Review for 10.1186/s12876-022-02542-0 (2022)

Reviewer’s report
Title: 
Drug-Related Adverse Events Potentially Predict the Efficacy of Apatinib
on Advanced Hepatocellular Carcinoma
Version: 
0 
Date: 
10 Feb 2022
Reviewer's report:
This study retrospectively collected 207 patients with advanced HCC who had
received apatinib therapy. Treatment-related AEs, such as HFS, proteinuria,
diarrhea were correlated with clinical outcomes of patients. After multivariate
adjustment, the authors claimed that occurrence of proteinuria could predict
better PFS in these patients and occurrence of diarrhea could predict better OS.
There are several concerns of the current manuscript. 
1. Apatinib has not been approved globally in advanced HCC. The impact of this
study may be less significant.
2. This is a retrospective study but not a clinical trial. It is not suitable to mention
it as a trial in line 96 of page 6. 
3. As mentioned by the authors, HTN was excluded from the analysis in this
study, because their previous work has explored the effect of HTN. However, it
is strange to exclude one kind of AE and perform a new study to analyze other
AEs.
4. The longer treatment duration, the occurrence of any AEs were more likely.
The associations of these AEs with PFS or OS may just be associations.
Prediction was a very strong word. The conclusion should be toned down.
5. About the inclusion criteria, in line 87 of page 6, is it correct for CCr
≤40mL/min ?
6. In page 6, the inclusion criteria allowed systemic therapy ≤1, but the first
exclusion criteria was "systemic anti-cancer therapy".
7. Since this is a retrospective study, it is hard to believe that every patient could
receive regular tumor assessment every 8 weeks, as mentioned in lines 111 and
112 in page 7. 
8. As shown in Table S1-3, the baseline data before PSM were not so different
between subgroups. Using PSM in this study was not very necessary.
9. A Fig 2C should be provided for comparison of PFS in non-diarrhea and
diarrhea patients.
10. The subgroup analysis in page 18 was not very relevant. It is difficult to
explain the findings.
11. The DISCUSSION part had too much elaboration and the logic was not very
clear. 
12. English editing is still needed.
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