Review for 10.1186/s12876-024-03508-0 (2024)

Title: Efficacy and Safety of Nivolumab in Advanced Gastric and Gastroesophageal Junction
Cancer: A Meta-Analysis of Randomized Controlled Trials
Version: 1 Date: 25 Aug 2024
Reviewer:  Kazuo Kobayashi
Reviewer's report:
Based on the review of the manuscript titled "Efficacy and Safety of Nivolumab in Advanced
Gastric and Gastroesophageal Junction Cancer: A Meta-Analysis of Randomized Controlled
Trials," here are some suggestions and considerations for the authors:
Strengths:
Comprehensive Meta-Analysis: The manuscript presents a thorough meta-analysis on the
efficacy and safety of Nivolumab in treating advanced gastric and gastroesophageal junction
cancer. The inclusion of nine randomized controlled trials (RCTs) with a large sample size
provides robust evidence supporting the findings.
Structured and Clear Presentation: The manuscript is well-organized, with clear sections
detailing the methodology, results, and discussion. The use of PRISMA guidelines enhances the
transparency and reproducibility of the systematic review process.
Areas for Improvement:
Introduction:
Contextualize the Importance: While the introduction provides an overview of the current
state of treatment for gastric cancer, it could benefit from a more detailed explanation of why
Nivolumab specifically represents a significant advancement over other treatment modalities.
Additionally, the potential for Nivolumab to overcome limitations in existing treatments should
be emphasized more strongly.
Hypothesis Statement: The introduction would be strengthened by a clear hypothesis or research
question that guides the meta-analysis. This could be articulated towards the end of the
introduction to frame the subsequent analysis.
Methods:
Search Strategy Details: The search strategy is adequately detailed, but the inclusion criteria
could be expanded to justify why certain studies were excluded. For example, the rationale
behind excluding studies with comorbid conditions or those using other treatments should be
clearly stated.
Risk of Bias Assessment: The risk of bias assessment is comprehensive, but it would be helpful
to include a more detailed explanation of how "some concerns" were determined for certain
studies. Providing examples or specific study characteristics that led to this designation would
enhance transparency.
Results:
Subgroup Analysis: The results section does a good job of presenting subgroup analyses.
However, it would benefit from a more in-depth interpretation of why certain subgroups
(e.g., those receiving Nivolumab monotherapy versus combination therapy) showed different
outcomes. This discussion could be expanded to explore potential biological or clinical reasons
behind these differences.
Heterogeneity Discussion: The manuscript mentions high heterogeneity in OS and PFS. While
sensitivity analyses were performed, a more thorough discussion of potential sources of
heterogeneity (e.g., variations in patient populations, treatment protocols, or study designs)
would be beneficial.
Discussion:
Clinical Implications: The discussion provides a solid interpretation of the results but could
be enhanced by offering more specific clinical recommendations. For example, under what
conditions should Nivolumab be preferred as monotherapy versus in combination with
chemotherapy? How should clinicians balance the increased risk of adverse events against the
survival benefits observed?
Limitations: The manuscript appropriately acknowledges its limitations, such as short follow-
up periods and potential publication bias. However, the discussion would benefit from a more
forward-looking perspective, suggesting how future studies might address these limitations,
particularly in the context of long-term safety and efficacy data.
Conclusion:
The manuscript provides a valuable contribution to the understanding of Nivolumab’s role in
treating advanced gastric and gastroesophageal junction cancer. The authors should consider
addressing the points above to further strengthen the manuscript, particularly in enhancing the
clarity of the discussion and ensuring that all methodological details are transparent. If these
revisions are addressed, the manuscript will be well-positioned for acceptance.