SCR7 br Discussion br This study
This study shows an association between individual cardiac dose distributions and subclinical systolic dysfunction of the LV after RT for BC. The subclinical marker, GLS of the LV, was most associated with the maximum dose to the LMCA. Notably, all DVH parameters that were selected for this endpoint were based on dose to the coronary arteries. The final model for diastolic function included age and hypertension at baseline. DVH parameters were less frequently selected for this endpoint.
Previous studies have shown similar results with regard to systolic function using LVEF as a primary endpoint.21-23 In these studies, with a median follow-up time of 6 to 13 years, no significant decrease in LVEF after RT treatment for BC was observed.21-23 Additionally, in a recently published meta-analysis, RT was found to be associated with an increased risk of coronary SCR7 disease, but not with a sig-nificant decline in LVEF.4 In the current study based on 3D cardiac dose distributions, no relation between RT dose and decline in LVEF was found either. Changes in LVEF reflect severe damage that may manifest relatively late because of compensation mechanisms.24 Given the median follow-up time of 7 years in the current study, the interval may be too short for the development of a decreased LVEF of <54%. Because of the limitations in sensitivity and reproducibility
Volume 104 Number 2 2019 Cardiac function after breast irradiation 397
Table 2 Tumor and treatment characteristics at the time of breast cancer diagnosis for all 109 breast cancer survivors
Variable At baseline
Tumor characteristics, n (%)
Size (T stage)
Nodes (N stage)
Radiation therapy, median (range) (Gy)
Mean heart dose
Additional systemic therapy, n (%)
Endocrine therapy only
Combination chemotherapy and
of the LVEF, we decided to also use the GLS of the LV, which is a more sensitive method to detect subclinical systolic dysfunction of the LV.25
Table 2 (continued )
Variable At baseline
Abbreviations: BC Z breast cancer; CX Z circumflex coronary artery; LAD Z left anterior descending coronary artery; LMCA Z left main coronary artery; LV Z left ventricle; N Z nodes; RCA Z right coronary artery; T Z tumor.
Two studies looked at both LVEF and GLS in BC survivors.26,27 They found no significant decrease in LVEF
after RT in patients with either left- or right-sided BC between 2 and 14 months of follow-up. However, a sig-nificant decrease in longitudinal strain immediately after RT and at 8 and 14 months after RT was found for left-sided BC survivors, but not for right-sided BC survivors, suggesting a dose-effect relationship. Another study found that patients with left-sided BC experienced a decline in apical and global strain values, whereas patients with right-sided BC showed a decline in the basal anterior segment of the LV. Furthermore, RT caused no changes in conventional LV systolic measurements.28 However, the researchers did not examine any associations between cardiac dose parameters and GLS of the LV. In line with the current study, these results indicate that GLS is a more sensitive measure for cardiac changes after BC RT and that these changes are already present relatively early after completion of RT.
Several studies suggest that GLS provides independent prognostic information regarding cardiovascular morbidity and mortality in the general population.29-31 Presence of worse LV strain at baseline was associated with a higher risk for incident heart failure and all-cause mortality over the follow-up period.31 This issue is particularly important in BC populations because it may take years for clinically overt cardiac damage to develop. The detection of early changes could be predictive for late RT-induced cardiac morbidity.26
Knowledge of the exact underlying mechanism behind radiation-induced cardiac toxicity is lacking. In particular, it is not clear whether coronary artery damage or myocar-dial damage, or both, are responsible for radiation-induced heart disease.32 Our results suggest that RT to the coronary arteries is associated with subclinical systolic dysfunction. As shown in Table 4, the most selected risk factor of posttreatment GLS is the maximum dose to the LMCA. This result was also supported by the frequency tables in the Supplemental Material (available online at https://doi. org/10.1016/j.ijrobp.2019.02.003); DVH parameters of the coronary arteries were strongly dominant relative to DVH parameters of the myocardium. Previous research has shown a direct link between radiation dose and the location of coronary stenosis, mostly in the left anterior descending coronary artery.33,34 These studies support the importance