Adult-type granulosa cell tumor: towards tailored diagnostics and personalized treatment

Abstract

This thesis focuses on adult-type granulosa cell tumors, a rare form of ovarian cancer that primarily affects women around the time of menopause. The diagnosis is often made only after surgery, which means treatment is not always optimal. This research explores how granulosa cell tumors can be better recognized and treated. Data from 208 patients across the country show that many women undergo unnecessary second surgeries, without reducing the risk of disease recurrence. Additionally, a large proportion of patients remain under follow-up for years, even though only one-third experience a relapse. Recognizing symptoms such as sudden abdominal pain may help diagnose the tumor earlier. We also investigated whether circulating tumor DNA (ctDNA) in blood can predict which patients are at higher risk of recurrence. This appears to be the case, and ctDNA also seems to reflect treatment effectiveness better than hormonal markers. However, these results still need to be confirmed in larger studies. Furthermore, we tested new treatments in the laboratory using patient-derived tumor cells. This revealed that the combination of carboplatin and gemcitabine is more effective than the current standard chemotherapy. The PI3K inhibitor alpelisib showed promising results. These findings form the basis for the GRACED study, a study protocol in which granulosa cell tumor patients receive treatment based on the laboratory response of their own tumor cells. This represents an important step towards personalized care and more effective treatment for women with this rare cancer.