(1) 12 weekly interactive sessions with a health coach to help them set goals and make changes toward becoming physically active and consuming the recommended number of fruits and vegetables.

This arm will receive personalized health coaching (behaviour change counseling)

interactive sessions

Participating in regular physical activity and consuming a diet high in fruits and vegetables can aid in the management of various acute and chronic side effects of cancer treatment; however, few rural-dwelling young adult cancer survivors are active enough and consume enough fruits and vegetables to accrue benefits. Telehealth interventions show promise for helping these young adults increase their motivation to participate in these behaviours by addressing barriers associated with accessing face-to-face behaviour counselling services (e.g., time commitment, travel distance). Yet, few researchers have examined the feasibility and acceptability of a telehealth intervention that provides motivational support grounded in self-determination theory for these health behaviours in rural-dwelling young adult cancer survivors. Based on previous research, the researchers reasoned that rural-dwelling young adult cancer survivors' physical activity and fruit and vegetable consumption would be more likely to increase if they participated in a telehealth intervention therefore, the researchers aim to test the feasibility, acceptability, and preliminary efficacy of the intervention. The researchers also aim to assess if changes in perceived basic psychological need satisfaction, behaviour regulation, and perceived autonomy support are associated with changes in physical activity and fruit and vegetable consumption.

Making Healthy Choices: Does Having an Online Health Coach Help?

Helping Rural-living Young Adult Cancer Survivors Make Healthy Lifestyle Choices: Does Having a Telehealth Personal Health Coach Help?

Change in self-reported physical activity (over the past 7 days) from baseline to post-intervention, with higher scores representing a better outcome.

Change in self-reported fruit and vegetable intake (over the past 7 days) from baseline to post-intervention, with higher scores representing a better outcome.

Change in basic psychological need satisfaction for physical activity from baseline to post-intervention, using a 1 (false) to 6 (true) scale with higher scores representing a better outcome.

Change in basic psychological need satisfaction for fruit and vegetable consumption from baseline to post-intervention, using a 1 (strongly disagree) to 7 (strongly agree) scale with higher scores representing a better outcome.

Change in motivational regulations for physical activity from baseline to post-intervention, using a 1 (not at all true) to 7 (very true) scale with higher scores representing a better outcome.

Change in motivational regulations for fruit and vegetable consumption from baseline to post-intervention, using a 1 (not at all true) to 7 (very true) scale with higher scores representing a better outcome.

Level of perceived autonomy support for health behaviours post-intervention, using a 1 (strongly disagree) to 7 (strongly agree) scale with higher scores representing a better outcome.

The number of eligible participants who enrol in the study out of the number assessed for eligibility

The number of participants completing the 12-week intervention.

The number of eligible participants completing ≥ 70% of the intervention sessions (i.e., 8/12)

Participants will be asked what they liked, disliked, and experienced during the intervention

University of Ottawa

Associate Professor

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Nutritional and Metabolic Diseases

Behaviors and Mental Disorders

Uterine Cervical Neoplasms

Malnutrition

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Quality of Life

Personalized dietary intervention, low residue diet

Dietary recommendations currently used in the INCan

Dietary intervention will consist on a low residue diet: 20% kcal from fat, 5g lactose/day, 20g fiber/day (5g from insoluble fiber).

Dietary intervention will be adapted to the patient's individual requirements, according to the presence of comorbidities or renal deterioration.

1. No comorbidities. Energy: 20-30 kcal/kg of body weight/day. Protein: 1.3 g/kg of body weight/day.
2. Comorbidities (diabetes, hypertension), or geriatric patient. Energy: 25-30 kcal/kg of body weight/day. Protein: 1.5 g/kg of body weight/day.
3. Renal deterioration. Energy: 30-35 kcal/kg of body weight/day. Protein: 1 g/kg of body weight/day. Sodium: 2000-2300 mg/day. Potassium: 1900-2730 mg/day. Phosphorus: 800-1000 mg/day.

Dietary modification

Lucely C Cetina, MD, MSc

In Mexico, cervical cancer (CC) ranks second in incidence and mortality among women. The National Institute of Cancer in Mexico (lNCan) receives annually about 500 patients with CC, 80% of which are diagnosed with locally advanced disease. The standard treatment for locally advanced disease consists in concomitant chemo-radiotherapy based on cisplatin (QT-RT), followed by brachytherapy, with an absolute benefit of 10%. Adverse effects include gastrointestinal toxicity, which is the most important factor limiting the dosage of pelvic radiation. Cancer treatment, in any modality, induces malnutrition, more so when combined treatments are administered. Radiation induced gastrointestinal toxicity is caused by different factors, among which are malabsorption of bile, fat and carbohydrates, decrease in brush border enzymes, diverticular disease, proctitis, and psychological factors. International guidelines for cancer patients recommend nutritional assessment in these patients before they start treatment, so nutritional risk can be detected and the patient may get started on dietary intervention to prevent malnutrition. Several authors have studied the dietary management that may help reduce the gastrointestinal effects in cancer patients receiving pelvic radiotherapy. To reduce diarrhea and prevent malnutrition the recommended dietary approach is a low residue diet consisting on 20-25% kcal from fat, 5g of lactose and 20g of fiber. Currently the INCan does not follow the nutrition care process for cervical cancer patients; written recommendations are given to the patients with a list of foods allowed or not allowed, with no further nutritional assessment or intervention. From previous studies, the investigators have demonstrated that the current recommendations do not help the patients maintain their nutritional status, during their treatment most patients become malnourished (81%, p\<0.01). Therefore, the aim of this clinical trial is to evaluate a diet low in residue in CC patients, considering the necessary modifications for each patient if morbidities are present, in comparison with the current dietary recommendations used in the INCan.

In Mexico, cervical cancer (CC) is the second most frequent cause of death among women, with a mortality rate of 4000 women/year. Among the patients attended by the INCan, 80% are diagnosed with locally advanced CC and 30% of these present comorbidities. Hypertension may be present in 20% of patients, obesity in 18% and diabetes in 6.8%. These comorbidities affect the efficacy of treatment, increase the risk of malnutrition, of adverse events, hospitalization, increase hospital stay and worsen the quality of life, and even increase the risk of death. Furthermore, 10 to 20% of patients present kidney deterioration. The main reason for kidney disease is ureteral obstruction. The glomerular filtration rate deteriorates with age and many patients have comorbid medical illnesses that further compromise the kidneys. The standard treatment for CC is concomitant chemo-radiotherapy using cisplatin as a radiosensitizer, and brachytherapy at the end of treatment. Studies developed in the INCan described the acute toxicity symptoms in CC patients using this treatment: nausea, vomiting, diarrhea, cystitis, radioepithelitis, leucopenia, neutropenia, thrombocytopenia. Pelvic radiotherapy causes gastrointestinal toxicity, which is the most important limiting factor for the patients to complete their treatment. Cancer treatment, along with the tumor itself and other factors, causes malnutrition, and this confers a bad prognosis for the patient's response to treatment and survival. There is a nutritional risk in these patients at the moment of diagnosis, because of the metabolic alterations caused by the tumor, and the treatment-induced side effects. International guidelines for cancer patients recommend nutritional assessment in these patients before they start treatment, so nutritional risk can be detected and the patient may get started on dietary intervention to prevent malnutrition. Several authors have studied the dietary management that may help reduce the gastrointestinal effects in cancer patients receiving pelvic radiotherapy. To reduce diarrhea and prevent malnutrition the recommended dietary approach is a low residue diet consisting on 20-25% fat, 5g of lactose and 20g of fiber. Currently the INCan does not follow the nutrition care process for cervical cancer patients; written recommendations are given to the patients with a list of foods allowed or not allowed, with no further nutritional assessment or intervention. The investigators described the nutritional status of CC patients undergoing concomitant chemo-radiotherapy. It was observed that by the end of cancer treatment, a period of 9 weeks, 81.8% of patients became malnourished; 96% of patients lost weight, 78% of which had severe weight loss.

The aim of this clinical trial is to evaluate a diet low in residue in CC patients, considering the necessary modifications for each patient if morbidities are present, in comparison with the current dietary recommendations used in the INCan. A thorough nutritional evaluation including anthropometric data, dietary data, gastrointestinal toxicity and quality of life evaluations, will be performed.

Particular objectives are the following:

1. Identify the nutritional status of CC patients before, during and after treatment with chemo-radiotherapy, in intervention and control groups.
2. Determine the association of malnutrition and gastrointestinal toxicity during and after treatment, in intervention and control groups.
3. Evaluate the quality of life of patients before, during and after treatment, in both groups.
4. Establish the association of nutritional status and response to treatment, in both groups.

The aim is based on the following hypothesis: Patients receiving the personalized nutritional intervention with the low residue diet will maintain a better nutritional status during treatment, reflected in fewer malnourished patients, compared to the control group.

Methods.

Study design. Randomized clinical trial, open, factorial 3X2. To evaluate the efficacy of a low residue diet on the nutritional status, gastrointestinal toxicity and quality of life of CC patients referring to the National Institute of Cancer in Mexico (INCan). 320 patients will be included, with cervical malignant tumors of epithelial origin in the neck of the uterus, candidates for chemo-radiotherapy.

Dietary intervention will consist on a low residue diet: 20% kcal from fat, 5g lactose/day, 20g fiber/day (5g from insoluble fiber).

Dietary intervention will be adapted to the patient's individual requirements, according to the presence of comorbidities or renal deterioration.

1. No comorbidities. Energy: 20-30 kcal/kg of body weight/day. Protein: 1.3 g/kg of body weight/day.
2. Comorbidities (diabetes, hypertension), or geriatric patient. Energy: 25-30 kcal/kg of body weight/day. Protein: 1.5 g/kg of body weight/day.
3. Renal deterioration.

Energy: 30-35 kcal/kg of body weight/day.

Protein: 1 g/kg of body weight/day.

Sodium: 2000-2300 mg/day

Potassium: 1900-2730 mg/day

Phosphorus: 800-1000 mg/day

Control group will receive the standard written recommendations from the INCan, which enlist allowed foods and not allowed foods.

Sample size.

A sample space of 320 patients will be included if prior consent is acquired and if they meet the inclusion criteria. This clinical trial contemplates 3 strata with 2 levels.

Statistical analysis.

A univariate analysis will be performed to describe the study population. Descriptive statistics will be used to obtain measures of central tendency and dispersion, as well as frequency of distribution for qualitative variables. Percentage change of nutritional status will be calculated using the Friedman test. Chi square test will be used to compare basal vs final assessment, and chi square test will be used to compare among study groups. All confidence intervals will be constructed with a confidence of 95% (α=0.05). The interpretation of the study results will be responsibility of researchers. Data processing and analysis will be performed with the SPSS package (version 19.0®) for Microsoft.

Efficacy analysis.

Efficacy will be evaluated in patients that qualify to be included in the protocol analysis. To evaluate efficacy, nutritional diagnosis through the clinical course will be analyzed in both, intervention and control, groups. Also, toxicity and quality of life responses will be obtained.

Procedures.

Treatment. Anticancer treatment will consist of Cisplatin as a radiosensitizer, at a dosage of 40 mg/m2/week for 6 weeks. For patients with renal deterioration Gemcitabine will be used instead of Cisplatin, at a dosage of 300 mg/m2/week for 6 weeks. Concomitantly, external pelvic radiotherapy will be applied at a total dosage of 50.4 Gy divided by 28 fractions, 1.8 Gy/day/5 days a week, for 6 weeks. After completing concomitant chemo-radiotherapy, intracavitary brachytherapy will be administered at low dosage (30 Gy of Cesium 137) or high dosage (Iridium). Before initiating chemo-radiotherapy, a complete evaluation will be applied as mentioned.

Once eligibility criteria are verified, patients will be randomly assigned to intervention group or control group.

Visits during the study. After signing the informed consent, the patient will be informed when she will begin participating in the study (screening visit). If the patient complies with the inclusion criteria, a total of 5 visits will be scheduled: (1) at week -2, 2 weeks before treatment; (2) at week 0, on initiation of treatment; (3) at week 3, on the 3rd cycle of chemotherapy; (4) at week 9, by the end of brachytherapy; and (5) at week 21, 3 months after treatment completion.

Monitoring.

A thorough evaluation on each visit will be performed using the following tools:

* Patient generated subjective global assessment.
* Anthropometric data: weight, height, waist circumference, hip circumference, arm circumference.
* Body mass index.
* Waist to hip ratio.
* Body composition (bioelectrical impedance).
* % weight loss.
* Hand dynamometry.
* Dietary data: 24 hour recall and frequency of food intake questionnaires.
* % recommended energy intake.
* Biochemical markers: serum albumin, number of lymphocytes.
* Gastrointestinal toxicity using the CTCAE v4.03.
* Quality of life using the QLQ-C30 and CxC24.

Sample collection. No tissue or additional blood samples will be obtained, other than the blood samples used as part of the routine clinical laboratory tests.

Informed consent acquisition. On the screening visit, the written consent will be read and explained to the patient, clarifying the risks and benefits involved in the study. Two witnesses, independent from the study, will be present. The patient will have the choice to not participate or withdraw from the study at any time, her decision will not affect the quality of care and treatment that the attending physician will provide. The researcher will be governed by the ethical principles established in the Helsinki Accord. The physician will adequately respond all the matters of interest to the patient.

Ethical considerations.

The Research Committee and the Ethics Committee of the National Institute of Cancer in Mexico has approved the protocol and the informed consent document.

Patients participating in this study will be informed, through the informed consent, of all the details concerning this trial. The patients who agree to participate in the trial will express their willingness by signing the informed consent document, being clarified that they can leave the trial at any time, if they wish to do so.

Regulatory considerations.

This study abides by the ethical principles established by the international community, in accordance to the Good Clinical Practices, the Nüremberg Code, the Helsinki Accord, the Statement of Compliance with International Conference on Harmonization Guidelines for Good Clinical Practice, and the Regulations of the General Law of Health in the matter of research for health.

Effect of a Low Residue Diet in Comparison to the Dietetic Recommendations From the INCan in Cervical Cancer Patients

Effect of a Low Residue Diet in Comparison to the Dietary Recommendations From the INCan: A Randomized Clinical Trial to Assess Malnutrition, Gastrointestinal Toxicity and Quality of Life of Advanced Cervical Cancer Patients (IB2-IVA)

Evaluation of the gastrointestinal symptoms according to the Common Toxicity Criteria for Adverse Events (CTCAE v4).

A grading scale is provided for each adverse event (AE) term. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:

Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.

Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.

Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Evaluation the change of the nutritional status by the Patient Generated Subjective Global Assessment.

The Patient Generated Subjective Global Assessment is a questionnaire that comprises 7 sections: weight, intake, symptoms, functional capacity, disease and its relationship to nutritional requirements, metabolic demand and physical evaluation. Based on the previous results the interviewer will define which of the following three groups the individual surveyed belongs to:

A: well nourished. B: moderately or suspiciously undernourished. C: severely malnourished.

Change in food intake assessed by 24-hour reminder This method consists of questioning the subject to find out everything he or she ingested the day before. It includes three lists of foods to help the interviewee remember, the first is a quick list that contains drinks and foods, the second list contains foods that are commonly forgotten and the interview closes with a detailed description of everything that was consumed

Evaluation the changes of the body weight (kilograms) The measurement will be done on a hospital scale SECA brand.

Evaluation the changes of the phase angle (grades) by the bioelectrical impedance Biolelectrical impedances will be evaluated by body composition analyzer Quantun IV The phase angle is a nutritional indicator which evaluates the distribution of intracellular and extracellular fluid, therefore, it has been described as an indicator of the quality of the cell membrane

Evaluation the change of the handgrip strength (kilograms)

Handgript strength will be evaluated by a dinamometer Takei Hand strength is a simple measure, it has been used to estimate total muscle strength and has been described as a marker of nutritional status, in addition, it is related to mortality and morbidity (56).

The instrument for measuring hand force is the dynamometer, and the cut-off points for making a diagnosis of sarcopenia in women is a result ﹤de 20 kg, while in men it is ﹤de 30 kg

Quality of life questionnaire developed and validated for cancer patients ((European Organization for Research and Treatment of Cancer Core 30 (EORTC QLQ-C30 v3)) will be applied, and the change in summary score will be evaluated.

The EORTC QLQ-C30 questionnaire evaluates the quality of life in oncological population, is composed of both multi-item and single-item measures. It has 30 items, including nine scales: five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, pain and nausea / vomiting) and one global health status/QoL scale. Six single items are also included (Dyspnea, Insomnia, Appetite loss, Constipation, Diarrhea and Financial difficulties). A high score for all functional and global health/QoL scales represents a high/healthy level of functioning/high QoL, whereas a high score for a symptom scale/item represents a high level of symptoms/problems.

Change in quality of life summary score and subescales using The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cervical Cancer Module (EORTC QLQ-CX24). The EORTC QLQ-CX24 is the supplementary module of the QLQ-C30 aimed to evaluate quality of life of cervical cancer patients.

The EORTC QLQ-CX24 is the supplementary module of the QLQ-C30 aimed to evaluate quality of life of cervical cancer patients. It consists of 24 items divided in three multi-item scales to assess symptoms experience (gastrointestinal and genitourinary), body image and sexual/vaginal functioning, and six single items to assess lymphedema, peripheral neuropathy, menopausal symptoms, sexual worry, sexual activity and sexual enjoyment. The last five questions are answered only by patients with an active sex life. Higher scores are equivalent to worse or more symptoms, except for items 49 and 54 (higher score indicates better quality of life).

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

National Institute of Cancerología

MD, MSc.

Skin and Connective Tissue Diseases

Breast Neoplasms

PA CONDITION: The goal of the PA condition is to encourage participants to gradually increase moderate to vigorous PA to 150 minutes per week and to increase resistance training to a total of 15 minutes per day twice per week.

DIET CONDITION: The goal of the dietary condition includes increasing intake of fruit and vegetable to 5-servings per day. The program also encourages participants to increase the consumption of colorful fruits and vegetables. The fat goals consist of reducing saturated fats to \<10% of total kilocalories per day, trans fats to \<3 grams per day, and added sugar to \<50 grams per day.

ALIVE is an email-based platform designed to help participants increase their physical activity, increase fruit and vegetable consumption, and decrease their intake of saturated and trans fats and added sugars. This automated system contains content and tailoring that is delivered in the form of emails obtained directly from cancer patients. Additional information they will receive included: tips for achieving those goals, health information, and opportunities for interaction and engagement.

ALIVE

Raheem Paxton, PhD

In this parallel group study, participants were randomized to either 1 of 3 conditions (a) fruit and vegetable consumption, (b) dietary fat and added sugars, or (c) physical activity.

In this study, the investigators will evaluate the feasibility and preliminary results of a 3-month web-based lifestyle intervention 500 female cancer survivors.

Specific aim 1: to determine the rates of recruitment, retention, attendance, satisfaction, adverse events, and barriers to participation in the proposed intervention.

Specific aim 2: to determine whether a home-based intervention is associated with greater improvements in mean minutes of moderate to vigorous physical activity, diet quality, body size, constructs of Social Cognitive Theory, and health-related quality of life than participants randomized to a sedentary behavior reduction condition.

Web-based Study for Cancer Survivors

A Lifestyle Intervention Via Email (ALIVE) for Cancer Survivors

Once data are compiled, the investigators will decide whether it will be available for sharing

Physical activity and sedentary behavior were assessed with the Work and Home Activity Questionnaire at baseline and at 3-months

Dietary intake was assessed with Block health habits and history questionnaire. This instrument is a validated food frequency questionnaire

Health-related quality of life will be assessed with instruments measuring functional status, pain and fatigue interference, and cognitive function at baseline and at 3-months.

M.D. Anderson Cancer Center

The University of Texas Health Science Center, Houston

University of Houston

University of Alberta

University of North Texas Health Science Center

Assistant Professor

Symptoms and General Pathology

Wasting Syndrome

Cachexia

Body Weight

Weight Loss

Body Weight Changes

Thinness

NUTRIDRINK Compact Protein Oral nutritional supplement Dietary advice

high-energy, high-protein, oral liquid nutritional supplement; dosage: 2x125 ml per day, 7 days per week for 12 weeks (3 months)

NUTRIDRINK Compact Protein

Sylwia Malgorzewicz, MD, PhD

Determine whether nutritional support with high protein ONS in adult oncologic patients in the first step of cancer cachexia - asymptomatic precachexia, influence on the toxicity of systemic therapy.

Other endpoints:

* to determine whether high protein ONS influence on the nutritional status
* to determine whether high protein ONS influence on the quality of life
* to determine whether high protein ONS influence on the performance status
* to determine high protein ONS tolerability / ONS intake compliance

Chemotherapy-related Toxicity, Nutritional Status and Quality of Life

Chemotherapy-related Toxicity, Nutritional Status and Quality of Life in Precachectic Oncologic Patients With or Without High Protein Nutritional Support. A Prospective, Randomized Study

publication in nutritional and oncological journals, presentation on the congresses

graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0); to determine whether nutritional support with high protein ONS in adult oncologic patients in the first step of cancer cachexia - asymptomatic precachexia, influence on the toxicity of systemic therapy during 3 months observation period (comparison of the results at the baseline and after 12 weeks)

the assessment according to Nutritional Risk Screening 2002 (NRS 2002), Subjective Global Assessment (SGA), body mass, body mass index (BMI), VAS for appetite, albumin, prealbumin, triglycerides, total cholesterol, fasting blood glucose, C-reactive protein (CRP), ferritin, complete blood count.

Body mass (in kg) will measure by the scales (Tanita BC 420). Hight ( in cm) measure by Stadiometer (Tanita)

Body mass index calculation (BMI) on the basis of the following formula:

BMI = body weight / height2 (kg/m2).

VAS for appetite is 100-mm line where 0 mm means "I had no appetite at all" and 100 mm means "My appetite was very good".

Laboratory parameters will measured by routine laboratory methods. All results will be compared between study groups (ONS vs without ONS) at the same time point (eg. baseline group ONS vs baseline group without ONS)

FAACT-ESPEN score Version 4 (Functional Assessment of Anorexia/Cachexia Therapy questionnaire) is a measure of the quality of life and it is completed by a patient, it has a total of 42 questions. Patients mark 0 (none) - 4 (very much) for each question. This tool consists of five subscales: functional well-being (7 items), physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items) and other aspects, including appetite (13 items).

The maximum score is 168. The lower the score, the lower overall quality of life.

To performance status assessment will be used Kornofsky scale and ECOG scale. The Karnofsky score allows to quantify the overall state and quality of life of a patient with neoplastic disease who qualifies to receive chemotherapy. The score has a range from 0 to 100, where 100 represents the ideal state and 0 - death.

The Eastern Cooperative Oncology Group(ECOG) score runs from 0 to 5, with 0 denoting perfect health and 5 death.

Nutricia Foundation

University Clinical Centre, Gdansk

After baseline examinations, participants are randomized to an active dietary intervention group.The intervention group is invited to attend six full days of life-style intervention activities over the next six months. These activities include six cookery courses followed by lunch, six physical activity sessions (walking for 45 minutes) and six conferences. The intervention and control groups both complete questionnaires on adherence to the Mediterranean diet (MEDAS) at baseline and at the end of the study, and are asked for at least two 24-hour recalls of the previous day's food intake, and details of their physical exercise during the six-month intervention.

All participants receive general recommendations for the dietary prevention of cancer. After baseline examinations, women randomized in the control group carry on following the baseline recommendations.

The main aim of the trial is to reduce serum levels of IGF-I and IRm with a a low- calorie and low-protein diet. In humans, calorie restriction alone does not seem to significantly lower IGF-I; protein restriction is also required. In detail, recommendations for participants included in the intervention arm include:

* reducing protein intake, mainly milk and animal protein (except fish), down to 10-12% of total calorie intake.
* reducing high glycemic index food and high insulinemic foods.
* reducing sources of saturated fat (red and processed meat, milk and dairy products).
* eating mostly food of plant origin, with a wide variety of seasonal products.

Dietary intervention

Insulin-like growth factor I (IGF-I) and other markers of insulin resistance (IRm) might modulate the penetrance of BRCA genes mutation.

The investigators have designed a demonstration project with BRCA mutation carriers (with or without a previous diagnosis of breast cancer) to test:

1. whether a lifestyle intervention significantly reduceIGF-I and the other IRm (randomized trial).
2. whether mutation carriers with a previous diagnosis of breast cancer have higher IRm than carriers without breast cancer (case-controlstudy).
3. whether IRm and their change over time affect subsequent breast cancer incidence and prognosis (cohort follow-up).

The investigators expect to significantly reduce IGF-I and IRm, to find that BRCA mutation carriers with a previous breast cancer have higher IRm levels, and, in the long term, that women with persistent higher IRm levels have higher penetrance and worst prognosis.

Confirming a significant reduction of IRm and the impact of their levels on prognosis would help to develop primary prevention recommendations for high risk families.

Abdominal obesity and high body weight are associated with a greater risk of breast cancer (BC) in women belonging to high risk families than in women without family history of BC. A case-control study showed that high energy intake, usually associated with higher bio-availability of growth factors, is associated with BC risk in BRCA mutation carriers. A multinational case-only study on 3000 young BC women suggested that patients with BRCA mutation had higher consumption of milk. Milk directly stimulates insulin production and release, and is associated with higher plasma levels of insulin-like growth factor I (IGF-I).

In a case-control analysis on 308 high genetic risk women, investigators showed that high serum levels of IGF-I are associated with a significantly increased penetrance.

Consistently, mechanistic studies hypothesized a functional interaction between the BRCA genes and the IGF-I system.

The lifetime cumulative risk (penetrance) of BC associated with BRCA mutations is of the order of 50%, and a sizeable proportion of mutation carriers does not develop the disease. Therefore, the penetrance of the genetic trait may be regulated trough other genetic or environmental factors, including dietary, metabolic, and growth factors. The investigators hypothesized that markers of insulin resistance (IRm), such as plasma level of glucose, insulin, IGF-I and the presence of metabolic syndrome, which affect risk and prognosis of sporadic BC, are relevant also for hereditary BC.

The investigators have designed a demonstration project with BRCA mutation carriers (with or without a previous diagnosis of BC) to test:

1. whether a lifestyle intervention significantly reduce IRm (randomized trial).
2. whether mutation carriers with a previous diagnosis of BC have higher IRm than carriers without BC (case-control study).
3. whether IRm and their change over time affect subsequent BC incidence and prognosis (cohort follow-up).

In a pilot phase the investigators have randomized 150 BRCA mutated women to a dietary intervention and a control group for a short term (6 months) trial to test the reduction of IRm levels. In the present study the investigators to recruit 600 BRCA mutation carriers to test if blood levels of IRm and their change over time influence the risk of BC and of BC relapse. All participants will receive the WCRF Decalogue for the prevention of cancer. Participants will be then randomized in an active lifestyle intervention group (6 full days of life-style intervention activities along the subsequent 6 months) and in a control group that will remain with the baseline recommendation. After 6 months also the control group will be invited to an active intervention.

The investigators expect to significantly reduce IRm, to find that BRCA mutation carriers with a previous BC have higher IRm levels, and, in the long term, that women with persistent higher IRm levels have higher penetrance and worst prognosis.

BRCA mutation carriers, with or without breast cancer, aged 18-70 years and without metastases are eligible. After the baseline examinations, women are randomized to an active dietary intervention or to a control group. The intervention group should attend six full days of activities over the next six months.

Dietary Intervention and BRCA Penetrance

Lifestyle and the Penetrance of BRCA Mutation

Individual participant data are not available to other researchers. The data software is blinded and protected.

Final analyses will be performed by intention to treat. By assuming that:

a) the planned lifestyle interventions may reduce IGF-I levels by 10%, b) alpha error = 0.05, the investigators shall have 96% power to compare 300 women included in the intervention group versus 300 in the control group.

By classifying the exposure status according to the IGF-I median level and by assuming that :

1. the probability of exposure among controls is 50 %,
2. a case/control ratio of 2/1 (as in a pilot study): 400 women with a previous diagnosis of BC and 200 unaffected,
3. the true odds ratio for BC in exposed versus unexposed subjects ranging between 1.5 to 2 (the lower confidence interval of a pilot study), the investigators will be able to reject the null hypothesis ( that this odds ratio equals 1) with a power ranging from 64% to 97% at the alpha level of 0.05.

This secondary aim requires the follow-up of the BRCA mutation carriers cohort. By assuming : a) equal number of exposed (IGF-I level\>median) and unexposed subjects of 300, b) 85% probability of event-free after 48 months of follow-up c) the true hazard ratio of exposed subjects relative to unexposed subjects ranging between 1.5 to 2, the investigators will be able to reject the null hypothesis that exposed and unexposed survival curves are equal with a power ranging from 41% to 78% at the alpha level of 0.05. Further follow-up will increase the power.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Making Healthy Choices: Does Having an Online Health Coach Help?	NCT03691545	Physical Activi... Dietary Modific...	interactive ses...	20 Years - 39 Years	University of Ottawa
Effect of a Low Residue Diet in Comparison to the Dietetic Recommendations From the INCan in Cervical Cancer Patients	NCT03100409	Uterine Cervica... Dietary Modific... Radiation Toxic... Gastrointestina...	Dietary modific...	18 Years -	National Institute of Cancerología
Web-based Study for Cancer Survivors	NCT02722850	Physical Activi... Dietary Modific...	ALIVE	18 Years - 80 Years	University of North Texas Health Science Center
Web-based Study for Cancer Survivors	NCT02722850	Physical Activi... Dietary Modific...	ALIVE	18 Years - 80 Years	University of North Texas Health Science Center
Chemotherapy-related Toxicity, Nutritional Status and Quality of Life	NCT02848807	Toxicity Due to... Cancer Cachexia Metastatic Colo... Quality of Life Dietary Modific...	NUTRIDRINK Comp...	18 Years -	University Clinical Centre, Gdansk
Dietary Intervention and BRCA Penetrance	NCT03066856	Dietary Modific... BRCA1 Mutation BRCA2 Mutation Breast Cancer	Dietary interve...	18 Years - 70 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for dietary modification