Reviewer ’s report  
 
Title: Transarterial Chemoembolization Combined with Iodine  125 Seeds Versus Transarterial 
Chemoembolization Combined with Radiofrequency Ablatio n in the Treatment of Early and 
Intermediate Hepatocellular Carcinoma  
 
Version: 0 Date: 14 Feb 2020  
 
Reviewer: Andrea Aglitti  
 
Reviewer's report:  
 
Dear Prof. Masarone,  
 
This paper by Lei Chen et al faces an interesting topic in hepatology, a comparison between two 
combination therapy for hepatocellular carcinoma (HCC) in e arly and intermediate stages: 
transarterial chemoembolization combined with Iodine125 seeds (TACE -Iodine 125) versus 
transarterial chemoembolization combined with radiofrequency ablation (TACE -RFA). With this 
aim, the authors made a single center retrospec tive cohort study enrolling 134 pts with early or 
intermediate HCC from January 2014 to May 2018; 87 patients were treated with TACE -RFA, 
while 47 subjects with TACE -Iodine 125.  
 
A slightly better median overall survival (OS) and progression -free survival (PFS) of the TACE -
RFA group than those of TACE -Iodine 125 (OS: 42 months vs. 37 months; PFS 18 months vs. 
15 months) was reported, but without statistical significance. After adjusting for age, gender, 
liver resection, CPT class, BCLC stage and alpha -fetop rotein, TACE -Iodine 125 treatment was 
not associated with an increased risk of death and recurrence. Finally, the authors performed a 
propensity score matching generating 47 patient pairs; in these two groups no significant 
differences in median OS and PFS  were found. Therefore, they concluded that the combination 
of TACE and Iodine 125 seeds implantation treatment may represent an effective treatment in 
patients with early and intermediate HCC.  
 
Even if the paper has some elements of interest, there are several points to discuss.  
 
 
Major points:  
 
* English language is poor, it is advisable to review the manuscript by an English native 
speaker.  
 
* Exclusion criteria are not reported and should be show n. 
 
* For some patients in both groups, a liver resection before TACE was reported. The 
authors should indicate the reason. If the cause was, as likely, a previous history of HCC, it isn't 
correct, in my opinion, to compare the natural history of a primary HCC with a recurrent HCC. 
Please report how many patients were treated for the first time for HCC and how many for HCC 
recurrence. Consider also to make the comparisons in OS and PFS divided by primary and 
recurrent HCC.  
 
* Moreover, if there were any HCC recurrences, which therapeutic strategy was used in 
this case? There were differences in treatment strategy between the two groups?  
 
* Sample size seems to be small. The authors should perform a power and sample size 
calculation to avoid a type 2 statistica l error.  
 
 
Minor points:  
 
* It would be interesting to know the causes of death (liver -related and not liver -related).  
 
* The background of the abstract should be reformulated because it is not an 
introduction, but the authors only have exposed the aim of the  study.  
 
* Page 5 line 23: please, change "iodine -25" with iodine -125. 
 
* Page 6: consider to place the inclusion criteria previously, in the Study Cohort section 
(after the first sentence for example).  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls a re 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 speci fy 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:  
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in t he past five years received reimbursements, fees, 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 organisat ion 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 reimbursemen ts, 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 t his 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.  
 
Nothing to declare  
 
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 with the authors' 
responses. I agree for my report to be ma de 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 in cluded as confidential com ments 
to the editors, wh ich will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Transarterial Chemoembolization Combined with Iodine  125 Seeds Versus Transarterial 
Chemoembolization Combined with Radiofrequency Ablatio n in the Treatment of Early and 
Intermediate Hepatocellular Carcinoma  
 
Version: 0 Date: 14 Feb 2020  
 
Reviewer: Andrea Aglitti  
 
Reviewer's report:  
 
Dear Prof. Masarone,  
 
This paper by Lei Chen et al faces an interesting topic in hepatology, a comparison between two 
combination therapy for hepatocellular carcinoma (HCC) in e arly and intermediate stages: 
transarterial chemoembolization combined with Iodine125 seeds (TACE -Iodine 125) versus 
transarterial chemoembolization combined with radiofrequency ablation (TACE -RFA). With this 
aim, the authors made a single center retrospec tive cohort study enrolling 134 pts with early or 
intermediate HCC from January 2014 to May 2018; 87 patients were treated with TACE -RFA, 
while 47 subjects with TACE -Iodine 125.  
 
A slightly better median overall survival (OS) and progression -free survival (PFS) of the TACE -
RFA group than those of TACE -Iodine 125 (OS: 42 months vs. 37 months; PFS 18 months vs. 
15 months) was reported, but without statistical significance. After adjusting for age, gender, 
liver resection, CPT class, BCLC stage and alpha -fetop rotein, TACE -Iodine 125 treatment was 
not associated with an increased risk of death and recurrence. Finally, the authors performed a 
propensity score matching generating 47 patient pairs; in these two groups no significant 
differences in median OS and PFS  were found. Therefore, they concluded that the combination 
of TACE and Iodine 125 seeds implantation treatment may represent an effective treatment in 
patients with early and intermediate HCC.  
 
Even if the paper has some elements of interest, there are several points to discuss.  
 
 
Major points:  
 
* English language is poor, it is advisable to review the manuscript by an English native 
speaker.  
 
* Exclusion criteria are not reported and should be show n. 
 
* For some patients in both groups, a liver resection before TACE was reported. The 
authors should indicate the reason. If the cause was, as likely, a previous history of HCC, it isn't 
correct, in my opinion, to compare the natural history of a primary HCC with a recurrent HCC. 
Please report how many patients were treated for the first time for HCC and how many for HCC 
recurrence. Consider also to make the comparisons in OS and PFS divided by primary and 
recurrent HCC.  
 
* Moreover, if there were any HCC recurrences, which therapeutic strategy was used in 
this case? There were differences in treatment strategy between the two groups?  
 
* Sample size seems to be small. The authors should perform a power and sample size 
calculation to avoid a type 2 statistica l error.  
 
 
Minor points:  
 
* It would be interesting to know the causes of death (liver -related and not liver -related).  
 
* The background of the abstract should be reformulated because it is not an 
introduction, but the authors only have exposed the aim of the  study.  
 
* Page 5 line 23: please, change "iodine -25" with iodine -125. 
 
* Page 6: consider to place the inclusion criteria previously, in the Study Cohort section 
(after the first sentence for example).  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls a re 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 speci fy 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:  
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in t he past five years received reimbursements, fees, 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 organisat ion 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 reimbursemen ts, 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 t his 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.  
 
Nothing to declare  
 
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 with the authors' 
responses. I agree for my report to be ma de 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 in cluded as confidential com ments 
to the editors, wh ich will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Transarterial Chemoembolization Combined with Iodine  125 Seeds Versus Transarterial 
Chemoembolization Combined with Radiofrequency Ablatio n in the Treatment of Early and 
Intermediate Hepatocellular Carcinoma  
 
Version: 0 Date: 14 Feb 2020  
 
Reviewer: Andrea Aglitti  
 
Reviewer's report:  
 
Dear Prof. Masarone,  
 
This paper by Lei Chen et al faces an interesting topic in hepatology, a comparison between two 
combination therapy for hepatocellular carcinoma (HCC) in e arly and intermediate stages: 
transarterial chemoembolization combined with Iodine125 seeds (TACE -Iodine 125) versus 
transarterial chemoembolization combined with radiofrequency ablation (TACE -RFA). With this 
aim, the authors made a single center retrospec tive cohort study enrolling 134 pts with early or 
intermediate HCC from January 2014 to May 2018; 87 patients were treated with TACE -RFA, 
while 47 subjects with TACE -Iodine 125.  
 
A slightly better median overall survival (OS) and progression -free survival (PFS) of the TACE -
RFA group than those of TACE -Iodine 125 (OS: 42 months vs. 37 months; PFS 18 months vs. 
15 months) was reported, but without statistical significance. After adjusting for age, gender, 
liver resection, CPT class, BCLC stage and alpha -fetop rotein, TACE -Iodine 125 treatment was 
not associated with an increased risk of death and recurrence. Finally, the authors performed a 
propensity score matching generating 47 patient pairs; in these two groups no significant 
differences in median OS and PFS  were found. Therefore, they concluded that the combination 
of TACE and Iodine 125 seeds implantation treatment may represent an effective treatment in 
patients with early and intermediate HCC.  
 
Even if the paper has some elements of interest, there are several points to discuss.  
 
 
Major points:  
 
* English language is poor, it is advisable to review the manuscript by an English native 
speaker.  
 
* Exclusion criteria are not reported and should be show n. 
 
* For some patients in both groups, a liver resection before TACE was reported. The 
authors should indicate the reason. If the cause was, as likely, a previous history of HCC, it isn't 
correct, in my opinion, to compare the natural history of a primary HCC with a recurrent HCC. 
Please report how many patients were treated for the first time for HCC and how many for HCC 
recurrence. Consider also to make the comparisons in OS and PFS divided by primary and 
recurrent HCC.  
 
* Moreover, if there were any HCC recurrences, which therapeutic strategy was used in 
this case? There were differences in treatment strategy between the two groups?  
 
* Sample size seems to be small. The authors should perform a power and sample size 
calculation to avoid a type 2 statistica l error.  
 
 
Minor points:  
 
* It would be interesting to know the causes of death (liver -related and not liver -related).  
 
* The background of the abstract should be reformulated because it is not an 
introduction, but the authors only have exposed the aim of the  study.  
 
* Page 5 line 23: please, change "iodine -25" with iodine -125. 
 
* Page 6: consider to place the inclusion criteria previously, in the Study Cohort section 
(after the first sentence for example).  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls a re 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 speci fy 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:  
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in t he past five years received reimbursements, fees, 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 organisat ion 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 reimbursemen ts, 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 t his 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.  
 
Nothing to declare  
 
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 with the authors' 
responses. I agree for my report to be ma de 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 in cluded as confidential com ments 
to the editors, wh ich will not be published.  
 
I agree to the open peer review policy of the journal  
assistant