Li et al. reported that the maximum point dose error due to respiration in intensity-modulated RT (IMRT) was estimated to be up to 6.2% based on RT plans, assuming a patient breathing cycle of 8 seconds (11). In our results, for IM, dose errors due to respiration in 3D-CRT were 2.8% and 6.2% for R05 and R10, respectively, while those in VMAT were slightly larger, 4.9% and 8.5%, respectively. For CW, they were − 0.5% and − 6.0% in 3D-CRT for R05 and R10, respectively, and those in VMAT were − 1.9% and − 5.3%, respectively. Therefore, it could be assumed that the experimental design with the anthropomorphic phantom used in this study reflected the clinical situation to some extent.
Currently, elective regional nodal irradiation after mastectomy for breast cancer has been used increasingly, based on the two large randomized clinical trials. The first trail, the European Organization for Research and Treatment of Cancer 22922/10925, showed a significant reduction in breast cancer mortality and breast cancer recurrence by IMN and medial supraclavicular lymph node irradiation in stage I–III breast cancer (12). The second trial, the NCIC Clinical Trials Group MA.20 study, showed that the addition of regional nodal irradiation to the whole-breast irradiation in patients with node-positive or high-risk node-negative breast cancer reduced the recurrence rate of breast cancer (3). In a population-based cohort study from the Danish Breast Cancer Cooperative Group, RT to IMN showed an increase in overall survival in patients with early stage node-positive breast cancer (13). To take the advantage of elective nodal irradiation after mastectomy in breast cancer, precise lesion targeting and avoidance of normal tissue irradiation are important. In a systematic review of radiation dosimetry of 13,000 women in 14 trials by the Early Breast Cancer Trialists Collaborative Group, nodal RT showed reduced breast cancer recurrence, breast cancer mortality, and overall mortality. However, the benefit was only achieved when the target nodal dose was > 85% and the mean heart dose was lower than 8 Gy (14).
One way to improve the coverage of CTV is using arc-therapy techniques such as VMAT. Previous dose-comparison studies showed that arc-therapy offered improved coverage of CTV compared to that of field-based RT (15, 16). However, in case of postmastectomy radiation, it has not been proven whether the benefit of VMAT would be achieved because the width of CW after mastectomy may be very narrow and respiratory movement existed. In our study, for example, the mean dose error of both IM and CW increased by a factor of 7.1 and 2.3 in 3D-CRT and VMAT, respectively, as the respiratory amplitude was doubled. However, the absolute value of the dose error of VMAT was higher than that of 3D-CRT in all cases. In addition, the dose errors of both 3D-CRT and VMAT were less than 5% under the shallow breathing of R05.
Meanwhile, from the viewpoint of overall dose errors due to breathing, dose distributions of VMAT were more accurate and robust than those of 3D-CRT in both R05 and R10, as shown in Fig. 4. A relatively high gamma passing rate of VMAT may be expected, since the VMAT could paint the prescribed dose evenly on the target while suppressing the absorbed dose to the surroundings by precise beam modulation, whereas the dose distribution of 3D-CRT was only dependent on the beam characteristics of the percent depth dose. However, it should be noted that dose errors could be concentrated on the spot, such as nodal lesions where the beam modulation is highly applied, as shown in Fig. 4f, when the respiratory movement is enlarged. Therefore, it is important to keep the patient’s breathing shallow during VMAT.
Pedersen et al. reviewed 16 CT scans of adjuvant RT plans for breast cancer and found that the mean chest wall excursion at the position of the xiphoid process was 2.5 mm (range: 1–4 mm) during free-breathing (17). Lowanichkiattikul et al. also reported the respiratory movement of CW using data from 38 patients. They placed radio-opaque markers at four anatomical landmark points and checked the width of maximal CW movement. Although the respiratory movement of CW in the anterior-posterior direction was the largest among the three directions in general, the movement only ranged from 4.2. to 5.4 mm at all points (18). Thus, we expected that the R05 condition would be generally achievable by patients and that VMAT could be implemented with sufficient accuracy.
The Dlung value of VMAT was only 39.9% of that of 3D-CRT, as expected, and we also noted that the difference in dose errors between R05 and R10 was negligible in both 3D-CRT and VMAT, as shown in Fig. 6. In VMAT, the effect of respiratory movement on the surrounding doses seems to be limited because VMAT intends to suppress the surrounding dose. However, in the case of 3D-CRT, various planning conditions such as beam geometry and patient anatomy should also be examined.
For LAD, all measured dose values were very low because the point was far from the PTV; hence, the dose errors caused by respiratory movement were not significant. However, we noted that the measured LAD dose of VMAT was higher than that of 3D-CRT by a factor of 7.5. Therefore, in spite of the prominent target coverage of VMAT, planned doses of organs at risk should be carefully monitored (16). According to a systematic review of heart doses for breast RTs published between 2003 and 2013, the mean heart dose was 4.2 Gy when no IMN was included, but it increased to 8 Gy with IMN (19).
For sparing the heart and eliminating the effect of respiratory movement during left breast RT, the deep inspiration breath-hold (DIBH) technique could be combined with VMAT. Nissen et al. reported that the mean heart dose was reduced by 48% (from 5.2 Gy to 2.7 Gy) using both DIBH and IMRT (20). Hayden et al. also reported that the DIBH showed a significant reduction in heart and LAD doses in IMRT compared to free breathing technique (21). Although the DIBH is optimal to avoid the dose error caused by respiratory movement, it could not be available in a variety of situations, such as long treatment time or in certain patient’s clinical conditions. The overall dosimetric impact caused by respiratory movement seemed to be relatively small in VMAT according to gamma evaluation results, as shown in Fig. 4. The gamma pass rate of VMAT under the R10 condition was even higher than that of 3D-CRT under the R05 condition. In particular, the gamma pass rate of VMAT reached 97.0% under R05 conditions. Therefore, we expect that the sufficient accuracy of VMAT could be maintained if the patient maintained shallow breathing during the treatment. Nevertheless, it may be necessary to evaluate PTV coverage in the case of complex target shapes owing to the concerns about possible underdose delivery.
This study has three limitations that come from our phantom-based experimental design. First, although the exact respiratory movement should be simulated using three-dimensional movements, we ignored the medial-lateral (M-L) movement due to the limitation of our experimental apparatus. It was also considered that the M-L movement was the smallest among the three-dimensional breathing motions (22). Second, although the anatomical geometry of the chest wall may be highly dependent on the individual patient, the analysis of dose errors implemented in this study was only based on the given anthropomorphic phantom. Nevertheless, we expected that our study could provide an overview of the dosimetric impact of respiratory movement on 3D-CRT and VMAT techniques, respectively. Third, we evaluated the relationship between respiratory movement and the corresponding dose errors measured from single fractionation. The dose errors arising from all the fractionations could be partially summed up or canceled out. The quality assurance of dose per fractionation is still important.