For adult granulosa cell tumors (aGCTs), the preferred treatment modality is surgery. Chemotherapy and anti-hormonal therapy are also frequently used in patients with recurrent aGCT. We aimed to review the existing literature on the response to chemotherapy and anti-hormonal therapy in patients with aGCT. Embase and MEDLINE were searched from inception to November 2021 for eligible studies. Objective response rate (ORR) was calculated as the total number of cases with a complete response (CR) or a partial response (PR). Disease control rate (DCR) was defined as the sum of cases with CR, PR or stable disease (SD). A total of 10 studies were included that reported on chemotherapy and 13 studies were included that reported on anti-hormonal therapy. The response rates of the 56 chemotherapy regimens that could be evaluated resulted in an ORR of 30% and DCR of 58%. For anti-hormonal therapy, the results of 73 regimens led to an ORR of 11% and a DCR of 66%. Evidence on systemic therapy in aGCT only is limited. For both chemotherapy and anti-hormonal therapy, the ORR is limited, but the response is considerably higher when patients achieving SD are included. New approaches are needed to provide more evidence and standardize treatment in aGCT.

CONTEXT: Gastroesophageal reflux (GER) is defined as GER disease (GERD) when it leads to troublesome symptoms and/or complications. We hypothesized that definitions and outcome measures in randomized controlled trials (RCTs) on pediatric GERD would be heterogeneous.OBJECTIVES: Systematically assess definitions and outcome measures in RCTs in this population.DATA SOURCES: Data were obtained through Cochrane, Embase, Medline, and Pubmed databases.STUDY SELECTION: We selected English-written therapeutic RCTs concerning GERD in children 0 to 18 years old.DATA EXTRACTION: Data were tabulated and presented descriptively. Each individual parameter or set of parameters with unique criteria for interpretation was considered a single definition for GER(D). Quality was assessed by using the Delphi score.RESULTS: A total of 2410 unique articles were found; 46 articles were included. Twenty-six (57%) studies defined GER by using 25 different definitions and investigated 25 different interventions. GERD was defined in 21 (46%) studies, all using a unique definition and investigating a total of 23 interventions. Respectively 87 and 61 different primary outcome measures were reported by the studies in GER and GERD. Eight (17%) studies did not report on side effects. Of the remaining 38 (83%) studies that did report on side effects, 18 (47%) included this as predefined outcome measure of which 4 (22%) as a primary outcome measure. Sixteen studies (35%) were of good methodological quality.LIMITATIONS: Only English-written studies were included.CONCLUSIONS: Inconsistency and heterogeneity exist in definitions and outcome measures used in RCTs on pediatric GER and GERD; therefore, we recommend the development of a core outcome set.

As current literature does not provide sufficient data to support clear guidelines in patients with a rare adult-type granulosa cell tumor, we aim to investigate: (1) whether additional staging surgery following primary surgical treatment is necessary; (2) how long standard follow-up should be and (3) risk factors for disease recurrence. A national multicenter prospective study was initiated in April 2018. Patients with suspected or confirmed adult-type granulosa cell tumor were eligible. Data on staging, follow-up and risk factors were both retrospectively and prospectively collected from medical records, and patients were followed until April 2024 or until death. Descriptive statistical analysis and survival analysis were performed using Cox regression methods and Kaplan-Meier analyses. In total, 208 patients with histopathologically confirmed adult-type granulosa cell tumor were included, with a median follow-up of 5.5 years (IQR: 2.2–12.3 years). Vaginal bleeding and abdominal pain were the most common symptoms at diagnosis. Median time until first recurrence was 4.2 years (range 2 months– 32 years). Additional staging surgery did not reduce the risk of recurrence. During follow-up, most patients had no symptoms at the time of detection of recurrence. No difference in overall survival was found between patients who were diagnosed with a recurrence during follow-up, and those who were no longer in follow-up and presented with symptoms. Staging surgery does not improve recurrence free survival in patients with adult-type granulosa cell tumor. Our results suggest that adult-type granulosa cell tumor patients can be discharged from follow-up of adult-type granulosa cell tumor after five years.

Objectives: The purpose of the study is to determine whether FOXL2 circulating tumor DNA can be used as a prognostic biomarker and marker for monitoring treatment response in patients with an adult-type granulosa cell tumor (aGCT). Methods: Plasma samples of patients included in the multicenter GRANULOSA study were collected before and after surgery for primary or recurrent aGCT, during follow-up, and during systemic treatment. The presence of ctDNA containing the FOXL2 402C>G mutation was analyzed in 284 samples from 20 primary and 34 recurrent aGCT patients, using digital droplet PCR. Clinical data were retrieved from electronic patient records, and patients were followed through January 2025. Results:FOXL2 mutant ctDNA was detected in 28 of 54 patients (48%). In primary aGCT, recurrences were more frequently seen in patients with detectable ctDNA (33% vs. 18%), and ctDNA remained detectable postoperatively in some cases despite complete cytoreduction. In recurrent aGCT patients, detectable ctDNA was associated with significantly worse overall survival (p = 0.023), and the postoperative presence of ctDNA following complete debulking surgery was significantly associated with a shorter recurrence-free survival (4.7 vs. 11.6 months, p = 0.025). Conclusions:FOXL2 mutant ctDNA could be a prognostic biomarker in aGCT, being associated with worse overall survival in recurrent aGCT patients. In addition, the presence of ctDNA after surgery could reflect the presence of minimal residual disease, negatively impacting the disease course. The implementation of FOXL2 ctDNA measurement in clinical practice may help to identify high-risk aGCT patients.

Ovarian cancer mortality rates have not decreased significantly in the past years. As most women are still diagnosed in an advanced stage, there is a need for new treatment strategies for recurrent disease. A potentially new developing targeted approach, theranostics, combines diagnostics and treatment using radiopharmaceuticals. Through target receptors, imaging and treatment of malignant tissue can be achieved. For ovarian malignancy, the follicle-stimulating hormone (FSH) receptor may serve as a possible target since expression appears to be limited to ovarian cells. In this systematic review, we aim to gather all available literature on the expression of the FSH receptor in ovarian tumors. Pubmed, Embase and the Cochrane databases were searched until December 2023 for eligible studies. The search yielded 41 studies, mostly regarding serous carcinomas, sex cord–stromal tumors (SCSTs) and cell lines of serous and SCSTs. Various techniques were used to analyze the expression of the FSH receptor. For serous carcinomas, conflicting results on the expression of the FSH receptor were found. Studies on SCSTs, mainly studying the subtype of granulosa cell tumors, all showed positive expression of the FSH receptor. In the cell lines studies, the KGN cell line derived from a granulosa cell tumor shows positive expression in all studies. Available studies show that SCSTs express the FSH receptor. A theranostic approach targeting the FSH receptor may, therefore, provide a useful new approach for this malignancy with limited therapeutic options in recurrent disease.

This study aims to evaluate signal transduction pathway (STP) activity in adult-type granulosa cell tumors (aGCT) in order to identify potential therapeutic targets. These results are compared with STP activity in healthy ovarian tissue and low and high grade serous ovarian carcinoma (LGSC and HGSC). STP activity was assessed by a RNA-based assay for the following oncogenic pathways: Hedhehog (HH), transforming growth factor beta (TGF-β), Notch, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), androgen receptor (AR) and estrogen receptor (ER). Samples of 31 aGCTs and a healthy granulosa cell were included and compared with 24 LGSC and 50 HGSC samples. In aGCT, significantly higher activity of the HH, Notch, PI3K and ER pathways was found, as compared to healthy granulosa cells. When compared with LGSC and HGSC, aGCT exhibited significantly higher PI3K pathway activity and lower HH, TGF-β, Notch, MAPK, AR, and ER pathway activity. Our results show high PI3K pathway activity in aGCT samples. Pathway activity contrasts with findings in both healthy granulosa cells and serous ovarian carcinoma. Therefore, the PI3K pathway may be a target for treatment, specifically for aGCT patients.