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Objective: Pancreatic cancer (PC) is a silent killer, because its detection is difficult and to date no effective treatment has been developed. In the US, the current 5-year survival rate of 11%. Therefore, PC has to be detected as early as possible., Methods and Procedures: In this work, we have combined the use of ultrasensitive nanobiosensors for protease/arginase detection with information fusion based hierarchical decision structure to detect PC at the localized stage by means of a simple Liquid Biopsy. The problem of early-stage detection of pancreatic cancer is modelled as a multi-class classification problem. We propose a Hard Hierarchical Decision Structure (HDS) along with appropriate feature engineering steps to improve the performance of conventional multi-class classification approaches. Further, a Soft Hierarchical Decision Structure (SDS) is developed to additionally provide confidences of predicted labels in the form of class probability values. These frameworks overcome the limitations of existing research studies that employ simple biostatistical tools and do not effectively exploit the information provided by ultrasensitive protease/arginase analyses., Results: The experimental results demonstrate that an overall mean classification accuracy of around 92% is obtained using the proposed approach, as opposed to 75% with conventional multi-class classification approaches. This illustrates that the proposed HDS framework outperforms traditional classification techniques for early-stage PC detection., Conclusion: Although this study is only based on 31 pancreatic cancer patients and a healthy control group of 48 human subjects, it has enabled combining Liquid Biopsies and Machine Learning methodologies to reach the goal of earliest PC detection. The provision of both decision labels (via HDS) as well as class probabilities (via SDS) helps clinicians identify instances where statistical model-based predictions lack confidence. This further aids in determining if more tests are required for better diagnosis. Such a strategy makes the output of our decision model more interpretable and can assist with the diagnostic procedure., Clinical Impact: With further validation, the proposed framework can be employed as a decision support tool for the clinicians to help in detection of pancreatic cancer at early stages.