Multi-Criteria Optimization of Multi-Stage Neuroblastoma Chemotherapy Based on a Nonlinear Compromise Scheme and the Hybrid Padé-Adomian-MSDTM Method

An algorithm for multi-criteria optimization of the multi-stage neuroblastoma chemotherapy process has been developed, based on Voronin's nonlinear compromise scheme and the hybrid Padé-Adomian-MsDTM. The terminal control problem for chemotherapeutic drug concentration is formulated as the minimization of a vector criterion that includes tumor burden, total toxicity, immune deficit, and control energy, subject to terminal conditions on residual tumor mass. The application of the differential transformation apparatus allows partial criteria to be expressed as analytical functions of the control free-parameter vector, reducing the multi-criteria problem to solving a system of nonlinear algebraic equations without numerical ODE integration. Numerical simulation results for various neuroblastoma morphotypes confirm the algorithm's ability to flexibly adapt the treatment strategy: a reduction in systemic toxicity of 6-62% and minimization of immune deficit by 47% are achieved while guaranteeing the target therapeutic outcome.