Current Perspectives on the Importance of Pathological Features in Prognostication and Guidance of Adjuvant Chemotherapy in Colon Cancer

Round 1

Reviewer 1 Report

The article entitled "Current perspectives on the importance of pathological features in prognostication and guidance of adjuvant chemotherapy in cancer” is a continuation of the PiCC UP study. This study highlights the attitude of the current medical professionals towards pathological features and biomarkers towards prognosis and its use to decide current treatment options. Here the authors have used questionnaire-based approach to collect the data and have analyzed. The reviewer agrees with the conclusion that it is a first in class study in the Asia Pacific region, however there are few concerns, which requires authors attention.

Minor

• It would be very easy, if authors add a section of abbreviations used in the manuscript.
• Some of the abbreviations are introduced long after mentioning the term in the manuscript, such as NCCN, ESMO, ASCRS, etc. Please correct it.
• Reviewer think that description about 164 specialist should be mentioned in the materials and method section, as they were serving as the data provider.
• In the reference section, some the reference has journal abbreviation (ref # 23, 28, 41,…..) and some of them has journal name. Please refer to guidelines for author and update the reference section accordingly.

Major:

• In the introduction section, authors have used colon cancer stage II and III, and associated features responsible for variable outcome in patients after different treatment as a basis to build the rationale for manuscript. However, in the rationale (page 2, line 58-60) just “colon cancer” is mentioned, which makes the importance of disease stage less important. So, the reviewer suggests including the disease stage in the rationale.
• Figure and table (1 and 2) are the different representation of the same date. Please include either of that in the manuscript. Reviewer think that the data presentation in the table format would be more understandable.
• Authors have made a decent attempt to discuss the findings in the discussion section. However, detailed background explanation dilutes the interest in the manuscript. A concise and specific discussion would be more appropriate.

 

Author Response

Thankyou for your comments

Minor

• It would be very easy, if authors add a section of abbreviations used in the manuscript.

• Thank you for your comment. We have added an additional section of abbreviations in the manuscript

• Some of the abbreviations are introduced long after mentioning the term in the manuscript, such as NCCN, ESMO, ASCRS, etc. Please correct it.

• This has been corrected

• Reviewer think that description about 164 specialist should be mentioned in the materials and method section, as they were serving as the data provider.

• This has been corrected

• In the reference section, some the reference has journal abbreviation (ref # 23, 28, 41,…..) and some of them has journal name. Please refer to guidelines for author and update the reference section accordingly.

• Thankyou for your comment. This reference section has been updated accordingly.

Major:

• In the introduction section, authors have used colon cancer stage II and III, and associated features responsible for variable outcome in patients after different treatment as a basis to build the rationale for manuscript. However, in the rationale (page 2, line 58-60) just “colon cancer” is mentioned, which makes the importance of disease stage less important. So, the reviewer suggests including the disease stage in the rationale.

• Thankyou for your comment. This section has been modified to accurately highlight the importance of different treatment modality especially in stage II colon cancer.

• Figure and table (1 and 2) are the different representation of the same date. Please include either of that in the manuscript. Reviewer think that the data presentation in the table format would be more understandable.

• Thank you for your comment. We have removed the figures and left the data in just table format.

• Authors have made a decent attempt to discuss the findings in the discussion section. However, detailed background explanation dilutes the interest in the manuscript. A concise and specific discussion would be more appropriate.

• Thank you for your comment. The discussion has been re-examined and compressed to be more concise. Detailed background explanation which is not in specific relevance to our study has been excluded. The word count has been reduced by 30%. 

Reviewer 2 Report

Chen et al present the results of a survey (PiCC UP) administered in Australia and New Zealand to oncologists, pathologists and surgeons to understand which pathologic features are used to guide prognostic discussions and adjuvant therapy. The study provides a real world pictures of what clinicians are using to help inform decision making, however adjuvant therapy selection for stage II colon cancer is quite well described in international guidelines. I think it is worth publication but do not think it will inform practice.

Minor Issues/Questions:

1) It is strange that EGFR status was considered as this is not a standard test used in colorectal oncology. Can the authors discuss this a bit more?

2) When discussing KRAS throughout the paper - I assume the authors also include NRAS and would suggest relabelling as KRAS/NRAS for clarity.

3) In the abstract the authors discuss IHC markers of EGFR, KRAS and BRAF status. These are not IHC markers. I would suggest rewording to clarify.

4) What is "apical lymph node positivity"? (Page 2, line 55). I have not heard this term before and it may also be called something else.

5) The second last and last paragraph of section one are very similar. Suggest condensing and combining.

6) Please include the dates the survey was performed in the methods.

7) In the abstract I would suggest describing that the survey was specific to stage II on line 14/15.

8) Figure  has part of the x-axis labels cut off. Also, for figures I do not think you need to include decimal points to the hundredths on Figure 1 and 2.

9) Suggest revising the BRAF comments to BRAF V600E to clarify that not all BRAF mutations are of the same significance.

Author Response

Thank you for your comments and support for our study.

Minor Issues/Questions:

1) It is strange that EGFR status was considered as this is not a standard test used in colorectal oncology. Can the authors discuss this a bit more?

• Thank you for your comment. A section for EGFR status has been added into the discussion.

2) When discussing KRAS throughout the paper - I assume the authors also include NRAS and would suggest relabelling as KRAS/NRAS for clarity.

• Thank you for the comment. To clarify, NRAS was not included in our study.

3) In the abstract the authors discuss IHC markers of EGFR, KRAS and BRAF status. These are not IHC markers. I would suggest rewording to clarify.

• This has been corrected

4) What is "apical lymph node positivity"? (Page 2, line 55). I have not heard this term before and it may also be called something else.

• An apical lymph node refers to lymph nodes within the origin of the major vessel that supplies the tumour. For example, in left sided colon cancer, ALN nodes would refer to nodes surrounding the inferior mesenteric artery. ALN positivity refers to the presence of tumour cells within the ALN. There are some studies which consider it a marker of systemic tumour spread instead of regional, and some systems (Japan and Australia) utilise it in colon cancer staging system.

5) The second last and last paragraph of section one are very similar. Suggest condensing and combining.

• This has been corrected.

6) Please include the dates the survey was performed in the methods.

• Dates survey was performed was added into the methods section

7) In the abstract I would suggest describing that the survey was specific to stage II on line 14/15.

• This has been corrected

8) Figure  2 has part of the x-axis labels cut off. Also, for figures I do not think you need to include decimal points to the hundredths on Figure 1 and 2.

• Thank you for your comment. In line with comments from another reviewer, figures have been removed for clarity as the tables present the same data.

9) Suggest revising the BRAF comments to BRAF V600E to clarify that not all BRAF mutations are of the same significance.

• This has been corrected. BRAF has been revised to BRAF VB600E as appropriate

Reviewer 3 Report

Chen et al. investigated on what pathological features of CRC clinicians decide to treat patients with or without adjuvant chemotherapy. The article covers a topic that would be interesting to the readers of Current Oncology, however, the following should be addressed first.

1. Discussion is very long and highly repetitive. Compression and rearrangement of the presented information is needed.
2. Line 70-74 contains the same information as the previous paragraph, it should be removed.
3. Line 101-102: Correct name of the statistical model is "item response theory model".
4. Tables 1 and 2: Instead of highlighting one column, I recommend to highlight the highest (and maybe the second highest) number for every row / questionnaire item.
5. Definition of various pathological properties should be moved to Methods.
6. Although for most of the readers these abbreviation are known, there are a lot of abbreviations which were never resolved (OS, DFS, PFS, etc.) or were resolved at a later part of the manuscript (e.g., ESMO).
7. There are a lot of 1-sentence paragraphs throughout the text. These should be avoided.
8. Merging paragraphs belonging to the same thread is recommended.
9. Lines 194-196 and 501-502: More careful wording is needed.
10. Line 441: anti-EGFR?
11. Throughout the manuscript a few typos can be found.

Author Response

Thank you for your comments 

1. Discussion is very long and highly repetitive. Compression and rearrangement of the presented information is needed.
   • Thank you for your comment. The discussion has been re-examined and compressed to be more concise. Detailed background explanation which is not in specific relevance to our study has been excluded. The word count has been reduced by 30%. 
2. Line 70-74 contains the same information as the previous paragraph, it should be removed.
   • This has been corrected
3. Line 101-102: Correct name of the statistical model is "item response theory model".
   • This has been corrected
4. Tables 1 and 2: Instead of highlighting one column, I recommend to highlight the highest (and maybe the second highest) number for every row / questionnaire item.
   • This has been corrected
5. Definition of various pathological properties should be moved to Methods.
   • Thankyou for your comment. Definitions have been removed from discussion to facilitate a clearer and concise discussion. For simplicity and word count purposes, they have not been included in the methods section as it does not fit in the scope of this manuscript
6. Although for most of the readers these abbreviation are known, there are a lot of abbreviations which were never resolved (OS, DFS, PFS, etc.) or were resolved at a later part of the manuscript (e.g., ESMO).
   • Thank you for your comment. We have added an additional section of abbreviations in the manuscript
7. There are a lot of 1-sentence paragraphs throughout the text. These should be avoided.
   • This has been corrected
8. Merging paragraphs belonging to the same thread is recommended.
   • Thank you for your comment. Paragraphs within the same thread have been merged as appropriate
9. Lines 194-196 and 501-502: More careful wording is needed.
   • Thank you for your comment. The wording has been adjusted
10. Line 441: anti-EGFR?
    • This is been corrected
11. Throughout the manuscript a few typos can be found.
    • Thankyou for your comment. The manuscript has been re-examined and typos fixed

Round 2

Reviewer 3 Report

Authors addressed all my concerns. My recommendation is acceptance.