Development and validation of a risk prediction model for venous thromboembolism in lung cancer patients treated with immune checkpoint inhibitors_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SU Yunhan , ZHANG Jiarui , YANG Linhui , LIU Yi , FANG Wanqin ,  LIU Dan

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

LIU Dan, Email: liudan10965@wchscu.cn

Keywords：

Lung cancer; immune checkpoint inhibitors; venous thromboembolism; prediction score; performance

DOI：

10.7507/1671-6205.202511051

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To develop a risk prediction model for venous thromboembolism (VTE) in lung cancer patients receiving immune checkpoint inhibitors (ICIs). Methods A retrospective analysis was conducted on lung cancer patients treated with ICIs at West China Hospital of Sichuan University between January 2018 and March 2022. The primary outcome was newly diagnosed VTE within 12 months. Independent risk factors for VTE were identified using multivariable logistic regression analysis in the training cohort and used to construct a risk prediction model, which was subsequently validated in a validation cohort. The performance of the model was evaluated using receiver operating characteristic (ROC) curve. Results During the 12-month follow-up period, a total of 105 patients developed VTE, with an incidence rate of 9.4% (105/1115). Multivariable logistic regression analysis identified an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, severe pulmonary disease, respiratory failure, abnormal pulmonary function, a history of VTE, prior chemotherapy, and corticosteroid therapy as independent predictors of VTE. The area under the ROC curve (AUC) of the prediction model was 0.822 (95%CI 0.762-0.882) in the training cohort and 0.779 (95%CI 0.687-0.871) in the validation cohort. Based on the model score, the patients were stratified into three risk categories for VTE: low risk (0-1 points), intermediate risk (2-3 points), and high risk (≥4 points). Conclusion The VTE risk prediction model developed in this study demonstrated good predictive performance in lung cancer patients receiving ICIs, and may serve as a practical tool for guiding individualized thromboprophylaxis strategies in clinical practice.

Citation： SU Yunhan, ZHANG Jiarui, YANG Linhui, LIU Yi, FANG Wanqin, LIU Dan. Development and validation of a risk prediction model for venous thromboembolism in lung cancer patients treated with immune checkpoint inhibitors. Chinese Journal of Respiratory and Critical Care Medicine, 2026, 25(3): 171-178. doi: 10.7507/1671-6205.202511051 Copy

1.	Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol, 2023, 41(16): 3063-3071.
2.	Falanga A, Ay C, Di Nisio M, et al. Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline. Ann Oncol, 2023, 34(5): 452-467.
3.	Mulder FI, Horváth-Puhó E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood, 2021, 137(14): 1959-1969.
4.	Kacimi SEO, Moeinafshar A, Haghighi SS, et al. Venous thromboembolism in cancer and cancer immunotherapy. Crit Rev Oncol Hematol, 2022, 178: 103782.
5.	Sussman TA, Li H, Hobbs B, et al. Incidence of thromboembolism in patients with melanoma on immune checkpoint inhibitor therapy and its adverse association with survival. J Immunother Cancer, 2021, 9(1): e001719.
6.	S?rensen HT, Mellemkjaer L, Olsen JH, et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med, 2000, 343(25): 1846-1850.
7.	Blom JW, Doggen CJ, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. Jama, 2005, 293(6): 715-722.
8.	Deschênes-Simard X, Richard C, Galland L, et al. Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study. Thromb Res, 2021, 205: 29-39.
9.	Khorana AA, Palaia J, Rosenblatt L, et al. Venous thromboembolism incidence and risk factors associated with immune checkpoint inhibitors among patients with advanced non-small cell lung cancer. J Immunother Cancer, 2023, 11(1): e006072.
10.	Moik F, Chan WE, Wiedemann S, et al. Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy. Blood, 2021, 137(12): 1669-1678.
11.	Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 2012, 141(2 Suppl): e195S-e226S.
12.	Elshoury A, Schaefer JK, Lim MY, et al. Update on guidelines for the prevention of cancer-associated thrombosis. J Natl Compr Canc Netw, 2022, 20(13).
13.	Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet, 1975, 2(7924): 45-51.
14.	Sevitt S, Gallagher NG. Prevention of venous thrombosis and pulmonary embolism in injured patients. A trial of anticoagulant prophylaxis with phenindione in middle-aged and elderly patients with fractured necks of femur. Lancet, 1959, 2(7110): 981-989.
15.	Pabinger I, van Es N, Heinze G, et al. A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts. Lancet Haematol, 2018, 5(7): e289-e298.
16.	Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood, 2008, 111(10): 4902-4907.
17.	van Es N, Ventresca M, Di Nisio M, et al. The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta-analysis. J Thromb Haemost, 2020, 18(8): 1940-1951.
18.	Alma S, Eloi D, Léa V, et al. Incidence of venous thromboembolism and discriminating capacity of Khorana score in lung cancer patients treated with immune checkpoint inhibitors. J Thromb Thrombolysis, 2022, 54(2): 287-294.
19.	Bj?rnhart B, Kristiansen C, Asmussen J, et al. Clinical impact of venous thromboembolism in non-small cell lung cancer patients receiving immunotherapy. Thromb Res, 2023, 221: 164-172.
20.	Ando Y, Hayashi T, Sugimoto R, et al. Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors. Invest New Drugs, 2020, 38(4): 1200-1206.
21.	Cánovas MS, Garay DF, Moran LO, et al. Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group. Clin Transl Oncol, 2022, 24(10): 2010-2020.
22.	Gong J, Drobni ZD, Alvi RM, et al. Immune checkpoint inhibitors for cancer and venous thromboembolic events. Eur J Cancer, 2021, 158: 99-110.
23.	Guven DC, Aksun MS, Sahin TK, et al. Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy. Support Care Cancer, 2021, 29(9): 5417-5423.
24.	Kewan T, Ko T, Flores M, et al. Prognostic impact and risk factors of cancer-associated thrombosis events in stage-IV cancer patients treated with immune checkpoint inhibitors. Eur J Haematol, 2021, 106(5): 682-688.
25.	Esmon CT. Inflammation and thrombosis. J Thromb Haemost, 2003, 1(7): 1343-1348.
26.	Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol, 2013, 13(1): 34-45.
27.	Franco AT, Corken A, Ware J. Platelets at the interface of thrombosis, inflammation, and cancer. Blood, 2015, 126(5): 582-588.
28.	Li A, May SB, La J, et al. Venous thromboembolism risk in cancer patients receiving first-line immune checkpoint inhibitor versus chemotherapy. Am J Hematol, 2023 Aug;98(8): 1214-1222.
29.	Icht O, Darzi N, Shimony S, et al. Venous thromboembolism incidence and risk assessment in lung cancer patients treated with immune checkpoint inhibitors. J Thromb Haemost, 2021, 19(5): 1250-1258.
30.	Scotté F, Leroy P, Chastenet M, et al. Treatment and prevention of cancer-associated thrombosis in frail patients: tailored management. Cancers (Basel), 2019, 11(1).
31.	Farmakis IT, Barco S, Mavromanoli AC, et al. Performance status and long-term outcomes in cancer-associated pulmonary embolism: insights from the Hokusai-VTE cancer study. JACC CardioOncol, 2022, 4(4): 507-518.
32.	Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon, 2005, 51(2-3): 70-78.
33.	Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost, 2010, 8(11): 2450-2457.
34.	Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J, 2010, 35(4): 830-836.
35.	Soler Artigas M, Wain LV, Miller S, et al. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation. Nat Commun, 2015, 6: 8658.
36.	Kubota Y, London SJ, Cushman M, et al. Lung function, respiratory symptoms and venous thromboembolism risk: the Atherosclerosis Risk in Communities Study. J Thromb Haemost, 2016, 14(12): 2394-2401.
37.	Gutierrez-Sainz L, Martinez-Marin V, Vi?al D, et al. Incidence of venous thromboembolic events in cancer patients receiving immunotherapy: a single-institution experience. Clin Transl Oncol, 2021, 23(6): 1245-1252.
38.	Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med, 2000, 160(6): 809-815.
39.	Yust-Katz S, Mandel JJ, Wu J, et al. Venous thromboembolism (VTE) and glioblastoma. J Neurooncol, 2015, 124(1): 87-94.
40.	Lin S, Zhu N, YihanZhang, et al. Development and validation of a prediction model of catheter-related thrombosis in patients with cancer undergoing chemotherapy based on ultrasonography results and clinical information. J Thromb Thrombolysis, 2022, 54(3): 480-491.

1. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol, 2023, 41(16): 3063-3071.
2. Falanga A, Ay C, Di Nisio M, et al. Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline. Ann Oncol, 2023, 34(5): 452-467.
3. Mulder FI, Horváth-Puhó E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood, 2021, 137(14): 1959-1969.
4. Kacimi SEO, Moeinafshar A, Haghighi SS, et al. Venous thromboembolism in cancer and cancer immunotherapy. Crit Rev Oncol Hematol, 2022, 178: 103782.
5. Sussman TA, Li H, Hobbs B, et al. Incidence of thromboembolism in patients with melanoma on immune checkpoint inhibitor therapy and its adverse association with survival. J Immunother Cancer, 2021, 9(1): e001719.
6. S?rensen HT, Mellemkjaer L, Olsen JH, et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med, 2000, 343(25): 1846-1850.
7. Blom JW, Doggen CJ, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. Jama, 2005, 293(6): 715-722.
8. Deschênes-Simard X, Richard C, Galland L, et al. Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study. Thromb Res, 2021, 205: 29-39.
9. Khorana AA, Palaia J, Rosenblatt L, et al. Venous thromboembolism incidence and risk factors associated with immune checkpoint inhibitors among patients with advanced non-small cell lung cancer. J Immunother Cancer, 2023, 11(1): e006072.
10. Moik F, Chan WE, Wiedemann S, et al. Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy. Blood, 2021, 137(12): 1669-1678.
11. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 2012, 141(2 Suppl): e195S-e226S.
12. Elshoury A, Schaefer JK, Lim MY, et al. Update on guidelines for the prevention of cancer-associated thrombosis. J Natl Compr Canc Netw, 2022, 20(13).
13. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet, 1975, 2(7924): 45-51.
14. Sevitt S, Gallagher NG. Prevention of venous thrombosis and pulmonary embolism in injured patients. A trial of anticoagulant prophylaxis with phenindione in middle-aged and elderly patients with fractured necks of femur. Lancet, 1959, 2(7110): 981-989.
15. Pabinger I, van Es N, Heinze G, et al. A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts. Lancet Haematol, 2018, 5(7): e289-e298.
16. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood, 2008, 111(10): 4902-4907.
17. van Es N, Ventresca M, Di Nisio M, et al. The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta-analysis. J Thromb Haemost, 2020, 18(8): 1940-1951.
18. Alma S, Eloi D, Léa V, et al. Incidence of venous thromboembolism and discriminating capacity of Khorana score in lung cancer patients treated with immune checkpoint inhibitors. J Thromb Thrombolysis, 2022, 54(2): 287-294.
19. Bj?rnhart B, Kristiansen C, Asmussen J, et al. Clinical impact of venous thromboembolism in non-small cell lung cancer patients receiving immunotherapy. Thromb Res, 2023, 221: 164-172.
20. Ando Y, Hayashi T, Sugimoto R, et al. Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors. Invest New Drugs, 2020, 38(4): 1200-1206.
21. Cánovas MS, Garay DF, Moran LO, et al. Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group. Clin Transl Oncol, 2022, 24(10): 2010-2020.
22. Gong J, Drobni ZD, Alvi RM, et al. Immune checkpoint inhibitors for cancer and venous thromboembolic events. Eur J Cancer, 2021, 158: 99-110.
23. Guven DC, Aksun MS, Sahin TK, et al. Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy. Support Care Cancer, 2021, 29(9): 5417-5423.
24. Kewan T, Ko T, Flores M, et al. Prognostic impact and risk factors of cancer-associated thrombosis events in stage-IV cancer patients treated with immune checkpoint inhibitors. Eur J Haematol, 2021, 106(5): 682-688.
25. Esmon CT. Inflammation and thrombosis. J Thromb Haemost, 2003, 1(7): 1343-1348.
26. Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol, 2013, 13(1): 34-45.
27. Franco AT, Corken A, Ware J. Platelets at the interface of thrombosis, inflammation, and cancer. Blood, 2015, 126(5): 582-588.
28. Li A, May SB, La J, et al. Venous thromboembolism risk in cancer patients receiving first-line immune checkpoint inhibitor versus chemotherapy. Am J Hematol, 2023 Aug;98(8): 1214-1222.
29. Icht O, Darzi N, Shimony S, et al. Venous thromboembolism incidence and risk assessment in lung cancer patients treated with immune checkpoint inhibitors. J Thromb Haemost, 2021, 19(5): 1250-1258.
30. Scotté F, Leroy P, Chastenet M, et al. Treatment and prevention of cancer-associated thrombosis in frail patients: tailored management. Cancers (Basel), 2019, 11(1).
31. Farmakis IT, Barco S, Mavromanoli AC, et al. Performance status and long-term outcomes in cancer-associated pulmonary embolism: insights from the Hokusai-VTE cancer study. JACC CardioOncol, 2022, 4(4): 507-518.
32. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon, 2005, 51(2-3): 70-78.
33. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost, 2010, 8(11): 2450-2457.
34. Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J, 2010, 35(4): 830-836.
35. Soler Artigas M, Wain LV, Miller S, et al. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation. Nat Commun, 2015, 6: 8658.
36. Kubota Y, London SJ, Cushman M, et al. Lung function, respiratory symptoms and venous thromboembolism risk: the Atherosclerosis Risk in Communities Study. J Thromb Haemost, 2016, 14(12): 2394-2401.
37. Gutierrez-Sainz L, Martinez-Marin V, Vi?al D, et al. Incidence of venous thromboembolic events in cancer patients receiving immunotherapy: a single-institution experience. Clin Transl Oncol, 2021, 23(6): 1245-1252.
38. Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med, 2000, 160(6): 809-815.
39. Yust-Katz S, Mandel JJ, Wu J, et al. Venous thromboembolism (VTE) and glioblastoma. J Neurooncol, 2015, 124(1): 87-94.
40. Lin S, Zhu N, YihanZhang, et al. Development and validation of a prediction model of catheter-related thrombosis in patients with cancer undergoing chemotherapy based on ultrasonography results and clinical information. J Thromb Thrombolysis, 2022, 54(3): 480-491.

Chinese Journal of Respiratory and Critical Care Medicine

Development and validation of a risk prediction model for venous thromboembolism in lung cancer patients treated with immune checkpoint inhibitors

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content