Invasive Epithelial Ovarian Cancer Research Articles

Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study

Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study. Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors. Insomnia was associated with higher risk of endometrioid EOC (OR=1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR=0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR=1.45, 95% CI 1.13-1.87) and HGSOC (OR=1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR=2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors. This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival. National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.

Abstract 2195: Intrauterine device use and risk of invasive epithelial ovarian cancer: A population-based case-control study

Abstract Introduction: Ovarian, fallopian tube, and primary peritoneal cancers (hereafter referred to as ovarian cancer) are the most fatal gynecologic cancers. Thus, it is imperative to identify strategies that can reduce the risk of the disease. Several contraceptive methods have been shown to be associated with a reduced risk of ovarian cancer, including combined oral contraceptives, injectable progestins, and tubal ligation. However, the use of these contraceptive methods has been decreasing in the U.S., with a growing preference for intrauterine devices (IUDs) for pregnancy prevention. Previous case-control studies on the association between IUD use and ovarian cancer risk have found inconsistent results. Notably, previous studies had small sample sizes and did not restrict to invasive epithelial tumors. The current analysis assessed the association between IUD use and risk of invasive epithelial ovarian cancer in a large population-based case-control study. Methods: This analysis used data from 1,713 people diagnosed with primary invasive epithelial ovarian cancer (cases) and 2,348 cancer-free people (controls) participating in a case-control study conducted in Los Angeles, CA from 1992-2010. The study consisted of four waves of recruitment with similar enrollment and data collection methods. Logistic regression models were fit to assess the association between IUD use and risk of invasive epithelial ovarian cancer. All models were adjusted for age, race/ethnicity, education, first-degree family history of ovarian cancer, endometriosis, body mass index, duration of combined oral contraceptive use, parity, duration of breastfeeding, tubal ligation, and study wave. Heterogeneity across the study waves and the ovarian cancer histotypes was evaluated using standard meta-analysis techniques. Results: There was no statistically significant association between IUD use and risk of invasive epithelial ovarian cancer (odds ratio=1.09, 95% confidence interval 0.93-1.28). This result was consistent across the study waves and the ovarian cancer histotypes (p-values for heterogeneity>0.05). Conclusion: IUD use was not associated with the risk of invasive epithelial ovarian cancer. Analysis by IUD type (i.e., hormone-releasing vs copper IUDs) was not possible in this study as these data were not collected. Future research should examine whether the type of IUD (i.e. copper versus hormone-releasing) may have different effects on risk of ovarian cancer. Citation Format: Minh Tung Phung, Yuting Wang, Alice W. Lee, Malcolm C. Pike, Anna H. Wu, Celeste Leigh Pearce. Intrauterine device use and risk of invasive epithelial ovarian cancer: A population-based case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2195.

Abstract 4974: Development of an ovarian cancer diagnosis score using electronic health records

Abstract Background: Diagnosis of invasive epithelial ovarian, fallopian tube, and primary peritoneal cancers (hereafter referred to as ovarian cancer) is often delayed, worsening both survival and quality of life for ovarian cancer patients. Diagnosis is delayed in ovarian cancer both because there is no effective screening method and because the symptoms commonly associated with ovarian cancer (i.e., abdominal/pelvic pain, bloating, loss of appetite, urinary symptoms) are non-specific to the disease. It would be beneficial to develop a flag in the electronic health record (EHR) when a patient’s healthcare utilization indicates further investigation for possible ovarian cancer is warranted. Thus, we used EHR data to develop a diagnosis score that identifies people who should be further assessed for potential ovarian cancer. Methods: EHR data from 211,123 female patients, including 135 ovarian cancer patients, at the University of Michigan Medical System during 2012-2023 were analyzed. Time-varying Cox proportional hazard models were fit to identify the association between ovarian cancer and the diagnostic codes recorded for healthcare visits in the EHR, including the temporal sequence of the diagnostic codes. The beta coefficients for the diagnosis codes from the Cox models were summed to create a weighted diagnosis score for each patient. The weighted diagnosis score was tested for association with ovarian cancer in the same population. Results: A total of 79 diagnostic codes were statistically significantly associated with ovarian cancer after applying a Bonferroni correction (p<9x10-5). The temporal sequence of the diagnoses was not associated with ovarian cancer. There were 11 pairs of diagnosis codes that were correlated (correlation coefficient >0.25); the diagnosis code with the higher p-value was excluded from further consideration. The remaining 68 codes were used to construct the diagnosis score. There was a statistically significant trend of increasing rate of ovarian cancer per quartile of the diagnosis score (hazard ratio=3.75, 95% confidence interval 3.50-4.03). Conclusion: A score for ovarian cancer diagnosis was developed based on 68 diagnostic codes in the EHR. The next step is to validate the diagnosis score in an external dataset. This validation is underway using administrative data from British Columbia, Canada. Citation Format: Minh Tung Phung, Karen McLean, Gillian E. Hanley, Celeste Leigh Pearce. Development of an ovarian cancer diagnosis score using electronic health records [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4974.

Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study.

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer.

Childhood body fatness and the risk of epithelial ovarian cancer: A population-based case-control study in Montreal, Canada

ObjectiveTo assess the association between childhood body fatness and epithelial ovarian cancer (EOC), and whether this association differs by type of EOC. MethodsUsing data from a population-based case-control study (497 cases and 902 controls) in Montreal, Canada conducted 2011–2016, we examined the association between childhood body fatness and EOC, overall and separately for invasive vs. borderline EOCs. A figure rating scale was used to measure body fatness at ages 5 and 10. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Quantitative bias analyses were conducted to assess the impact of exposure misclassification and non-participation. ResultsThe aOR (95% CI) of overall EOC for high vs. low body fatness was 1.07 (0.85–1.34) at age 5 and 1.28 (0.98–1.68) at age 10. The associations were stronger for invasive EOC, specifically the endometrioid histological type. For borderline cancers, the aORs were below the null value with wide confidence intervals. Bias analyses did not reveal a strong influence of non-participation. Non-differential exposure misclassification may have biased aORs towards the null for invasive cancers but did not appear to have an appreciable influence on the aORs for borderline cancers. ConclusionsChildhood body fatness may be a risk factor for invasive EOC in later adult life. Our study highlights the potential importance of examining early life factors for a comprehensive understanding of EOC development.

Epithelial ovarian cancer survival by race and ethnicity in an equal-access healthcare population

BackgroundPrevious studies in the general population observed that compared with non-Hispanic White women, Pacific Islander and Black women have higher age-adjusted mortality rates from epithelial ovarian cancer (EOC), while Asian American patients have lower mortality. We investigated whether race and ethnicity is associated with differences in EOC survival in a United States Military population where patients have equal access to healthcare.MethodsThis retrospective study included women diagnosed with EOC between 2001 and 2018 among Department of Defense beneficiaries. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models adjusting for age and year of diagnosis, histology and stage.ResultsIn our study population of 1230 invasive EOC cases (558 non-Hispanic White, 74 non-Hispanic Black, 73 Asian, 30 Pacific Islander and 36 Hispanic cases), 63% of the women died (all-cause death) after a mean = 4.8 years (SD = 4.1) of follow-up following diagnosis. Compared with non-Hispanic White cases, Asian cases had better overall survival, HR = 0.76 (95% CI = 0.58–0.98), whereas there were no differences in survival for other racial and ethnic groups.ConclusionsThese findings highlight the need to investigate how differences in access to healthcare may influence observed racial and ethnic disparities for EOC.

Ovarian cancer symptoms in pre-clinical invasive epithelial ovarian cancer – An exploratory analysis nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

ObjectiveUKCTOCS provides an opportunity to explore symptoms in preclinical invasive epithelial ovarian cancer (iEOC). We report on symptoms in women with pre-clinical (screen-detected) cancers (PC) compared to clinically diagnosed (CD) cancers. MethodsIn UKCTOCS, 202638 postmenopausal women, aged 50–74 were randomly allocated (April 17, 2001-September 29, 2005) 2:1:1 to no screening or annual screening till Dec 31,2011, using a multimodal or ultrasound strategy. Follow-up was through national registries. An outcomes committee adjudicated on OC diagnosis, histotype, stage. Eligible women were those diagnosed with iEOC at primary censorship (Dec 31, 2014). Symptom details were extracted from trial clinical-assessment forms and medical records. Descriptive statistics were used to compare symptoms in PC versus CD women with early (I/II) and advanced (III/IV/unable to stage) stage high-grade-serous (HGSC) cancer. ISRCTN-22488978; ClinicalTrials.gov-NCT00058032. Results1133 (286PC; 847CD) women developed iEOC. Median age (years) at diagnosis was earlier in PC compared to CD (66.8PC, 68.7CD, p = 0.0001) group. In the PC group, 48% (112/234; 90%, 660/730CD) reported symptoms when questioned. Half PC (50%, 13/26PC; 36%, 29/80CD; p = 0.213) women with symptomatic HGSC had >1symptom, with abdominal symptoms most common, both in early (62%, 16/26, PC; 53% 42/80, CD; p = 0.421) and advanced (57%, 49/86, PC; 74%, 431/580, CD; p = 0.001) stages. In symptomatic early-stage HGSC, compared to CD, PC women reported more gastrointestinal (change in bowel habits and dyspepsia) (35%, 9/26PC; 9%, 7/80CD; p = 0.001) and systemic (mostly lethargy/tiredness) (27%, 7/26PC; 9%, 7/80CD; p = 0.017) symptoms. ConclusionsOur findings, add to the growing evidence, that we should reconsider what constitutes alert symptoms for early tubo-ovarian cancer. We need a more nuanced complex of key symptoms which is then evaluated and refined in a prospective trial.

Association between hospital volume and outcomes in invasive ovarian cancer in Belgium: A population-based study

ObjectivesTo study the association between hospital volume and outcomes in patients with invasive epithelial ovarian cancer (EOC). MethodsThis study included 3988 patients diagnosed with invasive EOC between 2014 and 2018, selected from the population-based database of the Belgian Cancer Registry (BCR), and coupled with health insurance and vital status data. The associations between hospital volume and observed survival since diagnosis were assessed with Cox proportional hazard models, while volume associations with 30-day post-operative mortality and complicated recovery were evaluated using logistic regression models. ResultsTreatment for EOC was very dispersed with half of the 100 centres treating fewer than six patients per year. The median survival of patients treated in centres with the highest-volume quartile was 2.5 years longer than in those with the lowest-volume quartile (4.2 years versus 1.7 years). When taking the case-mix of hospitals into account, patients treated in the lowest volume centres had a 47% higher hazard to die than patients treated in the highest volume centres (HR: 1.47, 95% CI: 1.11–1.93, p = 0.006) over the first five years after incidence. A similar association was found when focussing on the surgical volume of the hospitals and considering only operated patients with invasive EOC. Lastly, the 30-day post-operative mortality decreased significantly with increasing surgical volume. ConclusionsThe large dispersion of care and expertise within Belgium and the volume-outcome associations observed in this study support the implementation of the concentration of care for patients with invasive EOC in reference centres.

Salpingectomy and the Risk of Ovarian Cancer in Ontario

A body of pathological and clinical evidence supports the position that the fallopian tube is the site of origin for a large proportion of high-grade serous ovarian cancers. Consequently, salpingectomy is now considered for permanent contraception (in lieu of tubal ligation) or ovarian cancer prevention (performed opportunistically at the time of surgical procedures for benign gynecologic conditions). To evaluate the association between salpingectomy and the risk of invasive epithelial ovarian, fallopian tube, and peritoneal cancer. This population-based retrospective cohort study included all women aged 18 to 80 years who were eligible for health care services in Ontario, Canada. Participants were identified using administrative health databases from Ontario between January 1, 1992, and December 31, 2019. A total of 131 516 women were included in the primary (matched) analysis. Women were followed up until December 31, 2021. Salpingectomy (with and without hysterectomy) vs no pelvic procedure (control condition) among women in the general population. Women with a unilateral or bilateral salpingectomy in Ontario between April 1, 1992, and December 31, 2019, were matched 1:3 to women with no pelvic procedure from the general population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs for ovarian, fallopian tube, and peritoneal cancer combined. Among 131 516 women (mean [SD] age, 42.2 [7.6] years), 32 879 underwent a unilateral or bilateral salpingectomy, and 98 637 did not undergo a pelvic procedure. After a mean (range) follow-up of 7.4 (0-29.2) years in the salpingectomy group and 7.5 (0-29.2) years in the nonsurgical control group, there were 31 incident cancers (0.09%) and 117 incident cancers (0.12%), respectively (HR, 0.82; 95% CI, 0.55-1.21). The HR for cancer incidence was 0.87 (95% CI, 0.53-1.44) when comparing those with salpingectomy vs those with hysterectomy alone. In this cohort study, no association was found between salpingectomy and the risk of ovarian cancer; however, this observation was based on few incident cases and a relatively short follow-up time. Studies with additional years of follow-up are necessary to define the true level of potential risk reduction with salpingectomy, although longer follow-up will also be a challenge unless collaborative efforts that pool data are undertaken.

The downregulation of miR-509-3p expression by collagen type XI alpha 1-regulated hypermethylation facilitates cancer progression and chemoresistance via the DNA methyltransferase 1/Small ubiquitin-like modifier-3 axis in ovarian cancer cells

BackgroundMicroRNAs are a group of small non-coding RNAs that are involved in development and diseases such as cancer. Previously, we demonstrated that miR-335 is crucial for preventing collagen type XI alpha 1 (COL11A1)-mediated epithelial ovarian cancer (EOC) progression and chemoresistance. Here, we examined the role of miR-509-3p in EOC.MethodsThe patients with EOC who underwent primary cytoreductive surgery and postoperative platinum-based chemotherapy were recruited. Their clinic-pathologic characteristics were collected, and disease-related survivals were determined. The COL11A1 and miR-509-3p mRNA expression levels of 161 ovarian tumors were determined by real-time reverse transcription-polymerase chain reaction. Additionally, miR-509-3p hypermethylation was evaluated by sequencing in these tumors. The A2780CP70 and OVCAR-8 cells transfected with miR-509-3p mimic, while the A2780 and OVCAR-3 cells transfected with miR-509-3p inhibitor. The A2780CP70 cells transfected with a small interference RNA of COL11A1, and the A2780 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis, luciferase, and chromatin immunoprecipitation assays were performed in this study.ResultsLow miR-509-3p levels were correlated with disease progression, a poor survival, and high COL11A1 expression levels. In vivo studies reinforced these findings and indicated that the occurrence of invasive EOC cell phenotypes and resistance to cisplatin are decreased by miR-509-3p. The miR-509-3p promoter region (p278) is important for miR-509-3p transcription regulation via methylation. The miR-509-3p hypermethylation frequency was significantly higher in EOC tumors with a low miR-509-3p expression than in those with a high miR-509-3p expression. The patients with miR-509-3p hypermethylation had a significantly shorter overall survival (OS) than those without miR-509-3p hypermethylation. Mechanistic studies further indicated that miR-509-3p transcription was downregulated by COL11A1 through a DNA methyltransferase 1 (DNMT1) stability increase. Moreover, miR-509-3p targets small ubiquitin-like modifier (SUMO)-3 to regulate EOC cell growth, invasiveness, and chemosensitivity.ConclusionThe miR-509-3p/DNMT1/SUMO-3 axis may be an ovarian cancer treatment target.

GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of ovarian cancer.

e17604 Background: Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers but they have never before been quantified in OC. We investigated the diagnostic utility GD2 and GD3 for diagnosis of all subtypes and stages of OC. Methods: This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299), and in two cohorts of serum samples by quantitative ELISA. A Discovery Cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent Model Cohort (n=200) was used to train and cross-validate a diagnostic model. Results: GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A novel diagnostic model that included serum levels of GD2 and GD3 was superior to the standard of care (CA125, p&lt;0.001) at detecting OC, as well as, in early-stage (I/II) OC samples. Conclusions: GD2 and GD3 are high value candidates for building a novel diagnostic panel. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early-stage. Further research exploring the utility GD2 and GD3 for diagnosis of OC is warranted. Future work will aim to validate these biomarkers in independent prospective studies. [Table: see text]

Characterization of ovarian cancer survival by histotype and stage: A nationwide study in Norway.

Contemporary population-based data on ovarian cancer survival using current subtype classifications and by surgical status are sparse. We evaluated 1-, 3-, 5- and 7-year relative (and overall) survival, and excess hazards in patients with borderline tumors or invasive epithelial ovarian cancer diagnosed 2012 to 2021 in a nationwide registry-based cohort in Norway. Outcomes were evaluated by histotype, FIGO stage, cytoreduction surgery and residual disease. Overall survival was evaluated for non-epithelial ovarian cancer. Survival of women with borderline ovarian tumors was excellent (≥98.0% 7-year relative survival). Across all evaluated invasive epithelial ovarian cancer histotypes, 7-year relative survival for cases diagnosed with stages I or II disease was ≥78.3% (stage II high-grade serous). Survival for ovarian cancers diagnosed at stage ≥III differed substantially by histotype and time since diagnosis (eg, stage III, 5-year relative survival from 27.7% [carcinosarcomas] to 76.2% [endometrioid]). Overall survival for non-epithelial cases was good (91.8% 5-year overall survival). Women diagnosed with stage III or IV invasive epithelial ovarian cancer and with residual disease following cytoreduction surgery had substantially better survival than women not operated. These findings were robust to restriction to women with high reported functional status scores. Patterns for overall survival were similar to those for relative survival. We observed relatively good survival with early stage at diagnosis even for the high grade serous histotype. Survival for patients diagnosed at stage ≥III invasive epithelial ovarian cancer was poor for all but endometrioid disease. There remains an urgent need for strategies for risk reduction and earlier detection, together with effective targeted treatments.

Association of Protein Intake with Recurrence and Survival Following Primary Treatment of Ovarian Cancer

BackgroundMalnutrition is common during treatment of ovarian cancer, and 1 in 3 patients report multiple symptoms affecting food intake after primary treatment. Little is known about diet posttreatment in relation to ovarian cancer survival; however, general recommendations for cancer survivors are to maintain a higher level of protein intake to support recovery and minimize nutritional deficits. ObjectivesTo investigate whether intake of protein and protein food sources following primary treatment of ovarian cancer is associated with recurrence and survival. MethodsIntake levels of protein and protein food groups were calculated from dietary data collected ∼12 mo postdiagnosis using a validated FFQ in an Australian cohort of women with invasive epithelial ovarian cancer. Disease recurrence and survival status were abstracted from medical records (median 4.9 y follow-up). Cox proportional hazards regression was used to calculate adjusted HRs and 95% CIs for protein intake and progression-free and overall survival. ResultsAmong 591 women who were progression-free at 12 mo follow-up, 329 (56%) subsequently experienced cancer recurrence and 231 (39%) died. A higher level of protein intake was associated with better progression-free survival (>1–1.5 compared with ≤1 g/kg body weight, HRadjusted: 0.69, 95% CI: 0.48, 1.00; >1.5 compared with ≤1 g/kg, HRadjusted: 0.61, 95% CI: 0.41, 0.90; >20% compared with ≤20% total EI from protein, HRadjusted: 0.77, 95% CI: 0.61, 0.96). There was no evidence for better progression-free survival with any particular protein food sources. There was a suggestion of better overall survival among those with higher total intakes of animal-based protein foods, particularly dairy products (HR: 0.71; 95% CI: 0.51, 0.99 for highest compared with lowest tertiles of total dairy intake). ConclusionsAfter primary treatment of ovarian cancer, a higher level of protein intake may benefit progression-free survival. Ovarian cancer survivors should avoid dietary practices that limit intake of protein-rich foods.

Impact of complete surgical staging on survival of patients with early-stage (FIGO I or II) ovarian cancer: Data from the Cote d'Or Registry of Gynecological Cancers from 1998 to 2015.

Early-stage ovarian cancer represents 20 to 33% of all ovarian cancers and is thus quite rare in France, with around 1200 new cases per year. No study to date has convincingly demonstrated the utility of lymphadenectomy in early-stage ovarian cancer. We sought to evaluate the impact on overall survival of complete surgical staging in patients management for FIGO stage I and II ovarian cancer. We performed a retrospective observational study using data from the Cote d'Or Registry of Gynecological Cancers. We included patients with invasive early stage epithelial ovarian cancer (FIGO stages I and II), diagnosed between 1 January 1998 and 31 December 2015. A total of 179 patients were included in the study. Patients who had lymphadenectomy were younger on average (P<0.001) and had fewer comorbidities (P=0.03). Lymphadenectomy was performed during the first surgery in 59.2% of cases (58 patients) and during a second, re-staging surgery in 40.8% (n=40). When complete surgical staging was performed, the rate of up-staging (to at least FIGO stage III) was 11.2% (11/98). The median follow-up was 8.4 years. At the study, 31.6% patients with complete surgical staging had died and 48.4% patients also died in the group without lymphadenectomy, HR 0.59 CI [0.36-0.97] P<0.04. In patients with early-stage ovarian cancer, complete surgical staging appears to yield a benefit in terms of overall survival. In 10 to 15% of cases, it leads to upstaging, with the resultant indication for maintenance therapy, which has also shown a survival benefit.

Oncologic and obstetric outcomes of early-stage epithelial ovarian cancer patients who underwent fertility-sparing surgery: A retrospective study.

This study aimed to assess the long-term oncologic and obstetric outcomes of women with epithelial ovarian cancer who underwent fertility-sparing surgery. A total of 68 patients observed between March 2007 and July 2021 were included in this retrospective study. Unilateral salpingo-oophorectomy and uterine preservation with staging surgery were the main procedures for fertility-sparing surgery. Disease-free, overall survival, and obstetric outcomes were measured as primary outcomes. The median age of the patients was 30.5 years. The median follow-up time was 60.5months. Disease recurrence occurred in 15 (22.1%) of the patients. Five-year disease-free survival and overall survival (OS) percentages were 75.6% and 83.3%, respectively, for all stages. The FIGO (International Federation of Gynecology & Obstetrics) stage was the only significant factor that affected OS (P= 0.001). Twenty-three patients tried to conceive, and 15 (65.2%) patients became pregnant. Twelve (80%) pregnancies reached term and resulted in 15 live births. Chemotherapy administration and surgical intervention (cystectomy or unilateral salpingo-oophorectomy) showed no difference in pregnancy results (P= 0.806 and P= 0.066, respectively). Fertility preservation is safe for invasive epithelial ovarian cancer at early stages for women in the reproductive era. Disease recurrence and OS results are similar to standard treatment at early stages with decent obstetric outcomes.

Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

Racial differences in the association of body mass index and ovarian cancer risk in the OCWAA Consortium.

Obesity disproportionately affects African American (AA) women and has been shown to increase ovarian cancer risk, with some suggestions that the association may differ by race. We evaluated body mass index (BMI) and invasive epithelial ovarian cancer (EOC) risk in a pooled study of case-control and nested case-control studies including AA and White women. We evaluated both young adult and recent BMI (within the last 5 years). Associations were estimated using multi-level and multinomial logistic regression models. The sample included 1078 AA cases, 2582 AA controls, 3240 White cases and 9851 White controls. We observed a higher risk for the non-high-grade serous (NHGS) histotypes for AA women with obesity (ORBMI 30+= 1.62, 95% CI: 1.16, 2.26) and White women with obesity (ORBMI 30+= 1.20, 95% CI: 1.02, 2.42) compared to non-obese. Obesity was associated with higher NHGS risk in White women who never used HT (ORBMI 30+= 1.40, 95% CI: 1.08, 1.82). Higher NHGS ovarian cancer risk was observed for AA women who ever used HT (ORBMI 30+= 2.66, 95% CI: 1.15, 6.13), while in White women, there was an inverse association between recent BMI and risk of EOC and HGS in ever-HT users (EOC ORBMI 30+= 0.81, 95% CI: 0.69, 0.95, HGS ORBMI 30+= 0.73, 95% CI: 0.61, 0.88). Obesity contributes to NHGS EOC risk in AA and White women, but risk across racial groups studied differs by HT use and histotype.

Patterns of genomic testing for epithelial ovarian cancer across a large community-based health care network: A real world experience (596)

Patterns of genomic testing for epithelial ovarian cancer across a large community-based health care network: A real world experience (596)

Abstract 30: A pedigree-based approach to ovarian cancer risk variant discovery in the Utah Population Database

Abstract Introduction: Genetic risk variants are critical to risk prediction for invasive epithelial ovarian cancer (EOC), yet an estimated 50-55% of EOC heritability remains missing. Novel approaches to risk variant discovery are needed to detect variants that have not been uncovered by linkage analysis or genome-wide association studies (GWAS). We approach risk variant discovery using Shared Genomic Segment analysis (SGS), a novel statistical genetics method that enables risk variant discovery in extended high-risk pedigrees. Methods: The Utah Population Database (UPDB) is a population-based resource of over ten million individuals connected to the state of Utah, five million of whom are linked to a minimum of three generations of genealogy data. By linking this genealogy data with cancer data from the Utah Cancer Registry, we identified pedigrees with an excess risk of EOC. We generated germline genotyping data from cases (diagnosed 1983-2018) in a subset of these high-risk pedigrees, focusing on pedigrees well-suited for SGS (i.e., at least 3 cases separated by a total of at least 12 meioses). SGS identifies all runs of consecutive alleles that are shared identical-by-state by cases in a pedigree and determines which of these genomic segments are longer than would be expected by chance. These long segments are likely to be identical-by-descent, inherited from a common founder, and may harbor risk variants. Results: We successfully linked UPDB genealogy data to information from the Utah Cancer Registry to identify approximately 2,000 extended high-risk pedigrees with ≥5 ovarian cancer cases, an average of 7-10 meioses between pairs cases, and a statistically significant excess risk of ovarian cancer (α=0.05). We obtained biospecimens for 141 cases in 36 of the most promising pedigrees (i.e., high familial standardized incidence ratio, p-value&amp;lt;0.005, not attributable to known risk variants in BRCA1 or BRCA2 as observed in first-, second- or third-degree relatives of EOC cases). We genotyped 96 out of the 141 cases in these pedigrees (68%). SGS analyses to identify genomic regions that may harbor risk variants are currently underway. Conclusions: Using pedigrees identified in the UPBD, SGS has identified risk loci and novel risk variants for a number of diseases, including breast and hematologic cancers. We have identified a set of EOC high-risk pedigrees for SGS analysis and will leverage SGS to identify genomic regions that may harbor EOC risk variants. Citation Format: Mollie E. Barnard, Robert Sargent, G. Bryce Christensen, Bonita A. Mahaffey, James Albro, Elke A. Jarboe, Terence Rhodes, Nicola J. Camp, Jennifer A. Doherty. A pedigree-based approach to ovarian cancer risk variant discovery in the Utah Population Database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 30.

Outcomes of the BRCA quality improvement dissemination program in three health systems.

10603 Background: The BRCA Quality Improvement Dissemination Program (BQIDP) was disseminated to 3 community-based health systems’ oncology clinics in 2017. The BQIDP occurred over 3 years and aimed to increase rates of guideline-recommended referral (ref), genetic counseling (GC), and germline genetic testing (GT) for patients diagnosed with invasive epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC) and triple-negative breast cancer diagnosed at age 60 or younger (TNBC). The BQIDP applied virtual implementation facilitation to support sites’ development, implementation, and tracking of quality improvement (QI) interventions. Interventions were adapted from prior QI initiatives and published interventions. Methods: Baseline metrics (patients diagnosed 1/1/2015 to site’s BQIDP launch date Autumn 2017) were compared to metrics of patients diagnosed during BQIDP implementation (site launch dates Autumn 2017 to Autumn 2020). Two-sample test of proportions was used to assess for statistically significant change in rates pre and post BQIDP implementation at each site. QI interventions targeted provider and patient education, retrospective and prospective case finding with alerts to providers and patients, case finding by review of somatic test results and genetic counselor tumor board attendance, streamlined ref and scheduling processes, and infusion-suite based GC. Results: All clinics increased rates compared to baseline (Table). Statistically significant improvement was noted for patients with OC in receipt of GC at Site A, ref and receipt of GC at site B, and receipt of GC at site C. Statistically significant improvement was noted for patients with TNBC in ref and GT at sites A and B. Conclusions: Improved rates of ref, GC and GT for patients with OC and TNBC were observed at all 3 sites compared to baseline. Baseline ref, GC, and GT metrics for patients with TNBC were higher than for patients with OC at all sites. Tailored and facilitated QI efforts can promote patients’ receipt of guideline-recommended cancer genetics services in health system oncology clinics. [Table: see text]