Radiation Oncology/Ovary/Granulosa Cell Tumor

Granulosa Cell Tumor of the Ovary Epidemiology Uncommon, represents 2-5% of ovarian cancers Incidence 1/100,000 Adult GCT 95% of cases Median age at diagnosis: perimenopausal (50-54) Juvenile GCT 5% of cases Usually seen in prepubertal girls and women <30 Present with isosexual precocious pseudopuberty, or abdominal/pelvic pain due to large mass Typically favorable prognosis No association with known mutations, including BRCA1/BRCA2 Typically present with vaginal bleeding due to increased hormones Histology Derived from the granulosa cell (estradiol production) Convert androstenedione produced in thecal cells to estradiol via aromatase Categorized as sex cord-stromal tumor Tumor markers Estradiol Even though granulosa cells produce estradiol, it's not a great marker No elevation in ~30% of patients with GCT Inhibin Useful marker of GCT in pre- and post-menopausal women Negative feedback stimulator of FSH Levels should be low in post-menopausal women Mullerian inhibitory substance (MIS) Produced by granulosa cells in developing follicles, and is thus cyclical Undecetable in post-menopausal women Risk Factors Clinical factors Stage most important Path factors Large tumors (>10-15 cm worse) Tumor rupture High mitotic index Survival Staging uses FIGO System Majority present with Stage I disease (80-90%) Stage 5-year OS 10-year OS I 95% 90% II 65% 55% III/IV 35% 25% Treatment Overview Surgery is main initial management Patients are typically in the same way as epithelial ovarian CA Stage IA: Can consider fertility preservation with unilateral SO and careful staging Otherwise: TAH/BSO (2-8% bilateral) Perform endometrial biopsy to rule out concomitant uterine CA Adjuvant therapy Stage I (no RFs): none Stage I (high risk): Chemotherapy (BEP, EP, CAP, or single agent platinum) or RT to whole pelvis or whole abdomen Stage II: Same as high risk Stage I: chemo or RT Stage III/IV: Platinum-based chemo Whole abdomen RT if optimally debulked Stage III Recurrent disease: Secondary surgical debulking if feasible Abdominal RT Platinum-based chemo Hormonal approaches (GNRH, tamoxifen, progestins) in selected patients Radiation MD Anderson, 1999 (1949-1988) 10094877 -- "Radiation treatment of advanced or recurrent granulosa cell tumor of the ovary." (Wolf JK, Gynecol Oncol. 1999 Apr;73(1):35-41.) Retrospective. 14 patients treated with RT for measurable residual or recurrent disease. Median F/U 13 years RT: 10/14 moving strip whole abdomen to 27-28 Gy, 4/10 pelvic RT to 45-61 Gy Response: 6/14 CR, but 3/6 failed 4-5 years later. 8/14 PD with median survival 12 months Conclusion: RT can induce response, with occasional long-term remission Review Harvard, 2003 12637488 -- "Granulosa cell tumor of the ovary." (Schumer ST, J Clin Oncol. 2003 Mar 15;21(6):1180-9.)