A machine learning algorithm predicts molecular subtypes in pancreatic ductal adenocarcinoma with differential response to gemcitabine-based versus FOLFIRINOX chemotherapy

Purpose Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusionweighted-imaging-derived radiomic features. Methods The retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted with PyRadiomics. A gradientboosted-tree algorithm was trained on 70% of the patients (N = 28) and tested on 30% (N = 17) to predict KRT81+ vs. KRT81- tumor subtypes. A gradient-boosted survival regression model was fit to the disease-free and overall survival data. Chemotherapy response and survival were assessed stratified by subtype and radiomic signature. Radiomic feature importance was ranked. Results The mean +/- STDEV sensitivity, specificity and ROC-AUC were 0.90 +/- 0.07, 0.92 +/- 0.11, and 0.93 +/- 0.07, respectively. The mean +/- STDEV concordance indices between the disease-free and overall survival predicted by the model based on the radiomic parameters and actual patient survival were 0.76 +/- 0.05 and 0.71 +/- 0.06, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81-patients (7.0 vs. 22.6 months, HR 4.03, log-rank-test P = < 0.001) and a significantly improved response to gemcitabine-based chemotherapy over FOLFIRINOX (10.14 vs. 3.8 months median overall survival, HR 2.33, P = 0.037) compared to KRT81- patients, who responded significantly better to FOLFIRINOX over gemcitabine-based treatment (30.8 vs. 13.4 months median overall survival, HR 2.41, P = 0.027). Entropy was ranked as the most important radiomic feature. Conclusions The machine-learning based analysis of radiomic features enables the prediction of sub-types of PDAC, which are highly relevant for disease-free and overall patient survival and response to chemotherapy.