Personalized treatment outcome prediction based on trial data for small-sample and rare patient groups is a critical task in precision medicine. However, the high cost and scarcity of trial data limit the prediction performance. To address this issue, we propose a cross-fidelity knowledge distillation and adaptive fusion network (CFKD-AFN), which leverages abundant but low-fidelity simulation data to enhance the prediction on scarce but high-fidelity trial data. CFKD-AFN incorporates a dual-channel knowledge distillation module to extract complementary knowledge from the low-fidelity model, along with an attention-guided fusion module to adaptively integrate multi-source information. Experiments on chronic obstructive pulmonary disease show that CFKD-AFN reduces the mean squared error by 6.67% ~ 74.55% and the mean absolute percentage error by 1.43% ~ 51.54% compared to the evaluated competing methods and remains robust to varying high-fidelity dataset sizes. Furthermore, we extend the CFKD-AFN framework to an interpretable variant for exploratory analysis of feature-attribution patterns associated with treatment outcomes.

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