Imaging phenotype using 18F-fluorodeoxyglucose positron emission tomography-based radiomics and genetic alterations of pancreatic ductal adenocarcinoma

Abstract

Purpose: This study aimed to determine if major gene mutations including in KRAS, SMAD4, TP53, and CDKN2A were related to imaging phenotype using ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-based radiomics in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: Data on 48 PDAC patients with pretreatment FDG PET/CT who underwent genomic analysis of their tumor tissue were retrospectively analyzed. A total of 35 unique quantitative radiomic features were extracted from PET images, including imaging phenotypes such as pixel intensity, shape, and textural features. Targeted exome sequencing using a customized cancer panel was used for genomic analysis. To assess the predictive performance of genetic alteration using PET-based radiomics, areas under the receiver operating characteristic curve (AUC) were used.

Results: Mutation frequencies were KRAS 87.5%, TP53 70.8%, SMAD4 25.0%, and CDKN2A 18.8%. KRAS gene mutations were significantly associated with low-intensity textural features, including long-run emphasis (AUC = 0.806), zone emphasis (AUC = 0.794), and large-zone emphasis (AUC = 0.829). SMAD4 gene mutations showed significant relationships with standardized uptake value skewness (AUC = 0.727), long-run emphasis (AUC = 0.692), and high-intensity textural features such as run emphasis (AUC = 0.775), short-run emphasis (AUC = 0.736), zone emphasis (AUC = 0.750), and short-zone emphasis (AUC = 0.725). No significant associations were seen between the imaging phenotypes and genetic alterations in TP53 and CDKN2A.

Conclusion: Genetic alterations of KRAS and SMAD4 had significant associations with FDG PET-based radiomic features in PDAC. PET-based radiomics may help clinicians predict genetic alteration status in a noninvasive way.

Keywords: FDG PET/CT; Gene mutation; Genetic alteration; Pancreatic cancer; Radiomics.