A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study.

BACKGROUND: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC). OBJECTIVE: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC. STUDY DESIGN: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC. Treatment with E (10 mg daily) and L (2.5 mg daily) or T (20 mg twice daily) and M (200 mg daily alternating weeks) was randomly assigned, and stratified by prior adjuvant therapy. Treatments were administered orally. Primary endpoint was response rate. RESULTS: Between February 2015 and April 2016, everolimus/letrozole (n = 37) or MT (n = 37) was assigned to 74 patients. Median follow-up was 37 months. Eight (22%; 95% CI 11% to 37%) patients responded on EL (one CR) and nine (25%; 95% CI 14% to 41%) patients responded on MT (three CRs). Median PFS for EL and MT arms was 6 months and 4 months, respectively. On EL, chemo-nave patients demonstrated a 28 month median PFS; prior chemotherapy patients had a 4-month median PFS. On MT, patients without prior therapy had a 5-month median PFS; those with prior chemotherapy demonstrated a 3-month PFS. Common grade 3 adverse events were anemia (9 [24%] patients EL vs 2 [6%] MT) and mucositis (2 [5%] vs 0 [0%]). Grade 3/4 thromboembolic events were observed with MT but not with EL (0 [0%] vs 4 [11%]). CONCLUSIONS: EL and MT demonstrated clinically meaningful efficacy in recurrent EC patients. The higher PFS observed in chemo-naïve patients is worthy of confirmation in future studies.

GOG 244 - The Lymphedema and Gynecologic cancer (LeG) study: The impact of lower-extremity lymphedema on quality of life, psychological adjustment, physical disability, and function.

OBJECTIVE: To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244. METHODS: The prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy [FACT]), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%. RESULTS: In 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms. CONCLUSIONS: LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed.

GOG 244-The lymphedema and gynecologic cancer (LEG) study: Incidence and risk factors in newly diagnosed patients.

OBJECTIVES: To evaluate the incidence and risk factors for lymphedema associated with surgery for gynecologic malignancies on GOG study 244. METHODS: Women undergoing a lymph node dissection for endometrial, cervical, or vulvar cancer were eligible for enrollment. Leg volume was calculated from measurements at 10-cm intervals starting 10 cm above the bottom of the heel to the inguinal crease. Measurements were obtained preoperatively and postoperatively at 4-6 weeks, and at 3-, 6-, 9-, 12-, 18-, and 24- months. Lymphedema was defined as a limb volume change (LVC) ≥10% from baseline and categorized as mild: 10-19% LVC; moderate: 20-40% LVC; or severe: >40% LVC. Risk factors associated with lymphedema were also analyzed. RESULTS: Of 1054 women enrolled on study, 140 were inevaluable due to inadequate measurements or eligibility criteria. This left 734 endometrial, 138 cervical, and 42 vulvar patients evaluable for LVC assessment. Median age was 61 years (range, 28-91) in the endometrial, 44 years (range, 25-83) in the cervical, and 58 years (range, 35-88) in the vulvar group. The incidence of LVC ≥10% was 34% (n = 247), 35% (n = 48), and 43% (n = 18), respectively. The peak incidence of lymphedema was at the 4-6 week assessment. Logistic regression analysis showed a decreased risk with advanced age (p = 0.0467). An exploratory analysis in the endometrial cohort showed an increased risk with a node count >8 (p = 0.033). CONCLUSIONS: For a gynecologic cancer, LVC decreased with age greater than 65, but increased with a lymph node count greater than 8 in the endometrial cohort. There was no association with radiation or other risk factors.

GOG 244 - The LymphEdema and Gynecologic cancer (LEG) study: The association between the gynecologic cancer lymphedema questionnaire (GCLQ) and lymphedema of the lower extremity (LLE).

OBJECTIVE: To explore whether patient-reported lymphedema-related symptoms, as measured by the Gynecologic Cancer Lymphedema Questionnaire (GCLQ), are associated with a patient-reported diagnosis of lymphedema of the lower extremity (LLE) and limb volume change (LVC) in patients who have undergone radical surgery, including lymphadenectomy, for endometrial, cervical, or vulvar cancer on Gynecologic Oncology Group (GOG) study 244. METHODS: Patients completed the baseline and at least one post-surgery GCLQ and LVC assessment. The 20-item GCLQ measures seven symptom clusters-aching, heaviness, infection-related, numbness, physical functioning, general swelling, and limb swelling. LLE was defined as a patient self-reported LLE diagnosis on the GCLQ. LVC was measured by volume calculations based on circumferential measurements. A linear mixed model was fitted for change in symptom cluster scores and GCLQ total score and adjusted for disease sites and assessment time. RESULTS: Of 987 eligible patients, 894 were evaluable (endometrial, 719; cervical, 136; vulvar, 39). Of these, 14% reported an LLE diagnosis (endometrial, 11%; cervical, 18%; vulvar, 38%). Significantly more patients diagnosed versus not diagnosed with LLE reported ≥4-point increase from baseline on the GCLQ total score (p < 0.001). Changes from baseline were significantly larger on all GCLQ symptom cluster scores in patients with LLE compared to those without LLE. An LVC increment of >10% was significantly associated with reported general swelling (p < 0.001), heaviness (p = 0.005), infection-related symptoms (p = 0.002), and physical function (p = 0.006). CONCLUSIONS: Patient-reported symptoms, as measured by the GCLQ, discerned those with and without a patient-reported LLE diagnosis and demonstrated predictive value. The GCLQ combined with LVC may enhance our ability to identify LLE.

Pre-operative assessment and post-operative outcomes of elderly women with gynecologic cancers, primary analysis of NRG CC-002: An NRG oncology group/gynecologic oncology group study.

INTRODUCTION: CC-002 is a prospective cooperative group study conducted by NRG Oncology to evaluate whether a pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment (GA) is associated with major post-operative complications in elderly women with suspected ovarian, fallopian tube, primary peritoneal or advanced stage papillary serous uterine (GYN) carcinoma undergoing primary open cytoreductive surgery. METHODS: Patients 70 years or older with suspected advanced gynecologic cancers undergoing evaluation for surgery were eligible. A GA-GYN score was derived from a model utilizing the GA as a pre-operative tool. Patients were followed for six weeks post-operatively or until start of chemotherapy. Post-operative events were recorded either directly as binary occurrence (yes or no) using CTCAE version 4.0. RESULTS: There were 189 eligible patients, 117 patients with primary surgical intervention and 37 patients undergoing interval cytoreduction surgery. The association between higher GA-GYN score and major postoperative complications in patients undergoing primary surgery was not significant (p = 0.1341). In a subgroup analysis of patients with advanced staged malignant disease who underwent primary cytoreductive surgery, there was a trend towards an association with the GA-GYN score and post-operative complications. CONCLUSION: The pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment was not predictive of major post-operative complications in elderly patients undergoing primary open cytoreductive surgery. However, there was an association between GA-GYN score and post-operative complications in a subgroup of patients with advanced staged malignant disease.

Evaluation of exposures to healthcare personnel from cisplatin during a mock demonstration of intra-operative intraperitoneal chemotherapy administration.

UNLABELLED: Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. In 2006, the National Cancer Institute released an announcement supporting the use of intraperitoneal (IP) chemotherapy in advanced ovarian cancer. It remains unanswered how many cycles of IP chemotherapy are required to maintain a survival advantage. There may be a benefit with as few as three IP cycles and possibly as few as one IP chemotherapy cycle. OBJECTIVE: In preparation for a clinical trial in which chemotherapy would be administered intra-operatively, the question of exposure to healthcare personnel arose, therefore, the purpose of this study was to perform an evaluation of healthcare personnel exposure to cisplatin during a mock demonstration of intraperitoneal chemotherapy administration. MATERIALS AND METHODS: The National Institute of Occupational Safety and Health (NIOSH), the Women's Cancer Center of Nevada, and the staff of the University Medical Center, Las Vegas, participated in this mock demonstration. Employees wore personal protective equipment recommended by NIOSH. Wipe, area, and breathing zone air samples were taken from the pharmacy and operating room, and during sterilization of equipment. RESULTS: All samples were negative for cisplatin, except for one surface wipe from the floor of the operating room (OR) after the mock procedure. Upon sanitization of the OR, no cisplatin was detected on the floor. CONCLUSION: This was the first study evaluating the exposure of healthcare personnel to the administration of cisplatin intra-operatively. NIOSH endorsed this practice so long as the employees adhere to using the recommended personal protective equipment.

The use of argon beam coagulation in treating vulvar intraepithelial neoplasia III: a retrospective review.

UNLABELLED: Argon beam coagulation (ABC) has unique properties which make it suitable for the local treatment of superficial epithelial disorders such as vulvar intraepithelial neoplasia (VIN III). OBJECTIVE: To evaluate argon beam coagulation in treating multifocal VIN III. METHODS: Argon beam coagulation was used in twenty-nine patients. ABC was set at 80 W, 7 L/min. All patients were given 1% silvadene cream to apply to vulva. Patients had follow-up appointments two weeks and six weeks postoperatively. Patients were followed every three to six months for the subsequent year. RESULTS: 2 of 29 (6.8%) experienced moderate pain within the first two weeks postoperatively requiring prescriptions for perocet. 2 of 29 (6.8%) had yeast infection requiring diflucan. Mean follow-up time was 34.9 months (11.7-37.4). 15 of 29 (51.7%) had no recurrence within the follow-up period. 14 of 29 (48.3%) recurred within the follow-up period. The mean time to recurrence is 23.2 months. CONCLUSION: This small retrospective review is the first to evaluate argon beam coagulation in treating multifocal VIN III. This review indicates that ABC is comparable to other vulva organ conserving therapies. ABC retains cosmesis, and form of the vulva. This is a major advantage over surgery. Repeat treatments are also possible, which is important in a condition such as VIN, which tends to be multifocal and recurrent.

Primary uterine cancer in Maryland: impact of distance on access to surgical care at high-volume hospitals.

OBJECTIVE: To evaluate the influence of distance on access to high-volume surgical treatment for patients with uterine cancer in Maryland. METHODS: The Maryland Health Services Cost Review Commission database was retrospectively searched to identify primary uterine cancer surgical cases from 1994 to 2010. Race, type of insurance, year of surgery, community setting, and both surgeon and hospital volume were collected. Geographical coordinates of hospital and patient's zip code were used to calculate primary independent outcomes of distance traveled and distance from nearest high-volume hospital (HVH). Logistic regression was used to calculate odds ratios and confidence intervals. RESULTS: From 1994 to 2010, 8529 women underwent primary surgical management of uterine cancer in Maryland. Multivariable analysis demonstrated white race, rural residence, surgery by a high-volume surgeon and surgery from 2003 to 2010 to be associated with both travel 50 miles or more to the treating hospital and residence 50 miles or more from the nearest HVH (all P < 0.05). Patients who travel 50 miles or more to the treating hospital are more likely to have surgery at a HVH (odds ratio, 6.03; 95% confidence interval, 4.67-7.79) In contrast, patients, who reside ≥50 miles from a HVH, are less likely to have their surgery at an HVH. (odds ratio, 0.37; 95% confidence interval, 0.32-0.42). CONCLUSION: In Maryland, 50 miles or more from residence to the nearest HVH is a barrier to high-volume care. However, patients who travel 50 miles or more seem to do so to receive care by a high-volume surgeon at an HVH. In Maryland, Nonwhites are more likely to live closer to an HVH and more likely to use these services.

Stage I noninvasive and minimally invasive uterine serous carcinoma: comprehensive staging associated with improved survival.

OBJECTIVE: The aim of this study was to determine if comprehensive surgical staging is a better predictor of outcome than incomplete staging for women with stage I noninvasive or minimally invasive (≤3 mm) uterine serous carcinoma (USC). METHODS: Retrospective chart review was used to identify patients undergoing hysterectomy at the Johns Hopkins Hospital from 1989 to 2010. Relevant clinical and pathologic data were extracted. Patients with noninvasive and minimally invasive (≤3-mm myometrial invasion) USC were identified. Stage was assigned based on the 2009 International Federation of Gynecology and Obstetrics endometrial cancer criteria. Survival curves were generated using the Kaplan-Meier method. RESULTS: We identified 63 patients with noninvasive or minimally invasive (≤3 mm) USC. Stages I, II, III, and IV disease were noted in 65% (41/63), 6% (4/63), 14% (9/63), and 14% (9/63) of the patients, respectively. Lower stage was associated with a significantly improved disease-specific survival (P = 0.001). Comprehensive staging, including total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies, was completed in 29% (12/41) of the patients with stage I disease. There were no disease-specific deaths in the comprehensive staging group. Compared with incomplete staging, comprehensive staging was associated with a significantly improved disease-specific survival (P = 0.039). CONCLUSIONS: Patients with stage I noninvasive and minimally invasive USC on comprehensive staging have an excellent prognosis. Adjuvant therapy may not benefit this patient population.

A preliminary exploration of conversation sampling in pediatric voice disorders.

OBJECTIVE: Current methods of eliciting running speech for subjective rating, or perceptual analysis, in the assessment of pediatric voice disorders are not standardized. Whilst different assessment tools have different requirements, a commonality is the requirement to judge the perceptual characteristics of the individual's everyday speaking voice. However, it is unclear whether current practices yield ecologically valid running speech samples. The aim of this study was to analyse the length and characteristics of conversational responses, to stimuli that were designed to elicit running speech samples from pediatric clients. METHOD: Twenty conversations, conducted as part of the evaluation of voice in a pediatric population, were analysed. Length of responses, number of responses and question types were recorded. RESULTS: The median maximum utterance length was 15.9 s; seven participants presented with a maximum of less than 10 s. Response length was significantly associated with question type, F = 10.68, p<.001. The most frequent number of responses produced was 11 (range = 17, IQR = 5, 11). There was a moderate correlation between response length and number of responses, r(18)=.53, p=.02. DISCUSSION: These data demonstrated that informal conversational methods did not consistently yield running speech samples of greater than 10 s in length, the minimum sample length recommended by the CAPE-V protocol. There was considerable variability in the characteristics of the responses produced by participants. Using a task such as a narrative re-tell might allow for better standardization of responses, including elicitation of vocal behaviors of interest, as well as yield a longer sample.

Vocal health of sporting, fitness, and wellness leaders in Northern New York and Vermont.

INTRODUCTION: Fitness trainers and sporting coaches use their voices in acoustically poor conditions, for extended periods of time. Knowledge of the risk of voice problems in this cohort is emerging and has been documented in studies performed in Europe and Australia. This pilot study sought to identify the prevalence of voice problems of fitness trainers and sporting leaders in United States college towns. MATERIALS AND METHODS: An online questionnaire was distributed. The survey was based on the instrument developed by Rumbach (2013), "Vocal health of GFIs" (group fitness instructors (GFIs)) and adapted to account for the wider target population of this study. The survey included questions about participants' demographic information, as well as working conditions, including acoustic environment, leading requirements, equipment provision and maintenance and vocal diagnoses and symptoms. Questions on symptomatology included voice quality and physical symptoms (e.g. throat soreness). Recruitment took place between May and September 2018. RESULTS: Sixty-two participants completed the survey. Three participants (5.08%) reported having received a formal diagnosis of dysphonia, yet many more reported vocal symptoms, including physical symptoms (n = 15, 24.19%) and voice disturbance (n = 8, 12.90%). Few participants had received vocal education (n = 5, 8.06%) and many thought this should be included in their formal training (n = 24, 38.71%). CONCLUSIONS: In contrast to previous investigations, diagnosed voice disorders are less prevalent in this sample, based in US college towns. However, physical and vocal symptoms associated with voice overuse were common, suggesting that participants were unaware of their voice and the significance of the changes they reported.

Post fellowship training in "new-to-them" surgical techniques: assessment of learning curve characteristics.

OBJECTIVE: To evaluate surgically related quality outcomes during the learning curve for board-certified or board-eligible gynecologic oncologists developing "new-to-them" surgical techniques. METHODS: The study design was a retrospective review of patients with endometrial cancer clinically limited to the uterus and/or cervix undergoing TLH-BSO or TAH-BSO, aortic and pelvic lymphadenectomy(APLNDx), peritoneal washings with/without omentectomy from May 1996 to April /2006. A "senior" surgeon taught three board-certified or board-eligible gynecologic oncologists a "new-to-them" technique to perform both TLH-BSO and TAH-BSO with APLNDx using argon beam coagulation and endoscopic staplers in patients with early-stage endometrial cancer. The main outcome measures were: a) length of surgery; b) surgical measures, e.g. lymph node count; and c) peri-operative morbidity. A comparison of outcomes with the "senior" surgeon was undertaken. The learning curve characteristics were analyzed by ANOVA and curve estimate analysis. RESULTS: The mean operative times associated with learning a new technique to perform TLH-BSO with APLNDx and TAH-BSO with APLNDx were 155.39+/-26.32 and 102.28+/-34.22 min, respectively, with significant improvement after 20 cases (150.27+/-26.68 vs. 172.30+/-22.28, p=0.030) and 30 cases (93.30+/-24.97 vs. 124.63+/-29.73, p=0.030), respectively. Intra- and peri-operative morbidity and lymph node count were unaffected by experience. CONCLUSION: While mean operative times decreased, outcome measures of surgical quality were not adversely affected during the learning curve for post-fellowship training while acquiring "new-to-them" surgical techniques. This study emphasizes the need for "senior" surgical supervision during the initial training period. The results of this study are likely transferable to fellowship-trained gynecologic oncologists learning other "new-to-them" surgical techniques and procedures.

Abnormal cervical cytology in the diagnosis of uterine papillary serous carcinoma: earlier detection of a poor prognostic cancer subtype?

OBJECTIVE: Early detection of uterine papillary serous (UPSC), clear cell (CCC), and grade 3 endometrioid carcinomas (G3EC) - all poor prognostic variants of endometrial carcinoma (EC) - is of particular clinical relevance. The study objective was to assess the utility of liquid-based cytology (Pap) in the detection of high-grade EC. STUDY DESIGN: A retrospective, two-institution analysis of patients diagnosed with UPSC, CCC, or G3EC with a preoperative Pap from 1999 to 2010 was conducted. RESULTS: One hundred and one patients were evaluated; 51.5% had UPSC, 27.7% had CCC, and 20.8% had G3EC. Stage I/II disease was found in 69.3% of patients, and 46/101 patients (45.5%) had abnormal Paps. Significantly more patients with UPSC had abnormal Paps (65.7%) than those with CCC (25%) or G3EC (23.8%; p < 0.001). An abnormal Pap was the only presenting clinical finding in a significant number of asymptomatic UPSC patients (26.9%) compared with 4% of patients with CCC and G3EC (p = 0.005). On multivariate analysis, UPSC histology was the only variable associated with an abnormal Pap. CONCLUSIONS: A high incidence of abnormal cervical cytology was observed in women with high-grade EC, particularly in UPSC patients. Although hypothesis generating, a proportion of asymptomatic UPSC patients had abnormal cytology, signifying that Pap smear screening may help detect the disease before the patient develops symptoms.

Vulvar basal cell carcinoma in a 20-year-old: Case report and review of the literature.

► Vulvar basal cell carcinoma is a rare tumor. ► This report highlights the presentation of vulvar basal cell carcinoma in a very young, non-White patient. ► The importance of provider vigilance and timely biopsy of vulvar lesions is highlighted.