation) age of these seven patients was 64 (11) years, and six of them (85.7%) underwent needle biopsy. Two patients (28.6%) had grade ≥3 hemorrhage. The median number of administrations of bevacizumab before the onset of ICH was seven (range: 1‑32), and the duration from first administration to ICH was 4 months (range: 1‑22). Furthermore, ICH was associated with a comparatively short overall survival time (log‑rank, P=0.008). Tumor invasion into the corpus callosum on contrast‑enhanced magnetic resonance imaging before bevacizumab administration was associated with ICH according to univariate analysis (P=0.01) and multivariate analysis (P=0.02). In conclusion, bevacizumab‑associated ICH was associated with poor prognosis in the present cohort of patients with malignant glioma. Furthermore, corpus callosum infiltration shown on magnetic resonance imaging before bevacizumab administration was suggested to be a risk factor for ICH; however, further studies on larger cohorts are required for confirmation.

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1	Wen PY, Weller M, Lee EQ, Alexander BM, Barnholtz-Sloan JS, Barthel FP, Batchelor TT, Bindra RS, Chang SM, Chiocca EA, et al: Glioblastoma in adults: A society for neuro-oncology (SNO) and European society of neuro-oncology (EANO) consensus review on current management and future directions. Neuro Oncol. 22:1073–1113. 2020.PubMed/NCBI View Article : Google Scholar
2	Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005.PubMed/NCBI View Article : Google Scholar
3	Das S and Marsden PA: Angiogenesis in glioblastoma. N Engl J Med. 369:1561–1563. 2013.PubMed/NCBI View Article : Google Scholar
4	Yang SB, Gao KD, Jiang T, Cheng SJ and Li WB: . Bevacizumab combined with chemotherapy for glioblastoma: A meta-analysis of randomized controlled trials. Oncotarget. 8:57337–57344. 2017.PubMed/NCBI View Article : Google Scholar
5	Liu ZL, Chen HH, Zheng LL, Sun LP and Shi L: Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther. 8(198)2023.PubMed/NCBI View Article : Google Scholar
6	Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, et al: Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 370:709–722. 2014.PubMed/NCBI View Article : Google Scholar
7	Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, et al: A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 370:699–708. 2014.PubMed/NCBI View Article : Google Scholar
8	Brandes AA, Bartolotti M, Tosoni A, Poggi R and Franceschi E: Practical management of bevacizumab-related toxicities in glioblastoma. Oncologist. 20:166–175. 2015.PubMed/NCBI View Article : Google Scholar
9	Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Available at https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. Accessed on May 20, 2024.
10	Ostrowski RP, He Z, Pucko EB and Matyja E: Hemorrhage in brain tumor-an unresolved issue. Brain Hemorrhages. 3:98–102. 2022.
11	Guyon J, Chapouly C, Andrique L, Bikfalvi A and Daubon T: The normal and brain tumor vasculature: Morphological and functional characteristics and therapeutic targeting. Front Physiol. 12(622615)2021.PubMed/NCBI View Article : Google Scholar
12	Motoo N, Hayashi Y, Shimizu A, Ura M and Nishikawa R: Safety and effectiveness of bevacizumab in Japanese patients with malignant glioma: A post-marketing surveillance study. Jpn J Clin Oncol. 49:1016–1023. 2019.PubMed/NCBI View Article : Google Scholar
13	Kubo H, Fujiwara T, Jussila L, Hashi H, Ogawa M, Shimizu K, Awane M, Sakai Y, Takabayashi A, Alitalo K, et al: Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis. Blood. 96:546–553. 2000.PubMed/NCBI
14	Kamba T and McDonald DM: Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer. 96:1788–1795. 2007.PubMed/NCBI View Article : Google Scholar
15	Chen KT, Wu TW, Chuang CC, Hsu YH, Hsu PW, Huang YC, Lin TK, Chang CN, Lee ST, Wu CT, et al: Corpus callosum involvement and postoperative outcomes of patients with gliomas. J Neurooncol. 124:207–214. 2015.PubMed/NCBI View Article : Google Scholar
16	Dayani F, Young JS, Bonte A, Chang EF, Theodosopoulos P, McDermott MW, Berger MS and Aghi MK: Safety and outcomes of resection of butterfly glioblastoma. Neurosurg Focus. 44(E4)2018.PubMed/NCBI View Article : Google Scholar
17	Shen S, Feng S, Liu H, Jiang J and Yu X: Associations of histological and molecular alterations with invasion of the corpus callosum in gliomas. Acta Neurochir (Wien). 162:1691–1699. 2020.PubMed/NCBI View Article : Google Scholar
18	Bastola S, Pavlyukov MS, Sharma N, Ghochani Y, Nakano MA, Muthukrishnan SD, Yu SY, Kim MS, Sohrabi A, Biscola NP, et al: Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma. Nat Commun. 16(471)2025.PubMed/NCBI View Article : Google Scholar
19	Liebelt B, Boghani Z, Takei H, Fung S and Britz G: Epithelioid glioblastoma presenting as massive intracerebral hemorrhage: Case report and review of the literature. Surg Neurol Int. 6 (Suppl 2):S97–S100. 2015.PubMed/NCBI View Article : Google Scholar
20	Alexander MD, Cooke DL, Nelson J, Guo DE, Dowd CF, Higashida RT, Halbach VV, Lawton MT, Kim H and Hetts SW: Association between venous angioarchitectural features of sporadic brain arteriovenous malformations and intracranial hemorrhage. Am J Neuroradiol. 36:949–952. 2015.PubMed/NCBI View Article : Google Scholar