Multiparametric Modelling of Survival in Pancreatic Ductal Adenocarcinoma Using Clinical, Histomorphological, Genetic and Image-Derived Parameters

• Main Authors: Georgios A. Kaissis, Friederike Jungmann, Sebastian Ziegelmayer, Fabian K. Lohöfer, Felix N. Harder, Anna Melissa Schlitter, Alexander Muckenhuber, Katja Steiger, Rebekka Schirren, Helmut Friess, Roland Schmid, Wilko Weichert, Marcus R. Makowski, Rickmer F. Braren
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Journal of Clinical Medicine
• Subjects: pancreatic ductal adenocarcinoma; survival analysis; multiparametric modelling; genetics; molecular phenotyping; image-derived features
• Online Access: https://www.mdpi.com/2077-0383/9/5/1250

Rationale: Pancreatic ductal adenocarcinoma (PDAC) remains a tumor entity of exceptionally poor prognosis, and several biomarkers are under current investigation for the prediction of patient prognosis. Many studies focus on promoting newly developed imaging biomarkers without a rigorous comparison to other established parameters. To assess the true value and leverage the potential of all efforts in this field, a multi-parametric evaluation of the available biomarkers for PDAC survival prediction is warranted. Here we present a multiparametric analysis to assess the predictive value of established parameters and the added contribution of newly developed imaging features such as biomarkers for overall PDAC patient survival. Methods: 103 patients with resectable PDAC were retrospectively enrolled. Clinical and histopathological data (age, sex, chemotherapy regimens, tumor size, lymph node status, grading and resection status), morpho-molecular and genetic data (tumor morphology, molecular subtype, tp53, kras, smad4 and p16 genetics), image-derived features and the combination of all parameters were tested for their prognostic strength based on the concordance index (CI) of multivariate Cox proportional hazards survival modelling after unsupervised machine learning preprocessing. Results: The average CIs of the out-of-sample data were: 0.63 for the clinical and histopathological features, 0.53 for the morpho-molecular and genetic features, 0.65 for the imaging features and 0.65 for the combined model including all parameters. Conclusions: Imaging-derived features represent an independent survival predictor in PDAC and enable the multiparametric, machine learning-assisted modelling of postoperative overall survival with a high performance compared to clinical and morpho-molecular/genetic parameters. We propose that future studies systematically include imaging-derived features to benchmark their additive value when evaluating biomarker-based model performance.