Predicting chemotherapy-induced thrombotoxicity by NARX neural networks and transfer learning

J Cancer Res Clin Oncol. 2024 Oct 14;150(10):457. doi: 10.1007/s00432-024-05985-y.

Abstract

Background: Thrombocytopenia is a common side effect of cytotoxic chemotherapies, which is often dose-limiting. Predicting an individual's risk is of high clinical importance, as otherwise, a small subgroup of patients limits dosages for the overall population for safety reasons.

Methods: We aim to predict individual platelet dynamics using non-linear auto-regressive networks with exogenous inputs (NARX). We consider different architectures of the NARX networks, namely feed-forward networks (FNN) and gated recurrent units (GRU). To cope with the relative sparsity of individual patient data, we employ transfer learning (TL) approaches based on a semi-mechanistic model of hematotoxicity. We use a large data set of patients with high-grade non-Hodgkin's lymphoma to learn the respective models on an individual scale and to compare prediction performances with that of the semi-mechanistic model.

Results: Of the examined network models, the NARX with GRU architecture performs best. In comparison to the semi-mechanistic model, the network model can result in a substantial improvement of prediction accuracy for patients with irregular dynamics, given well-spaced measurements. TL improves individual prediction performances.

Conclusion: NARX networks can be utilized to predict an individual's thrombotoxic response to cytotoxic chemotherapy treatment. For reasonable model learning, we recommend at least three well-spaced measurements per cycle: at baseline, during the nadir phase and during the recovery phase. We aim at generalizing our approach to other treatment scenarios and blood lineages in the future.

Keywords: Artificial intelligence; Haematopoiesis; Non-Hodgkin’s lymphoma; Non-linear autoregressive models; Precision medicine; System identification.

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy
  • Neural Networks, Computer*
  • Thrombocytopenia* / chemically induced
  • Thrombosis / chemically induced

Substances

  • Antineoplastic Agents