In a joint program with the Oncology Nursing Society, AACR-ONS Special Session: Symptom Science, a panel of experts discussed the mechanisms of action related to cognitive impairment in cancer survivors, including chemotherapy-induced cognitive impairment, as well as potential interventions to mitigate the effects.

The session included a live Panel Discussion on Monday, April 12. Registrants can watch a replay of the sessions through June 21, 2021

“Chemo brain,” accelerated aging, and peripheral neuropathy as a result of chemotherapy

Cobi J. Heijnen, PhD, UT MD Anderson Cancer Center, talked about studies looking at the mechanisms of “chemo brain,” accelerated aging, as well as peripheral neuropathy as a result of chemotherapy.

“Chemo brain, or cognitive impairment, consists of memory problems, reduced cognitive flexibility, and confusion, and it often is accompanied by difficulties in multitasking, planning, and attention,” Heijnen said. “It persists in 17 percent to 34 percent of patients after completion of treatment and, most importantly, there are no FDA-approved preventive or curative interventions.”

Chemotherapy-induced peripheral neuropathy, she said, does not resolve in 25 percent to 30 percent of patients.

“The aim of our study, which is now is in a preclinical model, is to understand the mechanisms of cognitive deficits in response to treatment with cisplatin, and to explore potential cell therapy treatments for cognitive impairment and also peripheral neuropathy,” Heijnen said.

She reported that findings in animal models suggest that nasal administration of mesenchymal stem cells or isolated mitochondria can reverse mitochondrial deficits, reverse brain damage, and reverse cognitive deficits and pain.

Physical activity to attenuate cognitive decline

Catherine M. Bender, PhD, RN, University of Pittsburgh, discussed the use of physical activity and exercise as an intervention to mitigate cognitive impairments in cancer and the potential mechanisms underlying the influence of physical activity on cognitive function.

“Evidence has been shown in other populations that physical activity is associated with reductions in markers of aging and enhancement of cognitive reserve; however, whether this evidence extends to individuals with cancer is not clear,” Bender said.

There is some evidence, she said, that reductions in commonly occurring symptoms with physical activity may also partially mediate the influence of physical activity on cancer-related cognitive impairment.

“For example, there is evidence suggesting that exercise may be associated with improvements in cognitive function and that this may be partially mediated by reductions in symptoms, including fatigue, poor sleep quality, and anxiety,” Bender said.

Neurophenotypes of psychoneurologic symptoms in cancer

Shelli Kesler, PhD, University of Texas at Austin discussed ongoing work in her lab looking at the neurophenotypes of psychoneurologic symptoms in patients with cancer.

“Cognitive impairment, sleep disruption, pain, anxiety, fatigue, and depression are very common among patients with cancer,” she said. “These symptoms often co-occur and interact with each other, which has led to hypotheses about the existence of symptom clusters, which are associated with a greater impact on quality of life and other outcomes compared to individual symptoms.”

Patients with cancer, especially those treated with chemotherapy, show significant alterations of connectome organization compared with both healthy controls and chemotherapy naïve patients, she said, making this a consistent biomarker of psychoneurologic symptoms.

“And even though some psychoneurologic symptoms may co-occur, one symptom is not a sufficient explanation for another, and symptoms do appear to have distinct neurophenotypes,” Kesler said. “These neurophenotypes may help us improve the diagnosis and prognosis of these symptoms, as well as to better evaluate interventions for them. Going forward, it will be important to identify risk and resilience factors associated with these neurophenotypes.”

CNS-directed therapy for childhood leukemia

CNS-directed therapy does have consequences, said Ida M. (Ki) Moore, PhD, RN, University of Arizona. It’s essential for long-term survival, but adverse outcomes include neurodevelopmental and academic problems that can be experienced by up to 60 percent of childhood leukemia survivors.

Neurodevelopmental and academic problems, she said, can span areas such as memory, visual spatial skills, fine motor speed and dexterity, attention, processing speed, and some areas of academic achievement, especially math.

“These neurodevelopmental and academic problems can also be associated with secondary effects on psychological well-being; for example, anxiety and depression, social and adaptive skills, and overall vocational success,” Moore said.

She reported findings from ongoing work suggesting that apoptosis and oxidative stress play a role in CNS treatment-related neurologic injury, and that certain caspase enzymes may be potential biomarkers of cognitive decline.

“Additionally, there is some evidence beginning to suggest that epigenetic changes could be an underlying mechanism of CNS treatment-related neurologic injury, and this warrants further investigation,” Moore said. “This is important because epigenetic changes are dynamic and can be reversed, supporting the potential efficacy of behavioral and neuro-protective interventions.”

In addition to this on-demand session, the presenters participated in a live Panel Discussion on Monday, April 12. A recording of the session and companion panel discussion will be available to registered attendees until June 21.