Clinical trial NCT04861220: Surgical Pre-habilitation in Breast Cancer.
Official title: Pre-habilitation Program for Women Indicated to Breast Cancer Surgical Treatment.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Neoplasm
Keywords: Breast Neoplasm
Pre-habilitation
Lead sponsor: Instituto Nacional de Cancer, Brazil
Sponsor class: OTHER_GOV
First posted: 2021-04-27
Enrollment: 248
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized clinical trial in women diagnosed with breast cancer who will undergo cancer treatment with a curative therapeutic proposal. Women who attend the Hospital do Câncer III / INCA for clinical screening consultation, before starting cancer treatment, will be evaluated by physiotherapy and nutrition and recruited as to the eligibility criteria for the study. Women who agree to participate will sign the Informed Consent Form and will be submitted to an initial inclusion assessment. After recruitment and definition of their initial treatment - neoadjuvant treatment or immediate surgical treatment, women will be randomly allocated to the Intervention Group (Group A - Prehabilitation Program + neoadjuvant treatment or Group B - Prehabilitation Program + immediate surgical treatment) and Control Group (Group C - Usual activities + neoadjuvant treatment or Group D - Usual activities + immediate surgical treatment).
Primary purpose: PREVENTION

Brief summary: The National Cancer Institute estimated 625 thousand new cases of cancer (excluding cases of non-melanoma skin cancer) in Brazil for each year between 2020-2022. In 2018, there were 2.1 million new cases of breast cancer in the world, being the first in the ranking of cancers in women. Practices in healthy eating and exercise can protect and / or decrease the risk of breast cancer and improve treatment results. Breast cancer treatments cause cardiovascular changes due to age-related factors, pre-existing chronic diseases and comorbidities such as obesity, smoking and dyslipidemia. Obesity is associated with the development of several types of cancer, including breast cancer. Therapies for breast cancer have a strong association with impaired cardiac function, ranging from permanent, transient cardiotoxic effects and changes in lipid metabolism. In addition to the cardiotoxic effects, the pathophysiology of cancer and treatment favor the appearance of muscle changes, such as sarcopenia. There is sufficient evidence to support that exercise improves fitness before, during and after the completion of cancer treatment. Pre-qualification in cancer treatment is an opportunity to increase physiological reserves before neoadjuvant therapies or surgery, with the intention of improving results and accelerating recovery. It can be composed of physical exercises, nutritional interventions, and psychosocial. Excess weight or depletion are factors that negatively influence surgical and cancer outcomes. In view of the evidence, the aim of this project is to evaluate the effectiveness of physical exercise in a surgical pre-habilitation program for women diagnosed with breast cancer undergoing cancer treatment with a curative therapeutic proposal at the National Cancer Institute in Rio de Janeiro. This is a randomized clinical trial, where patients will be randomly allocated to the Intervention Group and the Control Group. The patients in the intervention group will be instructed to practice physical exercises at home until the date of surgery and those in the control group will only be instructed to maintain their usual activities. All patients will be guided individually by a nutritionist with a view to a healthier nutritional status and control of comorbidities.

Detailed description: INTRODUCTION The National Cancer Institute estimated 625 thousand new cases of cancer (excluding non-melanoma skin cancer cases) in Brazil for each year between 2020-2022, In 2018, 2.1 million new cases of breast cancer occurred in the world , equivalent to 11.6% of all estimated cancers, being the first in the ranking of cancers for females. Among the environmental and behavioral risk factors for breast cancer, alcohol consumption, excess body weight and physical inactivity, are some of the modifiable factors. Obesity, as a risk factor for breast cancer, makes many women obese when diagnosed and when starting treatment. Adhering to healthy eating and exercise can protect and / or decrease the risk of breast cancer, in addition to improving results during and after the active phase of treatment.

After the diagnosis of the disease and evaluation of its stage, the treatment can be defined as neoadjuvant or adjuvant; systemic or regional locus. Breast cancer treatments cause cardiovascular dysfunctions, which are due to age-related factors, pre-existing chronic diseases, comorbidities such as smoking, dyslipidemia and obesity, in addition to cancer treatment.Therapies for breast cancer have a strong association with impaired cardiac function, from transient and reversible changes to permanent dysfunctions, as well as changes in lipid metabolism.

The cardiotoxic effects of cancer treatments can also affect vagal activity and, thus, influence cardiac autonomic balance. In the long run, autonomic imbalance is associated with an increased risk of cardiovascular disease and mortality, and in addition, the autonomic dysfunction that is common in many types of cancer leads to an increase in sympathetic tone and a decrease in cardiac vagal tone. As a way of assessing autonomic activity and vagal response, measures of heart rate variability (HRV) have been adopted. A reduction in parasympathetic modulation and HRV indices was observed in women with breast cancer who underwent chemotherapy, radiotherapy and hormonal therapy after one year of treatment. Physical training, which already has satisfactory results in cancer patients in relation to quality of life related to health, functionality and other aspects, also showed benefits in the autonomic modulation of patients with breast cancer. In non-cancer patients, exercise interventions show improvements in the modulation of autonomic function, minimizing cardiovascular problems and reducing mortality after episodes of myocardial infarction.

In addition to the cardiotoxic effects, cancer treatment favors the appearance of muscle changes. A systematic review with 754 women with breast cancer showed sarcopenia as a risk factor for mortality in 68% of patients. Not only the pathophysiology of cancer, but also drugs used for its treatment contribute to the loss of muscle mass.

Research indicates that physical exercise can mitigate the declines induced by cancer treatment. There is sufficient evidence to support that exercise improves fitness before, during and after treatment is completed. A cardiovascular rehabilitation program based on education and behavioral counseling offers a modification of cardiac risk, increases functional capacity, ensures monitoring of the patient's functional status, improves psychosocial well-being and can reduce recurrent hospitalizations.

Home rehabilitation can be an alternative for patients with moderate cardiac risk, self-monitoring capacity and with difficulties to attend due to social or displacement reasons. Considering the profile of the user of the Unified Health System, interventions at home and in the community seem to be the best way, together with telephone contacts for questions and / or guidance.

Pre-qualification in cancer treatment is an opportunity to increase physiological reserves even before neoadjuvant therapies or surgery, with the intention of improving results and accelerating recovery. May consist of physical exercises, nutritional and psychosocial interventions.

Knowing the nutritional profile of patients is of great importance considering the negative impact of an impaired nutritional status on postoperative outcomes. Excess weight or depletion has been reported as a factor that negatively influences surgical and cancer outcomes. The identification of patients at nutritional risk and probable sarcopenia will define an early nutritional orientation through an individualized diet with a focus on improving body composition, glycemic control, since preoperative glycemic control is associated with a lower incidence of infectious complications; and management of symptoms related to cancer treatment.

Combined with treatment, behavioral counseling is effective in motivating changes in lifestyle, which are part of the modifiable risk factors for breast cancer. Thinking about the risks that accompany the diagnosis of breast cancer, a rehabilitation focused on treating current disorders and anticipating future complications are the first steps to improve the results of care and reduce costs.

GOALS Main goal To evaluate the effectiveness of physical exercise in a surgical pre-habilitation program for women diagnosed with breast cancer who underwent cancer treatment with a curative therapeutic proposal at the Cancer Hospital III of the National Cancer Institute.

Specific objectives

* Describe the sociodemographic and clinical characteristics of the study population
* Identify the rate of adherence to physical exercise and associated factors;
* To assess changes in functional and cardiopulmonary capacity, fatigue, health-related quality of life, level of physical activity, cardiac autonomic modulation and sarcopenia in women diagnosed with breast cancer, before and after surgical treatment and throughout the follow-up periods. according to the intervention group;
* Assess the nutritional status and body composition in the inclusion of patients in the study and before surgical treatment in all participating women;
* To verify the association between regular physical exercise before surgical treatment and functional and cardiopulmonary capacity, fatigue, level of physical activity, health-related quality of life, cardiac autonomic modulation and sarcopenia in comparison with the control group;
* Describe the perception of patients regarding the performance of pre-habilitation exercises;
* To evaluate the behavioral change in the practice of physical exercises after the surgical treatment of breast cancer.

SAMPLE SIZE For the calculation of the sample size, the incidence of complications (outcomes) was considered to be 10% in the intervention group and 30% in the control group, with an alpha error of 0.05, a beta error of 0.20 and a power of 80%. Based on these parameters, it will be necessary to include 62 patients in each group. However, due to the evaluation of different outcomes and the lack of data on the incidence of complications in this population, all eligible patients will be included in the study inclusion period.

LOSS CONTROL Losses related to change, lack of information and abandonment will represent a small number, as patients remain on cancer treatment for approximately 5 years at the institution. The non-recoverable losses will have data collected from the medical records to be compared with the patients who completed the follow-up.

DATA ANALYSIS The data will be analyzed by intention to treat. The descriptive analysis will be performed by measures of central tendency and dispersion (quantitative variables) and distribution of absolute and relative frequency (qualitative variables).

To assess the normal distribution of outcomes and quantitative control variables, the Kolmogorov-Smirnov test will be performed.

To assess changes between groups in the pre- and / or post-intervention stages, the mean values will be compared by the t-student test or Mann-Whitney U test (non-parametric distribution). When analyzing the pre-verus comparison after intra-group intervention, the paired t-student test will be considered. For all analyzes, p-value less than 0.05 will be considered statistically significant.

To assess the linearity between the outcome and the quantitative adjustment variables, the dispersion diagram will be performed. Quantitative independent variables that do not have a normal distribution will be categorized. To test the collinearity of the categorical independent variables, Pearson's correlation will be performed.

To assess the association between the intervention groups and the quantitative outcomes, the differences between the means will be calculated and tested by analysis of variance, considering a value of p \<0.20. Multiple linear regression will be performed using the enter method (stepwise forward), considering the 95% confidence interval. Homoscedasticity and possible biases of the model will be analyzed through residual analysis and all assumptions will be observed. To identify the explanatory power of the model, the determination coefficient will be performed. The association between intervention groups and categorical outcomes will be performed by univariate analysis, using the odds ratio (OR), assuming 95% confidence intervals (95% CI). Associations with clinical and statistical significance in the univariate analysis (considering p \<0, ETHICAL AND LEGAL ASPECTS This study was submitted to the Research Ethics Committee of the National Cancer Institute (CEP / INCA), under CAAE 42627521.6.0000.5274, and approved as per opinion 4.576.731. At the time of recruitment, women will be instructed on the objectives of the study and those who agree to participate will sign the Free and Informed Consent Form (ICF).

RISK AND BENEFITS Performing physical assessments will not pose any health risks to patients. The practice of unsupervised physical exercises is safe for people without any chronic health impairment, as already mentioned in the exclusion criteria. To reduce the risks, patients will be instructed on the level of effort during the practice and on signs and symptoms of decompensation, being instructed to contact the researcher, if necessary.Despite the small risk, palpitation, excessive sweating, dizziness and shortness of breath may occur when exercising at home. If this occurs, patients will be instructed to end the exercise and contact the research team.. The study population will benefit indirectly through the results, which will analyze the effectiveness of the pre-habilitation program in improving functional capacity, fatigue, health-related quality of life, level of physical activity and autonomic modulation of women undergoing treatment for breast cancer, making it possible to plan actions to control complications.The intervention group, which will perform home physical exercises according to the guidelines, will benefit from the effects of physical exercise on physical and emotional well-being. When adhering to a healthy habit, physical conditioning, mental health and health-related quality of life improve.

FINANCING This research will not impose any burden on the institution, since patients will be evaluated on the day they attend their routine consultations and other information will be collected from the physical and / or electronic medical record. The rest of the materials will be paid for by the researchers responsible.

Eligibility criteria: Inclusion criteria:

- have a diagnosis of breast cancer and indication for cancer treatment with a curative therapeutic proposal

Exclusion criteria:

* having a previous cancer diagnosis
* staging IV
* practitioner of physical exercise at least 90 minutes per week
* not being able to answer the questionnaires
* be unable to practice unsupervised exercises for any reason, including: dysfunctionss orthopedic, neurological, decompensated cardiorespiratory and severe renal.

Primary outcomes:
measure: Changes in functional capacity and muscle strength - dynamometry assessment using handgrip strength
timeFrame: Inclusion, post chemotherapy, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in functional and cardiopulmonary capacity - evaluation of the 6-minute walk test
timeFrame: Inclusion, post chemotherapy, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes cardiopulmonary capacity - evaluation of the cardiac autonomic modulation through heart rate variability.
timeFrame: Inclusion, post chemotherapy, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in Sarcopenia - muscle strength and performance assessment using Time Up and Go Test
timeFrame: Inclusion, post chemotherapy, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in Sarcopenia - muscle strength and performance assessment using SARC-F questionnaire
timeFrame: Inclusion, post chemotherapy, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in Sarcopenia - Evaluation of the corrected arm muscle area
timeFrame: Inclusion, post chemotherapy, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in functional and cardiopulmonary capacity - evaluation of the 6-minute step test
timeFrame: Inclusion, post chemotherapy, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
Secondary outcomes:
measure: Changes in Nutritional Risk
timeFrame: Inclusion and pre-surgical moment
measure: Changes in Fatigue
timeFrame: Inclusion, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in Physical activity level
timeFrame: Inclusion, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in Health-related quality of life
timeFrame: Inclusion, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Assessment of adherence to physical exercises
timeFrame: pre-surgical moment
measure: Assessment of behavioral change in physical exercise
timeFrame: pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Evaluation of the patients' perception regarding the performance of the exercises
timeFrame: pre-surgical moment
measure: Changes in alcohol consumption and smoking
timeFrame: Inclusion, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Changes in anthropometric data through body weight assessment
timeFrame: Inclusion, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
measure: Evaluation of anthropometric data by height
timeFrame: Inclusion
measure: Changes in anthropometric data through tricipital skin fold assessment
timeFrame: Inclusion, pre-surgical moment, 30 days after surgery, 6 months after surgery and 1 year after surgery.
Other outcomes:
Locations:
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional do Câncer / HCIII
Study officials:
affiliation: Instituto Nacional de Cancer, Brazil
name: Simone A Saraiva
role: PRINCIPAL_INVESTIGATOR
References: