Impact of Postoperative Chemotherapy in Patients with Gastric/Gastroesophageal Adenocarcinoma Treated with Perioperative Chemotherapy

Round 1

Reviewer 1 Report

Manuscript ID: curroncol-1607452 Thank you for the opportunity to review this manuscript. Authors address a clinically relevant and important problem which occurs frequently (i.e. many patients do not/don’t want to receive postop chemo) and clinicians cannot appropriately counsel patients regarding the implications of this. Primary outcomes are disease free survival (DFS) and overall survival (OS), compared in those who received preop and postop chemo (i.e. periop chemo) and those who received preop chemo only. The older chemo regimens are used in this study, and this makes sense given the timeframe of the study. However, I do point out that the conclusions from this study may be somewhat irrelevant given that most centers now are administering FLOT. The authors should mention this point in their discussion, in the context of general trends in FLOT administration in Europe in recent years. The cohort size (n=110) seems quite small for patients from multiple centers over a 4-year period. This may simply be due to the population in the authors’ geographic area. Can the authors please comment on these small numbers and provide an explanation? How many centers were patient data collected from and how were patients identified? Did each institution have its own database of gastric cancer patients? The study period is only up to 2010, which is now 12 years ago. Have the authors considered collecting additional data so that the cohort is more contemporary? Even going to 2016 would allow 5 years of follow up. The authors should provide justification of this study time frame. It would be helpful to know how local recurrence and distant metastatic disease were detected. Were the methods uniform throughout the participating centers (i.e. biopsy-proven versus imaging only versus both). I am troubled by the subgroup analyses in this manuscript. The numbers were small to begin with (n=110) and become much smaller with additional analyses. This is further confirmed by the very large confidence intervals that are reported for some of the outcomes (for example the DFS confidence interval is 0-62.4). While I believe the data has been appropriately analyzed, the conclusions that we can draw from this manuscript (based on low numbers) is extremely limited. The authors should provide their search strategy in an Appendix. They claimed to have done a systematic review, but it appears that only Pubmed was searched, and the number of trials retrieved is less than what I would have expected. The authors should comment on how rigorous their search strategy was and whether a knowledgeable librarian was part of the team. I think the authors’ review of the literature demonstrates heterogeneity amongst the conclusions which speaks to the weaknesses of the existing data. The authors appropriately recognize the need for randomized data in this domain, but large numbers will be required to perform any meaningful subgroup analyses (i.e. node positive versus node negative, responders versus non-responders, and other clinically relevant groups). It is possible that randomized trials are simply not possible due to small numbers of advanced gastric cancer in Western countries. The authors mention STOPEROPCHEM as recruiting, but I think it needs to be made clear that while we eagerly await results from randomized trials, that the feasibility of such trials in Western countries should be questioned. I think this manuscript provides a nice summary of the existing studies in this domain and the current gaps in the literature. I think that this information would be of interest to oncologists who manage patients with advanced gastroesophageal cancer. My main concerns are the study time frame (only up to 2010), the few numbers of patients (I would have expected more) and the conclusions that we can reasonably draw from such few patients, the utilization of older chemo regimens which may be minimally relevant in today’s clinical context and the rigorousness of the search strategy. I think there are major limitations to this study, and I would be interested to see how the authors address some of these points.

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

The authors compared patients undergoing perioperative vs preoperative chemotherapy with two different regimens for gastric cancer. The primary aim was to assess disease-free and overall survival. Median survival was increased by 16.5 months with perioperative protocols, but no survival advantage was found in patients staged ypN+. Major study limitations are the retrospective design and the limited sample size. Did you find any difference in survival between the 2 chemotherapy regimens? 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Thank you for the opportunity to review the revised manuscript. The authors have adequately addressed my comments. 

Reviewer 2 Report

The revised manuscript looks improved. Congratulations for your fine work.