Exercise for the Treatment of Cancer-Related Sarcopenia (HERA)

Exercise for the Treatment of Cancer-Related Sarcopenia: a Randomised Controlled Trial.

Our primary objective is to assess the effects of exercise on cancer-related sarcopenia and its hallmarks, including muscle strength, muscle mass, and physical performance. The secondary objectives are to examine exercise adherence and the effects of exercise on health-related quality of life (QoL), cancer-related fatigue, and sleep quality. Additionally, we will explore the effects of exercise on bone and fat mass as secondary outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer; Sarcopenia
• Intervention / Treatment: Other: Multimodal, supervised exercise training

Detailed Description

Cancer-related sarcopenia is a distinct and severe form of muscle atrophy, as no other condition (e.g., aging, immobilization, or microgravity) results in such profound impairment in patient prognosis. Sarcopenic cancer patients experience greater fatigue, poorer quality of life, longer hospital stays and higher costs, worse cancer outcomes, and increased mortality compared with non-sarcopenic patients. As no pharmacological treatments are approved for sarcopenia, management relies primarily on nutritional strategies and physical exercise. While exercise effectively prevents and attenuates sarcopenia in older adults, its efficacy in cancer patients remains uncertain.

Cancer-related sarcopenia is a multifactorial condition driven by tumor progression and cancer therapies. Tumors increase nutrient competition and promote hormonal dysregulation and chronic inflammation, impairing muscle protein balance. In addition, chemotherapy and radiotherapy induce oxidative stress and mitochondrial dysfunction, accelerating muscle wasting and contributing to anabolic resistance-a reduced responsiveness of muscle to stimuli such as exercise. These factors may limit exercise-induced gains in muscle mass and strength in cancer patients.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rafael Deminice, PhD; Phone Number: +5543991916013; Email: rdeminice@uel.br

Study Locations

• Brazil
  • Paraná
    • Londrina, Paraná, Brazil, 86047-597
      • State University of Londrina
      • Contact: Ivone Beraldo; Phone Number: +554333715953; Email: cefepos@uel.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• > 18 years old women with a confirmed diagnosis of breast or gynecological cancer.
• Any level of sarcopenia (pre-sarcopenia, sarcopenia, or severe sarcopenia).
• Patients must have completed their primary treatment regimen (surgery, chemotherapy, and/or radiotherapy) for at least 2 weeks and up to 2 years before enrolment.
• have received the medical consent to be engaged in physical exercise programs.

Exclusion Criteria:

• The presence of one or more comorbidities that could potentially interfere with attendance or test results (e.g., other cancers or acute or chronic renal failure);
• Already in exercise programs comparable to the HERA program;
• Evidence of severe cardiovascular disease as a result of an electrocardiogram.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise intervention group; The exercise group will be asked to complete 48 multicomponent, supervised exercise training sessions over 24 weeks, with a frequency of two sessions per week on non-consecutive days.	Other: Multimodal, supervised exercise training; The multicomponent exercise intervention included a 10-minute warm-up consisting of balance, coordination, and stretching exercises. The main component was resistance training targeting major upper and lower body muscle groups to improve muscle strength and mass. Six to eight exercises were performed using body weight, elastic bands, and dumbbells. Training progression was achieved by increasing load, repetitions, and/or sets, guided by the 0-10 Borg rating of perceived exertion when health status permitted. The aerobic component consisted of walking progressing to beginner-level running, using short running intervals (50-100 m) interspersed with walking until longer continuous distances were achieved. Heart rate was monitored throughout the aerobic session.
No Intervention: Control group; Patients in the waiting list control group received standard medical care without any exercise program or specific exercise recommendations. To maintain contact with the researchers and minimize drop-out, the waiting list control group received general health information through monthly online meetings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sarcopenia	Sarcopenia was determined using the revised European Consensus on Definition and Diagnosis of Sarcopenia [Cruz-Jentoft et al. 2019], with handgrip strength cut-offs adapted to the Brazilian population [Lima et al. 2025]. Any level of sarcopenia was considered to patients inclusion in the sarcopenic group, as follows: (i) pre-sarcopenia, low muscular strength (hand grip strength < 23 kg); (ii) sarcopenia, low muscular strength accompanied by low muscle mass (appendicular muscle mass < 15 kg); and severe sarcopenia, low muscular strength and low muscle mass accompanied by low physical performance assessed using the Short Physical Performance Battery (SPPB) score < 8).	baseline, week 24 (post exercise)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition	Body composition was assessed using dual-energy X-ray absorptiometry (DXA) with a GE Lunar system (GE Healthcare, USA). Total and appendicular fat-free mass, fat mass, and bone mineral content were estimated from whole-body DXA scans, following the manufacturer's standard protocols. All scans were performed by a trained technician, and analyses were conducted using the manufacturer's software.	Baseline and week 24 (post exercise intervention)
Cardiorespiratory endurance and functional capacity	6MWT was also performed as a parameter of cardiorespiratory endurance and functional capacity. Participants were instructed to walk back and forth along a flat, straight 25m corridor for six minutes, covering as much distance as possible at a self-selected pace. The total distance walked (in meters) was recorded as the primary outcome.	Baseline and week 24 (post exercise intervention)
Fatigue	Fatigue was assessed using the Portuguese language version of the EORTC QLQ-FA12 [Weis et al. 2017]. The EORTC QLQ-FA12 is a 12-item questionnaire that assesses multiple dimensions of fatigue, including physical, emotional, cognitive, interference with daily activities, and social sequelae.	Baseline and week 24 (post exercise intervention)
Health-related quality of life (HRQOL)	Health-related quality of life (HRQOL) was assessed using the Portuguese language version of the EORTC QLQ-C30 [Aaronson et al. 1993]. The EORTC QLQ-C30 is a 30-item questionnaire comprising five functional scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea and vomiting, and pain), and six single-item symptom measures (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores for both instruments range from 0 to 100, with higher scores indicating greater symptom burden. The exception is the functional scales of the EORTC QLQ-C30, for which higher scores reflect better functional status.	Baseline and week 24 (post exercise intervention)
Blood markers	Plasma concentration of Cystatin C, creatinine, and C-reactive protein was determined after a 10 to 12 h fasted blood collection (8 ml). Blood was collected in the laboratory analysis sampling room and assessed for blood markers.	Baseline and week 24 (post exercise intervention)
Disease progression	Participants will be followed for disease progression for 1 year beyond the 48-month study period. Information on disease progression and (all-cause and breast cancer-specific) death is retrieved	Up to 1 year after the 48-week intervention period
Survival	Participants will be followed for survival for 1 year beyond the 48-month study period. Information on disease progression and (all-cause and breast cancer-specific) death is retrieved	Up to 1 year after the 48-week intervention period
Safety and exercise program adherence	Safety was monitored through systematic documentation of all serious events occurring during physical fitness testing or exercise sessions. Serious adverse events were defined as incidents necessitating suspension of the exercise program, such as falls with fractures, orthopedic injuries requiring hospitalization, or any event posing an immediate threat to life. Adherence was evaluated based on both participation in supervised exercise sessions and conformity with the prescribed exercise protocol. Attendance and exercise compliance for each scheduled session were recorded by the supervising trainer using a case report form.	Baseline and week 24 (post exercise intervention)
Physical activity levels	Physical activity levels is assessed using the Portuguese version of the International Physical Activity Questionnaire	Baseline

Collaborators and Investigators

• Sponsor: State University of Londrina

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Resistance Training; Frail; muscle loss
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neoplasms; Sarcopenia; Muscular Atrophy
• Other Study ID Numbers: PBA2025201000211 (Other Grant/Funding Number: Fundação Araucaria)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No