Chemotherapy-Related Changes in Neurocognitive Function and Symptoms in Colorectal Cancer Patients: A Pilot Study

Cancer treatments have successfully improved cancer outcomes but frequently negatively impact quality of life in cancer survivors. In particular, chemotherapy (CTX) has been associated with impaired cognitive abilities such as concentration and memory. The goal is to investigate the neural mechanisms of chemotherapy-related cognitive impairment (CRCI) using an interdisciplinary translational approach. Previous research in this area lacks diversity in studied cancer populations and treatments focusing primarily on breast cancer and provides limited understanding of how CRCI emerges from changes in neural structure, function, and connectivity. To overcome these limitations, this feasibility/pilot study aims to investigate CRCI in patients with colorectal cancer (CRC).

A growing public health and oncology nursing concern is the likelihood of colorectal cancer (CRC) survivors experiencing decline in long-term physical and mental functional status following cancer diagnosis and treatment. Prior to receiving treatment, cognitive impairment in processing speed, spatial working memory, and verbal memory has been noted in 45% of CRC patients relative to 15% of healthy controls (HC). Following adjuvant chemotherapy, cognitive function is more impaired in CRC patients who received chemotherapy (Ctx+ group) compared to CRC patients not receiving chemotherapy (Ctx- group) and HC participants. These studies show: (1) CRC patients are at a high risk for cognitive impairment and (2) Ctx+ patients are more likely to decline in cognitive function during treatment. These cancer and chemotherapy-related changes in cognitive function have been associated with several quality of life factors, including physiological and concurrent symptoms, and physical and mental functional status. In contrast, the neural mechanisms of cognitive impairment in CRC patients is related to changes in the Executive Function Network (EFN). The EFN promotes long-range communication between frontal and parietal cortical regions, and is associated with attentional control processes. The empirical goals studying CRC patients are two-fold: (1) Develop a core set of cognitive function, event related potential (ERP) measures from electroencephalogram (EEG), and resting-state functional magnetic resonance imaging (rsfMRI) measures to elucidate the relationship between impaired attentional control and EFN dysfunction and (2) Increase understanding of the link between neurocognitive impairment with concurrent symptom severity and impact on functioning. The investigators propose a longitudinal, prospective cohort pilot design to study post-operative CRC patients scheduled to begin adjuvant chemotherapy (Ctx+ group). Comparison groups will include post-operative CRC patients not receiving chemotherapy (Ctx- group) and healthy controls demographically matched to Ctx+ participants (HC group). All participants (N=60; 20 per group) will complete an additional 1-hour study visits at baseline and 24-weeks to collect rsfMRI measurements Ctx+ patients will complete baseline assessment after surgery but before starting chemotherapy, CTx- patients will complete baseline assessments 4-6 weeks after surgery and HC after matched and consented.

Eligibility Criteria:
Inclusion Criteria:

CRC adenocarcinoma patients:

* Stage II/IV patients receiving adjuvant CTX (Ctx+ group)
* Stage I/III patients not receiving CTX (Ctx- group)
* Normal or corrected to normal vision (corrected far visual acuity of 20/50 or better)

For demographically-matched healthy controls (HC group)

* Matched to patient receiving CTX on demographics: age (plus or minus 5 years, gender, race, menopausal status, and education (plus or minus 2 years)
* Normal or corrected-to-normal vision (corrected far visual acuity of 20/50 or better)

Exclusion Criteria:

CRC patients:

Cancer diagnosis/treatment in last 3 yrs. in addition to CRC (exceptionpatients with localized skin cancer) Prior chemotherapy within 1 year for CRC Cognitive impairment (MMSE score \< 25) prior to baseline assessment

Demographically-matched healthy controls:

CRC cancer diagnosis All exclusion criteria for CRC patients.