Title: Evaluation of models to predict prognosis in patients with advanced hepatocellular
carcinoma treated with TACE combined with apatinib
Version: 2 Date: 25 Jan 2024
Reviewer's report:
This study aimed  to assess the predictive efficacy of HAP, Six-and-Twelve, Up to Seven,
and ALBI scores  in patients with intermediate and advanced HCC receiving a combination of
TACE and Apatinib. They studied patients with intermediate and advanced HCC who received
TACE combined with Apatinib. Cox proportional hazards model results revealed that the ALBI
score, presence of portal vein tumor thrombus (PVTT,) and tumor size were independent
determinants of survival. Significant differences in survival rates among patients classified by
the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods were demonstrated. The
HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742,
surpassing the alternative models (P<0.05). In addition, an analysis of the area under the AU-
ROC curve confirms the remarkable superiority of the HAP score in predicting short-term
survival outcomes. They concluded that their results confirm the predictive value of HAP, Six-
and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced HCC patients receiving
combined TACE and Apatinib therapy and the HAP model excels in predicting outcomes for
this specific HCC subgroup.
I have the following comments:
-Patient population: Child#Pugh A or B patients were included. However, all Child#Pugh B
classes (B7,B8, B9) were included?
-TACE procedures: please, specify which TACE technique was used (selective?
superselective?)
- APATINIB therapy: could the authors further provide details of adverse events management
and preventive measures (if adopted).
-Discussion: the authors stated that "Several prognostic models have been established to
ascertain which patients benefit most from TACE ..". In this regard,  it has been recently reported
that transient post-TACE hypertransaminasemia is significantly correlated with objective tumor
responsse, as recently demonstrated (J Pers Med. 2021 Oct 17;11(10):1041. doi: 10.3390/
jpm11101041.). This is a simple prognostic tool  to guide treatment strategy of HCC patients
in a tailored approach and should be discussed. In particular, whether available post-TACE
transaminase serum levels it would be of interest to assess the prognostic value of this prognostic
tool.
-In the evolving scenario of combined systemic treatment strategy, the emerging  combinations
based on tyrosine kinase inhibitors plus immunotherapies have demonstrated a significant
improvement of anti-tumor efficacy and safety profiles. However, an unmet need is still the
identification of prognostic tools for a tailored therapeutic management, as recently described
according to results of concluded and ongoing clinical trials (Expert Rev Anticancer Ther.
2023;23(3):279-291. doi: 10.1080/14737140.2023.2181162). In this regard, the performance of
HAP, Six-and-Twelve, Up to Seven, and ALBI scores  should be explored in future studies to
explore which prognostic score is better to allocate systemic combined treatments.
-discussing the efficacy of apatinib, the authors should recall the recent result of a network
meta-analysis demonstrating that camrelizumab plus apatinib in first-line therapy confers
comparable survival benefits as atezolizumab plus bevacizumab (J Clin Transl Hepatol. 2024
Jan 28;12(1):15-24. doi: 10.14218/JCTH.2023.00188).
Title: Evaluation of models to predict prognosis in patients with advanced hepatocellular
carcinoma treated with TACE combined with apatinib
Version: 2 Date: 25 Jan 2024
Reviewer's report:
This study aimed  to assess the predictive efficacy of HAP, Six-and-Twelve, Up to Seven,
and ALBI scores  in patients with intermediate and advanced HCC receiving a combination of
TACE and Apatinib. They studied patients with intermediate and advanced HCC who received
TACE combined with Apatinib. Cox proportional hazards model results revealed that the ALBI
score, presence of portal vein tumor thrombus (PVTT,) and tumor size were independent
determinants of survival. Significant differences in survival rates among patients classified by
the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods were demonstrated. The
HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742,
surpassing the alternative models (P<0.05). In addition, an analysis of the area under the AU-
ROC curve confirms the remarkable superiority of the HAP score in predicting short-term
survival outcomes. They concluded that their results confirm the predictive value of HAP, Six-
and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced HCC patients receiving
combined TACE and Apatinib therapy and the HAP model excels in predicting outcomes for
this specific HCC subgroup.
I have the following comments:
-Patient population: Child#Pugh A or B patients were included. However, all Child#Pugh B
classes (B7,B8, B9) were included?
-TACE procedures: please, specify which TACE technique was used (selective?
superselective?)
- APATINIB therapy: could the authors further provide details of adverse events management
and preventive measures (if adopted).
-Discussion: the authors stated that "Several prognostic models have been established to
ascertain which patients benefit most from TACE ..". In this regard,  it has been recently reported
that transient post-TACE hypertransaminasemia is significantly correlated with objective tumor
responsse, as recently demonstrated (J Pers Med. 2021 Oct 17;11(10):1041. doi: 10.3390/
jpm11101041.). This is a simple prognostic tool  to guide treatment strategy of HCC patients
in a tailored approach and should be discussed. In particular, whether available post-TACE
transaminase serum levels it would be of interest to assess the prognostic value of this prognostic
tool.
-In the evolving scenario of combined systemic treatment strategy, the emerging  combinations
based on tyrosine kinase inhibitors plus immunotherapies have demonstrated a significant
improvement of anti-tumor efficacy and safety profiles. However, an unmet need is still the
identification of prognostic tools for a tailored therapeutic management, as recently described
according to results of concluded and ongoing clinical trials (Expert Rev Anticancer Ther.
2023;23(3):279-291. doi: 10.1080/14737140.2023.2181162). In this regard, the performance of
HAP, Six-and-Twelve, Up to Seven, and ALBI scores  should be explored in future studies to
explore which prognostic score is better to allocate systemic combined treatments.
-discussing the efficacy of apatinib, the authors should recall the recent result of a network
meta-analysis demonstrating that camrelizumab plus apatinib in first-line therapy confers
comparable survival benefits as atezolizumab plus bevacizumab (J Clin Transl Hepatol. 2024
Jan 28;12(1):15-24. doi: 10.14218/JCTH.2023.00188).
Please review this paper.
user
Title: Evaluation of models to predict prognosis in patients with advanced hepatocellular
carcinoma treated with TACE combined with apatinib
Version: 2 Date: 25 Jan 2024
Reviewer's report:
This study aimed  to assess the predictive efficacy of HAP, Six-and-Twelve, Up to Seven,
and ALBI scores  in patients with intermediate and advanced HCC receiving a combination of
TACE and Apatinib. They studied patients with intermediate and advanced HCC who received
TACE combined with Apatinib. Cox proportional hazards model results revealed that the ALBI
score, presence of portal vein tumor thrombus (PVTT,) and tumor size were independent
determinants of survival. Significant differences in survival rates among patients classified by
the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods were demonstrated. The
HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742,
surpassing the alternative models (P<0.05). In addition, an analysis of the area under the AU-
ROC curve confirms the remarkable superiority of the HAP score in predicting short-term
survival outcomes. They concluded that their results confirm the predictive value of HAP, Six-
and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced HCC patients receiving
combined TACE and Apatinib therapy and the HAP model excels in predicting outcomes for
this specific HCC subgroup.
I have the following comments:
-Patient population: Child#Pugh A or B patients were included. However, all Child#Pugh B
classes (B7,B8, B9) were included?
-TACE procedures: please, specify which TACE technique was used (selective?
superselective?)
- APATINIB therapy: could the authors further provide details of adverse events management
and preventive measures (if adopted).
-Discussion: the authors stated that "Several prognostic models have been established to
ascertain which patients benefit most from TACE ..". In this regard,  it has been recently reported
that transient post-TACE hypertransaminasemia is significantly correlated with objective tumor
responsse, as recently demonstrated (J Pers Med. 2021 Oct 17;11(10):1041. doi: 10.3390/
jpm11101041.). This is a simple prognostic tool  to guide treatment strategy of HCC patients
in a tailored approach and should be discussed. In particular, whether available post-TACE
transaminase serum levels it would be of interest to assess the prognostic value of this prognostic
tool.
-In the evolving scenario of combined systemic treatment strategy, the emerging  combinations
based on tyrosine kinase inhibitors plus immunotherapies have demonstrated a significant
improvement of anti-tumor efficacy and safety profiles. However, an unmet need is still the
identification of prognostic tools for a tailored therapeutic management, as recently described
according to results of concluded and ongoing clinical trials (Expert Rev Anticancer Ther.
2023;23(3):279-291. doi: 10.1080/14737140.2023.2181162). In this regard, the performance of
HAP, Six-and-Twelve, Up to Seven, and ALBI scores  should be explored in future studies to
explore which prognostic score is better to allocate systemic combined treatments.
-discussing the efficacy of apatinib, the authors should recall the recent result of a network
meta-analysis demonstrating that camrelizumab plus apatinib in first-line therapy confers
comparable survival benefits as atezolizumab plus bevacizumab (J Clin Transl Hepatol. 2024
Jan 28;12(1):15-24. doi: 10.14218/JCTH.2023.00188).
assistant