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Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer

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Abstract

The primary cause of mortality in esophageal cancer survivors is cardiac death. Early identification of cardiac mortality risk during chemotherapy for esophageal cancer is crucial for improving the prognosis. We developed and validated a nomogram model to identify patients with high cardiac mortality risk after chemotherapy for esophageal cancer for early screening and clinical decision-making. We randomly allocated 37,994 patients with chemotherapy-treated esophageal cancer into two groups using a 7:3 split ratio: model training (n = 26,598) and validation (n = 11,396). 5- and 10-year survival rates were used as endpoints for model training and validation. Decision curve analysis and the consistency index (C-index) were used to evaluate the model’s net clinical advantage. Model performance was evaluated using receiver operating characteristic curves and computing the area under the curve (AUC). Kaplan–Meier survival analysis based on the prognostic index was performed. Patient risk was stratified according to the death probability. Age, surgery, sex, and year were most closely related to cardiac death and used to plot the nomograms. The C-index for the training and validation datasets were 0.669 and 0.698, respectively, indicating the nomogram’s net clinical advantage in predicting cardiac death risk at 5 and 10 years. The 5- and 10-year AUCs were 0.753 and 0.772 for the training dataset and 0.778 and 0.789 for the validation dataset, respectively. The accuracy of the model in predicting cardiac death risk was moderate. This nomogram can identify patients at risk of cardiac death after chemotherapy for esophageal cancer at an early stage.

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Abbreviations

AUC:

Area under the curve

C-index:

Consistency index

CVD:

Cardiovascular disease

DCA:

Decision curve analysis

EC:

Esophageal cancer

ICD-O-3:

International Classification of Diseases for Oncology: third edition

K-M:

Kaplan–Meier

LASSO:

Least absolute shrinkage and selection operator

NOS:

Not otherwise specified

ROC:

Receiver operating characteristic

SEER:

Surveillance, epidemiology, and end results

References

  1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71, 209–249.

    PubMed  Google Scholar 

  2. Xie, S. H., Wahlin, K., & Lagergren, J. (2017). Cause of death in patients diagnosed with esophageal cancer in Sweden: A population-based study. Oncotarget, 8, 51800–51809.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Deng, W., Yu, R., Yang, Z., Dong, X., & Wang, W. (2021). Trends in conditional overall survival of esophageal cancer: A population-based study. Ann Transl Med., 9, 102.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Astrup Søndergaard, M. M., Nordsmark, M., Sloth Møller, D., Melgaard Nielsen, K., & Poulsen, S. H. (2022). Reduction in myocardial function and oxygen consumption after chemoradiotherapy in patients with esophageal cancer. Acta Oncologica, 61, 566–574.

    Article  PubMed  Google Scholar 

  5. Lund, M., Alexandersson von Döbeln, G., Nilsson, M., Winter, R., Lundell, L., Tsai, J. A., & Kalman, S. (2015). Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction—A prospective cohort pilot study within a randomized clinical trial. Radiation Oncology, 10, 16.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Parr, S. K., Liang, J., Schadler, K. L., Gilchrist, S. C., Steele, C. C., & Ade, C. J. (2020). Anticancer therapy-related increases in arterial stiffness: A systematic review and meta-analysis. Journal of the American Heart Association, 9, e015598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Han, J., Wang, Z., & Liu, C. (2021). Survival and complications after neoadjuvant chemotherapy or chemoradiotherapy for esophageal cancer: A meta-analysis. Future Oncology, 17, 2257–2274.

    Article  CAS  PubMed  Google Scholar 

  8. Long, D., Chen, C., Li, W., Peng, W., Li, D., Zhou, R., et al. (2022). Cardiac expression of esophageal cancer-related gene-4 is regulated by Sp1 and is a potential early target of doxorubicin-induced cardiotoxicity. Cardiovascular Toxicology, 22, 404–418.

    Article  CAS  PubMed  Google Scholar 

  9. Frandsen, J., Boothe, D., Gaffney, D. K., Wilson, B. D., & Lloyd, S. (2015). Increased risk of death due to heart disease after radiotherapy for esophageal cancer. Journal of Gastrointestestinal Oncology, 6, 516–523.

    Google Scholar 

  10. Gharzai, L., Verma, V., Denniston, K. A., Bhirud, A. R., Bennion, N. R., & Lin, C. (2016). Radiation therapy and cardiac death in long-term survivors of esophageal cancer: An analysis of the surveillance, epidemiology, and end result database. PLoS ONE, 11, e0158916.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Xie, S. H., Santoni, G., Mälberg, K., Lagergren, P., & Lagergren, J. (2021). Prediction model of long-term survival after esophageal cancer surgery. Annals of Surgery, 273, 933–939.

    Article  PubMed  Google Scholar 

  12. Qie, S., Shi, H., Wang, F., Liu, F., Gu, J., Liu, X., et al. (2022). Construction of survival prediction model for elderly esophageal cancer. Frontiers in Oncology, 12, 1008326.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Öztürk, C., Validyev, D., Becher, U. M., Weber, M., Nickenig, G., & Tiyerili, V. (2021). A novel scoring system to estimate chemotherapy-induced myocardial toxicity: Risk assessment prior to non-anthracycline chemotherapy regimens. International Journal of Cardiology. Heart & Vasculature, 33, 100751.

    Article  Google Scholar 

  14. Park, H. S., Lloyd, S., Decker, R. H., Wilson, L. D., & Yu, J. B. (2012). Overview of the surveillance, epidemiology, and end results database: Evolution, data variables, and quality assurance. Current Problems in Cancer, 36, 183–190.

    Article  PubMed  Google Scholar 

  15. Guan, T., Zhang, H., Yang, J., Lin, W., Wang, K., Su, M., et al. (2020). Increased risk of cardiovascular death in breast cancer patients without chemotherapy or (and) radiotherapy: A large population-based study. Frontiers in Oncology, 10, 619622.

    Article  PubMed  Google Scholar 

  16. Lester, S. C., Lin, S. H., Chuong, M., Bhooshan, N., Liao, Z., Arnett, A. L., et al. (2017). A multi-institutional analysis of trimodality therapy for esophageal cancer in elderly patients. International Journal of Radiation Oncology Biology Physics, 98, 820–828.

    Article  PubMed  Google Scholar 

  17. Lagergren, J., Bottai, M., & Santoni, G. (2021). Patient age and survival after surgery for esophageal cancer. Annals of Surgical Oncology, 28, 159–166.

    Article  PubMed  Google Scholar 

  18. Takeuchi, S., Ohtsu, A., Doi, T., Kojima, T., Minashi, K., Mera, K., & Nihei, K. (2007). A retrospective study of definitive chemoradiotherapy for elderly patients with esophageal cancer. American Journal of Clinical Oncology, 30(6), 607–611.

    Article  PubMed  Google Scholar 

  19. Braiteh, F., Correa, A. M., Hofstetter, W. L., Rice, D. C., Vaporciyan, A. A., Walsh, G. L., et al. (2009). Association of age and survival in patients with gastroesophageal cancer undergoing surgery with or without preoperative therapy. Cancer, 115, 4450–4458.

    Article  PubMed  Google Scholar 

  20. Lettino, M., Mascherbauer, J., Nordaby, M., Ziegler, A., Collet, J. P., Derumeaux, G., Hohnloser, S. H., Leclercq, C., O’Neill, D. E., Visseren, F., & Weidinger, F. (2022). Cardiovascular disease in the elderly: Proceedings of the European Society of Cardiology—Cardiovascular Round Table. European Journal of Preventive Cardiology, 29(10), 1412–1424.

    Article  PubMed  Google Scholar 

  21. He, F., Wang, J., Liu, L., Qin, X., Wan, Z., Li, W., et al. (2021). Esophageal cancer: Trends in incidence and mortality in China from 2005 to 2015. Cancer Medicine, 10, 1839–1847.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lin, L., Li, Z., Yan, L., Liu, Y., Yang, H., & Li, H. (2021). Global, regional, and national cancer incidence and death for 29 cancer groups in 2019 and trends analysis of the global cancer burden, 1990–2019. Journal of Hematology & Oncology, 14, 197.

    Article  Google Scholar 

  23. Chen, M. F., Yang, Y. H., Lai, C. H., Chen, P. C., & Chen, W. C. (2013). Outcome of patients with esophageal cancer: A nationwide analysis. Annals of Surgical Oncology, 20, 3023–3030.

    Article  PubMed  Google Scholar 

  24. Sukocheva, O. A., Li, B., Due, S. L., Hussey, D. J., & Watson, D. I. (2015). Androgens and esophageal cancer: What do we know? World Journal of Gastroenterology, 21, 6146–6156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Dix, O., Thakur, M., & Genova, A. (2020). Increased risk of esophageal cancers among men in Taiwan. Cureus, 12, e6990.

    PubMed  PubMed Central  Google Scholar 

  26. Chen, J., Zhang, N., Wakai, T., Wei, L., He, Y., Kumagai, N., et al. (2010). Effect of the interaction between the amount and duration of alcohol consumption and tobacco smoking on the risk of esophageal cancer: A case-control study. Experimental and Therapeutic Medicine, 1, 991–997.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Nobel, T. B., Livschitz, J., Eljalby, M., Janjigian, Y. Y., Bains, M. S., Adusumilli, P. S., et al. (2020). Unique considerations for females undergoing esophagectomy. Annals of Surgery, 272, 113–117.

    Article  PubMed  Google Scholar 

  28. Bose, A., O’Neal, W. T., Wu, C., McClure, L. A., Judd, S. E., Howard, V. J., et al. (2019). Sex Differences in risk factors for incident atrial fibrillation (from the reasons for geographic and racial differences in stroke [REGARDS] study). American Journal of Cardiology, 123, 1453–1457.

    Article  PubMed  Google Scholar 

  29. Kittnar, O. (2020). Selected sex related differences in pathophysiology of cardiovascular system. Physiological Research, 69, 21–31.

    Article  CAS  PubMed  Google Scholar 

  30. Yang, C. J., Wang, Y., Raman, V., Patel, D., Lui, N., Backhus, L., et al. (2021). A national analysis of treatment patterns and outcomes for patients 80 years or older with esophageal cancer. Seminars in Thoracic and Cardiovascular Surgery, 33, 884–892.

    Article  PubMed  Google Scholar 

  31. Rahouma, M., Harrison, S., Kamel, M., Nasar, A., Lee, B., Port, J., et al. (2018). Consequences of refusing surgery for esophageal cancer: A National Cancer Database Analysis. Annals of Thoracic Surgery, 106, 1476–1483.

    Article  PubMed  Google Scholar 

  32. Li, C. C., Chen, C. Y., & Chien, C. R. (2018). Comparison of intensity-modulated radiotherapy vs 3-dimensional conformal radiotherapy for patients with non-metastatic esophageal squamous cell carcinoma receiving definitive concurrent chemoradiotherapy: A population-based propensity-score-matched analysis. Medicine (Baltimore), 97, e10928.

    Article  PubMed  Google Scholar 

  33. Song, E. Y., Frakes, J. M., Extermann, M., Klocksieben, F., Mehta, R., Saeed, S., et al. (2020). Clinical factors and outcomes of octogenarians receiving curative surgery for esophageal cancer. Journal of Surgical Research, 251, 100–106.

    Article  PubMed  Google Scholar 

  34. Abrams, J. A., Buono, D. L., Strauss, J., McBride, R. B., Hershman, D. L., & Neugut, A. I. (2009). Esophagectomy compared with chemoradiation for early stage esophageal cancer in the elderly. Cancer, 115, 4924–4933.

    Article  PubMed  Google Scholar 

  35. Motoyama, S., Maeda, E., Iijima, K., Sato, Y., Koizumi, S., Wakita, A., et al. (2022). Does esophagectomy provide a survival advantage to patients aged 80 years or older? Analyzing 5066 patients in the national database of hospital-based cancer registries in Japan. Annals of Surgery, 276, e16–e23.

    Article  PubMed  Google Scholar 

  36. Ruol, A., Portale, G., Castoro, C., Merigliano, S., Cagol, M., Cavallin, F., et al. (2007). Effects of neoadjuvant therapy on perioperative morbidity in elderly patients undergoing esophagectomy for esophageal cancer. Annals of Surgical Oncology, 14, 3243–3250.

    Article  PubMed  Google Scholar 

  37. Eads, J. R. (2021). Cardiovascular concerns in the management of esophageal cancer patients. JACC CardioOncology, 3, 722–724.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Li, X., Chen, L., Luan, S., Zhou, J., Xiao, X., Yang, Y., et al. (2022). The development and progress of nanomedicine for esophageal cancer diagnosis and treatment. Seminars in Cancer Biology, 86, 873–885.

    Article  CAS  PubMed  Google Scholar 

  39. Kakeji, Y., Oshikiri, T., Takiguchi, G., Kanaji, S., Matsuda, T., Nakamura, T., et al. (2021). Multimodality approaches to control esophageal cancer: Development of chemoradiotherapy, chemotherapy, and immunotherapy. Esophagus, 18, 25–32.

    Article  PubMed  Google Scholar 

  40. Amin, N. P., Desai, N., Kim, S. M., Agarwal, M., & Amin, N. P. (2020). Cardiac monitoring for thoracic radiation therapy: Survey of practice patterns in the United States. American Journal of Clinical Oncology, 43, 249–256.

    Article  PubMed  Google Scholar 

  41. Launay, L., Dejardin, O., Pornet, C., Morlais, F., Guittet, L., Launoy, G., et al. (2012). Influence of socioeconomic environment on survival in patients diagnosed with esophageal cancer: A population-based study. Diseases of the Esophagus, 25, 723–730.

    Article  CAS  PubMed  Google Scholar 

  42. Chen, H. Y., Chen, I. C., Chen, Y. H., Chen, C. C., Chuang, C. Y., & Lin, C. H. (2022). The influence of socioeconomic status on esophageal cancer in Taiwan: A population-based study. Journal of Personalized Medicine, 12(4), 595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Brusselaers, N., Mattsson, F., Lindblad, M., & Lagergren, J. (2015). Association between education level and prognosis after esophageal cancer surgery: A Swedish population-based cohort study. PLoS ONE, 10, e0121928.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Bus, P., Aarts, M. J., Lemmens, V. E., van Oijen, M. G., Creemers, G. J., Nieuwenhuijzen, G. A., et al. (2012). The effect of socioeconomic status on staging and treatment decisions in esophageal cancer. Journal of Clinical Gastroenterology, 46, 833–839.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank the National Cancer Institute for providing access to the data in the SEER database.

Funding

This work was supported by the National Natural Science Foundation of China [Number 81873132]; 2021 Annual Education Unveiling Hanging Project [Number 2021jyjbgs-03]; 2018 Chinese medicine research projects to prevent and treat major diseases [Number GZKZD-2018-02]; the Lanzhou Science and Technology Plan Project [Number 2022-3-27]; Special Open Project of Gansu Research Center of Traditional Chinese Medicine (No.zyzx-2020-zx8); and the Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital [Number CY2021-BJ-A17].

Author information

Author notes

  1. Xinfang Lv and Xue Wu have contributed equally and share first authorship.

Authors and Affiliations

  1. Department of Geriatrics, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou City, Gansu Province, China

    Xinfang Lv

  2. Department of Cardiology, The Second Hospital of Lanzhou University, Lanzhou City, Gansu Province, China

    Xue Wu

  3. School of Integrative Medicine, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, China

    Xinfang Lv, Xue Wu, Kai Liu, Xinke Zhao, Xiang Gao, Xiaodong Zhi, Chunzhen Ren, Qilin Chen, Hugang Jiang, Chunling Wang & Yingdong Li

  4. Cardiovascular Disease Center, The First Hospital of Lanzhou University, Lanzhou City, Gansu Province, China

    Chenliang Pan & Jing Zhao

  5. Department of Traditional Medicine, Gansu Provincial Hospital, Lanzhou City, Gansu Province, China

    Juan Chang

  6. Center for Translational Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou City, Gansu Province, China

    Huan Guo

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  1. Xinfang Lv
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Contributions

Lv XF, Wu X, Liu K, Zhao XK, and Li YD designed the research; Chang J, Guo H, Gao X, Zhi XD, Ren CZ and Chen QL obtained and organized the data for the article; Pan CL and Zhao J analyzed the data; Lv XF drafted the manuscript; The manuscript was corrected by Jiang HG and Wang CL. All authors contributed to editing the manuscript and approved the final version.

Corresponding author

Correspondence to Yingdong Li.

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Lv, X., Wu, X., Liu, K. et al. Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer. Cardiovasc Toxicol 23, 377–387 (2023). https://doi.org/10.1007/s12012-023-09807-4

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