Dose to cardiac substructures following contemporary radiotherapy for early breast cancer: evidence from 6,926 patients

Background/Introduction

Radiotherapy (RT) for early breast cancer (eBC) has been associated with increased long-term cardiovascular morbidity, primarily due to cardiac irradiation. Although advances in RT planning have substantially reduced mean heart dose (MHD), evidence suggests that dose to specific cardiac substructures may be more relevant for radiation-induced cardiotoxicity. Understanding contemporary cardiac and substructure dose exposure, as well as temporal trends, is essential for optimizing cardiac risk among cancer patients.

Purpose

The purpose is to quantify radiation dose to the heart and cardiac substructures in eBC patients treated with adjuvant RT and to evaluate changes in cardiac dose exposure over time in a real-world clinical cohort.

Methods

All eBC patients receiving adjuvant RT at a single institution between 2009 and 2020 were included. Planning CT scans were retrieved, and the heart and nine cardiac substructures were automatically delineated using the open-source AI-based tool PlatiPy. A random 10% of delineations underwent manual validation and were accepted without modification. Dose metrics were extracted from the treatment planning system and reported as EQD2 (α/β = 2 Gy). Temporal changes in cardiac and substructure dose exposure were assessed using Wilcoxon tests.

Results

In total, 6926 patients were included (3562 left-sided eBC patients and 3364 right-sided eBC patients). RT planning and delivery varied over time; deep inspiration breath-hold was available throughout the study period, and 3D-conformal RT was the predominant technique.

Figure 1 shows mean dose to the heart and 9 cardiac substructures. Changes in median mean doses over time are illustrated in Figure 2.

Median MHD for the entire cohort was 0.57 Gy (IQR: 0.29–0.99). For left-sided locoregional RT, MHD increased significantly over time (p < 0.001), whereas a significant decrease was observed for right-sided breast-only RT (p < 0.0001).

Dose exposure to cardiac substructures was generally low. The highest median doses were observed for the left anterior descending coronary artery (LAD) during left-sided locoregional RT (2.70 Gy, IQR: 2.12–4.77) and for the right coronary artery (RCA) during right-sided locoregional RT (1.45 Gy, IQR: 1.16–2.00). Median LAD dose increased significantly over time for left-sided locoregional RT (p < 0.01), but not for left-sided breast-only RT (p = 0.19).

These results likely reflect multiple factors, including the DBCG IMN study [2], which increased IMN-cover-age prioritization from 2015 and a shift toward a MHD rather than a LAD dose guidance in 2017.

Conclusions

Contemporary adjuvant RT for eBC results in very low cardiac and substructure doses for most patients. However, a significant increase in MHD and LAD dose over time was observed for left-sided locoregional RT due to changes in planning priorities. Further investigations include linkage of dosimetry data to cardiotoxicity outcomes.Boxplot with whiskers at 10% and 90%  Median mean dose over time