Use of aromatase inhibitors in menopausal deep endometriosis: a case report and literature review.

We report and review the clinical effectiveness of aromatase inhibitors in a patient with refractory, recurrent and infiltrating endometriosis. We demonstrate excellent clinical, radiological and endoscopic responses after failure of multiple other modalities. Our case and the literature show that single-agent letrozole is capable to treat deep infiltrative endometriosis involving the rectum and the urinary tract. The use of aromatase inhibitor treatment of endometriosis in postmenopausal women makes sense, is safe and is well tolerated. Difficult cases of deep infiltrative endometriosis might require use of combined surgical and medical treatment modalities. Multidisciplinary involvement of the gynecologist, bowel surgeon, urologist and invasive radiologist might be needed. Aromatase inhibitors should be considered to be an integral part of the armamentarium in the management of women with endometriosis, especially in refractory cases that have failed conventional therapeutic modalities.

Characterization of the endometrial, cervicovaginal and anorectal microbiota in post-menopausal women with endometrioid and serous endometrial cancers.

OBJECTIVE: To characterize the microbiota of postmenopausal women undergoing hysterectomy for endometrioid (EAC) or uterine serous cancers (USC) compared to controls with non-malignant conditions. METHODS: Endometrial, cervicovaginal and anorectal microbial swabs were obtained from 35 postmenopausal women (10 controls, 14 EAC and 11 USC) undergoing hysterectomy. Extracted DNA was PCR amplified using barcoded 16S rRNA gene V4 primers. Sequenced libraries were processed using QIIME2. Phyloseq was used to calculate α- and ß- diversity measures. Biomarkers associated with case status were identified using ANCOM after adjustment for patient age, race and BMI. PICRUSt was used to identify microbial pathways associated with case status. RESULTS: Beta-diversity of microbial communities across each niche was significantly different (R2 = 0.25, p < 0.001). Alpha-diversity of the uterine microbiome was reduced in USC (Chao1, p = 0.004 and Fisher, p = 0.007) compared to EAC. Biomarkers from the three anatomical sites allowed samples to be clustered into two distinct clades that distinguished controls from USC cases (p = 0.042). The USC group was defined by 13 bacterial taxa across the three sites (W-stat>10, FDR<0.05) including depletion of cervicovaginal Lactobacillus and elevation of uterine Pseudomonas. PICRUSTt analysis revealed highly significant differences between the USC-associated clades within the cervicovaginal and uterine microbiota. CONCLUSIONS: The microbial diversity of anatomic niches in postmenopausal women with EAC and USC is different compared to controls. Multiple bacteria are associated with USC case status including elevated levels of cervicovaginal Lactobacillus, depletion of uterine Pseudomonas, and substantially different functional potentials identified within cervicovaginal and uterine niches.

Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer.

BACKGROUND: Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. The objective of this study was to evaluate the association of cfDNA concentration with clinicopathologic variables of poor prognosis and overall survival among women with uterine cancer compared to benign cancer-free controls. METHODS: cfDNA was extracted from the serum of 91 women with multiple uterine cancer histologies and 22 post-menopausal controls without cancer. Low molecular weight (LMW) cfDNA was separated from contaminating genomic high molecular weight cfDNA using paramagnetic bead purification and its concentration was measured using fluorometric quantification. Clinicopathologic data was abstracted from the electronic medical record. The association between serum cfDNA concentration, clinicopathologic variables, and overall survival was assessed using linear regression modelling, Cox proportional hazards modelling, and the Kaplan-Meier method. RESULTS: Median total serum cfDNA concentration for the cohort was 69.2 ng/mL (IQR 37.4, 132.3) and median LMW cfDNA concentration was 23.8 ng/mL (IQR 14.9, 44.4). There were no significant differences in total serum cfDNA concentration with any clinicopathologic variables. However, LMW cfDNA concentration was significantly higher in serum of women with cancer (25.8 ng/mL IQR 16.0, 49.6) compared to benign controls (15.5 ng/mL IQR 9.3, 25.8 ng/mL) (p < 0.01). It is also significantly higher among women with early stage cancer than benign controls (p < 0.01). There were also significant associations between LMW cfDNA concentration and stage of cancer (p = 0.01) and histology (p = 0.02). Patients with leiomyosarcoma and carcinosarcoma had higher cfDNA concentrations than those with endometrioid cancer. Over a median follow-up of 51.9 months, 75th percentile for overall survival for women with cancer was 24.0 months. Higher LMW cfDNA concentrations is associated with lower survival among women with cancer (p < 0.01). CONCLUSIONS: Serum LMW cfDNA concentration is associated with overall survival in women with uterine cancer, and it is higher among women with uterine cancer compared to those of controls.

The association of sexual dysfunction with race in women with gynecologic malignancies.

Gynecologic cancer survivors report sexual health among their highest concerns. The aim of this study was to identify the prevalence of sexual dysfunction (SD) in survivors of gynecologic malignancies and to evaluate the association of sexual function with race, ethnicity and treatment modality. In this study, survivors of endometrial, cervical, vaginal, and vulvar cancer who presented to the gynecologic oncology practice were asked to self-administer the Female Sexual Function Index (FSFI) survey to evaluate their sexual function. The prevalence of SD was estimated and its association with demographic and clinical co-variates was analyzed. Of the 155 participants, the prevalence of SD was 44.5% (95%CI: 36.7-52.7). Patients were significantly more likely to report SD if they did not currently have a partner (69% vs 22% p < .01). Abstinence within six months of their cancer diagnosis was also associated with SD (72% vs 26% p < .01). Patients who self-identified as black race compared to white race were three times more likely to have SD (OR = 3.9, 95% CI 1.1-14.3). Patients who received adjuvant chemotherapy and radiation therapy compared to those who did not among the entire cohort had an increased risk of SD (OR = 3.4, 95% CI 1.2-9.6). In our diverse population, almost half of our patients were identified to have SD. Black as compared to white race reported significantly higher sexual dysfunction. An increased risk for sexual dysfunction was observed among those women who received chemotherapy and radiation with or without surgery. PRECIS: Survivorship is an important issue for women with gynecologic malignancies. This study addresses the high rates of sexual dysfunction in a racially diverse patient population.

Readability assessment of online gynecologic oncology patient education materials from major governmental, non-profit and pharmaceutical organizations.

OBJECTIVE: Patients are increasingly using online materials to learn about gynecologic cancer. Providers can refer patients to online educational materials produced by a number of different major medical organizations and pharmacology companies. The National Institutes of Health (NIH) and the American Medical Association (AMA) recommend that patient educational materials (PEMs) are written between a sixth and eighth grade reading level. In this study, we assess the readability of online PEMs published by major medical organizations and industry partners. METHODS: Websites from twelve websites providing educational materials for gynecologic oncology patients were surveyed. Online PEMs were identified and analyzed using seven validated readability indices. One-way ANOVA and Tukey's Honestly Significant Difference (HSD) post-hoc analysis were performed to detect differences in readability between publishers. RESULTS: Two-hundred and sixty PEMs were included in this analysis. Overall, PEMs were written at a mean 11th±0.6 grade reading level. Only 6.5% of articles were written at the AMA/NIH recommended reading grade level of 6th to 8th grade or below. ANOVA demonstrated a significant difference in readability between publishing associations (p<0.01). PEMs from the Centers for Disease Control had a mean 9th±1.2 grade reading level and were significantly lower than all other organizations. PEMs from The Foundation for Women's Cancer had a mean 13th±1.8 grade reading level and were significantly higher than most other organizations. PEMs from pharmaceutical companies (mean readability=10.1±1.1, N=30) required the lowest reading grade level and were significantly more readable than those from governmental organizations (11.1±1.7, p<0.05) and nonprofit medical associations (12.4±1.7, p<0.01) in ANOVA and Tukey-Kramer post hoc analysis. CONCLUSIONS: Gynecologic oncology PEMs available from twelve major organization websites are written well above the recommended sixth to eighth grade reading difficulty level.

Utilizing the Patient Reported Outcomes Measurement Information System (PROMIS®) to increase referral to ancillary support services for severely symptomatic patients with gynecologic cancer.

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS®) Network has developed a comprehensive repository of electronic patient reported outcomes measures (ePROs) of major symptom domains that have been validated in cancer patients. Their use for patients with gynecologic cancer has been understudied. Our objective was to establish feasibility and acceptability of PROMIS ePRO integration in a gynecologic oncology outpatient clinic and assess if it can help identify severely symptomatic patients and increase referral to supportive services. METHODS: English-speaking patients with a confirmed history of gynecologic cancer completed PROMIS ePROs on iPads in the waiting area of an outpatient gynecologic oncology clinic. Symptom scores were calculated for each respondent and grouped using documented severity thresholds. Response data was compared with clinicopathologic characteristics across symptom domains. Severely symptomatic patients were offered referral to ancillary services and asked to complete post-exposure surveys assessing acceptability of the ePRO. RESULTS: Of the 336 patients who completed ePROs, 35% had active disease and 19% had experienced at least one disease recurrence. Sixty-nine percent of the cohort demonstrated moderate to severe physical dysfunction (60%), pain (36%), fatigue (28%), anxiety (9%), depression (8%), and sexual dysfunction (32%). Thirty-nine (12%) severely symptomatic patients were referred to services such as psychiatry, palliative care, pain management, social work or integrative oncology care. Most survey respondents identified the ePROs as helpful (78%) and easy to complete (92%). CONCLUSIONS: Outpatient PROMIS ePRO administration is feasible and acceptable to gynecologic oncology patients and can help identify severely symptomatic patients for referral to ancillary support services.

Novel neurosensory testing in cancer patients treated with the epothilone B analog, ixabepilone.

BACKGROUND: We have previously established the recommended phase II dose (RPTD) of ixabepilone as 40 mg/m(2) administered over 1 h repeated every 3 weeks with neuropathy as a cumulative dose-limiting toxicity. We expanded the cohort at the RPTD to include detailed assessment of nerve damage in these patients. We report our findings on vibration perception threshold (VPT) and neuropathy. PATIENTS AND METHODS: Forty-four patients were treated with a median (range) of three (1-14) cycles of ixabepilone. The VPT (5-min duration) and nerve conduction test (NCT, 10-min duration) were carried out in the office, before ixabepilone dosing, and every two cycles thereafter. RESULTS: Neuropathy (grade 1 and grades 2-3) was observed in 17 (38.6%) and 11 (25%) patients, respectively. The mean increase in VPT as a function of grade 0-1 versus grades 2-3 neuropathy was 0.235 +/- 0.03 versus 0.869 +/- 0.09 (P = 0.049) vibration units. The F-wave frequency and distal motor latency, as assessed using the NCT, did not correlate with clinical neurotoxicity. CONCLUSION: The change in VPT is observed early and likely reflects early vibration perception change. Mean change in VPT correlates with the severity of clinical neuropathy. Whether VPT change predicts onset of severe neuropathy warrants prospective testing and validation.