We have reported the relationships between the primary tumor and OARs due to respiratory movement in RT for pancreatic cancer. To the best of our knowledge, this is the first detailed report about the synchronization of respiratory movements. In the present study, we examined the absolute value of respiratory movement in the primary tumor itself, and our results are similar to previously reported results for 4DCT and cine magnetic resonance images [6–8, 13]. In previous studies, the distances of the x-axis, y-axis and z-axis in respiratory movement were 0.7–4.9 mm, 2.0–6.5 mm and 5.2–13.4 mm, respectively. Therefore, we think that the results for synchronization of respiratory movement in our study are reliable. We believe that an understanding of this synchronization would make it easier for radiation oncologists to set RT doses and fields in pancreatic cancer.
Regarding the maximum distance of respiratory movement at OARs, the difference in respiratory movements between the duodenum and primary tumor was not significant, while there was a significant difference in movements in the antero-posterior direction in the stomach and respiratory movement of the stomach was large overall. Although there are a few previous reports on respiratory movements of the stomach and duodenum, our results are similar to the results of those previous studies [14–17]. Watanabe et al. reported that intrafractional gastric motions were 11.7 ± 8.3, 11.0 ± 7.1, 6.5 ± 6.5, 3.4 ± 2.3, 7.1 ± 8.2, and 6.6 ± 5.8 mm for the superior, inferior, right, left, ventral and dorsal points, respectively [16]. Uchinami et al. reported that the average respiratory amplitudes of the stomach was 4.1 ± 1.4, 2.9 ± 1.3, and 10.1 ± 4.5 mm in the anterior-posterior, left-right, and superior-inferior directions, respectively [17]. These results suggest that respiratory changes in the stomach and duodenum are as large as those in the primary lesion. The movements of the stomach and duodenum in the cranio-caudal direction were conspicuous as expected. Therefore, it seems necessary to consider the synchronization between GTV and the stomach/duodenum.
Regarding the synchronization of respiratory movements, it was found that there was no difference in the positional relationship between the duodenum and the primary tumor in each respiratory phase, but the distance between the stomach and primary tumor at the inspiratory phase was shortened. PTV overlap volume did not change significantly in the expiratory phase in both the ST and DU, but the mean dose to the ST clearly increased in the expiratory phase. As a result, it was found that the duodenum, but not the stomach, moved synchronously with the primary tumor and breathing. Taniguchi et al. reported how the respiratory phase impacts doses to normal organs during SRT for pancreatic cancer [18], and they demonstrated that the dose to the duodenum was higher in the inspiratory phase than in the expiratory phase and that there was a significant overlap of the PTV with the duodenum. Moreover, though there were no statistical differences in PTV overlap with the stomach, this overlap volume was increased at the inspiratory phase in their study. The results for the duodenum were different in their study and our study. Although there were differences in the number of cases, irradiation method, and PTV volume, the reason for the difference in the results is not clear. However, it is thought that the doses to the stomach and duodenum would be likely to change under the condition of free breathing. Changes in doses to the stomach and duodenum due to respiratory changes also occurred in SRT for hepatic cell carcinoma [19]. Therefore, a strict approach for respiratory movement may be required at dose escalation by SRT or IMRT. For example, Huguet et al. reported that gating around end-exhalation reduced pancreatic tumor motion by 46–60% [8]. In the cases undergoing IMRT or SRT in the present study, RT with gating was also performed. We consider that fiducial marker placement is also important as RT method against respiratory movement [20]. Taniguchi et al. reported that a large PTV volume produced more overlapping volume of the duodenum and stomach [18], and the PTV volumes was shown to be significantly correlated with the development of acute intestinal toxicity [21]. Therefore, those methods for respiratory movement would be necessary in the case of large PTV volume.
There were some limitations in the present study. First, the number of cases in this study was small. Second, the distance between each target was from the center of the target in the present study, and evaluation of the target edge was not performed. However, we consider that this point would be supplemented by the results of PTV overlap and mean dose in the stomach and duodenum due to respiratory movement. Third, only 4DCT in RT planning was used in the analysis in our study, and variations of the intrafraction and interfraction during RT were not considered. Akimoto et al. showed that there was a change in the position of the pancreatic tumor during interfraction and intrafraction [22], and some studies have shown that 4DCT alone does not adequately reflect respiratory movement of pancreatic cancer during daily treatment [23, 24]. Large deformation and displacement of the stomach and duodenum on CT images taken on separate days have also been reported [25, 26]. Furthermore, there has been a report showing dose changes in the stomach and duodenum during interfraction [27]. Therefore, it seems that not only the technique for considering respiratory movement but also the setting of PRV margins for the duodenum and stomach is important. In fact, PRV has been established to determine dose constraints of the stomach and duodenum in RT for pancreatic cancer [28]. A more reproducible treatment plan must be made when performing high-dose irradiation for pancreatic cancer.