Development and Validation of Ovarian Symptom Index-18 and Neurotoxicity-4 for Korean Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

PURPOSE: The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility. MATERIALS AND METHODS: In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting. CONCLUSION: Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.

Distinctive psychological and social experiences of women choosing prophylactic oophorectomy for cancer prevention.

Women known to have significantly elevated ovarian cancer risk due to genetic mutations or family history can reduce this risk by surgically removing both ovaries and fallopian tubes (RRBSO, risk-reducing bilateral salpingo-oophorectomy). We used interpretive phenomenological analysis (IPA) to explore the psychosocial experiences of women who chose RRBSO for cancer prevention. We extended the traditional use of IPA to compare the experiences of women who chose RRBSO for cancer prevention to those of women who underwent similar gynecologic surgery for benign indications. The analysis resulted in three superordinate themes describing women's psychosocial experiences related to RRBSO: (a) psychological facets of cancer risk (b) social support and (c) shared medical decision making. Findings illustrate that women choosing RRBSO for cancer prevention experience heightened psychosocial challenges before and after surgery compared to women undergoing surgery for benign indication. Furthermore, they may need distinct types of information and support from healthcare providers.

Targeting those with decreased meaning and peace: a supportive care opportunity.

PURPOSE: To evaluate if an individual's level of meaning/peace (M/P) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients. METHODS: Multi-site analysis of women with newly diagnosed stages II-IV ovarian, primary peritoneal, or fallopian tube cancer. Patients completed the following surveys: Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Edmonton Symptom Assessment System (ESAS), Hospital Anxiety and Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), Herth Hope Index (HHI), and Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS). Linear regression models were created to examine the effect of M/P (FACIT-Sp) upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site, race, age, stage, anaphylaxis to chemotherapy, and partner status as potential confounders. RESULTS: This study enrolled 104 patients from three separate sites. After adjusting for potential confounders, it was found that higher M/P predicted better QOL (FACT-O) (p < 0.0001). Higher M/P also predicted decreased death anxiety, depression, and anxiety (p ≤ 0.005). Finally, higher M/P predicted increased hope and coping scores (p ≤ 0.0005). CONCLUSIONS: Level of M/P is associated with several important mental and physical health states. This information may allow providers to identify patients at increased risk for mental/physical distress and may facilitate early referral to targeted psychotherapy interventions focused on improving patient QOL and decreasing anxiety and depression.

A qualitative study of ovarian cancer survivors' perceptions of endpoints and goals of care.

OBJECTIVES: A survey of the Ovarian Cancer National Alliance revealed a communication gap between physicians and survivors. This qualitative study explored the space between perceptions in hopes of better defining treatment endpoints meaningful to treating physicians and their patients. METHODS: A focus group of ovarian cancer survivors (n=22) was assembled via the survivor support network SHARE. A physician-guided session explored expectations of treatment, perceived outcomes, toxicity thresholds and decision making. The session was recorded, transcribed and coded. Common themes were identified and used to perform intra-case analysis by two independent reviewers. RESULTS: The main themes identified were barriers to communication, importance of frequent communication between patient and physician regarding goals, and expectations of treatment changing with position along the treatment continuum. One hundred percent of participants identified communication with their physician as an essential element in determining treatment course. However, only 14% reported having a discussion about goals, values and perceptions with their physician preceding treatment decisions. Participants reported that the terms progression free and overall survival held minimal significance for them and instead they preferred an individualized approach to care focusing on quality of life. Many women underreported side effects with reasons ranging from fear of dose reductions and additional tests to forgetting about symptoms due to anxiety. CONCLUSIONS: An objective measure of treatment success meaningful to survivors, physicians and regulators is, at present, elusive and may not exist. Ideally, future trial design would place equal weight on quantitative and qualitative measures and include information about goals of treatment.

Misperceptions of ovarian cancer risk in women at increased risk for hereditary ovarian cancer.

This study assessed the sociodemographic, medical and psychological predictors of accuracy of perceived risk in women at increased genetic risk for ovarian cancer. Women participating in a large cohort study who were at increased risk of ovarian and fallopian tube cancer, had no personal history of cancer and had ≥1 ovary in situ at cohort enrollment, were eligible. Women completed self-administered questionnaires and attended an interview at enrollment. Of 2,868 women unaffected with cancer at cohort enrollment, 561 were eligible. 335 women (59.8 %) overestimated their ovarian cancer risk, while 215 women (38.4 %) accurately estimated their risk, and 10 (1.8 %) underestimated it. Women who did not know their mutation status were more likely to overestimate their risk (OR 1.74, 95 % CI 1.10, 2.77, p = 0.018), as were those with higher cancer-specific anxiety (OR 1.05, 95 % CI 1.02, 1.08, p < 0.001) and/or a mother who had been diagnosed with ovarian cancer (OR 1.98, 95 % CI 1.23, 3.18, p = 0.005). Amongst the group of women who did not know their mutation status, 63.3 % overestimated their risk and the mean perceived lifetime risk of developing ovarian cancer was 42.1 %, compared to a mean objective risk of 6.4 %. A large number of women at increased risk for ovarian cancer overestimate their risk. This is of concern especially in women who are at moderately increased risk only; for this sub-group of women, interventions are needed to reduce potentially unnecessary psychological distress and minimise engagement in unnecessary surgery or screening.

Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. Preventive Services Task Force recommendation.

BACKGROUND: Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer. PURPOSE: To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. DATA SOURCES: MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists. STUDY SELECTION: English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality. DATA EXTRACTION: Individual investigators extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability by using established criteria. DATA SYNTHESIS: Five referral models accurately estimated individual risk for BRCA mutations. Genetic counseling increased the accuracy of risk perception and decreases the intention for genetic testing among unlikely carriers and cancer-related worry, anxiety, and depression. No trials evaluated the effectiveness of intensive screening or risk-reducing medications in mutation carriers, although false-positive rates, unneeded imaging, and unneeded surgeries were higher with screening. Among high-risk women and mutation carriers, risk-reducing mastectomy decreased breast cancer by 85% to 100% and breast cancer mortality by 81% to 100% compared with women without surgery; risk-reducing salpingo-oophorectomy decreased breast cancer incidence by 37% to 100%, ovarian cancer by 69% to 100%, and all-cause mortality by 55% to 100%. LIMITATION: The analysis included only English-language articles;efficacy trials in mutation carriers were lacking. CONCLUSION: Studies of risk assessment, genetic counseling, genetic testing, and interventions to reduce cancer and mortality indicate potential benefits and harms that vary according to risk.

Timing of referral for genetic counseling and genetic testing in patients with ovarian, fallopian tube, or primary peritoneal carcinoma.

OBJECTIVE: The objective of this study was to assess patients' preferences of the timing of referral for genetic counseling and testing in relation to the diagnosis, treatment, and recurrence of ovarian, tubal, or primary peritoneal cancers. METHODS: Ninety-two patients who underwent counseling and testing by 1 certified genetic counselor were identified. An introductory letter, consent form, and questionnaire were mailed to gather information regarding factors influencing the decision to undergo genetic counseling and testing and opinions regarding optimal timing. Medical records were reviewed for demographic and clinical data. RESULTS: Of 47 consenting women, 45 underwent testing. Eight (18%) were found to have a genetic mutation. Women lacked consensus about the optimal time for referral for and to undergo genetic testing, although women with stage I disease preferred testing after completion of chemotherapy. Most women were comfortable receiving the results by phone, but one third preferred an office visit. CONCLUSIONS: Patients' views regarding the best time to be referred for and undergo counseling and testing varied greatly. Because of the high mortality of this disease, clinicians should discuss referral early and personalize the timing to each patient. The subset of patients who prefer results disclosure during an office visit should be identified at the time of their initial counseling.

Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer.

OBJECTIVES: (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures. METHODS: A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, >1 hospitalization in the last 30 days, >1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤3 days. RESULTS: One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p=0.003), >1 hospitalization in the last 30 days (p<0.001), ICU admission in the last 30 days (p=0.005), dying in acute care setting (p=0.01), admitted to hospice ≤3 days (p=0.02). EOL discussion as outpatient was associated with fewer patients hospitalized >1 in the last 30days of life (p<0.001). CONCLUSIONS: End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions.

Does the diagnosis of breast or ovarian cancer trigger referral to genetic counseling?

OBJECTIVE: Kaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated cancers for genetic counseling. This study assesses adherence to genetic counseling referral guidelines within this health system. METHODS: Chart review was performed to identify patients with cancer who met the following pathology-based Kaiser Permanente Northern California guidelines for referral for genetic counseling: invasive breast cancer, younger than age 40; nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer, younger than age 60; women with synchronous or metachronous primary cancers of the breast and ovaries; and male breast cancer. We assessed compliance with referral guidelines. An electronic notice was sent to the managing physician of patients with newly diagnosed cancer to assess the feasibility of this intervention. RESULTS: A total of 340 patients were identified with breast cancer at younger than age 40 or with ovarian, peritoneal, or tubal cancer between January and June, 2008. Upon chart review, 105 of these patients met pathology-based criteria for referral to genetic counseling, of whom 47 (45%) were referred within the 2-year study period. Of the 67 subjects with breast cancer, 40 subjects (60%) were referred. In contrast, only 7 (21%) of 33 patients with ovarian cancer were referred (P < 0.001). A pilot study was performed to test the feasibility of notifying managing oncologists with an electronic letter alerting them of eligibility for genetic referral of patients with new diagnosis (n = 21). In the 3 to 6 months after this notification, 12 of these 21 patients were referred for counseling including 5 of 7 patients with a diagnosis of ovarian cancer. CONCLUSION: There is a missed opportunity for referring patients to genetic counseling, especially among patients with ovarian cancer. A pilot study suggests that alerting treating physicians is a feasible strategy to increase appropriate referral.

Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer.

Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p < 0.001) and having a mother and/or sister who died from ovarian cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.

The impact of prophylactic salpingo-oophorectomy on quality of life and psychological distress in women with a BRCA mutation.

OBJECTIVES: The objective of this study was to measure the impact of prophylactic salpingo-oophorectomy on health-related quality of life and psychological distress in women. METHODS: Women who underwent prophylactic salpingo-oophorectomy between August 20, 2003 and June 26, 2008 because of a BRCA1 or BRCA2 mutation were invited to participate. Participants completed three questionnaires (SF-12(®) Health Survey, Brief Symptom Inventory and the Impact of Events Scale) before prophylactic surgery and again 1 year after surgery. Measures of health-related quality of life, of general psychological distress and of ovarian cancer worry before and after surgery were compared. RESULTS: Few women who underwent salpingo-oophorectomy experienced a worsening in physical or mental health functioning after salpingo-oophorectomy. On average, women experienced less ovarian cancer-specific worry after surgery; 34.3% experienced moderate to severe ovarian cancer-specific distress before surgery, compared with 18.6% after surgery. CONCLUSIONS: For most women, physical and mental health-related quality of life did not deteriorate after prophylactic salpingo-oophorectomy, and they were less worried about ovarian cancer. A subset of women continued to experience moderate to severe cancer-specific distress. Identification of these women is important in order to provide continued counseling and support.

A study of symptoms described by ovarian cancer survivors.

OBJECTIVE: A cross-sectional, observational study to evaluate physical and psychological symptoms experienced by patients following completion of treatment for ovarian cancer and compared to symptoms documented in their hospital notes. METHODS: Women attending follow-up clinic at Hammersmith Hospital having undergone treatment for primary or relapsed ovarian cancer were asked to complete two validated questionnaires (EORTC QLQ-C30 and QLQ-OV28) and a "wellbeing thermometer". Results were assessed and stratified by patient age, tumour stage, relapse status, type of chemotherapy received and treatment-free interval. Symptoms reported in questionnaires were compared to those documented in patients' hospital notes. RESULTS: Of 116 women approached, 100 (86%) participated in this study and had received chemotherapy for ovarian cancer between 2003 and 2010. The most frequently described and severe symptoms reported in the questionnaires were emotional symptoms, negative feelings about treatment or prognosis, fatigue and pain. Dyspareunia, cognitive impairment and peripheral neuropathy were also frequently described. Symptom severity was independent of variables such as disease stage, type of chemotherapy received and relapse status. The "wellbeing thermometer" scores closely correlated with pain, fatigue, weakness, gastrointestinal symptoms and attitude to disease or treatment (p<0.001). There was a marked discordance between questionnaire-reported symptoms and those recorded in hospital notes. CONCLUSIONS: The majority of women surveyed experienced persistent psychological and physical symptoms following ovarian cancer treatment; in particular: psychological concerns, sexual inactivity and fatigue, all potentially reversible with appropriate interventions. Our results highlight the extent of symptoms described by ovarian cancer survivors and the need for them to be adequately acknowledged and addressed.

Health-related quality of life outcomes of docetaxel/carboplatin combination therapy vs. sequential therapy with docetaxel then carboplatin in patients with relapsed, platinum-sensitive ovarian cancer: results from a randomized clinical trial.

OBJECTIVES: A phase II clinical trial compared docetaxel in combination with carboplatin to sequential single agent docetaxel followed by carboplatin for treatment of recurrent platinum-sensitive ovarian, peritoneal, or tubal cancer. This manuscript reports prospectively collected health-related quality of life (HRQL). METHODS: Participants were randomized to either weekly docetaxel 30 mg/m(2)/days 1 and 8 and carboplatin AUC 6/day 1 every 3 weeks (cDC) or docetaxel 30 mg/m(2)/days 1 and 8, repeated every 3 weeks for 6 cycles followed by carboplatin AUC 6/day 1 every 3 weeks for 6 cycles or until disease progression (sDC). The primary HRQL endpoint was the trial outcome index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, and was assessed as an intent-to-treat analysis. The secondary HRQL endpoints included the FACT-O total score, the FACT-General, and several domain scores of the FACT-O instrument (physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and the ovarian cancer specific (OCS) module). The FACT-O was administered at randomization, prior to each of 6 cycles of treatment, and at study endpoint. RESULTS: One hundred forty-eight participants were randomized to each group. Sequential docetaxel followed by carboplatin (sDC) was associated with significant improvements in the FACT-O TOI (p=0.013), FACT-O total score (p=0.033), and OCS (p=0.029) compared to the combination docetaxel and carboplatin group (cDC). CONCLUSIONS: Sequential single agent docetaxel followed by carboplatin is associated with improved HRQL when compared to cDC. The improved progression-free survival observed with cDC should be weighed against lower quality of life during treatment.

Patients' preferences in mode of surgery of an adnexal mass.

OBJECTIVE: We assessed the preferences of women with an adnexal mass for the mode of surgery. METHODS: A structured interview was designed in which women, scheduled for surgery for an adnexal mass, were confronted with fictive scenarios of the different approaches. Women were asked at what probability of a false negative test result of frozen section diagnosis they would prefer frozen section diagnosis over primary radical surgery. Furthermore, the women were asked at what probability of ovarian malignancy they would prefer laparoscopy over laparotomy. RESULTS: We interviewed 43 women. When the probability of frozen section diagnosis being false negative was set at 90%, 97% of the women preferred primary radical surgery. The mean threshold at which women switched their preference from primary radical surgery to frozen section diagnosis was at a risk of 49% on a false negative test result of frozen section diagnosis. In the choice between laparoscopy over laparotomy, the mean threshold at which the women switched their preference from laparoscopy to laparotomy was at a risk of 55% on ovarian malignancy. CONCLUSION: Women scheduled for surgery of an adnexal mass at low risk of ovarian malignancy, prefer frozen section diagnosis over primary radical surgery and prefer laparoscopy over laparotomy.

[A study of the psychosomatic aspects of endometriosis]. / Eine Untersuchung zur Psychosomatik der Endometriose.

Based upon existing psychological studies of endometriosis, the hypothesis was tested if patients suffering from this disorder differ from other infertile females with respect to psychological characteristics. Using questionnaires as well as a semi-structured psychotherapeutic interview 38 patients with endometriosis and 18 females with tubal sterility were investigated. A comparison of both groups indicated a higher level of anxiety and some evidence for a somatic preoccupation in the endometriotic patients. The analysis of the interviews (which were judged by several independent raters) confirmed the hypothesis of gender role conflicts in combination with endometriosis. This conflict seemed to be characterized by a negative experience of menarche and puberty, early gynecological problems and negative sexual experiences. This constellation is illustrated using a typical case. Based upon these results, further studies of endometriosis using a psychosomatic perspective seem to be promising.