The Effect of Aerobic and Resistance Training With and Without Neurodynamic Exercises on Chemotherapy-induced Peripheral Neuropathy Symptoms and Associated Neuro-immune Mechanisms

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially persistent side effect of neurotoxic chemotherapy, characterized by symptoms such as numbness, tingling, pain, and sensory dysfunction in the hands and feet. These symptoms may negatively affect physical functioning, quality of life, and participation in daily activities. Exercise therapy has emerged as a promising non-pharmacological intervention for individuals with CIPN. However, it remains unclear which exercise approach is most effective. Neurodynamic interventions have shown beneficial effects in other peripheral neuropathic conditions but have not yet been adequately investigated in individuals with CIPN. The objective of the CIPN-NEXT trial is to evaluate the effectiveness of two exercise-based rehabilitation programmes in individuals with CIPN. Participants will be randomized to one of three study arms: (1) aerobic and resistance exercise, (2) aerobic and resistance exercise combined with neurodynamic interventions, or (3) a wait-list control group. The study aims to determine whether the addition of neurodynamic interventions provides additional benefit beyond exercise therapy alone with regard to CIPN symptoms, physical functioning, psychosocial functioning, and quality of life. Furthermore, the study will explore potential underlying mechanisms associated with symptom development and recovery.

Inclusion Criteria: * Age above 18 years * Primary diagnosis of breast, colon or gynaecological cancer * Undergoing taxane- or oxaliplatin-based chemotherapy, or having completed this treatment within the previous 3 months * At least one self-reported symptom consistent with chemotherapy-induced peripheral neuropathy, including numbness, tingling and/or pain in a stocking (feet) and/or glove (hand) distribution, as assessed by the EORTC QLQ-CIPN20 sensory subscale, which emerged during the current course of neurotoxic chemotherapy or within 3 months following its completion Exclusion Criteria: * Pre-existing peripheral neuropathy or neurological conditions that could account for the reported symptoms, including persistent CIPN from a previous chemotherapy regimen, radiculopathy, entrapment neuropathies, or other non-chemotherapy-related neuropathies * An Eastern Cooperative Oncology Group (ECOG) performance status above one * Life expectancy of less than six months according to the patient's oncologist or designee * Any medical condition that contraindicates safe participation in a low- to moderate-intensity aerobic and resistance exercise program * Meeting current physical activity guidelines (\>150 min/week of moderate-to-vigorous physical activity) or participation in a structured exercise program comparable to the study intervention * Not able to provide informed consent * Pregnancy