Reviewer’s report
Title: 
The monocyte to lymphocyte ratio not only at baseline but also at relapse
predicts poor outcomes in patients with hepatocellular carcinoma receiving
locoregional therapy
Version: 
0 
Date: 
21 Jan 2022
Reviewer's report:
Abstract
The abstract is well structured in all its sections, and therefore it properly reflects
the text, highlighting the most important aspects of this paper. Therefore, no
adjustments are needed. 
Introduction
I recommend introducing some lines about the role of TACE in the treatment of
HCC. It is important to briefly describe the different types of transarterial
treatments options. In particular, it is demonstrated that there is a non-superiority
of transarterial chemoembolization with respect to bland embolization in
hepatocarcinoma patients [United European Gastroenterol J. 2017;5(4):511-518.
doi:10.1177/2050640616673516]. Please, the Authors have to report why they
used TACE (and not TAE), citing the above-mentioned article.
I suggest introducing some lines also concerning combined treatments, for
example citing: Sequential transarterial chemoembolization and early
radiofrequency ablation improves clinical outcomes for early-intermediate
hepatocellular carcinoma in a 10-year single-center comparative study. BMC
Gastroenterol. 2021;21(1):182. Published 2021 Apr 20. doi:10.1186/s12876-021-
01765-x.
Materials & Methods
Some points need to be clarified:
- The authors must describe in which patients they performed combined
treatments. In particular: did they perform combined treatment in all patients
that, according to EASL guidelines, need to be treated or with ablation (alone) or
with TACE (alone)? Please, specify.
- The authors must report if they used mRECIST in the follow-up. Furthermore,
it is well known that the decision on whether a HCC patient is a responder or
progressor after treatment may vary among different radiologists, with different
experiences. Therefore, patients should be evaluated by experienced radiologists
to minimize the variability in this critical phase [Eur Radiol. 2018;28(9):3611-
3620. doi:10.1007/s00330-018-5393-3]. The Authors have to report if one or
more experienced radiologists evaluated imaging in the follow-up.? This is
important, according to the aforementioned paper [Eur Radiol. 2018;28(9):3611-
3620. doi:10.1007/s00330-018-5393-3] because the results are based on a correct
and reproducible evaluation of the imaging.
- The authors stated: "All enrolled patients were treated with TACE combined
with local ablation, which were performed by three qualified hepatologists".
Were The tace procedure performed by Hepatologists? Not by Interventional
Radiologists?
- Furthermore: could the authors specify the word "qualified"? Are the operators
expert in performing TACE? How many years of experience characterized the
operators? This point, in my opinion, is crucial. In fact, during the execution of
the procedures, did the authors consider accurately the amount of absorbed
radiant dose? In my opinion, it is also possible to reduce the number of rays
absorbed for both patients and radiologists and reduce possible stochastic and
non-stochastic effects [Med Phys. 2012;39(5):2491-2498.
doi:10.1118/1.3702457] if the procedures were performed by experienced
interventional radiologists. Were the interventional radiologists who performed
TACE, expert in order to reduce the dose in patients that received a systemic
treatment [cite the paper: Med Phys. 2012;39(5):2491-2498.
doi:10.1118/1.3702457]? In my opinion, this theme could be briefly analyzed in
this section but most of all, in the discussion section.
Results
Could the authors reduce in length the section results?.
It is not clear the tumor dimension: mean? It is important to understand your
study population.
Discussion
Could the authors cite and discuss this interesting Letter: "Sequential or
combined treatment? That is the question. Radiology. 2014;272(2):612-613.
doi:10.1148/radiol.14140678", highlighting their strategy of defining combined
treatment as a sequential treatment. 
The authors must discuss and stress an important theme: the association of a
percutaneous therapy such as ablation (which already has its complications) with
another locoregional therapy such as TACE (which has its complications)
requires that no further dramatic implications such as those of X-rays absorption.
Therefore, with the intent to highlight the results of this paper, especially for
these combined treatments, it is necessary that Interventional radiological
procedures must be performed by experienced radiologists (or hepatologists) to
reduce stochastic and non-stochastic risks from x-ray exposure [Med Phys.
2012;39(5):2491-2498. doi:10.1118/1.3702457]. 
Tables
The tables, in the present form, are difficult to read.
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Yes
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'
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
The monocyte to lymphocyte ratio not only at baseline but also at relapse
predicts poor outcomes in patients with hepatocellular carcinoma receiving
locoregional therapy
Version: 
0 
Date: 
21 Jan 2022
Reviewer's report:
Abstract
The abstract is well structured in all its sections, and therefore it properly reflects
the text, highlighting the most important aspects of this paper. Therefore, no
adjustments are needed. 
Introduction
I recommend introducing some lines about the role of TACE in the treatment of
HCC. It is important to briefly describe the different types of transarterial
treatments options. In particular, it is demonstrated that there is a non-superiority
of transarterial chemoembolization with respect to bland embolization in
hepatocarcinoma patients [United European Gastroenterol J. 2017;5(4):511-518.
doi:10.1177/2050640616673516]. Please, the Authors have to report why they
used TACE (and not TAE), citing the above-mentioned article.
I suggest introducing some lines also concerning combined treatments, for
example citing: Sequential transarterial chemoembolization and early
radiofrequency ablation improves clinical outcomes for early-intermediate
hepatocellular carcinoma in a 10-year single-center comparative study. BMC
Gastroenterol. 2021;21(1):182. Published 2021 Apr 20. doi:10.1186/s12876-021-
01765-x.
Materials & Methods
Some points need to be clarified:
- The authors must describe in which patients they performed combined
treatments. In particular: did they perform combined treatment in all patients
that, according to EASL guidelines, need to be treated or with ablation (alone) or
with TACE (alone)? Please, specify.
- The authors must report if they used mRECIST in the follow-up. Furthermore,
it is well known that the decision on whether a HCC patient is a responder or
progressor after treatment may vary among different radiologists, with different
experiences. Therefore, patients should be evaluated by experienced radiologists
to minimize the variability in this critical phase [Eur Radiol. 2018;28(9):3611-
3620. doi:10.1007/s00330-018-5393-3]. The Authors have to report if one or
more experienced radiologists evaluated imaging in the follow-up.? This is
important, according to the aforementioned paper [Eur Radiol. 2018;28(9):3611-
3620. doi:10.1007/s00330-018-5393-3] because the results are based on a correct
and reproducible evaluation of the imaging.
- The authors stated: "All enrolled patients were treated with TACE combined
with local ablation, which were performed by three qualified hepatologists".
Were The tace procedure performed by Hepatologists? Not by Interventional
Radiologists?
- Furthermore: could the authors specify the word "qualified"? Are the operators
expert in performing TACE? How many years of experience characterized the
operators? This point, in my opinion, is crucial. In fact, during the execution of
the procedures, did the authors consider accurately the amount of absorbed
radiant dose? In my opinion, it is also possible to reduce the number of rays
absorbed for both patients and radiologists and reduce possible stochastic and
non-stochastic effects [Med Phys. 2012;39(5):2491-2498.
doi:10.1118/1.3702457] if the procedures were performed by experienced
interventional radiologists. Were the interventional radiologists who performed
TACE, expert in order to reduce the dose in patients that received a systemic
treatment [cite the paper: Med Phys. 2012;39(5):2491-2498.
doi:10.1118/1.3702457]? In my opinion, this theme could be briefly analyzed in
this section but most of all, in the discussion section.
Results
Could the authors reduce in length the section results?.
It is not clear the tumor dimension: mean? It is important to understand your
study population.
Discussion
Could the authors cite and discuss this interesting Letter: "Sequential or
combined treatment? That is the question. Radiology. 2014;272(2):612-613.
doi:10.1148/radiol.14140678", highlighting their strategy of defining combined
treatment as a sequential treatment. 
The authors must discuss and stress an important theme: the association of a
percutaneous therapy such as ablation (which already has its complications) with
another locoregional therapy such as TACE (which has its complications)
requires that no further dramatic implications such as those of X-rays absorption.
Therefore, with the intent to highlight the results of this paper, especially for
these combined treatments, it is necessary that Interventional radiological
procedures must be performed by experienced radiologists (or hepatologists) to
reduce stochastic and non-stochastic risks from x-ray exposure [Med Phys.
2012;39(5):2491-2498. doi:10.1118/1.3702457]. 
Tables
The tables, in the present form, are difficult to read.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
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'
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
The monocyte to lymphocyte ratio not only at baseline but also at relapse
predicts poor outcomes in patients with hepatocellular carcinoma receiving
locoregional therapy
Version: 
0 
Date: 
21 Jan 2022
Reviewer's report:
Abstract
The abstract is well structured in all its sections, and therefore it properly reflects
the text, highlighting the most important aspects of this paper. Therefore, no
adjustments are needed. 
Introduction
I recommend introducing some lines about the role of TACE in the treatment of
HCC. It is important to briefly describe the different types of transarterial
treatments options. In particular, it is demonstrated that there is a non-superiority
of transarterial chemoembolization with respect to bland embolization in
hepatocarcinoma patients [United European Gastroenterol J. 2017;5(4):511-518.
doi:10.1177/2050640616673516]. Please, the Authors have to report why they
used TACE (and not TAE), citing the above-mentioned article.
I suggest introducing some lines also concerning combined treatments, for
example citing: Sequential transarterial chemoembolization and early
radiofrequency ablation improves clinical outcomes for early-intermediate
hepatocellular carcinoma in a 10-year single-center comparative study. BMC
Gastroenterol. 2021;21(1):182. Published 2021 Apr 20. doi:10.1186/s12876-021-
01765-x.
Materials & Methods
Some points need to be clarified:
- The authors must describe in which patients they performed combined
treatments. In particular: did they perform combined treatment in all patients
that, according to EASL guidelines, need to be treated or with ablation (alone) or
with TACE (alone)? Please, specify.
- The authors must report if they used mRECIST in the follow-up. Furthermore,
it is well known that the decision on whether a HCC patient is a responder or
progressor after treatment may vary among different radiologists, with different
experiences. Therefore, patients should be evaluated by experienced radiologists
to minimize the variability in this critical phase [Eur Radiol. 2018;28(9):3611-
3620. doi:10.1007/s00330-018-5393-3]. The Authors have to report if one or
more experienced radiologists evaluated imaging in the follow-up.? This is
important, according to the aforementioned paper [Eur Radiol. 2018;28(9):3611-
3620. doi:10.1007/s00330-018-5393-3] because the results are based on a correct
and reproducible evaluation of the imaging.
- The authors stated: "All enrolled patients were treated with TACE combined
with local ablation, which were performed by three qualified hepatologists".
Were The tace procedure performed by Hepatologists? Not by Interventional
Radiologists?
- Furthermore: could the authors specify the word "qualified"? Are the operators
expert in performing TACE? How many years of experience characterized the
operators? This point, in my opinion, is crucial. In fact, during the execution of
the procedures, did the authors consider accurately the amount of absorbed
radiant dose? In my opinion, it is also possible to reduce the number of rays
absorbed for both patients and radiologists and reduce possible stochastic and
non-stochastic effects [Med Phys. 2012;39(5):2491-2498.
doi:10.1118/1.3702457] if the procedures were performed by experienced
interventional radiologists. Were the interventional radiologists who performed
TACE, expert in order to reduce the dose in patients that received a systemic
treatment [cite the paper: Med Phys. 2012;39(5):2491-2498.
doi:10.1118/1.3702457]? In my opinion, this theme could be briefly analyzed in
this section but most of all, in the discussion section.
Results
Could the authors reduce in length the section results?.
It is not clear the tumor dimension: mean? It is important to understand your
study population.
Discussion
Could the authors cite and discuss this interesting Letter: "Sequential or
combined treatment? That is the question. Radiology. 2014;272(2):612-613.
doi:10.1148/radiol.14140678", highlighting their strategy of defining combined
treatment as a sequential treatment. 
The authors must discuss and stress an important theme: the association of a
percutaneous therapy such as ablation (which already has its complications) with
another locoregional therapy such as TACE (which has its complications)
requires that no further dramatic implications such as those of X-rays absorption.
Therefore, with the intent to highlight the results of this paper, especially for
these combined treatments, it is necessary that Interventional radiological
procedures must be performed by experienced radiologists (or hepatologists) to
reduce stochastic and non-stochastic risks from x-ray exposure [Med Phys.
2012;39(5):2491-2498. doi:10.1118/1.3702457]. 
Tables
The tables, in the present form, are difficult to read.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
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'
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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