Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Nervous System Diseases

Symptoms and General Pathology

Breast Neoplasms

Sarcopenia

Breast Diseases

Skin Diseases

Muscular Atrophy

Atrophy

Neuromuscular Manifestations

Neurologic Manifestations

Pathological Conditions, Anatomical

All Drugs and Chemicals

Aromatase Inhibitors

Structured and supervised aerobic and resistance training 2 times per week

Subjects will be counseled on American Cancer Society and American College of Sports Medicine physical activity and nutritional guidelines at the initiation of the study. Study participants will be contacted by a physician or nurse on weeks 2, 6, 10, and 14 to provide support and encouragement to patients.

Structured Exercise

Usual Care

Susan Kesmodel, MD

Hormone receptor-positive tumors are the most common breast cancers in postmenopausal women, and drug therapies, which block the production or effects of estrogen, are the mainstay of treatment in these patients. Due to their effectiveness in postmenopausal women, aromatase inhibitors (AIs) are the standard of care for long-term estrogen suppression in these patients. Estrogen deficiency, however, results in multiple side effects. Some of the most common side effects in women taking AIs are joint and muscle aches, which promote physical deconditioning. Because of the long term use of AIs in postmenopausal breast cancer patients and the improvements in cancer-related outcomes that are observed with their use, identifying methods to reduce these side effects to maintain adherence to treatment is important. Exercise interventions in breast cancer patients also improve quality of life and reduce fatigue. Understanding the role of exercise in AI side effect prevention will allow us to translate these findings into therapy guidelines.

Breast cancer is the most common malignancy in women in the United States and is the second leading cause of cancer deaths. In 2013, an estimated 230,000 women in the United States will be diagnosed with invasive breast cancer and approximately 40,000 with die.1 Women with breast cancer frequently experience significant functional and metabolic declines during and after treatment due to cancer-related fatigue (CRF), stress and depression.2,3 Cancer-related fatigue is associated with side effects from treatment, pain, functional disability, sleep disturbances, mood disturbances and co-morbid conditions.4 Patients with CRF have declines in physical activity and function, which significantly impacts quality of life (QOL).5 The mechanisms underlying functional declines and fatigue in breast cancer patients are likely multifactorial, but deconditioning, sarcopenia, increases in inflammatory cytokines, insulin resistance, and changes in muscle and fat metabolism seem to play important roles.4,6

Hormone receptor-positive tumors are the most common breast cancers in postmenopausal women, and endocrine therapies, which block the production or effects of estrogen, are the mainstay of treatment in these patients. Due to their superior efficacy in postmenopausal women, aromatase inhibitors (AIs) are the standard of care for long-term estrogen suppression in these patients.7 Estrogen deprivation, however, results in multiple side effects which may worsen fatigue and the functional and metabolic declines associated with cancer treatment.8 Some of the most common side effects in women taking AIs are musculoskeletal symptoms, including arthralgias and myalgias, which promote deconditioning and sarcopenia and their associated side effects.9 Because of the prolonged use of AIs in postmenopausal breast cancer patients and the improvements in cancer-related outcomes that are observed with their use, great efforts are taken to reduce AI induced musculoskeletal symptoms (AIMSS) to maintain adherence to treatment. While multiple strategies are used to manage AIMSS, current therapies mainly focus on interventions in patients who develop symptoms (tertiary prevention) rather than primary prevention.9 Exercise interventions in breast cancer patients also improve QOL, decrease fatigue, and increase physical function and strength.10,11 Understanding the role of exercise in AI side effect prevention will allow us to translate these findings into therapy guidelines.

Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients

Pilot Trial of Aerobic and Resistance Exercise Training for the Primary Prevention of Musculoskeletal Side Effects From Aromatase Inhibitors in Postmenopausal Breast Cancer Patients

Fatigue (questionnaires) and muscle performance (muscle strength, endurance, and function)

Fatigue (questionnaire) and muscle performance (muscle strength, endurance, and function)

Musculoskeletal symptoms (VASpain, HAQ-DI)

National Institute on Aging (NIA)

Baltimore VA Medical Center

Assistant Professor of Surgery

Musculoskeletal Diseases

Blood and Lymph Conditions

Muscle Weakness

Hematologic Neoplasms

Paresis

Asthenia

Hematologic Diseases

Muscular Diseases

Vasoconstrictor Agents

Respiratory System Agents

Cardiotonic Agents

Oxymetazoline

Phenylephrine

The lower extremity resistance exercise (REx) program was designed by reviewing the exercise principles recommended by the ACSM and the literature on physical activity and hematological cancer patients. The patients were treated for 40-60mins, 6 weeks. The exercise program includes active movements of the upper and lower extremities, stretching exercises, and resistance exercises for the lower extremities. REx to be applied with resistance bands of different resistance or with the patient's body weight. Clinical force generation of therapy bands follows a progression. Our proposed training protocol includes 4-6 different exercises for each extremity. Intensity, sets, and reps were adjusted to a target score of 12 to 14 using the Borg scale. Patients performed 1 set of 10 repetitions of each REx based on their fatigue level. Intensity (\~ RPE 15-16) and resistance were gradually increased. When the patient complained of extreme fatigue, the resistance was reduced to the previous level.

In addition to resistance exercises, NMES will be applied to the quadriceps muscles in both legs of the patients in this group. The application will be made with a portable device using disposable electrodes. One of the electrodes will be placed proximally, that is, at the midpoint of the quadriceps muscle, while the second electrode will be placed on the distal part. In order to ensure that the patients get used to the device, low-intensity current with a frequency range of 5 Hz, 10-30 minutes. Afterward, the treatment program will continue with a high-frequency current with a frequency range of 50 Hz, 15 minutes. Participants were instructed to voluntarily contract the quadriceps muscles during periods of HF-NMES stimulation to increase the strengthening effect and improve NMES tolerance.

Neuromuscular Electrical Stimulation (NMES) is based on the principle of creating a contraction by stimulating the nerve fibers innervating the related muscle in the healthy muscle and the muscle fibers in the denervated muscle with electrical current. The electric currents used in stimulation of muscles and nerves perform this function by changing the electrical potential of cell membranes.

It is contraindicated in pregnancy, presence of pacemaker, severe heart disease, epilepsy, fracture, dementia and impaired consciousness. We prevent contraindicated situations by excluding volunteer participants with these characteristics.

Neuromuscular Electrical Stimulation

Warm-up exercise, main training program and cool down exercise. Main training consists of resistance exercises to be applied with resistance bands of different resistance or with the patient's own body weight. Our prescribed training protocol includes 4-6 different exercises for each limb (bench press with resistance band, upper extremity proprioceptive neuromuscular facilitation exercises, biceps/triceps curl, leg press, knee extension, 4-way hip motion, mini squat). Intensity, sets, and number of repetitions will be adapted to a target score between 12 and 14 using the Borg scale. It will be applied as low intensity, long-term passive stretching exercises to the pectoral, hamstring, and gastrosoleus muscle groups. Patients will perform 1 set of 10 repetitions of each resistance exercise determined by their level of fatigue. Resistance will be increased every three visits. If the patient complains of excessive fatigue, the resistance will be reduced to the previous level.

Ant Uzay, MD

Fatma Mutluay, Prof

Elif Es Safran, MSc

Physical activity levels of adult hematologic cancer patients are deficient. The resulting physical inactivity causes fatigue, muscle loss, and deterioration in physical performance values. However, physical exercise programs still play a minor role in treating hematological malignancies. In addition, there are no reliable data in the literature regarding risk factors, feasibility, and exercise results in individuals with hematological malignancies. Although it is known that the use of corticosteroids, which are among the drugs given during chemotherapy, causes muscle weakness, there are no physical exercise programs performed with this patient group in the literature. The current study aims to compare the effects of resistance exercise and resistance exercise combined with neuromuscular electrical stimulation on muscle strength, functional lower extremity strength, and mobility in hematological cancer patients during chemotherapy.

Although people with hematological malignancies have to endure long stages of treatment and inactivity that are known to reduce their physical performance levels, it is still common practice to rest and avoid intense exercise. Although physical activity and exercise are important approaches to many diseases, their effects on cancer have been studied recently. There are still not enough studies in this area and it is not widely used. In recent studies, it is thought that exercise may benefit the symptoms that develop due to treatment in cancer patients. Even in the presence of severe muscle weakness and fatigue, skeletal muscle provides great adaptation when there is an appropriate exercise stimulus. In addition, exercise can increase immune functions, so it is thought that exercise practices in hematological cancer patients can specifically improve cellular functions such as microbial phagocytosis, T-cell proliferation, vaccine response, and killing tumor cells. There are various studies and approaches that try to create a different strategy and include physical exercise in the treatment strategy of hematological malignancies. These exercise programs generally include aerobics, flexibility, and resistance training methods. The necessity of developing alternative methods to exercise is emphasized in the literature due to the development of complications that affect participation in basic exercises such as walking. Resistance exercise training has been effective in improving muscle strength and endurance in cancer survivors, with most of the research on those with breast cancer, prostate cancer, and head and neck cancer. The number of studies providing strengthening training in patients with hematological cancer is limited. Neuromuscular electrical stimulation (NMES) has proven efficacy in improving muscle strength in a variety of populations. NMES training also has applicability for the cancer population to prevent treatment-related complications and improve health-related quality of life. However, there is still no high-level evidence to support the administration of NMES in cancer patients. In the present study, we aimed to evaluate the effect of resistance exercise improve muscle weakness in hematological cancer patients receiving intensive chemotherapy after HSCT. In addition, we aimed to evaluate the effect of resistance exercise and NMES training on fatigue, mobility, and quality of life in hematological cancer patients.

Effects of NMES and Exercise in Hematological Cancer

Effects of Neuromuscular Electrical Stimulation Combined With Resistance Exercises on Muscle Strength in Adult Hematological Cancer Patients: A Randomized Controlled Study

An overall assessment of activity level will be based on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale based on the degree of muscle weakness found in the Cancer Treatment Evaluation Program Common Toxicity Criteria, and patients with an ECOG performance status of 1-3 will be treated.

Participants' muscle strength measurements will be made using a digital hand dynamometer (J Tech Commander Muscle Tester). The patients will be seated in the appropriate position and the dynamometer will be placed in the dominant leg to give resistance to the muscle to be evaluated. While patients press the dynamometer as hard as possible for three seconds, the evaluator will give resistance to prevent any movement to provide an isometric contraction. Following the familiarization test, patients will perform three trials with standardized verbal encouragement and the highest strength (kilogram, kg) sustained for over half a second will be recorded.

Lower extremity functional strength will be evaluated using the "Sit and Stand for 30 sec" test. The patient will be instructed to stand up and sit back and forth from a standardized chair as quickly as possible in 30 seconds without using his arms. Participants will be able to use their hands to help them stand as needed, and standardized verbal encouragement will be provided to continue sitting and standing throughout the test.

Thigh circumference measurement will be made from the middle of the thigh over the Quadriceps muscle. By marking the inguinal region and the proximal part of the patella, the midpoint between the two points will be found. All measurements will be made on the right side and by the same physiotherapist.

"Timed Up-Go Test" will be applied before and after treatment to evaluate the patient's mobility and functional exercise capacity. The time taken to complete the task is strongly correlated with the level of functional mobility. In other words, the longer the person completes the task, the more dependent he is on daily life activities.

The Brief Fatigue Scale will be used to assess cancer-related fatigue in our study. This scale is one of the standard tests used to evaluate fatigue in cancer patients. Evaluates the level of fatigue in the last 24 hours and the effect of fatigue on daily activities (general activity, mood, walking ability, work life, relationships with other people, joy of life)

The assessment of quality of life will be carried out using the European Cancer Research and Treatment Organization Quality of Life Questionnaire Version 3.0. The scale consists of three subsections: general health status scale, functional scale, and symptom scale, and includes a total of 30 questions.

Medipol University

Acibadem University

Lecturer

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Androgens

Men with prostate cancer who are about to begin androgen-deprivation therapy (ADT) will attend structured progressive resistance exercise training sessions 2 times/week for six months.

Men with prostate cancer who are about to begin androgen-deprivation therapy (ADT) will attend flexibility and balance exercises training sessions 2 times/week for six months.

Progressive Resistance Training Exercise 2x weekly for 6 months.

Progressive Resistance Training Exercise

Flexibility and Balance Exercise Training Exercise 2x weekly for 6 months.

Flexibility and Balance Exercise

Shehzad Basaria, MD

Milena Braga, MD

Thomas Storer, PhD

The overall goal of this study is to determine if implementing structured exercises prevent decline in muscle mass, muscle strength and physical function in men with prostate cancer undergoing androgen deprivation therapy (ADT). Our main hypothesis is that structured resistance exercise training in men undergoing ADT will preserve physical function assessed by loaded stair climbing power compared with the control group. The trial will also examine the efficacy of the exercise regimen on muscle strength, QOL and fatigue. The findings of this trial will lay the groundwork for definitive intervention trials to prevent frailty and falls in these men.

This randomized, controlled, parallel group trial of 6-months duration is determining the efficacy of structured resistance exercise training in preventing the decline in physical function in older men with prostate cancer undergoing androgen deprivation therapy (ADT). It will compare the structured resistance exercise training with a control group of men undergoing flexibility and balance exercises training.

Men undergoing ADT for treatment of their prostate cancer experience a significant decline in muscle mass and muscle strength, which impacts their physical function. This predisposes them to frailty and a higher risk of falls. In addition to physical dysfunction, men undergoing ADT also experience a significant decrease in health-related quality of life and experience fatigue (tiredness).

This research study is taking a preventative approach to the physical function problems in men with prostate cancer by implementing exercise interventions before participants begin ADT that are specifically designed to improve muscle mass, muscle strength and physical function to lessen the impacts of muscle mass and strength decline.

The study includes a screening visit during which the following procedures will be conducted: Vitals, EKG, blood sample collection and a physical to determine eligibility. If qualified, participants will be randomly assigned to two different types of structured exercises: Resistance exercise training or flexibility and balance exercises. During the weekly exercise training 20 subjects will be assigned to the Exercise A group and 20 subjects to the Exercise B group. The exercise training sessions will occur approximately 2 times/week. In addition participants will also undergo DEXA scans, perform muscle strength testing and complete questionnaires at baseline, 3- and 6-month visits.

It is expected participants will be in this research study for up to 6 months. It is expected that about 40 people will take part in this research study.

Structured Resistance Exercise vs Control Exercise

Participants, Investigators and Research Staff will remain blinded.

Only exercise personnel and study statistician will be unblinded.

RESIST-ADT (Androgen Deprivation Therapy)

Preventing a Decline in Physical Function in Older Androgen-Deprived Men With Structured Exercise Training (RESIST-ADT Trial)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Compare the efficacy of a structured resistance exercise regimen vs a structured control regimen on loaded stair climb power. Assessment of physical function as measured by Loaded Stair Climbing Power.

Lean body mass measured by dual energy x-ray absorptiometry (DEXA)

Maximal voluntary muscle strength in the lower extremities will be assessed by conducting the leg and chest press exercise by the 1-repetition maximum method and assessing loaded stair climb power.

Measured by SF-36 questionnaire a multi-purpose survey designed to capture adult patients' perceptions of their own health and well-being

Fatigue will be assessed by the Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients	NCT01954706	Breast Cancer Sarcopenia	Structured Exer... Usual Care	40 Years - 80 Years	Baltimore VA Medical Center
Effects of NMES and Exercise in Hematological Cancer	NCT04755465	Hematologic Mal... Muscle Weakness	Neuromuscular E... Structured Exer...	18 Years - 65 Years	Acibadem University
RESIST-ADT (Androgen Deprivation Therapy)	NCT04485767	Prostate Cancer Physical Functi...	Progressive Res... Flexibility and...	60 Years -	Dana-Farber Cancer Institute
Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients	NCT01954706	Breast Cancer Sarcopenia	Structured Exer... Usual Care	40 Years - 80 Years	Baltimore VA Medical Center
RESIST-ADT (Androgen Deprivation Therapy)	NCT04485767	Prostate Cancer Physical Functi...	Progressive Res... Flexibility and...	60 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for structured exercise