Risks of heart disease from radiation
Heart radiation dose-response relationship
Studies since the 1960s showed that high dose radiotherapy to the chest area can cause heart disease. It became apparent in the 1990s that even lower doses may cause disease, but the size of the risk from modern radiotherapy was unknown.
In response to this need, we performed a case control study of heart disease after breast cancer radiotherapy. We produced the first heart radiation dose-response relationship based on a substantial number of cardiac events. This highlighted the cardiac risks from radiotherapy and enabled clinicians, for the first time, to predict the size of the absolute risk for each woman using her estimated radiation heart dose and other cardiac risk factors.
This study has influenced cancer practice worldwide, with over 100 references in national or international guidelines.
It led to the introduction of heart-sparing radiotherapy in many cancer centres in the UK and worldwide. Heart sparing radiotherapy is now widely available in many countries and it is recommended in national and international clinical guidelines.
We performed a further case control study in the context of Hodgkin lymphoma survivors, showing the presence of a remarkably similar dose response relationship in this very different patient group, demonstrating that this concept was applicable across a range of cancer types.
These studies also informed cardiology guidelines for follow-up of patients who previously received thoracic radiotherapy.
- Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of ischemic heart disease in women irradiated for breast cancer. New England Journal of Medicine 2013;368:987-98.
- van Nimwegen FA, Schaapveld M, Cutter DJ, Janus CP, Krol ADG, Hauptmann M, Kooijman K, Roesink J, van der Maazen R, Darby SC, Aleman BMP, van Leeuwen FE. A Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. Journal of Clinical Oncology 2016;34:235-43
radiation doses in modern breast cancer radiotherapy
We have developed a method called 'dose meta-analysis' to summarise modern doses in breast cancer radiotherapy, and their variation according to patient and tumour factors.
The main life-threatening risks from breast cancer radiotherapy are heart disease, lung cancer and oesophageal cancer. These risks increase according to heart radiation dose, lung dose and oesophageal dose respectively. We have performed dose meta-analyses of heart dose, lung dose and oesophageal dose from modern breast cancer radiotherapy. These have shown which breast cancer radiotherapy regimens have the lowest risks of heart disease (Taylor 2015) lung cancer (Aznar 2018) and oesophageal cancer (Duane 2021)
- Taylor CW, Wang Z, Macaulay E, Jagsi R, Darby SC. Exposure of the heart in breast cancer radiotherapy: A systematic review of heart doses published during 2003-2013. Int J Radiat Oncol Biol Phys 2015;93:845-53
- Aznar MC, Duane FK, Darby SC, Wang Z, Taylor CW. Exposure of the lungs in breast cancer radiotherapy: A systematic review of lung doses published 2010-2015. Radioth Oncol 2018;126:148-54.
- Duane FK, Kerr A, Wang Z, Darby SC, Ntentas G, Aznar MC, Taylor CW. Exposure of the oesophagus in breast cancer radiotherapy: A systematic review of oesophagus doses published 2010-2020. Radioth Oncol 2021;164:261-7
parts of the heart and radiation
We investigated the possibility that radiation dose to individual parts of the heart may result in different types of radiation-related heart disease. Through case control studies we showed that the radiation to the valves was related to valvular heart disease and radiation to the left ventricle was related to heart failure.
- Cutter DJ, Schaapveld M, Darby SC, Hauptmann M, van Nimwegen FA, Krol ADG, Janus C, van Leeuwen FE, Aleman BMP. Risk of Valvular Heart Disease after Treatment for Hodgkin Lymphoma. Journal of the Nationall Cancer Institute 2015;107(4)
- van Nimwegen FA, Ntentas G, Darby SC, Schaapveld M, Hauptmann M, Lugtenburg PJ, Janus CPM, Daniels L, van Leeuwen FE, Cutter DJ, Aleman BMP. Risk of heart failure in survivors of Hodgkin lymphoma: Effects of cardiac exposure to radiation and anthracyclines. Blood 2017;129:2257-2265
A further study of ~500 women who developed heart disease after breast cancer radiotherapy showed the risks of irradiating different parts of the heart including the left ventricle and major coronary arteries. We showed that all parts of the heart are sensitive to radiation, and should be avoided where possible.