https://doi.org/10.4081/monaldi.2025.3293
Prospective assessment of venous thromboembolism in lung cancer patients using a standardized screening protocol
Submitted: December 7, 2024
Accepted: February 12, 2025
Published: February 24, 2025
Accepted: February 12, 2025
Abstract Views: 201
PDF_EARLY VIEW: 45
SUPPLEMENTARY MATERIAL: 7
SUPPLEMENTARY MATERIAL: 7
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Venous thromboembolism (VTE) is highly prevalent in cancer patients. While its actual incidence remains disparate among studies, specific subpopulations, such as lung cancer patients, might be at an increased risk. We aimed to assess the impact of a screening protocol in determining both the incidence and risk factors for VTE and evaluate the usefulness of predictive biomarkers and risk stratification tools in lung cancer patients. For this purpose, we designed a prospective cohort study including all consecutive, newly diagnosed lung cancer patients between October 2023 and April 2024 in a tertiary center and assessed each patient using a standardized screening protocol. VTE screening included baseline and 3-month reassessment of coagulation tests, D-dimer levels, and imaging (duplex ultrasound of the lower limbs for deep vein thrombosis screening and contrast-enhanced thoracic computed tomography for pulmonary embolism screening). A total of 102 patients were included, of which 16 (15.7%) were diagnosed with VTE. VTE was more frequent in males (p=0.031), patients with COPD (p=0.004), and patients with metastatic disease (p=0.038), particularly those under immunotherapy (p=0.026). Patients with VTE presented a D-dimer concentration more than three times higher at baseline and fivefold the levels observed in non-VTE patients at 3 months (p=0.002). Paired with Khorana scores, D-dimer concentration 4.5 mg/L at 3 months improved the predictive capacity of this VTE risk assessment tool in patients under active treatment. Active VTE screening yielded a significant increase in diagnosis, suggesting the incidence of this complication in newly diagnosed lung cancer patients is underestimated. Risk assessment tools can be enhanced by the addition of D-dimer-based parameters.
Agnelli G, Verso M. Management of venous thromboembolism in patients with cancer. J Thromb Haemost 2011;9:316-24.
DOI: https://doi.org/10.1111/j.1538-7836.2011.04346.x
Falanga A, Ay C, Di Nisio M, et al. Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline. Ann Oncol 2023;34:452-67.
DOI: https://doi.org/10.1016/j.annonc.2022.12.014
Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 2020;38:496-520.
DOI: https://doi.org/10.1200/JCO.19.01461
Yan AR, Samarawickrema I, Naunton M, et al. Risk factors and prediction models for venous thromboembolism in ambulatory patients with lung cancer. Healthcare 2021;9:778.
DOI: https://doi.org/10.3390/healthcare9060778
Mulder FI, Horváth-Puhó E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood 2021;137:1959-69.
DOI: https://doi.org/10.1182/blood.2020007338
Walker AJ, Baldwin DR, Card TR, et al. Risk of venous thromboembolism in people with lung cancer: a cohort study using linked UK healthcare data. Br J Cancer 2016;115:115-21.
DOI: https://doi.org/10.1038/bjc.2016.143
Levitan N, Dowlati A, Remick SC, et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy: risk analysis using medicare claims data. Medicine 1999;78:285-91.
DOI: https://doi.org/10.1097/00005792-199909000-00001
Blom JW, Osanto S, Rosendaal FR. The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma. J Thromb Haemost 2004;2:1760-5.
DOI: https://doi.org/10.1111/j.1538-7836.2004.00928.x
Blom JW. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005;293:715-22.
DOI: https://doi.org/10.1001/jama.293.6.715
Chew HK, Davies AM, Wun T, et al. The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost 2008;6:601-8.
DOI: https://doi.org/10.1111/j.1538-7836.2008.02908.x
Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008;111:4902-7.
DOI: https://doi.org/10.1182/blood-2007-10-116327
Streiff MB, Bockenstedt PL, Cataland SR, et al. Venous thromboembolic disease. J Natl Compr Cancer Netw 2013;11:1402-29.
DOI: https://doi.org/10.6004/jnccn.2013.0163
Kuderer NM, Lyman GH. Guidelines for treatment and prevention of venous thromboembolism among patients with cancer. Thromb Res 2014;133:S122-7.
DOI: https://doi.org/10.1016/S0049-3848(14)50021-7
Kuderer NM, Poniewierski MS, Culakova E, et al. Predictors of venous thromboembolism and early mortality in lung cancer: results from a global prospective study (CANTARISK). Oncologist 2018;23:247-55.
DOI: https://doi.org/10.1634/theoncologist.2017-0205
Agnelli G, George DJ, Kakkar AK, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012;366:601-9.
DOI: https://doi.org/10.1056/NEJMoa1108898
Mansfield AS, Tafur AJ, Wang CE, et al. Predictors of active cancer thromboembolic outcomes: validation of the Khorana score among patients with lung cancer. J Thromb Haemost 2016;14:1773-8.
DOI: https://doi.org/10.1111/jth.13378
Verso M, Agnelli G, Barni S, et al. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012;7:291-2.
DOI: https://doi.org/10.1007/s11739-012-0784-y
Gerotziafas GT, Taher A, Abdel-Razeq H, et al. A predictive score for thrombosis associated with breast, colorectal, lung, or ovarian cancer: the prospective COMPASS–cancer-associated thrombosis study. Oncologist 2017;22:1222-31.
DOI: https://doi.org/10.1634/theoncologist.2016-0414
Swanton C, Bernard E, Abbosh C, et al. Embracing cancer complexity: hallmarks of systemic disease. Cell 2024;187:1589-616.
DOI: https://doi.org/10.1016/j.cell.2024.02.009
Connolly GC, Dalal M, Lin J, Khorana AA. Incidence and predictors of venous thromboembolism (VTE) among ambulatory patients with lung cancer. Lung Cancer 2012;78:253-8.
DOI: https://doi.org/10.1016/j.lungcan.2012.09.007
Joshi A, Kate S, Noronha V, et al. Thromboembolic events in patients with advanced stage non-small cell lung cancer treated with platinum-based chemotherapy: a prospective observational study. Ecancermedicalscience 2018;12:876.
DOI: https://doi.org/10.3332/ecancer.2018.876
Zhang Y, Yang Y, Chen W, et al. Prevalence and associations of VTE in patients with newly diagnosed lung cancer. Chest 2014;146:650-8.
DOI: https://doi.org/10.1378/chest.13-2379
Tiseo M, Bersanelli M, Barili MP, et al. Asymptomatic pulmonary embolism in lung cancer: prevalence and analysis of clinical and radiological characteristics in 141 outpatients. Tumori 2012;98:594-600.
DOI: https://doi.org/10.1177/030089161209800509
Connolly GC, Menapace L, Safadjou S, et al. Prevalence and clinical significance of incidental and clinically suspected venous thromboembolism in lung cancer patients. Clin Lung Cancer 2013;14:713-8.
DOI: https://doi.org/10.1016/j.cllc.2013.06.003
Hicks LK, Cheung MC, Ding K, et al. Venous thromboembolism and nonsmall cell lung cancer. Cancer 2009;115:5516-25.
DOI: https://doi.org/10.1002/cncr.24596
Sun JM, Kim TS, Lee J, et al. Unsuspected pulmonary emboli in lung cancer patients: The impact on survival and the significance of anticoagulation therapy. Lung Cancer 2010;69:330-6.
DOI: https://doi.org/10.1016/j.lungcan.2009.11.015
Muthu V, Narasimhan R, Prasad K, et al. Feasibility and impact of screening for venous thromboembolism in treatment-naive lung cancer patients–results of a prospective cohort study. Indian J Cancer 2022;59:203-11.
DOI: https://doi.org/10.4103/ijc.IJC_678_19
Roopkumar J, Poudel SK, Gervaso L, et al. Risk of thromboembolism in patients with ALK‐ and EGFR‐mutant lung cancer: a cohort study. J Thromb Haemost 2021;19:822-9.
DOI: https://doi.org/10.1111/jth.15215
Connolly GC, Khorana AA. Risk stratification for cancer-associated venous thromboembolism. Best Pract Res Clin Haematol 2009;22:35-47.
DOI: https://doi.org/10.1016/j.beha.2008.12.006
Roopkumar J, Swaidani S, Kim AS, et al. Increased incidence of venous thromboembolism with cancer immunotherapy. Med 2021;2:423-34.
DOI: https://doi.org/10.1016/j.medj.2021.02.002
Schorling RM, Pfrepper C, Golombek T, et al. Evaluation of biomarkers for the prediction of venous thromboembolism in ambulatory cancer patients. Oncol Res Treat 2020;43:414-27.
DOI: https://doi.org/10.1159/000508271
Ay C, Dunkler D, Pirker R, et al. High D-dimer levels are associated with poor prognosis in cancer patients. Haematologica 2012;97:1158-64.
DOI: https://doi.org/10.3324/haematol.2011.054718
Ma M, Cao R, Wang W, et al. The D-dimer level predicts the prognosis in patients with lung cancer: a systematic review and meta-analysis. J Cardiothorac Surg 2021;16:243.
DOI: https://doi.org/10.1186/s13019-021-01618-4
Lee AYY, Julian JA, Levine MN, et al. Clinical utility of a rapid whole-blood d-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis. Ann Intern Med 1999;131:417-23.
DOI: https://doi.org/10.7326/0003-4819-131-6-199909210-00004
Douma R, van Sluis G, Kamphuisen P, et al. Clinical decision rule and D-dimer have lower clinical utility to exclude pulmonary embolism in cancer patients. Thromb Haemost 2010;104:831-6.
DOI: https://doi.org/10.1160/TH10-02-0093
Righini M, Le Gal G, De Lucia S, et al. Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism. Thromb Haemost 2006;95:715-9.
DOI: https://doi.org/10.1160/TH05-12-0791
Chen C, Li G, Liu YD, Gu YJ. A new D-dimer cutoff value to improve the exclusion of deep vein thrombosis in cancer patients. Asian Pac J Cancer Prev 2014;15:1655-8.
DOI: https://doi.org/10.7314/APJCP.2014.15.4.1655
Chen C, Li J, Li J, et al. Application of an elevated plasma D-dimer cut-off value improves prognosis prediction of advanced non-small cell lung cancer. Ann Transl Med 2020;8:1153.
DOI: https://doi.org/10.21037/atm-20-5947
Callejas MF, Errázuriz JI, Castillo F, et al. Incidental venous thromboembolism detected by PET-CT in patients with cancer: Prevalence and impact on survival rate. Thromb Res 2014;133:750-5.
DOI: https://doi.org/10.1016/j.thromres.2014.02.005
Huang H, Korn JR, Mallick R, et al. Incidence of venous thromboembolism among chemotherapy-treated patients with lung cancer and its association with mortality: a retrospective database study. J Thromb Thrombolysis 2012;34:446-56.
DOI: https://doi.org/10.1007/s11239-012-0741-7
Şener YZ. Letter: Venous thromboembolism in lung cancer: shortcomings of Khorana score. Angiology 2024;33197241273375.
DOI: https://doi.org/10.1177/00033197241273375
Tsubata Y, Kawakado K, Hamai K, et al. Identification of risk factors for venous thromboembolism and validation of the Khorana score in patients with advanced lung cancer: based on the multicenter, prospective Rising-VTE/NEJ037 study data. Int J Clin Oncol 2023;28:69-78.
DOI: https://doi.org/10.1007/s10147-022-02257-y
Qin Y, Liang X, Wu H, et al. Development and validation of a modified Khorana score for predicting venous thromboembolism in newly diagnosed stage IV lung cancer. Angiology 2023;33197231213197.
DOI: https://doi.org/10.1177/00033197231213197
Li S, Gao P, Qiu J, et al. A modified Khorana score as a risk assessment tool for predicting venous thromboembolism in newly diagnosed advanced lung cancer. J Thromb Thrombolysis 2021;52:898-903.
DOI: https://doi.org/10.1007/s11239-021-02396-5
Ethics Approval
The study was conducted under the Declaration of Helsinki and was approved by the Ethics Committee of the Centro Hospitalar Universitário de São João (CHUSJ), Porto-Portugal (CES CHUSJ: 311/2022).How to Cite
Magalhães Ferreira, Pedro, Joana Ferreira, Cláudia Freitas, Catarina Sousa, David Araújo, Hélder Novais Bastos, Adriana Magalhães, and Maria Gabriela Fernandes. 2025. “Prospective Assessment of Venous Thromboembolism in Lung Cancer Patients Using a Standardized Screening Protocol”. Monaldi Archives for Chest Disease, February. https://doi.org/10.4081/monaldi.2025.3293.
Copyright (c) 2025 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Joana Almeida Borges, Antonio M. Esquinas, Biphasic cuirass ventilation in the escalation of non-invasive ventilation in COVID-19: Case report and review , Monaldi Archives for Chest Disease: Vol. 93 No. 4 (2023)
You may also start an advanced similarity search for this article.
