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Clinical and molecular determinants of bleeding-related adverse outcomes in high-grade glioma

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Abstract

Purpose

Cancer is an independent risk factor for the development of venous thromboembolism (VTE). However, patients with high-grade glioma (HGG) including glioblastoma (GBM) are at a particularly high risk of VTE with an incidence up to 20–30% per year. Patients are often placed on anticoagulation if they are found to have VTE. However, patients with primary brain tumors such as HGG are at increased risk for intracerebral hemorrhage (ICH) even without the administration of anticoagulation. The combination of risk factors for ICH with anticoagulation and HGG complicates decision-making. Currently it is not known which of the direct oral anticoagulants (DOACs) are safest for patients with HGG in terms of adverse bleeding-related outcomes such as ICH. Furthermore, a deeper understanding of the clinical and molecular determinants of bleeding-related adverse outcomes in HGG is not fully characterized.

Methods

In this retrospective study, we identified and gathered data on 75 consecutive patients with pathology-confirmed HGG with hospital encounters at two academic medical center hospitals in Austin between July 1, 2017 and June 30, 2022. We compared clinical and treatment-related factors among cohorts who had received various forms of anticoagulation or no anticoagulation.

Results

Patients who were on rivaroxaban (3/7 (43%)) had a statistically significant association with more bleeding-related adverse events compared to those on apixaban (0/12 (0%)) or enoxaparin (0/5 (0%), p = 0.022) even though the groups were similar in characteristics including total time on the respective anticoagulation. Patients on anticoagulation vs those never on anticoagulation did not differ in terms of their studied demographic and clinical characteristics. Intriguingly, logistic regression analysis revealed that patients Astrocytoma, isocitrate dehydrogenase (IDH) mutant, grade 4 had a significant association with more adverse bleeding-related events even when controlling for other relevant factors (Odds Ratio compared to reference GBM: 49.4, 95% CI: 2.8, 2084.7; p = 0.013).

Conclusion

In this study we found that the use of rivaroxaban was associated with more bleeding-related events compared to apixaban and enoxaparin in patients with high-grade glioma. In this study we also found that the diagnosis of astrocytoma, IDH mutant, grade 4 was associated with more bleeding events. However, this is based on a small study and there is a need for larger studies to further evaluate these results.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the co-corresponding author JFR on reasonable request at justin.rousseau@utsouthwestern.edu.

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Acknowledgements

We would like to thank Dr. Nazanin Majd for editorial advice

Funding

No funding was received to assist with the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Neuro-Oncology, UT MD Anderson Cancer Center, Houston, TX, 77030, USA

    Pushan Dasgupta

  2. Department of Neurology, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    Justin F. Rousseau

  3. Peter O’Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    Justin F. Rousseau

  4. Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, 78712, USA

    Justin F. Rousseau

  5. Department of Population Health, Dell Medical School, University of Texas at Austin, Austin, TX, 78712, USA

    Justin F. Rousseau

Authors
  1. Pushan Dasgupta
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  2. Justin F. Rousseau
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Contributions

PD: conceived the study, collected the data through chart review, conducted some of the statistics and processed the data, devised the study, wrote the manuscript, reviewed and approved the final version of the manuscript. JFR: generated the list of patients for the study, devised the study, conducted some of the statistics including the logistic regression analysis, edited, reviewed, and approved the final version of the manuscript.

Corresponding authors

Correspondence to Pushan Dasgupta or Justin F. Rousseau.

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Ethics approval

This study was approved and met criteria for exemption from IRB review by University of Texas at Austin’s Institutional Review Board (STUDY00003529).

Competing interests

The authors declare no competing interests.

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Dasgupta, P., Rousseau, J.F. Clinical and molecular determinants of bleeding-related adverse outcomes in high-grade glioma. J Neurooncol 166, 569–574 (2024). https://doi.org/10.1007/s11060-024-04574-w

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  • DOI: https://doi.org/10.1007/s11060-024-04574-w

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