Combination of Immunotherapy and Radiation Therapy in Gastrointestinal Cancers: An Appraisal of the Current Literature and Ongoing Research

Round 1

Reviewer 1 Report (Previous Reviewer 2)

The manuscript is now a much stronger paper in the revised form and the authors have addressed all of my suggestions.

Reviewer 2 Report (Previous Reviewer 3)

good edits overall with better structure

comprehensive review 

no attached reply to editors letter

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Kumar and colleagues have written a comprehensive review article on the current evidence from combination immunotherapy and radiation therapy in GI cancers, as well as an overview of ongoing clinical trials. They are to be commended for the comprehensiveness of scope in this important field.

There are a few minor points which may improve the manuscript:
1) A number of assertions are presented without references (namely lines 56, 57, 61, 263)

2) The PET images in Fig. 1 are hard to interpret readily. Please provide magnified regions as inserts.

3) Please include the RT dose for Cholangiocarcinoma and the SBRT doses for pancreatic cancer. Please also include RT doses for colorectal and anal cancer.

Author Response

Please see attachment

Author Response File: Author Response.docx

Reviewer 2 Report

A very comprehensive review of radiotherapy and immune checkpoint therapy use in gastrointestinal cancers with complete referencing of puiblished studies and oncoing trials.

1. However an important development that is not covered in this paper is that of radioembolisation with the use of yttrium 90 in hepatocellular carcinoma and I believe this should be included for completeness although this is not external beam radiotherapy.

Translational data supporting this:

https://gut.bmj.com/content/68/2/335?ijkey=ff4ed768532f3dca7eb5cea1a4fb9b35711da611&keytype2=tf_ipsecsha

 

https://gut.bmj.com/content/72/2/406

 

Published studies:

https://jitc.bmj.com/content/10/11/e005457

https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00305-8/fulltext

Ongoing radioembolisation and immunotherapy studies are listed in this paper:

https://onlinelibrary.wiley.com/doi/10.1111/1754-9485.13405

2. This second paper by Sharabi supports the augmentation of antitumour immune responses by SBRT.

https://pubmed.ncbi.nlm.nih.gov/25527358/

The generic names of drugs do not need to be be capitalised throughout the manuscript.

Author Response

Please see attachment

Author Response File: Author Response.docx

Reviewer 3 Report

The review paper: 

 

 Combination of Immunotherapy and Radiation Therapy in Gastrointestinal Cancers: An Appraisal of Current Literature  and Ongoing Research 

 

Is a clear, concise and timely appraisal of the current clinical evidence and practice. The breakdown of the GI neoplasm is excellent. However there are some areas needed expanded especially regarding discussion and limitations - See below 

 

Suggestions:

 

1. Abstract:

- Worth not drawing attention to just Esophageal and HCC - Better to remove and provide a broader narrative to all GI neoplasms

 

2. Introduction:

- Nice overview 

- Concise 

- No issues/ edits

 

3. Mechanism 

- Could expand on this more

- Does only radiation sensitive tumors work with ImmunoTx - Or does it work on all

- Highlight evidence base for this 

 

4. GI subsets 

-Good breakdown of GI cancers

- Nice reflection of current evidence 

 

5. I think an area of Discussion is needed

- What are the current limitations

- Little data on length of immunoTx - How long to continue it 

- What happens in setting of complete or suspected clinical response 

- Recurrence following ImmunoTx - Salvage impacted?

- What are issues with immunotx - Immune-mediated complications - Colitis etc - Lessons learned from Melanoma etc

- Anything on QoL 

- Limitations at present 

 

6. Future directions - What is on the horizon 

Author Response

Please see attachment

Author Response File: Author Response.docx