scholarly journals Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (2) ◽  
pp. 191-226
Author(s):  
Deborah K. Armstrong ◽  
Ronald D. Alvarez ◽  
Jamie N. Bakkum-Gamez ◽  
Lisa Barroilhet ◽  
Kian Behbakht ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Cancer ◽  
Germ Cell Tumors ◽  
Mucinous Carcinoma ◽  
The United States ◽  
Parp Inhibitors ◽  
Primary Treatment ◽  
Low Grade ◽  
Nccn Guidelines ◽  
Primary Surgery

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country’s fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

scholarly journals NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019

2019 ◽  
Vol 17 (8) ◽  
pp. 896-909 ◽  
Author(s):  
Deborah K. Armstrong ◽  
Ronald D. Alvarez ◽  
Jamie N. Bakkum-Gamez ◽  
Lisa Barroilhet ◽  
Kian Behbakht ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Cancer ◽  
The United States ◽  
Parp Inhibitors ◽  
Primary Treatment ◽  
Term Survival ◽  
Nccn Guidelines ◽  
Platinum Based Chemotherapy

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.

Ovarian Cancer

2008 ◽  
Vol 6 (8) ◽  
pp. 766 ◽  
Author(s):  
_ _
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Clinical Presentation ◽  
Advanced Disease ◽  
Gynecologic Cancer ◽  
The United States ◽  
Epidemiologic Studies ◽  
Nccn Guidelines ◽  
New Information ◽  
Recent Version

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer and the fifth most common cause of cancer mortality in women in the United States. Fewer than 40% of women with ovarian cancer are cured, and 70% of patients present with advanced disease; because of the location of the ovaries, ovarian cancer has been difficult to diagnose at earlier stages. Epidemiologic studies have identified risk factors, including family history. The NCCN guidelines discuss epithelial ovarian cancer as well as less common ovarian histopathologies, including germ cell neoplasms, carcinosarcomas (malignant mixed Müllerian tumors of the ovary), and ovarian stromal tumors. For 2008, updates include the addition of platinum-based combination therapy as a possible treatment modality for recurrence and a listing of preferred agents for acceptable recurrence modalities. New information was also added to the section on clinical presentation. For the most recent version of the guidelines, please visit NCCN.org

Obesity and Gynecologic Cancer Etiology and Survival

2013 ◽  
pp. e222-e228 ◽  
Author(s):  
Penelope M. Webb
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Strong Association ◽  
Gynecologic Cancer ◽  
The United States ◽  
Overweight And Obesity ◽  
Low Grade ◽  
Cancer Specific Survival ◽  
Increased Risk ◽  
Wide Range

The prevalence of overweight and obesity in the United States and elsewhere has increased dramatically in recent decades. It has long been known that obese women have an increased risk of developing endometrial cancer, but recent studies suggest this association is strongest for the most common low-grade endometrioid endometrial cancers and weaker for the other histologic subtypes. There are insufficient data to assess whether obesity affects endometrial cancer-specific survival or whether the relation with all-cause mortality is similar to that seen in the general population. Recent data suggest obesity also increases risk of ovarian cancer, although it may not influence risk of the high-grade serous cancers that account for the majority of ovarian cancer deaths, and that it is also associated with poorer outcomes. There is currently insufficient evidence to draw any clear conclusions regarding the relation between obesity and risk of/survival from other gynecologic cancers although there are suggestions that obesity may increase risk of cervical cancer, particularly adenocarcinoma, and perhaps vulvar cancer. Possible mechanisms whereby obesity might influence gynecologic cancer risk and survival include: its strong association with endogenous estrogen levels among postmenopausal women, its effects on glucose metabolism, its effects on the wide range of adipocytokines and inflammatory mediators that are produced by adipose tissue and altered in concentration among obese individuals, and its potential effects on patient management, particularly with regard to chemotherapy dosing.

scholarly journals European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis

2020 ◽  
Vol 30 (4) ◽  
pp. 428-433 ◽  
Author(s):  
Margaret Rees ◽  
Roberto Angioli ◽  
Robert L Coleman ◽  
Rosalind M Glasspool ◽  
Francesco Plotti ◽  
...  
Keyword(s):  
Hormone Therapy ◽  
Gynecological Cancer ◽  
Gynecologic Cancer ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
Position Statement ◽  
Menopausal Symptoms ◽  
Menopausal Hormone Therapy ◽  
Cervix Uteri ◽  
Low Grade

Worldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569 847, corpus uteri 382 069, ovary 295 414, vulva 44 235, and va​gina 17 600. Treatments include hysterectomy with or without bilateral salpingo-oophorectomy, radiotherapy, and chemotherapy. These can result in loss of ovarian function and, in women under the age of 45 years, early menopause. The aim of this position statement is to set out an individualized approach to the management, with or without menopausal hormone therapy, of menopausal symptoms and the prevention and treatment of osteoporosis in women with gynecological cancer. Our methods comprised a literature review and consensus of expert opinion. The limited data suggest that women with low-grade, early-stage endometrial cancer may consider systemic or topical estrogens. However, menopausal hormone therapy may stimulate tumor growth in patients with more advanced disease, and non-hormonal approaches are recommended. Uterine sarcomas may be hormone dependent, and therefore estrogen and progesterone receptor testing should be undertaken to guide decisions as to whether menopausal hormone therapy or non-hormonal strategies should be used. The limited evidence available suggests that menopausal hormone therapy, either systemic or topical, does not appear to be associated with harm and does not decrease overall or disease-free survival in women with non-serous epithelial ovarian cancer and germ cell tumors. Caution is required with both systemic and topical menopausal hormone therapy in women with serous and granulosa cell tumors because of their hormone dependence, and non-hormonal options are recommended as initial therapy. There is no evidence to contraindicate the use of systemic or topical menopausal hormone therapy by women with cervical, vaginal, or vulvar cancer, as these tumors are not considered to be hormone dependent.

scholarly journals Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kentaro Sugino ◽  
Ryo Tamura ◽  
Hirofumi Nakaoka ◽  
Nozomi Yachida ◽  
Manako Yamaguchi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Cancer Patients ◽  
Somatic Mutations ◽  
Clear Cell ◽  
Gene Mutations ◽  
Parp Inhibitors ◽  
Low Grade ◽  
Mmr Genes ◽  
Selection Of

AbstractWe explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes in major histological types of ovarian cancer. We performed targeted sequencing to assess germline and somatic mutations of 16 HR-associated genes and 4 mismatch repair (MMR) genes among 207 ovarian cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell carcinomas (CCC), 39 endometrioid carcinomas (EC), 13 mucinous carcinomas (MC), and 6 low-grade serous carcinomas (LGSC)). Germline or somatic mutations of HR-associated genes were detected in 44% of HGSC, 28% of CCC, 23% of EC, 16% of MC, and 17% of LGSC patients. The profile of HR-associated gene mutations was remarkably different among each histological type. Germline BRCA1/2 mutations were frequently detected in HGSC and were rarely observed in CCC, EC, and MC patients. ATM somatic mutation was more frequently detected in CCC (9%) and EC patients (18%) than in HGSC patients (4%). There was a positive correlation between MMR gene mutations and HR-associated gene mutations (p = 0.0072). Our findings might be useful in selection of ovarian cancer patients that should be treated with PARP inhibitors.

Prognostic significance of obesity in high-grade serous carcinoma of the ovary

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16528-e16528 ◽  
Author(s):  
M. Schlumbrecht ◽  
D. Urbauer ◽  
D. Gershenson ◽  
R. Broaddus
Keyword(s):  
Ovarian Cancer ◽  
Body Mass Index ◽  
Overall Survival ◽  
Body Mass ◽  
Neoadjuvant Treatment ◽  
The United States ◽  
Wilcoxon Test ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade

e16528 Background: Obesity is an epidemic public health problem in the United States. In gynecologic oncology, obesity is an established risk factor for endometrial cancer. However, its role in the pathogenesis and survival in ovarian cancer is debated. Recent studies have attempted to elucidate a possible relationship, but variations in design and heterogeneity in patient characteristics make it difficult to draw definitive conclusions. The purpose of our study was to determine if body mass index at the time of treatment initiation for high grade serous ovarian carcinoma has an effect on patient outcome. Methods: Nine-hundred four patients treated for ovarian cancer at M.D. Anderson Cancer Center were identified between 2002 and 2007. Patients were excluded for low grade or non-serous histology, neoadjuvant treatment, or if presenting with recurrent disease. Clinicopathologic data were extracted by retrospective chart review. Patients were stratified by body mass index (BMI) as normal (BMI<25), overweight (BMI 25-<30), or obese (BMI>30). All were treated with primary cytoreduction and standard platinum/taxane chemotherapy. Chemotherapy was dosed using adjusted body weights. Outcomes included time to recurrence, overall survival, success of surgical debulking, and chemotherapeutic toxicities. Statistical analysis was performed using Fisher's exact test, Wilcoxon test, and Kaplan-Meier estimates. Results: A total of 127 patients were included for analysis. Patients were followed for a mean of 37 months (range 3–86 months). Twenty-one patients were obese (16.5%), and 35 were overweight (27.5%). Diabetes was more prevalent in the obese cohort (p = 0.0038). There was a trend towards greater likelihood of suboptimal debulking in obese patients, but this did not reach statistical significance (p = 0.06). BMI had no effect on recurrence-free survival (HR 0.69 [CI 0.39–1.23], p = 0.21) or overall survival (HR 0.95 [CI 0.68–2.43], p = 0.91). There was no difference in chemotherapy side effects or chemoresistance across BMI strata. Conclusions: Body mass index has no effect on survival in women with high grade serous ovarian cancer. Effectively managing comorbidities and ensuring adequate chemotherapy dosing in the obese patient is crucial for optimizing outcome. No significant financial relationships to disclose.

Harnessing IMGN853-mediated cell cytoxicity response by modulating FRα expression in ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17061-e17061
Author(s):  
Rajesh Kumar ◽  
Wei Wei ◽  
Sam Lauffer ◽  
Giulia Fulci ◽  
Michael J. Birrer
Keyword(s):  
Ovarian Cancer ◽  
The United States ◽  
Therapeutic Window ◽  
Low Grade ◽  
Cancer Drugs ◽  
Phase I Clinical Trials ◽  
Expression Levels ◽  
Resistant Disease ◽  
Therapeutic Benefits ◽  
Anti Cancer

e17061 Background: Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women in the United States. Standard treatment includes debulking surgery followed by platinum based chemotherapy. While most tumors respond to this treatment, 70% of the tumors recur and develop into a chemo-resistant disease. There is a need for new therapies targeting recurrent chemoresistant OC. To address this need, Mirvetuximab Soravtansine (ImmunoGen, Waltham, MA) has developed an antigen-drug conjugate (ADC) containing DM4, a highly potent maytansinoid derivative that induces the cell cycle arrest, conjugated to an antibody targeting folate receptor alpha (FRα). Mirvetuximab Soravtansine (IMGN853), was tested in Phase I clinical trials on women with recurrent OC and showed low grade toxicity profile and activity in platinum-resistant disease. The goal of this study is to characterize the mechanism(s) leading to IMGN853 resistance in OC and test whether anticancer drugs targeting these mechanisms could be used in combination with IMGN853 for an additive/synergistic therapeutic effect. Methods: In vitro experiments were performed to detect and modulate FRα expression. Results: We show that sensitivity of OC cell lines to IMGN853 correlates with the expression levels of FRα (R = 0.82). Long-term exposure of sensitive cells to sublethal doses of IMGN853 induces drug resistance which correlates with decreased FRα expression. Anti-cancer drugs such as dexamethasone (Dex), which induces glucocorticoid receptors, or epigenetic modulators (Trichostatin A and 5-Azacytidine) induce FRα expression in SKOV3 and OVCAR8 OC cells, suggesting the possibility to use these drugs to maintain sensitivity of OC cells to IMGN853 and increase its therapeutic window. The therapeutic benefits of combining each of these drugs with IMGN853 will be further tested in mice using ovarian cancer patients’ derived xenografts with different FRα expression levels. Conclusions: These findings have clinical implications as they indicate that OC sensitivity to IMGN853 is modulated in part by changes in FRα levels. Resistance to this drug may be overcome by simultaneous treatment with Dex or other anti-cancer drugs such as TSA or AZA.

scholarly journals DSCAML1 is differentially expressed in ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Tumor ◽  
Cell Adhesion Molecule ◽  
Ovarian Tissue ◽  
Gynecologic Cancer ◽  
The United States ◽  
Human Ovarian Cancer ◽  
Cancer Death ◽  
Ovarian Cancers ◽  
Developed World

Ovarian cancer is the fifth leading cause of cancer death for women in the United States and the leading cause of death from a gynecologic cancer for women in the developed world (1, 2). We compared the transcriptional profiles of benign ovarian tissues to that ovarian tumors isolated from women diagnosed with ovarian cancer using published datasets (3, 4) and found that the Down Syndrome cell adhesion molecule-like 1, or DSCAML1 (5) was one of the genes whose expression was most different between ovarian tumor and healthy ovarian tissue using separate datasets. This was consistent between two independent datasets analyzed. This is the first report of differential expression of DSCAML1 in ovarian cancers. DSCAML1 should be evaluated for its ability to initiate, or maintain the tumorigenic state in human ovarian cancer.

scholarly journals Universal Tumor DNA BRCA1/2 Testing of Ovarian Cancer: Prescreening PARPi Treatment and Genetic Predisposition

2019 ◽  
Vol 112 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Janet R Vos ◽  
Ingrid E Fakkert ◽  
Joanne A de Hullu ◽  
Anne M van Altena ◽  
Aisha S Sie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Predisposition ◽  
Diagnostic Yield ◽  
Parp Inhibitors ◽  
Newly Diagnosed ◽  
Identification Rate ◽  
Pathogenic Variants ◽  
Primary Surgery ◽  
Genetic Predisposition Testing ◽  
Tumor Dna

Abstract Background Women with epithelial ovarian cancer (OC) have a higher chance to benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) therapy if their tumor has a somatic or hereditary BRCA1/2 pathogenic variant. Current guidelines advise BRCA1/2 genetic predisposition testing for all OC patients, though this does not detect somatic variants. We assessed the feasibility of a workflow for universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as a prescreen for PARPi treatment and cancer predisposition testing. Methods Formalin-fixed paraffin-embedded tissue was obtained from OC patients in seven hospitals immediately after diagnosis or primary surgery. DNA was extracted, and universal tumor BRCA1/2 testing was then performed in a single site. Diagnostic yield, uptake, referral rates for genetic predisposition testing, and experiences of patients and gynecologists were evaluated. Results Tumor BRCA1/2 testing was performed for 315 (77.6%) of the 406 eligible OC samples, of which 305 (96.8%) were successful. In 51 of these patients, pathogenic variants were detected (16.7%). Most patients (88.2%) went on to have a genetic predisposition test. BRCA1/2 pathogenic variants were shown to be hereditary in 56.8% and somatic in 43.2% of patients. Participating gynecologists and patients were overwhelmingly positive about the workflow. Conclusions Universal tumor BRCA1/2 testing in all newly diagnosed OC patients is feasible, effective, and appreciated by patients and gynecologists. Because many variants cannot be detected in DNA from blood, testing tumor DNA as the first step can double the identification rate of patients who stand to benefit most from PARP inhibitors.

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