Abstract

PurposeCorrect identification of tumour receptor status is important for treatment decisions in breast cancer. [18F]FES PET and [18F]FDHT PET allow non-invasive assessment of the oestrogen (ER) and androgen receptor (AR) status of individual lesions within a patient. Despite standardised analysis techniques, interobserver variability can significantly affect the interpretation of PET results and thus clinical applicability. The purpose of this study was to determine visual and quantitative interobserver variability of [18F]FES PET and [18F]FDHT PET interpretation in patients with metastatic breast cancer.MethodsIn this prospective, two-centre study, patients with ER-positive metastatic breast cancer underwent both [18F]FES and [18F]FDHT PET/CT. In total, 120 lesions were identified in 10 patients with either conventional imaging (bone scan or lesions > 1 cm on high-resolution CT, n = 69) or only with [18F]FES and [18F]FDHT PET (n = 51). All lesions were scored visually and quantitatively by two independent observers. A visually PET-positive lesion was defined as uptake above background. For quantification, we used standardised uptake values (SUV): SUVmax, SUVpeak and SUVmean.ResultsVisual analysis showed an absolute positive and negative interobserver agreement for [18F]FES PET of 84% and 83%, respectively (kappa = 0.67, 95% CI 0.48–0.87), and 49% and 74% for [18F]FDHT PET, respectively (kappa = 0.23, 95% CI − 0.04–0.49). Intraclass correlation coefficients (ICC) for quantification of SUVmax, SUVpeak and SUVmean were 0.98 (95% CI 0.96–0.98), 0.97 (95% CI 0.96–0.98) and 0.89 (95% CI 0.83–0.92) for [18F]FES, and 0.78 (95% CI 0.66–0.85), 0.76 (95% CI 0.63–0.84) and 0.75 (95% CI 0.62–0.84) for [18F]FDHT, respectively.ConclusionVisual and quantitative evaluation of [18F]FES PET showed high interobserver agreement. These results support the use of [18F]FES PET in clinical practice. In contrast, visual agreement for [18F]FDHT PET was relatively low due to low tumour-background ratios, but quantitative agreement was good. This underscores the relevance of quantitative analysis of [18F]FDHT PET in breast cancer.Trial registrationClinicalTrials.gov, NCT01988324. Registered 20 November 2013, https://clinicaltrials.gov/ct2/show/NCT01988324?term=FDHT+PET&draw=1&rank=2.

Highlights

  • Breast cancer is the most common malignancy in women in the Western world

  • Visual agreement for [18F]FDHT PET was relatively low due to low tumour-background ratios, but quantitative agreement was good. This underscores the relevance of quantitative analysis of [18F]FDHT PET in breast cancer

  • The androgen receptor (AR) is present in 70–80% of patients with breast cancer, and AR antagonists are under investigation in clinical trials [3,4,5,6]

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Summary

Introduction

The majority of breast tumours express the oestrogen receptor (ER), which is the main indicator of potential response to anti-oestrogen therapies [1, 2]. A tumour biopsy is the gold standard to determine receptor expression. This is an invasive procedure, is not always feasible in case of inaccessible tumour sites, and is subject to sampling errors [7]. The 16α-[18F]fluoro17β-oestradiol ([18F]FES) and 16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT) PET/CT have been developed to non-invasively visualise, respectively, the ER and AR status in the tumour lesions within a patient. It has been shown that [18F]FES and [18F]FDHT uptake correlate well with ER and AR expression levels in representative breast cancer biopsies [8,9,10]. As a diagnostic tool, [18F]FES PET leads to better diagnostic understanding in

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