Tumors of the Digestive System: Comprehensive Review of Ancillary Testing and Biomarkers in the Era of Precision Medicine

Round 1

Reviewer 1 Report

The authors present a review of the different immunotherapies in play for cancers of the digestive system.  They then expand on the current laboratory techniques key for detecting molecular changes in these cancers.  The known biomarkers for detecting the relevant cancers and then determined for their effectiveness.  The review captures the majority of current thoughts on precision medicine in this field.

Minor comments:

It would help to have an overview in the Introduction of the scope of digestive system cancers to be looked at in the review.

Line 72 – be specific when talking about the ‘minority’ of patients showing a detectable response to ICIs.

Line 172/3 – should be deoxynucleotide triphosphates (dNTPs) instead of deoxydinucleotides (dDNTPs).

Section 3.3 – it would help to expand the PCR section to cover digital PCR as well; especially as this is referred to later in the review.

Further comment about the utility of circulating tumour DNA would be good.

Between lines 332 and 333, is this Table 5 – please check formatting.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Major comments

-          Creating a figure or table to represent the immunotherapeutic agents that target tumors of the digestive system would add depth.

-          The authors should add a description of Cytokine-induced killer cells in the adoptive cell therapy section.

-          Having an executive summary before the conclusion section would make the manuscript more comprehensive.

Minor comments:

-          Line 72 needs to be corrected – “[6Only a minority of patients show a detectable response to ICIs [7], however, necessitating further screening with biomarkers to assess for eligible patients.”

-          On page 2, line 102, correct for spacing.

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

In this review, the authors summarised tumors of the digestive system: a comprehensive review of ancillary testing and biomarkers in the era of precision medicine. Overall, this review is compelling and may be helpful for the readership. I suggest a minor revision is required before publication. The primary concern is that the authors would better summarize the significant findings with a graphic abstract and put it at the end of this review, which will help the readers to know the contributions in the fields. Another concern is that the authors should provide more information in Part 5 (Immunotherapeutic biomarkers per organ system) and discuss the related immunotherapeutic biomarkers.

Author Response

Please see the attachment.

Author Response File: Author Response.docx