Round 1

Reviewer 1 Report (Previous Reviewer 3)

manuscript is well revised

Reviewer 2 Report (Previous Reviewer 1)

Revisions are well addressed

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Overall the review is well written and detailed described. Though there are articles on the same topic. PMID: 31569719 also a review article on the same topic.  In this review authors described in different way but there are lots of similarities.

 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Dr Kouroumalis and co-authors present a very comprehensive review of the current status of SSAs therapy for hepatocellular carcinoma. Their review summarises the results of prospective and retrospective studies on SSAs (in comparison with placebo, TACE and other drugs) in patients with non-resectable HCCs. Overall, their paper describes an intriguing topic that could interest the readers. The review is well-written and extremely comprehensive. However, there are just some issues I’d like to bring to the authors’ and editor’s attention:

 

-          Please, provide updated references for BCLC classification (the “2022 update”)

-          Please, specify the meaning of each acronym the first time they’re used (i.e.: HepG2)

-          Costs in medicine are indeed very important, but the primary endpoints of clinical trial should be the clinical impact/survival benefit. When authors make comments on costs, they should probably make references to the concept of cost-effectiveness and cost-benefit.

-          Conclusions should be mitigated (“SSAs have a place even today”). This review (not systematic) can provide some hints on future research topics in selected subgroup of patients (as described by the authors). However, at the moment, it’s definitively unable to provide solid evidence on the utilization of SSAs as an alternative to 1^st and 2^nd drugs as recommended by guidelines.

-          As it looks like there is still lack of equipoise on the subjects, authors should stress the ideas on how to design future observational or experimental studies: which subgroups of patients should be included, which confounding should be accounted for (i.e.: status of SSAs receptors), which mandatory work-up before the treatment is recommended, etc…

Minor issues:

 

Additional proofreading from a native English speaker is recommended (unneeded spaces, unneeded capital letters, etc..)

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 3 Report

This review is well written and authors seems to have enough knowledge for the subject.

I have just one query that, since the review listed many small related studies, readers might get lost during reading. Therefore, it is necessary to make two summary tables encompassing contents of part 3 and part 4. 

Since systemic therapy for HCC is still kind of weak, it is interesting to know about new candidates.

Author Response

Please see the attachment

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Overall authors clarify all the reviewer comments as edited as suggested.

Reviewer 2 Report

I have read again your manuscript with great interest. I believe its quality has been improved following reviewers' suggestions.