Lynch syndrome associated endometrial carcinomas in Western Australia: an analysis of universal screening by mismatch repair protein immunohistochemistry.

BACKGROUND: In 2016 universal screening with mismatch repair protein immunohistochemistry in all newly diagnosed endometrial carcinomas was introduced in Western Australia. OBJECTIVE: To compare the prevalence of Lynch syndrome associated endometrial carcinomas between 2016 and 2019 with a historical control (2015). Additionally, to compare the number of cases appropriately referred for genetic assessment. METHODS: A cross-sectional study of cases presented at the Western Australia gynecologic oncology tumor board was carried out. The primary outcome was the prevalence of Lynch syndrome associated endometrial carcinomas. A secondary outcome was the number of cases appropriately referred for genetic assessment. The following variables were extracted: date of birth; age at diagnosis; vital status; tumor mismatch repair protein expression status (retained or lost) and if lost, the specific mismatch repair protein deficiency; patients who were referred to a genetic clinic; and family history, if recorded. Data were collected from the clinical databases of the Familial Cancer Program at Genetic Services of Western Australia and WOMEN Center, to determine whether patients were appropriately referred for genetic evaluation and to ascertain the results of genetic testing. RESULTS: Between 2016 and 2019, there were 1040 new endometrial carcinomas. Tumors of 883 (85%) patients underwent mismatch repair protein immunohistochemistry compared with 117 of 199 patients (59%) in 2015 (χ2 73.14, p<0.001). Of 883 tumors tested, 242 (27%) showed loss of mismatch repair protein expression. In 2015, 30 (26%) tumors of 117 tested showed loss of mismatch repair protein expression. During the 4 years of universal screening, 13 (1.5%) of 883 patients screened were diagnosed with Lynch syndrome compared with 2 (1.7%) of 117 in 2015 (Fisher's exact test 0.04, p=0.69). In 2015, 11 (37%) of 30 patients with loss of mismatch repair protein expression were not referred for genetic assessment compared with 36 (17%) of 209 patients in the universal screening group (χ2 6.28, p=0.02). No cases of Lynch syndrome were diagnosed in patients aged over 70 years. CONCLUSIONS: Universal immunohistochemical screening did not increase the proportion of Lynch syndrome associated endometrial carcinomas identified, although the study was underpowered to detect small differences. There was an improvement in appropriate referrals for genetic assessment.

Predictors of endometrial carcinoma in patients with atypical endometrial hyperplasia at a tertiary gynaecological cancer centre in Western Australia.

AIM: Our objective was to assess clinical and pathological factors associated with a final diagnosis of endometrial carcinoma in patients with atypical endometrial hyperplasia with a particular emphasis on the grading of atypia. MATERIALS AND METHODS: A retrospective review over five years on patients (N = 97) who underwent hysterectomy for a diagnosis of atypical endometrial hyperplasia at a statewide public tertiary gynaecologic oncology centre. Clinical and pathological characteristics were obtained. RESULTS: The rate of concurrent endometrial carcinoma was 34% (n = 33) with most being stage 1A endometrioid. A significant group difference was reported for age at diagnosis (t = -2.20 P = 0.031 d = 0.43) with carcinoma patients on average older (Mage  = 60.2 (8.9) years) than patients without carcinoma (Mage  = 55.5 (12.3) years). No significant group differences were found for body mass index, endometrial thickness or time between diagnosis and treatment. Significantly higher rates of carcinoma were reported in patients with moderate atypical hyperplasia (27.6%) and severe atypical hyperplasia (66.7%), compared to mild atypical hyperplasia (7.1%). Only severe atypical hyperplasia (odds ratio (OR) = 21.5, 95% CI 2.8-163.1, P = 0.003) and postmenopausal status (OR = 13.2, 95% CI 1.3-139.0, P = 0.032) significantly increased the risk of carcinoma in a multivariate model. CONCLUSION: Severe atypical hyperplasia and postmenopausal status were significant predictors of concurrent endometrial carcinoma in patients with atypical endometrial hyperplasia. The grading of atypical hyperplasia may be utilised by gynaecologic oncologists in the triage and referral process of managing these patients; however, the grading system requires external validation in larger prospective studies.

Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy.

OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC). METHODS: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. RESULTS: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65). CONCLUSIONS: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.

Screening for sexual health concerns in survivors of gynecological cancer.

OBJECTIVE: To assess the impact of a screening tool, the Brief Sexual Symptom Checklist for Women, on referral rates to physiotherapists, sexual counselors, and psychologists for sexual issues among patients attending the practices of two gynecological oncologists. METHODS: A prospective observational cohort study. A retrospective cohort of consecutive patients matched for age, diagnosis, and stage was used as a control group. RESULTS: Seventy-eight women were recruited to the intervention group. Diagnoses were endometrial carcinoma (38%), ovarian carcinoma (33%), and cervical carcinoma (24%). Sixty percent had completed adjuvant treatment, and 89% were married or in a de facto relationship. More than half of participants reported at least one sexual difficulty and were not satisfied with their sexual function. The most commonly reported sexual issue was decreased sexual desire. Twelve of 77 (15%) women screened in the intervention group were referred to a sexual counselor and/or a physiotherapist for a sexual issue. Twelve percent of women in the intervention group were referred to a sexual counselor, compared with 5% in the control group (p = 0.072). There was no difference in the proportion of women referred to a pelvic floor physiotherapist between the two groups (8% of women in the intervention group vs. 8% in the control group; p = 1.000). CONCLUSIONS: In the current study, the Brief Sexual Symptom Checklist for Women identified sexual health concerns in over half of gynecological cancer survivors and resulted in a non-significant trend to more referrals for sexual counseling.

A randomized controlled trial of WATAAP to promote physical activity in colorectal and endometrial cancer survivors.

OBJECTIVE: The objective of this study was to ascertain whether wearable technology coupled with action planning was effective in increasing physical activity (PA) in colorectal and endometrial cancer survivors at cardiovascular risk. METHODS: Sixty-eight survivors who had cardiovascular risk factors and were insufficiently active were randomized to intervention and control arms. Intervention participants were given a wearable tracker for 12 weeks, two group sessions, and a support phone call. Participants in the control arm received print materials describing PA guidelines. Assessments at baseline and 12 weeks measured triaxial and uniaxial estimates of moderate-vigorous physical activity (MVPA), sedentary behaviour, blood pressure, and body mass index (BMI). RESULTS: The intervention group significantly increased MVPA by 45 min/wk compared with a reduction of 21 min/wk in the control group. Group by time interactions were significant for minutes of MVPA (F1,126  = 5.14, P = 0.025). For those with diastolic hypertension, there was a significant group by time interaction (F1,66  = 4.89, P = 0.031) with a net reduction of 9.89 mm Hg in the intervention group. CONCLUSIONS: Significant improvements in MVPA were observed following the intervention. The results display promise for the use of pragmatic, low-intensity interventions using wearable technology.

'If I Had Someone Looking Over My Shoulder ': Exploration of Advice Received and Factors Influencing Physical Activity Among Non-metropolitan Cancer Survivors.

BACKGROUND: There are significant geographic inequalities in cancer survival with poorer survival rates in non-metropolitan areas compared to major cities. Physical activity (PA) can reduce cancer recurrence and prevent cardiovascular disease. However, few survivors participate in sufficient PA and the prevalence of inactivity is significantly higher in non-metropolitan survivors. The study investigated non-metropolitan survivors' recollections regarding PA advice received following cessation of active treatment, their knowledge of PA guidelines, and the factors that impact on PA behaviour change. METHOD: Sixteen individuals (14 women and 2 men) with breast (n = 8), endometrial (n = 4) or colorectal cancer (n = 4), with a mean age of 60 years (SD = 12) completed semi-structured interviews as part of a larger study to examine the acceptability and utility of wearable trackers to increase PA. Interviews explored survivors' recollections regarding the advice they received concerning PA following active treatment, knowledge of PA guidelines for cancer survivors and the influences on PA behaviour change. Interview transcripts were analysed using thematic analysis. RESULTS: Four main themes emerged: (i) insufficient knowledge of guidelines, (ii) support from the treating oncology team, (iii) external accountability, and (iv) barriers to PA. CONCLUSIONS: Survivors' knowledge of PA guidelines was limited and they did not often recall their oncologists making specific recommendations concerning PA. Survivors' referred to the desire for accountability and monitoring in order to successfully change PA. Lack of motivation was the main barrier to PA participation. Other barriers included age, health status, and lack of facilities or exercise programs.

Intravascular leiomyomatosis with extension to the inferior vena cava.

Intravascular leiomyomatosis (IVL) is a rare benign smooth muscle neoplasm growing within the pelvic venous system, often with caval and intracardiac extension. It frequently coexists with uterine leiomyomas or occurs in women with a history of myomectomy or hysterectomy. IVL is often asymptomatic until intracardiac extension occurs, and carries a risk of sudden death, necessitating timely diagnosis and management. We present a case of IVL diagnosed on hysterectomy specimen with extension to the inferior vena cava found on follow-up imaging. The patient underwent complete resection with multidisciplinary involvement of Gynaecological Oncology and Vascular Surgery and remains disease free following 12 months of follow-up.

The wearable activity technology and action-planning trial in cancer survivors: Physical activity maintenance post-intervention.

OBJECTIVES: The study objective was to assess whether moderate-to-vigorous intensity physical activity (MVPA) change in cancer survivors (n = 68, mean age = 64 years) was maintained 12-weeks following the Wearable Activity Technology and Action Planning (WATAAP) intervention. Secondary aims were to assess the effects of the intervention on blood pressure (BP) and body mass index (BMI), and to explore group differences between baseline and 24-weeks. DESIGN: Randomized controlled trial. METHODS: MVPA and sedentary behaviour were assessed using an accelerometer at baseline, the end of the intervention (12-weeks), and at 24-weeks. Generalised linear mixed models with random effects were used to examine between-group and within-group changes in MVPA, sedentary behaviour, BP and BMI. RESULTS: MVPA was significantly higher in the intervention group compared with the control group at 24-weeks following adjustment for known confounders (141.4 min/wk. (95% CI = 9.1 to 273.8), p = 0.036). At 24-weeks participants in the intervention group had maintained their increased levels of MVPA (change from 12-weeks = 8.8 min/wk.; 95% CI = -43 to 61; p = 0.74). The reduction in MVPA in the control group over the first 12-weeks was also maintained at 24-weeks (5.4 min/wk.; 95% CI = -3.6 to 4.6; p = 0.80). Secondary outcomes did not differ between groups at 24-weeks. CONCLUSIONS: Our results suggest distance-based interventions using wearable technology produce increases in MVPA that endure at least 12-weeks after the intervention is completed.

Exploring Attitudes to Conception in Partners and Young Women with Gynecologic Cancers Treated by Fertility Sparing Surgery.

BACKGROUND: Approximately 20% of women with gynecologic cancers are under age 40 and with delayed childbearing, women may be diagnosed before their first pregnancy. Although fertility preservation is a priority for many women, attitudes to conception have not previously been investigated in these patients or their partners. We explored attitudes to conception in partners and young women, following fertility preserving treatment for gynecologic cancers. METHODS: A total of 16 telephone interviews were conducted with a purposive sample of patients who had had an early stage gynecologic cancer or borderline ovarian tumor treated by fertility sparing surgery in Western Australia between January 1st, 2005 to December 31st, 2016. The interviews were audio recorded, transcribed and thematic analysis was conducted. RESULTS: Four main themes were identified: (i) Emotions at diagnosis and perception of information given; (ii) Discussions of fertility and factors affecting childbearing; (iii) Role of partners in decision making and relationship pressures; (iv) Decision for treatment and postoperative regrets. CONCLUSIONS: Regret and relationship breakdown were commonly reported. Women need appropriate support including inviting their partners to attend clinic appointments and may need several appointments before treatment. Regret was commonly reported by women who opted for completion surgery.
.

Promoting physical activity in regional and remote cancer survivors (PPARCS) using wearables and health coaching: randomised controlled trial protocol.

INTRODUCTION: Physically active cancer survivors have substantially less cancer recurrence and improved survival compared with those who are inactive. However, the majority of survivors (70%-90%) are not meeting the physical activity (PA) guidelines. There are also significant geographic inequalities in cancer survival with poorer survival rates for the third of Australians who live in non-metropolitan areas compared with those living in major cities. The primary objective of the trial is to increase moderate-to-vigorous PA (MVPA) among cancer survivors living in regional and remote Western Australia. Secondary objectives are to reduce sedentary behaviour and in conjunction with increased PA, improve quality of life (QoL) in non-metropolitan survivors. Tertiary objectives are to assess the effectiveness of the health action process approach (HAPA) model variables, on which the intervention is based, to predict change in MVPA. METHODS AND ANALYSIS: Eighty-six cancer survivors will be randomised into either the intervention or control group. Intervention group participants will receive a Fitbit and up to six telephone health-coaching sessions. MVPA (using Actigraph), QoL and psychological variables (based on the HAPA model via questionnaire) will be assessed at baseline, 12 weeks (end of intervention) and 24 weeks (end of follow-up). A general linear mixed model will be used to assess the effectiveness of the intervention. ETHICS AND DISSEMINATION: Ethics approval has been obtained from St John of God Hospital Subiaco (HREC/#1201). We plan to submit a manuscript of the results to a peer-reviewed journal. Results will be presented at conferences, community and consumer forums and hospital research conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001743257; pre-results, U1111-1222-5698.

Acceptability and utility of, and preference for wearable activity trackers amongst non-metropolitan cancer survivors.

PURPOSE: The study purpose was to investigate the acceptability and utility of, and preference for, wearable activity trackers (WATs) amongst cancer survivors living in regional and remote areas of Western Australia. METHODS: Twenty participants were recruited (Mean age = 63 years, SD = 13) to test two to three trackers from five available models (Fitbit Alta, Garmin Vivofit 2, Garmin Vivosmart, Polar loop 2 and Polar A300). Participants wore each device for two weeks, followed by a one-week washout period between devices. Interviews were conducted with participants to explore user perceptions and experiences. Interview transcripts were analysed using thematic analysis. RESULTS: Four main themes emerged: (i) Consciousness raising; (ii) Prompts and Feedback; (iii) Accuracy and registry of activities; and, (iv) WAT preferences and features. CONCLUSIONS: WATs were acceptable and useful to cancer survivors. WATs increased self-awareness of physical activity, provided real time feedback in relation to step goals, and reinforced progress and efforts towards goals. The aesthetics of the WATs were deemed crucial in determining preference and likelihood of use. IMPLICATIONS FOR CANCER SURVIVORS: Future interventions may do well to have two different WATs available for participants to choose from, according to activity preferences, aesthetic preferences, and display size.

Wearable Activity Technology And Action-Planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol.

Background/Objective: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical framework for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. Method: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12-week intervention and control groups. Intervention group participants will receive: a Fitbit Alta™ to monitor physical activity, HAPA-based group sessions, booklet, and support phone-call. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. Conclusions: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors.

Antecedentes/Objetivo: Los sobrevivientes de cáncer tienen riesgo cardiovascular debido a la comorbilidad y al comportamiento sedentario, lo que justifica desarrollar una adecuada intervención para aumentar la práctica de actividad física. El Enfoque del Proceso de Acción de Salud (EPAS) constituye un marco teórico para el desarrollo de conductas saludables y los dispositivos electrónicos de actividad física son nuevas herramientas de automonitorización para los supervivientes de cáncer. Método: Sesenta y ocho sobrevivientes de cáncer colorrectal y ginecológico serán aleatorizados en grupos de intervención y control. Los participantes del grupo de intervención recibirán un Fitbit Alta™ para monitorizar la actividad física, sesiones grupales y aplicación de un folleto de EPAS, y una llamada telefónica de apoyo. Los participantes del grupo control únicamente recibirán un folleto basado en EPAS. Al inicio del estudio, a las 12 y 24 semanas, se evaluarán la actividad física (usando acelerómetros), la presión arterial, el Índice de Masa Corporal (IMC) y los constructos EPAS. El análisis de datos utilizará la interacción Grupo x Tiempo a partir de un análisis del Modelo Mixto Lineal General. Conclusiones: Las intervenciones de actividad física son factibles y tienen fundamentos teóricos que auguran mejorar la salud de los sobrevivientes de cáncer.