Abstract

Abstract Background: Neoadjuvant Cabozantinib targeted therapy (nCabo) has been shown to facilitate tumor size reduction in patients with renal cell carcinoma (RCC). However, there is unmet clinical need to identify pre-treatment markers predictive of response to nCabo to limit financial, dose-related toxicity. We investigated computationally derived radiomic signatures from baseline magnetic resonance imaging (MRI) for their association with response to tumor shrinkage following nCabo.Methods Seventeen patients with non-metastatic, clinical stage ≥T3, biopsy-confirmed clear cell RCC were enrolled in a phase II clinical trial (NCT04022343) examining primary tumor response to nCabo. Patients underwent 3 Tesla MRI at baseline, 6 and 12 weeks. Partial response (PR) or stable disease (SD) was determined per Response Evaluation Criteria in Solid Tumors at 12 weeks. Tumor regions of interest (ROI) were delineated on axial, arterial phase T1-weighted (T1W) series under the guidance of expert radiologist. T1W were normalized with respect to enhancement in cortex region of kidney. 75 radiomic features quantifying texture heterogeneity were derived from tumor ROI on a per-voxel basis at baseline. Wilcoxon ranksum test was used to evaluate significant differences in radiomics between patient groups PR and SD. Results: Following nCabo, 6/17 patients experienced PR. 22 radiomic features from T1W quantifying intensity based heterogeneity showed significant differences between patients with SD and PR after nCabo (p<0.05; top 3 in Table). None of the clinical variables showed significant differences between SD and PR. Conclusion: In this proof-of-concept preliminary study, we observed that radiomics at baseline MRI may allow for identifying RCC patients who would favorably respond to nCabo in terms of tumor shrinkage. Future studies will include analysis on longitudinal data, correlation against survival on large-scale datasets. Association between tumor shrinkage following nCabo and radiomic features, clinical variables Stable Disease (N=6) Partial Response (N=11) Category Feature P-value median IQR median IQR Radiomic Haralick 0.01 1.50 0.51 2.31 0.51 Gradient Filter 0.02 88.06 107.28 289.58 107.28 CoLlAGe 0.03 224.28 10.73 210.50 10.73 Clinical Age 0.12 56.00 14.00 52.50 14.00 BMI 0.48 29.90 8.50 27.30 8.50 modified Glasgow Prognostic Score 0.21 1.00 1.00 0.00 1.00 Baseline Tumor Size (cm) 0.48 9.50 5.15 9.50 5.15 ECOG PS at presentation 0.23 0.00 1.00 0.00 1.00 Charlson Comorbidity Index 0.72 6.00 6.00 4.00 6.00 Citation Format: Liping LI, Edouard Nicaise, Benjamin Schmeusser, Abhishek Midya, Amir Davarpanahfakhr, Anant Madabhushi, Mehmet Asim Bilen, Viraj A. Master, Rakesh Shiradkar. Radiomics at baseline MRI are associated with tumor shrinkage in patients with unresectable renal cell carcinoma treated with neo-adjuvant Cabozantinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 894.

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