[F]FDG-PET/CT radiomics for the identification of genetic clusters in pheochromocytomas and paragangliomas.

Objectives: Based on germline and somatic mutation profiles, pheochromocytomas and paragangliomas (PPGLs) can be classified into different clusters. We investigated the use of [F]FDG-PET/CT radiomics, SUV and biochemical profile for the identification of the genetic clusters of PPGLs.

Methods: In this single-centre cohort, 40 PPGLs (13 cluster 1, 18 cluster 2, 9 sporadic) were delineated using a 41% adaptive threshold of SUV ([F]FDG-PET) and manually (low-dose CT; ldCT). Using PyRadiomics, 211 radiomic features were extracted. Stratified 5-fold cross-validation for the identification of the genetic cluster was performed using multinomial logistic regression with dimensionality reduction incorporated per fold. Classification performances of biochemistry, SUV and PET(/CT) radiomic models were compared and presented as mean (multiclass) test AUCs over the five folds. Results were validated using a sham experiment, randomly shuffling the outcome labels.

Results: The model with biochemistry only could identify the genetic cluster (multiclass AUC 0.60). The three-factor PET model had the best classification performance (multiclass AUC 0.88). A simplified model with only SUV performed almost similarly. Addition of ldCT features and biochemistry decreased the classification performances. All sham AUCs were approximately 0.50.

Conclusion: PET radiomics achieves a better identification of PPGLs compared to biochemistry, SUV, ldCT radiomics and combined approaches, especially for the differentiation of sporadic PPGLs. Nevertheless, a model with SUV alone might be preferred clinically, weighing model performances against laborious radiomic analysis. The limited added value of radiomics to the overall classification performance for PPGL should be validated in a larger external cohort.

Key Points: • Radiomics derived from [F]FDG-PET/CT has the potential to improve the identification of the genetic clusters of pheochromocytomas and paragangliomas. • A simplified model with SUV only might be preferred clinically, weighing model performances against the laborious radiomic analysis. • Cluster 1 and 2 PPGLs generally present distinctive characteristics that can be captured using [F]FDG-PET imaging. Sporadic PPGLs appear more heterogeneous, frequently resembling cluster 2 PPGLs and occasionally resembling cluster 1 PPGLs.