For the standardization of prostate cancer IGRT, it is more valuable to train observers to eliminate the interobserver variability in CBCT-based soft-tissue matching. Therefore, in this study, we attempted to analyze the impact of simulated interobserver variability on targets and critical OARs, thereby providing a theoretical explanation for the clinical practice of CBCT-based soft-tissue matching. Our analysis shows that only the NTCPs of the rectum were highly influenced by the simulated interobserver variability.
The TCPs of CTV1 were insensitive to simulated interobserver variability, which suggests the robustness of CBCT-based soft-tissue matching in terms of target localization. Surprisingly, this result is consistent with previous clinical trials. Napieralska et al.14 reported that no significant differences in five-year progression-free survival were found between fiducial- and bone-based IGRT. As reported by Kotecha et al.15 and Li et al.16, CBCT-based soft-tissue matching is superior to fiducial-based IGRT in terms of target dosimetry, but a favorable rate of biochemical control was achievable using both IGRT techniques. This implies that a more accurate prostate target localization IGRT technique was not correlated with superior TCP.
Theoretically, various studies have demonstrated that a 3-mm PTV margin is sufficient17,18. Therefore, the CTV1 dosimetry would not be deteriorated by the 2-mm interobserver variability simulation because a 5-mm PTV margin was used in this study. Furthermore, several studies19–21 have confirmed that PTV dosimetry is not sensitive to anatomical changes. Under this condition, the factors affecting the CTV1 dosimetry are interfractional deformation and intrafractional motion. Mayyas et al.22 reported that prostate interfractional deformations were mainly due to rectal volume variation. Hence, the rectal emptying protocol was strictly carried out in our hospital. As a result, the absolute volume variations of the rectum were -4.9 ± 13.3 ml, negligibly small. In addition, Shelton et al.23 verified that the intrafractional prostate motion was almost within 1 mm for the use of VMAT. This implies that a 5-mm PTV margin is sufficient to compensate for interfractional deformation, intrafractional motion, and simulated interobserver variability.
For CTV2, the ESTRO guidelines2 recommended a 7-mm PTV margin, while a 5-mm PTV margin was used in this study. However, the changes in the CTV2 dosimetry induced by the simulated interobserver variability were similar to those in the CTV1 dosimetry (Fig. 1). A possible explanation for this is that the volumetric dose parameters in a larger target (CTV2) were less sensitive to the same couch shifts. In addition, pelvic lymph nodes were irradiated for prophylactic purposes. Therefore, the TCPs of CTV2 were not included in this study.
Interestingly, the NTCPs of the rectum were deemed to be highly influenced by the simulated interobserver variability, while the NTCPs of the bladder were not. This result may be explained by the fact that the average NTCPs of the bladder ranged from 0.75 (%) to 1.12 (%) among the potential patient positions. In other words, the changes in the NTCPs of the bladder were negligibly small. Moreover, this is consistent with the fact that the bladder is less radiosensitive than the rectum11. The volumetric dose parameters and NTCPs of the rectum were highly influenced by the couch shift in the AP direction, while those of the bladder were sensitive to the couch shifts in both the AP and SI directions (Supplementary Material B). This inconsistency may be due to the bladder being located in the direction superior to the high-dose PTV (PTV1).
Besides, Fiandra et al.3 reported that the average interobserver variability between senior radiation oncologist and radiation therapist in LR, SI, and AP directions were 1.32 mm, 1.69 mm, and 2.05 mm, respectively. Similarity, the results in the study of Jereczek-Fossa et al.6 were 1.9 mm, 0.9 mm, and -0.7 mm. Recently, Hirose et al. 5 took contour-based patient positioning as reference, and found that the average interobserver variations among six experienced radiation therapists in LR, SI, and AP directions were 0.5, 0.9, and 0.9 mm, respectively. Therefore, in this study, a maximum couch shift of 2 mm relative to the resulting patient position of prostate alignment were used for interobserver variability simulation. Furthermore, we simulated a maximum couch shift of 5 mm (with 1 mm stepwise) in anterior and posterior directions for one treatment fraction, and found highly linearity between the NTCPs of the rectum and couch shifts in anterior and posterior direction (Supplementary Material C).
The main drawback of this study is that the data from the prostate gland and the seminal vesicles were combined for analysis. As a result, the movements of the seminal vesicles independent of the prostate gland were not quantified. Therefore, in the process of CBCT-based soft-tissue matching, we ensured that the prostate gland and seminal vesicles were inside the prescription isodose line of the planned dose distribution.