Title: Use of ramucirumab for various treatment linesin real-world practice of patients with
advanced hepatocellular carcinoma
Version: 0 Date: 25 Nov 2022
Reviewer:  Seogsong Jeong
Reviewer's report:
Kanogawa et al. reported a case series of advanced HCC. Although the study population is not
sufficient to evaluate the effectiveness of ramucirumab, the reported real-world evidence may
strengthen the pre-existing knowledge on the treatment of advanced HCC. I have some concerns
that may improve the quality of the manuscript and the driven results.
1. Inclusion and exclusion criteria for the inclusion of study participants are not given. Did any
patient undergo TACE, PMCT, etc.?
2. Basic information is not given. Providing AFP, CEA, HBV DNA, liver cirrhosis, tumor
differentiation, smoking, etc. may support a better understanding of the study population.
3. The major weakness of this study is no consideration of potential confounding factors. Since
this study is non-RCT, attempts to balance the treatment groups need to be made even if the
study population is insufficient. Listing the median OS or PFS in tumor size-stratified groups
or any other potential confounding factors-stratified groups may be necessary before making
conclusions.
4. Efficacy is valid for well-controlled studies, such as RCT. From my point of view, this study
evaluated the effectiveness, not efficacy.
5. Better discussion regarding the underlying mechanisms of ramucirumab against advanced
HCC is needed.
6. Elucidations regarding the strengths and limitations of this study is needed.
Title: Use of ramucirumab for various treatment linesin real-world practice of patients with
advanced hepatocellular carcinoma
Version: 0 Date: 25 Nov 2022
Reviewer:  Seogsong Jeong
Reviewer's report:
Kanogawa et al. reported a case series of advanced HCC. Although the study population is not
sufficient to evaluate the effectiveness of ramucirumab, the reported real-world evidence may
strengthen the pre-existing knowledge on the treatment of advanced HCC. I have some concerns
that may improve the quality of the manuscript and the driven results.
1. Inclusion and exclusion criteria for the inclusion of study participants are not given. Did any
patient undergo TACE, PMCT, etc.?
2. Basic information is not given. Providing AFP, CEA, HBV DNA, liver cirrhosis, tumor
differentiation, smoking, etc. may support a better understanding of the study population.
3. The major weakness of this study is no consideration of potential confounding factors. Since
this study is non-RCT, attempts to balance the treatment groups need to be made even if the
study population is insufficient. Listing the median OS or PFS in tumor size-stratified groups
or any other potential confounding factors-stratified groups may be necessary before making
conclusions.
4. Efficacy is valid for well-controlled studies, such as RCT. From my point of view, this study
evaluated the effectiveness, not efficacy.
5. Better discussion regarding the underlying mechanisms of ramucirumab against advanced
HCC is needed.
6. Elucidations regarding the strengths and limitations of this study is needed.
Please review this paper.
user
Title: Use of ramucirumab for various treatment linesin real-world practice of patients with
advanced hepatocellular carcinoma
Version: 0 Date: 25 Nov 2022
Reviewer:  Seogsong Jeong
Reviewer's report:
Kanogawa et al. reported a case series of advanced HCC. Although the study population is not
sufficient to evaluate the effectiveness of ramucirumab, the reported real-world evidence may
strengthen the pre-existing knowledge on the treatment of advanced HCC. I have some concerns
that may improve the quality of the manuscript and the driven results.
1. Inclusion and exclusion criteria for the inclusion of study participants are not given. Did any
patient undergo TACE, PMCT, etc.?
2. Basic information is not given. Providing AFP, CEA, HBV DNA, liver cirrhosis, tumor
differentiation, smoking, etc. may support a better understanding of the study population.
3. The major weakness of this study is no consideration of potential confounding factors. Since
this study is non-RCT, attempts to balance the treatment groups need to be made even if the
study population is insufficient. Listing the median OS or PFS in tumor size-stratified groups
or any other potential confounding factors-stratified groups may be necessary before making
conclusions.
4. Efficacy is valid for well-controlled studies, such as RCT. From my point of view, this study
evaluated the effectiveness, not efficacy.
5. Better discussion regarding the underlying mechanisms of ramucirumab against advanced
HCC is needed.
6. Elucidations regarding the strengths and limitations of this study is needed.
assistant