Belief-Space Control for Personalized Cancer Treatment via Active Inference

Bladder cancer treatment requires personalized and adaptive decision-making, particularly for recurrent disease, where treatment effectiveness changes across successive clinical episodes. Conventional clinical decision support systems typically rely on static treatment guidelines or single-step predictive models, limiting their ability to capture disease progression over time. This paper presents a recurrent patient state-transition simulation framework for bladder cancer treatment planning that integrates predictive state-transition modeling with a Markov Decision Process (MDP) and a Deep Q-Network (DQN) reinforcement learning environment. The predictive module estimates changes in tumor characteristics following treatment, while the reinforcement learning agent sequentially optimizes treatment decisions by interacting with simulated patient trajectories. This framework enables dynamic, patient-specific treatment planning by continuously adapting recommendations to evolving clinical states. It also generates interpretable treatment trajectories and detailed simulation logs to improve transparency and support clinical decision-making. The proposed framework was evaluated against existing reinforcement learning-based treatment planning approaches. It achieved a cumulative reward of 63,918.87, an average training loss per episode of 0.0056, and a policy improvement score of 6.62%, demonstrating effective sequential learning and robust treatment optimization in a simulated recurrent treatment environment. These findings highlight the potential of recurrent patient state-transition simulation with reinforcement learning as a flexible decision-support framework for personalized bladder cancer treatment planning and AI-assisted precision oncology.

Active inference casts decision-making as inference, with the Expected Free Energy (EFE) unifying goal-directed and information-seeking behavior. Recent work showed that EFE minimization can be written as Variational Free Energy (VFE) minimization on a generative model augmented with epistemic priors. We prove that the VFE of the augmented model can be rewritten as the VFE of the predictive model plus explicit entropy-correction terms, making the EFE contribution transparent. We then show that proper EFE-based planning requires combining these epistemic corrections with a planning correction that turns marginal inference into policy optimization, yielding a full variational characterization of EFE-based planning. This clarifies which corrections are needed for cross-entropy planning and for full EFE-based planning. The same entropy-corrected formulation leads to a detailed message-passing scheme for EFE-based planning together with simpler ablations. Experiments on three grid-world environments show that full EFE-based planning outperforms ablations that omit either the planning correction or the epistemic corrections.

Designing effective chemotherapy regimens is hindered by tumor heterogeneity and drug resistance, which complicate the deployment of patient-specific model-based optimal control across diverse populations. We develop and compare closed-loop deep reinforcement learning (DRL) dosing policies with continuous (TD3) and discrete (DQN) action spaces trained on a high-dimensional heterogeneous tumor model. The DRL policies are benchmarked against a Pontryagin's Maximum Principle (PMP)-derived open-loop benchmark. We assess generalization under parametric heterogeneity using a 100-patient virtual cohort with plus or minus 10 percent uniform perturbations in growth and drug-sensitivity parameters. Across this cohort, TD3 achieves higher average tumor reduction, while DQN yields tighter inter-patient dosing consistency, revealing a clear efficacy-consistency trade-off in this study. Our simulations assume full observation of all tumor subpopulations; translation to sparse and noisy clinical measurements will require partial-observability formulations and/or state estimation. Overall, the results show that simulation-trained DRL can learn state-dependent feedback dosing policies that complement open-loop optimal control benchmarks.