Review for 10.1186/s12876-023-02661-2 (2023)

Reviewer’s report
Title: 
Real-world systemic sequential therapy with regorafenib for recurrent
hepatocellular carcinoma: analysis of 93 cases from a single center
Version: 
1 
Date: 
26 Nov 2022
Reviewer's report:
Dear authors,
I read with interest the manuscript entitled: "Regorafenib real-world systemic
sequential therapy for recurrent hepatocellular carcinoma: analysis of 93 single-
center cases".
This study reports a single center experience with regorafenib in patients with
hepatocellular carcinoma. The study showed efficacy and safety results in line
with prospective studies such as the pivotal trial (RESORCE).
After reading the manuscript, I would like to point out some suggestions.
- Inclusion criteria were restricted to a regorafenib exposure of ≥ 56 days. This
represents a selection bias, since patients who progressed earlier or who
discontinued treatment before 56 days are likely to have a worse prognosis. I
would sugegst discussing this.
- While on regorafenib treatment, 60 patients received at least one other
treatment, including resection, RFA, transarterial chemoembolization (TACE),
and immune checkpoint inhibitors (ICIs). Concomitant treatments may dilute the
actual efficacy of regorafenib. Considering that the number of 60 patients
represents more than 60% of the cohort, to what extent are the results more likely
to reflect the activity of combined strategies than that of regorafenib?
- The authors reported the time to progression (TTP) results. However, there is
no mention about the imaging assessment schedule . It can vary widely in
retrospective studies. Therefore, the TTP may not be an informative endpoint. I
would sugegst included it as a limitation of the study.
- The median TTP was 5 months and the median duration of treatment with
regorafenib was 9.2 months. These findings suggest that some patients were
treated even after disease progression. 
I would suggest discussing this scenario.
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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?
No
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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