Reviewer’ s report
Title: Using the preoperative prognostic nutritional index as a predictive factor for non-cancer-
related death in post-curative resection gastric cancer patients: A retrospective cohort study
Version: 0Date: 05 May 2020
Reviewer: Research Square Reviewer 1
Reviewer's report:
PEER REVIEWER ASSESSMENTS:OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Maybe - with major revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
This paper finds that the prognostic nutritional index is associated with survival outcomes. Aliterature search finds that this replicates many analyses. A major concern with the authors'analyses is that they do not perform any explicit analyses examining "non-cancer related deaths"as mentioned in the title. Best practice would be to perform analyses specific to the statedhypotheses, via a competing risk regression or other appropriate method, to support the assertionmade in the article's title. Also, the authors' cutpoint of 45 for the prognostic nutritional index is
not supported by a citation and is not consistent with cutpoints reported in the literature. Finally,
the authors propose using the prognostic nutritional index to predict outcomes but do not provide a
best practice nomogram style point system that clinicians and patients could use to map theircondition to the probability of death. The authors did register the study on a public website, whichis great.
REQUESTED REVISIONS:
A major limitation is that the authors discuss competing risks survival analyses in the title("predictive factor for non-cancer-related death…") but do not perform a competing risk analysis.It would seem that a competing risk survival analysis with non-cancer death as an outcome would
answer the hypothesis of interest. A method that accounts for competing risks, such as a Fine and
Gray competing risk regression, landmark analysis, or some other appropriate method would seemreasonable. Currently, there do not seem to be any explicit analyses that justify the article's title.Note that others in this field have appropriately used competing risk regressions (example:Pravisani, R, Mocchegiani, F, Isola, M, et al. Controlling Nutritional Status score does not predictpatients' overall survival or hepatocellular carcinoma recurrence after deceased donor livertransplantation. Clin Transplant. 2020; 34:e13786. https://doi.org/10.1111/ctr.13786).With a competing risk regression, the authors can separately identify effects associated with non-cancer mortality and cancer mortality.
Standard statistical analyses for prognostic modeling that justify the authors' conclusions such as
concordance indices and calibration plots seem to be missing. These statistics are readily estimablefor survival methods that account for competing risks.
Line 100: A citation would seem necessary for the following statement: "Generally, the resection
and anastomosis of gastrointestinal tracts can be performed safely on patients with a PNI score ofover 45, but these procedures may be dangerous for patients with a PNI score between 40 and 45.Additionally, these procedures may be contraindicated for patients with a PNI score of less than
40."
The authors' cutpoint is different from other cutpoints found in the literature. Xiao, H., Zhou, H.,
Zhang, P. et al. Association among the prognostic nutritional index, completion of adjuvantchemotherapy, and cancer-specific survival after curative resection of stage II/III gastric cancer.Eur J Clin Nutr 74, 555-564 (2020). https://doi.org/10.1038/s41430-019-0502-1 found a cutpointof 43.8. Migita K, Takayama T, Saeki K, et al. The prognostic nutritional index predicts long-termoutcomes of gastric cancer patients independent of tumor stage. Ann Surg Oncol.2013;20(8):2647‐2654. doi:10.1245/s10434-013-2926-5 found a cutpoint of 48.
A nomogram style point system that maps the salient prognostic variables to mortality outcomes
seems to be missing. The figures show that the prognostic nutritional index is not anoverwhelming predictor, so placing the relative importance of the index into a point system wouldseem prudent and standard. Examples of nomogram work of others in the field: Cui J, Chen S, BoQ, Wang S, Zhang N, Yu M, Wang W, Han J, Zhu Y, Shi B. Preoperative prognostic nutritionalindex and nomogram predicting recurrence-free survival in patients with primary non-muscle-invasive bladder cancer without carcinoma in situ. Onco Targets Ther. 2017;10:5541-5550
https://doi.org/10.2147/OTT.S146990. Go SI, Park S, Kang MH, Kim HG, Kim HR, Lee GW.
Clinical impact of prognostic nutritional index in diffuse large B cell lymphoma. Ann Hematol.2019;98(2):401‐411. doi:10.1007/s00277-018-3540-1
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
NoAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer has
agreed to publication of their comments online under a Creative Commons Attribution License
attributed to Research Square and was paid a small honorarium for completing the review within aspecified timeframe. Honoraria for reviews such as this are paid regardless of the reviewerrecommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.
Reviewer’ s report
Title: Using the preoperative prognostic nutritional index as a predictive factor for non-cancer-
related death in post-curative resection gastric cancer patients: A retrospective cohort study
Version: 0Date: 05 May 2020
Reviewer: Research Square Reviewer 1
Reviewer's report:
PEER REVIEWER ASSESSMENTS:OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Maybe - with major revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
This paper finds that the prognostic nutritional index is associated with survival outcomes. Aliterature search finds that this replicates many analyses. A major concern with the authors'analyses is that they do not perform any explicit analyses examining "non-cancer related deaths"as mentioned in the title. Best practice would be to perform analyses specific to the statedhypotheses, via a competing risk regression or other appropriate method, to support the assertionmade in the article's title. Also, the authors' cutpoint of 45 for the prognostic nutritional index is
not supported by a citation and is not consistent with cutpoints reported in the literature. Finally,
the authors propose using the prognostic nutritional index to predict outcomes but do not provide a
best practice nomogram style point system that clinicians and patients could use to map theircondition to the probability of death. The authors did register the study on a public website, whichis great.
REQUESTED REVISIONS:
A major limitation is that the authors discuss competing risks survival analyses in the title("predictive factor for non-cancer-related death…") but do not perform a competing risk analysis.It would seem that a competing risk survival analysis with non-cancer death as an outcome would
answer the hypothesis of interest. A method that accounts for competing risks, such as a Fine and
Gray competing risk regression, landmark analysis, or some other appropriate method would seemreasonable. Currently, there do not seem to be any explicit analyses that justify the article's title.Note that others in this field have appropriately used competing risk regressions (example:Pravisani, R, Mocchegiani, F, Isola, M, et al. Controlling Nutritional Status score does not predictpatients' overall survival or hepatocellular carcinoma recurrence after deceased donor livertransplantation. Clin Transplant. 2020; 34:e13786. https://doi.org/10.1111/ctr.13786).With a competing risk regression, the authors can separately identify effects associated with non-cancer mortality and cancer mortality.
Standard statistical analyses for prognostic modeling that justify the authors' conclusions such as
concordance indices and calibration plots seem to be missing. These statistics are readily estimablefor survival methods that account for competing risks.
Line 100: A citation would seem necessary for the following statement: "Generally, the resection
and anastomosis of gastrointestinal tracts can be performed safely on patients with a PNI score ofover 45, but these procedures may be dangerous for patients with a PNI score between 40 and 45.Additionally, these procedures may be contraindicated for patients with a PNI score of less than
40."
The authors' cutpoint is different from other cutpoints found in the literature. Xiao, H., Zhou, H.,
Zhang, P. et al. Association among the prognostic nutritional index, completion of adjuvantchemotherapy, and cancer-specific survival after curative resection of stage II/III gastric cancer.Eur J Clin Nutr 74, 555-564 (2020). https://doi.org/10.1038/s41430-019-0502-1 found a cutpointof 43.8. Migita K, Takayama T, Saeki K, et al. The prognostic nutritional index predicts long-termoutcomes of gastric cancer patients independent of tumor stage. Ann Surg Oncol.2013;20(8):2647‐2654. doi:10.1245/s10434-013-2926-5 found a cutpoint of 48.
A nomogram style point system that maps the salient prognostic variables to mortality outcomes
seems to be missing. The figures show that the prognostic nutritional index is not anoverwhelming predictor, so placing the relative importance of the index into a point system wouldseem prudent and standard. Examples of nomogram work of others in the field: Cui J, Chen S, BoQ, Wang S, Zhang N, Yu M, Wang W, Han J, Zhu Y, Shi B. Preoperative prognostic nutritionalindex and nomogram predicting recurrence-free survival in patients with primary non-muscle-invasive bladder cancer without carcinoma in situ. Onco Targets Ther. 2017;10:5541-5550
https://doi.org/10.2147/OTT.S146990. Go SI, Park S, Kang MH, Kim HG, Kim HR, Lee GW.
Clinical impact of prognostic nutritional index in diffuse large B cell lymphoma. Ann Hematol.2019;98(2):401‐411. doi:10.1007/s00277-018-3540-1
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
NoAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer has
agreed to publication of their comments online under a Creative Commons Attribution License
attributed to Research Square and was paid a small honorarium for completing the review within aspecified timeframe. Honoraria for reviews such as this are paid regardless of the reviewerrecommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.
Please review this paper.
user
Reviewer’ s report
Title: Using the preoperative prognostic nutritional index as a predictive factor for non-cancer-
related death in post-curative resection gastric cancer patients: A retrospective cohort study
Version: 0Date: 05 May 2020
Reviewer: Research Square Reviewer 1
Reviewer's report:
PEER REVIEWER ASSESSMENTS:OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Maybe - with major revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
This paper finds that the prognostic nutritional index is associated with survival outcomes. Aliterature search finds that this replicates many analyses. A major concern with the authors'analyses is that they do not perform any explicit analyses examining "non-cancer related deaths"as mentioned in the title. Best practice would be to perform analyses specific to the statedhypotheses, via a competing risk regression or other appropriate method, to support the assertionmade in the article's title. Also, the authors' cutpoint of 45 for the prognostic nutritional index is
not supported by a citation and is not consistent with cutpoints reported in the literature. Finally,
the authors propose using the prognostic nutritional index to predict outcomes but do not provide a
best practice nomogram style point system that clinicians and patients could use to map theircondition to the probability of death. The authors did register the study on a public website, whichis great.
REQUESTED REVISIONS:
A major limitation is that the authors discuss competing risks survival analyses in the title("predictive factor for non-cancer-related death…") but do not perform a competing risk analysis.It would seem that a competing risk survival analysis with non-cancer death as an outcome would
answer the hypothesis of interest. A method that accounts for competing risks, such as a Fine and
Gray competing risk regression, landmark analysis, or some other appropriate method would seemreasonable. Currently, there do not seem to be any explicit analyses that justify the article's title.Note that others in this field have appropriately used competing risk regressions (example:Pravisani, R, Mocchegiani, F, Isola, M, et al. Controlling Nutritional Status score does not predictpatients' overall survival or hepatocellular carcinoma recurrence after deceased donor livertransplantation. Clin Transplant. 2020; 34:e13786. https://doi.org/10.1111/ctr.13786).With a competing risk regression, the authors can separately identify effects associated with non-cancer mortality and cancer mortality.
Standard statistical analyses for prognostic modeling that justify the authors' conclusions such as
concordance indices and calibration plots seem to be missing. These statistics are readily estimablefor survival methods that account for competing risks.
Line 100: A citation would seem necessary for the following statement: "Generally, the resection
and anastomosis of gastrointestinal tracts can be performed safely on patients with a PNI score ofover 45, but these procedures may be dangerous for patients with a PNI score between 40 and 45.Additionally, these procedures may be contraindicated for patients with a PNI score of less than
40."
The authors' cutpoint is different from other cutpoints found in the literature. Xiao, H., Zhou, H.,
Zhang, P. et al. Association among the prognostic nutritional index, completion of adjuvantchemotherapy, and cancer-specific survival after curative resection of stage II/III gastric cancer.Eur J Clin Nutr 74, 555-564 (2020). https://doi.org/10.1038/s41430-019-0502-1 found a cutpointof 43.8. Migita K, Takayama T, Saeki K, et al. The prognostic nutritional index predicts long-termoutcomes of gastric cancer patients independent of tumor stage. Ann Surg Oncol.2013;20(8):2647‐2654. doi:10.1245/s10434-013-2926-5 found a cutpoint of 48.
A nomogram style point system that maps the salient prognostic variables to mortality outcomes
seems to be missing. The figures show that the prognostic nutritional index is not anoverwhelming predictor, so placing the relative importance of the index into a point system wouldseem prudent and standard. Examples of nomogram work of others in the field: Cui J, Chen S, BoQ, Wang S, Zhang N, Yu M, Wang W, Han J, Zhu Y, Shi B. Preoperative prognostic nutritionalindex and nomogram predicting recurrence-free survival in patients with primary non-muscle-invasive bladder cancer without carcinoma in situ. Onco Targets Ther. 2017;10:5541-5550
https://doi.org/10.2147/OTT.S146990. Go SI, Park S, Kang MH, Kim HG, Kim HR, Lee GW.
Clinical impact of prognostic nutritional index in diffuse large B cell lymphoma. Ann Hematol.2019;98(2):401‐411. doi:10.1007/s00277-018-3540-1
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
NoAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer has
agreed to publication of their comments online under a Creative Commons Attribution License
attributed to Research Square and was paid a small honorarium for completing the review within aspecified timeframe. Honoraria for reviews such as this are paid regardless of the reviewerrecommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.
assistant