Review for 10.1186/s12876-025-04107-3 (2025)

Title: Development and Validation of Predictive Models for Disease-free Survival and
Overall Survival in Non-metastatic Right-Sided Colon Adenocarcinoma Patients Based on
Inflammatory and Nutritional Indices
Version: 2 Date: 29 Apr 2025
Reviewer:  Akif Do#an
Reviewer's report:
Manuscript Title:
Development and Validation of Predictive Models for Disease-free Survival and Overall
Survival in Non-metastatic Right-Sided Colon Adenocarcinoma Patients Based on
Inflammatory and Nutritional Indices
Overall Evaluation:
The manuscript addresses an important and clinically relevant topic, aiming to develop and
validate predictive nomograms incorporating inflammatory (NLR) and nutritional (PNI) indices
for non-metastatic right-sided colon adenocarcinoma (NRCA) patients.
The study design is appropriate, with robust methodology, including training, internal, and
external validation cohorts. The results are generally convincing, and the statistical analyses are
comprehensive and well-executed.
However, there are substantial concerns regarding the structure and focus of the Discussion
section, which currently limits the impact and clarity of the manuscript. A major revision is
necessary to improve the alignment between results and interpretation.
Major Comments:
1. 1. Discussion Focus:
The Discussion section deviates from the primary aim of the study. Instead of emphasizing the
prognostic significance of NLR and PNI — the main focus of the study — too much space is
devoted to discussing traditional prognostic factors such as CEA levels, T stage, N stage, tumor
size, and patient age. This dilutes the originality and contribution of the study.
Revision Required:
- Summarize traditional prognostic factors (CEA, T stage, N stage, tumor size, age) briefly in
a single paragraph.
- Develop a more detailed and focused discussion on the prognostic value of NLR and PNI,
including their clinical significance, cut-off values, comparison with previous literature, and
their potential integration into clinical decision-making tools.
2. 2. Clinical Applicability of NLR and PNI:
While nomograms were developed and validated, the manuscript lacks an in-depth discussion
on how NLR and PNI could be implemented in real-world clinical practice.
Revision Required:
- Elaborate on how clinicians could use NLR and PNI values for individualized risk stratification
and postoperative management.
- Discuss potential limitations (e.g., variability in NLR/PNI measurements, impact of concurrent
inflammatory conditions).
3. 3. Variable Selection Process:
The statistical analysis section does not clearly specify how variables were selected for
multivariate Cox regression modeling.
Revision Required:
- Explicitly state whether a stepwise, backward, forward selection method was used, or whether
all significant univariate variables were included based on clinical judgment.
4. 4. Literature Context for NLR and PNI:
The Introduction could benefit from a brief justification for the selection of NLR and PNI over
other inflammatory or nutritional markers (e.g., PLR, LMR, GPS).
Revision Suggested:
- Add a short rationale in the Introduction explaining why NLR and PNI were prioritized as
prognostic indicators.
Minor Comments:
- The web calculators are a strong feature. It would be helpful to briefly discuss their usability
and future updates.
- Minor grammatical or stylistic editing may further improve the manuscript’s fluency.