Pilot study of angiogenic response to yttrium-90 radioembolization with resin microspheres.

PURPOSE: To investigate the impact of radioembolization with yttrium-90 resin microspheres on the regulation of angiogenesis through observation of serial changes in a spectrum of angiogenic markers and other cytokines after therapy. MATERIALS AND METHODS: This prospective pilot study enrolled 22 patients with liver-dominant disease deriving from biopsy-proven hepatocellular carcinoma (HCC) (n = 7) or metastatic colorectal carcinoma (mCRC) (n = 15). Circulating angiogenic markers were measured from serum samples drawn at baseline and at time points after therapy ranging from 6 hours to 120 days. Using multiplex enzyme-linked immunosorbent assay, several classic angiogenesis factors (vascular endothelial growth factor [VEGF], angiopoietin-2 [Ang-2], basic fibroblast growth factor [bFGF], platelet-derived growth factor subunit BB [PDGF-BB], thrombospondin-1 [Tsp-1]) and nonclassic factors (follistatin, leptin, interleukin [IL]-8) were evaluated. RESULTS: Increases in cytokine levels ≥ 50% over baseline were observed in more than half of all patients studied for many cytokines, including classic angiogenic factors such as VEGF, Ang-2, and Tsp-1 as well as nonclassic factors IL-8 and follistatin (range, 36%-82% for all cytokines). Baseline cytokine levels in patients with overall survival (OS) < 6 months differed significantly from patients with longer survival for Ang-2 (P = .033) and IL-8 (P = .041). Patients with OS ≤ 6 months exhibited transient increases in VEGF and PDGF-BB after therapy compared with patients with OS > 6 months. CONCLUSIONS: Radioembolization is associated with early transient increases in many angiogenic cytokines. In this small sample size, some of these changes were associated with worse OS. This research has important implications for future studies of radioembolization with antiangiogenic therapy performed during and after the procedure.

Evaluation of hepatic tumor response to yttrium-90 radioembolization therapy using texture signatures generated from contrast-enhanced CT images.

RATIONALE AND OBJECTIVES: The aim of this study was to explore the use of texture features generated from liver computed tomographic (CT) datasets as potential image-based indicators of patient response to radioembolization (RE) with yttrium-90 ((90)Y) resin microspheres, an emerging locoregional therapy for advanced-stage liver cancer. MATERIALS AND METHODS: Overall posttherapy survival and percent change in serologic tumor marker at 3 months posttherapy represent the primary clinical outcomes in this study. Thirty advanced-stage liver cancer cases (primary and metastatic) treated with RE over a 3-year period were included. Texture signatures for tumor regions, which were delineated to reveal boundaries with normal regions, were computed from pretreatment contrast-enhanced liver CT studies and evaluated for their ability to classify patient serologic response and survival. RESULTS: A series of systematic leave-one-out cross-validation studies using soft-margin support vector machine (SVM) classifiers showed hepatic tumor texton and local binary pattern (LBP) signatures both achieve high accuracy (96%) in discriminating subjects in terms of their serologic response. The image-based indicators were also accurate in classifying subjects by survival status (80% and 93% accuracy for texton and LBP signatures, respectively). CONCLUSIONS: Hepatic texture signatures generated from tumor regions on pretreatment triphasic CT studies were highly accurate in differentiating among subjects in terms of serologic response and survival. These image-based computational markers show promise as potential predictive tools in candidate evaluation for locoregional therapy such as RE.