Adaptive Chemotherapy Control under Tumor Heterogeneity via Reinforcement Learning

Chemotherapy dose optimization can be formulated as a dynamic treatment regime, requiring sequential decisions under uncertainty that must balance tumor suppression against toxicity. However, most reinforcement learning approaches assume full observability of the patient state, a condition rarely met in clinical practice. We investigate whether memory-augmented policies can improve chemotherapy control under partial observability. To this end, we employ a recurrent TD3-based approach with separate LSTM actor-critic networks and evaluate it on the AhnChemoEnv benchmark from DTR-Bench, considering both off-policy and on-policy recurrent architectures against feed-forward TD3 and Soft Actor-Critic. Pharmacokinetic and pharmacodynamic variability are held fixed to isolate hidden-state uncertainty and observation noise and to avoid confounding effects from inter-patient variability. Across ten random seeds, recurrence yields modest benefit under full observability but substantially stronger and more stable performance under partial observability, with more consistent tumor suppression and improved normal-cell preservation. These findings indicate that memory-based policies are particularly beneficial when clinically relevant state information is incomplete or noisy.

Cancer treatment is at the core a sequential decision-making problem with partial observability, latent patient heterogeneity, and explicit constraints on the budget for medical measurements. Unlike standard Reinforcement Learning (RL) approaches that control state trajectories, cancer treatments permanently modify patients' transition dynamics, changing how states evolve over time. We model cancer treatment as a belief-space planning problem using active inference, deriving an expected free-energy objective that unifies goal-directed control and information acquisition under measurement budgets without. We implement this framework using real clinical cancer data from the AACR Project GENIE Biopharma Collaborative dataset. Results on clinical data demonstrate a simultaneous patient categorization and high treatment efficacy, under real measurement and treatment constraints.

Brain tumor progression exhibits spatially heterogeneous growth, patient-specific treatment response, and complex interactions with surrounding anatomy, making accurate long-term prediction challenging. We propose an AI-augmented adaptive digital twin (DT) framework for brain tumor evolution prediction and treatment scheduling. The framework integrates an interpretable reaction--diffusion (RD) model, a 3D residual learning module for model-form correction, patient-specific DT updating during recursive rollout, and model predictive control (MPC) for constrained chemotherapy and radiotherapy scheduling. Experiments on 387 synthetic tumor trajectories with 120-step evolution show that the baseline RD model captures tumor location and overall temporal behavior but underestimates heterogeneous tumor burden during long-horizon prediction. Hybrid RD--residual modeling reduces masked voxel-wise mean squared error by 84.3% and increases Dice overlap by 43.5% relative to the RD baseline under dense simulated observations. Online DT updating further reduces mean squared error by 45.9% and improves Dice overlap by 9.6% compared with the non-updated hybrid model. In MPC-based scheduling simulations, the updated DT controller reduces final tumor burden by 22.4% relative to a fixed treatment schedule under the terminal-burden objective. Together, these results demonstrate a unified framework for patient-specific initialization, mechanistic modeling, adaptive learning, and constrained treatment optimization. Although validated using patient-data-informed synthetic trajectories rather than clinical longitudinal data, the proposed framework establishes a foundation for future translation to real-world adaptive treatment planning.