Radiomics in sporadic microsatellite instable, mismatch repair deficient and Lynch syndromeassociated pancreatic ductal adenocarcinoma: a pilot study

Ellis L Eikenboom^1,2,3Joséphine Magnin^1,4Natally Horvat⁵Mithat Gönen⁶William R Jarnagin¹Jeffrey Drebin¹Michael I D'angelica¹T Peter Kingham¹Vinod P Balachandran¹Kevin C Soares¹Anja Wagner²Manon C W Spaander³Jayasree Chakraborty^1*Alice C Wei^1*

• ¹Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States
• ²Department of Clinical Genetics, Erasmus Medical Centre Cancer institute, University Medical Center Rotterdam, Rotterdam, Netherlands
• ³Department of Gastroenterology and Hepatology, Erasmus Medical Centre Cancer institute, University Medical Centre Rotterdam, Rotterdam, Netherlands
• ⁴Department of Digestive Surgical Oncology, University Hospital of Dijon, University of Bourgogne, Dijon, Burgundy, France
• ⁵Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
• ⁶Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States

Introduction: Pancreatic cancer, mostly presenting as pancreatic ductal adenocarcinoma (PDAC), has a poor prognosis. The microsatellite-instable (MSI-H)/mismatch repair deficient (MMRd) subtype, however, is more susceptible to immune therapy and is expected to have a better prognosis. Presently, MSI-testing is not routinely performed on PDAC. We assessed whether quantitative imaging features (radiomics) of pretreatment computed tomography (CT) scans could diagnose MSI-H/MMRd. Methods: For this pilot study, we analyzed CT-scans of treatment-naïve sporadic or Lynch syndrome (LS)-associated MSI-H or MMRd PDACs, diagnosed or treated in a single center from 2007 to August 2022. CT-scans of resected MSI-stable, MMR proficient, non-LS PDACs formed a control group, after random selection in 1:4 ratio. Upon CT-scan segmentation, 254 well-defined radiomic features were extracted from pancreas and tumor regions. The predictability of the features was assessed within a repeated stratified 3-fold cross-validation framework by designing three models using random forest classifier, with the most discriminating features selected through the minimum redundancy maximum relevance method from three feature sets: tumor radiomics, pancreas radiomics, and combined tumor + pancreas radiomics. Performance was evaluated by area under receiver operating curve (AUC), sensitivity, specificity, positive and negative predictive value. Results: Overall, 95 patients were included: 19 patients with MSI-H/MMRd/LS (36.8% female; median age at diagnosis 72 [IQR 60-77 years]) and 76 matched controls with PDAC (53.9% female; median age at diagnosis 66 [IQR 57-74 years]). Median year when CT-scan was done was 2017 and 2018, respectively. The model using radiomic features from the pancreatic tumor reflecting MSI-H/MMRd, had an area under receiver operating curve (AUC) of 0.73. The performance of the model was improved by also incorporating radiomic features from pancreas texture (AUC of combined model 0.83 sensitivity 84%, specificity 78%, negative predictive value 95%). Conclusions: This pilot study suggests that radiomic features could be used to determine MSI/MMRd status in CT-scans of PDAC, but needs further independent multi-site validation in larger cohorts. Routine application of radiomics to determine MSI-status might be of interest in clinical practice to select patients who could benefit from immune therapy.