18F]FDG and [18F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary.

Joline F Roze,Arthur J.A.T Braat,Jolijn W Groeneweg,Glen R Monroe,Ronald P Zweemer,Wouter B Veldhuis,Hannah S Van Meurs,Geertruida N Jonges,Petronella O Witteveen,Roel J Bennink,Luc R.C.W Van Lonkhuijzen

doi:10.18632/oncotarget.27925

Joline F Roze, Arthur J.A.T Braat + Show 9 more

Open Access

https://doi.org/10.18632/oncotarget.27925

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Abstract

Purpose: Adult granulosa cell tumors (AGCTs) of the ovary represent a rare malignancy in which timing and choice of treatment is a clinical challenge. This study investigates the value of FDG-PET/CT and FES-PET/CT in monitoring recurrent AGCTs and assessing eligibility for anti-hormonal treatment.Materials and Methods: We evaluated 22 PET/CTs from recurrent AGCT patients to determine tumor FDG (n = 16) and FES (n = 6) uptake by qualitative and quantitative analysis. We included all consecutive patients from two tertiary hospitals between 2003-2020. Expression of ERα and ERβ and mitoses per 2 mm2 were determined by immunohistochemistry and compared to FES and FDG uptake, respectively.Results: Qualitative assessment showed low-to-moderate FDG uptake in most patients (14/16), and intense uptake in 2/16. One patient with intense tumor FDG uptake had a high mitotic rate (18 per 2 mm2) Two out of six patients showed FES uptake on PET/CT at qualitative analysis. Lesion-based quantitative assessment showed a mean SUVmax of 2.4 (± 0.9) on FDG-PET/CT and mean SUVmax of 1.7 (± 0.5) on FES-PET/CT. Within patients, expression of ERα and ERβ varied and did not seem to correspond with FES uptake. In one FES positive patient, tumor locations with FES uptake remained stable or decreased in size during anti-hormonal treatment, while all FES negative locations progressed.Conclusions: This study shows that in AGCTs, FDG uptake is limited and therefore FDG-PET/CT is not advised. FES-PET/CT may be useful to non-invasively capture the estrogen receptor expression of separate tumor lesions and thus assess the potential eligibility for hormone treatment in AGCT patients.

Highlights

Granulosa cell tumors are a well-defined ovarian cancer subtype, responsible for 2-5% of ovarian malignancies with an annual incidence of 0.6–1.0 per 100.000 women worldwide [1,2,3,4]
This study investigates the value of FDG-PET/CT for disease monitoring and FES-PET/CT for indicating anti-hormonal treatment eligibility in Adult granulosa cell tumors (AGCTs) patients
The current study shows that FDG avidity of AGCTs is low or moderate and result in low detection rates of disease by FDG-PET only

Summary

Introduction

Granulosa cell tumors are a well-defined ovarian cancer subtype, responsible for 2-5% of ovarian malignancies with an annual incidence of 0.6–1.0 per 100.000 women worldwide [1,2,3,4]. The tumor arises from the estrogen producing granulosa cells present in the ovarian stroma. Adult (95%) and juvenile (5%) subtypes can be distinguished based on clinical and histopathological characteristics. The juvenile subtype generally occurs in prepubertal girls and young women, whereas the adult type has its peak incidence between 5055 years [4]. Adult granulosa cell tumors (AGCTs) harbor a specific missense mutation in FOXL2 in approximately 95% of cases [5, 6]. Recurrences occur in approximately 50% of patients and often require repeated debulking surgeries. Of women with recurrent disease, 50–80% succumb to their disease [5, 8, 9]

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