BACKGROUND: More accurate predictive biomarkers in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are needed. This study aims to investigate radiomics-based tumour phenotypes as a surrogate biomarker of the tumour vasculature and response prediction to antiangiogenic targeted agents in patients with GEP-NETs.

METHODS: In this retrospective study, a radiomics signature was developed in patients with GEP-NETs and liver metastases receiving lenvatinib. Patients were selected from the multicentre phase II TALENT trial (NCT02678780) (development cohort). Radiomics variables were extracted from liver metastases in the pre-treatment CT-scans and selected using LASSO regression and minimum redundancy maximum relevance (mRMR). Logistic regression and Cox proportional-hazards models for radiomics and combined radiomics with clinical data were explored. The performance of the models was tested in an external cohort of patients treated with sunitinib (test cohort). Associations between the radiomics score and vascularisation factors in plasma were studied using hierarchical clustering and Mann-Whitney U test.

RESULTS: A total of 89 patients were included in the study, 408 liver metastases were analysed. The CT-based radiomics signature was associated with clinical benefit in the development (training and validation sets) and test cohorts (AUC 0.75 [0.66-0.90], 0.67 [0.49-0.92] and 0.67 [0.43-0.91], respectively). The combined radiomics-clinical signature (including the radiomics score, Ki-67 index and primary tumour site) improved on radiomics-only signature performance (AUC 0.79 [95% CI 0.64-0.93]; p < 0.001). A higher radiomics score indicated longer progression-free survival (hazard ration of 0.11 [0.03-0.45]; p = 0.002) and was associated with vascularisation factors (p = 0.01).

CONCLUSIONS: Radiomics-based phenotypes can provide valuable information about tumour characteristics, including the vasculature, that are associated with response to antiangiogenics.

CLINICAL TRIAL REGISTRATION: This is a study of the Lenvatinib Efficacy in Metastatic Neuroendocrine Tumours (TALENT) phase II clinical trial (NCT02678780).