A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation

Round 1

Reviewer 1 Report (Previous Reviewer 2)

While the authors reviewed the manuscript and made modifications, the main objective of this study is to demonstrate the feasibility of obtaining serial biopsies for molecular experiments (gene expression), and cell culture. Therefore, I feel that too much emphasis is put on the interpretation of the gene expression results while the sample size does not allow to draw any conclusion. The authors should reformat and shorten the manuscript to focus on the main objective of the study. 

Author Response

As rightly suggested by the reviewer, we have removed all the interpretations of the gene expression results. We have also reformatted as required in revised manuscript. 

Reviewer 2 Report (Previous Reviewer 1)

The authors are commended on their study. The study however, seems to suggest that repeat biopsy is safe and feasible, which is not novel, however the extensive analysis of biopsy specimens is interesting and certainly suggests the need for additional studies. 

Author Response

We thank the reviewer for the positive feedback. 

Round 2

Reviewer 1 Report (Previous Reviewer 2)

The authors adequately addressed the previous comments. 

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

Page 1 line 43: “validates longitudinal sampling by EUS-FNABs…” not sure how a case study validates anything. This is an overstatement.

 

 

Line 317 – I am still unclear on the statistics of how feasibility could be determined in a case report N=2. I think this is an overstatement of your findings. Just because the authors demonstrated that they could perform serial EUS-FNABs and RFA in 2 patients does not mean that this is truly feasible and safe. It needs to be formally determined in an appropriately powered study. I think the authors should simply describe the molecular and immune changes in these 2 patients and reserve determination of safety and feasibility for their larger study. Rare events after EUS biopsy such as hemorrhage, perforation, and pancreatitis need to be assessed in a larger cohort to determine the actual safety of this approach. Regarding the molecular findings - these are interesting and need to be analyzed in a larger data set before any clear conclusions can be made.

Reviewer 2 Report

This manuscript describes gene expression/TME modifications following systemic treatment of advanced pancreatic adenocarcinoma. The paper is well written and easy to read. The novelty of the work revolves around getting serial specimens from the tumor before and after the initiation of the treatment, which is interesting by itself. However, the low number of patients (n=2) does not allow to draw any conclusion, in particular keeping in mind that gene expression is highly variable. While the authors emphasize that fact that this is rather a feasibility study, most of the manuscript describes and discusses the gene expression/TME results, which are not by any means strong enough.