-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1246 Imaging Predictors of Intracerebral Hemorrhage in Patients with Brain Tumors Treated with Anticoagulation

Program: Oral and Poster Abstracts
Session: 332. Thrombosis and Anticoagulation: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Adverse Events
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Rani Barnea, MD1,2*, Jonathan Naftali, MD1,2*, Eva N. Hamulyák, MD, PhD3*, Andrew M. Peseski, DO4, Tzu-Fei Wang, MD, MPH5, Lisa Baumann Kreuziger, MD, MS6, Varun Iyengar, MD7, Brian J. Carney, MD7, Berna Özdemir, MD, PhD8*, Rosana D. Cordova Serrano, MD9*, Kristen M. Sanfilippo, MD10, Shira Rozenblatt, MD11*, Ludo F.M. Beenen, MD, PhD12*, Shlomit Yust-Katz, MD13*, Erez Halperin, MD14,15*, Aaron Lubetsky, MD, MSc16, Andriy Derkach, PhD17*, David Nemirovsky17*, Marc Carrier, MD, MSc18, Ben Massat, DO19, Ariela Arad, MD20*, Martinus P.G. Broen, MD, PhD21*, Gabriela N. Cesarman-Maus, MD, PhD9*, Ann Hoeben, MD, PhD22*, Michele Hoffmann, MD8*, Yossi Kalish, MD20*, Saskia Middeldorp, MD, PhD23, Pia Raanani, MD24,25, Hugo Ten Cate, MD26, Ariella Tvito, MD27*, Harry Büller, MD1*, Galia Spectre, MD, PhD14,15*, Jeffrey I. Zwicker, MD28,29, Eitan Auriel, MD1,2* and Avi Leader, MD28,30

1Department of Neurology, Rabin Medical Center, Petah Tikva, Israel
2Faculty of medical and health sciences, Tel Aviv University, Tel Aviv, Israel
3Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
4Division of Hematology, Duke University Medical Center, Durham, NC
5Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada
6Blood Research Institute, Versiti, Milwaukee, WI
7Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, MA
8Department of Medical Oncology, Inselspital Bern, Bern University Hospital, University of Bern, Bern, Switzerland
9Deparment of Hematology, Instituto Nacional de Cancerología, Mexico City, Mexico
10Washington University School of Medicine St Louis, Chesterfield, MO
11Department of Radiology, Rabin Medical Center, Petah Tikva, Israel
12Department of Radiology, Amterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands
13Neurooncology Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
14Rabin Medical Center, Institute of Hematology, Petah Tikva, Israel
15Tel Aviv University, The Faculty of Medicine & Health Sciences, Tel Aviv, Israel
16National Hemophilia Center and Thrombosis & Hemostasis Institute, Sheba Medical Center, Tel Hashomer, Israel
17Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
18Department of Medicine, University of Ottawa at The Ottawa Hospital and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
19Versiti, Medical College of Wisconsin, Milwaukee, WI
20Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
21Department of Neurology, GROW-School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands
22Division of Medical Oncology, Department of Internal Medicine, GROW-School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands
23Department of Internal Medicine, Radboud university medical center, Nijmegen, Netherlands
24Department of Hematology, Rabin Medical Center, Petah Tikva, Israel
25Tel Aviv University, The Faculty of Medicine and Health Sciences, Tel Aviv, Israel
26Cardiovascular Research Institute Maastricht (CARIM) and department of Internal medicine, Maastricht University Medical Center, Maastricht, Netherlands
27Department of Hematology, Shaare Zedek Medical Center, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel
28Weill Cornell Medical College, New York, NY
29Memorial Sloan Kettering Cancer Center, New York, NY
30Hematology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Introduction

Spontaneous intracerebral hemorrhage (sICH) frequently occurs in patients with primary or metastatic brain tumors treated with anticoagulation and presents primarily as intratumoral bleeding. While an association between the burden of cerebral small vessel disease (CSVD) on brain magnetic resonance imaging (MRI) and sICH has been observed in patients receiving anticoagulation, it is unknown whether this holds true for patients with brain tumors. Intratumoral siderosis, a marker of prior subclinical sICH, represents a potential risk factor for subsequent sICH.

Aim

To evaluate whether markers of CSVD on brain MRI and intratumoral siderosis are associated with sICH in patients with brain tumors treated with anticoagulation.

Methods

This was a preplanned sub-study of the ABC study, a retrospective multinational cohort study which included 745 adults with primary or metastatic brain tumors treated with therapeutic-dose anticoagulation (low molecular weight heparin [LMWH] or direct oral anticoagulant [DOAC]) for any indication or duration (1/1/2014 – 1/1/2022), with 12 month follow up.

All patients in whom baseline MRI images were available were included in the current study. MRI scans were analyzed for imaging markers of CSVD that are known to be independently associated with sICH in the general population, including white matter hyperintensities graded by Fazekas score (to reflect CSVD burden) and cerebral microbleeds. Baseline MRI scans were read and analyzed according to STRIVE-2 classification by a neurovascular research group specialized in CSVD imaging with excellent interrater reliability for these measures (Naftali 2023. PMID: 37978833). Intratumoral siderosis were also analyzed.

The study outcome was sICH over 12 months follow-up, identified by record review and confirmed by a neuroradiologist, who was blinded to baseline MRIs. Baseline MRI readers were blinded to occurrence of sICH outcomes during follow up. Univariate analysis assessed associations between baseline MRI parameters and sICH, stratified for study center and adjusted for stopping anticoagulation. An additional analysis adjusted for cancer type as well.

Results

This analysis included 294 with baseline MRI of the 745 ABC patients. The median age was 63.0 years and 148 (50%) were female. Cancer types included primary brain tumors (123; 42.0%), metastases from primary lung (105; 36.0%), breast (29; 9.9%), and melanoma grouped with renal cell carcinoma tumors (12; 4.1%), as well as other types of cancer (25; 8.5%). The indication for anticoagulation was venous thromboembolism in 265 (90%) patients; 169 (57.5%) patients were treated with LMWH and 125 (42.5%) were treated with a DOAC.

The 12-month cumulative incidence of sICH was 7.9% (95% confidence interval [CI] 5.3%-12.0%); 20/22 sICH events were intratumoral. The baseline MRI was performed at a median of 14 days (IQR 0-39) before study index date (i.e., first day of concurrent anticoagulation and brain tumor). Cerebral microbleeds and intratumoral siderosis could be assessed in the 224/294 patients with susceptibility weighted imaging (SWI) sequences performed. Fazekas score could be evaluated in the 290/294 patients with fluid attenuated inversion recovery (FLAIR) sequences. Nineteen of 224 (8.5%) patients had extratumoral cerebral microbleeds. Intratumoral siderosis was demonstrated in 83/224 (37%) patients. The Fazekas score was 0 or 1 (no or mild CSVD burden) in 261/290 (90%) patients and 2 or 3 (moderate to severe CSVD burden) in 29/290 (10%) patients.

On univariable analysis, intratumoral siderosis (hazard ratio [HR] 3.44; 95% CI 1.01-11.7); cerebral microbleeds (HR 8.13; 95% CI 1.81-36.6) and moderate to severe CSVD burden (HR 4.71; 95% CI 1.89-11.7) were associated with sICH. Adjustment for cancer type demonstrated similar associations for intratumoral siderosis (HR 2.59; 95% CI 0.70-9.67), cerebral microbleeds (HR 11.4; 95% CI 1.71 - 76.1) and moderate to severe CSVD burden (HR 5.28; 95% CI 1.94 - 14.4). In a cross-correlation analysis, no statistically significant associations between the 3 MRI parameters were observed at baseline.

Conclusion

Baseline MRI findings appear to be predictive of sICH in patients with brain tumors treated with anticoagulation. Future studies should assess whether these parameters can guide management of anticoagulation in this population.

Disclosures: Wang: Servier: Honoraria; Valeo: Honoraria; Leo Pharma: Research Funding. Baumann Kreuziger: CSL Behring: Research Funding; Takeda: Research Funding; Sanofi: Research Funding; Veralox: Research Funding. Carney: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Özdemir: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ipsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lubetsky: Neopharm Israel: Honoraria. Carrier: Sanofi: Consultancy; Regeneron: Consultancy; Anthos: Consultancy; Servier: Consultancy; Bayer: Consultancy; BMS: Consultancy; Pfizer: Consultancy, Other: Grants paid to institution; Leo Pharma: Consultancy, Other: Grants paid to institution. Middeldorp: Abbvie: Consultancy; Bayer: Consultancy; Astra Zeneca: Consultancy; Alverong: Consultancy; Hemab: Consultancy; Norgine: Consultancy; Sanofi: Consultancy; Synapse: Research Funding; Viatris: Consultancy. Raanani: GSK: Consultancy; Lilly: Consultancy; AstraZenecca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy; Pfizer: Consultancy, Honoraria; Novrtis: Consultancy, Honoraria. Ten Cate: Bayer: Research Funding; Alveron: Consultancy; Leo: Consultancy; Galapagos: Consultancy; Astra Zeneca: Consultancy; Coagulation Profile: Current equity holder in private company. Spectre: Bayer: Consultancy; Neopharm: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; SOBI: Consultancy. Zwicker: Calyx: Consultancy; BMS: Consultancy; Regeneron: Consultancy, Research Funding; Parexel: Consultancy; Quercegen: Research Funding; Incyte Corporation: Research Funding; Med Learning Group: Consultancy; UpToDate: Patents & Royalties; CSL Behring: Other: Personal fees; Sanofi: Other: Personal fees. Leader: Leo Pharma: Honoraria.

*signifies non-member of ASH