The Attenuation Distribution Across the Long Axis of Breast Cancer Liver Metastases at CT: A Quantitative Biomarker for Predicting Overall Survival.

Abstract

The objective of our study was to compare attenuation distribution across the long-axis (ADLA) measurements, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and Choi criteria for predicting overall survival (OS) in patients with metastatic breast cancer treated with bevacizumab. We obtained HIPAA-compliant data from a prospective, multisite, phase 3 trial of bevacizumab for the treatment of metastatic breast cancer. For patients with one or more liver metastases measuring 15 mm or larger at baseline, we evaluated up to two target liver lesions using RECIST, Choi criteria, and ADLA measurements, with the latter defined as the SD of the CT attenuation values of each pixel along the tumor long-axis diameter. The optimal percentage change threshold for defining an ADLA response was computed by cross-validation analysis in a Cox model. The log-rank test was applied to evaluate RECIST, Choi criteria, and ADLA for discriminating patients with superior OS. The predictive accuracies of all three techniques were compared using Brier scores and areas under the ROC curve (AUC). All analyses were performed separately using best overall response (BOR) and response at the first follow-up time point (FU1). One hundred sixty-four patients met the inclusion criteria. A 25% decrease in the ADLA measurement from baseline was the optimal ADLA response threshold for BOR and FU1. RECIST, Choi criteria, and ADLA successfully identified patients with superior OS when using BOR (RECIST, p = 0.02; Choi and ADLA, p < 0.001), but only Choi criteria and ADLA measurements were successful when using FU1 (RECIST, p = 0.43; Choi and ADLA, p < 0.001). In a direct comparison, ADLA measurements outperformed both RECIST and Choi criteria using BOR (95% CI for Brier score differences, ADLA-RECIST [-0.58 to -0.08] and ADLA-Choi [-0.55 to -0.06]; 95% CI for AUC differences, ADLA-RECIST [0.16-0.33] and ADLA-Choi [0.17-0.36]) as well as using FU1 (95% CI for Brier score differences, ADLA-RECIST [-0.77 to -0.08] and ADLA-Choi [-0.58 to -0.03]; 95% CI for AUC differences, ADLA-RECIST [0.22-0.39] and ADLA-Choi [0.01-0.22]). ADLA measurements may be a useful noninvasive indicator of cancer treatment response. Because ADLA measurements may be extracted relatively easily using existing radiologist workflows, further investigation of the ADLA technique is warranted.