Results of a large meta-analysis by the Early Breast cancer Trialists’ Group showed that postoperative radiotherapy could significantly improve the survival rate and decrease the local recurrence rate [14]. However, postoperative radiotherapy could lead to early and late side effects of OARs, especially in the heart, anterior cardiac structures and ipsilateral lung.
In recent years, DIBH technology has been widely used in patients with breast cancer to reduce the radiation dose of OARs [15, 16]. Different breath-holding methods have been utilized for DIBH. The two dominant methods were ABC system (Elekta, Stockholm, Sweden) and RPM system (Varian Medical Systems, Palo Alto, CA) [8]. In recent years, OSMS has become increasingly advanced tools (AlignRT, Vision RT Ltd., London, UK; Sentinel, C-RAD, Uppsala, Sweden) [9]. In addition, aDIBH had more advantages in reducing the irradiation dose of OARs than tDIBH [7]. In our study, we reported the experience of our single institution with OARs-sparing radiotherapy with aDIBH using an audio-guided device.
Firstly, radiation-related heart disease (RRHD) was the most serious adverse reaction to radiotherapy for breast cancer. Radiotherapy could cause small vessel microvascular and coronary artery macrovascular disease, which could lead to myocardial fibrosis, coronary artery disease, and ultimately ischemic heart disease [17,18,19]. There was a dose–response relationship between the cardiac exposure dose and the incidence of RRHD. Evidence existed that any reduction in radiation exposure to the heart would lower the incidence of ischemic heart disease in patients with breast cancer. A previous study [6] showed that mean cardiac dose of 300 cGy (1000 cGy) increased the risk of death from ischemic heart disease from 1.9% to 2.4% (1.9% to 3.4%) and the risk of at least one acute coronary event from 4.5% to 5.4% (1.9% to 7.4%) in patients with no preexisting cardiac risk factors. In addition, incidental exposure of the heart to radiotherapy for breast cancer would increase the rate of major coronary events by 7.4% per gray. In our study, due to the expansion of the lungs, location of heart was moved farther caudally and away from chest wall, and the volume of heart becomed smaller under the aDIBH (540.51 ± 101.39 cm3 and 605.79 ± 125.48 cm3). Because the above changes, the aDIBH could lead to lower radiation dose of heart and LADCA (D mean, V5, V10, V20 and V30), in which the D mean of the heart and LADCA were respectively reduced by 332.79 ± 264.61 cGy and 1290.37 ± 612.09 cGy. Meanwhile, the reduction on the radiation dose of LADCA was more significant than that in the heart (Fig. 2, Fig. 3). This meant that aDIBH could effectively reduce the incidence rate of RRHD, especially the occurrence of coronary artery disease.
Secondly, radiation pneumonitis (RP) was an acute manifestation of radiation-induced lung injury and one of the main dose-limiting toxicities in patients receiving thoracic radiation therapy. There was also a dose–response relationship between the pulmonary exposure dose and the incidence rate of RP. It mainly depended on the volume of the irradiated lung [20]. D mean and V20 were often associated with RP and were most commonly used in clinical practice, and other variables (V5, V10, and V30) were also predictive [21]. The dose-volume limit of the ipsilateral lung (V20 ≤ 30%) could reduce the incidence of RP and short-term changes in lung function [22]. In our study, compared with the FB, the volume of the left lung under the aDIBH increased by 458.36 ± 197.16 cm3, and the increase in pulmonary volume meant a decrease in radiation dose (D mean, V20, and V30), which in turn reduced the incidence rate of RP. Meanwhile, radiation therapy under aDIBH did not lead to a loss of dose for the PTV (D mean, D max) and target coverage (CI, HI).
Compared with previous studies, the dose of OARs in our study was higher. The reasons might be as follows: on the one hand, it might be due to the different of radiation field arrangements, such as the study of Sung K et al. [23], treatment plans were generated by the treatment planning system with a pair of wedged tangential fields, however six to eight main tangential conformal fields were used with the field-in-field technique in our study. On the other hand, all treatment plans had to meet the criterion that at least 95% of the PTV received 100% of the prescribed dosage in our study, which might have led to an increased radiation dose of OARs. However, in the other study [24], planning aims were to cover ≥ 95% of the PTV with ≥ 95% of the prescribed dose. Additionally, radiotherapy technologies also affect the dose of OARs. Among the three radiotherapy technologies (3D-CRT, IMRT, and VMAT), the D mean of the heart was lowest in aDIBH IMRT and 130 cGy lower than in aDIBH VMAT (P = 0.002), so aDIBH IMRT resulted in the best heart-sparing effect [25].
Finally, some problems about DIBH technique need to be explored. Regarding the selection criteria to predict which patients would benefit most from the DIBH technique other than left breast laterality, a strong linear correlation was found between the maximum heart distance (MHD) and the mean heart dose. For every 1 cm increase in MHD, the mean heart dose increased by 2.9% on average (95% CI: 2.5–3.3) [26]. In addition, parasagittal cardiac contact distance (CCD) was a potentially good predictor of cardiac exposure: the longer the CCD, the higher the dose, and at least 75% of patients with left-sided breast cancer might benefit from the DIBH technique in terms of potentially clinically relevant dose reduction to cardiac structures [27]. For selected patients with unfavorable cardiac anatomy, defined as having > 10 cm3 of the heart receiving 50% of the prescribed dose (V50% > 10 cm3) on the free-breathing automated treatment plan, the DIBH technique could significantly reduce the dose to the LADCA and heart, potentially reducing cardiac risk [28].
There was still controversy about whether to perform prophylactic irradiation on the ipsilateral internal mammary chain (IMC) because of conflicting data on the benefits and losses of this treatment strategy [29, 30]. In a study about aDIBH in postoperative adjuvant radiotherapy for left breast cancer with IMC coverage compared with FB, even if IMC was included in CTV, the radiation dose to the heart was reasonable low [21].
Our study has some limitations. The cohort size of 35 patients is modest. The patient comfort and treatment times are not recorded. Respiratory training and cooperation of patients are crucial for aDIBH, otherwise it may lead to a use of invalidated audio guided device and in actuality OARs may have received more dose as compared to as seen on planning scan.
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