Vascular Tumor Burden as a New Quantitative CT Biomarker for Predicting Metastatic RCC Response to Antiangiogenic Therapy

Abstract

Purpose To quantify initial changes in the vascular tumor burden (VTB), a measure of the area of vascularized tumor on computed tomographic (CT) images, and predict tumor response to antiangiogenic therapy in patients with metastatic renal cell carcinoma (RCC). Materials and Methods For this institutional review board-approved HIPAA-compliant secondary analysis of a prospective phase III trial, adult patients with digital CT images and metastatic clear-cell RCC treated with sunitinib were included (n = 275). Target lesions were selected by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines, and the CT images obtained after one cycle of sunitinib therapy were evaluated in comparison with baseline images. Tumor-response software was created to quantify tumor metrics (length, area, VTB, and mean attenuation) and automate response assessment. Progression-free survival (PFS) in responders and nonresponders according to VTB criteria was compared by using the Cox proportional hazard ratio (HR). The intraclass correlation coefficient (ICC) was used to assess interobserver agreement among three readers evaluating 28 randomly selected patients. Results VTB criteria nonresponders (n = 120) according to the initial posttherapy CT study were 5.7 times more likely to experience progression of disease (HR = 5.70; 95% confidence interval [CI]: 4.07, 7.97; P < .001) than responders (n = 155). There was not a statistically significant difference in PFS between RECIST nonresponders (n = 255) and responders (n = 20; HR = 1.54; 95% CI: 0.85, 2.77; P = .148). In a patient-level analysis, interobserver agreement was very good for assessing percentage change in length, area, and VTB (ICC = 0.82 [95% CI: 0.67, 0.91], 0.89 [95% CI: 0.79, 0.94], and 0.88 [95% CI: 0.79, 0.94], respectively) but was very poor for assessing percentage change in mean attenuation (ICC = 0.17 [95% CI: -0.05, 0.45]). Conclusion A quantitative CT imaging biomarker designed to measure initial changes in the VTB separated patients into responders and nonresponders, each with significantly different PFS, and showed very good interobserver agreement in patients with metastatic RCC treated with sunitinib. RSNA, 2016 Online supplemental material is available for this article.

Initial computed tomography imaging details during first-line systemic therapy is of significant prognostic value in patients with naïve, unresectable metastatic renal cell carcinoma

“…While the mean attenuation number representing the degree of enhancement and tumor density of the baseline primary renal lesion was a significant independent predictor of OS on multivariate analysis, the mean change in attenuation during therapy was not consistent with that found by Smith et al [33]. We attribute this to the small sample size and intra-operator variability in measuring the enhancement within the primary renal lesions (S1 Table, S1 and S2 Figs) [25].…”

Comparative effectiveness of tumor response assessment methods: Standard-of-care versus computer-assisted response evaluation.

“…and iteratively improved upon in collaboration with software engineers from ImageIQ. 22 In brief, eMASS software was designed to facilitate CARE of target lesions on baseline and initial post-therapy imaging studies by providing stepwise guidance of the required measurements and observations, interactive error identification and correction methods, and automated tumor metric extraction, calculations, response categorization, and data/image archiving. The software identifies common errors in tumor response assessment and implements corrective measures as detailed in Table 2.…”

“…20,21 A computer-assisted response evaluation (CARE) system has been developed to guide readers through and to automate many of the steps in tumor response assessment with the goal of reducing errors and improving efficiency and documentation. 22 In this study, we compared the effectiveness of metastatic tumor response evaluation in patients with RCC using standard of care versus a CARE method.…”

Imaging and Screening of Kidney Cancer

“…A recent study evaluating the use of DECT in patients on antiangiogenic therapy suggested iodine maps may be more sensitive in the detection of an early response when compared to traditional measurements of attenuation 115 . The use of automated segmentation algorithms to identify the amount of viable, enhancing tumor burden may facilitate the assessment of RCC response to TKIs 116 .…”