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Cardiovascular disease and survival in non-small cell lung cancer: a multicenter prospective assessment

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Abstract

Purpose

Chronic inflammation contributes to cancer development via multiple mechanisms. We hypothesized that cardiovascular diseases (CVD) are also an independent risk factor for survival in non-small cell lung cancer (NSCLC).

Materials and methods

Prospective multicenter data from 345 consecutive NSCLC patients treated from January 2013 to January 2017 were assessed. Median follow-up for all patients was 13 months (range 3–60 months). There were 109 patients with baseline heart disease (HD 32%), 149 with arterial hypertension (43%), 85 with diabetes mellitus (25%), 129 with hyperlipidemia (37%) and 45 with venous thromboembolism events (VTE 13%). A total of 289 patients (84%) were treated with platinum-based chemotherapy (CT), 300 patients (87%) received thoracic radiation therapy (RT; median radiation dose: 60 Gy [range 12–70]); and 50 (15%) patients underwent surgery.

Results

Our cohort consisted of 305 men (88%) and 40 (12%) women, with a median age of 67 years (range 31–88 years). Seventy percent had a Karnofsky performance status (KPS) ≥ 80. Multivariate analyses showed a lower OS and higher risk of distant metastasis in patients with advanced stages (p = 0.05 and p < 0.001, respectively) and HD (HR 1.43, p = 0.019; and HR 1.49, p = 0.025, respectively). Additionally, patients with VTE had lower local control (HR 1.84, p = 0.025), disease-free survival (HR 1.64, p = 0.020) and distant metastasis-free survival (HR 1.73, p = 0.025).

Conclusions

HD and VTE are associated with a higher risk of mortality and distant metastasis in NSCLC patients. Chronic inflammation associated with CVDs could be an additional pathophysiologic factor in the development of distant metastasis.

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References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. https://doi.org/10.1002/ijc.29210.

    Article  CAS  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: Cancer J Clin. 2013;63(1):11–30. https://doi.org/10.3322/caac.21166.

    Article  Google Scholar 

  3. Francisci S, Minicozzi P, Pierannunzio D, Ardanaz E, Eberle A, Grimsrud TK, et al. Survival patterns in lung and pleural cancer in Europe 1999–2007: results from the EUROCARE-5 study. Eur J Cancer. 2015;51(15):2242–53. https://doi.org/10.1016/j.ejca.2015.07.033.

    Article  PubMed  Google Scholar 

  4. Detterbeck FC. Stage classification and prognosis: an intersection of medicine, quantum physics and religion? Thorax. 2011;66(11):1016–7. https://doi.org/10.1136/thoraxjnl-2011-200214.

    Article  PubMed  Google Scholar 

  5. Chansky K, Sculier J-P, Crowley JJ, Giroux D, Van Meerbeeck J, Goldstraw P. The International Association for the Study of Lung Cancer Staging Project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol. 2009;4(7):792–801. https://doi.org/10.1097/jto.0b013e3181a7716e.

    Article  PubMed  Google Scholar 

  6. Little AG. National survey of non-small cell lung cancer in the United States: epidemiology, pathology and patterns of care. Lung Cancer. 2007;57(3):253–60.

    Article  PubMed  Google Scholar 

  7. Asmis TR, Ding K, Seymour L, Shepherd FA, Leighl NB, Winton TL, et al. Age and comorbidity as independent prognostic factors in the treatment of non-small-cell lung cancer: a review of national cancer institute of canada clinical trials group trials. J Clin Oncol. 2008;26(1):54–9. https://doi.org/10.1200/jco.2007.12.8322.

    Article  CAS  PubMed  Google Scholar 

  8. Grose D, Devereux G, Brown L, Jones R, Sharma D, Selby C, et al. Variation in comorbidity and clinical management in patients newly diagnosed with lung cancer in four Scottish centers. J Thorac Oncol. 2011;6(3):500–9. https://doi.org/10.1097/jto.0b013e318206dc10.

    Article  PubMed  Google Scholar 

  9. Piccirillo JF. Importance of comorbidity in head and neck cancer. Laryngoscope. 2000;110(4):593–602. https://doi.org/10.1097/00005537-200004000-00011.

    Article  CAS  PubMed  Google Scholar 

  10. Vlahos R, Bozinovski S. Protocols to evaluate cigarette smoke-induced lung inflammation and pathology in mice. In: Jenkins BJ, editor. Inflammation and cancer: methods and protocols. New York: Springer; 2018. p. 53–63.

    Chapter  Google Scholar 

  11. Janssen-Heijnen MLG, Schipper RM, Razenberg PPA, Crommelin MA, Coebergh J-WW. Prevalence of co-morbidity in lung cancer patients and its relationship with treatment: a population-based study. Lung Cancer. 1998;21(2):105–13. https://doi.org/10.1016/s0169-5002(98)00039-7.

    Article  CAS  PubMed  Google Scholar 

  12. Kravchenko J, Berry M, Arbeev K, Lyerly HK, Yashin A, Akushevich I. Cardiovascular comorbidities and survival of lung cancer patients: medicare data based analysis. Lung Cancer. 2015;88(1):85–93. https://doi.org/10.1016/j.lungcan.2015.01.006.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Nagel S, Berk B-A, Kortmann R-D, Hoffmann K-T, Seidel C. Can vascular risk factors influence number and size of cerebral metastases? A 3D-MRI study in patients with different tumor entities. Clin Neurol Neurosurg. 2018;165:55–9. https://doi.org/10.1016/j.clineuro.2018.01.001.

    Article  PubMed  Google Scholar 

  14. Faiz AS, Khan I, Beckman MG, Bockenstedt P, Heit JA, Kulkarni R, et al. Characteristics and risk factors of cancer associated venous thromboembolism(). Thromb Res. 2015;136(3):535–41. https://doi.org/10.1016/j.thromres.2015.06.036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Piccioli A, Falanga A, Baccaglini U, Marchetti M, Prandoni P. Cancer and venous thromboembolism. Semin Thromb Hemost. 2006;32(07):694–9. https://doi.org/10.1055/s-2006-951297.

    Article  PubMed  Google Scholar 

  16. Adelborg K, Horváth-Puhó E, Sundbøll J, Prandoni P, Ording A, Sørensen HT. Risk and prognosis of cancer after upper-extremity deep venous thrombosis: a population-based cohort study. Thromb Res. 2018;161:106–10. https://doi.org/10.1016/j.thromres.2017.11.017.

    Article  CAS  PubMed  Google Scholar 

  17. Eichinger S. Cancer associated thrombosis: risk factors and outcomes. Thromb Res. 2016;140:S12–7. https://doi.org/10.1016/s0049-3848(16)30092-5.

    Article  CAS  Google Scholar 

  18. Yamaguchi M. The therapeutic approaches applied in the treatment of non-small cell lung cancer in elderly patients. Jpn J Lung Cancer. 2017;57(6):739–45. https://doi.org/10.2482/haigan.57.739.

    Article  Google Scholar 

  19. Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2(8):706–14. https://doi.org/10.1097/jto.0b013e31812f3c1a.

    Article  PubMed  Google Scholar 

  20. Frazier TH, Stocker AM, Kershner NA, Marsano LS, McClain CJ. Treatment of alcoholic liver disease. Ther Adv Gastroenterol. 2011;4(1):63–81. https://doi.org/10.1177/1756283X10378925.

    Article  Google Scholar 

  21. Takenaka T, Katsura M, Shikada Y, Tsukamoto S, Takeo S. The impact of cardiovascular comorbidities on the outcome of surgery for non-small-cell lung cancer. Interact Cardiovasc Thorac Surg. 2013;16(3):270–4. https://doi.org/10.1093/icvts/ivs489.

    Article  PubMed  Google Scholar 

  22. Dominguez-Ventura A, Allen MS, Cassivi SD, Nichols FC III, Deschamps C, Pairolero PC. Lung Cancer in Octogenarians: Factors Affecting Morbidity and Mortality After Pulmonary Resection. Ann Thorac Surg. 2006;82(4):1175–9. https://doi.org/10.1016/j.athoracsur.2006.04.052.

    Article  PubMed  Google Scholar 

  23. King PT. Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clin Transl Med. 2015;4(1):68. https://doi.org/10.1186/s40169-015-0068-z.

    Article  Google Scholar 

  24. Hatlen P, Langhammer A, Carlsen SM, Salvesen O, Amundsen T. Self-reported cardiovascular disease and the risk of lung cancer, the HUNT study. J Thorac Oncol. 2014;9(7):940–6. https://doi.org/10.1097/JTO.0000000000000180.

    Article  PubMed  Google Scholar 

  25. Kuderer NM, Poniewierski MS, Culakova E, Lyman GH, Khorana AA, Pabinger I, et al. Predictors of venous thromboembolism and early mortality in lung cancer: results from a global prospective study (CANTARISK). Oncologist. 2018;23(2):247–55. https://doi.org/10.1634/theoncologist.2017-0205.

    Article  PubMed  Google Scholar 

  26. Thomas DC, Arnold BN, Hoag JR, Salazar MC, Boffa DJ, Detterbeck FC, et al. Timing and Risk Factors Associated with Venous Thromboembolism Following Lung Cancer Resection. Ann Thorac Surg. 2018. https://doi.org/10.1016/j.athoracsur.2018.01.072.

    Article  PubMed  Google Scholar 

  27. Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res. 2010;125(6):490–3. https://doi.org/10.1016/j.thromres.2009.12.023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood. 2017;130(13):1499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Xue J, Xie VK, Wang P, Cui J, Gao Y, Lu Z. Interrelationships of circulating tumor cells with metastasis and thrombosis: role of microRNAs. Curr Pharm Des. 2014;20(33):5298–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by grants from ISCIII (Fis: PI13/01155, PI16/02104) and Consejeria de Salud of the Junta de Andalucia (PI-0096-2012).

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Authors and Affiliations

  1. Department of Medical Oncology, University Hospital Virgen del Rocío, Seville, Spain

    D. Herrero Rivera & R. Bernabé Caro

  2. Department of Radiation Oncology, University Hospital Virgen del Rocío, Manuel Siurot Avenue, s/n, 41013, Seville, Spain

    J. M. Nieto-Guerrero Gómez, D. Delgado, M. J. Ortiz Gordillo, M. C. Fernández Fernández & J. L. Lopez Guerra

  3. Department of Radiation Oncology, Cruces University Hospital, Barakaldo, Spain

    J. Cacicedo Fernández de Bobadilla

  4. Department of Radiation Oncology, Tenon University Hospital, Paris, France

    E. Rivin del Campo

  5. Methodology Unit, University Hospital Virgen del Rocío, Seville, Spain

    J. M. Praena-Fernández

  6. Instituto de Biomedicina de Sevilla (IBIS/HUVR, CSIC/Universidad de Sevilla), Seville, Spain

    M. J. Ortiz Gordillo & J. L. Lopez Guerra

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  1. D. Herrero Rivera
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Correspondence to J. L. Lopez Guerra.

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All persons listed as authors have given their approval for the submission of the paper. Authors declare that we do not have any financial support or relationships that may suppose conflict of interest.

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The information collected in this research has been obtained exclusively from human participants with the previous acceptance of these through informed consent. No animals were involved in this study.

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Herrero Rivera, D., Nieto-Guerrero Gómez, J.M., Cacicedo Fernández de Bobadilla, J. et al. Cardiovascular disease and survival in non-small cell lung cancer: a multicenter prospective assessment. Clin Transl Oncol 21, 1220–1230 (2019). https://doi.org/10.1007/s12094-019-02047-5

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