Exercise to Thwart ‘Chemo Brain’ Shows Promise in Randomized Trial

Patients who adhered to a structured exercise program during cancer chemotherapy had significantly less cancer-related cognitive impairment versus patients who received usual care, a randomized trial showed.

The 6-week tailored exercise program was associated with better scores for multiple objective and subjective indicators of cognitive impairment, including overall cognitive impairment and mental fatigue. The differences had a significant association with changes in proinflammatory and anti-inflammatory cytokines implicated in cancer-related cognitive impairment.

The favorable effects of exercise on cognitive impairment were limited to patients on 2-week chemotherapy cycles and did not benefit patients treated on 3- and 4-week cycles, reported Karen Mustian, PhD, MPH, of the Wilmot Cancer Institute and University of Rochester in New York, and colleagues in the Journal of the National Comprehensive Cancer Network.

“Cancer care providers should consider incorporating structured, home-based exercise prescriptions, such as walking and resistance band exercises, into routine chemotherapy care,” Mustian said in a statement. “Providers should educate patients on these benefits, monitor cognitive and fatigue symptoms throughout treatment, and, as part of optimal supportive care, refer patients to exercise oncology specialists when needed, to tailor prescriptions for individual capabilities.”

Awareness of “chemo brain,” a common term for the adverse effects of cancer and chemotherapy on cognitive function, has increased, and many patients are concerned that they will be affected, said Lindsay L. Peterson, MD, of Washington University in St. Louis, who was not involved in the study.

“For many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life,” said Peterson, chair of the National Comprehensive Cancer Network (NCCN) survivorship guideline panel. “These findings reinforce the recommendation in the NCCN Guidelines for Survivorship that survivors with cancer-related cognitive dysfunction engage in routine physical activity.”

“Importantly, the NCCN guidelines also provide detailed information to keep people safe during exercise,” she added. “Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment.”

As many as three-fourths of patients report cancer-related cognitive impairment during treatment, persisting for as long as 10 years after treatment, Mustian and colleagues noted in their introduction. The deficits can affect treatment adherence and contribute to poor prognosis, morbidity, and mortality.

Chemotherapy may cause cognitive impairment and mental fatigue by compromising healthy systemic inflammatory responses, the authors explained. Evidence suggests chemotherapy disrupts immune function, upsetting the balance between pro- and anti-inflammatory responses and leading to a persistent proinflammatory state. Manifestations of the dysregulated state may include alterations in various molecular markers, such as interferon-gamma, several interleukins, and soluble tumor necrosis factor receptor 1.

Exercise may offer a nonpharmacologic intervention for cancer-related cognitive impairment and mental fatigue, as it induces a self-regulating inflammatory response with initial release of proinflammatory cytokines followed by release of anti-inflammatory cytokines. Exercise-induced immunocompetence is posited to improve cancer-related cognitive impairment and mental fatigue.

Mustian and colleagues previously reported that patients who received the Exercise for Cancer Patients (EXCAP) intervention exhibited higher immunocompetence, as reflected in biomarker status. They also evaluated the EXCAP intervention in a randomized phase III trial of patients undergoing cancer chemotherapy to assess its effects on peripheral neuropathy. Cancer-related cognitive impairment and mental fatigue were secondary outcomes.

Eligible patients could have any type of cancer and were scheduled to start chemotherapy. They were randomized to the 6-week, at-home, individually tailored EXCAP intervention or usual care, in addition to their primary cancer treatment. The investigators used the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire to assess cancer-related cognitive impairment before and after the intervention. They used a mental fatigue subscale of the validated Multidimensional Fatigue Symptom Inventory questionnaire to assess mental fatigue.

Data analysis included 687 patients randomized to EXCAP or usual care. Separate analyses examined the effects of EXCAP on patients treated with 2-week, 3-week, or 4-week chemotherapy cycles. The results showed significant differences from the control group only for patients treated with 2-week cycles.

• Less overall cognitive impairment: mean difference 7.0, P=0.04
• Perceived cognitive impairment: mean difference 4.1, P=0.05
• Comments by others identifying cognitive impairment: mean difference 0.6, P=0.02
• Mental fatigue: mean difference -0.7, P=0.02

The data also showed that increasing amounts of exercise were associated with less cancer-related cognitive impairment (P=0.03). Additionally, a healthy inflammatory response (balance between pro- and anti-inflammatory responses) had a positive association with cancer-related cognitive impairment score (P<0.01).