Elsevier

Thrombosis Research

Volume 196, December 2020, Pages 349-354
Thrombosis Research

Full Length Article
High plasma levels of soluble P-Selectin and Factor VIII predict venous thromboembolism in non-small cell lung cancer patients: The Thrombo-Nsclc risk score

https://doi.org/10.1016/j.thromres.2020.09.021Get rights and content

Highlights

  • Chemotherapy (CT) raises thrombotic risk (TR) in non-small cell lung cancer (NSCLC).

  • Association between pre-CT variables and TR was studied in 90 NSCLC patients.

  • Factor VIII and especially soluble P-selectin were independently associated with TR.

  • A score built on these variables efficiently identified high TR patients.

Abstract

Introduction

Venous thromboembolism (VTE) is common in non-small cell lung cancer (NSCLC) patients undergoing systemic chemotherapy. The usefulness of Khorana score (KRS) to predict risk in lung cancer patients is limited, and the identification of patients who would benefit most from thromboprophylaxis is challenging. We aimed to identify variables whose values before chemotherapy helped in predicting VTE occurrence, and build a model to assess VTE risk.

Materials and methods

A cohort of newly diagnosed NSCLC patients to undergo outpatient chemotherapy, not under anticoagulant treatment, was recruited. Pre-chemotherapy demographic, clinical, analytical and tumor-specific variables were collected. Patients were prospectively followed-up for 12 months to record VTE events. Bivariate and multivariate analyses were performed to identify VTE-associated variables, and a prediction model was built and compared with KRS.

Results

90 patients were recruited, 18 of whom had a VTE event during follow-up. High baseline levels of factor VIII (FVIII) and, especially, soluble P-selectin (sP-selectin), were independently associated with VTE risk (hazard ratio [HR] 4.15, 95% confidence interval [CI] 1.17–14.71, and 66.40 [8.70–506.69], respectively). Our so-called Thrombo-NSCLC risk score, which assigns 1 and 3 points to high FVIII and sP-selectin values, respectively, was significantly better than KRS in predicting VTE (area under the curve [AUC] 0.93 vs. 0.55, sensitivity 94.4 vs. 35.0%, specificity 93.1 vs. 60.0%). Our prediction model showed significant discriminating capacity between high risk vs. intermediate/low risk patients, while KRS did not.

Conclusions

The Thrombo-NSCLC risk score may be useful to identify those NSCLC patients who would benefit most from thromboprophylaxis.

Introduction

Cancer patients have a higher risk of developing venous thromboembolism (VTE), which is their most common cause of death after tumor progression [1]. Lung cancer is highly associated with VTE, and patients are six times more likely to have a pulmonary embolism (PE) compared to the healthy population in the 12 months before diagnosis [2]. Chemotherapy constitutes an additional risk for newly diagnosed patients. Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancers. NSCLC is primarily treated with platins, and VTE is a common finding during this therapy [3]. Therefore, anticoagulant prophylaxis should be considered during the treatment period. For safety and economic reasons, indiscriminate anticoagulation is not recommended, and treatment should be limited to those patients at highest thromboembolic risk. Nevertheless, the identification of the most appropriate candidates still poses a challenge to specialists. A decade ago, a risk prediction model, the Khorana score (KRS), was developed. Assessment of platelet and leukocyte count, haemoglobin level, body mass index (BMI) and tumor localization, makes it possible to allocate patients to high, intermediate or low VTE risk groups [4]. Nonetheless, KRS exhibits limitations, especially when used with lung cancer patients [[5], [6], [7], [8], [9]]. Furthermore, KRS and other alternative models have been built upon cohorts of patients with heterogeneous tumors [4,[10], [11], [12]]. Thus, designing NSCLC-specific tools to better detect suitable candidates for anticoagulation is mandatory. To fill this gap, we performed a study with a cohort of NSCLC patients, in order to construct a predictive VTE risk model based on the association of variables assessed before chemotherapy with subsequent occurrence of VTE.

Section snippets

Patients and study design

This is a prospective, observational one-center study with newly diagnosed patients with locally advanced or metastatic NSCLC who were about to undergo systemic outpatient chemotherapy. Ethical approval was received from the Medical Ethical Committee of Hospital Torrecárdenas (Almería, Spain). Signed informed consent was obtained from each patient. Inclusion criteria were age >18 years, ECOG 0-2, suitability for treatment with outpatient chemotherapy according to standard guidelines and life

Results and discussion

This is the first attempt to develop a VTE risk score to apply to NSCLC patients to face chemotherapy. 90 consecutive newly diagnosed NSCLC patients were recruited in our center between February 2015 and March 2016. Age, tumor histology and stage, metastasis, functional status and comorbidity profile did not differ from those in other series, although the proportion of male patients was higher than expected [3,9]. Median baseline levels of FVIII (%), fibrinogen, D-dimer and CRP were higher than

Conclusions

In summary, baseline sP-selectin and FVIII (%) were independently associated with a prospective study with newly diagnosed NSCLC patients due to undergo outpatient chemotherapy. The remarkably large risk imparted by high sP-selectin levels allowed us to build an encouraging model to predict the VTE risk which could thus be useful to identify candidates for thromboprophylaxis. These results should prompt further research to confirm the validity of the Thrombo-NSCLC risk score.

CRediT authorship contribution statement

V.E. Castellón planned research, obtained baseline data, followed-up patients, wrote the manuscript and approved the final version; P. Pérez Segura planned research, read critically the manuscript and approved the final version; A.J. Muñoz Martín contributed to study design, read critically the manuscript and approved the final version; A. López Farré performed non-routine analytical methods, read critically the manuscript and approved the final version; L. Canosa Ruiz followed-up patients,

Declaration of competing interest

None.

Acknowledgements

This work was supported by Leo Pharma. This entity has not contributed to the study design, data analysis, interpretation of the results, drafting of the document, or in the decision regarding publication in any way.

References (32)

Cited by (17)

  • Standardization of risk prediction model reporting in cancer-associated thrombosis: Communication from the ISTH SSC subcommittee on hemostasis and malignancy

    2022, Journal of Thrombosis and Haemostasis
    Citation Excerpt :

    The final sample size included 29 studies [see PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) diagram, Figure 1]. Details of the 29 included studies are listed in Table S2.4,6–33 The number of studies published increased from one per year between 2005 and 2015, to eight in 2020, with three published in 2021.

  • Biomimetic lipidic nanovectors for effective asparaginase supramolecule delivery

    2022, Nanomedicine: Nanotechnology, Biology, and Medicine
    Citation Excerpt :

    Regarding the overlapping target of SECD-SCLC, alpha-amylase (AMY2A, AMY1A) levels were very sensitive biomarkers of SCLC tumors.37,38 Regarding the overlapping target of PC-SCLC, p-selectin may predict venous thromboembolism in lung cancer patients.39 Regarding the overlapping target of cholesterol-SCLC, the androgen receptor was correlated with non-SCLC patient outcome.40

  • Factor VIII as a potential player in cancer pathophysiology

    2022, Journal of Thrombosis and Haemostasis
    Citation Excerpt :

    In the present study, bladder cancer was chosen as the model system to investigate a potential novel tumor‐derived coagulative protein, FVIII. Factor VIII was investigated not only because of an independent association to an increased risk of VTE in cancer patients,20–22 but also because of relevant extracoagulative functions that have recently emerged.19 Bladder cancer was selected as the model system because of its high VTE incidence rate,5,6 which correlates with elevated plasma levels of early coagulative markers.31

  • The pathogenesis of cancer-associated thrombosis

    2024, International Journal of Hematology
View all citing articles on Scopus
View full text