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Published on: September 30, 2021
Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model
1Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Insights
The BALAD-2 model refines prognostic assessment for hepatocellular carcinoma (HCC) using continuous biomarkers. This validated international model accurately predicts individual patient survival, improving upon the original BALAD tool.
Area of Science:
- Hepatocellular Carcinoma Research
- Biomarker Discovery
- Prognostic Modeling
Background:
- The original BALAD model was the first objective, biomarker-based tool for hepatocellular carcinoma (HCC) prognosis.
- Limitations included dichotomized data, lack of external validation, and inability to assess individual patients.
- International collaboration sought to address these limitations.
Purpose of the Study:
- To externally validate the original BALAD model in a UK cohort.
- To develop an improved model (BALAD-2) using continuous variables from raw Japanese data.
- To enable accurate, patient-level survival prediction for HCC.
Main Methods:
- Replication of the BALAD model on a UK cohort.
- Development of BALAD-2 using continuous variables and flexible parametric regression models.
- Validation of both models in Japanese and UK cohorts.
Main Results:
- Key prognostic factors confirmed: Bilirubin, Albumin, AFP-L3, AFP, and DCP.
- Recalibrated models showed clinically relevant discrimination of prognosis in both cohorts.
- Accurate prediction of patient-level survival was achieved.
Conclusions:
- The original BALAD model is validated internationally.
- The refined BALAD-2 model provides patient-level survival estimates for UK and Japanese cohorts.
- BALAD-2 enhances prognostic accuracy for hepatocellular carcinoma.
Background:
The Japanese 'BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients.
Methods:
In this Japanese/UK collaboration, we replicated the original BALAD model on a UK cohort and then built a new model, BALAD-2, on the original raw Japanese data using variables in their continuous form. Regression analyses using flexible parametric models with fractional polynomials enabled fitting of appropriate baseline hazard functions and functional form of covariates. The resulting models were validated in the respective cohorts to measure the predictive performance.
Results:
The key prognostic features were confirmed to be Bilirubin and Albumin together with the serological cancer biomarkers, AFP-L3, AFP, and DCP. With appropriate recalibration, the model offered clinically relevant discrimination of prognosis in both the Japanese and UK data sets and accurately predicted patient-level survival.
Conclusions:
The original BALAD model has been validated in an international setting. The refined BALAD-2 model permits estimation of patient-level survival in UK and Japanese cohorts.
