Measuring Tumour Imatinib Concentrations in Gastrointestinal Stromal Tumours: Relevant or Redundant?

SIMPLE SUMMARY: It is largely unknown how imatinib distributes within gastrointestinal stromal tumours (GISTs) and whether imatinib plasma concentrations correlate with tumour concentrations, whilst plasma concentrations are used to optimize treatment. In this exploratory study imatinib tumour concentrations were measured in different tumour regions after neoadjuvant treatment. The goal of this study was to reveal tumour distribution patterns and to investigate the possible correlation between plasma and tumour concentrations. Imatinib appears to accumulate in tumour tissue since tumour concentrations were higher compared to plasma concentrations. No clear distribution pattern within the tumour could be identified. Interpatient variability in tumour concentration was almost threefold higher than interindividual variability in plasma concentration. No correlation between tumour and plasma concentrations could be identified, nor with pathological treatment response. ABSTRACT: Imatinib plasma trough concentrations are associated with efficacy for patients treated for advanced or metastatic KIT-positive gastrointestinal stromal tumours (GISTs). This relationship has not been studied for patients treated in the neoadjuvant setting, let alone its correlation with tumour drug concentrations. In this exploratory study we aimed to determine the correlation between plasma and tumour imatinib concentrations in the neoadjuvant setting, investigate tumour imatinib distribution patterns within GISTs, and analyse its correlation with pathological response. Imatinib concentrations were measured in both plasma and in three regions of the resected primary tumour: the core, middle part, and periphery. Twenty-four tumour samples derived from the primary tumours of eight patients were included in the analyses. Imatinib tumour concentrations were higher compared to plasma concentrations. No correlation was observed between plasma and tumour concentrations. Interpatient variability in tumour concentrations was high compared to interindividual variability in plasma concentrations. Although imatinib accumulates in tumour tissue, no distribution pattern of imatinib in tumour tissue could be identified. There was no correlation between imatinib concentrations in tumour tissue and pathological treatment response.