Reviewer ’s report  
 
Title: The development of early ascites is associated with shorter ov erall s urvival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 0 Date: 28 Jan 2020  
 
Reviewer: Alejandro Forner  
 
Reviewer's report:  
 
This is a single -centre cohort study aimed to identify the independent factors associated with the 
overall survival (O S) of hepatocellular carcinoma (HCC) patients treated with transarterial 
chemoembolization with drug -eluting beads (DEB - TACE). A total of of 216 HCC patients were 
consecutively recruited. The objective response according to mRECIST criteria to the first D EB-
TACE (DEB -TACE -1) was 70.3%; the median OS from DEB -TACE -1 was 27 months (95% 
confidence interval (CI), 24 - 30). The most important clinical event associated with poor survival 
was the development of early ascites after DEB -TACE -1 (median OS, 17 months) , which was 
closely related to the history of ascites, albumin and hemoglobin but not to tumour load or to 
response to therapy.  
 
 
Comments:  
 
 - M&amp; M: Platelets units should be expressed in SI Units.  
 
-  Response rate: 35 patients experimented PD and you sta ted that 31% BCLC -C. The sentence is 
misleading. I imagine that you want to express that 31% patients with PD after TACE -1 migrated 
from BCLC B to BCLC C. I would suggest to edit this sentence to avoid misinterpretation.  
 
- Multivariate analysis: You have i ncluded number and nodule size in the model (correct) but 
also BCLC classification. Since you included BCLC 0 -A-B, the different tumor stages are 
defined by size -number of nodules. Therefore, BCLC stage and number nodules+ nodule size are 
covariates. I wou ld suggest to conduct the multivariate analysis without including BCLC stage.  
 
- Alkaline phosphatase was found as an independent prognostic factor of OS in both t0 and t1. 
Can you speculate any potential justification for this finding?  
 
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.  
 
Unable to assess  
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to as sess the statistics  
 
Quality 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 i n the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organi sation t hat 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 reimburse ments, 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.  
 
No COIs  
 
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 f or publication, my named report 
including any attachments I upload will be posted on the website along w ith 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 c an be in cluded 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: The development of early ascites is associated with shorter ov erall s urvival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 0 Date: 28 Jan 2020  
 
Reviewer: Alejandro Forner  
 
Reviewer's report:  
 
This is a single -centre cohort study aimed to identify the independent factors associated with the 
overall survival (O S) of hepatocellular carcinoma (HCC) patients treated with transarterial 
chemoembolization with drug -eluting beads (DEB - TACE). A total of of 216 HCC patients were 
consecutively recruited. The objective response according to mRECIST criteria to the first D EB-
TACE (DEB -TACE -1) was 70.3%; the median OS from DEB -TACE -1 was 27 months (95% 
confidence interval (CI), 24 - 30). The most important clinical event associated with poor survival 
was the development of early ascites after DEB -TACE -1 (median OS, 17 months) , which was 
closely related to the history of ascites, albumin and hemoglobin but not to tumour load or to 
response to therapy.  
 
 
Comments:  
 
 - M&amp; M: Platelets units should be expressed in SI Units.  
 
-  Response rate: 35 patients experimented PD and you sta ted that 31% BCLC -C. The sentence is 
misleading. I imagine that you want to express that 31% patients with PD after TACE -1 migrated 
from BCLC B to BCLC C. I would suggest to edit this sentence to avoid misinterpretation.  
 
- Multivariate analysis: You have i ncluded number and nodule size in the model (correct) but 
also BCLC classification. Since you included BCLC 0 -A-B, the different tumor stages are 
defined by size -number of nodules. Therefore, BCLC stage and number nodules+ nodule size are 
covariates. I wou ld suggest to conduct the multivariate analysis without including BCLC stage.  
 
- Alkaline phosphatase was found as an independent prognostic factor of OS in both t0 and t1. 
Can you speculate any potential justification for this finding?  
 
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.  
 
Unable to assess  
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to as sess the statistics  
 
Quality 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 i n the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organi sation t hat 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 reimburse ments, 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.  
 
No COIs  
 
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 f or publication, my named report 
including any attachments I upload will be posted on the website along w ith 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 c an be in cluded 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: The development of early ascites is associated with shorter ov erall s urvival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 0 Date: 28 Jan 2020  
 
Reviewer: Alejandro Forner  
 
Reviewer's report:  
 
This is a single -centre cohort study aimed to identify the independent factors associated with the 
overall survival (O S) of hepatocellular carcinoma (HCC) patients treated with transarterial 
chemoembolization with drug -eluting beads (DEB - TACE). A total of of 216 HCC patients were 
consecutively recruited. The objective response according to mRECIST criteria to the first D EB-
TACE (DEB -TACE -1) was 70.3%; the median OS from DEB -TACE -1 was 27 months (95% 
confidence interval (CI), 24 - 30). The most important clinical event associated with poor survival 
was the development of early ascites after DEB -TACE -1 (median OS, 17 months) , which was 
closely related to the history of ascites, albumin and hemoglobin but not to tumour load or to 
response to therapy.  
 
 
Comments:  
 
 - M&amp; M: Platelets units should be expressed in SI Units.  
 
-  Response rate: 35 patients experimented PD and you sta ted that 31% BCLC -C. The sentence is 
misleading. I imagine that you want to express that 31% patients with PD after TACE -1 migrated 
from BCLC B to BCLC C. I would suggest to edit this sentence to avoid misinterpretation.  
 
- Multivariate analysis: You have i ncluded number and nodule size in the model (correct) but 
also BCLC classification. Since you included BCLC 0 -A-B, the different tumor stages are 
defined by size -number of nodules. Therefore, BCLC stage and number nodules+ nodule size are 
covariates. I wou ld suggest to conduct the multivariate analysis without including BCLC stage.  
 
- Alkaline phosphatase was found as an independent prognostic factor of OS in both t0 and t1. 
Can you speculate any potential justification for this finding?  
 
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.  
 
Unable to assess  
 
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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to as sess the statistics  
 
Quality 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 i n the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organi sation t hat 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 reimburse ments, 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.  
 
No COIs  
 
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 f or publication, my named report 
including any attachments I upload will be posted on the website along w ith 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 c an be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant