Discussion
Uhl, toxicity, CRS, prostate, GI toxicity
PROSTATE
Our study confirmed reduced rectum doses shown by several studies using mainly PEG-spacers [In this study, the CRS decreased during RT, resulting in a larger relative rectum volume receiving dose in MR2 and MR3 than in MR1. This might be due to changes in HA viscosity, size or in the position of the spacer. The MRI used for treatment planning (MR1) was, in median, performed the day after the application of HA with a range from 0 to 5 days. Our results indicate that the spacer is not stable at this time, but it is between MR2 and MR3. Since no MRI was performed between MR1 and MR2, we can not determine when stabilisation of the spacer occurs. However, HA still significantly reduced the rectal V50%-V90%.Susil et al. [We noticed that the patient with rectal grade 3 toxicity fulfilled the rectum criteria for V90% of 15% in MR1 but not in MR2 and MR3. Surprisingly, the CRS were around 10 mm in all levels in MR1/MR2/MR3, so the HA was separating the rectum from the prostate as intended. Relating CRS to rectal dose or side effects is complex, the dose optimisation is based on one image occasion, and our data shows a variation in rectal dose during RT, see Fig. A strength of the imaging part of the study is the comprehensive MRI protocol enabling evaluation of the HA spacer over time. Possible limitations could be that we measured CRS in only three levels and assumed that the CTV centre did not vary in base-apex extension during RT. Moreover, we used automatic registrations to transfer ROIs from MR1 to MR2/MR3, resulting in more edgy structures compared to ROIs delineated by a radiation oncologist. This is because manual outlining in the clinic tends to smooth edges; registrations operate only on pixel intensities. In addition, the form and placement changes of the HA-spacer can lead to the underestimation of HA-thickness.Uhl et al. [The proportion with GI toxicity grade ≥ 1 at 2- and 5-years follow-up seem to be lower in this study than in the HYPO-RT-PC control arm (7% vs. 18% and 4% vs. 15%). Furthermore, the grade ≥ 2 GI toxicity at 2 and 5 years were slightly lower here than in the HYPO control arm, as well as the cumulative late grade ≥ 2 GI toxicity [Even though we noted a reduced rectal dose, there were no big differences in the PROs compared to results from the HYPO-RT-PC [There are limitations in this study regarding the PROs. For example, different scales were used in the follow-up questionnaires since the questionnaires changed during the long inclusion period. Furthermore, there was a considerable loss of questionnaires in the study. This may explain the possible difference in outcomes between physician-evaluated side effects and patient-reported ones. On the other hand, there are weaknesses with the RTOG scale that could lead to underestimating late bowel toxicity [In this study a mostly low-risk PC population treated with conventionally fractionated RT was included. This group may initially have a relatively low risk of toxicity and limited benefit from a spacer. However, rectal spacing could probably be particularly beneficial in ultra-hypofractionated RT as well as in high-risk PC treated with dose-escalated RT since doses to the rectum potentially could be higher. Similarly, Hutchinson et al.[