Review for 10.1186/s12876-025-03883-2 (2025)

Title: Dynamic Variations in Peripheral Blood Indices and Their Association with Efficacy
and Adverse Reactions of PD-1 Inhibitor Combined Chemotherapy in Patients with Advanced
Gastric Cancer
Version: 4 Date: 25 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study design is described as retrospective, which is appropriate for evaluating real-
world data, there could be a brief discussion about the potential limitations of retrospective
studies, such as selection bias and the lack of randomization. Addressing these limitations
upfront could enhance the transparency and validity of the findings.
-The inclusion criteria mention a performance status score of 0–1 and a minimum of four cycles
of immunotherapy, but it would be useful to briefly clarify how this threshold was determined
and whether patients who had previously received other treatments were included.
-Exclusion criteria like autoimmune diseases and corticosteroid use are well-justified, but
including further detail on the rationale for excluding these conditions could help readers
understand their potential impact on treatment response.
-The introduction lists several biomarkers (e.g., PD-L1 CPS, AFP, CA199, CEA), but it would
be helpful to elaborate more on how these biomarkers are expected to correlate with treatment
efficacy. For instance, explaining how PD-L1 expression or AFP levels might influence immune
response or treatment outcomes would provide a clearer rationale for their inclusion in the study.
-Additionally, the cutoffs for defining clinical significance for tumor markers like CEA and
CA199 (e.g., 0–5 ng/ml for CEA) are mentioned. It would be helpful to provide references or
justify why these specific thresholds were used for binary categorization.
-Although the study will assess both baseline and 12-week post-treatment levels of biomarkers,
the timing of post-treatment assessment could be more clearly explained. Why is 12 weeks
chosen? Is it based on previous studies showing significant changes in biomarkers around this
time, or is it simply a standard practice in your institution? Clarifying this would strengthen the
rationale for using this specific time point.
-While the discussion does a good job explaining the prognostic value of specific markers,
it would benefit from a more explicit explanation of how these findings can be implemented
in clinical practice. For example, how might these markers inform treatment decisions on an
individual level? Could the reductions in markers like NLR or CAR serve as early indicators of
treatment efficacy or the need for therapy adjustments?
-The mention of immune-related adverse events (irAEs) as a potential predictor of treatment
outcomes is intriguing, but the manuscript could further explore this relationship. Specifically,
the small sample size and lack of statistical significance in this study make it difficult to draw
firm conclusions regarding the impact of irAEs on PFS and OS. It would be helpful to mention
how future studies could investigate this relationship further, perhaps through a larger cohort
or multi-center design. Additionally, a brief discussion on the potential mechanisms behind
irAEs in the context of immune checkpoint inhibitors (ICIs) would be valuable, as it might help
contextualize why patients with irAEs could experience better outcomes.
-The manuscript touches on the relationship between AFP and a specific gastric cancer subtype
(AFP-producing gastric cancer, or AFPGC), but this is not deeply explored. Given that AFPGC
is a distinct subtype with a poorer prognosis, a more detailed exploration of the potential
biological mechanisms driving this form of GC would strengthen the discussion.
-Additionally, it would be interesting to discuss whether the prognostic markers evaluated in
this study are consistent across different GC subtypes or whether they might vary based on
histological differences.