Intracranial Hemorrhage in Patients with Anticoagulant Therapy Undergoing Stereotactic Radiosurgery for Brain Metastases: A Bi-Institutional Analysis

Felix Ehret; David Kaul; Lucas Mose; Volker Budach; Peter Vajkoczy; Christoph Fürweger; Alfred Haidenberger; Alexander Muacevic; Felix Mehrhof; Markus Kufeld

doi:10.3390/cancers14030465

Intracranial Hemorrhage in Patients with Anticoagulant Therapy Undergoing Stereotactic Radiosurgery for Brain Metastases: A Bi-Institutional Analysis

Cancers (Basel). 2022 Jan 18;14(3):465. doi: 10.3390/cancers14030465.

Authors

Felix Ehret^{1

2

3}, David Kaul^{2

4}, Lucas Mose³, Volker Budach^{2

4}, Peter Vajkoczy^{4

5}, Christoph Fürweger^{3

6}, Alfred Haidenberger³, Alexander Muacevic³, Felix Mehrhof², Markus Kufeld³

Affiliations

¹ Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
² Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, 13353 Berlin, Germany.
³ European Radiosurgery Center, 81377 Munich, Germany.
⁴ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité CyberKnife Center, 13353 Berlin, Germany.
⁵ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, 10117 Berlin, Germany.
⁶ Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, 50937 Cologne, Germany.

Abstract

Background: Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body, affected patients have an increased risk of comorbidities, such as atrial fibrillation (AF) and venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT). These may require therapeutic anticoagulant therapy (ACT). Limited data are available on the risk of intracranial hemorrhage (ICH) after SRS for patients with BM who are receiving ACT. This bi-institutional analysis aimed to describe the bleeding risk for this patient subgroup.

Methods: Patients with ACT at the time of single-fraction SRS for BM from two institutions were eligible for analysis. The cumulative incidence of ICH with death as a competing event was assessed during follow-up with magnetic resonance imaging or computed tomography.

Results: Forty-one patients with 97 BM were included in the analyses. The median follow-up was 8.2 months (range: 1.7-77.5 months). The median and mean BM volumes were 0.47 and 1.19 cubic centimeters, respectively. The most common reasons for ACT were PE (41%), AF (34%), and DVT (7%). The ACT was mostly performed utilizing phenprocoumon (37%), novel oral anticoagulants (32%), or low-molecular-weight heparin (20%). Nine BM from a group of five patients with ICH after SRS were identified: none of them caused neurological or any other deficits. The 6-, 12-, and 18-month cumulative bleeding incidences per metastasis were 2.1%, 12.4%, and 12.4%, respectively. The metastases with previous bleeding events and those originating from malignant melanomas were found to more frequently demonstrate ICH after SRS (p = 0.02, p = 0.01). No surgical or medical intervention was necessary for ICH management, and no observed death was associated with an ICH.

Conclusion: Patients receiving an ACT and single-fraction SRS for small- to medium-sized BM did not seem to have a clinically relevant risk of ICH. Previous bleeding and metastases originating from a malignant melanoma may favor bleeding events after SRS. Further studies are needed to validate our reported findings.

Keywords: CyberKnife; anticoagulant therapy; anticoagulation; brain metastases; intracranial hemorrhage; intratumoral hemorrhage; stereotactic radiosurgery.