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Although adaptive cancer therapy shows promise in integrating evolutionary dynamics into treatment scheduling, the stochastic nature of cancer evolution has seldom been taken into account. Various sources of random perturbations can impact the evolution of heterogeneous tumors, making performance metrics of any treatment policy random as well. In this paper, we propose an efficient method for selecting optimal adaptive treatment policies under randomly evolving tumor dynamics. The goal is to improve the cumulative “cost” of treatment, a combination of the total amount of drugs used and the total treatment time. As this cost also becomes random in any stochastic setting, we maximize the probability of reaching the treatment goals (tumor stabilization or eradication) without exceeding a pre-specified cost threshold (or a “budget”). We use a novel Stochastic Optimal Control formulation and Dynamic Programming to find such “threshold-aware” optimal treatment policies. Our approach enables an efficient algorithm to compute these policies for a range of threshold values simultaneously. Compared to treatment plans shown to be optimal in a deterministic setting, the new “threshold-aware” policies significantly improve the chances of the therapy succeeding under the budget, which is correlated with a lower general drug usage. We illustrate this method using two specific examples, but our approach is far more general and provides a new tool for optimizing adaptive therapies based on a broad range of stochastic cancer models. 

We consider a task of surveillance-evading path-planning in a continuous setting. An Evader strives to escape from a 2D domain while minimizing the risk of detection (and immediate capture). The probability of detection is path-dependent and determined by the spatially inhomogeneous surveillance intensity, which is fixed but a priori unknown and gradually learned in the multi-episodic setting. We introduce a Bayesian reinforcement learning algorithm that relies on a Gaussian Process regression (to model the surveillance intensity function based on the information from prior episodes), numerical methods for Hamilton-Jacobi PDEs (to plan the best continuous trajectories based on the current model), and Confidence Bounds (to balance the exploration vs exploitation). We use numerical experiments and regret metrics to highlight the significant advantages of our approach compared to traditional graph-based algorithms of reinforcement learning. 

Recent clinical trials have shown that adaptive drug therapies can be more efficient than a standard cancer treatment based on a continuous use of maximum tolerated doses (MTD). The adaptive therapy paradigm is not based on a preset schedule; instead, the doses are administered based on the current state of tumour. But the adaptive treatment policies examined so far have been largely ad hoc. We propose a method for systematically optimizing adaptive policies based on an evolutionary game theory model of cancer dynamics. Given a set of treatment objectives, we use the framework of dynamic programming to find the optimal treatment strategies. In particular, we optimize the total drug usage and time to recovery by solving a Hamilton–Jacobi–Bellman equation. We compare MTD-based treatment strategy with optimal adaptive treatment policies and show that the latter can significantly decrease the total amount of drugs prescribed while also increasing the fraction of initial tumour states from which the recovery is possible. We conclude that the use of optimal control theory to improve adaptive policies is a promising concept in cancer treatment and should be integrated into clinical trial design.