Exercise for the Treatment of Cancer-Related 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).

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.

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.

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.

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.

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.

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

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

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.

Physical activity levels is assessed using the Portuguese version of the International Physical Activity Questionnaire