Tumour volume change

Previous studies on NSCLC SABR treatment have reported changes in tumour volume, despite a short treatment duration of typically 7–12 days. Using various imaging modalities, some studies [41, 42] reported a consistent decrease in GTV, whereas others [43,44,45] noted a slight initial increase in GTV during the treatment course, followed by a decrease. At our institute, treatment records document the ITV instead of the GTV; therefore, this study investigated the changes in the ITV volume during the course of treatment. Considering the average volume differences per fraction for both the ITV and PTV are nearly zero and significantly smaller than the SD in Fig. 4(c) and (d), volume changes during the SABR treatment did not constitute a significant concern in this study.

In the ACTs, the ITVs and PTVs were automatically recontoured following the DVF obtained from the DIR using commercial software, and their volumetric differences were consistently negative. These plots indicate that the recontoured structures exhibit a marginally smaller volume than their original volume, and the volume difference may originate from the differences in the method of treating the respiratory motion between PCT and CBCT. The ITV in the PCT was delineated based on the MIP of the GTV, whereas the CBCT was acquired with free-breathing. This might have affected the ITV in the ACT, reflecting that the volumes recorded in the free-breathing CBCT are marginally smaller than the ITV and PTV in the PCT. However, this volume difference was significantly smaller than the SD. Comparing the values in Fig. 4(c) and (d), the average ITV differences are approximately twice as large as those of the PTV. These discrepancies might have occurred because the ITV, when used as the denominator to calculate the volume difference, is smaller than the PTV.

Recontoured structures for dose evaluation

Concerns may arise regarding the accuracy of the aRS recontoured automatically using the commercial software. When applying the ACT for adaptive planning, it is essential for a radiation oncologist to review and correct the delineation of the ITV and PTV prior to treatment approval. Nonetheless, the automatically recontoured ITV and PTV on ACT, based on the DVF, were considered adequate for evaluating the dose delivered to the patients. This study was performed to investigate how the original PTV was deformed in the treatment and whether the planned dose was actually delivered to the original PTV. Among the collected patient data, the ITV and PTV delineations were randomly selected and reviewed by an expert for comparison with manual recontouring. This comparison revealed no significant differences in dosimetric evaluation, thus supporting the use of automatically recontoured structures for dose evaluation across all 288 ACT cases.

PTV parameters depending on the tumour location

The PTV located in the lower lobes showed a greater discrepancy in the position between the treatment and simulation. The mean Warpmean value was notably higher and the mean D95% value was significantly lower for tumours located in the lower lobes compared with those of tumours in the upper lobes (Table 4). Furthermore, the SDs for PTVs in the lower lobes exhibited a significant increase, indicating that tumours located in the upper lobes allow for more consistent patient setup reproducibility, thereby enhancing the accuracy of the prescribed dose delivery to the PTV. Among the seven outliers, six had PTV located in the lower lobes. This may be attributed to the observed higher Warpmean and lower D95% values in the lower lobes, a trend that these outliers similarly exhibited.

Outliers of the multiple linear regression model prediction

Seven outliers marked in Figs. 5 and 6 are characterised by having the highest ΔHI and small PTV volume. These outliers show significant deviations from linearity, as shown in Fig. 8. The PTV D95% values of the outliers calculated from the ACTs in the TPS deviated from the PTV D95% predictions of the multiple linear regression. Two geometric and two dosimetric parameters were found to be significantly related to the D95% in the multiple linear regression, and the detailed results are listed in the Table 3.

Fig. 8

Scattered plot of the residual of the dose prediction vs. the predicted valued of the regression model. Concerned outliers were highlighted in the scatter plot

To evaluate the effect of ACTs with a high ΔHI, stepwise multiple linear regression was repeated, excluding ACT cases of HI > 17, based on the distribution in Fig. 5(b). The results summarised in Table 5 indicate that only the dosimetric parameters maintained a significant correlation with D95%. This indicates that the outliers may be closely linked to the two geometric parameters that represent the PTV displacement. Such displacement might imply uncertainties from the patient setup and respiratory motion, resulting in dosimetric uncertainty. Kim et al. [46] highlighted that geometric uncertainties in patient positioning can limit the clinical advantages of IMRT. Therefore, during SABR treatment, a more thorough consideration of patient setup and respiratory motion is imperative.

Although these cases exhibited suboptimal dosimetric outcomes for the PTV, Fig. 3 confirms that the dose was accurately delivered to the ITV. This demonstrates that the margin between the ITV and PTV effectively ensures sufficient dose coverage of the ITV. As the patients were treated under the prescription of one radiation oncologist, the ITV and PTV were consistently determined. However, it is worth studying whether the margin can be further reduced with respect to various parameters obtained. In this study, analysis of multiple parameters enabled a more precise evaluation of the dose delivered.

Table 5 Results of the multiple linear regression by SPSS® (v27, IBM®, Chicago, IL, USA) with cases having ΔHI less than 17Uncertainties affecting the deformed image

In DIR, the PCT is a moving image, while the daily CBCT is a stationary image. When the PCT is deformed to the daily CBCT, the deformed PCT is called an ACT, retaining patient information at the time of the treatment setup. In the TPS dose calculation, the delivered dose based on the ACT was calculated using the original beam plan. Thus, we believe that the setup error implied by the ACT affects the estimated delivered dose.

Although the QA parameters of DIR [39] were assessed and included in the analysis (Table 2), the uncertainty of the DIR algorithm was not considered. Repeating the DIR using the same CBCT and PCT images is insufficient to estimate the DIR uncertainty; however, the DIR uncertainty is expected to be systematic without giving a rise to an outlier. As the outliers of interest occurred randomly among the 288 ACT cases, they likely originated from a random source, such as the setup error rather than the DIR algorithm error.

Limitations of this study

One limitation is the resolution of the parameters obtained by comparing the images. The image resolutions of the PCT and daily CBCT are presented in Table 1. Recalling the method of generating the ACT, it is a result of the deformation of the PCT to the daily CBCT, thus the resolution of the ACT is same as that of the PCT; the transverse and vertical resolutions of the ACT were approximately 1.3 and 3 mm, respectively. Considering the Warpmean, which showed a peak around 1.3 mm (Fig. 7b), it is challenging to calculate any finer displacement. However, we used the average value of the displacement calculated from PTV voxels; thus, we did not rely on a single movement value but on the movement trend of the PTV structure.

Secondly, a methodology covering intra-fractional motion during SABR was lacking. Monitoring the intra-fractional motion might be optimal for IMRT treatment using an MR-Linac. In the CBCT-Linac option, it is difficult to track real-time respiratory motion during treatment. In particular, for SABR, respiratory motion-controlled treatments, such as DIBH, are not normally considered. Although we observed one case of using continuous positive airway pressure breathing, the respiratory motion was not monitored.

Intra-fractional motion was considered as the respiratory motion in the PCT and ACT images, and the patients were subjected to treatment with a free-breathing. In PCT, the respiratory motion was assessed using the MIP of the tumour. As we did not control the patient’s respiration during CBCT acquisition, which took approximately 1 min, the image was expected to represent the average motion of the GTV. Surrounding OARs were also obtained with average intensity projection (AIP) on PCT and with the free-breathing on CBCT.

Comparison of the result with previous studies

Previous studies utilised the same commercial software to evaluate the dose delivered to patients with NSCLC. Czajkowski P et al. [35] evaluated the accuracy of dose delivery in the stereotactic radiation therapy for both brain and lung cancers. Although they analysed only 10 patients for the lung SABR dose evaluation, they reported no significant change on the ITV volume during the treatment and agreement within ± 10% on the dose in 99% volume of the PTV between the PCT and ACT. They assessed only the PTV volume and DSC regarding the PTV change. On the contrary, Wang B et al. [36] investigated the differences of delivered and planned dose to PTV as well as to the OARs, which were clinically acceptable. They used records of 27 patients with locally advanced NSCLC who were treated with 51 Gy in 17 fractions. They generated ACTs for treatment in 1,5,9,13, and 17. A significant tumour shrinkage (11.1%) was observed through the course. However, no significant difference was discovered in the volume of 51 Gy isodose line corresponding to the PTV, but limited increase (< 5%) was observed in total lung, oesophagus, and heart.

Compared with previous studies, we calculated delivered dose for every fraction and assessed the PTV parameters as much as possible with an increased number of patients. We were able to obtain distributions of the significant PTV parameters and the parameters were proven to be related to the PTV D95%. Besides the delivered dose evaluation, the PTV D95% and the PTV displacement from the PCT were observed significantly related to the tumour location.