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Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer : A sub-study of RASTEN - A randomized trial with low molecular weight heparin

Gezelius, E. LU ; Flou Kristensen, A. ; Bendahl, P. O. LU ; Hisada, Y. ; Risom Kristensen, S. ; Ek, L. LU ; Bergman, B. ; Wallberg, M. LU ; Falkmer, U. and Mackman, N. , et al. (2018) In PLoS ONE 13(11).
Abstract

Coagulation activation and venous thromboembolism (VTE) are hallmarks of cancer; however, there is an unmet need of improved biomarkers for individualized anticoagulant treatment. The present sub-study of the RASTEN trial was designed to explore the role of coagulation biomarkers in predicting VTE risk and outcome in a homogenous cancer patient population. RASTEN is a multicenter, randomized phase-3 trial investigating the survival effect of low molecular weight heparin enoxaparin when added to standard treatment in newly diagnosed small cell lung cancer (SCLC) patients. Plasma collected at baseline, during treatment, and at follow-up was used in this ad hoc sub-study (N = 242). Systemic coagulation was assessed using four assays... (More)

Coagulation activation and venous thromboembolism (VTE) are hallmarks of cancer; however, there is an unmet need of improved biomarkers for individualized anticoagulant treatment. The present sub-study of the RASTEN trial was designed to explore the role of coagulation biomarkers in predicting VTE risk and outcome in a homogenous cancer patient population. RASTEN is a multicenter, randomized phase-3 trial investigating the survival effect of low molecular weight heparin enoxaparin when added to standard treatment in newly diagnosed small cell lung cancer (SCLC) patients. Plasma collected at baseline, during treatment, and at follow-up was used in this ad hoc sub-study (N = 242). Systemic coagulation was assessed using four assays reflecting various facets of the coagulation system: Total tissue factor (TF); extracellular vesicle associated TF (EV-TF); procoagulant phospholipids (PPL); and thrombin generation (TG). We found small variations of biomarker levels between baseline, during treatment and at follow-up, and appeared independent on low molecular weight heparin treatment. Overall, none of the measured biomarkers at any time-point did significantly associate with VTE incidence, although increased total TF at baseline showed significant association in control patients not receiving low molecular weight heparin (P = 0.03). Increased TG-Peak was significantly associated with decreased overall survival (OS; P = 0.03), especially in patients with extensive disease. Low baseline EV-TF predicted a worse survival in the low molecular weight heparin as compared with the control group (HR 1.42; 95% CI 1.04–1.95; P = 0.03; P for interaction = 0.12). We conclude that the value of the analyzed coagulation biomarkers for the prediction of VTE risk was very limited in SCLC patients. The associations between TG-Peak and EV-TF with patient survival and response to low molecular weight heparin therapy, respectively, warrant further studies on the role of coagulation activation in SCLC aggressiveness.

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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
13
issue
11
article number
e0207387
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:30412630
  • scopus:85056361006
ISSN
1932-6203
DOI
10.1371/journal.pone.0207387
language
English
LU publication?
yes
id
ad8fd316-9a00-4188-9bd7-6a9c9cdd0094
date added to LUP
2018-11-22 12:29:43
date last changed
2021-10-06 03:02:30
@article{ad8fd316-9a00-4188-9bd7-6a9c9cdd0094,
  abstract     = {<p>Coagulation activation and venous thromboembolism (VTE) are hallmarks of cancer; however, there is an unmet need of improved biomarkers for individualized anticoagulant treatment. The present sub-study of the RASTEN trial was designed to explore the role of coagulation biomarkers in predicting VTE risk and outcome in a homogenous cancer patient population. RASTEN is a multicenter, randomized phase-3 trial investigating the survival effect of low molecular weight heparin enoxaparin when added to standard treatment in newly diagnosed small cell lung cancer (SCLC) patients. Plasma collected at baseline, during treatment, and at follow-up was used in this ad hoc sub-study (N = 242). Systemic coagulation was assessed using four assays reflecting various facets of the coagulation system: Total tissue factor (TF); extracellular vesicle associated TF (EV-TF); procoagulant phospholipids (PPL); and thrombin generation (TG). We found small variations of biomarker levels between baseline, during treatment and at follow-up, and appeared independent on low molecular weight heparin treatment. Overall, none of the measured biomarkers at any time-point did significantly associate with VTE incidence, although increased total TF at baseline showed significant association in control patients not receiving low molecular weight heparin (P = 0.03). Increased TG-Peak was significantly associated with decreased overall survival (OS; P = 0.03), especially in patients with extensive disease. Low baseline EV-TF predicted a worse survival in the low molecular weight heparin as compared with the control group (HR 1.42; 95% CI 1.04–1.95; P = 0.03; P for interaction = 0.12). We conclude that the value of the analyzed coagulation biomarkers for the prediction of VTE risk was very limited in SCLC patients. The associations between TG-Peak and EV-TF with patient survival and response to low molecular weight heparin therapy, respectively, warrant further studies on the role of coagulation activation in SCLC aggressiveness.</p>},
  author       = {Gezelius, E. and Flou Kristensen, A. and Bendahl, P. O. and Hisada, Y. and Risom Kristensen, S. and Ek, L. and Bergman, B. and Wallberg, M. and Falkmer, U. and Mackman, N. and Pedersen, S. and Belting, M.},
  issn         = {1932-6203},
  language     = {eng},
  month        = {11},
  number       = {11},
  publisher    = {Public Library of Science (PLoS)},
  series       = {PLoS ONE},
  title        = {Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer : A sub-study of RASTEN - A randomized trial with low molecular weight heparin},
  url          = {http://dx.doi.org/10.1371/journal.pone.0207387},
  doi          = {10.1371/journal.pone.0207387},
  volume       = {13},
  year         = {2018},
}