Monika Janda

Pre-post feasibility trial of a telephone-delivered exercise intervention for patients during chemotherapy for recurrent ovarian cancer: the ECHO-R trial protocol

Introduction The benefits of exercise in reducing treatment-related morbidity and improving quality of life following a primary diagnosis of cancer have been well documented and have led to exercise being recommended by oncology societies for all people with a cancer diagnosis. However, these recommendations are derived from research typically involving cohorts with more common cancers and relatively good prognosis, such as breast and prostate. Evidence from these cancers may not apply to women with recurrent ovarian cancer. Therefore, the primary objective of this trial is to evaluate the feasibility and safety of a home-based, telephone-delivered exercise intervention for women undergoing chemotherapy for recurrent ovarian cancer. Methods and analysis The Exercise During Chemotherapy for Recurrent Ovarian Cancer (ECHO-R) trial is a single-arm, phase II, pre/postintervention trial of a 6-month, telephone-delivered exercise intervention (consistent with recommended exercise oncology prescription). The target sample size is 80 women who are currently undergoing (or are scheduled to receive) chemotherapy for recurrent ovarian cancer. Recruitment is through participating hospital sites in Queensland, Australia, or via self-referral. The exercise intervention comprises 12 telephone sessions over a 6-month period delivered by trial-trained exercise professionals and supplemented (where feasible) by five sessions face to face. Exercise prescription is individualised and works towards an overall goal of achieving a weekly target of 150 min of moderate-intensity, mixed-mode exercise. Assessments via self-administered survey and physical fitness and function tests occur at baseline and then at 6 and 9 months postbaseline. Data to inform feasibility and safety are recorded as case notes by the exercise professional during each session. Ethics and dissemination Ethics approval for the ECHO-R trial was granted by the Metro North Human Research Ethics Committee (HREC/2020/QRBW/67223) on 6 November 2020. Findings from the trial are planned to be disseminated via peer-reviewed publications and both national and international exercise and oncology conferences. Trial registration number ACTRN12621000042842.

Toward Incorporating Health-Related Quality of Life as Coprimary End Points in Clinical Trials: Time to Achieve Clinical Important Differences and QoL Profiles

PURPOSE Besides morbidity and mortality, quality of life (QoL) is a key outcome of cancer treatments. Trials on the basis of clinical outcomes have expectations that QoL outcomes can be either tolerated or improved. Simultaneously considering QoL and clinical outcomes is challenging with lack of suitable metrics allowing incorporation of QoL as coprimary end points in clinical trial design and utilization of hierarchical hypothesis testing. METHOD We propose combining time to achieving a minimal clinically important difference (MCID) and probabilities of a MCID occurring in each QoL domain to provide QoL metrics analogous to those used for clinical end points. For QoL domains of interest, these yield QoL profiles, time to MCID, and number needed to treat. Incorporation of QoL as coprimary end points in clinical trial designs through hierarchical hypothesis testing can easily be achieved. The noninferiority designed Laparoscopic Approach to Carcinoma of the Endometrium trial, evaluating laparoscopic versus open abdominal surgery for endometrial cancer with Functional Assessment of Cancer Therapy–General QoL domains, is used to illustrate the usefulness of these metrics. RESULTS This analysis revealed that laparoscopic surgery had a significant shorter time to MCID for physical and functional well-being QoL domains (physical mean: 1.5 months, 95% CI, 0.5 to 2.6; P = .002; and functional mean: 1.4 months; 95% CI, 0.4 to 2.4; P = .003) than abdominal surgery, but little difference between the two approaches for psychologic social and emotion well-being. Probability profile plots show a consistent > 2-fold higher chance of attaining a MCID for physical and functional well-being over time for laparoscopic compared with abdominal surgery. CONCLUSION This analysis reinforces the potential value of novel MCID metrics and their usefulness in raising the profile of QoL outcomes to complement clinical end points. The methods will allow health professionals to counsel patients about QoL outcomes and clinical outcomes simultaneously.

A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer – ENDO-3: ANZGOG trial 1911/2020

Sentinel node biopsy is a surgical technique to explore lymph nodes for surgical staging of endometrial cancer, which has replaced full retroperitoneal lymph node dissection. However, the effectiveness of sentinel node biopsy, its value to patients, and potential harms compared with no-node dissection have never been shown in a randomized trial. Stage 1 will test recovery from surgery. Stage 2 will compare disease-free survival at 4.5 years between patients randomized to sentinel node biopsy versus no retroperitoneal node dissection. The primary hypothesis for stage 1 is that treatment with sentinel node biopsy will not cause detriment to patient outcomes (lymphedema, morbidity, loss of quality of life) and will not increase treatment-related morbidity or health services costs compared with patients treated without a retroperitoneal node dissection at 12 months after surgery. The primary hypothesis for stage 2 is that disease-free survival at 4.5 years after surgery in patients without retroperitoneal node dissection is not inferior to those receiving sentinel node biopsy. This phase III, open-label, two-arm, multistage, randomized non-inferiority trial (ENDO-3) will determine the value of sentinel node biopsy for surgical management of endometrial cancer. Patients with endometrial cancer are randomized to receive: (1) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy with sentinel node biopsy or (2) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection. In stage 1, 444 patients will be enrolled to demonstrate feasibility and quality of life. If this is demonstrated, we will enroll another 316 patients in stage 2. Inclusion criteria include women aged 18 years or older with histologically confirmed endometrial cancer; clinical stage 1, who meet the criteria for laparoscopic or robotic total hysterectomy and bilateral salpingo-oophorectomy. Patients with uterine mesenchymal tumors are excluded. The endpoint for stage 1 is surgical recovery, with the proportion of patients returning to usual daily activities at 3 months post-surgery as measured with the EQ-5D. Stage 2 is disease-free survival at 4.5 years. 760 participants (both stages). Stage 1 commenced in January 2021 and is planned to be completed in December 2024 when 444 participants have completed 12 months' follow-up. Stage 2 will enroll a further 316 participants for a total of 760 patients. NCT04073706.

Weight and weight control behaviors during long‐term endometrial cancer survivorship: Results of the Laparoscopic Approach to Cancer of the Endometrium long‐term follow‐up study

AbstractBackgroundOverweight or obesity is common in endometrial cancer (EC). This study aimed to examine sociodemographic, clinical, and psychosocial characteristics associated with being discontent with current weight and use of weight control methods among long‐term EC survivors.MethodsWomen diagnosed with early‐stage EC who participated in the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial (n = 516) were invited to complete a long‐term follow‐up survey at least 4.5 years after treatment. Chi‐square test and multivariate logistic regression models adjusted for time since surgery were used to determine factors associated with being discontent with current weight.ResultsOn average 9 years after surgery, 190/259 (73%) of participants were currently discontent with their weight, and 146 (56%) had used one or more weight loss methods during the past 12 months. Women who were discontent with their weight were more likely to be younger than 70 years (p < 0.000), and used one or more weight loss methods ever or during the past 12 months (p < 0.000). Among the weight loss methods used, exercise (40.1%), meal reductions (52.7%), or fat/sugar reductions (48.5%) were much more commonly reported than fasting (2.6%) or designated weight loss programs (2.3%).ConclusionsOur study provides evidence that the majority of long‐term EC survivors in this clinical trial population are discontent with their weight and over half continue to use multiple methods to lose weight each year. These data indicate that health professionals and lifestyle educators need to assess weight issues, and develop a tailored plan to address the specific needs of long‐term survivors to assist them become content with their weight after treatment for EC.

Exercise during CHemotherapy for Ovarian cancer (ECHO) trial: design and implementation of a randomised controlled trial

IntroductionEpidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. TheExercise duringCHemotherapy forOvarian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer.Methods and analysisParticipants (target sample size: n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either theexercise intervention(plus usual care) orusual carealone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage.Ethics and disseminationEthics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences.Trial registration numberAustralian New Zealand Clinical Trial Registry (ANZCTRN12614001311640;https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367123&isReview=true).

Reasons behind Low Cervical Screening Uptake among South Asian Immigrant Women: A Qualitative Exploration

Despite advancements in prevention strategies, cervical cancer remains a leading cause of death among underprivileged women. Although Australia has low age-standardized cervical cancer incidence rates compared with other countries, disparities exist in cervical screening uptake among certain population subgroups, especially those from culturally and linguistically diverse (CALD) backgrounds. South Asian immigrant women have been reported to have lower cervical screening uptake than Australian-born women and those from other immigrant backgrounds. The objective of this study was to gain insight into the reasons and barriers for low cervical screening participation among South Asian immigrant women, through qualitative exploration. Semi-structured, in-depth interviews were conducted with 20 women, aged 26–50 years, living in Queensland, Australia, who were recruited via purposive sampling. After translation and transcription of recorded interviews, data was analysed via inductive thematic approach. Resulting themes, illustrating barriers towards screening, included: lack of cervical cancer and screening knowledge, especially of the changes in the revised screening program; effect of preventive, health-seeking behaviours; health care system factors; role of practical constraints and influence of sociocultural beliefs. Results suggest that culturally informed interventions, that involve relevant information provision and behavioural change strategies, to clarify women’s misconceptions, are required.

Sentinel Node Biopsy in Endometrial Cancer

Endometrial cancer (EC) is the most common gynaecological cancer. Current treatment of EC typically includes removal of the uterus and to determine the extent of the disease (removal of fallopian tubes, ovaries \& if required a lymph node dissection (surgical staging)). While lymph node dissection may be valuable to guide the need for adjuvant treatment (chemo or radiotherapy) after surgery, it has been a topic of controversy for the last 30 years. In some patients it causes morbidity, specifically lymphoedema. This recently has been replaced with sentinel node biopsy (SNB). It requires an injection of a dye into the cervix with specific equipment \& surgical dissection of the lymph node in which the dye first becomes visible. Despite this promising proposition \& similar to a lymph node dissection, the value to patients, cost effectiveness \& potential harms (e.g. lymphedema) of SNB compared to no-node dissection in EC has never been established. Aim: determine the value of SNB for patients, the healthcare system and exclude detriment to patients using a randomised approach 1:1. Stage 1 - 444 patients. Stage 2 additional 316 patients. Primary Outcome Stage 1: Proportion of participants returning to usual daily activities at 12 months from surgery using the EQ-5D which will determine when women in both groups can return to their usual activities. Primary Outcome Stage 2: Treatment non-inferiority as evaluated by disease-free survival status at 4.5 years post-surgery, as measured by the time interval between the date of randomisation and date of first recurrence. Confirmation of recurrent disease will be ascertained through clinical assessment, radiological work-up and/or histological results.

Laparoscopic Approach to Cancer of the Endometrium

The primary objective of this study is to assess disease-free survival at 4.5 years postoperatively for women with apparent Stage 1 endometrial cancer, comparing patients who are randomised to receive Total Laparoscopic Hysterectomy (TLH) and patients who are randomised to receive Total Abdominal Hysterectomy (TAH).