Exercise and Cognitive Rehabilitation Interventions for Older Cancer Survivors

Cancer-Related Cognitive Dysfunction (CRCD) is a prevalent problem for older cancer survivors. Sixty-four percent of current cancer survivors are aged ≥65, and by 2040, it is estimated that over 19 million older cancer survivors will be living in the United States. Up to 50% of these individuals experience CRCD post-treatment, which can persist for years after treatment completion. For older adults, CRCD can affect their ability to perform daily tasks, such as taking medications or managing finances, reducing their overall independence. Although evidence-based interventions exist to treat CRCD, older adults were underrepresented in these trials, despite them being most at risk for CRCD and its consequences. The National Cancer Institute, topic experts, and patient advocates have highlighted the urgent need for accessible interventions to address CRCD symptoms, particularly for older adults.

Exercise for Cancer Patients (EXCAP) is an individually tailored, low-to-moderate intensity, home-based walking and progressive resistance exercise program designed for patients with cancer delivered by an exercise physiologist. The Investigators adapted EXCAP for digital health applications, allowing the tracking of exercise adherence, barriers to exercise, and symptoms. In a large randomized controlled trial (RCT), EXCAP improved patient-reported cognition compared to usual care. In older adults with cancer, EXCAP patients demonstrated improvements in cognitive impairment, as assessed via the Trail-Making Test, which evaluates processing speed.

Memory and Attention Adaptation Training (MAAT) was previously shown to improve CRCD and psychological function in three clinical trials. The Investigators tailored aspects for the particular needs of older adults, including support for telehealth delivery. The intervention, based on cognitive behavioral therapy principles, integrates cognitive rehabilitation skills and provides education and training in adaptive behavioral coping skills, stress management techniques, and compensation strategies to address CRCD. MAAT is standardized via a manual and delivered one-on-one via video-conferencing over 10 weekly workshops by a trained clinician. In a pilot RCT, MAAT improved perceived cognition [Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) and objective cognition (e.g., processing speed). In a separate study of 34 older adults with cancer, improvements from baseline to post-intervention were observed in objective cognitive measures and perceived cognition.

Exercise and Cognition (ECO) leverages the synergy between EXCAP and MAAT, and enhances both general and exercise self-efficacy, improves adherence, and promotes lasting behavior change for sustained cognitive benefits. Adapted with input from the patient advisory board, ECO is a 12-week program delivered virtually by an exercise physiologist and a trained clinician, facilitated through digital health applications. Delivering both interventions simultaneously was evaluated in a single-arm pilot study of eight older adults with cancer who had completed curative treatments and were experiencing residual CRCD symptoms. Preliminary results suggest greater self-efficacy and exercise adherence. From baseline to post-intervention, all patients reported clinically meaningful improvements in FACT-Cog; these improvements were greater than those observed with EXCAP or MAAT intervention alone.

However, it is unknown which behavioral intervention is most effective at addressing CRCD symptoms. It is also unknown which type of CRCD intervention is the "best fit" for each patient. To inform the design of a future R01-funded definitive RCT to fill these gaps, the Investigators need to obtain more precise estimates of ECO's effects and identify the most appropriate comparison arms.

Inclusion criteria

• Age ≥65 years (from date of consent, confirmed on the electronic medical record)
• A diagnosis of any cancer
• Have completed curative intent treatments

• Patients on endocrine therapies are allowed to enroll
• Patients with hematologic malignancies after autologous or allogeneic stem cell transplant are allowed to enroll if they have completed curative-intent treatment
• Answered "yes" to the verbal question "Do you have concerns about memory or other thinking abilities following your cancer treatment?"
• Able to speak English (interventions are available in English only)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3#
• No medical contraindications to exercise#
• Able to walk 4 meters#
• Able to provide informed consent#

• Confirmed through eligibility confirmation with the patient's oncologist or their designee

Exclusion criteria

• Any physical, psychological, or social impairments that would interfere with a patient's ability to participate in the study as determined by the patient's oncologist or their designee
• Unwilling to complete study procedures