Imaging Biomarkers of Tumor Response in Neuroendocrine Liver Metastases Treated with Transarterial Chemoembolization: Can Enhancing Tumor Burden of the Whole Liver Help Predict Patient Survival?

Abstract

Purpose To investigate whether whole-liver enhancing tumor burden [ETB] can serve as an imaging biomarker and help predict survival better than World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) methods in patients with multifocal, bilobar neuroendocrine liver metastases (NELM) after the first transarterial chemoembolization (TACE) procedure. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 51 patients (mean age, 57.8 years ± 13.2; range, 13.5-85.8 years) with multifocal, bilobar NELM treated with TACE. The largest area (WHO), longest diameter (RECIST), longest enhancing diameter (mRECIST), largest enhancing area (EASL), and largest enhancing volume (ETB) were measured at baseline and after the first TACE on contrast material-enhanced magnetic resonance images. With three-dimensional software, ETB was measured as more than 2 standard deviations the signal intensity of a region of interest in normal liver. Response was assessed with WHO, RECIST, mRECIST, and EASL methods according to their respective criteria. For ETB response, a decrease in enhancement of at least 30%, 50%, and 65% was analyzed by using the Akaike information criterion. Survival analysis included Kaplan-Meier curves and Cox regressions. Results Treatment response occurred in 5.9% (WHO criteria), 2.0% (RECIST), 25.5% (mRECIST), and 23.5% (EASL criteria) of patients. With 30%, 50%, and 65% cutoffs, ETB response was seen in 60.8%, 39.2%, and 21.6% of patients, respectively, and was the only biomarker associated with a survival difference between responders and nonresponders (45.0 months vs 10.0 months, 84.3 months vs 16.7 months, and 85.2 months vs 21.2 months, respectively; P < .01 for all). The 50% cutoff provided the best survival model (hazard ratio [HR]: 0.2; 95% confidence interval [CI]: 0.1, 0.4). At multivariate analysis, ETB response was an independent predictor of survival (HR: 0.2; 95% CI: 0.1, 0.6). Conclusion Volumetric ETB is an early treatment response biomarker and surrogate for survival in patients with multifocal, bilobar NELM after the first TACE procedure. ^© RSNA, 2016.

Figure 1:

Whole-liver segmentation. Baseline contrast-enhanced arterial phase T1-weighted MR images in 60-year-old man with NELM in axial, coronal, and sagittal planes. A, Automatic segmentation produced a 3D liver segmentation mask, which was adjusted semiautomatically in control mode or contour mode. B, In control mode, an interactive balloon was expanded or contracted to include or exclude 3D regions. C, In contour mode, liver edge was identified with an arrowhead, and the software grew or shrunk the 3D liver mask accordingly. D, Images show adjustments made to original segmentation shown in A.

Figure 2:

ETB. Pre- and post-TACE contrast-enhanced arterial phase T1-weighted MR images in 70-year-old man with NELM. A 3D ROI, depicted as white box in, A, liver segmentation outline and, B, 3D mask, was placed in normal liver tissue. C, On the basis of the definition of enhancement (>2 standard deviations the ROI’s average signal intensity), the software automatically generated 3D color maps of liver, with red representing maximum enhancement and blue representing no enhancement.

Figure 3:

Kaplan-Meier survival curves. Survival difference between responders and nonresponders was statistically significant for all response cutoff values, that is, A, 30%, B, 50%, and, C, 65%. OS = overall survival.