Review for 10.1186/s12876-025-04207-0 (2025)

Title: Efficacy and safety of programmed death-1 inhibitors combined with chemotherapy in
patients with advanced gastric cancer
Version: 1 Date: 10 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
Major Concerns
-Study Design & Controls
Lack of Control Group: As a retrospective, single#arm study, there is no concurrent
chemotherapy-only or placebo cohort for direct comparison. This limits your ability to attribute
observed efficacy/safety specifically to the addition of PD-1 inhibitors.
Selection Bias: The inclusion criteria (e.g. patients unwilling or unable to undergo surgery,
elderly) suggest a highly heterogeneous, possibly non-representative population. More detail
is needed on how patients were selected and whether any consecutive or propensity-matching
methods were used.
-Sample Size & Power
With only 45 patients (and 23 lost to follow-up), the study is likely underpowered for meaningful
survival analysis or subgroup comparisons. This needs acknowledgment in the limitations and
—ideally—some formal power calculation or at least a statement on minimum detectable effect
size.
-Outcome Definitions & Assessment
iRECIST Application: It is not clear whether “immune” RECIST was strictly applied (e.g.
confirmation of progression). Please specify how pseudoprogression was handled.
Timing & Frequency of Imaging: While you state “every 2 months,” report the actual median
number of scans per patient and any deviations from the schedule.
-Statistical Analysis
Missing Statistical Detail: You present the PFS median but do not report confidence intervals.
No hazard ratios, and no multivariate analyses adjusting for key covariates (e.g. ECOG PS,
histology, number/site of metastases).
Handling of Censored Data: Given high loss to follow-up (51%), describe how censoring was
handled, and consider a sensitivity analysis (e.g. best-/worst-case scenarios).
-Interpretation of Efficacy Results
Your ORR (22.2%) is markedly lower than prior studies, yet you ascribe this solely to older age
and metastases. Other factors (e.g. prior lines of therapy, PD-L1 status, MSI status) may also
explain differences—yet these biomarkers are neither collected nor discussed.
The notably longer median PFS (14.6 m) despite low ORR is counterintuitive. Were any
patients continuing treatment beyond RECIST progression? Clarify whether treatment beyond
progression or maintenance strategies might have influenced this.
-Safety Reporting
You list hematologic AEs but omit any immune-related toxicities (e.g. dermatitis, colitis,
hepatitis)—even though PD-1 inhibitors can provoke them. Were these systematically captured?
If none occurred, state that explicitly.
-Minor Points & Clarifications
-Demographics Table: Provide a baseline characteristics table, including prior lines of therapy,
PD-L1 expression, MSI status, tumor burden, and sites of metastasis.
-Terminology Consistency: You alternate between “PD-1 inhibitors + chemotherapy” and
naming individual agents. Suggest consistent terminology and a breakdown of how many
patients received each PD-1 agent/regimen.
-Ethics Statement Redundancy: The phrase “approved by the Ethics Committee…under the
Ethics approval” is repetitive. Streamline to: “This retrospective study was approved by the
Institutional Review Board of Anqing 116 Hospital (Approval no. XXX).”
-COVID#19 Impact: Quantify how many missed follow-ups were due to the pandemic versus
financial issues. This will help gauge bias.
-Grammar/Typos:
“host’s immune system to kill tumor cells” # “host immune system to eliminate tumor cells”
“elevated progression-free survival” # “improved PFS”
“These four patients might have extreme values” # more precise wording (e.g. “...may represent
outliers due to small subgroup size.”)