Visual and quantitative evaluation of [18F]FES and [18F]FDHT PET in patients with metastatic breast cancer: an interobserver variability study

Lemonitsa H Mammatas, Clasina M Venema, Carolina P Schröder, Henrica C W de Vet, Michel van Kruchten, Andor W J M Glaudemans, Maqsood M Yaqub, Henk M W Verheul, Epie Boven, Bert van der Vegt, Erik F J de Vries, Elisabeth G E de Vries, Otto S Hoekstra, Geke A P Hospers, C Willemien Menke-van der Houven van Oordt, Lemonitsa H Mammatas, Clasina M Venema, Carolina P Schröder, Henrica C W de Vet, Michel van Kruchten, Andor W J M Glaudemans, Maqsood M Yaqub, Henk M W Verheul, Epie Boven, Bert van der Vegt, Erik F J de Vries, Elisabeth G E de Vries, Otto S Hoekstra, Geke A P Hospers, C Willemien Menke-van der Houven van Oordt

Abstract

Purpose: Correct 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.

Methods: In 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.

Results: Visual 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.

Conclusion: Visual 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 registration: ClinicalTrials.gov, NCT01988324. Registered 20 November 2013, https://ichgcp.net/clinical-trials-registry/NCT01988324?term=FDHT+PET&draw=1&rank=2.

Keywords: Androgen receptor; Breast cancer; FDHT PET; FES PET; Interobserver variability; Oestrogen receptor.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Tumour lesions detected with conventional imaging, [18F]FES and [18F]FDHT PET
Fig. 2
Fig. 2
The difference in tumour-background ratio between [18F]FES and [18F]FDHT PET shown visually (a) and quantitatively (mean ± SD) for bone and lymph node lesions (b). The arrows in a show a bone lesion in the right os ilium visible on [18F]FES PET which is only subtly visible on [18F]FDHT PET. Note, there is physiological tracer uptake of [18F]FES in the liver, gallbladder, intestine, bladder and for [18F]FDHT also in the bloodpool
Fig. 3
Fig. 3
Intraclass correlation coefficients for all quantified tumour lesions on [18F]FES (n = 94) using SUVmax, SUVpeak and SUVmean (a, b and c) and [18F]FDHT PET (n = 95) (d, e and f). Note: not quantifiable lesions by one or both of the observers were excluded as a result of overlap with adjacent organs with high physiological tracer uptake
Fig. 4
Fig. 4
Bland Altman plots showing the % differences in SUVmax, SUVpeak and SUVmean between observers for lesions visible on [18F]FES PET (a, b, c) or only visible on conventional imaging (d, e, f). The dashed lines represent the mean difference between observers ± 95% limits of agreement (LOA95%)
Fig. 5
Fig. 5
Bland Altman plots showing the % differences in SUVmax, SUVpeak and SUVmean between observers for lesions visible on [18F]FDHT PET (a, b, c) or only visible on conventional imaging (d, e, f)

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