Reviewer ’s report  
 
Title:  Survival benefit of transarterial chemoemboliza tion in patients with metastatic 
hepatocellular carcinoma: a single center experience  
 
Version: 0 Date: 05 Jun 2017 
 
Reviewer:  Quirino  Lai 
 
Reviewer’s report:  
 
Article number: BMGE -D-17-00240  
 
Article title: Survival benefit of transarterial chemoembolization in patients with metastati c 
hepatocellular carcinoma: a single center experience  
 
This is a retrospective analysis based on 215 HCC patients from Germany investigating the role 
of TACE alone or TACE combined with sorafenib as therapeutic strategies to adopt in case of 
metastatic di sease.  
 
The paper is really interesting and investigates a poorly explored field of liver oncology. 
However, some corrections should be taken into account before accepting the article.  
 
 
Major comment:  
   
1) I think the main problem is to perform a multiva riable model aimed at verifying the additive 
role of combined TACE -sorafenib constructing it only using 65 cases. As a consequence, it is 
very hard to say that the biological effect of this additive combination is minimal. I think it is 
somewhat hard to ob tain definitive conclusions on this argument. I suggest to report the observed 
results, however clearly underlying during the discussion the potential biases connected with the 
small sample size investigated.     
 
 
Minor comments  
 
1) Page 9, lines 4,5: It i s not fully clear how exactly the percentages have been calculated. I 
suppose the percentages have been calculated on the total number of 65 cases treated with 
TACE, however, at this moment of the article, the different types of patients have not been 
already clarified, so it is better to change the following sentence:  
 
"11 patients received drug -eluting beads TACE (DEB -TACE; 16.9%) and 54 patients were 
treated with conventional TACE (cTACE; 83.1%)."  
 
In: 
 
"On the total number of 65 patients treated with any type of TACE, 11 cases received drug -
eluting beads TACE (DEB -TACE; 16.9%) and 54 patients were treated with conventional TACE 
(cTACE; 83.1%)."  
 
2) Page 9, lines 8 -13: similarly, the percentages here repo rted should be clarified, reporting at 
this point of the article how many cases treated with sorafenib were present in the analysis.  
 
3) Page 11, line 6: the sum of the percentages of viral cases is not 100%. HBV cases percentage 
should be corrected in 60 .3% in the text and in Table 1.  
 
4) Page 11, lines 11,12: the sum of the percentages of Child -Pugh score is not 100%. Child C is 
5.6% as reported also in Table 1: please correct it in the text accordingly.  
 
5) Page 11, line 17: The following sentence pre sents a typo. "None of the patients extrahepatic 
portal vein thrombosis."  
 
6) Page 12, line 10: I think it is better to write "less commonly".  
 
7) Table 1: please check all the percentages. The sum must be always 100.0%, but in some cases 
it is not. Pleas e amend.  
 
8) In discussion, I think that TARE should be also reported with SBRT as an innovative 
treatment useful for treating locally advanced HCC.  
 
9) Figure 2: the sub -group treated with TACE + sorafenib looks to be "zeroed" after 30 months, 
as the cu rve intercepts the absciss line.  However, 1 case remains at risk. Please amend.  
 
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 nec essary 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 statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections 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 th e 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 website 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:  Survival benefit of transarterial chemoemboliza tion in patients with metastatic 
hepatocellular carcinoma: a single center experience  
 
Version: 0 Date: 05 Jun 2017 
 
Reviewer:  Quirino  Lai 
 
Reviewer’s report:  
 
Article number: BMGE -D-17-00240  
 
Article title: Survival benefit of transarterial chemoembolization in patients with metastati c 
hepatocellular carcinoma: a single center experience  
 
This is a retrospective analysis based on 215 HCC patients from Germany investigating the role 
of TACE alone or TACE combined with sorafenib as therapeutic strategies to adopt in case of 
metastatic di sease.  
 
The paper is really interesting and investigates a poorly explored field of liver oncology. 
However, some corrections should be taken into account before accepting the article.  
 
 
Major comment:  
   
1) I think the main problem is to perform a multiva riable model aimed at verifying the additive 
role of combined TACE -sorafenib constructing it only using 65 cases. As a consequence, it is 
very hard to say that the biological effect of this additive combination is minimal. I think it is 
somewhat hard to ob tain definitive conclusions on this argument. I suggest to report the observed 
results, however clearly underlying during the discussion the potential biases connected with the 
small sample size investigated.     
 
 
Minor comments  
 
1) Page 9, lines 4,5: It i s not fully clear how exactly the percentages have been calculated. I 
suppose the percentages have been calculated on the total number of 65 cases treated with 
TACE, however, at this moment of the article, the different types of patients have not been 
already clarified, so it is better to change the following sentence:  
 
"11 patients received drug -eluting beads TACE (DEB -TACE; 16.9%) and 54 patients were 
treated with conventional TACE (cTACE; 83.1%)."  
 
In: 
 
"On the total number of 65 patients treated with any type of TACE, 11 cases received drug -
eluting beads TACE (DEB -TACE; 16.9%) and 54 patients were treated with conventional TACE 
(cTACE; 83.1%)."  
 
2) Page 9, lines 8 -13: similarly, the percentages here repo rted should be clarified, reporting at 
this point of the article how many cases treated with sorafenib were present in the analysis.  
 
3) Page 11, line 6: the sum of the percentages of viral cases is not 100%. HBV cases percentage 
should be corrected in 60 .3% in the text and in Table 1.  
 
4) Page 11, lines 11,12: the sum of the percentages of Child -Pugh score is not 100%. Child C is 
5.6% as reported also in Table 1: please correct it in the text accordingly.  
 
5) Page 11, line 17: The following sentence pre sents a typo. "None of the patients extrahepatic 
portal vein thrombosis."  
 
6) Page 12, line 10: I think it is better to write "less commonly".  
 
7) Table 1: please check all the percentages. The sum must be always 100.0%, but in some cases 
it is not. Pleas e amend.  
 
8) In discussion, I think that TARE should be also reported with SBRT as an innovative 
treatment useful for treating locally advanced HCC.  
 
9) Figure 2: the sub -group treated with TACE + sorafenib looks to be "zeroed" after 30 months, 
as the cu rve intercepts the absciss line.  However, 1 case remains at risk. Please amend.  
 
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 nec essary 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 statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections 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 th e 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 website 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:  Survival benefit of transarterial chemoemboliza tion in patients with metastatic 
hepatocellular carcinoma: a single center experience  
 
Version: 0 Date: 05 Jun 2017 
 
Reviewer:  Quirino  Lai 
 
Reviewer’s report:  
 
Article number: BMGE -D-17-00240  
 
Article title: Survival benefit of transarterial chemoembolization in patients with metastati c 
hepatocellular carcinoma: a single center experience  
 
This is a retrospective analysis based on 215 HCC patients from Germany investigating the role 
of TACE alone or TACE combined with sorafenib as therapeutic strategies to adopt in case of 
metastatic di sease.  
 
The paper is really interesting and investigates a poorly explored field of liver oncology. 
However, some corrections should be taken into account before accepting the article.  
 
 
Major comment:  
   
1) I think the main problem is to perform a multiva riable model aimed at verifying the additive 
role of combined TACE -sorafenib constructing it only using 65 cases. As a consequence, it is 
very hard to say that the biological effect of this additive combination is minimal. I think it is 
somewhat hard to ob tain definitive conclusions on this argument. I suggest to report the observed 
results, however clearly underlying during the discussion the potential biases connected with the 
small sample size investigated.     
 
 
Minor comments  
 
1) Page 9, lines 4,5: It i s not fully clear how exactly the percentages have been calculated. I 
suppose the percentages have been calculated on the total number of 65 cases treated with 
TACE, however, at this moment of the article, the different types of patients have not been 
already clarified, so it is better to change the following sentence:  
 
"11 patients received drug -eluting beads TACE (DEB -TACE; 16.9%) and 54 patients were 
treated with conventional TACE (cTACE; 83.1%)."  
 
In: 
 
"On the total number of 65 patients treated with any type of TACE, 11 cases received drug -
eluting beads TACE (DEB -TACE; 16.9%) and 54 patients were treated with conventional TACE 
(cTACE; 83.1%)."  
 
2) Page 9, lines 8 -13: similarly, the percentages here repo rted should be clarified, reporting at 
this point of the article how many cases treated with sorafenib were present in the analysis.  
 
3) Page 11, line 6: the sum of the percentages of viral cases is not 100%. HBV cases percentage 
should be corrected in 60 .3% in the text and in Table 1.  
 
4) Page 11, lines 11,12: the sum of the percentages of Child -Pugh score is not 100%. Child C is 
5.6% as reported also in Table 1: please correct it in the text accordingly.  
 
5) Page 11, line 17: The following sentence pre sents a typo. "None of the patients extrahepatic 
portal vein thrombosis."  
 
6) Page 12, line 10: I think it is better to write "less commonly".  
 
7) Table 1: please check all the percentages. The sum must be always 100.0%, but in some cases 
it is not. Pleas e amend.  
 
8) In discussion, I think that TARE should be also reported with SBRT as an innovative 
treatment useful for treating locally advanced HCC.  
 
9) Figure 2: the sub -group treated with TACE + sorafenib looks to be "zeroed" after 30 months, 
as the cu rve intercepts the absciss line.  However, 1 case remains at risk. Please amend.  
 
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 nec essary 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 statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections 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 th e 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 website 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