Association Between Thoracic Radiotherapy and Severity of Coronary Artery Calcification in Lung Cancer: A Retrospective Cohort Study
Main Article Content
Abstract
Objective To investigate the association between thoracic irradiation (TIR) and the severity of coronary artery calcification (CAC) in patients with lung cancer, and to provide evidence-based basis for cardiovascular risk stratification and early intervention in lung cancer patients undergoing radiotherapy. Methods A retrospective cohort study design was adopted. A total of 126 patients with primary lung cancer who received thoracic radiotherapy in the oncology department of a tertiary hospital from January 2018 to December 2023 were consecutively enrolled as the radiotherapy group, and 126 lung cancer patients diagnosed during the same period but without radiotherapy were matched at a 1:1 ratio as the non-radiotherapy group. Propensity score matching was performed for baseline characteristics including age, sex, smoking history, hypertension, diabetes, dyslipidemia and tumor stage. The CAC score was semiquantitatively calculated by the Agatston method based on follow-up chest CT images obtained at least 12 months after radiotherapy, and the severity was classified into three grades according to the number of involved vessels: no calcification, single-vessel calcification and multi-vessel calcification. Dosimetric parameters of the radiotherapy group were collected, including mean heart dose (MHD), heart V30 and left anterior descending artery (LAD) dose. Inter-group differences were compared using t-test, χ2 test and rank-sum test. Multivariate ordinal Logistic regression was used to analyze the independent influencing factors of CAC severity. Results The median CAC score in the radiotherapy group was significantly higher than that in the non-radiotherapy group [426.3 (IQR: 118.5–982.7) AU vs. 187.6 (IQR: 42.3–563.2) AU, Z=-4.215, P<0.001]. The proportion of multi-vessel calcification in the radiotherapy group was significantly higher than that in the non-radiotherapy group (46.0% vs. 27.0%, χ2=10.286, P=0.006). Multivariate ordinal Logistic regression analysis showed that after adjusting for age, hypertension, diabetes, dyslipidemia and smoking history, thoracic radiotherapy was an independent risk factor for increased CAC severity (OR=2.87, 95%CI: 1.64–5.02, P<0.001). In the subgroup analysis of the radiotherapy group, MHD≥10 Gy (OR=2.31, 95%CI: 1.12–4.76, P=0.023) and LAD maximum dose≥35 Gy (OR=2.05, 95%CI: 1.03–4.08, P=0.041) were independently associated with more severe CAC. Conclusion Thoracic radiotherapy in lung cancer patients is independently associated with increased severity of coronary artery calcification, and patients with higher cardiac radiation dose tend to have greater CAC severity. Routine baseline CAC assessment before radiotherapy, optimization of cardiac dose constraints during treatment, and strengthened cardiovascular event monitoring and early intervention during follow-up are recommended.
Downloads
Article Details

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
References
Chinese Society of Oncology and Chinese Medical Association Publishing House, “Chinese Medical Association clinical guidelines for the diagnosis and treatment of lung cancer (2024 edition),” National Medical Journal of China, vol. 104, no. 16, pp. 1169–1201, 2024.
M. X. Yang, W. T. Xu, R. R. Dai, et al., “Imaging manifestations and research progress of radiotherapy-related cardiovascular injury,” Journal of Clinical Cardiology, vol. 40, no. 8, pp. 625–630, 2024.
W. Zhang, G. F. Li, and J. J. Wang, “Research progress on heart injury caused by radiotherapy for thoracic tumors,” Chinese Journal of Radiation Oncology, vol. 32, no. 5, pp. 435–440, 2023.
J. Liu, Y. Zhang, and M. Zhang, “Clinical application value of coronary artery calcium scoring,” Chinese Journal of Cardiology, vol. 50, no. 3, pp. 295–300, 2022.
A. S. Agatston, W. R. Janowitz, F. J. Hildner, et al., “Quantification of coronary artery calcium using ultrafast computed tomography,” J Am Coll Cardiol, vol. 15, no. 4, pp. 827–832, 1990.
S. C. Darby, M. Ewertz, P. McGale, et al., “Risk of ischemic heart disease in women after radiotherapy for breast cancer,” N Engl J Med, vol. 368, no. 11, pp. 987–998, 2013.
M. Chen, X. L. Fu, and G. L. Jiang, “Relationship between cardiac dose and cardiac complications in lung cancer radiotherapy,” China Oncology, vol. 31, no. 8, pp. 745–752, 2021.
R. L. J. van der Palen, C. M. R. Zegers, E. C. Schimmel, et al., “Heart dose and coronary artery calcification in patients receiving thoracic irradiation for lung cancer,” J Thorac Dis, vol. 12, no. 5, pp. 2256–2266, 2020.
J. J. Wang, H. Z. Zhang, and J. R. Dai, “Research progress on cardiac substructure dose in predicting radiation-induced heart injury,” Chinese Journal of Radiological Medicine and Protection, vol. 43, no. 10, pp. 793– 800, 2023.
A. McWilliam, E. Spezi, R. Pai, et al., “Moving beyond mean heart dose: The importance of cardiac substructures in radiation therapy toxicity,” Acta Radiol, vol. 68, no. 5, pp. 974–986, 2024.
N. Yegya-Raman, M. Simon, S. Ganti, et al., “Understanding cardiac toxicity and immune responses to thoracic radiation therapy in non-small cell lung cancer – implications for future research,” Cancers (Basel), vol. 14, no. 15, p. 3685, 2022.
B. He and C. Wang, “Application of chest CT in coronary artery calcification assessment,” Chinese Journal of Tuberculosis and Respiratory Diseases, vol. 45, no. 6, pp. 580–585, 2022.
P. Greenland, M. J. Blaha, M. J. Budoff, et al., “2018 AHA/ACC/ AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines,” Circulation, vol. 139, no. 25, pp. e1082–e1143, 2019.
J. Li and Y. Zhang, “Pathogenesis and clinical significance of coronary artery calcification,” Chinese Journal of Cardiology, vol. 51, no. 2, pp. 185–190, 2023.
F. Liu, J. Zhu, and L. H. Wang, “Research progress on pathophysiological mechanisms of radiation-induced heart injury,” Chinese Journal of Radiation Oncology, vol. 31, no. 11, pp. 1098–1103, 2022.
A. Seaward, J. J. Kengwoung-Keumo, D. Gadi, et al., “Radiation-induced heart disease: current status and challenges,” Cells, vol. 12, no. 15, p. 1994, 2023.
F. Rodriguez, K. J. Lavine, S. Ormaza, et al., “Coronary atherosclerosis in patients with cancer and survivors: a scientific statement from the American Heart Association,” J Am Heart Assoc, vol. 15, no. 3, p. e031245, 2026.
L. H. Wang, X. L. Fu, M. Chen, et al., “Expert consensus on cardiac dose constraints in radiotherapy for locally advanced nonsmall cell lung cancer,” Chinese Journal of Radiation Oncology, vol. 32, no. 3, pp. 185– 192, 2023.
C. W. Taylor, Y. Zheng, P. Hall, et al., “Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous dose-response relationships,” Int J Radiat Oncol Biol Phys, vol. 99, no. 4, pp. 927–935, 2017.
J. D. Bradley, R. Paulus, R. Komaki, et al., “Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-smallcell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study,” Lancet Oncol, vol. 16, no. 2, pp. 187–199, 2015.
G. F. Li, J. J. Wang, and W. Zhang, “Limitations of mean heart dose in predicting cardiac toxicity of lung cancer radiotherapy and alternative indicators,” Chinese Journal of Lung Cancer, vol. 26, no. 7, pp. 485–493, 2023.
V. Gondi, C. Shah, S. Hardy, et al., “Mean heart dose is an inadequate surrogate for left anterior descending coronary artery dose and the risk of major adverse cardiac events in lung cancer radiation therapy,” Int J Radiat Oncol Biol Phys, vol. 111, no. 3, pp. 680–690, 2021.
H. Z. Zhang, J. J. Wang, and J. R. Dai, “Radiation dose constraints for cardiac substructures and radiotherapy plan optimization strategies,” Chinese Journal of Radiological Medicine and Protection, vol. 44, no. 6, pp. 455–462, 2024.
Y. D. Chen and Q. H. Jin, “Prevention and management of cancer therapy-related cardiovascular toxicity,” Chinese Journal of Cardiology, vol. 51, no. 4, pp. 345–352, 2023.
J. R. Dai and Y. M. Hu, “Progress and clinical application of intensity-modulated radiotherapy technology,” Chinese Journal of Radiation Oncology, vol. 31, no. 9, pp. 825–832, 2022.
Y. Huo, J. B. Ge, and W. Y. Fang, “Chinese expert consensus on clinical application of coronary artery calcium scoring,” Chinese Journal of Interventional Cardiology, vol. 31, no. 4, pp. 181–190, 2023.
J. Li, Y. Zhang, and Y. D. Chen, “Cardiovascular risk assessment and intervention of coronary calcification in elderly cancer patients,” Chinese Circulation Journal, vol. 39, no. 8, pp. 785–792, 2024.