Ovarian Germ Cell Tumors Research Articles

Survival Rate of Non-Epithelial Ovarian Tumors in Iran

Background: The aim of this study was to estimate the overall survival and relapse free survival (RFS) of the non-epithelial ovarian tumors (NEOTs) of ovarian germ cell tumors (OGCT) and ovarian sex cord tumors (OSCT) in Iranian women; we also evaluated the relative prognostic factors. Method: In this retrospective study, we screened the documents of all the women diagnosed with OGCTs and OSCTs from 2012 to 2019. We further assessed the overall survival (OS), relapse free survival (RFS), and different prognostic factors. Results: A statistically significant association existed between RFS and stage of the disease at diagnosis in OSCTs group by univariate analysis and multivariate analysis (HR: 0.25 (95% CI (0.08-0.78), p-value: 0.01) and multivariate analysis (HR: 0.27 (95% CI (0.08-0.97), p-value: 0.04), respectively. The kaplan-meier analysis and the Log Rrank (Mantel-Cox) showed a statistically significant relationship between the stage at diagnosis and RFS in OGCT group (P-value=0.042). RFS was 96% for OGCT patients, and 92.7% for OSCT patients. During the follow-up, only one patient passed away in the dysgerminoma group; the OS rate was 98% for OGCT patients, and 100% for OSCT patients. Conclusion: The overall survival and RFS obtained in this study confirmed that the ovarian germ cell and sex cord malignancies were among the highly treatable solid tumors. Stage can be proposed as the main prognostic factor; also, larger series of studies are needed for detecting the prognostic significance of serum markers.

Peptide receptor radionuclide therapy controls inappropriate calcitriol secretion in a pancreatic neuro-endocrine tumor: a case report

BackgroundHypercalcemia of malignancy is not uncommon in patients with advanced stage cancer. In rare cases the cause of the hypercalcemia is excessive production of calcitriol, the active form of vitamin D. Although inappropriate tumoral secretion of calcitriol is typically associated with lymphomas and some ovarian germ cell tumors, we present a case of calcitriol overproduction-induced hypercalcemia due to a pancreatic neuroendocrine tumor. The high expression of somatostatin receptors on this neuroendocrine neoplasm opened up the opportunity to treat the patient with radiolabelled somatostatin analogs, which successfully controlled the refractory hypercalcaemia and calcitriol levels. This case documents a rare finding of refractory hypercalcaemia of underlying malignancy due to a calcitriol-producing pancreatic neuroendocrine tumor, responding to peptide receptor radionuclide therapy (PRRT).Case presentationA 57 years-old patient presented with back pain, general discomfort, polydipsia, polyuria, fatigue and recent weight loss of 10 kg. Clinical examination was normal and there was no relevant medical history. Biochemical evaluation showed hypercalcemia with markedly increased calcitriol levels. CT-thorax-abdomen and ultrasound guided biopsy revealed a pancreatic neuroendocrine tumor with multifocal liver metastases, suggesting that excessive overproduction of calcitriol by this neuroendocrine tumor was the cause of the refractory hypercalcemia. The patient was eligible for PRRT. Four cycles of 177Lu-DOTATATE PRRT resulted in a morphological response and a normalization of serum calcium levels, confirming the hypothesis of a calcitriol producing pancreatic neuroendocrine tumor. Progression of liver metastases warranted further therapy and temozolomide-capecitabine was started with morphological and biochemical (serum calcium, calcitriol) stabilization.ConclusionAlthough up to 30–40% of gastroenteropancreatic neuroendocrine tumors are known to be functional (i.e. producing symptoms associated with the predominant hormone/peptide secreted), calcitriol secreting pancreatic neuroendocrine tumors are very rare. However, treatment with PRRT resulted in normalization of calcium and calcitriol levels, strongly supporting the hypothesis of a calcitriol-producing pancreatic neuroendocrine tumor.

Molecular characterization of uterine and ovarian tumors with mixed epithelial and germ cell features confirms frequent somatic derivation

Ovarian germ cell tumors, including yolk sac tumors, are most commonly diagnosed in children and young women. Most so-called yolk sac tumors reported in women >35 years old have been associated with an epithelial proliferation (endometriosis or carcinoma). Here, we describe eight cases clinically diagnosed as uterine or ovarian germ cell tumors in women >35 years old. In addition to routine morphologic examination and immunohistochemical evaluation, we present data from targeted next-generation sequencing (NGS) and isochromosome (12p) fluorescence in situ hybridization (FISH). We identified two groups of tumors with mixed germ cell and epithelial features: (1) tumors with background endometriosis and endometrioid carcinoma-like mutations (PTEN, PIK3CA, FGFR2, and CTNNB1), and (2) high-grade morphology, presumptive presence of isochromosome (12p) by FISH, and TP53 or PIK3CA mutations. These findings support the notion that the “germ cell tumor” component of these tumors is often somatically derived. Two tumors in our cohort were from premenopausal women; one showed no detectable mutations by NGS (suggestive of germ cell derivation), whereas the other showed PIK3CA, PTEN, and CTNNB1 mutations (suggestive of somatic derivation). Accurate classification of these tumors is likely important for selection of appropriate chemotherapy.

The potential of programmed death ligand-1 expression in ovarian malignant germ cell tumors as a prognostic factor

Abstract Background: Ovarian malignant germ cell tumors (OMGCT) that fail to recover with conventional management have a poor prognosis. Several recurrent events after chemotherapy have been found. Programmed death ligand-1 (PD-L1) is expressed in various malignancies and tumor infiltrating lymphocytes (TILs) with a known role as a prognostic factor. Objective: To determine the role of PD-L1 expression in OMGCT in determining overall survival (OS) and progression-free survival (PFS). Methods: Expression of PD-L1 was assessed from PD-L1 immunohisto-chemistry in paraffin block preparations from 40 patients diagnosed with OMGCT who met the inclusion criteria. The relationship between clinicopathological characteristics and OS and PFS was analyzed using the Kaplan-Meier method and multivariate analysis using the Cox regression model. Results: No significant relationship was found between PD-L1 expression in tumor cells with 2-year OS (p=0.275) and PFS (p=0.421) in OMGCT. A significant association was found between histopathologic types with 2-year OS (p=0.002), and cancer stage with 2- year OS (p=0.028) and PFS (p=0.014). Conclusion: PD-L1 expression in tumor cells was not related to OS and PFS in OMGCT patients. There is a tendency for death and recurrence in patients OMGCTs with low PD-L1 expression in tumor cells.

Role of complete staging surgery and adjuvant chemotherapy in adults with apparent stage I pure immature ovarian teratoma after fertility-sparing surgery: Experience at a tertiary center in China

Objective: The standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma (IMT), is unilateral salpingo-oophorectomy with complete staging surgery (CSS) followed by platinum-based chemotherapy. However, the role of CSS and adjuvant chemotherapy remains controversial.

A Mature Cyst Teratoma with Malignant Transformation in Squamous Cell Carcinoma Presenting Like a Sigmoid Fistula: A Case Report of a Rare Differential Diagnosis of a Giant Colonic Diverticulum

Mature cystic teratoma is the most common form of ovarian germ cell tumor. Mature cystic teratoma is a benign tumor, mainly diagnosed in young women, with non-specific symptoms. However, the risk of malignant transformation exists (1-2%). Squamous cell carcinoma is the most frequently encountered histological form. Giant colonic diverticulum is a rare complication of diverticular disease, characterized by a diverticulum larger than 4 cm which can sometimes be confused with other digestive pathologies (appendicitis, small bowel perforation ...). We report a case of an ovarian squamous cell carcinoma arising from a mature cystic teratoma, presenting like a sigmoid fistula, with an initial doubt with the diagnosis of a giant colonic diverticulum. A 68-year-old woman was admitted for chronic hypogastric abdominal pain with a doubt concerning the diagnosis between a mature cystic teratoma and a giant colonic diverticulum. A computed tomography scan was performed revealing a perisigmoid cyst with hydro-aeric level in favor of a giant colonic diverticulum. The pelvic MRI rather suggested a left ovarian cyst, fistulated in the sigmoid colon. Finally, the colonoscopy confirmed this hypothesis with the visualization of a sigmoid fistula located 15cm from the anal margin in connection with a cavity containing hairs. Biopsies revealed a squamous cell carcinoma. After a negative extension assessment, a posterior pelvectomy was performed with pelvic and lumbo-aortic lymph node dissection. The pathological diagnosis was an ovarian pT4N1R0 squamous cell carcinoma. An adjuvant chemotherapy is still in progress.

A Mature Cyst Teratoma with Malignant Transformation in Squamous Cell Carcinoma Presenting Like a Sigmoid Fistula: A Case Report of a Rare Differential Diagnosis of a Giant Colonic Diverticulum

Mature cystic teratoma is the most common form of ovarian germ cell tumor. Mature cystic teratoma is a benign tumor, mainly diagnosed in young women, with non-specific symptoms. However, the risk of malignant transformation exists (1-2%). Squamous cell carcinoma is the most frequently encountered histological form. Giant colonic diverticulum is a rare complication of diverticular disease, characterized by a diverticulum larger than 4 cm which can sometimes be confused with other digestive pathologies (appendicitis, small bowel perforation ...). We report a case of an ovarian squamous cell carcinoma arising from a mature cystic teratoma, presenting like a sigmoid fistula, with an initial doubt with the diagnosis of a giant colonic diverticulum. A 68-year-old woman was admitted for chronic hypogastric abdominal pain with a doubt concerning the diagnosis between a mature cystic teratoma and a giant colonic diverticulum. A computed tomography scan was performed revealing a perisigmoid cyst with hydro-aeric level in favor of a giant colonic diverticulum. The pelvic MRI rather suggested a left ovarian cyst, fistulated in the sigmoid colon. Finally, the colonoscopy confirmed this hypothesis with the visualization of a sigmoid fistula located 15cm from the anal margin in connection with a cavity containing hairs. Biopsies revealed a squamous cell carcinoma. After a negative extension assessment, a posterior pelvectomy was performed with pelvic and lumbo-aortic lymph node dissection. The pathological diagnosis was an ovarian pT4N1R0 squamous cell carcinoma. An adjuvant chemotherapy is still in progress.

Germinal ovarian tumors in reproductive age women: Fertility-sparing and outcome.

MOGCTs (malignant ovarian germ cell tumors) are rare tumors that mainly affect patients of reproductive age. The aim of this study was to evaluate the fertility and survival outcomes in young women with MOCGTs treated with fertility-sparing surgery (FSS).From 2000 to 2018, data from 28 patients of reproductive age with a diagnosis of MOGCT at the University of Bari were collected. Most received FSS, and in patients treated conservatively, the reproductive outcome and survival were investigated. Data of patient demographics, clinical presentation, oncology marker dosage, staging, type of surgery, histological examination, survival, and reproductive outcome were collected from hospital and office charts. All informed consent was obtained from all patients. The median age was 24 (range: 9–45 years). The majority of the patients had stage IIIC. Twenty-four woman received FSS consisting of unilateral ovariectomy and omentectomy, whereas only 4 women, based on their stage (IIIC), received a radical surgery (hysterectomy with bilateral adnexectomy, lymphadenectomy, and omentectomy). Our study shows that FSS in MOGCTs can produce good results both on reproductive outcomes and on survival. Indeed, in our group, there was only 1 case of exitus as result of recurrence. Furthermore, patients after FSS maintained normal ovarian function and 5 of 5 women who tried to get pregnant succeeded spontaneously. The median follow-up was 90 months (range 3–159).Conservative surgery for MOGCTs should be considered for women of reproductive age who wish to preserve fertility.

YOLK SAC TUMOR OVARIUM

Yolk sac tumor called endodermal sinus tumor, is a rare and very malignant germ cell tumor. The second largest ovarian germ cell tumor after dysgerminoma, with an incidence of 1% of ovarian malignancies. Tumors usually appear as fast-growing masses in young women. The radiological imaging of this tumor is seen as a large dense cystic mass with heterogeneous enhancement, a component of dilated intratumoralblood vessels accompanied by an intralesional hemorrhagic focus. The best radiological modality is CT scan or MRI. CT imaging useful for distinguishing yolk sac tumors from other ovarian tumors. In this article was reported a case of ovarial york sac tumor in 7 years old girl. USGand CT scan examination showed solid with cystic mass in the pelvic cavity. Histologically was malignant germ cell as york sac tumor.

The individualized significance of lymphadenectomy across all age groups and histologies in malignant ovarian germ cell tumors.

To evaluate the therapeutic role of lymphadenectomy on patients with malignant ovarian germ cell tumor (MOGCT) and to investigate the risk factors of lymph node metastasis. Patients of MOGCT between 1988 and 2013 with definite lymph node information were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival curves were estimated using the Kaplan-Meier method, and Cox regression analyses were performed to evaluate the effects of clinical and pathologic variables on survival. 2424 MOGCT patients with information on lymph nodes were included. Of the entire cohort, 46.2% patients received lymphadenectomy. The most common (42.2%) histologic type was teratoma, and 70.6% patients had FIGO stage I disease. Cox proportional model verified that age, grade, and log odds of positive lymph nodes (LODDS) were independent prognostic factors. Subgroup analysis showed that the association between the lymph node resection and better survival in the different age cohort. Lymphadenectomy is not recommended for children (0-14years). For patients 40years of age and older, and for those who have the dysgerminoma type or endodermal sinus type, lymphadenectomy had an outstanding therapeutic role. As a parameter to assess lymph node status, LODDS could be used to classify MOGCTs.

Heterogeneous Differentiation of Highly Proliferative Embryonal Carcinoma PCC4 Cells Induced by Curcumin: An In Vitro Study

Curcumin, the yellow pigment derived from turmeric rhizomes, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. We have previously reported in a study that curcumin could induce differentiation in embryonal carcinoma cell (EC). EC cells are the primary constituents of teratocarcinoma tumors, and hence differentiating them to a non-proliferative cell type may be useful in anticancer therapies. Here, we conducted a detailed study using various molecular approaches to characterize this differentiation at the cellular and molecular levels. The cells were treated with 20 µM curcumin, which was the optimal concentration to produce the highest amount of differentiated cells. Changes in protein and RNA expression, membrane dynamics, and migration of these cells after treatment with curcumin were then studied in a time-dependent manner. The differentiated cells were morphologically distinct from the precursor cells, and gene expression profiles were altered in curcumin-treated cells. Curcumin promoted cell motility and cell adhesion. Curcumin also induced changes in membrane fluidity and the lateral mobility of lipids in the plasma membrane. The findings of this study suggest that curcumin might have therapeutic potential in differentiation therapy for the treatment of teratocarcinomas or germ cell tumors (GCTs) such as testicular and ovarian GCTs.

876P The effect of surgical techniques on sexuality and global quality of life (Qol) in women with ovarian germ cell (OGCT) and sex cord stromal tumours (SCST): An analysis of the AGO-CORSETT database

876P The effect of surgical techniques on sexuality and global quality of life (Qol) in women with ovarian germ cell (OGCT) and sex cord stromal tumours (SCST): An analysis of the AGO-CORSETT database

Abstract 2125: Evaluating pathogenic germline variants in checkpoint kinase 2 (CHEK2) in ovarian germ cell tumors

Abstract Introduction: Ovarian germ cell tumors (OGCT) are exceedingly rare cancers primarily afflicting young girls leading to potentially disproportionate life years lost. In the United States, the 30-year age-adjusted incidence rate per 100,000 women-years is 0.338. Due in part to the infrequency of this neoplasm, to date no Mendelian OGCT predisposition gene has been identified, thus limiting the ability to provide molecular-based personalized clinical care. Recently, we showed that germline complete and partial loss-of-function variants in CHEK2 confer an increased susceptibility to testicular germ cell tumors, a cancer with similar pathological and cytogenetic features. In this study, we hypothesized that inherited CHEK2 defects may account for a proportion of OGCT heritability and provide clinically informative markers for OGCT susceptibility. Methods: Using a deep-learning-based germline variant calling algorithm and identical quality control standards, a targeted case-control gene-based enrichment analysis of pathogenic germline CHEK2 variants was performed in 49 OGCT patients and 1,873 ancestry-matched cancer-free adults. A secondary gene-level enrichment analysis of 50 established cancer predisposition DNA repair and cell cycle genes (DRG) was conducted in the same cohort. Results: In our cases (n=49), the coding bases of CHEK2 were sufficiently covered by over 15 reads 99.97% of the time. For our controls (n=1,873), the coding bases of CHEK2 was sufficiently covered by over 15 reads 96.05% of the time. There was no significant difference in the coverage of CHEK2 between cases and controls (P=0.96). We detected two OGCT patients with a rare, likely pathogenic CHEK2 variant. These two variants predicted transcript consequence were missense (c.1412C>T) and frameshift (c.1229del). Our analysis found CHEK2 pathogenic variants as significantly enriched in OGCT cases compared to controls. Specifically, we identified that OGCT patients were seven times as likely to carry a rare, pathogenic germline mutation in CHEK2 compared to controls (n=2, 4.08%, OR=7.18, 95% CI=1.11- 30.94, P=0.04). The CHEK2 low-penetrance allele, c.599T>C, was not observed in our case cohort. With respect to pathogenic alterations found in DRG, 20.41% (95% CI= 3.05-14.59) of our cases had a rare likely pathogenic mutation in a DRG compared to 6.03% (95% CI= 3.05-14.59) of our controls. Aside from CHEK2, there was no DRG significantly enriched for pathogenic variants in our cases. Conclusion: Our case-control analysis provides preliminary evidence for CHEK2 as a novel moderately-penetrant OGCT risk gene that may explain a portion of the monogenic heritability of OGCT. Critically, these findings require validation using other cohorts. CHEK2 is a known risk gene in breast cancer and colorectal cancer. Citation Format: Sabrina Yvonne Camp, Seunghun Han, Saud H. AlDubayan, Eliezer M. Van Allen. Evaluating pathogenic germline variants in checkpoint kinase 2 (CHEK2) in ovarian germ cell tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2125.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network

BackgroundMalignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. Patients and methodsData from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. ResultsWe collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. ConclusionAdjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

Clinical Characteristics and Treatment Outcomes of Patients with Ovarian Germ Cell Tumor Treated at a Tertiary Care Center in Patna, India

Ovarian germ cell tumors are rare tumors, mainly diagnosed in young females with a good prognosis if presented earlier. The objective of this study was to evaluate the clinicopathological features, treatment and outcome of the malignant ovarian germ cell tumors. We retrospectively reviewed 37 patients of malignant ovarian germ cell tumors registered at the Department of Radiation Oncology All India Institute of Medical Sciences (AIIMS), Patna, from August 2014 to September 2019, and analyzed their demographic profile, treatment, outcome and survival. The median age at presentation was 15 years with a median duration of symptoms of 18 weeks. Abdominal pain and abdominal pain with lump were the main presenting symptoms of 45.9% and 45.9%, respectively. The median pre-chemotherapy value of AFP was 286 ng/ml, βHCG was 8.2 mIU/ml, and LDH was 470 U/L. Fertility-preserving surgery was done in 64.9% of cases. 35.1%, 21.6%, 29.7% and 13.5% cases were in stage I, stage II, stage III and stage IV, respectively. Adjuvant systemic chemotherapy was indicated in 94.6%, and chemotherapy was not indicated in 5.4% of patients. Non-dysgerminoma was the most common histopathological type (67.7%) followed by mixed germ cell tumors and dysgerminoma in 18.9% and 13.5%, respectively. The mean follow-up duration was 40 months, 32.4% of patients developed recurrence, and mean time to recurrence was 25 months. Malignant ovarian germ cell tumor is a treatable disease, and selected patients may be managed with fertility-preserving surgery. It was observed in this study that malignant ovarian germ cell tumors have a good prognosis.

ESGO-SIOPE guidelines for the management of adolescents and young adults with non-epithelial ovarian cancers.

The European Society of Gynaecological Oncology and the European Society for Paediatric Oncology jointly developed clinically relevant and evidence-based guidelines for the management of adolescents and young adults aged 15 to 25 years with non-epithelial ovarian cancers, including malignant ovarian germ cell tumours, sex cord-stromal tumours, and small cell carcinoma of the ovary of hypercalcaemic type. The developmental process of these guidelines is based on a systematic literature review and critical appraisal process involving an international multidisciplinary developmental group consisting of experts from relevant disciplines (paediatric oncology, paediatric surgery, medical oncology, pathology, psycho-oncology, gynaecological oncology, and reproductive endocrinology). Given the specific and often complex issues involved in treating this group of patients, fertility sparing surgery and decrease of acute and long-term toxicities from treatment were important criteria for guidelines definition. Prior to publication, the guidelines were reviewed by 54 independent international practitioners in cancer care delivery.

Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord–Stromal Tumors: A Contemporary Review

Non-epithelial ovarian tumors are heterogeneous and account for approximately 10% of ovarian malignancies. The most common subtypes of non-epithelial ovarian tumors arise from germ cells or sex cord and stromal cells of the gonads. These tumors are usually detected at an early stage, and management includes surgical staging and debulking. When indicated for advanced disease, most respond to chemotherapy; however, options for patients with refractory disease are limited, and regimens can be associated with significant toxicities, including permanent organ dysfunction, secondary malignancies, and death. Targeted therapies that potentially decrease chemotherapy-related adverse effects and improve outcomes for patients with chemotherapy-refractory disease are needed. Here, we review the molecular landscape of non-epithelial ovarian tumors for the purpose of informing rational clinical trial design. Recent genomic discoveries have uncovered recurring somatic alterations and germline mutations in subtypes of non-epithelial ovarian tumors. Though there is a paucity of efficacy data on targeted therapies, such as kinase inhibitors, antibody–drug conjugates, immunotherapy, and hormonal therapy, exceptional responses to some compounds have been reported. The rarity and complexity of non-epithelial ovarian tumors warrant collaboration and efficient clinical trial design, including high-quality molecular characterization, to guide future efforts.

Wise Management of Ovarian Cancer: On the Cutting Edge.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations.

Feasibility and efficacy of gonadotropin-releasing hormone agonists for the prevention of chemotherapy-induced ovarian insufficiency in patients with malignant ovarian germ cell tumours (KGOG 3048R)

BackgroundThis study assessed the effects of gonadotropin-releasing hormone agonists (GnRHa) on the prevention of chemotherapy-induced ovarian insufficiency among young patients with malignant ovarian germ cell tumour (MOGCT) receiving chemotherapy. MethodsThis multicentre, retrospective study was conducted at 15 sites affiliated with the Korean Gynecologic Oncology Group and enrolled 354 patients between January 1995 and September 2018. Among them, 227 patients were included in this study and divided into two groups according to the use of GnRHa during chemotherapy (GnRHa versus no GnRHa groups). The primary objective was to compare the rates of menstrual resumption between the two groups. We also assessed the clinical determinants affecting menstrual resumption among the study groups. ResultsThere were no significant differences between the GnRHa (n = 63) and no GnRHa (n = 164) groups regarding age at diagnosis, parity, ethnicity, age at menarche, body mass index, International Federation of Gynecology and Obstetrics stage, mode of surgery and surgery type. The rate of menstrual resumption after chemotherapy was 100% (63 of 63) in the GnRHa group and 90.9% (149 of 164) in the no GnRHa group (p = 0.013). The mean periods from last chemotherapy to menstrual resumption were 7.4 and 7.3 months in the GnRHa and no GnRHa groups, respectively. GnRHa co-administration during chemotherapy reduced the likelihood of amenorrhoea after chemotherapy, although statistical significance was not confirmed in the univariate analysis (odds ratio: 0.276; 95% confidence interval, 0.004–1.317; p = 0.077). ConclusionTemporary ovarian suppression with GnRHa during chemotherapy does not significantly increase the chances of menstrual resumption in young patients with MOGCT.

Huge ovarian embryonal cell carcinoma in an adolescent girl: A case report

Pure ovarian embryonal carcinoma is a rare type of germ cell tumor, usually presenting in adolescent age group with only 30 odd cases reported in literature. They are mostly reported as one of the component of mixed malignant ovarian germ cell tumor. Tumor markers such as Human Chorionic Gonadotropin (HCG), and alpha-fetoprotein (AFP) and Lactate Dehydrogenase (LDH) also contribute to the diagnosis, prognosis and follow - up of germ cell tumors. Here, we report a rare case of a pure ovarian embryonal cell carcinoma in an adolescent girl with atypically raised LDH levels whereas the other markers such as AFP, HCG, CA-125 were normal.A 13 year old adolescent girl presented with pain abdomen and abdominal mass. Ultrasound and CT scanning showed a huge multi-cystic septate abdomino -pelvic mass involving the right ovary. We performed fertility sparing staging laparotomy with right salpingo-oopherectomy, saving the uterus and the left ovary. Presently, patient has completed 3 cycles of adjuvant chemotherapy (BEP regimen). Pure embryonal carcinoma, being an extremely rare tumor, the treatment outcomes and long-term disease-free survival is unknown, often data is extrapolated from its testicular counterpart, however treatment is standardized with fertility sparing USO and combination chemotherapy as the patients are very young. Recurrences occur mostly in the first 2 years following primary treatment. Also, secondary malignancies due to chemo-toxicity is a concern, as patients are very young, warranting a long and intensive surveillance.