Individual modelling of haematotoxicity with NARX neural networks: A knowledge transfer approach()()()()

Cytotoxic cancer therapy often results in dose-limiting haematotoxic side effects. Predicting an individual's risk is a major objective in precision medicine of cancer treatment. In this regard, patient heterogeneity presents a significant challenge. In this paper, we explore the use of hypothesis-free machine learning models based on recurrent nonlinear auto-regressive networks with exogenous inputs (NARX) as an approach to achieve this goal. Also, we propose a knowledge transfer approach to ameliorate the issue of sparse individual data, which typically hampers learning of individual networks. We demonstrate the feasibility of our approach based on a virtual patient population generated using a semi-mechanistic model of haematopoiesis and imposing different cytotoxic therapy scenarios on it. Employing different techniques of model optimisation, we derive robust and parsimonious individual networks with good generalisation performances. Moreover, we analyse in detail possible factors influencing the generalisation performance. Results suggest that our transfer learning approach using NARX networks can provide robust predictions of individual patient's response to treatment. As a practical perspective, we apply our approach to individual time series data of two patients with non-Hodgkin's lymphoma.