Reviewer ’s report  
 
Title: Evaluation of dose -efficacy of sorafenib and effect of transarterial chemoembolization in  
hepatocellular carcinoma patients: A retrospective study  
 
 
Version: 0 Date: 02 Feb 2016  
 
 
Reviewer: Veena  Sangwan  
 
 
Reviewer's report:  
 
The manuscript by Hsiao et al. evaluates the dose efficacy of sorafenib  and effect of TACE on 
HCC patients.   Although several studies have shown a benefit of a combination therapy of 
TACE and sorafenib, this is the first study to show that TACE increases overall survival, even if 
sorafenib treatment has been discontinued due to adverse effects of the drug.  However, these 
results need to be tempered with caution since the size of cohorts used to draw this conclusion is 
small.  This point needs to be addressed in the discussion.  More background on the success of 
the combination of TACE and sorafenib needs to be provided in the discussion.  
 
 
It is intriguing that th e lower dose of sorafenib along with TACE does not give a survival benefit 
to the patient, but a switch from 800 to 400 mg  does.  A possible explanation for these results 
need to be addressed in the Discussion.  
 
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.  
 
Yes 
 
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 st atistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality o f language in the manuscript:  
 
Needs some language corr ections before being published  
 
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 way 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 salary 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 rep ort to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creat ive 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 t he open peer review policy of the journal  
Reviewer ’s report  
 
Title: Evaluation of dose -efficacy of sorafenib and effect of transarterial chemoembolization in  
hepatocellular carcinoma patients: A retrospective study  
 
 
Version: 0 Date: 02 Feb 2016  
 
 
Reviewer: Veena  Sangwan  
 
 
Reviewer's report:  
 
The manuscript by Hsiao et al. evaluates the dose efficacy of sorafenib  and effect of TACE on 
HCC patients.   Although several studies have shown a benefit of a combination therapy of 
TACE and sorafenib, this is the first study to show that TACE increases overall survival, even if 
sorafenib treatment has been discontinued due to adverse effects of the drug.  However, these 
results need to be tempered with caution since the size of cohorts used to draw this conclusion is 
small.  This point needs to be addressed in the discussion.  More background on the success of 
the combination of TACE and sorafenib needs to be provided in the discussion.  
 
 
It is intriguing that th e lower dose of sorafenib along with TACE does not give a survival benefit 
to the patient, but a switch from 800 to 400 mg  does.  A possible explanation for these results 
need to be addressed in the Discussion.  
 
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.  
 
Yes 
 
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 st atistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality o f language in the manuscript:  
 
Needs some language corr ections before being published  
 
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 way 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 salary 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 rep ort to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creat ive 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 t he open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Evaluation of dose -efficacy of sorafenib and effect of transarterial chemoembolization in  
hepatocellular carcinoma patients: A retrospective study  
 
 
Version: 0 Date: 02 Feb 2016  
 
 
Reviewer: Veena  Sangwan  
 
 
Reviewer's report:  
 
The manuscript by Hsiao et al. evaluates the dose efficacy of sorafenib  and effect of TACE on 
HCC patients.   Although several studies have shown a benefit of a combination therapy of 
TACE and sorafenib, this is the first study to show that TACE increases overall survival, even if 
sorafenib treatment has been discontinued due to adverse effects of the drug.  However, these 
results need to be tempered with caution since the size of cohorts used to draw this conclusion is 
small.  This point needs to be addressed in the discussion.  More background on the success of 
the combination of TACE and sorafenib needs to be provided in the discussion.  
 
 
It is intriguing that th e lower dose of sorafenib along with TACE does not give a survival benefit 
to the patient, but a switch from 800 to 400 mg  does.  A possible explanation for these results 
need to be addressed in the Discussion.  
 
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.  
 
Yes 
 
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 st atistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality o f language in the manuscript:  
 
Needs some language corr ections before being published  
 
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 way 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 salary 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 rep ort to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creat ive 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 t he open peer review policy of the journal  
assistant