Textural differences between renal cell carcinoma subtypes: Machine learning-based quantitative computed tomography texture analysis with independent external validation

Objective: To develop externally validated, reproducible, and generalizable models for distinguishing three major subtypes of renal cell carcinomas (RCCs) using machine learning-based quantitative computed tomography (CT) texture analysis (qCT-TA).

Materials and methods: Sixty-eight RCCs were included in this retrospective study for model development and internal validation. Another 26 RCCs were included from public databases (The Cancer Genome Atlas-TCGA) for independent external validation. Following image preparation steps (reconstruction, resampling, normalization, and discretization), 275 texture features were extracted from unenhanced and corticomedullary phase CT images. Feature selection was firstly done with reproducibility analysis by three radiologists, and; then, with a wrapper-based classifier-specific algorithm. A nested cross-validation was performed for feature selection and model optimization. Base classifiers were the artificial neural network (ANN) and support vector machine (SVM). Base classifiers were also combined with three additional algorithms to improve generalizability performance. Classifications were done with the following groups: (i), non-clear cell RCC (non-cc-RCC) versus clear cell RCC (cc-RCC) and (ii), cc-RCC versus papillary cell RCC (pc-RCC) versus chromophobe cell RCC (chc-RCC). Main performance metric for comparisons was the Matthews correlation coefficient (MCC).

Results: Number of the reproducible features is smaller for the unenhanced images (93 out of 275) compared to the corticomedullary phase images (232 out of 275). Overall performance metrics of the machine learning-based qCT-TA derived from corticomedullary phase images were better than those of unenhanced images. Using corticomedullary phase images, ANN with adaptive boosting algorithm performed best for discrimination of non-cc-RCCs from cc-RCCs (MCC = 0.728) with an external validation accuracy, sensitivity, and specificity of 84.6%, 69.2%, and 100%, respectively. On the other hand, the performance of the machine learning-based qCT-TA is rather poor for distinguishing three major subtypes. The SVM with bagging algorithm performed best for discrimination of pc-RCC from other RCC subtypes (MCC = 0.804) with an external validation accuracy, sensitivity, and specificity of 69.2%, 71.4%, and 100%, respectively.

Conclusions: Machine learning-based qCT-TA can distinguish non-cc-RCCs from cc-RCCs with a satisfying performance. On the other hand, the performance of the method for distinguishing three major subtypes is rather poor. Corticomedullary phase CT images provide much more valuable texture parameters than unenhanced images.