Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration-resistant cancer patients.
AR-directed signaling inhibitors
biomarker
metastatic castration-resistant prostate cancer
plasma tumor DNA
venous thromboembolism
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
revised:
20
09
2021
received:
19
05
2021
accepted:
22
09
2021
pubmed:
5
10
2021
medline:
15
2
2022
entrez:
4
10
2021
Statut:
ppublish
Résumé
Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration-resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next-generation sequencing was performed to determine ptDNA fraction from pretreatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR). At a median follow-up of 58 months (range 0.5-111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12 months of 17.1% (95% confidence interval [CI] 10.3-23.9). Elevated ptDNA, visceral metastasis, prior chemotherapy and lactate dehydrogenase (LDH) were significantly associated with higher VTE incidence compared to patients with no thrombosis (12-month estimate, 18.6% vs 3.5%, P = .0003; 44.4% vs 14.8%, P = .015; 24.7% vs 4.5%, P = .006; and 30.0% vs 13.5%, P = .05, respectively). In the multivariate analysis including ptDNA level, visceral metastases, number of lesions and serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% CI 1.63-20.44, P = .006). These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed-up more closely for the VTE risk, and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA.
Substances chimiques
DNA, Neoplasm
0
L-Lactate Dehydrogenase
EC 1.1.1.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1166-1173Subventions
Organisme : Cancer Research UK
ID : A22744
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C416/A26822
Pays : United Kingdom
Informations de copyright
© 2021 UICC.
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