Paul A. Cohen

The multidisciplinary tumor conference in gynecologic oncology--does it alter management?

Objective: To assess the role of the multidisciplinary tumor conference in patient management in a tertiary gynecologic oncology service. Methods: Data were analyzed from the records of all patients presented at the gynecologic oncology tumor conferences at Auckland City Hospital from August 1, 2005, to August 1, 2006. Patient information including referral source, cancer site, stage, whether surgery had been performed before the tumor conference and if so where and by whom, and benign versus malignant was extracted from the records. The radiological and pathological findings and diagnosis for each patient both before and after each tumor conference were compared. A discrepancy was defined as a change in tumor site, histological type, grade, or stage that resulted from findings discussed at the conferences. Diagnostic discrepancies that resulted in a change in patient management were classified as major discrepancies. Discrepancies that did not affect patient management were classified as minor discrepancies. Results: A total of 509 cases were discussed during the study period. Forty-six discrepancies (9%) were noted, with 30 major (5.9%) and 16 minor (3.1%) discrepancies. The most common changes to patient management that resulted from the tumor conferences were the addition of chemotherapy and surgery. Conclusions: This study demonstrates that gynecologic oncology tumor conferences alter the diagnosis in a significant number of cases and therefore affect patient management.

Adult granulosa cell tumours (GCT): Clinicopathological outcomes including FOXL2 mutational status and expression

OBJECTIVES The aim of this research was to use nucleic acids isolated from formalin-fixed paraffin-embedded (FFPE) tissue to investigate the diagnostic potential and prognostic significance of FOXL2 in adult-type GCTs, particularly as a marker of identifying early stage patients that are likely to relapse. METHODS We performed a retrospective review of GCT patients referred to the Auckland Gynae-Oncology Multidisciplinary Team from 1955 to 2012. Baseline characteristics, clinical course, histopathology and survival data was recorded. Using nucleic acids extracted from FFPE tumour blocks, FOXL2 mutation status and expression was determined by DNA sequencing and RT-qPCR, respectively, and correlated with clinical data. RESULTS 57 adult GCT patients were identified, however FFPE tumour blocks were available for only 37 of these patients. Sequencing results confirmed the presence of the FOXL2 mutation in 70% of patients. FOXL2 mutation positive adult tumours showed a trend towards higher FOXL2 expression than wildtype adult tumours, particularly in stage I patients (p=0.051). In addition, patients with homozygous FOXL2 mutations had a significantly higher relapse rate (p=0.04). There was no significant correlation between FOXL2 mutation status or FOXL2 expression and any other clinical variables. CONCLUSIONS FFPE tumour blocks are a valuable resource of molecular information, especially when studying rare tumours such as GCTs. The FOXL2 mutation appears to have some diagnostic potential, however additional work in a larger cohort needs to be completed to confirm the prognostic significance of this gene mutation, and its expression.

Prevalence of sexual dysfunction after risk-reducing salpingo-oophorectomy.

OBJECTIVES To determine the prevalence of sexual dysfunction in women after risk-reducing salpingo-oophorectomy (RRSO) and to assess factors which may influence sexual wellbeing following this procedure. METHODS This work is a cross-sectional study of women who underwent RRSO at a tertiary gynecologic oncology unit between January 2009 and October 2014. Data collection involved a comprehensive questionnaire including validated measures of sexual function, sexual distress, relationship satisfaction, body image, impact of event, menopause specific quality of life, and general quality of life. Participants were invited to undergo blood testing for serum testosterone and free androgen index (FAI). RESULTS 119 of the 206 eligible women participated (58%), with a mean age of 52years. The prevalence of female sexual dysfunction (FSD) was 74% and the prevalence of hypoactive sexual desire disorder (HSDD) was 73%. Common sexual issues experienced included; lubrication difficulty (44%), reduced sexual satisfaction (41%), dyspareunia (28%) and orgasm difficulty (25%). Relationship satisfaction, the use of topical vaginal estrogen and lower generalized body pain were significantly associated with a decreased likelihood of sexual dysfunction. Serum testosterone, FAI, the use of systemic hormone replacement therapy (HRT), prior history of breast cancer, menopausal status at the time of surgery and hysterectomy did not correlate with sexual dysfunction. CONCLUSION The prevalence of FSD and HSDD after RRSO was 74% and 73% respectively. Relationship satisfaction, low bodily pain and use of topical vaginal estrogen were associated with a lower likelihood of sexual dysfunction. There was no correlation between serum testosterone or FAI, and sexual dysfunction.

Spontaneous regression of CIN2 in women aged 18-24 years: A retrospective study of a state-wide population in Western Australia

CIN2 has a high rate of spontaneous regression in young women and may be managed conservatively in appropriately selected patients. This study aimed to investigate health outcomes in women aged 18–24 years with biopsy‐confirmed CIN2.

Comparison of cold knife cone biopsy and loop electrosurgical excision procedure in the management of cervical adenocarcinoma in situ: What is the gold standard?

OBJECTIVE To compare the outcomes of patients with cervical adenocarcinoma in situ (ACIS) treated with cold knife cone (CKC) biopsy or loop electrosurgical excision procedure (LEEP) for the treatment of cervical adenocarcinoma in situ (ACIS). STUDY DESIGN This is a retrospective, population-based cohort study of Western Australian patients with ACIS diagnosed between 2001 and 2012. Outcomes included pathological margin status and the incidence of persistent or recurrent endocervical neoplasia (ACIS and adenocarcinoma) during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS The study group comprised 338 patients including 107 (32%) treated initially by LEEP and 231 (68%) treated by CKC biopsy. The mean age was 33.2 years (range 18 to 76 years) and median follow-up interval was 3.6 years (range <1 year to 11.8 years). Overall, 27 (8.0%) patients had ACIS persistence/recurrence while 9 (2.7%) were diagnosed with adenocarcinoma during the follow-up and surveillance periods. No patient died of cervical cancer within the study period. There were no significant differences in the incidence of persistent and/or recurrent endocervical neoplasia according to the type of excisional procedure. Patients with positive biopsy margins were 3.4 times more likely to have disease persistence or recurrence. CONCLUSION(S) LEEP and CKC biopsy appear equally effective in the treatment of ACIS for women wishing to preserve fertility. Patients undergoing conservative management for ACIS should be closely monitored, particularly if biopsy margins are positive in initial excision specimens. Patients and their clinicians should be aware of the potential risks of residual and recurrent disease.

Impact of Clinical Genetics Attendance at a Gynecologic Oncology Tumor Board on Referrals for Genetic Counseling and BRCA Mutation Testing.

Objectives The objectives of this work were to determine the proportion of eligible patients with ovarian cancer discussed at a gynecologic oncology tumor board who were referred for counseling and BRCA mutation testing; to compare referral rates before genetics attendance at the tumor board to referral rates after genetics attendance; and to ascertain the proportions of women with germline BRCA mutations. Materials and Methods Eligible cases were identified from the minutes of the weekly Western Australian gynecologic oncology tumor board from July 1, 2013 to June 30, 2015. Patients with ovarian cancer who met eligibility criteria for genetics referral were identified and checked against the records of the genetic services database to ascertain whether a referral was received. Outcomes including attendance for counseling and results of mutation testing were analyzed. Results Two hundred sixty-one patients were eligible for referral during the 24-month study period. One hundred six patients (40.6%) were referred for counseling and germline mutation testing. Of the eligible patients, 26.7% were referred in the 12 months before genetics attendance at the tumor board compared to 51.7% of the eligible patients in the 12 months after genetics attendance (P ≤ 0.0001). Ninety-seven patients were offered BRCA mutation testing, and 73 underwent testing with 65 results reported to date. Twenty-two patients (33.8 %) tested positive for a germline BRCA mutation. Conclusions Patients with ovarian cancer had a high rate of BRCA mutations. Attendance of a genetics service at a tumor board was associated with an improved rate of referral of patients for genetic counseling and BRCA mutation testing.

The effects of pre-operative menopausal status and hormone replacement therapy (HRT) on sexuality and quality of life after risk-reducing salpingo-oophorectomy

OBJECTIVES Investigate the effects of pre-operative menopausal status and HRT use on sexual outcomes following risk-reducing salpingo-oophorectomy (RRSO). STUDY DESIGN Cross-sectional study of 119 women who underwent RRSO between 2009 and 2014. MAIN OUTCOME MEASURES Data was collected via a questionnaire and serum test for testosterone and free androgen index (FAI). The questionnaire comprised demographic data and validated measures of sexual function, sexual distress, relationship satisfaction, body image, psychological stress, menopause quality of life and general quality of life. RESULTS Rates of sexual issues were similar despite menopause status at operation. Women who were pre-menopausal at operation (mean age=44 years ± 5) had significantly higher rates of sexual distress (p=0.020), dissatisfaction with sex life (p=0.011) and bothersome sexual menopause symptoms (p=0.04) than women who were post-menopausal (mean age=55 years ± 7). Pre-menopausal women reported higher psychological distress from surgery (p=0.005) and poorer emotional (p=0.052) wellbeing. HRT use reduced the rates of dyspareunia (p=0.027) and the severity of sexual menopausal symptoms (p=0.030). Androgen levels were not significantly associated with desire or arousal scores. CONCLUSIONS Regardless of menopausal status at operation, women experienced the same sexual issues at equivalent rates. However, pre-menopausal women reported higher sexual distress and dissatisfaction with sex life. Pre-menopausal women also had greater psychological distress and poorer emotional function.

Homologous Recombination DNA Repair Pathway Disruption and Retinoblastoma Protein Loss Are Associated with Exceptional Survival in High-Grade Serous Ovarian Cancer.

Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths. Experimental Design: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival. Patient samples were characterized immunohistochemically and by genome sequencing. Results: Different patterns of clinical response were seen: long progression-free survival (Long-PFS), multiple objective responses to chemotherapy (Multiple Responder), and/or greater than 10-year overall survival (Long-Term Survivors). Pathogenic germline and somatic mutations in genes involved in homologous recombination (HR) repair were enriched in all three groups relative to a population-based series. However, 29% of 10-year survivors lacked an identifiable HR pathway alteration, and tumors from these patients had increased Ki-67 staining. CD8+ tumor-infiltrating lymphocytes were more commonly present in Long-Term Survivors. RB1 loss was associated with long progression-free and overall survival. HR deficiency and RB1 loss were correlated, and co-occurrence was significantly associated with prolonged survival. Conclusions: There was diversity in the clinical trajectory of exceptional survivors associated with multiple molecular determinants of exceptional outcome in HGSC patients. Concurrent HR deficiency and RB1 loss were associated with favorable outcomes, suggesting that co-occurrence of specific mutations might mediate durable responses in such patients. Clin Cancer Res; 24(3); 569–80. ©2017 AACR. See related commentary by Peng and Mills, p. 508

Morcellation of occult uterine malignancies: an Australian single institution retrospective study

Morcellation for tissue extraction during laparoscopic hysterectomy or myomectomy has recently been questioned because of the potential to spread occult uterine cancers. The Australian Therapeutic Goods Administration (TGA) issued a safety advisory in August 2014, estimating the risk of occult malignancy in the Australian population to be one in 1000 or lower, based on estimates from overseas studies in the absence of any local data.

Discussing Sexuality With Women Considering Risk-Reducing Salpingo-oophorectomy: An International Survey of Current Practice in Gynecologic Oncology.

Objective To determine how frequently gynecologic oncologists discuss sexuality with women considering risk-reducing salpingo-oophorectomy. Secondary objectives were to assess the availability of resources, and the barriers to discussing sexuality. Methods Members of the Australian Society of Gynaecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncology were invited to complete an online survey. Questions addressed frequency of, and barriers to, discussing sexuality, and availability of resources related to sexual issues. Results Three hundred eighty-eight physicians in 43 countries responded from 4,006 email invitations (9.7%). Ninety-one percent reported discussing sexuality preoperatively, and 61% discuss it with every patient. Factors associated with higher rates of discussion were female sex (P = 0.020), higher level of training (P = 0.003), time in practice (P = 0.003), and consulting more risk-reducing salpingo-oophorectomy patients per month (P = 0.006). Commonly discussed issues were vasomotor menopausal symptoms (91%) and vaginal dryness (85%). Eighty-eight percent of respondents believed that sexuality should be discussed preoperatively, and most felt that it is their responsibility (82%). Fear of causing distress was the most common barrier to discussing sexuality (49%). Twenty-four percent felt that they did not have adequate training to discuss sexual function. Conclusions Although most respondents believed that discussing sexuality should occur preoperatively, only 61% discuss this with every patient. Resources specifically relating to sexuality are limited. The most common barrier to discussing sexuality was fear of causing distress. Nearly one quarter of gynecologic oncologists felt inadequately trained to discuss sexual function.