Evaluating the Impact of Bowel Gas Variations for Wilms’ Tumor in Pediatric Proton Therapy

Round 1

Reviewer 1 Report

In this study, the authors conducted a comprehensive analysis of thirteen patients diagnosed with Wilms’ tumor, treated by proton therapy in the prospective SJWT21 clinical trial. The study aimed to evaluate the impact of bowel gas variations and the potential inaccuracies in the proton range caused by varying gantry beam angles during therapy of selected Wilms’ tumor pediatric patients. In terms of not many pediatric articles dedicated to proton therapy that article should be of high interest to readers. I have three minor comments for the authors.

1. In this sentence "….but it encounters challenges when dealing with beam path heterogeneities and daily variabilities including tissue discrepancies...", in my opinion should be clear that each radiotherapy type, not only proton beam dealing with "beam path heterogeneities and daily variabilities including tissue discrepancies". If authors specifically understand “beam path heterogeneities” - I mean observed for heavy ions, and protons that should be cleared.

2. Authors indicated doses in GyRBE, for clarity they should add also doses in Gy.

3. For prospective trial studies information about future directions is important. The authors should add a few sentences about the continuation/future of this study.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

This is a nice writeup of a study for a rare pediatric cancer and relevant to proton therapy of other abdominal tumors. I think the methodology is sound. I just have a few minor comments on the text and discussion:

-          Line 139: it’s not clear why sometimes 3%/3mm is used and sometimes 5%/5mm is used for setup/range uncertainty. In the Discussion, line 369, it seems the decision of which to use is based on a subjective estimate of the uncertainty, perhaps made by the planner? Please elaborate on this decision in the text.

-          Line 226 states that Table 2 shows the differences in WEPL for each field. But I only see one DeltaWEPL per patient, although all patients had 2-3 fields. So is this DeltaWEPL averaged over all fields and all fractions? Is it possible to show the average DeltaWEPL for each field, or at least give a sense of which fields had the largest DeltaWEPL?

-          Line 270: text labels the figures as 2A and 2B but the captions label them Figure 1 and 2 (which seems more correct).

-          Line 459: One thing missing from the Discussion is a discussion of how these results could be used to improve plan robustness for the patients with very large DeltaWEPL and dose discrepancies. Based on this information, would you have recommended changing any of the treatment angles for those patients? Or is there some other reason the angles with the least WEPL variation are not clinically acceptable? Like if the target is on the left, is it acceptable to use a right-sided gantry angle to minimize daily variation?

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

This study aimed to evaluate the influence of bowel gas variability on treatment plan accuracy and proton range uncertainties in pediatric proton therapy for Wilms’ tumor. This is an important study in this field and can help improve treatment quality in clinical practice. I only have minor comments to the authors.

1. Please more clearly describe the purpose of this study in the Abstract.

2. Had the authors tried to use real time adaptive plan or AI-based plan to overcome the influence of bowel gas and proton range uncertainties in these patients? 

3. It is unclear the influence of intra-fraction bowel movement on proton therapy in these patients.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf