Abstract B024: Tumor Resection Status Modulates Cardiometabolic Response to Imatinib in GIST

Abstract Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the GI tract. Depending on tumor risk, surgery and imatinib are standard treatment options; however, for metastatic disease, systemic imatinib therapy alone is the standard of care. Notably, imatinib has been shown to influence metabolic effects, especially on lipid and glycemic profiles. In this study, we compare the effects of imatinib on resected versus unresected/metastatic GIST patients, aiming to understand if tumor burden modulates imatinib’s effects on metabolism. Methods: This retrospective cohort study utilizes de-identified patient data from the TriNetX database, which compiles information from over 170 million individuals across 145 healthcare systems in 18 countries. We evaluated metabolic biomarkers including total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), TG/HDL ratio, low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c, body mass index (BMI), and thyroid-stimulating hormone (TSH). Results: In patients with resected GIST on imatinib (N=148), total cholesterol, TG, and LDL showed significant (p<0.05) negative correlations (R=-0.71, R=-0.73, R=-0.67, respectively) over the 24 month treatment duration. No significant associations were observed for HDL, TGL/HDL ratio, hemoglobin A1c, BMI or TSH (p>0.05). In unresected GIST patients (N=112) on imatinib, TG and TGL/HDL decreased significantly (p<0.05, R=-0.68, R=-0.74) while HDL increased significantly (p<0.05, R=0.90). No significant associations were noted for total cholesterol, LDL, A1c, BMI and TSH (p>0.05). Conclusion: This study found that GIST tumor status may potentiate imatinib’s metabolic effects. In the resected cohort, the significant negative downtrends in total cholesterol and LDL may indicate that tumor removal could be alleviating the chronic inflammatory and metabolic demands utilized by neoplastic tissue - possible due imatinib’s OCTN2 effects on carnitine transport, fatty acid absorption, and total cholesterol and LDL uptake. Conversely, in the unresected cohort, the improvement in TG, HDL and TG/HDL ratio could suggest an anti-inflammatory response driven by ongoing tumor burden. We also suspect that the absence of improvements in LDL or total cholesterol are due to active disease interfering with lipid metabolism. These findings highlight the importance of considering tumor status when evaluating GIST patients’ lipid biomarkers. Citation Format: Allen Seylani, Allen L. Luo, Assal Sadighian, Yohannes Haile, Sadaf Sadighian. Tumor Resection Status Modulates Cardiometabolic Response to Imatinib in GIST [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr B024.