Dual Energy CT for Monitoring Targeted Therapies in Patients with Advanced Gastrointestinal Stromal Tumor: Initial Results

N.      Schramm; M.      Schlemmer; E.      Englhart; M.      Hittinger; C.      Becker; M.      Reiser; F.      Berger

doi:10.2174/138920111795164066

Abstract

Purpose: Advanced gastrointestinal stromal tumors (GISTs) are treated with tyrosine kinase inhibitors, which also have antiangiogenic properties. Dual-energy CT (DECT) allows to acquire semi-quantitative iodine images which might correlate with blood pool and tumor vascularity. In this feasibility-study, we correlated lesional iodine uptake estimations in correlation to tumor size changes under targeted therapy as first step in the evaluation of dedicated DECT based strategies for monitoring molecular therapies in GIST. Patients and Methods: 48 tumor lesions in 18 patients with metastasized histologically proven GIST under tyrosine kinase inhibitor (TKI) therapy were analyzed. Patients were examined with a dual-source CT in dual-energy mode (Voltage tube A: 80 kV, tube B: 140 kV). Using the dual-energy software virtual unenhanced, selective iodine (overlay) and mixed CT numbers (similar to CT numbers at 120 kV) of lesions were calculated. The largest diameter of each lesion on cross-sectional axial images was measured. The mean difference of overlay CT numbers in the baseline and follow-up examinations was calculated and this marker of lesional iodine uptake was compared to lesional size changes under molecular therapy. Results: Utilizing the cut-off value 15 HU of change in overlay, DECT allowed to identify lesions with a stable, increased or decreased lesional iodine uptake with corresponding typical lesion size change patterns after 3 months of targeted therapy: 30 lesions had no significant change of overlay CT numbers (OL) (mean: -2.4 HU) or lesion size (mean: +1.5%). A strong decline of the OL (mean: - 24 HU) in 13 lesions was combined with a pronounced growth (mean: + 26%). 5 lesions showed a strong increase of the absolute OL (mean: + 23 HU) associated with a moderate increase in size (+ 8%). Conclusion: Determination of the overlay CT number with DECT enables to stratify metastases with stable, increasing or decreasing iodine uptake over time with – in our collective- typical lesion size change patterns. Investigation of a larger patient cohort, comparison to histology, alternate imaging biomarkers and correlatrion to long-term response will further clarify the significance of these findings for monitoring targeted therapies in GIST.

Keywords: GIST, Dual energy, CT, targeted therapy, therapy monitoring, Dual-energy CT (DECT), semi-quantitative iodine images, lesional iodine uptake, molecular therapies, tyrosine kinase inhibitor (TKI) therapy, lesion size, imaging biomarkers, radiotherapy, pharmacotherapy, imaging based response assessment