Guideline- Versus Non-Guideline-Based Neoadjuvant Management of Clinical T4 Rectal Cancer

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Authors have modified the original version of the manuscript according with the recommendations. The study is now suitable for publication.

The english language is correct, only minor corrections are needed 

Author Response

The revised version is in the attachment

Author Response File: Author Response.docx

Reviewer 2 Report (Previous Reviewer 2)

I think it has improved overall.

Author Response

The revised version is in the attachment

Author Response File: Author Response.docx

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

In the present manuscript the authors analyze the survival of T4 stage rectal cancers in order to evaluate the influence on survival of adherence to the current Chinese National Guidelines for the treatment of Rectal cancers. The paper may have interest but the authors need to introduce some modifications in the text.

Material and Methods.

1. Although the Chinese National Guidelines are referred in the text, it would be necessary to present its principals points. A Table would be of great interest 

2- The authors define the primary and secondary end-points of the study: Overall Survival and Disease Specific Survival. But no mention is made regarding Disease-free survival wich is analyzed Results section. 

3- In statistical Analysis the authors mention that they use Cox´s proportional Regression analysis to evaluate prognostic factor of survival. But no reference is made to the use of binary logistic regression analysis, which they perform in the Results Section to evaluate predictive factors of adherence to National Guidelines for treatment.

Results

4- Table 1, which shows patient´s characteristics is not mentioned in the text.

5- Table 1, please, explain in the material and methods section, what you want to say by "passive compliance, objective compliance and positive compliance"

6- Which were the discrepancies detected between the recomendations of the National Guidelines and the measures observed in the population of study. A new Table showing the points of deviation is necessary.

7- The results of Disease-free survival and Specific Survival should be more clearly presented. They should not be presented solely by a Figure.

7. Table 2. Results of logistic reggresion model of factors predictives of guideline compliance. The results of the variables analyzed should be presented more clearly. Which is the group of reference?

 

   

English language need minor revision

Author Response

Dear reviewer:

We gratefully thank the editor and all reviewers for their time spend making their constructive remarks and useful-suggestions, which has significantly raised the quality of the manuscript and has enable us to improve the manuscript. Each suggested revision and comment, brought forward by the reviewers was accurately incorporated and considered.

At the same time, we carefully reviewed our research process. Although our research ideas are correct, when responding to the key points raised by the reviewers about how to distinguish whether to follow the guidelines for neoadjuvant therapy, the research team found after discussion, there may be a little problem in the processing of original data, and the processing of these original data may affect some of the results and discussions of the article. Therefore, for the sake of rigorous scientific research, we re-examined and processed the original data, analyzed and further verified the results.

Because the article has been thoroughly combed through, with significant adjustments to the raw data and textual adjustments, we didn't respond to the comments of the reviewers point by point. In revised version, we have presented the points of guidelines and deviation, described the results of the analysis in more detail, explained patient compliance, and corrected spelling errors.

We deeply appreciate your suggested revision and comment, and we hope that the revised manuscript is accepted for publication of Current Oncology.

Thank you and best regards.

Yours sincerely,

Xi, Chen

Corresponding author: Xiaodong, Wang

E-mail: [email protected]

Reviewer 2 Report

I appreciate the authors' attempt to investigate the impact of guideline and non-guideline based neoadjuvant management for rectal cancer. It may be useful because conforms to real clinical practice, but there are some questions and I think that improvement is necessary. 

1; line41-43, 74-78, line222-224; What kind of neoadjuvant therapy does the Oncology Branch of the Chinese Medical Association recommend for advanced CRC? (eg, chemotherapy only, radiotherapy only,　chemoradiotherapy, content of each, etc.).

It may be different for each country, so it is desirable to describe it.

If you changed your treatment during neoadjuvant therapybecause of an adverse event, did you categorize it as guideline therapy or non-guideline therapy? Were you classified as guideline therapy only when treatment was completed?

 2; line83-85, Table1; How did you define Rectal cancer? Are the low rectum, mid rectum, and high rectum evenly divided into three?  Does it include anal canal cancer?

What is the ratio of T4a to T4b in T4?

Are all surgical procedures limited to rectal resection? Is there a combined resection of other organs? Do you perform lateral lymph node dissection?

 3; line 106-107, Table 1; Median age was 83 years (range 80–94 years) ?　37% of patients was male?

 4; line108, Table1; Doesn't the influence of distant metastasis increase if TNM stage IV is included?　Do you conclude neoadjuvant therapy for rectal cancer is not effective for advanced rectal cancer with distant metastasis (stage IV)?

 5; line124-129; Isn't it "Patients who received non-guideline care hadn't reduced OS compared with patients who received neoadjuvant therapy according to guidelines"?

(Isn't it better to consider patients who received neoadjuvant therapy according to guidelines as a standard?)

 6; line124-137,148-156, Figure2, 3; Did you evaluate everything in cTNM?

Were there any differences in the examination at the pathological stage(pTNM)?　Was there any difference in therapeutic effect between guideline-based neoadjuvant therapy and non-guideline therapy (eg. down staging)? 

7; Table1, 2, 3; What are the classifications of low, medium, and high in Differentiation? 

8; line240-242; All patients were not carried out adjuvant therapy?

9; line251-253, 263-266, 269-272, 274-276; It's a retrospective study, so I can't think that strong of it.　Based on the guidelines, but it is important to discuss well with the patient and determine the treatment policy.

Author Response

Dear reviewer:

We gratefully thank the editor and all reviewers for their time spend making their constructive remarks and useful-suggestions, which has significantly raised the quality of the manuscript and has enable us to improve the manuscript. Each suggested revision and comment, brought forward by the reviewers was accurately incorporated and considered.

At the same time, we carefully reviewed our research process. Although our research ideas are correct, when responding to the key points raised by the reviewers about how to distinguish whether to follow the guidelines for neoadjuvant therapy, the research team found after discussion, there may be a little problem in the processing of original data, and the processing of these original data may affect some of the results and discussions of the article. Therefore, for the sake of rigorous scientific research, we re-examined and processed the original data, analyzed and further verified the results.

Because the article has been thoroughly combed through, with significant adjustments to the raw data and textual adjustments, we didn't respond to the comments of the reviewers point by point. In revised version, we have presented the points of guidelines and deviation, described the results of the analysis in more detail, explained differentiation, and improved expression.

We deeply appreciate your suggested revision and comment, and we hope that the revised manuscript is accepted for publication of Current Oncology.

Thank you and best regards.

Yours sincerely,

Xi, Chen

Corresponding author: Xiaodong, Wang

E-mail: [email protected]