Preoperative Assessment for Event-Free Survival With Hepatoblastoma in Pediatric Patients by Developing a CT-Based Radiomics Model

Abstract

Objective: To explore a CT-based radiomics model for preoperative prediction of event-free survival (EFS) in patients with hepatoblastoma and to compare its performance with that of a clinicopathologic model. Patients and Methods: Eighty-eight patients with histologically confirmed hepatoblastoma (mean age: 2.28 ± 2.72 years) were recruited from two institutions between 2002 and 2019 for this retrospective study. They were divided into a training cohort (65 patients from institution A) and a validation cohort (23 patients from institution B). Radiomics features were extracted manually from pretreatment CT images in the portal venous (PV) phase. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to construct a "radiomics signature" and radiomics score (Rad-score) for EFS prediction. Then, a nomogram incorporating the Rad-score, updated staging system, and significant variables of clinicopathologic risk (age, alpha-fetoprotein (AFP) level, histology subtype, tumor diameter) as the radiomic model, clinicopathologic model, and combined clinicopathologic-radiomic model were built for EFS estimation in the training cohort, the performance of which was assessed in an external-validation cohort with respect to clinical usefulness, discrimination, and calibration. Results: Nine survival-relevant features were selected for a radiomics signature and Rad-score building. Multivariable analysis revealed that histology subtype (P = 0.01), PV (P = 0.001) invasion, and metastasis (P = 0.047) were independent risk factors of EFS. Patients were divided into low- and high-risk groups based on the Rad-score with a cutoff of 0.08 according to survival outcome. The radiomics signature-incorporated nomogram showed good performance (P < 0.001) for EFS estimation (C-Index: 0.810; 95% CI: 0.738-0.882), which was comparable with that of the clinicopathological model for EFS estimation (C-Index: 0.81 vs. 0.85). The radiomics-based nomogram failed to show incremental prognostic value compared with that using the clinicopathologic model. The combined model (radiomics signature plus clinicopathologic parameters) showed significant improvement in the discriminatory accuracy, along with good calibration and greater net clinical benefit, of EFS (C-Index: 0.88; 95% CI: 0.829-0.933). Conclusion: The radiomics signature can be used as a prognostic indicator for EFS in patients with hepatoblastoma. A combination of the radiomics signature and clinicopathologic risk factors showed better performance in terms of EFS prediction in patients with hepatoblastoma, which enabled precise clinical decision-making.

Keywords: computer tomography imaging; hepatoblastoma; nomogram; pediatric; prognosis; radiomics.

Figure 1

Radiomics framework of predicting the EFS of patients with hepatoblastoma.

Figure 2

Kaplan-Meier survival analysis of event-free survival of patients with HB. Graphs show results of Kaplan-Meier survival analyses according to the radiomics score cutoff value (A) for patients in the training data set (B) and those in the validation data set (C). A significant association of the radiomics score with the EFS was shown in the training data set, which was then confirmed in the validation data set.

Figure 3

A prediction performance analysis with combined clinicopathologic-Rad-score of patients with HB. Significant codes: ^***0; ^**0.001; ^*0.01; .0.05; ’ ’0.1; 1.

Figure 4

Calibration curves for each model in the internal validation (A) and external validation (B) set.

Figure 5

Decision curve analysis for each model between the observed 1-, 3-, and 5-year outcomes.