Practical guide to implementing pre-emptive pharmacogenetic screening in routine pediatric oncology care.

Interindividual variability in drug response is a challenge in pediatric oncology, where the risk of treatment-related toxicity is exacerbated by narrow therapeutic windows and combination therapies. Pharmacogenetics (PGx) aims to reduce this variability by linking genetic variants to differences in drug pharmacokinetics, efficacy, and toxicity. Although evidence-based pharmacogenetic guidelines are available covering over 100 gene-drug pairs, systematic use of pre-emptive PGx screening is not yet embedded in routine pediatric oncology care. In a recent study, we demonstrated the relevance of pre-emptive PGx screening in pediatric oncology by showing that 16% of 1,151 patients were eligible for genotype-based drug dose or treatment modifications. Building on these findings, we implemented pre-emptive PGx screening into clinical practice of pediatric oncology in the Netherlands. Successful implementation required addressing challenges, including adaptation of existing infrastructure, interpretation of pharmacogenetic results for a pediatric population, integration into electronic health records, and education of clinical staff. We repurposed diagnostic germline whole genome sequencing (WGS) for individual genetic profiling and applied existing pharmacogenetic guidelines to guide drug dosing and treatment decisions. Here, we describe our implementation strategy for pre-emptive PGx screening in pediatric oncology and share insights to support other centers aiming to integrate PGx screening into routine care.