Supplementary results Table S1. Agreement of predefined classifiers (n=90). Figure S1. Scatterplot of imaging parameter agreement. Figure S2. Association of clinical benefit (progression-free survival > 6 months on endocrine therapy) with quantitative imaging biomarkers predicting endocrine response, defined in Table 1. A. FES dynSUV B. FES SULmean3 C. FES/FDG ratio3. â-¬ is median, â-Š is mean. None are associated with PFS6 by logistic regression (N=76, Wald test p>0.10). Figure S3. Results of analysis using recursive partitioning to predict PFS by selected imaging parameters (FES SUVmax3, FES SULmax3, and FDG SUVmax3) Figure S4. Association of log(FDG SULmax) with reconstruction of the same scan by filtered back-projection (X axis) or ordered-subset expectation maximization (Y axis). Figure S5. Association FES SULmean with reconstruction of the same scan by filtered backprojection (X axis) or ordered-subset expectation maximization (Y axis) for 93 lesions in 16 patients from this study.
ARTICLE ABSTRACT
Purpose:18F-fluoroestradiol (FES) PET scans measure regional estrogen binding, and 18F-fluorodeoxyglucose (FDG) PET measures tumor glycolytic activity. We examined quantitative and qualitative imaging biomarkers of progression-free survival (PFS) in breast cancer patients receiving endocrine therapy.Experimental Design: Ninety patients with breast cancer from an estrogen receptor–positive (ER+), HER2− primary tumor underwent FES PET and FDG PET scans prior to endocrine therapy (63% aromatase inhibitor, 22% aromatase inhibitor and fulvestrant, 15% other). Eighty-four had evaluable data for PFS prediction.Results: Recursive partitioning with 5-fold internal cross-validation used both FES PET and FDG PET measures to classify patients into three distinct response groups. FDG PET identified 24 patients (29%) with low FDG uptake, suggesting indolent tumors. These patients had a median PFS of 26.1 months (95% confidence interval, 11.2–49.7). Of patients with more FDG-avid tumors, 50 (59%) had high average FES uptake, and 10 (12%) had low average FES uptake. These groups had median PFS of 7.9 (5.6–11.8) and 3.3 months (1.4–not evaluable), respectively. Patient and tumor features did not replace or improve the PET measures' prediction of PFS. Prespecified endocrine resistance classifiers identified in smaller cohorts did not individually predict PFS.Conclusions: A wide range of therapy regimens are available for treatment of ER+ metastatic breast cancer, but no guidelines are established for sequencing these therapies. FDG PET and FES PET may help guide the timing of endocrine therapy and selection of targeted and/or cytotoxic chemotherapy. A multicenter trial is ongoing for external validation. Clin Cancer Res; 23(2); 407–15. ©2016 AACR.
