Skip to main content

Advertisement

Log in

Effects of Radiotherapy in Coronary Artery Disease

  • Evidence-Based Medicine, Clinical Trials and Their Interpretations (L. Roever, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review describes the effects of radiotherapy (RT) on coronary artery disease, its mechanisms, and clinical and laboratory evidence and discusses ways to minimize radiation-induced coronary atherosclerosis.

Recent Findings

Radiation-induced cardiac toxicity is known in patients undergoing thoracic RT. One of the damages occurs in the coronary arteries, with accelerated atherosclerosis manifesting decades later. There is clinical and laboratory evidence of coronary damage in retrospective studies, systematic reviews, and meta-analyses. Clinical studies have shown that RT cardiotoxicity occurs decades after radiation, regardless of chemotherapy, and may occur earlier in patients with pre-existing risk factors or disease.

Summary

The pathogenesis of radiation-induced coronary artery disease is complex and multifactorial, including endothelial dysfunction, altered vascular tone, hemostatic imbalance, and inflammatory activation. Some factors are responsible, such as mean heart dose, RT chest site, patient position, techniques, and breathing maneuvers. There are approaches to reduce radiation-induced cardiac toxicity. Among them, besides the mentioned factors, metformin and anti-inflammatory agents can minimize coronary damage, with impact on morbidity and mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. https://doi.org/10.3322/caac.21551.

    Article  PubMed  Google Scholar 

  3. Thompson MK, Poortmans P, Chalmers AJ, Faivre-Finn C, Hall E, Huddart RA, et al. Practice-changing radiation therapy trials for the treatment of cancer: where are we 150 years after the birth of Marie Curie? Br J Cancer. 2018;119(4):389–407. https://doi.org/10.1038/s41416-018-0201-z.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Armanious MA, Mohammadi H, Khodor S, Oliver DE, Johnstone PA, Fradley MG. Cardiovascular effects of radiation therapy. Curr Probl Cancer. 2018;42(4):433–42. https://doi.org/10.1016/j.currproblcancer.2018.05.008.

    Article  PubMed  Google Scholar 

  5. Stewart JR, Fajardo LF. Radiation-induced heart disease: an update. Prog Cardiovasc Dis. 1984;27(3):173–94.

    Article  CAS  Google Scholar 

  6. Demirci S, Nam J, Hubbs JL, Nguyen T, Marks LB. Radiation-induced cardiac toxicity after therapy for breast cancer: interaction between treatment era and follow-up duration. Int J Radiat Oncol Biol Phys. 2009;73(4):980–7. https://doi.org/10.1016/j.ijrobp.2008.11.016.

    Article  PubMed  Google Scholar 

  7. • Baselet B, Sonveaux P, Baatout S, Aerts A. Pathological effects of ionizing radiation: endothelial activation and dysfunction. Cell Mol Life Sci. 2019;76(4):699–728. https://doi.org/10.1007/s00018-018-2956-z This is a recent review article on the mechanisms of radiotherapy-related endothelial dysfunction.

    Article  CAS  PubMed  Google Scholar 

  8. Venkatesulu BP, Mahadevan LS, Aliru ML, Yang X, Bodd MH, Singh PK, et al. Radiation-induced endothelial vascular injury: a review of possible mechanisms. JACC Basic Transl Sci. 2018;3(4):563–72. https://doi.org/10.1016/j.jacbts.2018.01.014.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Milgrom SA, Varghese B, Gladish GW, Choi AD, Dong W, Patel ZS, et al. Coronary artery dose-volume parameters predict risk of calcification after radiation therapy. J Cardiovasc Imaging. 2019;27:e38. https://doi.org/10.4250/jcvi.2019.27.e38.

    Article  Google Scholar 

  10. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–98. https://doi.org/10.1056/NEJMoa1209825.

    Article  CAS  PubMed  Google Scholar 

  11. Taylor CW, Wang Z, Macaulay E, Jagsi R, Duane F, Darby SC. Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013. Int J Radiat Oncol Biol Phys. 2015;93(4):845–53. https://doi.org/10.1016/j.ijrobp.2015.07.2292.

    Article  PubMed  Google Scholar 

  12. Pierce LJ, Feng M, Griffith KA, Jagsi R, Boike T, Dryden D, et al. Moran JM; Michigan Radiation Oncology Quality Consortium. Recent time trends and predictors of heart dose from breast radiation therapy in a large quality consortium of radiation oncology practices. Int J Radiat Oncol Biol Phys. 2017;99(5):1154–61. https://doi.org/10.1016/j.ijrobp.2017.07.022.

    Article  PubMed  Google Scholar 

  13. Boero IJ, Paravati AJ, Triplett DP, Hwang L, Matsuno RK, Gillespie EF, et al. Modern radiation therapy and cardiac outcomes in breast cancer. Int J Radiat Oncol Biol Phys. 2016;94(4):700–8. https://doi.org/10.1016/j.ijrobp.2015.12.018.

    Article  PubMed  Google Scholar 

  14. van Nimwegen FA, Schaapveld M, Cutter DJ, Janus CP, Krol AD, Hauptmann M, et al. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. J Clin Oncol. 2016;34(3):235–43. https://doi.org/10.1200/JCO.2015.63.4444.

    Article  CAS  PubMed  Google Scholar 

  15. Niska JR, Thorpe CS, Allen SM, Daniels TB, Rule WG, Schild SE, et al. Radiation and the heart: systematic review of dosimetry and cardiac endpoints. Expert Rev Cardiovasc Ther. 2018;16(12):931–50. https://doi.org/10.1080/14779072.2018.1538785.

    Article  CAS  PubMed  Google Scholar 

  16. Wang K, Eblan MJ, Deal AM, Lipner M, Zagar TM, Wang Y, et al. Cardiac toxicity after radiotherapy for stage III non-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy. J Clin Oncol. 2017;35(13):1387–94. https://doi.org/10.1200/JCO.2016.70.0229.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Shiraishi Y, Xu C, Yang J, Komaki R, Lin SH. Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or intensity-modulated radiation therapy. Radiother Oncol. 2017;125(1):48–54. https://doi.org/10.1016/j.radonc.2017.07.034.

    Article  PubMed  Google Scholar 

  18. Ntentas G, Dedeckova K, Andrlik M, Aznar MC, George B, Kubeš J, et al. Clinical intensity modulated proton therapy for Hodgkin lymphoma: which patients benefit the most? Pract Radiat Oncol. 2019;9(3):179–87. https://doi.org/10.1016/j.prro.2019.01.006.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Teoh S, Fiorini F, George B, Vallis KA, Van den Heuvel F. Proton vs photon: a model-based approach to patient selection for reduction of cardiac toxicity in locally advanced lung cancer. Radiother Oncol. 2019. https://doi.org/10.1016/j.radonc.2019.06.032.

  20. Bartlett FR, Colgan RM, Donovan EM, McNair HA, Carr K, Evans PM, et al. The UK HeartSpare Study (Stage IB): randomised comparison of a voluntary breath-hold technique and prone radiotherapy after breast conserving surgery. Radiother Oncol. 2015;114(1):66–72. https://doi.org/10.1016/j.radonc.2014.11.018.

    Article  PubMed  Google Scholar 

  21. Zagar TM, Kaidar-Person O, Tang X, Jones EE, Matney J, Das SK, et al. Utility of deep inspiration breath hold for left-sided breast radiation therapy in preventing early cardiac perfusion defects: a prospective study. Int J Radiat Oncol Biol Phys. 2017;97(5):903–9. https://doi.org/10.1016/j.ijrobp.2016.12.017.

    Article  PubMed  Google Scholar 

  22. Bartlett FR, Donovan EM, McNair HA, Corsini LA, Colgan RM, Evans PM, et al. The UK HeartSpare Study (Stage II): multicentre evaluation of a voluntary breath-hold technique in patients receiving breast radiotherapy. Clin Oncol (R Coll Radiol). 2017;29(3):e51–6. https://doi.org/10.1016/j.clon.2016.11.005.

    Article  CAS  PubMed  Google Scholar 

  23. • Das D, Asher A, Ghosh AK. Cancer and coronary artery disease: common associations, diagnosis and management challenges. Curr Treat Options Oncol. 2019;20(6):46. https://doi.org/10.1007/s11864-019-0644-3 Review of the diagnosis of ischemic heart disease secondary to radiotherapy and its management in cancer patients.

    Article  PubMed  Google Scholar 

  24. Haffty BG. Supine or prone breast radiation: upsides and downsides. Int J Radiat Oncol Biol Phys. 2018;101(3):510–2. https://doi.org/10.1016/j.ijrobp.2018.03.023.

    Article  PubMed  Google Scholar 

  25. Yao S, Zhang Y, Nie K, Liu B, Haffty BG, Ohri N, et al. Setup uncertainties and the optimal imaging schedule in the prone position whole breast radiotherapy. Radiat Oncol. 2019;14(1):76. https://doi.org/10.1186/s13014-019-1282-4.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kang HJ, Kim SW, Son SH. The feasibility of a heart block with an electron compensation as an alternative whole breast radiotherapy technique in patients with underlying cardiac or pulmonary disease. PLoS One. 2017;12(9):e0184137. https://doi.org/10.1371/journal.pone.0184137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kowalchuk RO, Romano KD, Trifiletti DM, Dutta SW, Showalter TN, Morris MM. Preliminary toxicity results using partial breast 3D-CRT with once daily hypo-fractionation and deep inspiratory breath hold. Radiat Oncol. 2018;13(1):135. https://doi.org/10.1186/s13014-018-1079-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Roychoudhuri R, Robinson D, Putcha V, Cuzick J, Darby S, Møller H. Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study. BMC Cancer. 2007;7:9. https://doi.org/10.1186/1471-2407-7-9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Henson KE, McGale P, Taylor C, Darby SC. Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer. Br J Cancer. 2013;108(1):179–82. https://doi.org/10.1038/bjc.2012.575.

    Article  CAS  PubMed  Google Scholar 

  30. •• Zagar TM, Cardinale DM, Marks LB. Breast cancer therapy-associated cardiovascular disease. Nat Rev Clin Oncol. 2016;13(3):172–84. https://doi.org/10.1038/nrclinonc.2015.171 This is a review of the risks of cardiovascular disease resulting from radiotherapy and chemotherapy in breast cancer patients. Strategies to minimize this risk are discussed.

    Article  CAS  PubMed  Google Scholar 

  31. Darby SC, McGale P, Taylor CW, Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol. 2005;6(8):557–65. https://doi.org/10.1016/S1470-2045(05)70251-5.

    Article  PubMed  Google Scholar 

  32. McGale P, Darby SC, Hall P, Adolfsson J, Bengtsson NO, Bennet AM, et al. Incidence of heart disease in 35 000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol. 2011;100(2):167–75. https://doi.org/10.1016/j.radonc.2011.06.016.

    Article  PubMed  Google Scholar 

  33. Sardar P, Kundu A, Chatterjee S, Nohria A, Nairooz R, Bangalore S, et al. Long-term cardiovascular mortality after radiotherapy for breast cancer: a systematic review and meta-analysis. Clin Cardiol. 2017;40(2):73–81. https://doi.org/10.1002/clc.22631.

    Article  PubMed  Google Scholar 

  34. Cheng YJ, Nie XY, Ji CC, Lin XX, Liu LJ, Chen XM, et al. Long-term cardiovascular risk after radiotherapy in women with breast cancer. J Am Heart Assoc. 2017;6(5):e005633. https://doi.org/10.1161/JAHA.117.005633.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Taylor C, Correa C, Duane FK, Aznar MC, Anderson SJ, Bergh J, et al. McGale P; Early Breast Cancer Trialists’ Collaborative Group. Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. J Clin Oncol. 2017;35(15):1641–9. https://doi.org/10.1200/JCO.2016.72.0722.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wennstig AK, Garmo H, Isacsson U, Gagliardi G, Rintelä N, Lagerqvist B, et al. The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiat Oncol. 2019;14(1):40. https://doi.org/10.1186/s13014-019-1242-z.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Moignier A, Broggio D, Derreumaux S, Beaudré A, Girinsky T, Paul JF, et al. Coronary stenosis risk analysis following Hodgkin lymphoma radiotherapy: a study based on patient specific artery segments dose calculation. Radiother Oncol. 2015;117(3):467–72. https://doi.org/10.1016/j.radonc.2015.07.043.

    Article  PubMed  Google Scholar 

  38. Wu W, Masri A, Popovic ZB, Smedira NG, Lytle BW, Marwick TH, et al. Long-term survival of patients with radiation heart disease undergoing cardiac surgery: a cohort study. Circulation. 2013;127(14):1476–85. https://doi.org/10.1161/CIRCULATIONAHA.113.001435.

    Article  PubMed  Google Scholar 

  39. • Lee Chuy K, Nahhas O, Dominic P, Lopez C, Tonorezos E, Sidlow R, et al. Cardiovascular complications associated with mediastinal radiation. Curr Treat Options Cardiovasc Med. 2019;21(7):31. https://doi.org/10.1007/s11936-019-0737-0 This is a review article on cardiovascular complications (including myocardium, endocardium, pericardium, and carotid and cerebrovascular arteries) associated with mediastinal radiotherapy.

    Article  PubMed  Google Scholar 

  40. Skyttä T, Tuohinen S, Boman E, Virtanen V, Raatikainen P, Kellokumpu-Lehtinen PL. Troponin T-release associates with cardiac radiation doses during adjuvant left-sided breast cancer radiotherapy. Radiat Oncol. 2015;10:141. https://doi.org/10.1186/s13014-015-0436-2.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Michel L, Rassaf T, Totzeck M. Biomarkers for the detection of apparent and subclinical cancer therapy-related cardiotoxicity. J Thorac Dis. 2018;10(Suppl 35):S4282–95. https://doi.org/10.21037/jtd.2018.08.15.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Zhang C, Shi D, Yang P. BNP as a potential biomarker for cardiac damage of breast cancer after radiotherapy: a meta-analysis. Medicine (Baltimore). 2019;98(29):e16507. https://doi.org/10.1097/MD.0000000000016507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Demissei BG, Freedman G, Feigenberg SJ, Plastaras JP, Maity A, Smith AM, et al. Early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy for breast cancer, lung cancer, and lymphoma. Int J Radiat Oncol Biol Phys. 2019;103(4):851–60. https://doi.org/10.1016/j.ijrobp.2018.11.013.

    Article  CAS  PubMed  Google Scholar 

  44. Hawkins PG, Sun Y, Dess RT, Jackson WC, Sun G, Bi N, et al. Circulating microRNAs as biomarkers of radiation-induced cardiac toxicity in non-small-cell lung cancer. J Cancer Res Clin Oncol. 2019;145(6):1635–43. https://doi.org/10.1007/s00432-019-02903-5.

    Article  CAS  PubMed  Google Scholar 

  45. University of Pennsylvania. Pragmatic randomized trial of proton vs. photon therapy for patients with non-metastatic breast cancer: a radiotherapy comparative effectiveness (RADCOMP) consortium trial. ClinicalTrials.gov Identifier: NCT02603341

  46. Yu JM, Hsieh MC, Qin L, Zhang J, Wu SY. Metformin reduces radiation-induced cardiac toxicity risk in patients having breast cancer. Am J Cancer Res. 2019;9(5):1017–26 PMC6556611.

    PubMed  PubMed Central  Google Scholar 

  47. Saraei P, Asadi I, Kakar MA, Moradi-Kor N. The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer Manag Res. 2019;11:3295–313. https://doi.org/10.2147/CMAR.S200059.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Roshan MH, Shing YK, Pace NP. Metformin as an adjuvant in breast cancer treatment. SAGE Open Med. 2019;7:2050312119865114. https://doi.org/10.1177/2050312119865114.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Boulet J, Peña J, Hulten EA, Neilan TG, Dragomir A, Freeman C, et al. Statin use and risk of vascular events among cancer patients after radiotherapy to the thorax, head, and neck. J Am Heart Assoc. 2019;8(13):e005996. https://doi.org/10.1161/JAHA.117.005996.

    Article  PubMed  PubMed Central  Google Scholar 

  50. O’Herron T, Lafferty J. Prophylactic use of colchicine in preventing radiation induced coronary artery disease. Med Hypotheses. 2018;111:58–60. https://doi.org/10.1016/j.mehy.2017.12.021.

    Article  CAS  PubMed  Google Scholar 

  51. Christersdottir T, Pirault J, Gisterå A, Bergman O, Gallina AL, Baumgartner R, et al. Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade. Eur Heart J. 2019;40(30):2495–503. https://doi.org/10.1093/eurheartj/ehz206.

    Article  PubMed  PubMed Central  Google Scholar 

  52. •• Ridker PM, JG MF, Thuren T, Everett BM, Libby P, Glynn RJ, et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10105):1833–42. https://doi.org/10.1016/S0140-6736(17)32247-X Randomized, double-blind, placebo-controlled study that demonstrated the critical importance of inhibition of inflammation in lung cancer.

    Article  CAS  PubMed  Google Scholar 

  53. Ma CX, Zhao XK, Li YD. New therapeutic insights into radiation-induced myocardial fibrosis. Ther Adv Chronic Dis. 2019;10:2040622319868383. https://doi.org/10.1177/2040622319868383.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Mehta LS, Watson KE, Barac A, Beckie TM, Bittner V, Cruz-Flores S, et al. Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from the American Heart Association. Circulation. 2018;137(8):e30–66. https://doi.org/10.1161/CIR.0000000000000556.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Campia U, Moslehi JJ, Amiri-Kordestani L, Barac A, Beckman JA, Chism DD, et al. Cardio-oncology: vascular and metabolic perspectives: a scientific statement from the American Heart Association. Circulation. 2019;139(13):e579–602. https://doi.org/10.1161/CIR.0000000000000641.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Strnad V, Major T, Polgar C, Lotter M, Guinot JL, Gutierrez-Miguelez C, et al. ESTRO-ACROP guideline: interstitial multi-catheter breast brachytherapy as accelerated partial breast irradiation alone or as boost - GEC-ESTRO Breast Cancer Working Group practical recommendations. Radiother Oncol. 2018;128(3):411–20. https://doi.org/10.1016/j.radonc.2018.04.009.

    Article  PubMed  Google Scholar 

  57. Abdel-Qadir H, Thavendiranathan P, Austin PC, Lee DS, Amir E, Tu JV, et al. Development and validation of a multivariable prediction model for major adverse cardiovascular events after early stage breast cancer: a population-based cohort study. Eur Heart J. 2019. https://doi.org/10.1093/eurheartj/ehz460.

Download references

Author information

Authors and Affiliations

Authors

Ethics declarations

Conflict of Interest

Rose Mary Ferreira Lisboa da Silva declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Evidence-Based Medicine, Clinical Trials and Their Interpretations

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silva, R.M.F.L. Effects of Radiotherapy in Coronary Artery Disease. Curr Atheroscler Rep 21, 50 (2019). https://doi.org/10.1007/s11883-019-0810-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-019-0810-x

Keywords

Navigation