nach oben

Erschienen in:

19.02.2024 | Case Study

The risk and burden of thromboembolic and hemorrhagic events in patients with malignant gliomas receiving bevacizumab

verfasst von: Pushan Dasgupta, Alexander Ou, Heather Lin, Timothy Gregory, Kristin D. Alfaro-Munoz, Ying Yuan, Vahid Afshar-Khargan, Carlos Kamiya-Matsuoka, Justin F. Rousseau, Nazanin K. Majd

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2024

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Bevacizumab has evolved as an integral treatment option for patients with high-grade gliomas. Little is known about clinical risk factors that predispose patients with high-grade gliomas receiving bevacizumab to VTE or ICH. We sought to characterize the clinical risk factors associated with risk of either event.

Methods

In this multi-institutional retrospective study, we first evaluated patients with high-grade gliomas who were treated with bevacizumab at University of Texas MD Anderson Cancer Center from 2015–2021. We compared clinical and treatment-related factors among three cohorts: those who developed VTE, ICH, or neither. We further compared survival outcomes of these patients from the time of bevacizumab initiation. Then to further confirm our results in a non-cancer center hospital setting we evaluated patients from two Ascension Seton Hospitals in Austin, Texas which are affiliated with Dell Medical School at the University of Texas at Austin from 2017–2022.

Results

We found that the presence of cerebral macrobleeding, defined as a magnetic susceptibility of > 1 cm³ on magnetic resonance imaging, was highly associated with risk of developing ICH after initiation of bevacizumab. Development of ICH was significantly associated with poorer survival outcomes. We did not find a statistically significant effect of VTE on survival after bevacizumab initiation.

Conclusion

In order to stratify the risk for developing ICH before the initiation of bevacizumab, we recommend to assess for the presence of cerebral macrobleeding as it is associated with ICH development.

Nur mit Berechtigung zugänglich

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987–96. doi: https://doi.org/10.1056/NEJMoa043330. PMID: 15758009.

Marras LC, Geerts WH, Perry JR (2000) The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 89(3):640–646CrossRefPubMed

Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B … van den Bent MJ (2014) Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. The Lancet. Oncology, 15(9), 943–953. https://doi.org/10.1016/S1470-2045(14)70314-6

Chinot OL, de La Motte Rouge T, Moore N, Zeaiter A, Das A, Phillips H, Modrusan Z, Cloughesy T (2011) AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Ther 28(4):334–340. https://doi.org/10.1007/s12325-011-0007-3CrossRefPubMed

Simanek R, Vormittag R, Hassler M, Roessler K, Schwarz M, Zielinski C, Pabinger I, Marosi C. Venous thromboembolism and survival in patients with high-grade glioma. Neuro Oncol. 2007 Apr;9(2):89–95. doi: https://doi.org/10.1215/15228517-2006-035. Epub 2007 Feb 27. PMID: 17327573; PMCID: PMC1871666.

Streiff MB, Segal J, Grossman SA, Kickler TS, Weir EG. ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas. Cancer. 2004 Apr 15;100(8):1717-23. doi: https://doi.org/10.1002/cncr.20150. PMID: 15073862

Mir Seyed Nazari P, Riedl J, Preusser M, Posch F, Thaler J, Marosi C, Birner P, Ricken G, Hainfellner JA, Pabinger I, Ay C. Combination of isocitrate dehydrogenase 1 (IDH1) mutation and podoplanin expression in brain tumors identifies patients at high or low risk of venous thromboembolism. J Thromb Haemost. 2018 Jun;16(6):1121–1127. doi: https://doi.org/10.1111/jth.14129. Epub 2018 May 20. PMID: 29676036; PMCID: PMC6099350.

Nabi S, Kahlon P, Bozorgnia F, Arshad A, Mikkelsen T, Donthireddy V. Predictors of Venous Thromboembolism in Patients with Glioblastoma. Pathol Oncol Res. 2016 Apr;22(2):311-6. doi: https://doi.org/10.1007/s12253-015-0008-7. Epub 2015 Nov 7. PMID: 26547860

Thaler J, Ay C, Kaider A, Reitter EM, Haselböck J, Mannhalter C, Zielinski C, Marosi C, Pabinger I. Biomarkers predictive of venous thromboembolism in patients with newly diagnosed high-grade gliomas. Neuro Oncol. 2014 Dec;16(12):1645–51. doi: https://doi.org/10.1093/neuonc/nou106. Epub 2014 Jul 1. PMID: 24987133; PMCID: PMC4232082.

10.

Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. doi: https://doi.org/10.1200/JCO.2008.19.8721. Epub 2009 Aug 31. PMID: 19720927

11.

Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. doi: https://doi.org/10.1056/NEJMoa1308345. PMID: 24552318

12.

Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med. 2017 Nov 16;377(20):1954-1963. doi: https://doi.org/10.1056/NEJMoa1707358. PMID: 29141164

13.

Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014 Aug;15(9):943-53. doi: https://doi.org/10.1016/S1470-2045(14)70314-6. Epub 2014 Jul 15. PMID: 25035291

14.

Fraum TJ, Kreisl TN, Sul J, Fine HA, Iwamoto FM. Ischemic stroke and intracranial hemorrhage in glioma patients on antiangiogenic therapy. J Neurooncol. 2011 Nov;105(2):281–9. doi: https://doi.org/10.1007/s11060-011-0579-4. Epub 2011 Apr 27. PMID: 21603965; PMCID: PMC3168718.

15.

Zwicker JI, Karp Leaf R, Carrier M. A meta-analysis of intracranial hemorrhage in patients with brain tumors receiving therapeutic anticoagulation. J Thromb Haemost. 2016 Sep;14(9):1736-40. doi: https://doi.org/10.1111/jth.13387. Epub 2016 Jul 29. PMID: 27306689

16.

Porfidia A, Giordano M, Sturiale CL et al (2020) Risk of intracranial bleeding in patients with primary brain cancer receiving therapeutic anticoagulation for venous thromboembolism: A meta-analysis. Brain Behav 10(6):e01638. https://doi.org/10.1002/brb3.1638CrossRefPubMedPubMedCentral

17.

Lee I, Adimadhyam S, Nutescu EA, Zhou J, Asfaw AA, Sweiss KI, Patel PR, Calip GS. Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High-Grade Gliomas: A Nested Case-Control Study. Pharmacotherapy. 2019 Sep;39(9):921–928. doi: https://doi.org/10.1002/phar.2310. Epub 2019 Aug 6. PMID: 31332810; PMCID: PMC7395667.

18.

Kamiya-Matsuoka C, Hamza MA, de Groot JF. Impact of adverse events of bevacizumab on survival outcomes of patients with recurrent glioblastoma. J Clin Neurosci. 2020 Apr;74:36-40. doi: https://doi.org/10.1016/j.jocn.2020.01.066. Epub 2020 Jan 23. PMID: 31982279

19.

Lin X, Daras M, Pentsova E, Nolan CP, Gavrilovic IT, DeAngelis LM, Kaley TJ. Bevacizumab in high-grade glioma patients following intraparenchymal hemorrhage. Neurooncol Pract. 2017 Mar;4(1):24–28. doi: https://doi.org/10.1093/nop/npw008. Epub 2016 Dec 9. PMID: 31044081; PMCID: PMC6479824.

20.

Mantia C, Uhlmann EJ, Puligandla M, Weber GM, Neuberg D, Zwicker JI. Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin. Blood. 2017 Jun 22;129(25):3379-3385. doi: https://doi.org/10.1182/blood-2017-02-767285. Epub 2017 May 3. PMID: 28468796

21.

Lim G, Ho C, Roldan Urgoti G, Leugner D, Easaw J. Risk of Venous Thromboembolism in Glioblastoma Patients. Cureus. 2018 May 23;10(5):e2678 https://doi.org/10.7759/cureus.2678 PMID: 30050733; PMCID: PMC6059517

22.

Alkhachroum A, Bustillo AJ, Asdaghi N, Marulanda-Londono E, Gutierrez CM, Samano D, Sobczak E, Foster D, Kottapally M, Merenda A, Koch S, Romano JG, O’Phelan K, Claassen J, Sacco RL, Rundek T (2021) Withdrawal of Life-Sustaining Treatment Mediates Mortality in Patients With Intracerebral Hemorrhage With Impaired Consciousness. Stroke 52(12):3891–3898. https://doi.org/10.1161/STROKEAHA.121.035233CrossRefPubMedPubMedCentral

23.

Khoury MN, Missios S, Edwin N, Sakruti S, Barnett G, Stevens G, Peereboom DM, Khorana AA, Ahluwalia MS (2016) Intracranial hemorrhage in setting of glioblastoma with venous thromboembolism. Neuro-oncology practice 3(2):87–96. https://doi.org/10.1093/nop/npv028CrossRefPubMed

24.

Tawil, N., Bassawon, R., Meehan, B., Nehme, A., Montermini, L., Gayden, T., De Jay, N., Spinelli, C., Chennakrishnaiah, S., Choi, D., Adnani, L., Zeinieh, M., Jabado, N., Kleinman, C. L., Witcher, M., Riazalhosseini, Y., Key, N. S., Schiff, D., Grover, S. P., Mackman, N., … Rak, J. (2021). Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles. Blood advances, 5(6), 1682–1694. https://doi.org/10.1182/bloodadvances.2020002998

25.

RAK J, Magnusa N, Garniera D, Meehana B, McGrawa S, Leea TH, Caronb M, Bourqueb G, Milsomc C, Jabadoa N, Traslera J. Procoagulant tissue factor expression is linked to distinct subtypes in glioblastoma and plays a role in tumor dormancy. Neuro Oncol. 2014 Jul;16(Suppl 3):iii1–iii22. doi: https://doi.org/10.1093/neuonc/nou206.77. PMCID: PMC4144547.

Titel: The risk and burden of thromboembolic and hemorrhagic events in patients with malignant gliomas receiving bevacizumab
verfasst von: Pushan Dasgupta
Alexander Ou
Heather Lin
Timothy Gregory
Kristin D. Alfaro-Munoz
Ying Yuan
Vahid Afshar-Khargan
Carlos Kamiya-Matsuoka
Justin F. Rousseau
Nazanin K. Majd
Publikationsdatum: 19.02.2024
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2024
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-023-04551-9

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2024

CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization

Intrathecal chemotherapy for leptomeningeal disease in high-grade gliomas: a systematic review

The development of a custom RNA-sequencing panel for the identification of predictive and diagnostic biomarkers in glioma

Ki-67 labeling index predicts tumor progression patterns and survival in patients with atypical meningiomas following stereotactic radiosurgery

Correction to: Intrathecal chemotherapy for leptomeningeal disease in high-grade gliomas: a systematic review