The Lifestyle and Empowerment Techniques in Survivorship of Gynecologic Oncology Study

Study Overview
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Brief Summary
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This study compares traditional follow-up of gynaecological cancer patients to an alternative follow-up model. In the alternative follow-up model the patients will meet a nurse at every second consultation. The nurse will focus on psychosocial health and educate the patients in the use of a study specific smartphone-application.

Detailed Description
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The goal is to improve follow-up of past and present cancer patients to have the best quality of life possible, despite having a serious illness. Todays' survivors differ from the survival population for whom the traditional follow-up was designed. Improvements in treatment assure that many cancer patients survive longer after diagnosis often with age-related comorbidities. Consequently, new evidence-based models for follow-up after cancer treatment with focus on techniques to improve coping with and management of late effects without increasing the costs are warranted. The chronic care model, which uses self-management interventions, is used for many chronic diseases-such as diabetes and asthma and is a valid model to consider for cancer follow-up care(1). Another relevant model is the risk stratified model where patients are stratified into low, moderate, or high-risk on the basis of expected recurrence rate and late-effects(2). Gynecological cancer patients constitute an underrepresented group in clinical cancer research. The research group has developed a follow-up model based on the principles of the risk-stratified model and the chronic care model with one or three year's hospital follow-up for low- versus medium/high-risk patients. Physicians will be replaced by nurses in 50% of the consultations. The nurses will use evidence-based behavior change techniques to coach the cancer patients on how to take an active role in management of their physical and mental late effects. These techniques will be further reinforced with a multifunctional smart phone-application (app). The Lifestyle and Empowerment Techniques in Survivorship of Gynecologic Oncology-app (LETSGO-app) has three main functions: 1) Self-evaluated symptoms (on recurrence or late effects) regularly reported through the app; 2) Targeted information on treatment, signs of recurrence, and late-effects on each cancer type and 3) Facilitation of early rehabilitation through physical activity instructions, goal-setting and electronic reminders. The investigators will conduct a multicenter study including 754 cancer survivors in Norway. Ten Norwegian hospitals will participate whereof five hospitals are intervention hospitals and five are control hospitals.

Official Title
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Lifestyle and Empowerment Techniques in Survivorship of Gynecologic Oncology

Conditions
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Gynecologic Cancer, Gynecologic Neoplasm, Ovarian Cancer, Endometrial Cancer, Cervical Cancer, Vulvar Cancer

Intervention / Treatment
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* Other: LETSGO follow-up


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified gynaecological cancer Cervical cancer restricted to squameous cell carcinoma, adeno carcinoma and adeno-squameous carcinoma) or Endometrial cancer or Ovarian cancer (restricted to epithelial type) or Vulvar cancer Must have completed primary treatment and scheduled to follow-up Exclusion Criteria: Participating in other cancer treatment trial or follow-up trial Cervical cancer patients treated with trachelectomy On maintenance therapy Dementia or other mental/cognitive impairment Illiterate in Norwegian

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multicenter controlled clinical trial of individualized nurse/physician-led follow-up (treatment group) versus standard care (control group) in approximately 754 women treated for gynecological cancer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>New follow-up model | Other: LETSGO follow-up<br>* Nurse-led follow-up in 50% of the consultations Access to the LETSGO-app<br>|
| No Intervention: Control arm<br>Usual care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' score on the Health Education Impact Questionnaire (HEI-Q) | Evaluating the immediate effects of self-management interventions in cancer follow-up. It contains the following domains: Health-directed activities, Positive and active engagement in life, Emotional distress, Constructive attitudes and approaches, Self-monitoring and insight, Skill and technique acquisition, Social integration and support, Health service navigation. Individuals are asked to indicate their level of agreement with 42 statements across the eight domains on four-point Likert scales (1 strongly disagree to 4 Strongly agree). Higher scores indicate greater performance of specific self-management behaviors. Higher scores on the emotional well-being domain denote higher levels of negative affect. Data from each domain will be used individually and the results reported as mean domain score. The primary outcome is the change of the insight subscale scores of the HEI-Q from right after treatment (baseline) to 12 months after treatment. | Assessed right after initial treatment, and 3, 6, 12, 24 and 36 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), measuring ´Health related quality of life (HRQL) | The EORTC QLQ-C30 uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 (Not at all), 2 (A little), 3 (Quite a bit) and 4 (Very much). Half points are not allowed. For the raw score, lower scored are considered a better outcome. The EORTC QLQ-C30 uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 (very poor) to 7 (excellent). Half points are not allowed. Firstly, raw score has to be calculated with mean values. Afterwards linear transformation is performed Higher transformed scores are considered a better outcome. We will analyze change in Global Health Status and other subscales of the C30 questionnaire from end of treatment to 12, 24 and 36 months, respectively. | Questionnaires are administered at end of treatment, 3, 6, 12, 24 and 36 months after treatment, respectively | 
| Change adherence to physical activity recommendations | Physical activity level recorded objectively with an activity monitor. Daily steps recorded by the activity device will be averaged over the time periods between patient visits, with days of zero daily steps excluded from the average. The data will be recoded into 10-min epochs of moderate-to-vigorous physical activity. | Change from baseline to 12, 24 and 36 months after completion of primary treatment | 
| Physical activity goals | The investigators have developed an app where the participants may choose activity goals. Number and type of goals will be reported with descriptive statistics. | Change from baseline to 12, 24 and 36 months after completion of primary treatment | 
| Changes in physical activity level based on International Physical Activity Questionnaire - Short Form (IPAQ) | Physical activity level will be measured using the short-form of the International Physical Activity Questionnaire (IPAQ). The measure uses open-ended questions covering an individual's last 7-day recall of physical activity. There are no subscales. IPAQ-SF quantifies physical activity during the last seven days divided into four categories: vigorous intensity, moderate intensity, walking and sitting. In addition to intensity, frequency and duration of physical activity are assessed. Using the instrument's scoring protocol, weekly physical activity will be estimated by weighting time spent in each activity intensity with its estimated metabolic equivalent (MET) energy expenditure. The scoring protocol assigns the following MET values to walking, moderate, and vigorous intensity activity: 3.3 METs, 4.0 METs, and 8.0 METs, respectively. | Change from baseline to 12, 24 and 36 months after completion of primary treatment | 
| Patients' score on the Health Education Impact Questionnaire (HEI-Q) | Evaluating immediate effects of self-management interventions in cancer follow-up. It contains the following domains: Health-directed activities, Positive and active engagement in life, Emotional distress, Constructive attitudes and approaches, Self-monitoring and insight, Skill and technique acquisition, Social integration and support, Health service navigation. Individuals are asked to indicate their level of agreement with 42 statements across the eight domains on four point Likert scales (1 strongly disagree to 4 Strongly agree). Higher scores indicate greater performance of specific self-management behaviors. Higher scores on the emotional well-being domain denote higher levels of negative affect. Each domain is assessed separately and the scores are reported as the overall mean for each domain. We intend to assess change in the remaining subscales of the HEI-Q from end of treatment to 12, 24 and 36 months after treatment in addition to the primary outcome subscale. | Questionnaires are administered at end of treatment, 3, 6, 12, 24 and 36 months after treatment, respectively | 
| Costs-effectiveness using the EuroQol 5-Dimensional (EQ5D) | Cost-effectiveness from the health care perspective using the EuroQol five-Dimensional (EQ5D) measure. EQ5D measures individual generic health status using 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and each dimension has 5 levels depending on severity of symptoms (1 no problems, 5 extreme problems) and a VAS (visual analogue scale ranging from 0-100). The scores can then be converted into a single index number. The index value will be used for calculation of quality-adjusted life years (QALYs) for a health economic analysis of the intervention. Crude differences between groups will be assessed. | Change from end of treatment (baseline) to 36 months after completion of primary treatment | 
| Frequency of health care use | Frequency of health care use will be obtained through registries on health care services | Change from baseline to 36 months after completion of primary treatment | 
| Time to recurrence | In this study we will compare proportions of women who experienced their first recurrence in both groups, and for those who had a recurrence, compare the times from inclusion to the first recurrence assessed at 36 months after the end of primary treatment | Compare findings between intervention group and control group at 36 months after completion of primary treatment | 
| Time to recurrence | In this study we will compare proportions of women who experienced their first recurrence in both groups, and for those who had a recurrence, compare the times from inclusion to the first recurrence assessed at 60 months after the end of primary treatment | Differences between intervention group and control group at 60 months after completion of primary treatment | 
| Survival | In this study we will describe cause specific survival and overall survival defined as time from the inclusion to death or end of follow up (whichever comes first) and compare crude survival between the intervention group and control group. The end of follow up is set at 60 months after completion of primary treatment. | Differences between intervention group and control group at 60 months after completion of primary treatment | 
| Differences in expression of biomarkers in cancer tissue in relation to recurrence of disease | Biomarker expression including CXCR4, SMAD4, SOX9 and IFIT3 in cancer tissue will be assessed by immunohistochemistry and verified by PCR from tumor | Compare differences between patients with and without recurrence at 36 months after completion of primary treatment | 
| Impact of physical activity changes on inflammatory biomarkers in blood | Change in inflammatory biomarkers including PGE2, TNF alpha, IL1 beta, IL-8 and IL-10 will be assessed in blood samples. Differences in concentrations between the two study groups will be assessed by enzyme-linked immunosorbent assay and multiplex bead assays. | Change from baseline to 36 months after completion of primary treatment | 
| Impact of physical activity changes on insulin biomarkers in blood | Change in the insulin pathway including adiponectin, leptin, insulin, IGF1, and IGFBP3 will be assessed in blood samples. Differences in concentrations between the two study groups will be assessed by immunoassays. | Change from baseline to 36 months after completion of primary treatment | 
| Examination of Circulating tumor DNA (ctDNA) at the point of disease progression compared with 3 months values | Analyze of absolute quantities of ctDNA molecules presenting in blood at 3 months and at progression | At 3 months and at progression | 
| Changes in the use of a study specific smartphone application | We will explore how frequent different parts of the app are used. Which elements of the app and frequency of use will be reported with descriptive statistics. | 36 months after completion of primary treatment | 
| 4.Cancer type specific quality of life using the EORTC Endometrial Cancer Module (EORTC QLQ-EN24) | EORTC QLQ-EN24 is a validated questionnaire to assess the overall health-related quality of life in patients with all stages of endometrial cancer, and consists of 24 questions including multi-item scales and single item measures. These include three functional scales (sexual interest, activity, and enjoyment), five symptom scales (lymphoedema, urological symptoms, GI symptoms, poor body image, and sexual/vaginal problems), and five single items (back/pelvis pain, tingling/numbness, muscular pain, hair loss, and taste change). Questions use a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment. Change from baseline to 6, 12, 24 and 36 months respectively. | Questionnaires are administered at end of treatment, 3, 6, 12, 24 and 36 months after treatment, respectively | 
| 4.Cancer type specific quality of life using the EORTC Ovarian Cancer Module (EORTC QLQ-OV28) | EORTC QLQ-OV28 is a validated questionnaire to assess the overall health-related quality of life in patients with all stages of ovarian cancer, and consists of 28 questions including multi-item scales and single item measures. The module covers abdominal/gastrointestinal symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal/menopausal symptoms, body image, attitude to disease/treatment and sexual functioning. Questions use a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment. Change from baseline to 6, 12, 24 and 36 months respectively. | Questionnaires are administered at end of treatment, 3, 6, 12, 24 and 36 months after treatment, respectively | 
| 4.Cancer type specific quality of life using the EORTC Cervical Cancer Module (EORTC QLQ-CX24) | EORTC QLQ-CX24 is a validated questionnaire to assess the overall health-related quality of life in patients with all stages of cervical cancer, and consists of 24 questions including multi-item scales and single item measures. The EORTC QLQ-CX24 can be summarized in three multi-item scales, namely, symptom experience (eleven items), body image (three items), and sexual/vaginal functioning (four items). The other dimensions of the questionnaire are single-item scales, covering lymphedema, peripheral neuropathy, menopausal symptoms, sexual worry, sexual activity, and sexual enjoy. Questions use a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment. Change from baseline to 6, 12, 24 and 36 months respectively. | Questionnaires are administered at end of treatment, 3, 6, 12, 24 and 36 months after treatment, respectively | 
| 4.Cancer type specific quality of life using the EORTC Vulvar Cancer Module (EORTC QLQ-VU34) | EORTC QLQ-VU34 is a questionnaire to assess the overall health-related quality of life in patients with all stages of vulvar cancer, and consists of 34 questions including multi-item scales and single item measures. The module covers abdominal/gastrointestinal symptoms, vaginal and inguinal problems, other treatment related side-effects, hormonal/menopausal symptoms, body image, attitude to disease/treatment and sexual functioning. Questions use a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment. Change from baseline to 6, 12, 24 and 36 months respectively. | Questionnaires are administered at end of treatment, 3, 6, 12, 24 and 36 months after treatment, respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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follow-up, app, lifestyle, empowerment, nurse-led