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: 3 Date: 09 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Lack of Molecular and Genetic Markers
Due to incomplete data, the manuscript acknowledges the absence of molecular markers such
as MSI and BRAF mutations. Given the well-known prognostic impact of these markers—
especially in right-sided colon cancer—the lack of their inclusion weakens the biological depth
and modern relevance of the model.Address this limitation more thoroughly in the discussion,
and if feasible, provide a brief subgroup analysis (e.g., even partial MSI data) or explain the
proportion of patients missing these markers.
2. Potential Confounding Variables Not Fully Accounted For
While NLR and PNI are important markers, their values can be influenced by acute
inflammation, infection, chronic diseases, and medications (e.g., corticosteroids), which are not
controlled for or excluded. Mention this as a limitation, and ideally include exclusion criteria or
sensitivity analyses if any patients with inflammatory comorbidities were removed.
3. Cutoff Determination for NLR and PNI
The cutoff values were selected using X-tile software but may be overfitted to the training cohort.
These values may not generalize to other populations.Consider comparing your cutoffs with
those reported in the literature and discuss discrepancies. It would also strengthen the paper if
you validated performance across different clinically used thresholds.
4. Calibration and DCA Presentation
The text describes calibration and decision curve analysis (DCA), but details on calibration
intercept/slope or net benefit values are not presented.Provide quantitative results from
calibration (e.g., slope, intercept, Brier score) and DCA (net benefit at clinically relevant
thresholds) in the text or supplementary material.
5. Web Calculator Utility Not Evaluated
While the manuscript introduces web-based nomograms, it does not assess their usability,
clinician acceptance, or potential clinical impact.
Include a brief discussion on plans for implementation or a user testing strategy in future
research.
6. Discussion Is Heavy on Literature Recap
The discussion reiterates findings from previous studies at length, sometimes at the expense of
critically analyzing the current study’s novelty or limitations. Focus more on how your study
adds new value (e.g., specific to right-sided colon adenocarcinoma, external validation, or web
tools) and streamline redundant references.
7. Lack of Comparison With Other Models
The manuscript does not benchmark its models against existing nomograms or prognostic tools
for right-sided colon cancer or non-metastatic CRC. A comparative analysis, even narrative, with
other published models (if any) would enhance the perceived contribution of your nomogram.
8. Short Follow-Up Period
The inclusion criterion of “follow-up longer than 1 month” is not robust, especially for survival
analysis.Report median follow-up time and consider excluding extremely short follow-up
durations unless justified (e.g., perioperative deaths).
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: 3 Date: 09 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Lack of Molecular and Genetic Markers
Due to incomplete data, the manuscript acknowledges the absence of molecular markers such
as MSI and BRAF mutations. Given the well-known prognostic impact of these markers—
especially in right-sided colon cancer—the lack of their inclusion weakens the biological depth
and modern relevance of the model.Address this limitation more thoroughly in the discussion,
and if feasible, provide a brief subgroup analysis (e.g., even partial MSI data) or explain the
proportion of patients missing these markers.
2. Potential Confounding Variables Not Fully Accounted For
While NLR and PNI are important markers, their values can be influenced by acute
inflammation, infection, chronic diseases, and medications (e.g., corticosteroids), which are not
controlled for or excluded. Mention this as a limitation, and ideally include exclusion criteria or
sensitivity analyses if any patients with inflammatory comorbidities were removed.
3. Cutoff Determination for NLR and PNI
The cutoff values were selected using X-tile software but may be overfitted to the training cohort.
These values may not generalize to other populations.Consider comparing your cutoffs with
those reported in the literature and discuss discrepancies. It would also strengthen the paper if
you validated performance across different clinically used thresholds.
4. Calibration and DCA Presentation
The text describes calibration and decision curve analysis (DCA), but details on calibration
intercept/slope or net benefit values are not presented.Provide quantitative results from
calibration (e.g., slope, intercept, Brier score) and DCA (net benefit at clinically relevant
thresholds) in the text or supplementary material.
5. Web Calculator Utility Not Evaluated
While the manuscript introduces web-based nomograms, it does not assess their usability,
clinician acceptance, or potential clinical impact.
Include a brief discussion on plans for implementation or a user testing strategy in future
research.
6. Discussion Is Heavy on Literature Recap
The discussion reiterates findings from previous studies at length, sometimes at the expense of
critically analyzing the current study’s novelty or limitations. Focus more on how your study
adds new value (e.g., specific to right-sided colon adenocarcinoma, external validation, or web
tools) and streamline redundant references.
7. Lack of Comparison With Other Models
The manuscript does not benchmark its models against existing nomograms or prognostic tools
for right-sided colon cancer or non-metastatic CRC. A comparative analysis, even narrative, with
other published models (if any) would enhance the perceived contribution of your nomogram.
8. Short Follow-Up Period
The inclusion criterion of “follow-up longer than 1 month” is not robust, especially for survival
analysis.Report median follow-up time and consider excluding extremely short follow-up
durations unless justified (e.g., perioperative deaths).
Please review this paper.
user
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: 3 Date: 09 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Lack of Molecular and Genetic Markers
Due to incomplete data, the manuscript acknowledges the absence of molecular markers such
as MSI and BRAF mutations. Given the well-known prognostic impact of these markers—
especially in right-sided colon cancer—the lack of their inclusion weakens the biological depth
and modern relevance of the model.Address this limitation more thoroughly in the discussion,
and if feasible, provide a brief subgroup analysis (e.g., even partial MSI data) or explain the
proportion of patients missing these markers.
2. Potential Confounding Variables Not Fully Accounted For
While NLR and PNI are important markers, their values can be influenced by acute
inflammation, infection, chronic diseases, and medications (e.g., corticosteroids), which are not
controlled for or excluded. Mention this as a limitation, and ideally include exclusion criteria or
sensitivity analyses if any patients with inflammatory comorbidities were removed.
3. Cutoff Determination for NLR and PNI
The cutoff values were selected using X-tile software but may be overfitted to the training cohort.
These values may not generalize to other populations.Consider comparing your cutoffs with
those reported in the literature and discuss discrepancies. It would also strengthen the paper if
you validated performance across different clinically used thresholds.
4. Calibration and DCA Presentation
The text describes calibration and decision curve analysis (DCA), but details on calibration
intercept/slope or net benefit values are not presented.Provide quantitative results from
calibration (e.g., slope, intercept, Brier score) and DCA (net benefit at clinically relevant
thresholds) in the text or supplementary material.
5. Web Calculator Utility Not Evaluated
While the manuscript introduces web-based nomograms, it does not assess their usability,
clinician acceptance, or potential clinical impact.
Include a brief discussion on plans for implementation or a user testing strategy in future
research.
6. Discussion Is Heavy on Literature Recap
The discussion reiterates findings from previous studies at length, sometimes at the expense of
critically analyzing the current study’s novelty or limitations. Focus more on how your study
adds new value (e.g., specific to right-sided colon adenocarcinoma, external validation, or web
tools) and streamline redundant references.
7. Lack of Comparison With Other Models
The manuscript does not benchmark its models against existing nomograms or prognostic tools
for right-sided colon cancer or non-metastatic CRC. A comparative analysis, even narrative, with
other published models (if any) would enhance the perceived contribution of your nomogram.
8. Short Follow-Up Period
The inclusion criterion of “follow-up longer than 1 month” is not robust, especially for survival
analysis.Report median follow-up time and consider excluding extremely short follow-up
durations unless justified (e.g., perioperative deaths).
assistant