Statistical harmonization can improve the development of a multicenter CT-based radiomic model predictive of nonresponse to induction chemotherapy in laryngeal cancers

Purpose: To develop a radiomic model predicting nonresponse to induction chemotherapy in laryngeal cancers, from multicenter pretherapeutic contrast-enhanced computed tomography (CE-CT) and evaluate the benefit of feature harmonization in such a context.

Methods: Patients (n = 104) eligible for laryngeal preservation chemotherapy were included in five centers. Primary tumor was manually delineated on the CE-CT images. The following radiomic features were extracted with an in-house software (MIRAS v1.1, LaTIM UMR 1101): intensity, shape, and textural features derived from Gray-Level Co-occurrence Matrix (GLCM), Neighborhood Gray Tone Difference Matrix (NGTDM), Gray-Level Run Length Matrix (GLRLM), and Gray-Level Size Zone Matrix (GLSZM). Harmonization was performed using ComBat after unsupervised hierarchical clustering, used to determine labels automatically, given the high heterogeneity of imaging characteristics across and within centers. Patients with similar feature distributions were grouped with unsupervised clustering into an optimal number of clusters (2) determined with "silhouette scoring." Statistical harmonization was then carried out with ComBat on these 2 identified clusters. The cohort was split into training/validation (n = 66) and testing (n = 32) sets. Area under the receiver operating characteristics curves (AUC) were used to evaluate the ability of radiomic features (before and after harmonization) to predict nonresponse to chemotherapy, and specificity (Sp) and sensitivity (Se) were used to quantify their performance in the testing set.

Results: Without harmonization, none of the features identified as predictive in the training set remained significant in the testing set. After ComBat, one textural feature identified in the training set keeps a predictive trend in the testing set-Zone Percentage, derived from the GLSZM, was predictive of nonresponse in the training set (AUC = 0.62, Se = 70%, Sp = 64%, P = 0.04) and obtained a satisfactory performance in the testing set (Se = 80%, Sp = 67%, P = 0.03), although significance was limited by the size of the testing set. These results are consistent with previously published findings in head and neck cancers.

Conclusions: Radiomic features from CE-CT could help in the selection of patients for induction chemotherapy in laryngeal cancers, with relatively good sensitivity and specificity in predicting lack of response. Statistical harmonization with ComBat and unsupervised clustering seems to improve the predictive value of features extracted in such a heterogeneous multicenter setting.