Reviewer ’s report  
 
Title:  Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild -type 
metastatic colorectal cancer  
 
Version: 0 Date: 02 Jun 2017 
 
Reviewer:  H. Modjtahedi  
 
Reviewer’s report:  
 
In this study,  Kim and colleagues investigated whether the primary location of tumour in patients 
with RAS wild -type metasta tic colorectal cancer influences response to therapy with cetuximab. 
They examined 170 patients which included 23 and 147 patients with right and left side tumours 
respectively. They found that patients with right side tumours contained more mutations of R AF, 
PIK3CA, poorly differentiated and had more peritoneal involvement that those of left colon and 
rectal cancer. Right colon cancer was also associated with poorer progression -free survival and 
overall survival. On the basis of their data they concluded t hat, in patients with metastatic wild -
type RAS colon cancer, right colon primary tumour is associated with poorer clinical response to 
cetuximab as salvage treatment.  
 
Overall, this is an interesting study and in particular I am glad that the authors ackno wledged 
some of the limitations of their study (e.g. small sample size, very small number of right side 
colon, lacking of control group without cetuximab etc.,). However, my suggestion is that this 
manuscript can be strengthen if the authors could also inc lude and discuss the results of the 
following related article at the relevant section of discussion.  
 
Arnold D, Lueza B2, Douillard et al., Prognostic and predictive value of primary tumour side in 
patients with RAS wild -type metastatic colorectal cancer t reated with chemotherapy and EGFR 
directed antibodies in six randomised trials. Ann Oncol. 2017 Apr 12. doi: 
10.1093/annonc/mdx175. [Epub ahead of print]  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in  the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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 w ay 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 sal ary 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.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the websi te along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild -type 
metastatic colorectal cancer  
 
Version: 0 Date: 02 Jun 2017 
 
Reviewer:  H. Modjtahedi  
 
Reviewer’s report:  
 
In this study,  Kim and colleagues investigated whether the primary location of tumour in patients 
with RAS wild -type metasta tic colorectal cancer influences response to therapy with cetuximab. 
They examined 170 patients which included 23 and 147 patients with right and left side tumours 
respectively. They found that patients with right side tumours contained more mutations of R AF, 
PIK3CA, poorly differentiated and had more peritoneal involvement that those of left colon and 
rectal cancer. Right colon cancer was also associated with poorer progression -free survival and 
overall survival. On the basis of their data they concluded t hat, in patients with metastatic wild -
type RAS colon cancer, right colon primary tumour is associated with poorer clinical response to 
cetuximab as salvage treatment.  
 
Overall, this is an interesting study and in particular I am glad that the authors ackno wledged 
some of the limitations of their study (e.g. small sample size, very small number of right side 
colon, lacking of control group without cetuximab etc.,). However, my suggestion is that this 
manuscript can be strengthen if the authors could also inc lude and discuss the results of the 
following related article at the relevant section of discussion.  
 
Arnold D, Lueza B2, Douillard et al., Prognostic and predictive value of primary tumour side in 
patients with RAS wild -type metastatic colorectal cancer t reated with chemotherapy and EGFR 
directed antibodies in six randomised trials. Ann Oncol. 2017 Apr 12. doi: 
10.1093/annonc/mdx175. [Epub ahead of print]  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in  the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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 w ay 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 sal ary 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.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the websi te along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title:  Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild -type 
metastatic colorectal cancer  
 
Version: 0 Date: 02 Jun 2017 
 
Reviewer:  H. Modjtahedi  
 
Reviewer’s report:  
 
In this study,  Kim and colleagues investigated whether the primary location of tumour in patients 
with RAS wild -type metasta tic colorectal cancer influences response to therapy with cetuximab. 
They examined 170 patients which included 23 and 147 patients with right and left side tumours 
respectively. They found that patients with right side tumours contained more mutations of R AF, 
PIK3CA, poorly differentiated and had more peritoneal involvement that those of left colon and 
rectal cancer. Right colon cancer was also associated with poorer progression -free survival and 
overall survival. On the basis of their data they concluded t hat, in patients with metastatic wild -
type RAS colon cancer, right colon primary tumour is associated with poorer clinical response to 
cetuximab as salvage treatment.  
 
Overall, this is an interesting study and in particular I am glad that the authors ackno wledged 
some of the limitations of their study (e.g. small sample size, very small number of right side 
colon, lacking of control group without cetuximab etc.,). However, my suggestion is that this 
manuscript can be strengthen if the authors could also inc lude and discuss the results of the 
following related article at the relevant section of discussion.  
 
Arnold D, Lueza B2, Douillard et al., Prognostic and predictive value of primary tumour side in 
patients with RAS wild -type metastatic colorectal cancer t reated with chemotherapy and EGFR 
directed antibodies in six randomised trials. Ann Oncol. 2017 Apr 12. doi: 
10.1093/annonc/mdx175. [Epub ahead of print]  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in  the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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 w ay 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 sal ary 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.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the websi te along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant