Nutritional and Metabolic Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Digestive System Diseases

Wasting Syndrome

Cachexia

Gastrointestinal Neoplasms

Digestive System Neoplasms

Syndrome

Weight Loss

Body Weight

Body Weight Changes

Thinness

Metabolic Diseases

Nutrition Disorders

Gastrointestinal Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Patients with cancer of digestive system requiring resection surgery will be included. They will have measure of height and weight, blood samples, skeletal muscle force, skeletal muscle index and muscle biopsy.

V1: Inclusion will be effectuated at the time of anaesthetic consultation V2: The day before and day of resection surgery about 1 month after V3: Follow-up at 1 month V4: Follow-up at 3 months V6: Follow-up at 6 months

Height and weight will be measured to estimate cachexia degree at the time of anaesthetic consultation. (V1)

Height and weight

Blood samples will be collected for measuring myostatin on blood at the time of anaesthetic consultation, the day before resection surgery, follow-ups at 1, 3 and 6 months. (V1, V2, V3, V4, V6)

Blood samples

Skeletal muscle force will be determined from Computerized Tomography (CT)-scan at the time of anaesthetic, follow-ups at 1, 3 and 6 months. (V1, V3, V4, V6)

Skeletal muscle force

Skeletal muscle index will be determined from Computerized Tomography (CT)-scan at the time of anaesthetic, follow-ups at 1, 3 and 6 months. (V1, V3, V4, V6)

Skeletal muscle index

Muscle biopsy will be performed during resection surgery under general anaesthesia. (V2)

Muscle biopsy

Karine ABBOUD, MD

Cancer cachexia is responsible for the death of approximately 20% of patients. Myostatin is a master negative regulator of skeletal muscle mass. If the role of myostatin in cancer cachexia is now well established in murine models, no study has focused on muscle expression of Myostatin in relation to the degree of cachexia. the hypothesize is that muscle Myostatin a biological marker of cachexia in patients with cancer of digestive system. The main objective is to compare skeletal muscle Myostatin messenger RiboNucleic Acid (mRNA) level as a function of cachexia in cancer of digestive system patients. Myostatin messenger RiboNucleic Acid (mRNA) level will be determined in a muscle sample taken during the resection under general anaesthesia. Skeletal muscle index will be determined before surgery, 3 and 6 months after surgery. Muscle strength of the lower and upper limbs will be determined before resection, at 1 month, 3 months and 6 months postoperatively. Blood sampling will also be performed on these 4 occasions.

Skeletal Muscle Expression of Myostatin and Cancer of Digestive System Associated Cachexia

Skeletal Muscle Expression of Myostatin and Cancer of Digestive System Associated Cachexia(MYOCAC Study)

Evaluate correlation between skeletal muscle force/index and degree myostatin. Skeletal muscle force/index will be determinated by skeletal muscle force/index results.

Degree myostatin will be determinated by blood samples with Enzyme Linked ImmunoSorbent Assay (ELISA) method.

Evaluate Correlation between skeletal muscle force and index before resection surgery to estimate the extent of cachexia-induced muscle dysfunction by results tests.

Evaluate correlation between level of myostatin muscular expression and degree myostatin.

Level of myostatin muscular expression will be determinated by muscle biopsy. Degree myostatin will be determinated by blood samples with Enzyme Linked ImmunoSorbent Assay (ELISA) method.

Determinate correlation between level of myostatin muscular expression and skeletal muscle force and index after resection surgery.

Analysis level of myostatin muscular expression and blood samples results according to cancer stage, neoadjuvant treatment and chemotherapy.

Centre Hospitalier Universitaire de Saint Etienne

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

All volunteers be subjected to 16 - 20 weeks of full body resistance exercise training (2 times per week. However, usual care program.

All volunteers be subjected usual care (diagnosis confirmation, chemotherapy treatment planning and an initial education session).

The volunteers in the intervention group will be subjected to 16 - 20 weeks of whole-body resistance-type exercise training (2x/wk).

Prehabilitation with resistance-exercise training

The volunteers in the intervention group will be subjected to usual care (diagnosis confirmation, chemotherapy treatment planning and an initial education session).

Usual care program

Macarena Artigas, PT, MSc

Gabriel N Marzuca-Nassr, PT, MSc, PhD

Breast cancer stands as the foremost cause of cancer-related deaths among women worldwide, with the highest incidence of any cancer type. The choice of therapeutic interventions hinges upon factors like cancer stage, cell subtype, and tumor size. Consequently, individuals with more aggressive tumors, such as HER+2 and Triple Negative, or larger tumors often undergo neoadjuvant chemotherapy before breast surgery. However, these anticancer treatments come with side effects like cancer-related fatigue, reduced functional capacity, and changes in body composition, notably skeletal muscle atrophy. Skeletal muscle loss correlates with heightened mortality rates, cardiotoxicity, and diminished quality of life, underscoring the need for early therapeutic interventions. One such promising strategy is prehabilitation, which involves resistance-exercise training aimed at bolstering skeletal muscle mass from the outset of the disease, even preceding breast surgery. Resistance-exercise training has shown favorable effects on women undergoing adjuvant therapy or survivors of breast cancer, however, its molecular and clinical effects in women with breast cancer undergoing neoadjuvant therapy are unknown.

Hypothesis: Prehabilitation based on resistance-exercise training before surgery in women with breast cancer undergoing neoadjuvant therapy increases skeletal muscle mass compared with usual care.

Secondary, prehabilitation based on resistance-exercise training before surgery in women with breast cancer undergoing neoadjuvant therapy generates better results in body composition, physical performance, clinical parameters (serious adverse events, hospital readmission, infection, complications), physiological parameters and quality of life at one-month hospital discharge compared to usual care.

Objective: To determine the effects of prehabilitation based on resistance-exercise training versus usual care, before and after breast surgery, on skeletal muscle mass in women with breast cancer undergoing neoadjuvant chemotherapy.

Methodology: A single-blind, randomized controlled clinical trial will be developed. Sixty-eight postmenopausal women with stage I, II and III breast cancer with HER2+ type breast tumor and Triple negative breast cancer undergoing neoadjuvant therapy and with an indication for breast surgery will be divided into two groups: usual care (CONTROL, n=34) versus Prehabilitation (P-REHAB, n=34). All participants will receive an education session 20 weeks before surgery + neoadjuvant chemotherapy for 16-20 weeks as is normally done for this type of patien. Only participants in the P-REHAB group will undergo 16-20 weeks of whole-body resistance-exercise training (twice a week). At baseline, after prehabilitation program and 4 weeks after surgery, the cross-sectional area of the quadriceps muscle and of the muscle region at lumbar level 3 will be determined by CT-Scan. Also, fasting blood samples will be obtained to measure biochemical and molecular markers (e.g. miRNAs). Maximal strength will be determined by 1 repetition maximum (1RM) leg press, leg extension, lat pull down, chest press, horizontal row, and handgrip. In addition, physical performance will be assessed with the short physical performance battery (SPPB), functional capacity with the 6-minute walk test, quality of life with the BR23 questionnaire, and cancer-related fatigue with the Brief Fatigue Inventory scale at the same time points. Finally, samples from tumor breast cancer and pectoralis muscle will be obtained on the day of breast surgery.

Expected results: It is expected that prehabilitation based on resistance-exercise training results in increased muscle mass in women with breast cancer undergoing neoadjuvant chemotherapy compared to participants receiving usual care. Also, it is expected that this intervention before surgery in women with breast cancer undergoing neoadjuvant therapy will generate better results in clinical parameters (serious adverse events, hospital readmission, infection, complications) and quality of life one month after hospital discharge compared to usual care . These results will allow the creation of local, regional, national and international strategies to combat the adverse effects of breast cancer and its antineoplastic treatment, especially in women with more aggressive breast cancer.

Prehabilitation With Resistance-exercise Training for Breast Cancer Neoadjuvant Therapy

Prehabilitation Based on Resistance-exercise Training in Women With Breast Cancer Undergoing Neoadjuvant Therapy: From Molecular Mechanism to Clinical Benefits

Cross-sectional area of the quadriceps and L3 region via single-slice CT scan

Maximal strength assessment via 1RM testing of horizontal row, lat pull down, chest press, leg press, and leg extension)

Maximal strength assessment via 1RM testing of JAMAR handheld dynamometer.

Measurement of physical performance via SPPB Short physical performance battery (0 to 12 points, whether higher scores mean a better outcome).

Measurement of quality of life via EORTC QLQ-30, this questionnaire has 30 question covering functional state and cancer related symptoms. Besides, there are two specific question covering the "overall health" and "overall quality of life". The scores obtained are standardized and a score between 0 and 100 is obtained. High values on the global health and functional status scales indicate a better quality of life. However, high values on the symptom scale indicate a lower quality of life

The instrument consists of nine items, each rated on a scale from 0 to 10, aimed at assessing fatigue. By averaging the scores of all items, a fatigue score is derived, wherein higher values signify more severe fatigue.

Measurement in blood samples, the insulin will evaluate by ELISA using the Human Insulin ELISA Kit, following the manufacturer's recommendations

It will be measured from a muscle sample obtained at the time of surgery using the western blot technique.

Universidad de La Frontera

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Testicular Neoplasms

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

Endocrine System Diseases

Testicular Diseases

Gonadal Disorders

Germ Cells Tumors

Testicular Germ Cell Tumor

TGCT survivors, men, 25-55 yrs old, 3 and more years after successful treatment of TGCT, with the capacity to undergo aerobic-strength intervention assessed by cardiologist

6 month supervised exercise intervention in TGCT survivors (1 hour sessions 3 x per week),

aerobic-strength exercise intervention (6-months)

Barbara Ukropcova, MD, PhD, Prof

Regular exercise is effective in prevention \& treatment of chronic diseases. Exercise can reduce late toxicity of chemotherapy, commonly found in cancer survivors, which is yet to be translated into clinical practice.

Mechanisms of exercise benefits in oncologic patients are far from being elucidated, and include increase in muscle mass, reduction of fat mass, systemic inflammation and cardiometabolic risk. Synchronization of exercise adaptive response is, to an extent, mediated by bioactive molecules released from muscle, with anti-inflammatory \& tumor-suppressing properties. Muscle satellite cells are a source of regeneration, muscle structural integrity \& functional capacity. Phenotypes of muscle cells, such as secretory profile, lipid \& glucose metabolism, mirror clinical phenotypes of the donor. Importantly, muscle cells' metabolism in vitro can be modulated by 8-12 week training in vivo. Epigenetic mechanisms regulating muscle \& systemic metabolism in cancer survivors are not yet understood.

Aims:

* To assess the impact of 6-month supervised, individualized aerobic-strength exercise training intervention in cancer survivors with chemotherapy-induced late toxicity . (i) on the whole-body energy and glucose metabolism, anthropometric parameters, physical fitness \& activity profile, motor functions and quality of life in testicular germ cell cancer (TGCC) survivors, more than 3 years after cisplatin-based chemotherapy; with the 2-year follow up; . (ii) on skeletal muscle mass, morphology as well as functional and metabolic state detected in vivo (31P-MR spectroscopy).

(iii) on metabolic characteristics of primary skeletal muscle cells;

* To determine the impact of exercise intervention on circulating bioactive molecules (exerkines), putative mediators of exercise health benefits as well as on levels of circulating inflammatory cytokines, which likely contribute to the pathogenesis of chemotherapy-induced late toxicity;
* To evaluate the role of (a) selected exercise-regulated bioactive molecules, (b) exercise-mimicking treatment (by electric pulse stimulation) and (c) cisplatin treatment on metabolism and mitochondrial function of differentiated human muscle cells in culture;
* To investigate the associations between intervention-induced shifts in circulating bioactive molecules and selected metabolic, anthropometric and motor parameters.

The generated results will enable us (i) to gain a better insight into pathomechanisms of muscle-associated chemotherapy-induced late toxicity and the role of skeletal muscle \& systemic mediators in the exercise-induced health benefits in TGCC survivors; and (ii) to validate the effectiveness of the individually-tailored exercise intervention in reducing chemotherapy-related toxicity in patients with TGCC, with the aim to transfer this knowledge into clinical practice.

controled trial with exercise intervention

lab technicians and statistician are blinded.

Exercise in Testicular Germ Cell Cancer Survivors

Exercise in Prevention & Treatment of Chemotherapy-related Late Toxicity in Testicular Germ Cell Cancer Survivors: the Role of Skeletal Muscle

we will share IPD upon reasonable request

change in glucose tolerance (as measured by oral glucose tolerance test)

change in resting energy expenditure calculated by Weir equation from VO2 and metabolic substrate preference RQ VCO2/VO2 (as measured by indirect calorimetry)

BMI (kg.m-2) , fat mass (% electric bioimpedance), lean body mass (% electric bioimpedance), visceral adiposity (%, elecgtric bioimpedance)

VO2max (mlO2 per kg BW min) as measured by bicycle spiroergometry

Comenius University

Slovak Academy of Sciences

PhD, DSc

Malnutrition

the intervention, specific to the study, is to take samples on patients with advanced gastrointestinal cancer

the intervention, specific to the study, is to take samples on non-undernourished patients supported for adjuvant chemotherapy as part of colorectal cancer

Blood samples, muscle biopsy and sample of hair

Samples

Thierry LECOMTE, MD-PhD

Undernutrition associated with cancer, or cancer cachexia results from a deterioration of the energy balance that leads to a gradual mobilization of energy reserves in the body and to increasing deterioration of the nutritional status of patients. This will thus significantly reduce quality of life and survival of patients with a lower tolerance to cancer treatments. Despite undeniable progress in knowledge, many pathophysiological mechanisms remain few or not explored, which could explain that there is still no satisfactory therapeutic solution to halt the gradual deterioration of the nutritional status of patients. In this sense, apart from preclinical data obtained in animal models, there is currently no clinical study on the functioning of skeletal muscle energy metabolism in undernourished patients suffering of cancer.

Skeletal Muscle Energy Metabolism in Undernourished Patients With Gastrointestinal Cancer

Study of Alterations in Skeletal Muscle Energy Metabolism in Undernourished Patients With Gastrointestinal Cancer

Measurement of muscle mitochondrial bioenergetics by high resolution oxygraphy

Quantification of muscle lipid droplets by electron microscopy

Analysis of the expression of target genes and proteins involved in 1/ mitochondrial metabolism 2/ lipid metabolism 3/ the regulation of energy metabolism and 4/ muscle proteolysis by RTqPCR with SYBR Green and by Western Blot

Determination of body composition ( fat mass / lean mass ) by an imaging method scannographic

Determining the isotopic composition of nitrogen hair spectrometry .

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Skeletal Muscle Expression of Myostatin and Cancer of Digestive System Associated Cachexia	NCT03172403	Cancer of Diges...	Height and weig... Blood samples Skeletal muscle... Skeletal muscle... Muscle biopsy	40 Years - 80 Years	Centre Hospitalier Universitaire de Saint Etienne
Prehabilitation With Resistance-exercise Training for Breast Cancer Neoadjuvant Therapy	NCT06309290	Prehabilitation Breast Cancer Postmenopause Resistance Trai...	Prehabilitation... Usual care prog...	-	Universidad de La Frontera
Exercise in Testicular Germ Cell Cancer Survivors	NCT05063760	Testicular Germ...	aerobic-strengt...	25 Years - 55 Years	Slovak Academy of Sciences
Skeletal Muscle Energy Metabolism in Undernourished Patients With Gastrointestinal Cancer	NCT02573974	Undernutrition Gastrointestina...	Samples	18 Years - 80 Years	University Hospital, Tours
Prehabilitation With Resistance-exercise Training for Breast Cancer Neoadjuvant Therapy	NCT06309290	Prehabilitation Breast Cancer Postmenopause Resistance Trai...	Prehabilitation... Usual care prog...	-	Universidad de La Frontera
Skeletal Muscle Expression of Myostatin and Cancer of Digestive System Associated Cachexia	NCT03172403	Cancer of Diges...	Height and weig... Blood samples Skeletal muscle... Skeletal muscle... Muscle biopsy	40 Years - 80 Years	Centre Hospitalier Universitaire de Saint Etienne

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