The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors

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Abstract

Background

To assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC).

Methods

The study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient’s original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location.

Results

The odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) ( p = 0.005). Women receiving mean doses of 1–5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47–1.74) for a later coronary intervention compared to women receiving mean doses of 0–1 Gy to the mid LAD. In women receiving mean doses of 5–20 Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52–2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01–13.6) for mean doses over 20 Gy, when compared to women receiving mean doses of 0–1 Gy to the mid LAD.

Conclusions

In women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

Electronic supplementary material

The online version of this article (10.1186/s13014-019-1242-z) contains supplementary material, which is available to authorized users.

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Most cited references 7

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Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment.

Yeen Hwang, João C. F. Corrêa, Lawrence Solin … (2006)

Several studies have reported increased cardiac mortality related to the use of left-sided breast or chest-wall irradiation. This study was undertaken as a comprehensive examination of the long-term cardiac mortality and morbidity after breast irradiation using contemporary irradiation techniques. The medical records of 961 consecutive patients presenting between 1977 and 1994 with stage I or II breast cancer treated with breast conservation treatment were reviewed. Data was recorded on baseline pretreatment patient, tumor and treatment characteristics and on subsequent cancer or cardiac related events. The median follow-up time was 12 years. There was no difference in overall mortality from any cardiac cause (P = .25). Death from any cardiac cause occurred in 2% of right-sided patients and 3.5% of left-sided patients. However, in the second decade after treatment, there was a higher rate of cardiac deaths in left-sided patients, with a cumulative risk of 6.4% (95% CI, 3.5% to 11.5%) for left-sided compared with 3.6% (95% CI, 1.8% to 7.2%) for right-sided patients at 20 years. There were statistically higher rates of chest pain, coronary artery disease, and myocardial infarction diagnosed in left-sided patients (all P < or = .002). The presence of hypertension was associated with a higher risk of coronary artery disease in left-sided patients. Irradiation to the left breast is not associated with a higher risk of cardiac death up to 20 years after treatment, but is associated with an increased rate of diagnoses of coronary artery disease and myocardial infarction compared with right breast treatment.

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Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study

Rahul Roychoudhuri, David Robinson, Venkata Putcha … (2007)

Background Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right. Methods All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD) or any cardiovascular disease (CVD). A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis. Results A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21–2.08; p = 0.001) and all CVD (hazard ratio 1.27; 95% confidence interval 1.07–1.51; p = 0.006). When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95–1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05–1.49; p = 0.014). Conclusion We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long-term cardiac toxicity. In absolute terms, the increase in cardiovascular mortality induced by radiotherapy may be substantial, as these mortality events are relatively common.

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Cardiac Structure Injury After Radiotherapy for Breast Cancer: Cross-Sectional Study With Individual Patient Data

Carolyn L Taylor, Paul McGale, Dorthe Brønnum … (2018)

Purpose Incidental cardiac irradiation can cause cardiac injury, but little is known about the effect of radiation on specific cardiac segments. Methods For 456 women who received breast cancer radiotherapy between 1958 and 2001 and then later experienced a major coronary event, information was obtained on the radiotherapy regimen they received and on the location of their cardiac injury. For 414 women, all with documented location of left ventricular (LV) injury, doses to five LV segments were estimated. For 133 women, all with documented location of coronary artery disease with ≥ 70% stenosis, doses to six coronary artery segments were estimated. For each segment, numbers of women with left-sided and right-sided breast cancer were compared. Results Of women with LV injury, 243 had left-sided breast cancer and 171 had right-sided breast cancer (ratio of left v right, 1.42; 95% CI, 1.17 to 1.73), reflecting the higher typical LV radiation doses in left-sided cancer (average dose left-sided, 8.3 Gy; average dose right-sided, 0.6 Gy; left minus right dose difference, 7.7 Gy). For individual LV segments, the ratios of women with left- versus right-sided radiotherapy were as follows: inferior, 0.94 (95% CI, 0.70 to 1.25); lateral, 1.42 (95% CI, 1.04 to 1.95); septal, 2.09 (95% CI, 1.37 to 3.19); anterior, 1.85 (95% CI, 1.39 to 2.46); and apex, 4.64 (95% CI, 2.42 to 8.90); corresponding left-minus-right dose differences for these segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy, respectively ( P trend < .001). For women with coronary artery disease, the ratios of women with left- versus right-radiotherapy for individual coronary artery segments were as follows: right coronary artery proximal, 0.48 (95% CI, 0.26 to 0.91); right coronary artery mid or distal, 1.69 (95% CI, 0.85 to 3.36); circumflex proximal, 1.46 (95% CI, 0.72 to 2.96); circumflex distal, 1.11 (95% CI, 0.45 to 2.73); left anterior descending proximal, 1.89 (95% CI, 1.07 to 3.34); and left anterior descending mid or distal, 2.33 (95% CI, 1.19 to 4.59); corresponding left-minus-right dose differences for these segements were −5.0, −2.5, 1.6, 3.5, 9.5, and 38.8 Gy ( P trend = .002). Conclusion For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized.

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Author and article information

Contributors

Anna-Karin Wennstig: +46 703537880 , anakinwen@gmail.com

Hans Garmo: hans.garmo@kcl.ac.uk

Ulf Isacsson: ulf.isacsson@akademiska.se

Giovanna Gagliardi: giovanna.gagliardi@sll.se

Niina Rintelä: niina.rintela@sll.se

Bo Lagerqvist: bo.lagerqvist@ucr.uu.se

Lars Holmberg: lars.holmberg@kcl.ac.uk

Carl Blomqvist: carl.blomqvist@helsinki.fi

Malin Sund: malin.sund@umu.se

Greger Nilsson: greger.nilsson@bahnhof.se

Journal

Journal ID (nlm-ta): Radiat Oncol

Journal ID (iso-abbrev): Radiat Oncol

Title: Radiation Oncology (London, England)

Publisher: BioMed Central (London )

ISSN (Electronic): 1748-717X

Publication date (Electronic): 7 March 2019

Publication date PMC-release: 7 March 2019

Publication date Collection: 2019

Volume: 14

Electronic Location Identifier: 40

Affiliations

[1 ]ISNI 0000 0001 1034 3451, GRID grid.12650.30, Department of Surgical and Perioperative Science, Surgery, , Umeå University, ; SE-901 85 Umeå, Sweden

[2 ]ISNI 0000 0004 0624 0320, GRID grid.416729.f, Department of Oncology, , Sundsvall Hospital, ; SE-85186 Sundsvall, Sweden

[3 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, , King’s College London, ; London, UK

[4 ]Regional Cancer Centre, SE-75185 Uppsala, Sweden

[5 ]Department of Immunology, Genetics and Pathology, Section of Medical Radiation Science, Uppsala University, University Hospital, SE-751 85 Uppsala, Sweden

[6 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Department of Medical Radiation Physics and Nuclear Medicine, , Karolinska University Hospital, ; SE-17176 Stockholm, Sweden

[7 ]ISNI 0000 0004 1936 9457, GRID grid.8993.b, Department of Medical Sciences, , Uppsala University, ; SE-75185 Uppsala, Sweden

[8 ]ISNI 0000 0004 1936 9457, GRID grid.8993.b, Department of Surgical Sciences, , Uppsala University, ; SE-75185 Uppsala, Sweden

[9 ]Department of Oncology, Örebro University, University Hospital, SE-701 82 Örebro, Sweden

[10 ]Department of Immunology, Genetics and Pathology, Section of Experimental and Clinical Oncology, Uppsala University, University Hospital, SE-751 85 Uppsala, Sweden

[11 ]ISNI 0000 0004 0624 062X, GRID grid.413607.7, Department of Oncology, , Gävle Hospital, ; SE-801 07 Gävle, Sweden

[12 ]GRID grid.440124.7, Department of Oncology, , Visby Hospital, ; SE-621 84 Visby, Sweden

Article

Publisher ID: 1242

DOI: 10.1186/s13014-019-1242-z

PMC ID: 6407212

PubMed ID: 30845947

SO-VID: a7c98cd0-8799-4af0-bfea-021fcd36df4f

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 28 November 2018

Date accepted : 21 February 2019

Funding

Funded by: Swedish Cancer Society

Award ID: Not applicable

Award Recipient : Malin Sund

Funded by: Lion's Cancer Research Foundation University of Umeå

Award ID: Not applicable

Award Recipient : Malin Sund

Funded by: Department of Research and Development Västernorrland County Council

Award ID: Not applicable

Award Recipient : Anna-Karin Wennstig

Funded by: Emil Andersson Foundation for medical research

Award ID: Not applicable

Award Recipient : Anna-Karin Wennstig

Funded by: Percy Falk Foundation for medical research

Award ID: Not applicable

Award Recipient : Greger Nilsson

Funded by: Lions Cancer Research Foundation in Uppsala.

Award ID: Not applicable

Award Recipient : Greger Nilsson

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: breast cancer,radiotherapy,radiation doses,3dcrt,coronary stenosis,left anterior descending artery

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: breast cancer, radiotherapy, radiation doses, 3dcrt, coronary stenosis, left anterior descending artery

The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors

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Karger: Oncology

Most cited references 7

Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment.

Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study

Cardiac Structure Injury After Radiotherapy for Breast Cancer: Cross-Sectional Study With Individual Patient Data

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