Abstract 4139: Dual energy analysis of TKI response in GIST - results of a prospective trial
Authors: Hohenberger Peter , Meyer Mathias , Henzler Thomas , Riedel Richard F. , Messiou Christina , Marin Daniele , Schoenberg Stefan 
Published: June 2022

Abstract
Objective: Within in a prospectively conducted trial (‘Unifying Advanced Treatment With Advanced Imaging’, GISTm3, NCT 03404076) we aimed at developing and validating a CT radiomics model to predict to response to tyrosine kinase inhibitors in GIST patients. We used the intratumoral iodine concentration which is less corroborated by tumor sclerosis or intratumoral hemorrhage than classical CT criteria.
Materials and Methods: This is a prospective multi-center study of 94 patients (mean age 61 years; age range 28-83 years; 51m, 43f) who underwent a single-energy contrast-enhanced staging CT in a portal venous phase. All patients underwent subsequent preoperative imatinib therapy for at least 6 months (median 12 months, range 4-36 months) and follow-up CT examination. Patients were graded binary as responders and non-responders using their best response throughout the drug treatment course according to the vascular tumor burden to account for pseudo-progression under therapy. Response assessment was performed using RECIST 1.1, modified Choi (mChoi), vascular tumor burden (VTB), DECT vital iodine TB. Two radiologists performed a 3D-segmentation analysis of the GIST lesions on the pre-treatment CT using a dedicated radiomics software (Radiomics Version 1.0.9, Siemens Healthineers, Forchheim, Germany) and a visual evaluation of enhancement and non-enhancement parameters of each GIST lesion. Using a training dataset (n=17), a multivariable logistic regression by least absolute shrinkage and selection operator identified features that predicted therapy response was build. This model was then evaluated in the independent cohort (n=78) for temporal validation.
Results: 77 GIST lesions responded to the drug. A total of 53 radiological visual features and radiomic features were rated reproducible (intraclass correlation &gt;0.8). The radiological visual grading and the radiomic features alone resulted in a similar AUC (0.62, 95%CI 0.49-0.76 vs 0.64 95%CI 0.50-0.77). The final model which combined both radiological visual grading (3 features) and also 3 radiomic features had a significantly higher AUC (0.75, 95%CI 0.64-0.86; both p&lt;0.01) when compared to both separate predictive models alone. Using DECT vital iodine TB, median PFS was significantly different between non-responders and responders (18.8 mos vs. 5.6 mos, resp.; p=.02). HR for progression for DECT vital iodine TB non-responders vs. responders was 6.9, 3.3 for VTB, 2.3 for RECIST 1.1, and 2.1 for mChoi.
Conclusion: The study presents a predictive model that incorporates radiologist grading and radiomics features. DECT vital iodine TB criteria outperformed RECIST 1.1, VTB and mChoi for response assessment of metastatic GIST under TKI therapy. The technique should be very useful in guiding early management decisions in patients.
Citation Format: Peter Hohenberger, Mathias Meyer, Thomas Henzler, Richard F. Riedel, Christina Messiou, Daniele Marin, Stefan Schoenberg. Dual energy analysis of TKI response in GIST - results of a prospective trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4139.