Title: Development and validation of prognostic nomograms for early-onset colon cancer in
different tumor locations: a population-based study
Version: 2 Date: 24 Aug 2023
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?
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?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is an interesting paper regarding the development and
validation of prognostic nomograms for early-onset colon cancer. The authors use some best
practices, such as the use of Cox regressions, calibration plots, and Area under the Curve (AUC)
statistics. The exclusion of those who died from competing causes of death is problematic,
particularly when examining early onset disease (overall survival is biased). Also, SEER data
does not really support the use of radiation and chemotherapy for prognostic purposes due to
misclassification of chemotherapy in the dataset and inability to control for all confounders
related to chemotherapy selection bias.
REQUESTED REVISIONS:
Comment 1: The authors should justify the exclusion of “(3) patients who passed away as a result
of non-neoplastic disease.” For many early stage cancers, such exclusion would remove most
people from a study as the majority (with hope) would be functionally cured of the cancer and
hence die from other causes. Often, investigators examine overall survival and cause specific
survival separately.
Comment 2: SEER data for chemotherapy and radiation therapy are not complete. Hence,
the chemotherapy and radiation therapy effects are biased. Further, it is not really useful to
tell patients that they will die more quickly if they have radiation (as the nomogram does),
as it is likely not the radiation causing deaths. It is the association of radiation with worse
disease. SEER does not contain all possible confounders of treatment selection. This is covered
in the SEER data use agreement: https://seer.cancer.gov/data-software/documentation/seerstat/
nov2022/treatment-limitations-nov2022.html.
Comment 3: The “all” and “none” groups in the decision curve analyses could be better defined.
Minor comment 4: Multivariate would better be termed “multivariable” throughout. Multivariate
methods include principal components analyses, among others, which are different.
ADDITIONAL REQUESTS/SUGGESTIONS:
I have no further comments.
Title: Development and validation of prognostic nomograms for early-onset colon cancer in
different tumor locations: a population-based study
Version: 2 Date: 24 Aug 2023
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?
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?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is an interesting paper regarding the development and
validation of prognostic nomograms for early-onset colon cancer. The authors use some best
practices, such as the use of Cox regressions, calibration plots, and Area under the Curve (AUC)
statistics. The exclusion of those who died from competing causes of death is problematic,
particularly when examining early onset disease (overall survival is biased). Also, SEER data
does not really support the use of radiation and chemotherapy for prognostic purposes due to
misclassification of chemotherapy in the dataset and inability to control for all confounders
related to chemotherapy selection bias.
REQUESTED REVISIONS:
Comment 1: The authors should justify the exclusion of “(3) patients who passed away as a result
of non-neoplastic disease.” For many early stage cancers, such exclusion would remove most
people from a study as the majority (with hope) would be functionally cured of the cancer and
hence die from other causes. Often, investigators examine overall survival and cause specific
survival separately.
Comment 2: SEER data for chemotherapy and radiation therapy are not complete. Hence,
the chemotherapy and radiation therapy effects are biased. Further, it is not really useful to
tell patients that they will die more quickly if they have radiation (as the nomogram does),
as it is likely not the radiation causing deaths. It is the association of radiation with worse
disease. SEER does not contain all possible confounders of treatment selection. This is covered
in the SEER data use agreement: https://seer.cancer.gov/data-software/documentation/seerstat/
nov2022/treatment-limitations-nov2022.html.
Comment 3: The “all” and “none” groups in the decision curve analyses could be better defined.
Minor comment 4: Multivariate would better be termed “multivariable” throughout. Multivariate
methods include principal components analyses, among others, which are different.
ADDITIONAL REQUESTS/SUGGESTIONS:
I have no further comments.
Please review this paper.
user
Title: Development and validation of prognostic nomograms for early-onset colon cancer in
different tumor locations: a population-based study
Version: 2 Date: 24 Aug 2023
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?
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?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is an interesting paper regarding the development and
validation of prognostic nomograms for early-onset colon cancer. The authors use some best
practices, such as the use of Cox regressions, calibration plots, and Area under the Curve (AUC)
statistics. The exclusion of those who died from competing causes of death is problematic,
particularly when examining early onset disease (overall survival is biased). Also, SEER data
does not really support the use of radiation and chemotherapy for prognostic purposes due to
misclassification of chemotherapy in the dataset and inability to control for all confounders
related to chemotherapy selection bias.
REQUESTED REVISIONS:
Comment 1: The authors should justify the exclusion of “(3) patients who passed away as a result
of non-neoplastic disease.” For many early stage cancers, such exclusion would remove most
people from a study as the majority (with hope) would be functionally cured of the cancer and
hence die from other causes. Often, investigators examine overall survival and cause specific
survival separately.
Comment 2: SEER data for chemotherapy and radiation therapy are not complete. Hence,
the chemotherapy and radiation therapy effects are biased. Further, it is not really useful to
tell patients that they will die more quickly if they have radiation (as the nomogram does),
as it is likely not the radiation causing deaths. It is the association of radiation with worse
disease. SEER does not contain all possible confounders of treatment selection. This is covered
in the SEER data use agreement: https://seer.cancer.gov/data-software/documentation/seerstat/
nov2022/treatment-limitations-nov2022.html.
Comment 3: The “all” and “none” groups in the decision curve analyses could be better defined.
Minor comment 4: Multivariate would better be termed “multivariable” throughout. Multivariate
methods include principal components analyses, among others, which are different.
ADDITIONAL REQUESTS/SUGGESTIONS:
I have no further comments.
assistant