Optimizing treatment combination for lymphoma using an optimization heuristic.


University of Lyon, Lyon F-69007, France; CNRS, GATE Lyon Saint-Etienne, F-69130, France. Electronic address: [Email]


The standard treatment for high-grade non-Hodgkin lymphoma involves the combination of chemotherapy and immunotherapy. We characterize in-silico the optimal combination protocol that maximizes the overall survival probability. We rely on a pharmacokinetics/pharmacodynamics (PK/PD) model that describes the joint evolution of tumor and effector cells, as well as the effects of both chemotherapy and immunotherapy. The toxicity is taken into account through ad-hoc constraints. We develop an optimization algorithm that belongs to the class of Monte-Carlo tree search algorithms. Our simulations rely on an in-silico population of heterogeneous patients differing with respect to their PK/PD parameters. The optimization objective consists in characterizing the combination protocol that maximizes the overall survival probability of the patient population under consideration.


High-grade non-Hodgkin lymphoma,Monte-Carlo tree search,PK/PD model,Protocol combination,

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