Vascular Normalization Caused by Short-Term Lenvatinib Could Enhance Transarterial Chemoembolization in Hepatocellular Carcinoma

Round 1

Reviewer 1 Report

I did not see any information about lenvatinib or TKIs in the introduction. Please explain why this medicine is important. Please do a better literature review for lenvatinib. Also, I suggest that authors cite some significant reviews on lenvatinib and TKIs such as https://link.springer.com/article/10.1007/s11030-022-10406-8. 

Is lenvatinib an FDA-approved drug? Is it approved by other reputed agencies? Please explain this within the text.

Maybe, authors can use "multi-kinase inhibitor" as an important keyword.

Author Response

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Reviewer 2 Report

1. The authors reported an interesting finding that pre-TACE lenvatinib use normalized the tumor vessels which may improve lipiodol retention in HCC.

2. In a prior phase II study, lenvatinib was prescribed for 14 to 21 days prior to TACE, while 4 and 7 days respectively for two patients in this study.

3. It is logic that high-dose and/or long-term antiangiogenic therapy might induce tumor starvation and suppress the effect of TACE , thereafter the optimal dosing period of lenvatinib administered in the combination therapy is uncertain. Further study with large patient number is warranted to draw a definitive conclusion.

Author Response

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Reviewer 3 Report

The case report (2 cases here) was well described and the rationale to this study was strong and properly explained in the text. My comments:

1) English grammar should be improved. There are some typos in the text

2) CT-scan could underestimate the presence of viable residual tumoral tissue after cTACE due to lipiodolo staining effect. RMI should be the preferred imaging modality to assess the response to cTACE.

3) The authors should provide some further data on the toxicity of the procedures, considering that it was recently demonstrated that hypertransaminasemia after TACE is related to a better response (cite PMID: 34683182)

4) Could the authors speculate a little on whether this approach could be useful also with other loco-regional treatment for HCC? (in this regard cite the recent comprehensive overview on the state of the art in this field PMID: 33339274 )

Author Response

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Round 2

Reviewer 1 Report

1. Please shorten the title since it occupies a lot of space.

2. Please provide a response within the introduction.

"What was the rationale for investigating the combination of lenvatinib and transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC)?"

"What are the next steps for research in this area, and how might these findings be incorporated into clinical practice?"

3. Please provide a response for this within the results and discussion

"Are there any limitations to the study that should be taken into consideration when interpreting the results? If so, what are they, and how might they be addressed in future studies?"

4. Please discuss and highlight this more in the conclusion

"What were the main findings of the study, and what are the implications of these findings for the treatment of HCC?"

5. In the introduction section of your article, it would be beneficial to include a citation to a relevant review article about lenvatinib. This article provides a wealth of information about lenvatinib, including its chemical structure, and readers of your article may find it useful to access this information. https://link.springer.com/article/10.1007/s11030-022-10406-8

6. Please compare the results with the literature.

Author Response

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Reviewer 3 Report

None of my previous comments were adequately addressed by the authors. English grammar is still poor. References are all from Eastern studies, so i would suggest to consider the suggested references that are from Western studies. Toxicity data are still not adequately reported.

Author Response

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Round 3

Reviewer 1 Report

I have no more comments.