Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first-line treatment within the randomized Phase III trial FIRE-3 (AIO KRK-0306).

Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE-3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS-WT tumors (ie, wild-type in KRAS and NRAS exons 2-4). The prognostic and predictive relevance of early weight loss (EWL) regarding patient outcomes and treatment side effects were evaluated. Retrospective data on body weight during first 6 months of treatment were evaluated (N = 326). To correlate with efficacy endpoints and treatment side effects, patients were grouped according to clinically significant EWL ≥5% and <5% at Month 3. Age constituted the only significant predictor of EWL following a linear relationship with the corresponding log odds ratio (P = .016). EWL was significantly associated with the incident frequencies of diarrhea, edema, fatigue, nausea and vomiting. Further, a multivariate analysis revealed EWL to be an independent negative prognostic factor for overall survival (32.4 vs 21.1 months; hazard ratio [HR]: 1.64; 95% confidence interval [CI] = 1.13-2.38; P = .0098) and progression-free survival (11.8 vs 9.0 months; HR: 1.72; 95% CI = 1.18-2.5; P = .0048). In conclusion, EWL during systemic treatment against mCRC is significantly associated with patient age. Patients exhibiting EWL had worse survival and higher frequencies of adverse events. Early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL.

Patient-reported outcome measures obtained via E-Health tools ease the assessment burden and encourage patient participation in cancer care (PaCC Study).

Patient-reported outcome measures obtained via E-Health tools ease the assessment burden and encourage patient participation in cancer care (PaCC Study) BACKGROUND: E-health based patient-reported outcome measures (PROMs) have the potential to automate early identification of both nutrition status and distress status in cancer patients while facilitating treatment and encouraging patient participation. This cross-sectional study assessed the acceptability, accuracy, and clinical utility of PROMs collected via E-Health tools among patients undergoing treatment for stomach, colorectal, and pancreatic tumors. RESULTS: Eight-nine percent mostly, or completely, agreed that PROMs via tablets should be integrated in routine clinical care. Men were significantly more likely to require help completing the questionnaires than women (inv.OR= 0.51, 95% CI=(0.27, 0.95), p = 0.035). The level of help needed increased by 3% with each 1-year increase in age (inv. OR=1.03, 95% CI=(1.01, 1.06), p = 0.013). On average, a patient tended to declare weight which was 0.84 kg inferior to their true weight (Bland and Altman 95 % CI=(-3.9, 5.6); SD: 2.41) and a height which was 0.95 cm superior to their true height (Bland and Altman 95 % CI=(-5, 3.1); SD 2.08). Patient-reported nutrition status was significantly associated with the professionally generated assessment (95% CI=(2.27, 4.15), p < 0.001). As nutrition status declined, the distress score increased (95%CI=(0.88, 1.68), p < 0.001). Of the patients, 48.8% who were both distressed and malnourished requested supportive care to address their problems. CONCLUSION: Patient-reported assessments utilizing E-health tools are an accurate and efficient method to encourage patient participation in cancer care while simultaneously ensuring that regular assessment of psycho-social and nutritional aspects of care are efficiently integrated in the daily clinical routine.

Optimizing the Analytical Value of Oncology-Related Data Based on an In-Memory Analysis Layer: Development and Assessment of the Munich Online Comprehensive Cancer Analysis Platform.

BACKGROUND: Many comprehensive cancer centers incorporate tumor documentation software supplying structured information from the associated centers' oncology patients for internal and external audit purposes. However, much of the documentation data included in these systems often remain unused and unknown by most of the clinicians at the sites. OBJECTIVE: To improve access to such data for analytical purposes, a prerollout of an analysis layer based on the business intelligence software QlikView was implemented. This software allows for the real-time analysis and inspection of oncology-related data. The system is meant to increase access to the data while simultaneously providing tools for user-friendly real-time analytics. METHODS: The system combines in-memory capabilities (based on QlikView software) with innovative techniques that compress the complexity of the data, consequently improving its readability as well as its accessibility for designated end users. Aside from the technical and conceptual components, the software's implementation necessitated a complex system of permission and governance. RESULTS: A continuously running system including daily updates with a user-friendly Web interface and real-time usage was established. This paper introduces its main components and major design ideas. A commented video summarizing and presenting the work can be found within the Multimedia Appendix. CONCLUSIONS: The system has been well-received by a focus group of physicians within an initial prerollout. Aside from improving data transparency, the system's main benefits are its quality and process control capabilities, knowledge discovery, and hypothesis generation. Limitations such as run time, governance, or misinterpretation of data are considered.

Tri-country translation, cultural adaptation, and validity confirmation of the Scored Patient-Generated Subjective Global Assessment.

PURPOSE: The Scored Patient-Generated Subjective Global Assessment (PG-SGA) is the only malnutrition (risk) assessment tool that combines patient-generated measures with professional-generated (medical) factors. We aimed to apply international standards to produce a high quality, validated, translation and cultural adaptation of the original PG-SGA for the Austrian, German, and Swiss setting. METHODS: Analogue to methodology used for the Dutch, Portuguese, and Thai versions of PG-SGA, the ten steps of the International Society for Pharmacoeconomics and Outcomes Research's principles of good practice for translation and cultural adaptation were followed. Comprehensibility and difficulty of the translation were assessed in 103 patients and 104 healthcare professionals recruited from all three German-speaking countries. Content validity of the translation was assessed among healthcare professionals (HCP). Item and scale indices were calculated for content validity (I-CVI; S-CVI), comprehensibility (I-CI; S-CI), and difficulty (I-DI; S-DI). RESULTS: Patients' perceived comprehensibility and difficulty of the PG-SGA fell within the range considered to be excellent (S-CI = 0.90, S-DI = 0.90), HCP-perceived content validity (S-CVI = 0.90) was also excellent, while HCP-perceived comprehensibility fell within the high range of acceptable (S-CI = 0.87). The professional component of the PG-SGA was perceived as below acceptable (S-DI = 0.72) with the physical exam being rated the most difficult (I-DI=0.29-0.75). CONCLUSIONS: The systematic approach resulted in a high-quality validation of the German language version of the PG-SGA, that is internationally comparable, comprehensible, easy to complete, and considered relevant for use in Austria, Germany and Switzerland.

Validation of the German version of the Mediterranean Diet Adherence Screener (MEDAS) questionnaire.

BACKGROUND: Health benefits of the Mediterranean Diet (MD) have been shown in different at-risk populations. A German translation of the Mediterranean Diet Adherence Screener (MEDAS) from the PREvención con DIeta MEDiterránea (PREDIMED) consortium was used in the LIBRE study, investigating effects of lifestyle-intervention on women with BRCA1/2 mutations. The purpose of the present study is to validate the MEDAS German version. METHODS: LIBRE is a multicentre (three university hospitals during this pilot phase), unblinded, randomized, controlled clinical trial. Women with a BRCA1/2 mutation of age 18 or over who provided written consent were eligible for the trial. As part of the assessment, all were given a full-length Food Frequency Questionnaire (FFQ) and MEDAS at baseline and after 3 months. Data derived from FFQ was compared to MEDAS in order to evaluate agreement or concordance between the two questionnaires. Additionally, the association of dietary intake biomarkers in the blood (ß-carotene, omega-3, omega-6 and omega-9 fatty acids and high-sensitivity C-reactive protein (hsCRP)) with some MEDAS items was analyzed using t-Tests and a multivariate regression. RESULTS: The participants of the LIBRE pilot study were 68 in total (33 Intervention, 35 Control). Only participants who completed both questionnaires were included in this analysis (baseline: 66, month three: 54). The concordance between these two questionnaires varied between the items (Intraclass correlation coefficient of 0.91 for pulses at the highest and -0.33 for sugar-sweetened drinks). Mean MEDAS scores (sum of all items) were 9% higher than their FFQ counter-parts at baseline and 15% after 3 months. Higher fish consumption (at least 3 portions) was associated with lower omega-6 fatty acid levels (p = 0.026) and higher omega-3 fatty acid levels (p = 0.037), both results being statistically significant. CONCLUSIONS: We conclude that the German MEDAS in its current version could be a useful tool in clinical trials and in practice to assess adherence to MD. TRIAL REGISTRATION: ClinicalTrials.gov , registered on March 12, 2014, identifier: NCT02087592 . World Health Organization Trial Registration, registered on 3 August 2015, identifier: NCT02087592 .

Empowering of Oncology Patients and Informal Caregivers: Analysis of an Interdisciplinary Seminar Model for Breast Cancer and Gyneco-Oncological Patients.

INTRODUCTION: The interdisciplinary empowerment seminar aims to familiarize patients and informal caregivers (ICs) with supportive measures, focusing on understanding disease, therapy, and side effect management. METHODS: The seminar, conducted in two courses over 1-month intervals prior to chemotherapy, included lectures, supportive materials, Q and A sessions, and individual discussions with experts in nutrition, exercise, psycho-oncology, and complementary medicine. Evaluation is based on a self-developed questionnaire and questionnaires on QoL (EORTC-QLQ-C30, BR23, CX24, OV28), anxiety and depression (HADS-D) at week 0, 5, 9, and 12. A control group with standard of care was evaluated at baseline and after 12 weeks. RESULTS: Between October 2020 and May 2021, 19 patients and 9 ICs participated in the seminar. The control group included 20 patients. 96.4% of participants were highly satisfied with the seminar and would recommend it. QoL deterioration was more pronounced in the control group (control: week 0 = 67.6; week 12 = 61.7; intervention: week 0 = 60.8; week 12 = 60.7). This trend could not be proven by analysis of interaction (mixed ANOVA: p = 0.114). Increased confidence of participants' knowledge about side effects was shown, and ICs reported higher confidence in knowledge and coping with the disease. CONCLUSIONS: The seminar received positive feedback and indicated increased knowledge and a trend toward better QoL preservation. Larger studies are needed for confirmation. The seminar effectively addressed unique needs, bolstering confidence and knowledge. Interdisciplinary patient and caregiver empowerment seminars can improve disease-related knowledge and positively affect QoL at the start of chemotherapy. Informational needs can be satisfied. Offering educational seminars and fostering individualized support networks can increase quality of care.

Global Leadership Initiative on Malnutrition (GLIM) for the diagnosis of malnutrition - a framework for consistent dietetic practice.

Malnutrition is an alarming and ongoing healthcare problem globally. Malnutrition has a negative impact on the individual patient, leading to poorer clinical outcomes and increased mortality, but also poses an economic burden on society. Proper identification and diagnostics are prerequisites for initiation of treatment. In 2019, the Global Leadership Initiative on Malnutrition, a consensus-based global framework to uniformly diagnose malnutrition across populations, healthcare settings, and countries was published. Identifying and treating malnutrition is an interdisciplinary team effort. Nonetheless, the nutrition and dietetics profession is specifically trained for diagnosing and treating nutrition(-related) conditions, and therefore has a key role in the interdisciplinary team in implementing the GLIM framework in clinical practice. For the nutrition and dietetics profession, GLIM offers a great opportunity for moving both the scientific and clinical knowledge of malnutrition management forward. While the GLIM framework has been extensively studied since its launch, various knowledge gaps still remain. For the nutrition and dietetics profession, these knowledge gaps mainly relate to the GLIM implementation process, to the role of GLIM in relation to the nutrition care process, and to treatment strategies for various nutrition-related conditions. In this opinion paper, we aimed to describe the rationale for implementing the GLIM framework in clinical dietetic practice, and propose a research agenda based on knowledge gaps regarding GLIM in relation to nutrition care from a dietetic point of view.

Nutrition care is an integral part of patient-centred medical care: a European consensus.

While healthcare is becoming more patient-centred, evidence-based nutrition interventions are still not accessible to all patients with cancer. As nutrition interventions directly improve clinical and socioeconomic outcomes, patient-centred care is not complete without nutrition care. While awareness of the negative impact of malnutrition on clinical outcomes, quality of life, and functional and emotional wellbeing in cancer is growing, there is relatively poor awareness amongst patients, clinicians, policymakers, and payers that nutrition interventions -particularly those begun in the early stages of the disease course- are an effective method for improving such outcomes. The European Beating Cancer Plan recognises the need for a holistic approach to cancer but lacks actionable recommendations to implement integrated nutrition cancer care at member state level. When considering nutrition care as a human right, the impact on quality of life and functional status must be prioritized, as these may be equally as important to patients, especially in advanced cancer where improvements in clinical outcomes such as survival or tumour burden may not be attainable. We formulate actions needed at the regional and the European level to ensure integrated nutrition care for all patients with cancer. The 4 main Take Home Messages are as follows: 1. The goals of Europe's Beating Cancer Plan cannot be achieved without integrating nutrition across the cancer care continuum. 2. Malnutrition negatively impacts clinical outcomes and has socioeconomic consequences for patients and healthcare systems. 3. Championing integrating nutrition care into cancer care is therefore the duty and ethical responsibility of clinicians (Hippocratic Oath-primum non nocere) and 4. Nutrition care is a cost effective, evidence-based therapy.

Swapping data: A pragmatic approach for enabling academic-industrial partnerships.

Objectives: Academic institutions have access to comprehensive sets of real-world data. However, their potential for secondary use-for example, in medical outcomes research or health care quality management-is often limited due to data privacy concerns. External partners could help achieve this potential, yet documented frameworks for such cooperation are lacking. Therefore, this work presents a pragmatic approach for enabling academic-industrial data partnerships in a health care environment. Methods: We employ a value-swapping strategy to facilitate data sharing. Using tumor documentation and molecular pathology data, we define a data-altering process as well as rules for an organizational pipeline that includes the technical anonymization process. Results: The resulting dataset was fully anonymized while still retaining the critical properties of the original data to allow for external development and the training of analytical algorithms. Conclusion: Value swapping is a pragmatic, yet powerful method to balance data privacy and requirements for algorithm development; therefore, it is well suited to enable academic-industrial data partnerships.

Closing the cancer care gap with a patient-reported nutrition screening: A retrospective analysis of a quality improvement project on an oncology ward (CCC study).

BACKGROUND & AIMS: Early identification of patients at risk for malnutrition followed by individualized nutrition interventions is a central step to the provision of appropriate nutrition care. However, a health care professional (HCP)-based nutrition screening is not always consistently integrated into routine care. Patient-reported (PR) nutrition screening could thus potentially alleviate the burden on the HCPs and contribute to a greater number of patients who are identified and treated for malnutrition. METHODS: In 2021 a Quality Improvement Project (QIP) at our out-patient oncology clinic was undertaken to implement the change from a HCP-based nutrition screening to a PR-screening. This was followed by a retrospective analysis in which the primary outcome measure was the rate of nutrition consultations initiated for patients undergoing cancer therapy. RESULTS: In total n = 1657 patient data sets derived from comparable time periods before and after the QIP were analyzed and compared. Both groups had a comparable mean age and gender distribution. The most common diagnosis in both groups was gastrointestinal tumors. The change in routine care from a HCP-based nutrition screening to a PR-screening led to a significant increase in nutrition consultation rates (RD = 19%; p < 0.001; 95% CI 14.4%-23.5%) and screening rates (RD = 30.5%; p < 0.001; 95% CI 26.2%-34.7%). CONCLUSIONS: The change to PR-screening potentially facilitates an increase in nutrition screening rates. This in turn leads to an increased rate of patients identified at risk for malnutrition and thus referrals for nutrition consultations. Our findings indicate that a PR nutrition screening tool could play a role in closing the care gap and contribute to reducing rates of malnutrition among this population where screening is not consistently integrated into routine care.

Should routine risk reduction procedures for the prevention and control of pandemics become a standard in all oncological outpatient clinics? The prospective COVID-19 cohort study: protect-CoV.

Limited knowledge exists on the effectiveness of preventive preparedness plans for the care of outpatient cancer patients during epidemics or pandemics. To ensure adequate, timely and continuous clinical care for this highly vulnerable population, we propose the establishment of preventive standard safety protocols providing effective early phase identification of outbreaks at outpatient cancer facilities and communicating adapted standards of care. The prospective cohort study Protect-CoV conducted at the LMU Klinikum from mid-March to June 2020 investigated the effectiveness of a rapid, proactive and methodical response to protect patients and interrupt SARS-CoV-2 transmission chains during the first pandemic wave. The implemented measures reduced the risk of infection of individual cancer patients and ensured safe adjunctive infusion therapy in an outpatient setting during the early COVID-19 pandemic. In addition to the immediate implementation of standard hygiene procedures, our results underscore the importance of routine PCR testing for the identification of asymptomatic or pre-symptomatic COVID-19 cases and immediate tracing of positive cases and their contacts. While more prospective controlled studies are needed to confirm these results, our study illustrates the importance of including preventative testing and tracing measures in the standard risk reduction procedures at all out patient cancer centers.

Quality of life, symptoms and dietary habits in oncology outpatients with malnutrition: A cross-sectional study.

Cancer-related malnutrition has a high prevalence, reduces survival and increases side effects. The aim of this study was to assess oncology outpatients and risk of malnutrition. Reported symptoms and quality of life (QoL) in patients found to be at risk of malnutrition or malnourished were compared to patients without malnutrition. Using a standardized questionnaire, the European Organization for Research and Treatment of Cancer Questionnaire for Quality of Life and the Mini Nutritional Assessment (MNA), patients in an outpatient cancer clinic undergoing chemotherapy treatment at a German University Hospital were assessed for nutrition, risk of malnutrition and quality of life. Based on the MNA, 39 (45.9%) patients were categorized as malnourished or at risk for malnutrition. Loss of appetite (n = 37.6%, p < 0.001) and altered taste sensation (n = 30,3%, p < 0.001) were the symptoms most frequently associated with reduced food intake. Patients with risk of malnutrition scored lower on the global health status (n = 48.15%, p = 0.001). Side effects of cancer treatments lead to a higher risk of malnutrition and as a consequence lower QoL. These side effects should be addressed more efficiently in cancer care.

Evaluating the Lipid-Lowering Effects of α-lipoic Acid Supplementation: A Systematic Review.

Dietary supplementation of α-lipoic acid, an 8-carbon organosulfur compound, has been widely reported to lower blood glucose concentration and/or improve insulin sensitivity in previous randomized controlled trials. Although animal model studies further report fairly consistent lipid lowering in both blood and tissue pools in response to α-lipoic acid supplementation, results from human studies are mixed. According to PRISMA guidelines, we conducted a systematic review of published randomized controlled studies (RCTs) to assess the efficacy of α-lipoic acid supplementation as a strategy to improve dyslipidemia, with a focus on serum lipid endpoints including TC, low density lipoprotein cholesterol (LDL-C), HDL-C, and TG. PubMed, EMBASE, Cochrane Evidence-Based Medicine Reviews, Proquest, Web of Science, and Scopus were searched to identify RCTs that reported the effects of α-lipoic acid on blood lipid concentrations from 1970 to 2017. We included RCTs reporting blood lipid responses in adults supplemented with oral α-lipoic acid versus a placebo or control for at least one month. Studies were reviewed and data were extracted by two independent study authors. Seventeen studies were deemed eligible for inclusion. Overall, mean percent changes in blood lipid endpoints in response to α-lipoic acid varied considerably between studies for total cholesterol (-10.5 to +13.9), low-density lipoprotein cholesterol (-19.67 to +9.06), high-density lipoprotein cholesterol (-12.5 to +29.20), and triglycerides (-38.57 to +17.0). Results of this systematic review suggest little consistent benefit on serum lipids in response to α-lipoic acid supplementation. Further well-controlled studies designed and powered to detect improvements in blood lipids in hypercholesterolemic individuals are warranted (PROSPERO registration number: CRD42018105933).

[Primary and Secondary Prevention of Multiple Myeloma - Lifestyle Factors and Supportive Measures]. / Primär- und Sekundärprävention des Multiplen Myeloms ­ Lebensstilfaktoren und Supportivmaßnahmen.

Lifestyle factors such as diet, physical activity and exposure to noxious agents are modifiable factors that have a significant impact on the state of health and life expectancy of humans. The following article is intended to provide an overview of current knowledge on the influence of these lifestyle factors on the development and progression of multiple myeloma and is dedicated to the question of the extent to which prevention strategies can be usefully applied.

[Vitamins and Minerals in Oncology]. / Vitamine und Spurenelemente in der Onkologie.

The use of vitamins and minerals to prevent cancer as well as their supportive use in oncological patients is widespread and often occurs without the knowledge of the treating physician. Beyond general recommendations with regard to a balanced and healthy diet, no evidence exists supporting the use of vitamins and minerals in the prevention of cancer. Furthermore, the diet of oncological patients should contain vitamins and minerals of the same quantity as for healthy individuals. In particular, there is currently no rationale for a high-dosage administration of antioxidants.

[Dietary Recommendations in Metabolic Vascular Syndrome]. / Ernährungsempfehlungen beim metabolisch-vaskulären Syndrom.

Cardiovascular disease is the number one cause of death globally. Poor diet constitutes a key factor in the initiation and progression of cardiovascular disease and has become the leading risk factor for disability and death worldwide. Therefore, addressing suboptimal nutrition is of key prognostic relevance in primary and secondary prevention of metabolic vascular syndrome.Metabolic vascular syndrome is a multidimensional network of acquired cardiometabolic risk factors closely related to insulin resistance (IR) and concomitant hyperinsulinemia. IR, being the underlying cause of metabolic vascular syndrome and certain types of cancer, should attract the attention of every clinician. As changes in lipoprotein metabolism are one of the earliest indicators of metabolic dysfunction, a relevant biomarker for identifying individuals with IR is the TAG/HDL-C ratio.IR - and concomitant metabolic vascular risk - can be effectively treated by lifestyle intervention. If IR is present, dietary carbohydrate restriction has consistently been shown to be superior to dietary fat restriction in reversing metabolic dysfunction. The beneficial effects of carbohydrate restricted diets on metabolic vascular risk are independent of BMI - diet quality therefore confers patient benefit beyond weight reduction.The effect of single nutrients on isolated lipid surrogate markers such as LDL-C does not capture their global effect on metabolic vascular risk.Targeting IR with a low glycemic load, real food diet will reduce overall energy density and will improve all risk factors of metabolic vascular syndrome. In particular, replacing refined carbohydrates with healthy fats in the context of a Mediterranean style-, low carbohydrate and calorie-unrestricted dietary pattern has been shown to significantly reduce burden of metabolic vascular disease.

Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial.

BACKGROUND: Women with highly penetrant BRCA mutations have a 55-60 % lifetime risk for breast cancer and a 16-59 % lifetime risk of developing ovarian cancer. However, penetrance differs interindividually, indicating that environmental and behavioral factors may modify this risk. It is well documented that the risk for sporadic breast cancer disease can be modified by changing lifestyle factors that primarily include physical activity, dietary habits, and body weight. It can thus be hypothesized that the modification of these lifestyle factors may also influence the incidence and progression of cancer in BRCA mutation carriers. METHODS/DESIGN: This multicenter, interdisciplinary, prospective, two-armed, randomized (1:1) controlled trial aims to enroll a minimum of 600 BRCA1 and BRCA2 mutation carriers to partake in either a lifestyle intervention or usual care. The study primarily aims to demonstrate an improvement of nutritional behavior (adherence to the Mediterranean diet), body mass index, and physical fitness. Furthermore, the effects on quality of life, stress coping capacity, breast cancer incidence, and mortality will be investigated. The intervention group (IG) will receive a structured lifestyle intervention over 12 months, whereas the control group (CG) will only receive information regarding a healthy lifestyle. During the first 3 months, women in the IG will receive structured, individualized, and mainly supervised endurance training with a minimum of 18 MET-h physical activity per week and nutrition education based on the Mediterranean diet. Over the following 9 months, IG monthly group training sessions and regular telephone contacts will motivate study participants. The CG will receive one general training session about healthy nutrition in accordance with the recommendations of the German Society of Nutrition (standard of care in Germany) and the benefits of regular physical activity on health status. At randomization and subsequent time points (3 and 12 months), cardiopulmonary fitness will be assessed by spiroergometry, and nutritional and psychological status will be assessed by validated questionnaires, interviews, and clinical examinations. DISCUSSION: As data on the role of lifestyle intervention in women with a hereditary risk for breast and ovarian cancer are currently lacking, this study will be of major importance from a scientific, as well as a practical advice viewpoint. It will investigate the optimal strategy to improve physical fitness, nutritional status, and psychological factors such as quality of life, perceived stress, optimism, as well as incidence and outcome of cancer in this selected group of women at high risk. If the study indicates a positive long-term outcome, a structured lifestyle intervention program could be added to health care prevention strategies for BRCA1 and BRCA2 mutation carriers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02516540 . Registered on 22 July 2015.

Lifestyle intervention in BRCA1/2 mutation carriers: study protocol for a prospective, randomized, controlled clinical feasibility trial (LIBRE-1 study).

BACKGROUND: Women with highly penetrant BRCA mutations have a 55-60% lifetime risk for breast cancer and a 16-59% lifetime risk for ovarian cancer. However, penetrance differs interindividually, indicating that environmental and behavioral factors may modify this risk. These include lifestyle factors such as physical activity status, dietary habits, and body weight. The modification of penetrance by changing lifestyle factors has not thus far been investigated in a randomized trial in BRCA mutation carriers. METHODS: Therefore, we intend to enroll 60 BRCA1/2 mutation carriers in a pilot feasibility study (Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) pilot). This multi-center, prospective, controlled trial aims to randomize (1:1) participants into a (1) multi-factorial lifestyle intervention group (IG) versus (2) the control group with usual care (CG). The primary endpoint is feasibility and acceptance of a structured interdisciplinary lifestyle intervention program over 12 months (at least 70% of the patients to complete the 1-year intervention). Furthermore, the effects on physical fitness, BMI, quality of life, and stress coping capacity will be investigated. During the first 3 months, women in the IG will receive structured, individualized and mainly supervised endurance training of ≥18 MET*h/week (MET = metabolic equivalent task) and personal nutritional counseling based on the Mediterranean diet. During the subsequent 9 months, the IG will receive monthly group training sessions and regular telephone contacts for motivation, whereas the CG will only receive usual care (one general counseling on healthy nutrition and benefits of regular physical activity on health status). At randomization and subsequent time points (3, 6, 12 months), cardiopulmonary fitness will be assessed by spiroergometry and nutritional and psychological status by validated questionnaires. DISCUSSION: This pilot study will investigate the optimal strategy to improve physical fitness, nutritional habits, and psychological factors in women at high risk for developing breast or ovarian cancer. The results of this pilot feasibility study will be the basis for a larger prospective randomized trial including clinical events (LIBRE). TRIAL REGISTRATION: ClinicalTrials.gov, NCT02087592.