Myocardial functional and structural abnormalities after adjuvant radiotherapy for breast cancer. Relation to cardiac radiation exposure
Authors: Krug P , Berliere M , Kirkove C , Ledoux B , Pasquet A , Vancraeynest D , Beauloye C , Pouleur AC , Geets X , Gerber BL 
Published: July 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): The Funds Pierre Masure, Alphonse and Marie Walckiers & De Winter-Vermant, by King Baudouin Foundation

Background
Radiation therapy (RXT) is a keystone in breast cancer (BC) treatment which allows to reduce risk of local recurrence and cancer related mortality. Yet these benefits may be offset by increases in cardiovascular mortality due to late radiation induced cardiotoxicity. Indeed, prior works in patients exposed to high cardiac radiation dose demonstrated development of diffuse and focal myocardial fibrosis by cMR. However, whether such effects may also occur after contemporary BC-RXT with lower cardiac dose exposure, has not yet been evaluated.

Purpose
To evaluate the long-term cardiac safety of contemporary RXT for BC, we sought to estimate the prevalence of cardiac functional and structural focal and myocardial abnormalities in BC survivors treated by RXT 10 years earlier, in direct relation to measured local radiation dose exposure.

Methods
In a prospective cross-sectional study, we studied 27 women (mean age 62 ± 7 years) treated with adjuvant RXT but without chemotherapy for a first left (n= 12) or right sided (n= 15) BC between 2009 and 2011, which had no history of coronary artery or cardiac disease and compared them to 20 age matched (64 ± 10 years) healthy female controls (without history of BC or RXT). All subjects underwent 3T cMR to measure LV volumes, function, global longitudinal (GLS), circumferential (GRS) and radial strains (GRS) as well as extracellular volume (ECV) and late gadolinium enhancement (LGE). Functional and structural abnormalities in women with BC were compared to healthy controls. We also compared abnormalities among patients with left vs right BC and related them to mean heart radiation dose measured at the time of RXT (Figure).

Results
Mean cardiac radiation exposure in BC survivors was 1.87 ± 1.7 Gy (range 0-7.9 Gy). Exposure was significantly (p &lt; 0.001) higher in left (3.3 ± 0.66 Gy) than in right (0.84 ± 0.65 Gy) sided BC. Indexed LV mass was slightly lower in BC patients than in controls (46 ± 6 vs 51 ± 9 g/m2, p = 0.03), whereas indexed end-diastolic (66 ± 11 vs 66 ± 12 ml/m2, p = NS) and end-systolic volumes (25 ± 8 vs 24 ± 7 ml/m2, p = NS) were similar. Also, LV ejection fraction (63 ± 6 vs 64 ± 6, p = NS), GLS (-14.7 ± 1.9 vs -15.5 ± 1.8, p = NS), GCS (-20.0 ± 3.6 vs -19.3 ± 5.9, p = NS) and GRS (40.9 ± 10.7 vs 37.0 ± 9.0, p = NS) were not statistically different in BC survivors than in controls. No patient presented LGE, and ECV was similar in BC patients exposed to RXT (28.3 ± 2.8) than in controls (29.3 ± 2.4, p = 0.58). Also, no differences in ECV between left and right sided BC and no statistical correlation between ECV and mean heart dose (r = 0.01, p = NS) was observed.

Conclusions
In this preliminary work, patients with BC treated by adjuvant RXT 10 years ago, presented no significant structural or functional abnormalities in relation to cardiac dose exposure nor in comparison to healthy controls. This suggests that current RXT protocols for BC are safe without long-term functional or morphological cardiac side effects.