Exercise During Chemotherapy Treatment as an Adjuvant Programme in Patients With Lymphoma (EDONOLA): Study Protocol for a Randomised Controlled Trial
Sara Maldonado-Martin, Izaskun Zeberio-Etxetxipia, Marene Martinez de Rituerto-Zeberio, Jon Madinabeitia-Murillo, Mikel Tous-Espelosin, Ana Vega-Gonzalez de Viñaspre, Eukene Gainza-Gonzalez,Introduction
Lymphomas are a heterogeneous group of haematological malignancies commonly treated with chemotherapy. Hodgkin lymphoma predominantly affects younger adults, while Non-Hodgkin lymphoma is more prevalent among older adults. Although survival outcomes have improved, treatment-related cardiovascular, musculoskeletal, and functional adverse effects contributing to fatigue, reduced cardiorespiratory fitness (CRF), diminished quality of life (QoL), and increased frailty risk, remain, particularly among older adults. Reduced CRF, measured by peak oxygen uptake (VO 2peak ), is an independent predictor of all-cause and cancer-specific mortality, and chemotherapy tolerance, making its preservation a clinically meaningful target. Evidence supporting exercise during active chemotherapy remains limited. This study aims to evaluate the effect of a 20-week combined exercise (EX) intervention on CRF in people with lymphoma receiving chemotherapy, compared with a treatment-as-usual (TAU) group.
Methods
EDONOLA is a randomised (1:1), multicentre, parallel-group, open-label controlled clinical trial involving adults aged >18 years (n=180, EX, n=90; TAU, n=90). The exercise intervention comprises supervised sessions (two days/week) of low-to high-intensity resistance and aerobic interval training, plus two days/week of unsupervised exercise. The TAU group will receive standard clinical care and physical activity advice. Assessments will be conducted at baseline, 10 weeks, and 20 weeks. The primary outcome will be CRF, measured as VO 2peak . Secondary outcomes will include muscular strength, frailty, body composition, physical activity, sedentary behaviour, QoL, fatigue, sleep, and biochemical profile, including immune biomarkers. Older participants (≥70 years) will additionally undergo a comprehensive geriatric assessment, and EX participants will be invited to a voluntary semi-structured qualitative interview.
Discussion
This multidisciplinary project integrates structured exercise into standard oncology care, aligned with Sustainable Development Goal 3. The intervention aims to mitigate treatment-related side effects, preserve CRF and muscular strength, improve QoL, and reduce frailty risk in people with lymphoma undergoing chemotherapy, while potentially decreasing long-term healthcare burden.