Reviewer’s report
Title: 
Nomogram to predict cause-specific mortality of patients with rectal
adenocarcinoma undergoing surgery: a competing risk analysis.
Version: 
0 
Date: 
19 Apr 2021
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?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
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 minor 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?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The authors present a thoughtful nomogram paper to predict survival outcomes
among those with rectal adenocarcinoma. The authors generally used standard of
care approaches to building nomograms, but the methods could be improved
with respect to the competing risk nature of the algorithm. The authors do not
use some methods that have been in common use with competing risk
nomograms for 10+ years. Some more comments follow.
REQUESTED REVISIONS: 
Major Comment 1) Something appears incorrect with Table 3. The coefficients
are much too large. For example, one of the coefficients for age is 186.948, but
the hazard ratio of 1.467 which is not equal to exp(186.948). 
Comment 2) The concordance indices used were not designed for competing risk
regressions but for Cox regressions. The methods of Ruan and Gray can be used
to calculate concordance statistics for the competing risk regression (Ruan PK,
Gray RJ. Analyses of cumulative incidence functions via non
‐
parametric
multiple imputation. Stat Med. 2008; 27: 5709
‐
5724.) Others have used the
method for competing risk nomograms.
Comment 3) Including race in a nomogram may be inadvisable, as the authors
could not control for characteristics that could confound the relationship of race
with outcomes, such as socio-economic status, access to insurance, and other
factors. Marital status is similarly fraught. While there might be scientific
reasons to investigate the impact of race and marital status on outcomes, the
authors have not necessarily motivated how the use of race and marital status via
the nomogram would improve clinical decision making without exacerbating
health disparities. The authors attribute the marital effect to "mental health and
well-being" without citations. Often the marital effect is seen as a proxy for
social support which affects the ability to travel to medical appointments and
hence seek appropriate care.
Comment 4) The chemotherapy effect may be due to those who do not receive
chemotherapy being poor candidates for chemotherapy (i.e. selection bias based
on health characteristics not available in SEER), rather than a true effect of
chemotherapy. 
Comment 5) Chemotherapy and radiation are not well collected by SEER, so
there is substantial misclassification. Comparing outcomes between those who
did and did not receive such therapy in SEER is generally not recommended.
The authors could cite the following web page so that others know the
limitations: https://seer.cancer.gov/data-
software/documentation/seerstat/nov2020/treatment-limitations-nov2020.html as
accessed on April 15, 2021.
Comment 6) The initial drop in sample size from 108,017 to 34,700 (Figure 1)
could be better documented in Figure 1. If this is due to many being diagnosed
prior to 2004, such a large decrease could be viewed as acceptable. However, if
the reason is due to missing data that is not well collected by SEER, missing data
could bias the results. 
Minor comment: Discussion: The authors state: "Recently, a parameter termed as
'cumulative incidence', calculated by the competing-risk model, has been
recommended to conquer the defects of traditional survival analysis [16-17]."
The authors describe their methods as novel, but actually competing risk
nomograms and cumulative incidence curves have been in common use for over
20 years. Michael W. Kattan published many competing risk nomograms in high
impact journals in the early 2000s, and is widely considered the modern founder
for the method. Perhaps his work should be cited.
Minor comment: The term multivariate might be more appropriately termed
multivariable. The authors did not use true multivariate methods (e.g., principal
component analysis).
ADDITIONAL REQUESTS/SUGGESTIONS: 
No further concerns beyond those already stated.
Publons Reviewer Recognition
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review directly to Publons (a subsidiary of Clarivate Analytics). If you would
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No
Declaration 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 this manuscript, 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 a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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 manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. 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 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Nomogram to predict cause-specific mortality of patients with rectal
adenocarcinoma undergoing surgery: a competing risk analysis.
Version: 
0 
Date: 
19 Apr 2021
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?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
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 minor 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?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The authors present a thoughtful nomogram paper to predict survival outcomes
among those with rectal adenocarcinoma. The authors generally used standard of
care approaches to building nomograms, but the methods could be improved
with respect to the competing risk nature of the algorithm. The authors do not
use some methods that have been in common use with competing risk
nomograms for 10+ years. Some more comments follow.
REQUESTED REVISIONS: 
Major Comment 1) Something appears incorrect with Table 3. The coefficients
are much too large. For example, one of the coefficients for age is 186.948, but
the hazard ratio of 1.467 which is not equal to exp(186.948). 
Comment 2) The concordance indices used were not designed for competing risk
regressions but for Cox regressions. The methods of Ruan and Gray can be used
to calculate concordance statistics for the competing risk regression (Ruan PK,
Gray RJ. Analyses of cumulative incidence functions via non
‐
parametric
multiple imputation. Stat Med. 2008; 27: 5709
‐
5724.) Others have used the
method for competing risk nomograms.
Comment 3) Including race in a nomogram may be inadvisable, as the authors
could not control for characteristics that could confound the relationship of race
with outcomes, such as socio-economic status, access to insurance, and other
factors. Marital status is similarly fraught. While there might be scientific
reasons to investigate the impact of race and marital status on outcomes, the
authors have not necessarily motivated how the use of race and marital status via
the nomogram would improve clinical decision making without exacerbating
health disparities. The authors attribute the marital effect to "mental health and
well-being" without citations. Often the marital effect is seen as a proxy for
social support which affects the ability to travel to medical appointments and
hence seek appropriate care.
Comment 4) The chemotherapy effect may be due to those who do not receive
chemotherapy being poor candidates for chemotherapy (i.e. selection bias based
on health characteristics not available in SEER), rather than a true effect of
chemotherapy. 
Comment 5) Chemotherapy and radiation are not well collected by SEER, so
there is substantial misclassification. Comparing outcomes between those who
did and did not receive such therapy in SEER is generally not recommended.
The authors could cite the following web page so that others know the
limitations: https://seer.cancer.gov/data-
software/documentation/seerstat/nov2020/treatment-limitations-nov2020.html as
accessed on April 15, 2021.
Comment 6) The initial drop in sample size from 108,017 to 34,700 (Figure 1)
could be better documented in Figure 1. If this is due to many being diagnosed
prior to 2004, such a large decrease could be viewed as acceptable. However, if
the reason is due to missing data that is not well collected by SEER, missing data
could bias the results. 
Minor comment: Discussion: The authors state: "Recently, a parameter termed as
'cumulative incidence', calculated by the competing-risk model, has been
recommended to conquer the defects of traditional survival analysis [16-17]."
The authors describe their methods as novel, but actually competing risk
nomograms and cumulative incidence curves have been in common use for over
20 years. Michael W. Kattan published many competing risk nomograms in high
impact journals in the early 2000s, and is widely considered the modern founder
for the method. Perhaps his work should be cited.
Minor comment: The term multivariate might be more appropriately termed
multivariable. The authors did not use true multivariate methods (e.g., principal
component analysis).
ADDITIONAL REQUESTS/SUGGESTIONS: 
No further concerns beyond those already stated.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration 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 this manuscript, 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 a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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 manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. 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 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Nomogram to predict cause-specific mortality of patients with rectal
adenocarcinoma undergoing surgery: a competing risk analysis.
Version: 
0 
Date: 
19 Apr 2021
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?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
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 minor 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?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The authors present a thoughtful nomogram paper to predict survival outcomes
among those with rectal adenocarcinoma. The authors generally used standard of
care approaches to building nomograms, but the methods could be improved
with respect to the competing risk nature of the algorithm. The authors do not
use some methods that have been in common use with competing risk
nomograms for 10+ years. Some more comments follow.
REQUESTED REVISIONS: 
Major Comment 1) Something appears incorrect with Table 3. The coefficients
are much too large. For example, one of the coefficients for age is 186.948, but
the hazard ratio of 1.467 which is not equal to exp(186.948). 
Comment 2) The concordance indices used were not designed for competing risk
regressions but for Cox regressions. The methods of Ruan and Gray can be used
to calculate concordance statistics for the competing risk regression (Ruan PK,
Gray RJ. Analyses of cumulative incidence functions via non
‐
parametric
multiple imputation. Stat Med. 2008; 27: 5709
‐
5724.) Others have used the
method for competing risk nomograms.
Comment 3) Including race in a nomogram may be inadvisable, as the authors
could not control for characteristics that could confound the relationship of race
with outcomes, such as socio-economic status, access to insurance, and other
factors. Marital status is similarly fraught. While there might be scientific
reasons to investigate the impact of race and marital status on outcomes, the
authors have not necessarily motivated how the use of race and marital status via
the nomogram would improve clinical decision making without exacerbating
health disparities. The authors attribute the marital effect to "mental health and
well-being" without citations. Often the marital effect is seen as a proxy for
social support which affects the ability to travel to medical appointments and
hence seek appropriate care.
Comment 4) The chemotherapy effect may be due to those who do not receive
chemotherapy being poor candidates for chemotherapy (i.e. selection bias based
on health characteristics not available in SEER), rather than a true effect of
chemotherapy. 
Comment 5) Chemotherapy and radiation are not well collected by SEER, so
there is substantial misclassification. Comparing outcomes between those who
did and did not receive such therapy in SEER is generally not recommended.
The authors could cite the following web page so that others know the
limitations: https://seer.cancer.gov/data-
software/documentation/seerstat/nov2020/treatment-limitations-nov2020.html as
accessed on April 15, 2021.
Comment 6) The initial drop in sample size from 108,017 to 34,700 (Figure 1)
could be better documented in Figure 1. If this is due to many being diagnosed
prior to 2004, such a large decrease could be viewed as acceptable. However, if
the reason is due to missing data that is not well collected by SEER, missing data
could bias the results. 
Minor comment: Discussion: The authors state: "Recently, a parameter termed as
'cumulative incidence', calculated by the competing-risk model, has been
recommended to conquer the defects of traditional survival analysis [16-17]."
The authors describe their methods as novel, but actually competing risk
nomograms and cumulative incidence curves have been in common use for over
20 years. Michael W. Kattan published many competing risk nomograms in high
impact journals in the early 2000s, and is widely considered the modern founder
for the method. Perhaps his work should be cited.
Minor comment: The term multivariate might be more appropriately termed
multivariable. The authors did not use true multivariate methods (e.g., principal
component analysis).
ADDITIONAL REQUESTS/SUGGESTIONS: 
No further concerns beyond those already stated.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration 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 this manuscript, 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 a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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 manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. 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 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant