J Natl Compr Canc Netw. 2026 Mar;24(3):91-99. doi: 10.6004/jnccn.2025.7118.
ABSTRACT
BACKGROUND: Up to 75% of patients experience cancer-related cognitive impairment (CRCI) during treatment. CRCI often co-occurs with mental fatigue. Chemotherapy may cause cognitive impairment and mental fatigue by compromising systemic inflammatory responses, whereas exercise may induce a self-regulating inflammatory response and promote immunocompetence. Exercise-induced immunocompetence may lead to improvements in CRCI and mental fatigue. We examined the effects of exercise on CRCI and mental fatigue, as well as the relationships between exercise and CRCI and between inflammatory responses and CRCI, in patients receiving chemotherapy in a multicenter phase III randomized controlled trial.
PATIENTS AND METHODS: Patients diagnosed with any cancer type and scheduled to start chemotherapy were randomized to either a 6-week home-based, individually tailored exercise intervention-Exercise for Cancer Patients (EXCAP)-or usual care. The Functional Assessment of Cancer Therapy-Cognitive Function and the Multidimensional Fatigue Symptom Inventory were used to assess cognitive impairment and mental fatigue, respectively. Blood samples were collected to assess inflammation (ie, IL-1β, IL-6, IL-8, IL-10, IFN-γ, and sTNFR1). Analysis of covariance (ANCOVA) was used to examine between-group differences in CRCI and mental fatigue. Structural equation modeling was conducted to examine the relationships between exercise and CRCI and between inflammatory responses and CRCI.
RESULTS: Compared with participants receiving usual care, EXCAP participants undergoing chemotherapy on 2-week cycles reported less overall cognitive impairment (mean difference [SE], 7.0 [3.3]; P=.04), perceived cognitive impairment (4.1 [2.1]; P=.05), comments from others identifying cognitive impairment (0.6 [0.2]; P=.02), and mental fatigue (-1.6 [0.5]; P<.01). All EXCAP participants, regardless of chemotherapy cycle duration, reported less mental fatigue compared with participants receiving usual care (-0.7 [0.3]; P=.02). Suppressed inflammatory responses were associated with CRCI in participants receiving chemotherapy (0.2 [0.1]; P<.01).
CONCLUSIONS: EXCAP may reduce CRCI and mental fatigue, particularly in patients receiving 2-week cycles of chemotherapy. A healthy inflammatory response, characterized by increases in both proinflammatory and anti-inflammatory cytokines, is associated with less cognitive impairment during chemotherapy.
PMID:41825129 | DOI:10.6004/jnccn.2025.7118
