Adjuvant radiotherapy is a standard of care in treatment of breast cancer in patients undergoing both breast-conserving (BCT) or mastectomy, improving loco-regional control and overall survival [1, 2].
Despite the benefits of RT, left-sided breast cancer radiotherapy showed a higher incidence of adverse cardiac health effects, occurring even many years after treatment and even causing premature mortality. Cardiovascular mortality from left-sided RT is significantly higher compared with right-sided RT and is more evident after ≥ 15 years of follow-up (RR: 1.23, 95% CI: 1.08–1.41, P < 0.001) [3]. The development of these long-term cardiovascular toxicities seems to be caused by microvascular endothelial injury and myocardial remodeling, as well as oxidative stress and inflammation. This damage has shown to be related to incidental cardiac dose linearly associated with increased risk of major coronary events [4, 5]. Incidental cardiac dose appears to also be related to the risk of early post radiotherapy perfusion defects on functional imaging [6].
Left descending artery (LAD) irradiation has been increasingly recognized as a relevant mechanism of cardiac damage in preclinical [7 ]and clinical studies. In fact, left sided breast cancer patients showed myocardial perfusion changes in the LAD distribution [8] and LAD stenosis measured by angiography was more common in left sided than right sided breast cancer patients undergoing adjuvant radiotherapy [9]. In addition, both LAD maximum and mean dose were associated with coronary artery calcium score > 0 [10] and women receiving mean doses between 1-5Gy to the mid LAD had an increased risk for a later coronary intervention compared to women receiving mean doses of 0–1Gy [11] .
Nowadays, there are several radiation technique that allow heart sparing: those that reduce treatment volume to tumor bed (partial breast irradiation, PBI); those able to decrease the delivery of higher dose to the heart, using intensity modulated radiation therapy (IMRT) or volumetric arc therapy (VMAT); and those that reduce cardiac exposure to radiation by moving the heart away from the target, such us prone position or deep inspiration breath hold (DIBH). Particularly, the latter increases the physical separation between the chest wall and the heart during inspiration and has recently been recommended as the best heart sparing technique available [12]. Literature data reports a reduction of mean heart dose ranging from 38–59% and a reduction of mean dose to left descending artery (LAD) ranging from 31–71% with DIBH [13].
However, even if the benefit from this technique is clearly recognized, not all patients achieve the same degree of benefit. Therefore, as not all patients are compliant in performing DIBH, showing different degrees of cooperation, as the treatment itself prolongs simulation and treatment delivery times increase staff workload, patient commitment and treatment cost, it would be useful to identify predictors of dosimetric benefit, especially in the context of limited resources.
Several studies have mainly evaluated anatomical predictors of mean heart dose (MHD) reduction with BH technique [13, 14]. However, mean heart dose does not seem to be representative of dose to the LAD [15].
In fact in the BACCARAT study, among left-sided breast cancer patients with a mean heart dose lower than 3 Gy, more than half of patients could receive dose greater than 40 Gy. Therefore the authors concluded that the dose delivered to the cardiac substructures, such as the LAD, should also be assessed [15].
Based on the above considerations, the aim of this study was to identify in a large dataset of patients anatomical and/or treatment preplanning characteristics correlated with LAD dose in order to guide selection of patients with left-breast cancer that could benefit the most from the use of DIBH-RT.