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      [ 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

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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 mm 2 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 mm 2) Two out of six patients showed FES uptake on PET/CT at qualitative analysis. Lesion-based quantitative assessment showed a mean SUV max of 2.4 (± 0.9) on FDG-PET/CT and mean SUV max 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.

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          Most cited references30

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          FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0

          The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.
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            Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials.

            The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.
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              Mutation of FOXL2 in granulosa-cell tumors of the ovary.

              Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The pathogenesis of these tumors is unknown. Moreover, their histopathological diagnosis can be challenging, and there is no curative treatment beyond surgery. We analyzed four adult-type GCTs using whole-transcriptome paired-end RNA sequencing. We identified putative GCT-specific mutations that were present in at least three of these samples but were absent from the transcriptomes of 11 epithelial ovarian tumors, published human genomes, and databases of single-nucleotide polymorphisms. We confirmed these variants by direct sequencing of complementary DNA and genomic DNA. We then analyzed additional tumors and matched normal genomic DNA, using a combination of direct sequencing, analyses of restriction-fragment-length polymorphisms, and TaqMan assays. All four index GCTs had a missense point mutation, 402C-->G (C134W), in FOXL2, a gene encoding a transcription factor known to be critical for granulosa-cell development. The FOXL2 mutation was present in 86 of 89 additional adult-type GCTs (97%), in 3 of 14 thecomas (21%), and in 1 of 10 juvenile-type GCTs (10%). The mutation was absent in 49 SCSTs of other types and in 329 unrelated ovarian or breast tumors. Whole-transcriptome sequencing of four GCTs identified a single, recurrent somatic mutation (402C-->G) in FOXL2 that was present in almost all morphologically identified adult-type GCTs. Mutant FOXL2 is a potential driver in the pathogenesis of adult-type GCTs. 2009 Massachusetts Medical Society
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Impact Journals LLC
                Oncotarget
                Impact Journals LLC
                1949-2553
                30 March 2021
                30 March 2021
                : 12
                : 7
                : 665-673
                Affiliations
                1Department of Gynecological Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
                2Department of Gynecological Oncology, Amsterdam University Medical Center, Amsterdam, The Netherlands
                3Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
                4Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
                5Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
                6Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
                7Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
                Author notes
                Correspondence to: Joline F. Roze, email : J.F.Roze-2@ 123456umcutrecht.nl
                Article
                27925
                10.18632/oncotarget.27925
                8021033
                33868587
                b05e2f7d-2f85-45e0-8c73-8cb61335cbb2
                Copyright: © 2021 Roze et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 January 2021
                : 15 March 2021
                Categories
                Research Paper

                Oncology & Radiotherapy
                positron emission tomography (pet),18f-fluoroestradiol (18f-fes),18f-fluoro-deoxyglucose (18f-fdg),granulosa cell tumors (gcts),hormone receptors

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