Estimated Doses to the Heart, Lungs and Oesophagus and Risks From Typical UK Radiotherapy for Early Breast Cancer During 2015-2023

Abstract

Purpose: Breast cancer radiotherapy can increase the risks of heart disease, lung cancer and oesophageal cancer. At present, the best dosimetric predictors of these risks are mean doses to the whole heart, lungs and oesophagus, respectively. We aimed to estimate typical doses to these organs and resulting risks from UK breast cancer radiotherapy.

Methods: A systematic review and meta-analysis was conducted of planned or delivered mean doses to the whole heart, lungs or oesophagus from UK breast cancer radiotherapy in studies published during 2015-2023. Average mean doses were summarised for combinations of laterality and clinical targets. Heart disease and lung cancer mortality risks were then estimated using established models.

Results: For whole heart, thirteen studies reported 2893 doses. Average mean doses were higher in left than in right-sided radiotherapy and increased with extent of clinical targets. For left-sided radiotherapy, average mean heart doses were: 2.0 Gy (range 1.2-8.0 Gy) breast/chest wall, 2.7 Gy (range 0.6-5.6 Gy) breast/chest wall with either axilla or supraclavicular nodes and 2.9 Gy (range 1.3-4.7 Gy) breast/chest wall with nodes including internal mammary. For right-sided radiotherapy, average mean heart doses were: 1.0 Gy (range 0.3-1.0 Gy) breast/chest wall and 1.2 Gy (range 1.0-1.4 Gy) breast/chest wall with either axilla or supraclavicular nodes. There were no whole heart dose estimates from right internal mammary radiotherapy. For whole lung, six studies reported 2230 doses. Average mean lung doses increased with extent of targets irradiated: 2.6 Gy (range 1.4-3.0 Gy) breast/chest wall, 3.0 Gy (range 0.9-5.1 Gy) breast/chest wall with either axilla or supraclavicular nodes and 7.1 Gy (range 6.7-10.0 Gy) breast/chest wall with nodes including internal mammary. For whole oesophagus, two studies reported 76 doses. Average mean oesophagus doses increased with extent of targets irradiated: 1.4 Gy (range 1.0-2.0 Gy) breast/chest wall with either axilla or supraclavicular nodes and 5.8 Gy (range 1.9-10.0 Gy) breast/chest wall with nodes including internal mammary.

Conclusions: The typical doses to these organs may be combined with dose-response relationships to estimate radiation risks. Estimated 30-year absolute lung cancer mortality risks from modern UK breast cancer radiotherapy for patients irradiated when aged 50 years were 2-6% for long-term continuing smokers, and <1% for non-smokers. Estimated 30-year mortality risks for heart disease were <1%.

Keywords: Breast cancer radiotherapy; Heart dose; Lung dose; Oesophagus dose; Radiotherapy risks; UK radiotherapy.

Fig 1

Estimated typical mean whole heart doses from UK breast cancer radiotherapy according to breast cancer laterality and clinical targets. ∗Average mean whole heart dose, weighted by the number of individual dose estimates, was calculated for each category of breast cancer laterality and clinical targets. †The range refers to the range of individual dose estimates. Where this was unavailable, the range of reported mean doses was used. P_trend values are for association of average dose with increasing targets irradiated. Abbreviations: Ax=axilla lymph nodes, Br=breast, CI=confidence interval, CW=chest wall, Gy=gray, IM=internal mammary lymph nodes, SE=standard error, SF=supraclavicular fossa lymph nodes.

Fig 2

Estimated typical mean whole lung doses from UK breast cancer radiotherapy according to clinical targets. ∗Average mean whole lung dose, weighted by the number of individual dose estimates, was calculated for each category of clinical targets. †The range refers to the range of individual dose estimates. Where this was unavailable, the range of reported mean doses was used. P_trend values are for association of average dose with increasing targets irradiated. Abbreviations: Ax=axilla lymph nodes, Br=breast, CI=confidence interval, CW=chest wall, Gy=gray, IM=internal mammary lymph nodes, SE=standard error, SF=supraclavicular fossa lymph nodes.

Fig 3

Estimated typical mean whole oesophagus doses from UK breast cancer radiotherapy according to clinical targets. ∗Average mean whole oesophagus dose, weighted by the number of individual dose estimates, was calculated for each category of clinical targets. †The range refers to the range of individual dose estimates. Where this was unavailable, the range of reported mean doses was used. P_trend values are for association of average dose with increasing targets irradiated. Abbreviations: Ax=axilla lymph nodes, Br=breast, CI=confidence interval, CW=chest wall, Gy=gray, IM=internal mammary lymph nodes, SE=standard error, SF=supraclavicular fossa lymph nodes.

Fig 4

Estimated typical absolute 30-year risks (%) of radiotherapy-induced mortality for a patient who receives modern UK breast cancer radiotherapy with typical heart and lung doses when aged 50 years. Absolute risks were estimated using average mean doses to whole organs at risk (Gy) from modern UK radiotherapy for early breast cancer (Fig 1, Fig 2) and the dose-response relationships described in Text S5. Cardiac risk factors include smoking, see Text S5 for details. The risks are shown in Table 1. Risks of radiation-induced lung cancer mortality in ex-smokers are likely to be much closer to those in never-smokers than in current smokers because stopping smoking substantially reduces lung cancer risk. Figure 1 shows average mean whole heart doses for nine categories of laterality and target. Absolute risks in Table 1 and in this figure are shown for the following five categories, i.e., all categories excluding “targets unspecified” and “some left and some right”: Breast cancer laterality and target: Average mean whole heart dose (Gy), Left Br/CW only: 2.0, Left Br/CW+Ax/SF: 2.7, Left Br/CW±Ax/SF+IM: 2.9, Right Br/CW only: 1.0, Right Br/CW+Ax/SF: 1.2, Abbreviations: Ax=axilla lymph nodes, Br=breast, CW=chest wall, IM=internal mammary lymph nodes, SF=supraclavicular fossa lymph nodes.