Small Bowel Dose Constraints in Radiation Therapy—Where Omics-Driven Biomarkers and Bioinformatics Can Take Us in the Future

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In this study, the authors review radiation-induced gastrointestinal (GI) dose constraints in image-guided intensity-modulated radiation therapy (IMRT), stereotactic ablative radiotherapy (SABR) since they are a matter of concern in the ongoing evolution of patient outcomes and treatment related toxicity. They highlight the pathophysiology and dose response of small bowel injury leading to the current small bowel (SB) constraints, and look into the proteomic, metabolomic and microbiome surrogates for acute and late to incorporate them into standard of care. I consider the content of this manuscript will meet the reading interests of the readers of the journal but the paper needs revision before accepting for publication. Consider the following suggestions.

1. Title too long. Consider rephrasing to make it shorter.

2. Need to elaborate on abbreviations before using them. For example, PTV, RCT, etc.

3.  The quality of Figures are very poor and the contents are not clearly visible.

4.  Elaborate more on the what dose/volume parameters are used for each technique? I would suggest to add them to the figure 1 or a make a separate table to mention them with references.

5. I would recommend adding a table with summary of evidence for biomarkers including for example study design, evidence, measurements, etc. with references

6. Need to rework on the conclusions based on the above revisions

Comments on the Quality of English Language

The english needs some minor revisions.

Author Response

Please see the attachment:

Bethesda, November 27, 2023

 

 

Dear reviewers and editor,

Thank you for your work on our manuscript. Please find our corrections and response in italics below. The corrections have been made with track changes.

Thank you kindly.

Reviewer 1:

In this study, the authors review radiation-induced gastrointestinal (GI) dose constraints in image-guided intensity-modulated radiation therapy (IMRT), stereotactic ablative radiotherapy (SABR) since they are a matter of concern in the ongoing evolution of patient outcomes and treatment related toxicity. They highlight the pathophysiology and dose response of small bowel injury leading to the current small bowel (SB) constraints, and look into the proteomic, metabolomic and microbiome surrogates for acute and late to incorporate them into standard of care. I consider the content of this manuscript will meet the reading interests of the readers of the journal but the paper needs revision before accepting for publication. Consider the following suggestions.

1. Title too long. Consider rephrasing to make it shorter.

We agree with the comment and have shortened the title to read: “Small bowel dose constraints in radiation therapy - a use case of where omic driven biomarkers and bioinformatics can take us in the future.”

2. Need to elaborate on abbreviations before using them. For example, PTV, RCT, etc.

We agree with the comment and have added a list of abbreviations.

3. The quality of Figures are very poor and the contents are not clearly visible.

The figures have now been submitted as separate png files.

4. Elaborate more on the what dose/volume parameters are used for each technique? I would suggest to add them to the figure 1 or a make a separate table to mention them with references.

Dose/volume parameters overlap between techniques and most often have been adapted from one technique to another. They are too elaborate to do justice by fully adding to Figure 1 but are already present in Tables 1, 2, 3, 4, 5 and referenced in the text. We have enhanced this link by modifying Figure 1 to reflect the linkage as closely as possible given the overlap, adding general dose/volume parameters and referencing the Tables that correspond most closely.

5. I would recommend adding a table with summary of evidence for biomarkers including for example study design, evidence, measurements, etc. with references

This is an excellent suggestion. This table has been added as Table 7 with corresponding references.

6. Need to rework on the conclusions based on the above revisions

Conclusion is based on the revised manuscript.

 

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

In this review, the authors talked about how omic-driven biomarkers and bioinformatics can potentially improve small bowel dose constraints in radiation therapy planning. The authors stress the need for comprehensive omic analyses, including proteomic and microbiomic data, to identify individuals at greater risk of experiencing toxicity. They recommend that such biospecimens be collected prospectively across all oncology studies to facilitate future analyses and improve our biological understanding of treatment outcomes. They also highlight the urgency of establishing a well-planned strategy for collecting omic and microbiome data, especially as radiation doses and technology are advancing rapidly. The authors advocate for a unified bioinformatic toolkit that integrates both types of data to improve treatment personalization and side effect management. This integrated approach is vital for optimizing therapeutic outcomes in the modern era of radiation therapy. 

In this review, the authors have included an overview of the current state of radiation therapy for small bowel cancer and the challenges associated with it. An explanation of omic-driven biomarkers and bioinformatics and how they can be used to improve radiation therapy planning for small bowel cancer, a discussion of the potential benefits of using omic-driven biomarkers and bioinformatics in radiation therapy planning, including improved treatment efficacy and reduced toxicity, a conclusion summarizing the current state of knowledge on the use of omic-driven biomarkers and bioinformatics in radiation therapy planning for small bowel cancer, as well as future directions for research and clinical practice

However, the review still lacks the following information:

1. A review of the current literature on the use of omic-driven biomarkers and bioinformatics in radiation therapy planning for small bowel cancer, including both preclinical and clinical studies.

2. A discussion of the limitations and challenges associated with using omic-driven biomarkers and bioinformatics in radiation therapy planning, including issues related to data quality, standardization, and interpretation.

3. An overview of ongoing research and clinical trials in this field, including their potential impact on future radiation therapies. 

 

Author Response

Please see the attachment:

Reviewer 2:

In this review, the authors talked about how omic-driven biomarkers and bioinformatics can potentially improve small bowel dose constraints in radiation therapy planning. The authors stress the need for comprehensive omic analyses, including proteomic and microbiomic data, to identify individuals at greater risk of experiencing toxicity. They recommend that such biospecimens be collected prospectively across all oncology studies to facilitate future analyses and improve our biological understanding of treatment outcomes. They also highlight the urgency of establishing a well-planned strategy for collecting omic and microbiome data, especially as radiation doses and technology are advancing rapidly. The authors advocate for a unified bioinformatic toolkit that integrates both types of data to improve treatment personalization and side effect management. This integrated approach is vital for optimizing therapeutic outcomes in the modern era of radiation therapy. 

In this review, the authors have included an overview of the current state of radiation therapy for small bowel cancer and the challenges associated with it. An explanation of omic-driven biomarkers and bioinformatics and how they can be used to improve radiation therapy planning for small bowel cancer, a discussion of the potential benefits of using omic-driven biomarkers and bioinformatics in radiation therapy planning, including improved treatment efficacy and reduced toxicity, a conclusion summarizing the current state of knowledge on the use of omic-driven biomarkers and bioinformatics in radiation therapy planning for small bowel cancer, as well as future directions for research and clinical practice

However, the review still lacks the following information:

1. A review of the current literature on the use of omic-driven biomarkers and bioinformatics in radiation therapy planning for small bowel cancer, including both preclinical and clinical studies.

This is an excellent suggestion. However, while biomarkers are of interest in current literature, further work remains in adapting these diagnostic tools for practical use.

2. A discussion of the limitations and challenges associated with using omic-driven biomarkers and bioinformatics in radiation therapy planning, including issues related to data quality, standardization, and interpretation.

This is an excellent suggestion. This content has now been added.

 

3. An overview of ongoing research and clinical trials in this field, including their potential impact on future radiation therapies. 

This content has been included.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

It is recommended to format the paper according to journal style.

Author Response

Thank you for your comment. Please find attached a revised version formatted according to journal style.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors made revisions based on the earlier comments. 

 

Author Response

Thank you