Daily Vaginal Dilator Use During Radiation for Women With Squamous Cell Carcinoma of the Anus: Vaginal Wall Dosimetry and Patient-Reported Sexual Function.

PURPOSE: At our institution, we treat patients with a daily vaginal dilator (VD) during chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). We evaluated compliance with daily VD use, radiation dose to the vaginal wall (VW), and anterior vaginal wall (AVW), and patient-reported long-term sexual function. METHODS AND MATERIALS: We included women with SCCA who received definitive, intensity-modulated radiation therapy-based CRT. Women who were alive without evidence of disease received a patient-reported outcome survey, which included the Female Sexual Function Index (FSFI). We identified factors associated with FSFI, such as radiation dose to the VW and AVW using linear regression models and used Youden index analysis to estimate a dose cutoff to predict sexual dysfunction. RESULTS: Three hundred thirty-nine consecutively treated women were included in the analysis; 285 (84.1%) were treated with a daily VD. Of 184 women alive without disease, 90 patients (49%) completed the FSFI, and 51 (56.7%) were sexually active with valid FSFI scores. All received therapy with a daily VD. Forty-one women (80%) had sexual dysfunction. Univariate analysis showed higher dose to 50% (D50%) of the AVW correlated with worse FSFI (ß -.262; P = .043), worse desire FSFI subscore (ß -.056; P = .003), and worse pain FSFI subscore (ß -.084; P = .009). Younger age correlated with worse pain FSFI subscale (ß .067; P = .026). Age (ß .070; P = .013) and AVW D50% (ß -.087; P = .009) were significant on multivariable analysis. AVW D50% >48 Gy predicted increased risk of sexual dysfunction. CONCLUSIONS: Daily VD use is safe and well tolerated during CRT for SCCA. Using a VD during treatment to displace the AVW may reduce the risk for sexual dysfunction. Limiting the AVW D50% <48 Gy may further reduce the risk but additional data are needed to validate this constraint.

Remotely Delivered Cancer Genetic Testing in the Making Genetic Testing Accessible (MAGENTA) Trial: A Randomized Clinical Trial.

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress. Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing. Design, Setting, and Participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US residents, and had access to the internet and a health care professional. Previous cancer genetic testing or counseling was exclusionary. In the family history cohort, participants had a personal or family history of breast or ovarian cancer. In the familial pathogenic variant (PV) cohort, participants reported 1 biological relative with a PV in an actionable cancer susceptibility gene. Data analysis was performed between December 13, 2020, and May 31, 2023. Intervention: Participants completed baseline questionnaires, watched an educational video, and were randomized to 1 of 4 arms: the control arm with pretest and/or posttest genetic counseling, or 1 of 3 study arms without pretest and posttest counseling. Genetic counseling was provided by phone appointments and testing was done using home-delivered saliva kits. Main Outcomes and Measures: The primary outcome was participant distress measured by the Impact of Event Scale 3 months after receiving the results. Secondary outcomes included completion of testing, anxiety, depression, and decisional regret. Results: A total of 3839 women (median age, 44 years [range 22-91 years]), most of whom were non-Hispanic White and college educated, were randomized, 3125 in the family history and 714 in the familial PV cohorts. In the primary analysis in the family history cohort, all experimental arms were noninferior for distress at 3 months. There were no statistically significant differences in anxiety, depression, or decisional regret at 3 months. The highest completion rates were seen in the 2 arms without pretest counseling. Conclusions and Relevance: In the MAGENTA clinical trial, omitting individualized pretest counseling for all participants and posttest counseling for those without PV during remote genetic testing was not inferior with regard to posttest distress, providing an alternative care model for genetic risk assessment. Trial Registration: ClinicalTrials.gov Identifier: NCT02993068.

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

An Accessible Communication System for Population-Based Genetic Testing: Development and Usability Study.

BACKGROUND: Genetic testing uptake is low, despite the well-established connection between pathogenic variants in certain cancer-linked susceptibility genes and ovarian cancer risk. Given that most major insurers cover genetic testing for those with a family history suggestive of hereditary cancer, the issue may lie in access to genetic testing. Remotely accessible web-based communication systems may improve awareness, and uptake, of genetic testing services. OBJECTIVE: This study aims to present the development and formative evaluation of the multistep web-based communication system required to support the implementation of, and access to, genetic testing. METHODS: While designing the multistep web-based communication system, we considered various barriers and facilitators to genetic testing, guided by dimensions of accessibility. In addition to conducting usability testing, we performed ongoing assessments focusing on the function of the web-based system and participant response rates, with the goal of continuing to make modifications to the web-based communication system as it is in use. RESULTS: The combined approach of usability testing and expert user experience consultation resulted in several modifications to the multistep web-based communication system, including changes that related to imagery and content, web accessibility, and general organization of the web-based system. All recommendations were made with the goal of improving the overall accessibility of the web-based communication system. CONCLUSIONS: A multistep web-based communication system appears to be an effective way to address many potential barriers to access, which may otherwise make genetic testing difficult for at-risk individuals to participate in. Importantly, some dimensions of access were easy to assess before study recruitment, but other aspects of the communication system required ongoing assessment during the implementation process of the Making Genetic Testing Accessible study.

Using Social Media to Facilitate Communication About Women's Testing: Tool Validation Study.

BACKGROUND: Strong participant recruitment practices are critical to public health research but are difficult to achieve. Traditional recruitment practices are often time consuming, costly, and fail to adequately target difficult-to-reach populations. Social media platforms such as Facebook are well-positioned to address this area of need, enabling researchers to leverage existing social networks and deliver targeted information. The MAGENTA (Making Genetic Testing Accessible) study aimed to improve the availability of genetic testing for hereditary cancer susceptibility in at-risk individuals through the use of a web-based communication system along with social media advertisements to improve reach. OBJECTIVE: This paper is aimed to evaluate the effectiveness of Facebook as an outreach tool for targeting women aged ≥30 years for recruitment in the MAGENTA study. METHODS: We designed and implemented paid and unpaid social media posts with ongoing assessment as a primary means of research participant recruitment in collaboration with patient advocates. Facebook analytics were used to assess the effectiveness of paid and unpaid outreach efforts. RESULTS: Over the course of the reported recruitment period, Facebook materials had a reach of 407,769 people and 57,248 (14.04%) instances of engagement, indicating that approximately 14.04% of people who saw information about the study on Facebook engaged with the content. Paid advertisements had a total reach of 373,682. Among those reached, just <15% (54,117/373,682, 14.48%) engaged with the page content. Unpaid posts published on the MAGENTA Facebook page resulted in a total of 34,087 reach and 3131 instances of engagement, indicating that around 9.19% (3131/34,087) of people who saw unpaid posts engaged. Women aged ≥65 years reported the best response rate, with approximately 43.95% (15,124/34,410) of reaches translating to engagement. Among the participants who completed the eligibility questionnaire, 27.44% (3837/13,983) had heard about the study through social media or another webpage. CONCLUSIONS: Facebook is a useful way of enhancing clinical trial recruitment of women aged ≥30 years who have a potentially increased risk for ovarian cancer by promoting news stories over social media, collaborating with patient advocacy groups, and running paid and unpaid campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT02993068; https://clinicaltrials.gov/ct2/show/NCT02993068.

MAGENTA (Making Genetic testing accessible): a prospective randomized controlled trial comparing online genetic education and telephone genetic counseling for hereditary cancer genetic testing.

BACKGROUND: Studies have consistently indicated that the majority of individuals meeting the US Prevention Services Task Force guidelines for genetic testing have not had genetic counseling or testing. Despite increased availability and lower costs of multiplex cancer gene panels, there remains a gap in genetics services that has not been addressed by the current care delivery models. Lower cost of DNA sequencing with online patient-initiated ordering could increase test availability, but the ideal quantity and delivery method of patient education is not known. We hypothesized that online genetic education and testing with access to board certified genetic counselors could improve access to genetic testing while maintaining test quality and clinical utility. The MAGENTA (MAking GENetic Testing Accessible) trial is a nationwide randomized study designed to compare the effectiveness of online genetic education with pre- and post-test telephone genetic counseling to three potentially more accessible alternative approaches: online genetic education with optional telephone counseling, online genetic education with required pre-test telephone genetic counseling, and online genetic education with required post-test telephone genetic counseling. METHODS: 3000 women nationwide will undergo genetic testing for 19 hereditary cancer genes. This is a randomized four-arm non-inferiority study with equal randomization. The four study arms were selected to independently assess the delivery of genetic information both before and after genetic testing (pre-test and post-test) by either requiring telephone genetic counseling or providing only online education with optional telephone counseling. Patients have post-test telephone counseling when testing positive for a pathogenic inherited mutation in all four arms. Surveys measuring psychological, behavioral and cognitive state are completed online at baseline, 3 months, 12 months and 24 months post-results disclosure. The primary study outcome is cancer-risk distress at 3 months post-result disclosure. DISCUSSION: This trial will assess the use of a genetic service model using online access and electronic education, while evaluating the need for personal pre- and post-test genetic counseling. Data from this study may lead to increased options for delivery of genetic testing and possibly increase access to genetic testing. Identifying more individuals with inherited cancer susceptibility will allow targeted cancer prevention. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02993068 (registered December 14, 2016).

Novel Approaches to Ovarian Cancer Screening.

PURPOSE OF REVIEW: Both conventional and novel approaches to early detection of ovarian cancer are reviewed in the context of new developments in our understanding of ovarian cancer biology. RECENT FINDINGS: While CA125 as a single value lacks adequate specificity or sensitivity for screening, large studies have shown that a 2-stage strategy which tracks CA125 change over time and prompts transvaginal ultrasound (TVS) for a small subset of women with abnormally rising biomarker values achieves adequate specificity and detects a higher fraction of early-stage disease. Sensitivity could clearly be improved in both blood tests and in imaging. Metastasis can occur from ovarian cancers too small to increase blood levels of protein antigens and a significant fraction of ovarian cancers arise from the fimbriae of fallopian tubes that cannot be imaged with TVS. Autoantibodies, miRNA, ctDNA, DNA methylation in blood, and cervical mucus might improve sensitivity of the initial phase and magnetic relaxometry and autofluorescence could improve imaging in the second phase. Enhancing the sensitivity of two-stage strategies for early detection could reduce mortality from ovarian cancer.

Women's preferences for cancer risk management strategies in Lynch syndrome.

OBJECTIVE: We assessed preferences for cancer risk management strategies for Lynch syndrome (LS) in LS-affected women. METHODS: Women with LS aged ≥25 years evaluated 9 cancer risk management strategies using a visual analog scale (VAS) and modified standard gamble (SG). For the VAS, women ranked each strategy ranging from 0 (least preferred) to 100 (most preferred). VAS scores were calculated by dividing the corresponding number by 100. Scores closer to 1.0 reflected more favorable strategies. For the SG, participants were asked to specify their expected threshold of lifetime risk of endometrial or colorectal cancer, ranging from 0 to 100%, at which they would consider undertaking each strategy. Strategies included chemoprevention, cancer screening, and preventive surgery. Cancer worry and perceived cancer risk measures were collected on a subset of participants. RESULTS: Sixty-one women completed preference assessments. By VAS, annual combined screening was the most preferred, followed by annual screenings and chemoprevention with oral contraceptives. By SG, women were the most willing to endorse oral contraceptives and biannual screening strategies at the lowest threshold of lifetime risk followed by annual screening strategies. Surgical interventions were the least preferred strategies using both VAS and SG. Women with a family history of gynecologic or colorectal cancer were less likely to consider prevention or screening options compared to women without a family history. Cancer worry was higher among women with a positive family history of LS cancer. CONCLUSION: Understanding women's preferences may facilitate optimal use and adherence to cancer risk management strategies.

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure. METHODS: In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms. RESULTS: Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P < 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses. CONCLUSIONS: In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.

Prospective Randomized Biomarker Study of Metformin and Lifestyle Intervention for Prevention in Obese Women at Increased Risk for Endometrial Cancer.

Obesity increases risk of endometrial cancer through dysregulation of estrogen and insulin signaling. The primary aim of this study was to evaluate the impact of metformin or lifestyle intervention on endometrial proliferation in postmenopausal obese women. Secondary aims included evaluating obesity-related biomarkers and adverse events experienced. Obese, postmenopausal women with prediabetes were randomized into four groups for a 16-week intervention using a 2 (metformin 1700 mg/day vs. placebo) × 2 (lifestyle intervention vs. no lifestyle intervention) factorial design. Pre- and postintervention endometrial proliferation, anthropometrics, body composition, and serum biomarkers (sex hormones, sex hormone binding globulin, IGF-I, adiponectin, omentin, insulin, glucose, and others) were assessed. Data were analyzed with linear regression models and false-discovery rate correction. Of 576 women approached for the study, 52 attended initial screening, 29 were eligible and randomized, and 26 completed the study. Lifestyle intervention resulted in significant loss of weight (-4.23 kg, P = 0.006) and total fat mass (-3.23 kg, P < 0.001). Participants receiving metformin lost 3.43 kg of weight (P = 0.023), but this was not statistically significant after multiple comparisons adjustment controlling false-discovery rate to 10%. Endometrial proliferation was low at baseline (mean 7.1%) and remained unchanged by 16 weeks, but included substantial variability. Metformin and lifestyle intervention produced minor changes to serum biomarkers. Lifestyle intervention produced the most significant changes in weight and body composition. While it is known that obese postmenopausal women are at increased risk for endometrial cancer, improved biomarkers are needed to stratify risk and test prevention strategies, particularly at the endometrial tissue level. Cancer Prev Res; 11(8); 477-90. ©2018 AACR.

Abnormal Uterine Bleeding as the Presenting Symptom of Hematologic Cancer.

OBJECTIVE: To estimate the percentage of women with a hematologic cancer who present with abnormal uterine bleeding (AUB). METHODS: We performed a retrospective analysis of the records of women with hematologic malignancies treated at our institution from January 2002 through January 2016. Women with AUB as the chief presenting symptom were identified. RESULTS: Of the 10,682 women with hematologic malignancies, 38 had AUB as their chief presenting symptom. These women were young (median age 34 years), premenopausal, and otherwise healthy. The top four additional presenting symptoms were fatigue, dyspnea or shortness of breath, bruising or petechiae, and fever, with means (95% confidence interval) of 58% (41-74%), 42% (26-59%), 42% (26-59%), and 24% (11-40%), respectively. The complete blood count on initial presentation with AUB revealed that 33 (87%) women had anemia (mean hemoglobin level 8.6 g/dL) and 34 (89%) had thrombocytopenia (mean platelet count 81,000/microliter). Twelve (32%) women had neutropenia, eight (21%) women had normal white blood cell counts, and 18 (47%) women had leukocytosis. Thirty-three women (87%) were diagnosed with acute leukemia, one with myelodysplastic syndrome (3%) and four (11%) with chronic leukemia. CONCLUSION: We estimate the incidence of AUB as the chief presenting symptom is 3.6 cases per 1,000 women with hematologic cancer. These young, otherwise healthy women who present with acute, new-onset heavy menstrual bleeding in conjunction with thrombocytopenia or pancytopenia should be referred to hematology for evaluation of possible hematologic malignancy.

Cancer Incidence in First- and Second-Degree Relatives of BRCA1 and BRCA2 Mutation Carriers.

BACKGROUND: Mutations in the BRCA1 and BRCA2 genes are associated with increased risk of breast, ovarian, and several other cancers. The purpose of the present study was to evaluate the incidence of cancer in first- and second-degree relatives of BRCA mutation carriers compared with the general population. MATERIALS AND METHODS: A total of 1,086 pedigrees of BRCA mutation carriers was obtained from a prospectively maintained, internal review board-approved study of persons referred for clinical genetic counseling at the University of Texas MD Anderson Cancer Center. We identified 9,032 first- and second-degree relatives from 784 pedigrees that had demonstrated a clear indication of parental origin of mutation. Standardized incidence ratios (SIRs) were used to compare the observed incidence of 20 primary cancer sites to the expected incidence of each cancer based on the calculated risk estimates according to each subject's age, sex, and ethnicity. RESULTS: BRCA1 families had increased SIRs for breast and ovarian cancer (p < .001) and decreased SIRs for kidney, lung, prostate, and thyroid cancer and non-Hodgkin's lymphoma (p < .001). BRCA2 families had increased SIRs for breast, ovarian, and pancreatic cancer (p < .001) and decreased SIRs for kidney, lung, thyroid, and uterine cancer and non-Hodgkin's lymphoma (p < .0025). Analysis of only first-degree relatives (n = 4,099) identified no decreased SIRs and agreed with the increased SIRs observed in the overall study population. CONCLUSION: We have confirmed previous reports of an association between breast, ovarian, and pancreatic cancers with BRCA mutations. Additional research to quantify the relative risks of these cancers for BRCA mutation carriers can help tailor recommendations for risk reduction and enhance genetic counseling. IMPLICATIONS FOR PRACTICE: BRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer. However, the implications and risks of other cancers continues to be investigated. Evaluating the risks for other cancers further is key in identifying and managing risk reduction strategies.

Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian.

BACKGROUND: Previous studies have reported additional cancers associated with BRCA mutations; however, the type, magnitude of risk, and sex differences remain to be clarified. The purpose of this study was to evaluate the incidence of cancers other than breast and ovarian cancer in known mutation carriers. METHODS: An institutional review board-approved study identified 1072 patients who had genetic counseling at the authors' institution and tested positive for a deleterious BRCA mutation. The expected number of cancer cases was calculated from the number of individuals in the study sample multiplied by the cancer incidence rates for the general population. The expected and observed numbers of cases were calculated in 5-year intervals to accommodate different age-related incidence rates. Standardized incidence ratios (SIRs) for each cancer type were calculated. RESULTS: Among the 1072 mutation carriers, 1177 cancers of 30 different cancer types were identified. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian cancer; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P < .001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P = .002). CONCLUSIONS: The results of this study uphold the current recommendations for hereditary breast and ovarian cancer screening of cancers other than breast and ovarian cancer by the National Comprehensive Cancer Network. Larger cohorts and collaborations are needed to further verify these findings.

Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome.

OBJECTIVE: Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. METHODS: We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1-2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. RESULTS: Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. CONCLUSIONS: Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1-2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer.

The incidence, attitudes and practices of the removal of pubic hair as a body modification.

OBJECTIVE: To evaluate the incidence, attitudes, and practices of the removal of pubic hair as a body modification. DESIGN: A voluntary, anonymous survey was conducted among adolescents and young women 12-20 years of age seen in gynecology clinics in Houston, Texas. RESULTS: There were a total of 171 adolescent participants surveyed, of whom 70.4% of reported routinely shaving or waxing their pubic hair. More traditional body modification methods were evaluated, and 3.5% reported tattoos and 57.1% reported piercings. Sexually active participants were more likely to remove pubic hair routinely. The areas of the body where the participants felt there was "too much" hair included the genital area, upper lip, and abdomen. Of total respondents, 14.7% reported feeling "pressure" from friends or family to participate in body modification such as tattooing, piercing, or removal of pubic hair. The decision to participate in body modification was mostly influenced by friends and family. CONCLUSION: Based on this study, removal of pubic hair as a body modification is common. The results of this study demonstrated that removal of pubic hair was more common in sexually active participants compared to non-sexually active participants. Therefore, providers should additionally be aware that removal of pubic hair may be a warning sign of sexual behaviors or impending sexual activity.