Epithelial Ovarian Cancer Survivors Research Articles

Abstract 5906: Epidemiologic risk factors and survival trajectories among epithelial ovarian cancer survivors: A population-based cohort study

Abstract Background: Despite a poor 5-year survival rate of 45%, survival following a diagnosis of epithelial ovarian cancer stabilizes after 10 years. Although various clinical and tumor characteristics are established prognostic factors, the role of epidemiologic risk factors on short- versus long-term survival are unclear. The aim of this study was to evaluate the association between various hormonal, reproductive, and lifestyle risk factors on ovarian cancer mortality by survival trajectory time intervals across the survivorship phase. Methods: This population-based retrospective cohort study included 1,421 unselected women diagnosed with epithelial ovarian cancer from 1995 to 2004 in Ontario, Canada. Clinical information was obtained from medical records, risk factor information from telephone interview, and vital status was updated by linkage to the Ontario Cancer Registry up until 2020. We examined clinical risk factors, hormonal and reproductive related factors, lifestyle factors, and family history. Extended Cox proportional hazards models with Heaviside functions were used to estimate the association between risk factors and mortality by survival trajectory time interval (<3, 3-<6, 6-<10, and ≥10 years). Results: After a mean follow-up of 11.6 years, 65% (n=926) subjects died of which 51% (n=731) were due to ovarian cancer. Clinical factors such as late stage and presence of residual disease were strongly associated with short-term mortality, which attenuated over survival time. Stage IV disease significantly increased the risk of mortality compared to stage I disease for the survival interval within 3 years of diagnosis (HR 50.05; 95% CI 6.78, 369.57), however this association declined for survival beyond 10 years (HR 2.76; 95% CI 1.35, 5.65). Similarly, presence of residual disease increased the risk of mortality in the short-term (HR 2.47; 95% CI 1.40, 4.34), yet attenuated for long-term survival (HR 1.26; 95% CI 0.83, 1.93). Risk factors such as breastfeeding, smoking, and BMI were not associated with short-term survival, but significantly associated with long-term survival. History of breastfeeding decreased the risk of mortality (HR 0.65; 95% CI 0.46, 0.93), while a history of smoking (HR 1.75; 95% CI 1.27, 2.40) and obesity (HR 1.81; 95% CI 1.24, 2.65) increased the risk of mortality among long-term survivors. Conclusions: This study confirmed that clinical risk factors such as stage at ovarian cancer diagnosis and residual disease following debulking surgery are important prognostic factors in the short-term survival trajectory while breastfeeding, smoking, and BMI play a stronger role for long-term ovarian cancer survival. These findings suggest a role of modifiable factors in improving long-term outcomes across the survivorship phase. Citation Format: Shana Jean Kim, Barry Rosen, John R. McLaughlin, Harvey Risch, Shelly S. Tworoger, Steven A. Narod, Joanne Kotsopoulos. Epidemiologic risk factors and survival trajectories among epithelial ovarian cancer survivors: A population-based cohort study [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 5906.

Menopausal symptoms in epithelial ovarian cancer survivors: a GINECO VIVROVAIRE2 study

ObjectiveWe have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). Methods166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). ResultsMean age at the survey was 62 [21–83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). ConclusionsVMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.

Menopausal symptoms in epithelial ovarian cancer survivors: The GINECO VIVROVAIRE2 study.

5555 Background: We have previously shown that Epithelial Ovarian Cancer and its treatments have significant negative effects on Quality of Life (QoL) and long term fatigue. The aim of the present multicentric VIVROVAIRE2 study was to report the main menopausal, VasoMotor Symptoms (VMS) of Epithelial Ovarian Cancer survivors (EOCS). Methods: 166 patients of the 322 EOCS without relapse ≥3 years after first line of treatment accepted to participate to a gynecological consultation carried out by a gynecologist, including a questionnaire related to menopausal symptoms, a clinical examination, and an osteodensitometry. VMS (hot flashes and/or night sweats) were described according to natural menopause (NM) or surgically induced menopause (SIM). QoL and Fatigue were measured with the validated questionnaires FACT-G and FACT Fatigue. Results: Median age was 62 years [20-83], FIGO stage III/IV (48%) and &lt; 10% BRCA1&amp;2 mutated. Histological subtypes were: high grade serous 31%, low grade serous 23%, endometrioid G2-3 (14%) endometriod G1( 4%), clear-cell 21%, mucinous 5%. All EOCS had surgery, 97% of patients received platinum and taxane chemotherapy, median delay from treatment was 5 years [3-24] and 59 (36%) had SIM. 14% of EOCS had osteoporosis; this rate was similar to the general population. 52% of patients (85) reported either hot flashes (47%) or night sweats (32%). 72% with SIM had VMS compared to 41% with NM (p &lt; 0.001). VMS were not associated with poor global QoL or fatigue. At the time of the survey, only 8 (5 SIM &amp; 3 NM) EOCS received hormone replacement therapy (HRT). Among the 85 EOCS with VMS, 80 (94%) (38 SIM (93%) 42 NM (95%)) did not benefit from HRT after cancer treatment. Among 80 EOCS with VMS and no HRT, 25 (66%) with SIM and 34 (81%) of NM had high grade serous, endometriod G2-3, clear cell and mucinous histology. Conclusions: Vasomotor symptoms are frequently reported by EOCS, particularly among surgically induced menopause patients. A majority of EOCS with these symptoms might have beneficiated from hormone replacement therapy.

Long-term fatigue and quality of life among epithelial ovarian cancer survivors: a GINECO case/control VIVROVAIRE I study.

Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women. EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score <37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS. A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P < 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P < 0.0001), and poorer FACT-Ntx scores (35 versus 39, P < 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P < 0.01). Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.

Determinants of severe chronic fatigue among epithelial ovarian cancer survivors: A GINECO VIVROVAIRE study.

5573Background: Vivrovaire was a large case-control study comparing patients reported outcomes (PROs) between 318 Epithelial Ovarian Cancer Survivors (EOCS) without relapse ≥3 years after 1st line ...

Prevalence and Determinants of Metabolic Syndrome and Elevated Framingham Risk Score in Epithelial Ovarian Cancer Survivors

Bilateral oophorectomy has been associated with increased risk of metabolic syndrome (MetS) and coronary heart disease; however, the risk in women oophorectomized for epithelial ovarian cancer has not been studied previously. Among 287 epithelial ovarian cancer survivors (EOCSs) alive in 2004 and treated with bilateral oophorectomy between 1979 and 2003 at the Norwegian Radium Hospital, 189/287 (66%) participated and 165/189 (87%) provided demographic and health history data and fasting serum samples. Controls were women from the general population. Metabolic syndrome was defined according to the International Diabetes Federation and 2005 Adult Treatment Program III criteria. Framingham risk score assessing the 10-year risk of coronary heart disease was calculated. We found that to be an EOCS was significantly associated with increased risk of MetS (odds ratio, 1.7; 95% confidence interval, 1.1-2.8) but not with Framingham risk score of more than 10% (odds ratio, 0.4; 95% confidence interval, 0.2-1.1) compared with controls. Older age and higher body mass index were also significantly associated with increased risk of MetS, whereas less education and not living with a partner were associated with an increased level in the Framingham risk score. The association between EOCSs and increased risk of MetS may imply that EOCSs can be at higher risk of type 2 diabetes and cardiovascular disease. In view of the increasing number of EOCSs, these novel findings should be given therapeutic considerations when such patients are followed up by health care professionals.

Morbidity associated with "self-rated health" in epithelial ovarian cancer survivors

BackgroundEpithelial ovarian cancer survivors (EOCSs) frequently report multiple complaints after their treatment. The objective was to study somatic and mental morbidity in EOCSs associated with their Self- Rated Health (SRH) assessed by a single item.Findings were compared to age-matched controls from the general population.MethodsIn a cross -sectional follow-up design 189/287 (66%) EOCSs treated at The Norwegian Radiumhospital 1979–2003 responded to a mailed questionnaire on demographic data, and somatic and mental morbidity. SRH last week was rated on item #29 of the European Organization and Treatment of Cancer Quality of Life Questionnaire in 84/189 (97%) of responding EOCSs. For comparisons "good" and "poor" SRH groups were defined by the median score on the SRH item.ResultsEOCSs with "poor SRH" had higher level of somatic symptoms, anxiety, depression and fatigue than those with "good SRH" (p < .001). In multivariate analyses somatic symptoms, age and fatigue, were significantly associated with the SRH score in EOCSs, but not the cancer-related variables (FIGO stage, recurrence in < 6 months or chemotherapy ever). The model explained 70% of the variance in SRH in linear and 77% in logistic regression analyses. The distribution of the SRH scores in EOCSs did not differ significantly from that of normative controls; however a higher proportion of controls recorded a high SRH score.ConclusionSRH is strongly related to common somatic complaints, impairment and fatigue but not to cancer-related variables. A single question concerning SRH last week might be a quick screening method for collecting important information on symptoms in EOCSs, in addition to cancer – related questions.

A controlled study of sexual activity and functioning in epithelial ovarian cancer survivors. A therapeutic approach

Objectives. To explore sexual activity and functioning in epithelial ovarian cancer survivors (EOCSs) compared to age-adjusted controls from the general population (NORM) with focus on findings that should be given therapeutic considerations. Methods. A cross-sectional study of 189/287 (66%) EOCSs treated at The Norwegian Radiumhospital 1979–2003 using a mailed questionnaire including demographic and somatic issues, and schedules concerning sexuality, fatigue, mental distress and quality of life. Blood tests for sex hormone determination were taken at their GPs. Results. Among EOCSs 47% (95% CI 40–54%) were sexually active compared to 53% (95% CI 48–58%) in NORM. The sexually active EOCSs reported lower levels sexual pleasure ( p < 0.001) and higher levels of sexual discomfort than NORM ( p < 0.001). In sexually active EOCSs an association between higher level of sexual discomfort and both lower serum levels of estradiol ( p = 0.02) and higher levels of SHBG ( p = 0.04) was observed. Sexually active EOCSs were significantly more often in a paired relation and showed lower levels of fatigue and better quality of life compared to inactive EOCSs. Lack of interest (36%) and physical problems (23%) were significantly more common in sexually inactive EOCSs compared to NORM. In multivariable analyses of sexually active EOCSs premenopausal oophorectomy, having had chemotherapy, age at survey, mental health and body image were significantly associated with sexual functioning. Conclusions. Our findings on sexual inactivity and poorer sexual functioning among EOCSs point to issues in need of consideration. We present therapeutic strategies for evaluation and treatment for sexual problems in EOCSs.

Controlled Study of Fatigue, Quality of Life, and Somatic and Mental Morbidity in Epithelial Ovarian Cancer Survivors: How Lucky Are the Lucky Ones?

There are few studies of somatic and mental morbidity in epithelial ovarian cancer survivors (EOCSs). The aim of this controlled, cross-sectional study was to explore fatigue, quality of life (QOL), and somatic and mental morbidity in EOCSs. Among 287 EOCSs treated according to protocols at The Norwegian Radium Hospital between 1977 and 2003, 189 patients (66%) participated. Information was collected by a questionnaire containing demographic and morbidity items and self-rating scales. Internal comparisons of various subgroups of EOCSs were performed, and EOCSs were compared with age-adjusted controls from the general population. Minimal differences were observed relating to somatic and mental morbidity, fatigue, and QOL between EOCSs with and without relapse, long or short follow-up time, and prognostic index status. Chronic fatigue was found in 22% (95% CI, 16% to 28%), and only body image was significantly associated with chronic fatigue in multivariable analyses. EOCSs showed significantly more somatic and mental morbidity, somatic complaints, use of medications, and use of health care services than controls. The levels of anxiety and fatigue were also significantly higher in EOCSs than in controls, whereas the levels of depression and of several QOL dimensions were lower. The prevalence of chronic fatigue was 12% among controls. EOCSs had more somatic and mental morbidity, more fatigue, poorer QOL, and used more medication and health services than controls. Minimal differences were observed between various EOCS subgroups. Health care professionals should try to improve and be attentive to the health of EOCSs.

Hormone replacement therapy and cancer

Sex steroids are not known to damage DNA directly. They can stimulate or inhibit cell proliferation, and thus can modulate tumor developmental progression. Sex steroid-related tumors in women are represented by breast cancer and endometrial cancer, and a possible relationship exists between sex steroids and both ovarian and colon cancer. Among current ERT users or those who stopped use 1-4 years previously, the relative risk of having breast cancer diagnosed increases by a factor of 1.023 for each year of hormone use. This increase is comparable with the effect on breast cancer of delaying menopause, and seems to be largely limited to lean women. The breast cancers diagnosed during ERT are more likely to contain ER and are less aggressive. Some reports indicate no increase in breast cancer mortality in HRT users. Recent data suggest that an estrogen-progestin regimen may increase breast cancer risk beyond that associated with estrogen alone. However, the effect of progestogens on the breast awaits further clarification. ERT/HRT is generally considered to be contraindicated in breast cancer patients, as no firm data are yet available from randomized clinical trials. Despite the potential risks, ERT/HRT could be considered for breast cancer patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given, particularly in women with ER--(hormone-resistant) cancers. Unopposed estrogen therapy is known to increase endometrial cancer risk, and is appropriate only for hysterectomized women. To negate the excess risk of endometrial hyperstimulation, an adequate progestin dose must be given in a continuous combined regimen or for an appropriate number of days in sequential regimens (10 days or more for some progestogens or 12 days or more for other progestogens). An appropriate combination of estrogen and progestin does not appear to increase, and may even decrease, the risk of endometrial cancer. HRT is generally considered to be contraindicated in endometrial cancer patients. Despite the potential risks, HRT could be considered for patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given. Available data suggest a reduced risk of colorectal adenoma and colon cancer in current users of HRT, but definitive studies are still needed. There is no contraindication to HRT prescription in colon cancer survivors. Consistent epidemiological data describe a decreased incidence of ovarian cancer with oral contraceptive use during the reproductive years. Studies on HRT and risk of epithelial ovarian cancer have produced conflicting results but most data seem to exclude a strong association. While no data contraindicate HRT use in epithelial ovarian cancer survivors, current studies do not allow us to exclude the possibility that estrogens alone could stimulate ovarian cancer growth in a small fraction of patients. Additional studies are required. It is important to consider that not all estrogens and progestins are used with the same dosage, route of administration (oral, transdermal and for estradiol intranasal) and, mostly, different estrogens do not show the same bioavailability and tissue effects. The available data do not allow to discriminate for all these variables and therefore it is inappropriate to consider jointly all forms of hormonal therapy. This issue is considered as an important area for future evaluation and research. The International Menopause Society is in the process of drawing up specific recommendations for further research in the field of HRT and cancer.