Is an Endorectal Balloon Beneficial for Rectal Sparing after Spacer Implantation in Prostate Cancer Patients Treated with Hypofractionated Intensity-Modulated Proton Beam Therapy? A Dosimetric and Radiobiological Comparison Study

Round 1

Reviewer 1 Report

The Dalia Ahmad Khalil et al reported examining the dosimetric influence of endorectal balloons in rectal sparing with implanted hydrogel rectum spacers treat with does escalated IMPT in  prostate cancer patients. The authors showed that the endorectal balloons decreased the rectal volumes exposed to intermediate dose levels. There is no significant reduction in rectal volumes receiving high doses. In addition, they also concluded no benefit and no disadvantage of the ERB for late rectal toxicity for NTCP models.

The manuscript is well written and overall convincing. The results will be of interest not only for cancer researchers but more in general. I think the manuscript should be considered for publication, as long as the authors are able to address some specific concerns (see below).

1, The table 2 showed that ERB could reduce the Dmax, D1, RV72Gy, RV70Gy, RV65Gy, RV60Gy, RV55G, RV50G, RV40G, 156 RV30Gy, RV20Gy, and RV10Gy, but no statistically significant differences could be reached. There are two P value are 0.059. So the tread is obvious. Do the authors think whether larger number of experiment affect the results?

2, The ten patients were treated with does escalated hypofractionated IMPT. I think if the authors increased the number of patients, it will be better for statistics.

3, are there patients healthy condition or other factors affect the results?

4, does the endorectal balloon for rectal sparing after spacer implantation in prostate cancer bring patients benefits such as survival time, treatment and prognosis and so on? Perhaps this will be interest of some people.

5, The author showed figure1, 2, 3, but it seems the figure2, figure3 were not cited in the manuscript. Even if the figure results were analyzed in the manuscript, the figures need to appropriately cite.

Author Response

To whom it may concern, 

Thank you very much for your critical review and positive assessment of our manuscript. We were able to substantially improve the manuscript through your valuable comments. 

Re 1 + 2: 
Thank you very much for the important information. In the pilot phase, patients underwent a Planugns CT with and without a rectal balloon in order to determine the advantages of the balloon for the individual patient. This work is the first time that a systemic analysis of these data has been conducted. This is the first systemic analysis in patients with intensity-modulated proton therapy in the context of a hypofractionated SIB concept, which is therefore of great clinical relevance. 
Our results show an advantage for the rectal balloon, so that we considered it ethically and for radiation protection reasons not justifiable to further evaluate patients with two planning CTs. It is therefore not possible for us to increase the number of patients. 
Please note, however, that a planning CT with and without rectal balloon was carried out in the same patients and therefore these data are extremely homogeneous. This internal direct control makes it scientifically possible to draw reliable conclusions on the basis of the rather small number of patients. 

However we do understand your point and have stated this within the limitations of our mansucript. 
3: 
The patients were in a good general condition without further life-limiting diseases with a life expectancy of over 5 years. Thank you very much for the important information. We have included this in the manuscript accordingly. 

4: 
No clinical endpoints can be collected in the planning study, as the same patients were planned with and without balloon. However, in this internal control, the patients were all treated with balloon. Basically, the idea of the balloon is to reduce side effects with an already very good oncological outcome. We have included this important point accordingly in the discussion. 
5: 
Thank you very much. Firugen 2 +3 were referred to accordingly in the text. 

Reviewer 2 Report

This study examined whether the use of an endorectal balloon during intensity-modulated proton radiotherapy could reduce rectal dose and the probability of adverse rectal events.

The use of a balloon only partially reduced the rectal dose and the probability of complications calculated using the NTCP values did not change with or without the use of a balloon. This is also the case in previous studies of IMRT.

It is reasonable to assume that the intestinal dose is sufficiently reduced in high-precision radiotherapy that there was no difference.

The ability to fix the position, shape and size of the rectum also provides stability in the actual treatment, and the conclusions are understandable.

 

∙1. Can you add a note about the Gleason score and risk classification of the patients who were included?

 

2. Can you elaborate a little more on the h-strategy? Is it common practice to set PTV1 and treat with the SIB method, as you have done?  Is this method used regardless of risk group?

 

3. It would be easier to understand if the NTCP values were explained a little more.

Author Response

We are thankful to the  Reviewer for the valuable comments and much work dedicated to our manuscript. In this rebuttal we provide a point-by-point reply to all issues raised. In the file the revision appears highlighted in yellow 

Thank you very much for your feedback 

1. Thank you. Gleason score and risk classification of the patients were included.
2. Yes this is the standard also supported by national and internatinal guidlines- We agree with your suggestion and included this in the text. 
3. We agree- A describtion for NTCP had been added in the manuscript.  

Round 2

Reviewer 1 Report

The revised manuscript solved my questions. So I think that this manuscript should be accepted.