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Thank you for submitting the revised version of your manuscript.
We have now completed the evaluation of your revision. All three reviewers have carefully assessed the updated manuscript and independently confirm that their previous comments and concerns have been satisfactorily addressed. The reviewers note that the manuscript has improved substantially in clarity, structure, and scientific rigor, and that the remaining limitations of the study are now appropriately acknowledged.
Based on the reviewers’ recommendations and our own assessment, I am pleased to inform you that your manuscript is accepted for publication.
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I am satisfied that the authors have addressed all of my previous concerns about the article. It is now much improved and I feel that it is now suitable for publication.
I am satisfied that the authors have addressed all of my previous concerns about the article. It is now much improved and I feel that it is now suitable for publication.
I am satisfied that the authors have addressed all of my previous concerns about the article. It is now much improved and I feel that it is now suitable for publication
I am satisfied that the authors have addressed all of my previous concerns about the article. It is now much improved and I feel that it is now suitable for publication.
The authors responded to the comments of this reviewer in the satisfactory fashion including the mentioning potential flaws as the limitation of this particular study.
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The authors have adequately addressed my comments.
The reviewers agree that the manuscript addresses a clinically relevant question, but all highlight the need for substantial clarifications and methodological improvements. Key concerns include strengthening the rationale and originality, refining subgroup and sensitivity analyses, and improving mechanistic discussion and interpretation of heterogeneity in assessment methods. Overall, the reviewers recommend major revisions to address these issues before the work can be considered for publication.
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The manuscript presents an interesting and relevant investigation with the potential to contribute meaningful insights to the field. It addresses a clinically significant question and provides data that appear to be collected and analyzed with acceptable rigor. The structure is logical, and the manuscript is generally clear and well-organized. However, several important scientific and methodological aspects require clarification or expansion.
Please consider including subgroup analyses (e.g., by tumor type, performance status, or treatment line).
The research question is relevant, but the authors should better articulate the study’s originality compared with existing literature. Clarify the novel insight or clinical application that distinguishes this work from prior studies.
Recent literature has highlighted the Albumin–Myosteatosis Gauge (AMG) as a promising composite biomarker reflecting nutritional and metabolic reserve, which has demonstrated prognostic value in cancer patients treated with immunotherapy and chemotherapy.
This is the meta-analysis demonstrating the significant association of the status of myosteatosis detected by routine CT evaluation with poor or adverse clinical outcomes of the patients with esophageal carcinoma or gastroesophageal carcinoma. This study could provide important information for the improved management of those patients in real clinical settings for those managing those patients. This reviewer has the following comments on this manuscript.
1. The potential status of cancer-related cytokines or tissue microenvironments is different between squamous cell carcinoma and adenocarcinoma. I assume that the majority of those with EC could be the former and GEC the latter, but this should be clarified if possible.
2. Myosteatosis could be caused by various factors. The authors may have to correlate its extent with the BMI of the patients and to explore the possible differences among different skeletal muscles, such as the lower or upper thigh, if the data are available.
3. Discussion is mostly descriptive. More mechanistic insights, such as the potential factors inducing the adipocytes in the muscle based on reported in vitro studies, should be incorporated.
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Clear but improvements can be made. References, tables, and figures meet the standards for publication.
Appropriate for a meta-analysis.
Findings appear to be valid but improvements can be made. Please see additional comments for authors below.
This meta-analysis aimed to determine the prognostic value of myosteatosis among patients with esophageal and gastro-esophageal cancer. The manuscript is well-written. However, several limitations need to be addressed to improve clarity. My comments are as follows:
1. Abstract: It is stated that myosteatosis based on intramuscular adipose tissue content rather than muscle attenuation had a stronger effect on overall survival. However, muscle attenuation in HUs, which is a measure of muscle density, is a proxy measure of fat infiltration in the muscle (PMID: 27837297; PMID: 35732268). Please revise to enhance clarity.
2. Introduction (lines 61-64): The differences between muscle attenuation, intramuscular vs. intermuscular fat need to be explained accurately.
3. The rationale of the study needs to be strengthened. Was this meta-analysis conducted solely due to the mixed evidence on this topic? Why is myosteatosis important to study in the selected population?
4. Methods/results/discussion: It is apparent that the studies by Ichinohe 2023, Ito 2023, and Kitajima 2023 have the largest effect size. However, the method used to assess myosteatosis in these 3 studies is not validated or in line with most studies in the literature. The authors must be cautious when interpreting the findings of these studies and their impact on the overall effect on OS. This is very important.
5. It is stated that a sensitivity analysis was performed by removing one dataset at a time, and the results remain stable. What do you mean by that and what is the rationale for this sensitivity analysis? Where did you report the results?
6. The sensitivity analysis for men >80% needs to be better justified. It would be more meaningful to run a sensitivity analysis by sex.
7. Why did you select 64 and not 65 years as the cutoff for a sensitivity analysis? Please revise to 65 years, which characterizes older adults with cancer, and update your analysis.
8. Discussion (lines 263-268): Is cachexia common among patients with EC and GEC? Add prevalence and relevance for this population.
9. Lines 307-311: Given the heterogeneity in the assessment of myosteatosis, it would be useful to discuss how myosteatosis should be assessed for risk stratification in this population. Discuss different methods and potential strengths and limitations - this also relates to comment #4.
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