EARLY SUBCLINICAL CARDIOVASCULAR CHANGES AFTER RADIOTHERAPY FOR BREAST CANCER DETECTED
BY ECHOCARDIOGRAPHY: CONTRIBUTION OF THE MEDIRAD EARLY-HEART COHORT

M. Locquet¹, A. Crijns², J. Langendijk², D. Spoor², A. Eraso³, F. Guedea³, M. Fiuza⁴, S. Constantino Rosa Santos⁴, S. Combs⁵, K. Borm⁵, G. Frija⁶, E. Cardis⁷, S. Jacob¹

(1) Institute for Radiation protection and Nuclear Safety (IRSN), Laboratory of Epidemiology, Fontenay-Aux-Roses, France

(2) Department of Radiation Oncology, University Medical Center Groningen (UMCG), University of Groningen, Groningen, Netherlands
(3) Institut Catala Oncologia (ICO), Department of Radiation Oncology, Girona, Spain

(4) Centro Cardiovascular da Universidade de Lisboa (CCUL), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
(5) Technical University of Munich (TUM-MED), Department of Radiation Oncology, Munich, Germany

(6) Paris-Descartes University, Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France
(7) Barcelona Institute for Global Health (ISGlobal), Radiation Programme, Barcelona, Spain

BACKGROUND

Breast cancer (BC) represents a major public health burden. Radiotherapy (RT) allows reducing local recurrence and deaths resulting from BC. However, RT for BC can lead to cardiotoxicity.

OBJECTIVE

- To determine the short-term impact of BC RT on subclinical cardiac function by means of echocardiography.

- To consequently explore the dose-response relationship.

METHODS

The MEDIRAD EARLY-HEART study (www.medirad-project.eu): a multicenter cohort study (women with BC RT, aged 40 to 75, chemotherapy naive).

Myocardial deformation analysis provided by 2D-speckle-tracking echocardiography. Global longitudinal strain (GLS) and its worsening > 15% considered to evaluate subclinical cardiac dysfunction.

Echocardiographic exams after the RT+6-month,
September 2021: subclinical cardiac function
alterations occurred?

Echocardiographic exams after the RT+24-month,
December 2021: subclinical cardiac function
alterations persisted?

RESULTS

The EARLY-HEART cohort included 258 women with BC, mean age of 58.2±8.1 years, 63.5% left-sided BC.

RT total dose varied from 40.05 Gray (Gy) to 50.40 Gy, and 46.1% received a boost.

Echocardiography exams (n=242): mean GLS of -19.3±3.3% at baseline and of -19.2±3.6% after the RT+6-month (p-value = 0.81).

<table><thead><tr><th colspan="2">Baseline characteristics of the EH cohort from the echocardiography analysis (n=258)</th></tr></thead><tbody><tr><td>Study center</td><td></td></tr><tr><td>CCUL</td><td>26 (10.1%)</td></tr><tr><td>ICO</td><td>42 (16.3%)</td></tr><tr><td>IRSN</td><td>50 (19.4%)</td></tr><tr><td>TUM-MED</td><td>20 (7.7%)</td></tr><tr><td>UMCG</td><td>120 (46.5%)</td></tr><tr><td>Type of RT</td><td></td></tr><tr><td>3D-CRT</td><td>132 (51.8%)</td></tr><tr><td>IMRT</td><td>2 (0.8%)</td></tr><tr><td>VMATRapidArc</td><td>121 (47.4%)</td></tr><tr><td>Body mass index, kg/m<sup>2</sup></td><td>26.4±4.6</td></tr><tr><td>Smoking status</td><td></td></tr><tr><td>Current</td><td>38 (14.8%)</td></tr><tr><td>Former</td><td>85 (33.1%)</td></tr><tr><td>No</td><td>134 (52.1%)</td></tr><tr><td>Total cholesterol, mg/dl</td><td>210.5±46.6</td></tr><tr><td>Hypertension, Yes</td><td>51 (19.9%)</td></tr><tr><td>Menopause, Yes</td><td>193 (76.6%)</td></tr><tr><td>Hormonotherapy, Yes</td><td>163 (63.9%)</td></tr><tr><td>CV treatment, Yes</td><td>33 (12.8%)</td></tr></tbody></table>

<table><thead><tr><th colspan="2">Description of radiation doses received by patients from the MEDIRAD EARLY HEART study (n=258)</th></tr></thead><tbody><tr><td>Minimum dose LV, Gy</td><td>0.53±0.32</td></tr><tr><td>Maximum dose LV, Gy</td><td>16.81±17.42</td></tr><tr><td>Mean dose LV, Gy</td><td>2.01±1.76</td></tr><tr><td>V5 LV, %</td><td>5.02±7.84</td></tr><tr><td>Minimum dose WH, Gy</td><td>0.36±0.25</td></tr><tr><td>Maximum dose WH, Gy</td><td>22.49±17.68</td></tr><tr><td>Mean dose WH, Gy</td><td>1.76±1.07</td></tr><tr><td>V5 WH, %</td><td>3.61±5.35</td></tr></tbody></table>

<table><thead><tr><th colspan="5">Preliminary analyses regarding the relationship between dose and restriction of GLS > 15% in the MEDIRAD EARLY-HEART study (n=242)</th></tr><tr><th></th><th>OR (95% CI)</th><th>P-value</th><th>aOR* (95% CI)</th><th>P-value</th></tr></thead><tbody><tr><td>Dmean (Gy), left ventricle</td><td>1.47 (1.22-1.81)</td><td>0.0001</td><td>1.70 (1.26-2.39)</td><td>0.001</td></tr><tr><td>Dmean (Gy), whole heart</td><td>2.03 (1.46-2.93)</td><td>&lt;0.0001</td><td>2.61 (1.60-4.65)</td><td>0.0003</td></tr></tbody></table>

CONCLUSION

The impact of RT on subclinical cardiac function in patients with BC are being explored within the MEDIRAD EARLY-HEART project. Preliminary analyses suggested an association between dose received during RT and subclinical cardiac dysfunction. The 24-month follow-up analyses will allow to determine if the alterations observed remained at longer term.

<footnote>* Adjusted for age, BMI, smoking status, total cholesterol, hypertension, menopause, laterality, center hormonotherapy, CV treatment, laterality.</footnote>