Prediction of Early Distant Recurrence in Upfront Resectable Pancreatic Adenocarcinoma: A Multidisciplinary, Machine Learning-Based Approach

SIMPLE SUMMARY: If pancreatic adenocarcinoma is assessed to be technically resectable, curative surgery is still suggested as the primary treatment option; however, the recurrence rate can be very high even in this selected population. The aim of our retrospective study was to develop a preoperative model to accurately stratify upfront resectable patients according to the risk of early distant disease relapse after surgery (<12 months from index procedure). Through a machine learning-based approach, we identified one biochemical marker (serum level of CA19.9), one radiological finding (necrosis) and one radiomic feature (SurfAreaToVolumeRatio), all significantly associated with the early resurge of distant recurrence. A model composed of these three variables only allowed identification of those patients at high risk for early distant disease relapse (50% chance of developing metastases within 12 months after surgery), who would benefit from neoadjuvant chemotherapy instead of upfront surgery. ABSTRACT: Despite careful selection, the recurrence rate after upfront surgery for pancreatic adenocarcinoma can be very high. We aimed to construct and validate a model for the prediction of early distant recurrence (<12 months from index surgery) after upfront pancreaticoduodenectomy. After exclusions, 147 patients were retrospectively enrolled. Preoperative clinical and radiological (CT-based) data were systematically evaluated; moreover, 182 radiomics features (RFs) were extracted. Most significant RFs were selected using minimum redundancy, robustness against delineation uncertainty and an original machine learning bootstrap-based method. Patients were split into training (n = 94) and validation cohort (n = 53). Multivariable Cox regression analysis was first applied on the training cohort; the resulting prognostic index was then tested in the validation cohort. Clinical (serum level of CA19.9), radiological (necrosis), and radiomic (SurfAreaToVolumeRatio) features were significantly associated with the early resurge of distant recurrence. The model combining these three variables performed well in the training cohort (p = 0.0015, HR = 3.58, 95%CI = 1.98–6.71) and was then confirmed in the validation cohort (p = 0.0178, HR = 5.06, 95%CI = 1.75–14.58). The comparison of survival curves between low and high-risk patients showed a p-value <0.0001. Our model may help to better define resectability status, thus providing an actual aid for pancreatic adenocarcinoma patients’ management (upfront surgery vs. neoadjuvant chemotherapy). Independent validations are warranted.