Association between multitarget tyrosine kinase inhibitors and changes in CT appearance of submucosal fat in the gastrointestinal tract

Abstract

Introduction: Submucosal fat deposition (SMF) in the gastrointestinal tract can be seen in patients treated with vascular endothelial growth factor receptor multitarget tyrosine kinase inhibitors (mtTKIs). We aimed to assess the association between mtTKIs treatment and appearance of SMF on computed tomography (CT). Methods: We performed retrospective evaluation of patients who started mtTKI treatment between 2016 and 2018, with a comparison patient cohort treated with single-target tyrosine kinase inhibitors (stTKIs). SMF amount for each gastrointestinal tract segment (stomach, duodenum, jejunum, ileum, terminal ileum, right colon, left colon) was scored as follows: 0 = none; 1 = low amount (<2 mm thick); 2 = high amount (>2 mm layer). For each CT, segment scores were aggregated to create an SMF index (SMFI). Maximal increase in SMFI between pretreatment and posttreatment CTs was documented. SMF ⩾3 was defined as positive. Results: Forty patients treated with mtTKIs and 23 patients receiving stTKIs were included. Maximal increase in SMFI during treatment was 0–1 in 56/63 patients (89%) and 3–6 in 7/63 patients (11%). All patients with positive SMFI received mtTKIs compared to 0 patients treated with stTKIs (17.5% vs. 0%; p = 0.04). mtTKI treatment was associated with higher incidence of nausea/vomiting (4/7) and diarrhea (4/7) when positive SMF was noted, as compared to patients with negative SMF (6/33 patients each; p = 0.048). Conclusion: Gastrointestinal tract SMF deposition occurs in a considerable proportion of patients treated with mtTKIs with association to abdominal symptoms. This may be unique to mtTKIs and was not found in patients receiving stTKIs.