We assessed internal and external marker motions during VMAT under EE-BH conditions for pancreatic cancer patients. Lens et al. reported a mean positional repeatability between consecutive BHs during the inhalation phase of -0.5 ± 0.8 and − 0.2 ± 1.7 mm in the AP and SI direction, respectively, for pancreatic cancer patients (as indicated by the Visicoil marker) (10). In the present study, the overall positional repeatability for the CoIM was 0.6 ± 1.5 and − 0.1 ± 2.2 mm in the X- and Y-axis, respectively. Regarding other disease sites, Lu et al. investigated the positional repeatability between BHs for eight liver and seven lung cancer patients under active breathing conditions, by comparing three consecutive CT scans (6). For liver cancer patients, the repeatability of systematic and random errors was 1.4 and 1.0 mm in AP direction and 1.6 and 1.4 mm in SI direction, respectively; for lung cancer patients, the respective values were 1.5 and 1.1 mm in the AP direction and 4.0 and 1.9 mm in the SI direction. Although the disease sites were different from ours, our BH approach showed comparable positional repeatability with active breathing control.
Regarding positional repeatability, the CoIM in the Y-axis > 2 mm was observed in 19.1% of all BH sessions, despite the external marker position being ≤ 2 mm. Based on these results, it is difficult to estimate the positional repeatability of the tumor only by referencing the position of the external marker during each BH session; an optimal internal margin is thus required to ensure positional repeatability of a pancreatic tumor without an internal marker.
Regarding positional variation, we found that both the internal and external markers drifted, even during BH [Fig. 6(a, c)]. According to Takao et al., this could be due mainly to physiological movements such as pulsations and muscle relaxation, or an incomplete BH (15). Meanwhile, the correlation between internal and external marker motions during BH was weak in a majority (51%) [Fig. 5(a)], which may be represented the physiological movements. Of these BH sessions, most of the positional variations of both markers were within 2 mm. From these results, we confirmed that most of the internal marker displacement can be ensured to be within 2 mm as long as one monitors that the external marker displacement is < 2 mm, even in a BH session with a weak correlation. In contrast, 60% of BH sessions where external marker displacement exceeded 2 mm (from the reference position) showed a strong correlation between the internal and external marker motions [Fig. 5(b)]. This might represent the incomplete BH, as a transition to inhalation phase due to limits of the BH. In the BH sessions with a strong correlation between the internal and external markers, monitoring the external marker motions during the BH could predict motion of the pancreatic tumor, as reported by Shen et al. (16); therefore, we are convinced that external marker motion can generally be used as a surrogate for internal marker motion during BH, despite a correlation coefficient.
In the intra-fractional subanalyses, the positional variation gradually decreased from the 1st to 3rd BH session, while the variation increased in the group with more than 3 BH sessions [Fig. 3 (d, e)]. In the inter-fraction subanalyses, positional variation improved during the 3rd 5-day treatment section (day 11–15), compared to that during the 1st 5-day treatment section (day 1–5). According to Lee et al., BH training before treatment improved the positional consistency of lung tumors (17). To further improve the positional consistency of pancreatic cancer motion during the 1st BH session within the first few days after beginning treatment, sufficient training of the patient in BH would be useful.
One limitation of this study was that positional variation was analyzed only in the SI direction because the motion magnitudes in the AP and LR directions were unclear due to the dependence on the gantry angle. Whitfield et al. reported that the inter- and intra-fractional pancreatic cancer motion was larger in the SI direction than in other directions under free breathing conditions (18), and Lens et al. reported that pancreatic cancer motion under inhalation-BH conditions was greater in the SI direction than in the AP direction (10); therefore, we assume that positional repeatability and variation would be smaller in the AP and LR directions than in the SI direction.
According to Nakamura et al., positional repeatability of > 5 mm for the pancreas was occasionally observed in daily CBCT, even when using visual feedback (9). In addition, the usefulness of visual feedback for positional variation during BH has not been reported. Considering these aspects, our institutional BH protocols are implemented without visual feedback, which may be another limitation. In contrast, several studies have reported that visual feedback provided high repeatability of BH (12, 17, 19). Given the visual feedback, it may have improved the positional repeatability and variation.