Title: Construction and validation of a survival prognostic model for stage III hepatocellular
carcinoma: a real-world, multicenter clinical study
Version: 2 Date: 05 Mar 2023
Reviewer's report:
In this study, the author aimed to set up a survival prediction model for patients with TNM stage
# hepatocellular carcinoma (HCC), to guide the diagnosis and treatment of HCC patients and
to improve the prognosis. Based on the data of patients with stage # (AJCC 7th TNM stage)
recorded by the American Institute of Cancer Research from 2010 to 2013, the risk factors
affecting the prognosis were screened by Cox univariate and multivariate regression to construct
a line graph, and the credibility of the model was verified by Boostrap method. External survival
data of patients newly diagnosed with stage III hepatocellular carcinoma during 2014-2015 were
then used to verify and fit the model and optimize the model.
They found that age>75 y, stage IIIC, lobotomy, radiotherapy, chemotherapy, positive serum
AFP before treatment were independent prognostic factors for patients with stage # HCC.
The consistency index of the improved prognosis model was 0.725.
They concluded that the traditional TNM staging has certain limitations for clinical diagnosis
and treatment, and the Nomogram model modified by TNM staging has good predictive efficacy
and clinical significance.
The study is of interest, however, several points need details and should be addressed.
-Why the authors used the TNM staging system? Current international guidelines used the most
worldwide used Barcelona Clic Liver Staging System (BCLC) as it is an integrated staging
system taking into account the prognosis of any stages and the corresponding best treatment in
terms of survival gain.  The application of the BCLC staging system would make the study of
current better clinical impact.
- Exclusion criteria: this section should be further detailed.
-The authors should expand the conclusion by suggesting recent perspectives in terms of the
current promising treatment approach based on the immunotherapy-tyrosine kinase inhibitors
combination treatments as recently described and summarized (TKIs in combination with
immunotherapy for hepatocellular carcinoma. Expert Rev Anticancer Ther. 2023 Feb 26:1-13.
doi: 10.1080/14737140.2023.2181162).
-The authors need to add a paragraph discussing the impact of etiology in HCC treatments
as recently suggested (Role of Etiology in Hepatocellular Carcinoma Patients Treated with
Lenvatinib: A Counterfactual Event-Based Mediation Analysis. Cancers (Basel). 2023 Jan
6;15(2):381. doi: 10.3390/cancers15020381) as well as the relevant impact of liver function on
the treatment indications as recently described (The importance of liver functional reserve in
the non-surgical treatment of hepatocellular carcinoma. J Hepatol. 2022 May;76(5):1185-1198.
doi: 10.1016/j.jhep.2021.11.013.).
-the manuscript would benefit from English proofreading.
Title: Construction and validation of a survival prognostic model for stage III hepatocellular
carcinoma: a real-world, multicenter clinical study
Version: 2 Date: 05 Mar 2023
Reviewer's report:
In this study, the author aimed to set up a survival prediction model for patients with TNM stage
# hepatocellular carcinoma (HCC), to guide the diagnosis and treatment of HCC patients and
to improve the prognosis. Based on the data of patients with stage # (AJCC 7th TNM stage)
recorded by the American Institute of Cancer Research from 2010 to 2013, the risk factors
affecting the prognosis were screened by Cox univariate and multivariate regression to construct
a line graph, and the credibility of the model was verified by Boostrap method. External survival
data of patients newly diagnosed with stage III hepatocellular carcinoma during 2014-2015 were
then used to verify and fit the model and optimize the model.
They found that age>75 y, stage IIIC, lobotomy, radiotherapy, chemotherapy, positive serum
AFP before treatment were independent prognostic factors for patients with stage # HCC.
The consistency index of the improved prognosis model was 0.725.
They concluded that the traditional TNM staging has certain limitations for clinical diagnosis
and treatment, and the Nomogram model modified by TNM staging has good predictive efficacy
and clinical significance.
The study is of interest, however, several points need details and should be addressed.
-Why the authors used the TNM staging system? Current international guidelines used the most
worldwide used Barcelona Clic Liver Staging System (BCLC) as it is an integrated staging
system taking into account the prognosis of any stages and the corresponding best treatment in
terms of survival gain.  The application of the BCLC staging system would make the study of
current better clinical impact.
- Exclusion criteria: this section should be further detailed.
-The authors should expand the conclusion by suggesting recent perspectives in terms of the
current promising treatment approach based on the immunotherapy-tyrosine kinase inhibitors
combination treatments as recently described and summarized (TKIs in combination with
immunotherapy for hepatocellular carcinoma. Expert Rev Anticancer Ther. 2023 Feb 26:1-13.
doi: 10.1080/14737140.2023.2181162).
-The authors need to add a paragraph discussing the impact of etiology in HCC treatments
as recently suggested (Role of Etiology in Hepatocellular Carcinoma Patients Treated with
Lenvatinib: A Counterfactual Event-Based Mediation Analysis. Cancers (Basel). 2023 Jan
6;15(2):381. doi: 10.3390/cancers15020381) as well as the relevant impact of liver function on
the treatment indications as recently described (The importance of liver functional reserve in
the non-surgical treatment of hepatocellular carcinoma. J Hepatol. 2022 May;76(5):1185-1198.
doi: 10.1016/j.jhep.2021.11.013.).
-the manuscript would benefit from English proofreading.
Please review this paper.
user
Title: Construction and validation of a survival prognostic model for stage III hepatocellular
carcinoma: a real-world, multicenter clinical study
Version: 2 Date: 05 Mar 2023
Reviewer's report:
In this study, the author aimed to set up a survival prediction model for patients with TNM stage
# hepatocellular carcinoma (HCC), to guide the diagnosis and treatment of HCC patients and
to improve the prognosis. Based on the data of patients with stage # (AJCC 7th TNM stage)
recorded by the American Institute of Cancer Research from 2010 to 2013, the risk factors
affecting the prognosis were screened by Cox univariate and multivariate regression to construct
a line graph, and the credibility of the model was verified by Boostrap method. External survival
data of patients newly diagnosed with stage III hepatocellular carcinoma during 2014-2015 were
then used to verify and fit the model and optimize the model.
They found that age>75 y, stage IIIC, lobotomy, radiotherapy, chemotherapy, positive serum
AFP before treatment were independent prognostic factors for patients with stage # HCC.
The consistency index of the improved prognosis model was 0.725.
They concluded that the traditional TNM staging has certain limitations for clinical diagnosis
and treatment, and the Nomogram model modified by TNM staging has good predictive efficacy
and clinical significance.
The study is of interest, however, several points need details and should be addressed.
-Why the authors used the TNM staging system? Current international guidelines used the most
worldwide used Barcelona Clic Liver Staging System (BCLC) as it is an integrated staging
system taking into account the prognosis of any stages and the corresponding best treatment in
terms of survival gain.  The application of the BCLC staging system would make the study of
current better clinical impact.
- Exclusion criteria: this section should be further detailed.
-The authors should expand the conclusion by suggesting recent perspectives in terms of the
current promising treatment approach based on the immunotherapy-tyrosine kinase inhibitors
combination treatments as recently described and summarized (TKIs in combination with
immunotherapy for hepatocellular carcinoma. Expert Rev Anticancer Ther. 2023 Feb 26:1-13.
doi: 10.1080/14737140.2023.2181162).
-The authors need to add a paragraph discussing the impact of etiology in HCC treatments
as recently suggested (Role of Etiology in Hepatocellular Carcinoma Patients Treated with
Lenvatinib: A Counterfactual Event-Based Mediation Analysis. Cancers (Basel). 2023 Jan
6;15(2):381. doi: 10.3390/cancers15020381) as well as the relevant impact of liver function on
the treatment indications as recently described (The importance of liver functional reserve in
the non-surgical treatment of hepatocellular carcinoma. J Hepatol. 2022 May;76(5):1185-1198.
doi: 10.1016/j.jhep.2021.11.013.).
-the manuscript would benefit from English proofreading.
assistant