Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study

Objectives: To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM). Design: Prospective randomised trial. Setting: Breast health centre of a tertiary care centre. Participants: 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash. Interventions Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks. Outcome measures The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). Results: 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups. Conclusions: Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary. Trial registration clinicaltrials.gov (NCT00711529)

Abstract P6-12-13: Developing a non-hormonal treatment for vaginal dryness for breast cancer survivors: A pilot study of a therapeutic ultrasound device

Abstract Objectives: Breast cancer survivors need a non-hormonal treatment for vaginal dryness, as estrogen replacement therapy is often contraindicated or undesired. Therapeutic ultrasound applied to the vaginal introitus is safe and was shown to increase vaginal temperature and blood flow in our phase I study. We now report results from a twelve-week trial of daily, self-applied therapeutic ultrasound to the vaginal introitus. Methods: Breast cancer survivors and post-menopausal women with symptomatic vaginal atrophy were enrolled. A gynecologic oncologist supervised participants in application of a gel-pad equipped ultrasound head (Intelect TranSport, Chattanooga Group) to the vaginal introitus at an enrollment visit, and instructed women on self-application. Daily, 8-minute treatment applications for 12 weeks were planned, and dose was titrated as needed for comfort. Vaginal Maturation Index (VMI) specimens were collected and Vaginal Health Index (VHI) was recorded at study visits. Patient-reported outcomes for vaginal dryness and personal lubrication were recorded on a Likert-type scale (0-3). Student's t-test was used to analyze ordinal and continuous variables in an intent-to-treat analysis. Results: From December 2015 to January 2017, 20 women were enrolled, including 7 breast cancer survivors. Mean VMI for the study population was 25.1 (median 25) at baseline, and 21.4 (median 6) after 12 weeks of treatment (p&amp;gt;0.05). Similarly, there were no significant changes seen in mean VHI, which was 12.8 (median 13) at baseline and 14.1 (median 14) at 12 weeks (p&amp;gt;0.05). Statistically significant improvements were seen in both vaginal dryness and lubrication as reported by patients' scores. The mean vaginal dryness score for the population was 1.9 (median 2) at baseline and 1 (median 1) at 12 weeks (p&amp;lt;0.05). The effect was more pronounced in a subset of women (n=6) who did not use ultrasound jelly with their device (mean baseline score of 2.3 reduced to 1 at 12 weeks). Baseline vaginal lubrication scores (mean 0.6, median 1) for the population also improved after 12 weeks (mean 1.4, median 1, p&amp;lt;0.05), though the scores remained in the “mild” range. The six women who used the ultrasound device without jelly reported essentially no lubrication at the start of the study (mean 0.17, median 0), and had notably improved symptoms, reporting moderate lubrication after 12 weeks (mean and median score 1.5). Of the 15 women who completed the treatment according to protocol, 93% reported an improvement in at least one of their symptoms. Conclusions: Self-application of therapeutic ultrasound to the vaginal introitus decreased symptoms of vaginal atrophy in the majority of users. While no detectable changes in tissue physiology were noted with the VMI or VHI tools, the notable improvement in patient-reported outcomes warrants further study. A phase III clinical trial with a customized device is planned. Citation Format: MacLaughlan David S, Rockweiler H, Krone R, Middelton S, Blayney D. Developing a non-hormonal treatment for vaginal dryness for breast cancer survivors: A pilot study of a therapeutic ultrasound device [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-13.</jats:p

Mediation of Racial and Ethnic Inequities in the Diagnosis of Advanced-Stage Cervical Cancer by Insurance Status

ImportanceBlack and Hispanic or Latina women are more likely than White women to receive a diagnosis of and to die of cervical cancer. Health insurance coverage is associated with diagnosis at an earlier stage of cervical cancer.ObjectiveTo evaluate the extent to which racial and ethnic differences in the diagnosis of advanced-stage cervical cancer are mediated by insurance status.Design, Setting, and ParticipantsThis retrospective, cross-sectional population-based study used data from the Surveillance, Epidemiology, and End Results (SEER) program on an analytic cohort of 23 942 women aged 21 to 64 years who received a diagnosis of cervical cancer between January 1, 2007, and December 31, 2016. Statistical analysis was performed from February 24, 2022, to January 18, 2023.ExposuresHealth inusurance status (private or Medicare insurance vs Medicaid or uninsured).Main Outcomes and MeasuresThe primary outcome was a diagnosis of advanced-stage cervical cancer (regional or distant stage). Mediation analyses were performed to assess the proportion of observed racial and ethnic differences in the stage at diagnosis that were mediated by health insurance status.ResultsA total of 23 942 women (median age at diagnosis, 45 years [IQR, 37-54 years]; 12.9% were Black, 24.5% were Hispanic or Latina, and 52.9% were White) were included in the study. A total of 59.4% of the cohort had private or Medicare insurance. Compared with White women, patients of all other racial and ethnic groups had a lower proportion with a diagnosis of early-stage cervical cancer (localized) (American Indian or Alaska Native, 48.7%; Asian or Pacific Islander, 49.9%; Black, 41.7%; Hispanic or Latina, 51.6%; and White, 53.3%). A larger proportion of women with private or Medicare insurance compared with women with Medicaid or uninsured received a diagnosis of an early-stage cancer (57.8% [8082 of 13 964] vs 41.1% [3916 of 9528]). In models adjusting for age, year of diagnosis, histologic type, area-level socioeconomic status, and insurance status, Black women had higher odds of receiving a diagnosis of advanced-stage cervical cancer compared with White women (odds ratio, 1.18 [95% CI, 1.08-1.29]). Health insurance was associated with mediation of more than half (ranging from 51.3% [95% CI, 51.0%-51.6%] for Black women to 55.1% [95% CI, 53.9%-56.3%] for Hispanic or Latina women) the racial and ethnic inequities in the diagnosis of advanced-stage cervical cancer across all racial and ethnic minority groups compared with White women.Conclusions and RelevanceThis cross-sectional study of SEER data suggests that insurance status was a substantial mediator of racial and ethnic inequities in advanced-stage cervical cancer diagnoses. Expanding access to care and improving the quality of services rendered for uninsured patients and those covered by Medicaid may mitigate the known inequities in cervical cancer diagnosis and related outcomes.</jats:sec

Stage 1 results of BrUOG 354: A randomized phase II trial of nivolumab alone or in combination with ipilimumab for people with ovarian and other extra-renal clear cell carcinomas (NCT03355976).

5598 Background: Clear Cell Carcinoma (CCC) outside the kidney is a rare tumor that can arise from multiple organs, including the ovary, endometrium and cervix. Extra-renal CCC is chemoresistant and has a poor prognosis. Data suggest that CCC of the gynecologic tract resembles the genomic profile of Renal Cell Carcinoma (RCC), which is responsive to immune checkpoint inhibition (ICI) therapy. We are conducting a two-stage phase 2 trial evaluating immunotherapy for extra-renal CCC. The primary objective is to assess overall rate of response (ORR); Progression-Free (PFS), Overall Survival (OS), and correlative biomarker studies are secondary. Here we present the results of Stage 1. Methods: This is a randomized two-stage non-comparative phase II study evaluating nivolumab (240mg IV every two weeks) alone (N) and in combination with ipilimumab (1mg/kg every six weeks, [N+I]) in patients with relapsed extra-renal CCC after at least one prior chemotherapy (no prior ICI), and measurable disease. Treatment was continued until disease progression or unacceptable toxicity. Stage 1 of this trial called for up to 30 volunteers (15 per arm) after which the study was closed. Consideration to reopen to stage 2 called for two or more responses in either arm. Here we present the completion of Stage 1; the release of results was approved by Brown University Oncology Group (BrUOG) Data Safety and Monitoring Committee. Results: Between July 2018 and October 2021, 30 patients were enrolled and 29 were treated (Table). The majority (83%) had CCC of the ovary (n=24). The ORR with N and N+I was 14.2 and 26.7%, respectively. The 6 month PFS rate was 19.1 and 43.8%; median PFS was 2.7 (95%CI 1.3-5.1) and 5.1 months (95%CI 0.9-NR), respectively. Grade ≥3 treatment-related toxicities occurred in 4 (28.6%) on N and 5 (33.3%) on N+I. There were no treatment-related deaths and no new safety signals. One volunteer enrolled on N+I stopped treatment after two years and remains in CR to date. Conclusions: Although sufficient activity was seen in CCC in both arms, the single-agent activity of N is similar to published reports in platinum-resistant epithelial ovarian cancer and decision made not to pursue it further. However, the combination of ipilimumab and nivolumab warrants additional investigation, and the second stage of this study will enroll 14 more patients to receive N+I. Clinical trial information: NCT03355976. [Table: see text] </jats:p