Associations of anticoagulant use with outcome in newly diagnosed glioblastoma

Rhun, Émilie Le; Genbrugge, Els; Stupp, Roger; Chinot, Olivier; Nabors, Louis B.; Cloughesy, Timothy; Reardon, David A.; Wick, Wolfgang; Weller, Michael

doi:10.1016/j.ejca.2018.06.029

Cited by 11 publications

(10 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No decrease in survival was observed in patients treated with prophylactic doses of anticoagulants or with antiplatelet agents. It remains unclear whether venous thromboembolic events caused this survival difference [63]. VTE has been less investigated in patients with brain metastases; however, a retrospective study reported an incidence of 20% [64].…”

Section: Incidence and Epidemiologymentioning

confidence: 99%

Neurological and vascular complications of primary and secondary brain tumours: EANO-ESMO Clinical Practice Guidelines for prophylaxis, diagnosis, treatment and follow-up

et al. 2021

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Section: Incidence and Epidemiologymentioning

confidence: 99%

Neurological and vascular complications of primary and secondary brain tumours: EANO-ESMO Clinical Practice Guidelines for prophylaxis, diagnosis, treatment and follow-up

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A recent study of more than 1,000 patients with newly diagnosed glioblastoma, however, did not support this hypothesis. 59 In fact, patients who were treated with anticoagulant drugs while on radio/chemotherapy had a worse survival compared with patients who did not use anticoagulants. This analysis is likely to be confounded by the fact that patients on anticoagulants mainly had prior VTE events, which might per se be associated with poor prognosis.…”

Section: Use Of Anticoagulant Therapy and Survival In Gliomamentioning

confidence: 99%

Venous Thromboembolism in Brain Tumors: Risk Factors, Molecular Mechanisms, and Clinical Challenges

Riedl

2019

Semin Thromb Hemost

View full text Add to dashboard Cite

Venous thromboembolism (VTE) is a common complication in patients with primary brain tumors, with up to 20% of patients per year having a VTE event. Clinical risk factors for VTE include glioblastoma subtype, paresis, or surgery. Furthermore, specific factors playing a role in tumor biology were recently identified to predispose to prothrombotic risk. For instance, mutations in the isocitrate dehydrogenase 1 (IDH1) gene, which occurs in a subgroup of glioma, correlate with risk of VTE, with low incidence in patients with presence of an IDH1 mutation compared with those with IDH1 wild-type status. In addition, expression of the glycoprotein podoplanin on brain tumors was associated with both intratumoral thrombi and high risk of VTE. As podoplanin has the ability to activate platelets, a mechanistic role of podoplanin-mediated platelet activation in VTE development has been suggested. From a clinical point of view, the management of patients with primary brain tumors and VTE is challenging. Anticoagulation is required to treat patients; however, it is associated with increased risk of intracranial hemorrhage. This review focuses on describing the epidemiology, risk factors, and mechanisms of brain tumor-associated thrombosis and discusses clinical challenges in the prevention and treatment of VTE in patients with brain tumors.

show abstract

“…The status of baseline metformin use or other baseline antidiabetic drug use was flagged as “positive” when they were used at any point in the period between the date of randomization minus 2 weeks and the date of the first TMZ treatment dose, and was flagged as “negative” otherwise. The status of the respective metformin use concomitant to the TMZ/RT treatment or other concomitant antidiabetic drug use was flagged as “yes” when they were used in the period between the first TMZ/RT treatment dose and start of the TMZ maintenance phase and “no” otherwise, as described . Different durations of baseline or concomitant use were summated, also for patients who used metformin on multiple occasions in the same or overlapping periods to account for the higher dose intensity for these patients.…”

Section: Exposuresmentioning

confidence: 99%

“…The status of the respective metformin use concomitant to the TMZ/RT treatment or other concomitant antidiabetic drug use was flagged as "yes" when they were used in the period between the first TMZ/RT treatment dose and start of the TMZ maintenance phase and "no" otherwise, as described. 21,22 Different durations of baseline or concomitant use were summated, also for patients who used metformin on multiple occasions in the same or overlapping periods to account for the higher dose intensity for these patients. The day of initial surgery for glioblastoma was set as the earliest time point to compute the duration of use.…”

Section: Antidiabetic Drug Usementioning

confidence: 99%

Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis

Seliger

Genbrugge

Gorlia

et al. 2019

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Metformin has been linked to improve survival of patients with various cancers. There is little information on survival of glioblastoma patients after use of metformin. We assessed the association between metformin use and survival in a pooled analysis of patient data from 1,731 individuals from the randomized AVAglio, CENTRIC and CORE trials. We performed multivariate Cox analyses for overall survival (OS) and progression‐free survival (PFS) comparing patients' use of metformin at baseline and/or during concomitant radiochemotherapy (TMZ/RT). Further exploratory analyses investigated the effect of metformin with a history of diabetes and nonfasting glucose levels in relation to OS or PFS of glioblastoma patients. Metformin alone or in any combination was not significantly associated with OS or PFS (at baseline, hazard ratio [HR] for OS = 0.87; 95% confidence interval [CI] = 0.65–1.16; HR for PFS = 0.84; 95% CI = 0.64–1.10; during TMZ/RT HR for OS = 0.97; 95% CI = 0.68–1.38; HR for PFS = 1.02; 95% CI = 0.74–1.41). We found a statistically nonsignificant association of metformin monotherapy with glioblastoma survival at baseline (HR for OS = 0.68; 95% CI = 0.42–1.10; HR for PFS = 0.57; 95% CI = 0.36–0.91), but not during the TMZ/RT period (HR for OS = 0.90; 95% CI = 0.51–1.56; HR for PFS = 1.05; 95% CI = 0.64–1.73). Diabetes mellitus or increased nonfasting glucose levels were not associated with a difference in OS or PFS in our selected study population. Metformin did not prolong survival of patients with newly diagnosed glioblastoma in our analysis. Additional studies may identify patients with specific tumor characteristics that are associated with potential benefit from treatment with metformin, possibly due to metabolic vulnerabilities.

show abstract

Associations of anticoagulant use with outcome in newly diagnosed glioblastoma

Cited by 11 publications

References 22 publications

Neurological and vascular complications of primary and secondary brain tumours: EANO-ESMO Clinical Practice Guidelines for prophylaxis, diagnosis, treatment and follow-up

Neurological and vascular complications of primary and secondary brain tumours: EANO-ESMO Clinical Practice Guidelines for prophylaxis, diagnosis, treatment and follow-up

Venous Thromboembolism in Brain Tumors: Risk Factors, Molecular Mechanisms, and Clinical Challenges

Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis

Contact Info

Product

Resources

About