Reviewer's report
Title:Management of stage II colon cancer-the use of molecular biomarkers for
adjuvant therapy decision
Version: 1Date:2 December 2012
Reviewer: Lars Henrik Henrik Jensen
Reviewer's report:
The authors report the results from a retrospective and exploratory marker study
in stage II colon cancer. Sixty patients treated with adjuvant 5FU and a matched
control group of 60 untreated patients were included. Classical histopathological
variables were included together with molecular markers. Primary endpoint was
DFS.
Adjuvant treatment in stage II colon cancer is a clinical challenge and new or
validated markers would be helpful. The study represents a major work effort.
Major
1. Please include the reference J Natl Cancer Inst. 2011;103:863 in 'Background'
together with ref. 16+17. Comment.
2. The last paragraph in 'Background* should be moved to 'Methods'.
3. In 'Methods, patients' please state how patients were selected.
4. Even though the control group was matched for sex/age and they seemed
alike (table 1), confounding is a major issue.
5. Please state exactly how the patients were followed up. A specific scheme is
mandatory for using recurrence as an endpoint.
6. In 'Pathological examination' state the kappa-values for the two pathologists.
Especially for tumour budding, vein and nerve invasion.
7. For TMA justify the use by comparison to whole slice. How was the method
validated? P53 and beta-catenin are probably not suitable for TMA (APMIS
120,819).
8. Were PMS2 and MSH6 included?
9. In 'Statistical analysis', clarify DFS. Is it time-to-recurrence or
disease-free-survival? State events and censoring events.
10. Give a rationale for the sample size of 120 patients. How small a difference
was considered clinically meaningful?
11. Provide a reference for the definition of borderline statistical significance.
12. Describe the model for survival analysis. When was a variable included in the
final model? Cut off? Has a statistician been involved?
13. In 'Results, Survival analysis', which end point is death from colon cancer
progression and where is it defined?
14. As I understand figure 3, all patients with dMMR had a relapse. This in
unlikely in stage II colon cancer.
15. Is there any relationship between the last sentence in 'Results' and figure 3?
16. I lost track in the 'Discussion'. Please rewrite and shorten.
17. In 'Conclusion', TS expression is mentioned. Protein or gene expression?
Minor essential revisions have not been evaluated.
The aim of the study was to add to the knowledge of markers in stage II colon
cancer. Due to the major issues above, the results do not fulfil the aim in the
present form.
The authors should have the opportunity to rewrite and focus the manuscript. It
might be an idea to focus on validation of their previous results (ref. 28).
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Management of stage II colon cancer-the use of molecular biomarkers for
adjuvant therapy decision
Version: 1Date:2 December 2012
Reviewer: Lars Henrik Henrik Jensen
Reviewer's report:
The authors report the results from a retrospective and exploratory marker study
in stage II colon cancer. Sixty patients treated with adjuvant 5FU and a matched
control group of 60 untreated patients were included. Classical histopathological
variables were included together with molecular markers. Primary endpoint was
DFS.
Adjuvant treatment in stage II colon cancer is a clinical challenge and new or
validated markers would be helpful. The study represents a major work effort.
Major
1. Please include the reference J Natl Cancer Inst. 2011;103:863 in 'Background'
together with ref. 16+17. Comment.
2. The last paragraph in 'Background* should be moved to 'Methods'.
3. In 'Methods, patients' please state how patients were selected.
4. Even though the control group was matched for sex/age and they seemed
alike (table 1), confounding is a major issue.
5. Please state exactly how the patients were followed up. A specific scheme is
mandatory for using recurrence as an endpoint.
6. In 'Pathological examination' state the kappa-values for the two pathologists.
Especially for tumour budding, vein and nerve invasion.
7. For TMA justify the use by comparison to whole slice. How was the method
validated? P53 and beta-catenin are probably not suitable for TMA (APMIS
120,819).
8. Were PMS2 and MSH6 included?
9. In 'Statistical analysis', clarify DFS. Is it time-to-recurrence or
disease-free-survival? State events and censoring events.
10. Give a rationale for the sample size of 120 patients. How small a difference
was considered clinically meaningful?
11. Provide a reference for the definition of borderline statistical significance.
12. Describe the model for survival analysis. When was a variable included in the
final model? Cut off? Has a statistician been involved?
13. In 'Results, Survival analysis', which end point is death from colon cancer
progression and where is it defined?
14. As I understand figure 3, all patients with dMMR had a relapse. This in
unlikely in stage II colon cancer.
15. Is there any relationship between the last sentence in 'Results' and figure 3?
16. I lost track in the 'Discussion'. Please rewrite and shorten.
17. In 'Conclusion', TS expression is mentioned. Protein or gene expression?
Minor essential revisions have not been evaluated.
The aim of the study was to add to the knowledge of markers in stage II colon
cancer. Due to the major issues above, the results do not fulfil the aim in the
present form.
The authors should have the opportunity to rewrite and focus the manuscript. It
might be an idea to focus on validation of their previous results (ref. 28).
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Management of stage II colon cancer-the use of molecular biomarkers for
adjuvant therapy decision
Version: 1Date:2 December 2012
Reviewer: Lars Henrik Henrik Jensen
Reviewer's report:
The authors report the results from a retrospective and exploratory marker study
in stage II colon cancer. Sixty patients treated with adjuvant 5FU and a matched
control group of 60 untreated patients were included. Classical histopathological
variables were included together with molecular markers. Primary endpoint was
DFS.
Adjuvant treatment in stage II colon cancer is a clinical challenge and new or
validated markers would be helpful. The study represents a major work effort.
Major
1. Please include the reference J Natl Cancer Inst. 2011;103:863 in 'Background'
together with ref. 16+17. Comment.
2. The last paragraph in 'Background* should be moved to 'Methods'.
3. In 'Methods, patients' please state how patients were selected.
4. Even though the control group was matched for sex/age and they seemed
alike (table 1), confounding is a major issue.
5. Please state exactly how the patients were followed up. A specific scheme is
mandatory for using recurrence as an endpoint.
6. In 'Pathological examination' state the kappa-values for the two pathologists.
Especially for tumour budding, vein and nerve invasion.
7. For TMA justify the use by comparison to whole slice. How was the method
validated? P53 and beta-catenin are probably not suitable for TMA (APMIS
120,819).
8. Were PMS2 and MSH6 included?
9. In 'Statistical analysis', clarify DFS. Is it time-to-recurrence or
disease-free-survival? State events and censoring events.
10. Give a rationale for the sample size of 120 patients. How small a difference
was considered clinically meaningful?
11. Provide a reference for the definition of borderline statistical significance.
12. Describe the model for survival analysis. When was a variable included in the
final model? Cut off? Has a statistician been involved?
13. In 'Results, Survival analysis', which end point is death from colon cancer
progression and where is it defined?
14. As I understand figure 3, all patients with dMMR had a relapse. This in
unlikely in stage II colon cancer.
15. Is there any relationship between the last sentence in 'Results' and figure 3?
16. I lost track in the 'Discussion'. Please rewrite and shorten.
17. In 'Conclusion', TS expression is mentioned. Protein or gene expression?
Minor essential revisions have not been evaluated.
The aim of the study was to add to the knowledge of markers in stage II colon
cancer. Due to the major issues above, the results do not fulfil the aim in the
present form.
The authors should have the opportunity to rewrite and focus the manuscript. It
might be an idea to focus on validation of their previous results (ref. 28).
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
assistant