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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Colorectal Cancer

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CRC patients (Ctx+ group)<br>Postoperative CRC patients scheduled to begin CTX | |
| CRC patients (CT- group)<br>Postoperative CRC patients who do not receive CTX | |
| Healthy control group<br>Study participants that are demographically matched to CRC study patients and meet all inclusion criteria | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Trails A baseline at 12 weeks and 24 weeks (Specific Aim 1) | Neurocognitive measure of processing speed; Completion time (milliseconds), where longer completion times are interpreted as slower processing speed | Change from baseline to 12 and 24 weeks | 
| Change from Trails B baseline at 12 weeks and 24 weeks (Specific Aim 1) | Neurocognitive measure of executive functioning; Completion time (milliseconds) where larger differences in completion time are interpreted as slower executive functioning processes | Change from baseline to 12 weeks and 24 weeks | 
| Change from Symbol Digit Modalities baseline at 12 weeks and 24 weeks (Specific Aim 1) | Neurocognitive measure of psychomotor speed; Total correct complete, where greater number completed is interpreted as faster psychomotor speed | Change from baseline to 12 weeks and 24 weeks | 
| Change from Stroop baseline at 12 weeks and 24 weeks (Specific Aim 1) | Neurocognitive measure of inhibitory control; Total number completed, where greater number completed is interpreted as better inhibitory control.Interference scores are obtained to estimate inhibitory control, where more negative values are interpreted as lower inhibitory control (estimated by subtracting expected performance from observed performance in color-word condition) | Change from baseline to 12 weeks and 24 weeks | 
| Change from Auditory Verbal Learning Task baseline at 12 weeks and 24 weeks (Specific Aim 1) | Neurocognitive measure of verbal memory; Total number recalled (immediate), where greater number immediately recalled is interpreted as better verbal short-term memory. Total number recalled (delayed), where greater number recall following delay is interpreted as better verbal long-term memory | Change from Baseline to 12 and 24 weeks | 
| Change from Visual Search Performance baseline at 12 weeks and 24 weeks (Specific Aim IIa) | Measure of Response time (milliseconds), where longer response times are interpreted as slower processing speed and lower inhibitory control. | Change from baseline to 12 and 24 weeks | 
| Change from Change Detection Performance baseline at 12 weeks and 24 weeks (Specific Aim IIa) | Measure of response accuracy, where larger response accuracies are interpreted as larger working memory capacity and higher inhibitory control. | Change from baseline to 12 and 24 weeks | 
| Change from N2pc amplitude during visual search baseline at 12 weeks and 24 weeks (Specific Aim IIa) | Measure of attentional control. Larger amplitudes are interpreted as more resources allocated towards stimulus selection and poor attentional control | Change from baseline to 12 and 24 weeks | 
| Change from Contralateral delay activity (CDA) amplitude change during task performance baseline at 12 weeks and 24 weeks (Specific Aim IIa) | Measure of working memory storage. Where larger amplitudes are interpreted as more resources allocated towards working memory storage. | Change from baseline to 12 and 24 weeks | 
| Change from MRI white matter volume baseline at 12 weeks and 24 weeks (Specific Aim IIb) | Measure of white matter volume within executive function network | Change from baseline to 6 months (only CTx+ group) | 
| Change from MRI Grey matter volume baseline at 12 weeks and 24 weeks (Specific Aim IIb) | Measure of grey matter volume within executive function network | Change from baseline to 6 months (only CTx+ group) | 
| Change from Executive Functional Network functional connectivity baseline at 12 weeks and 24 weeks (Specific Aim IIb) | EFN function | Change from baseline to 6 months (only CTx+ group) | 
| Change from M.D. Anderson Symptom Inventory-Gastro-Intestinal (MDASI-GI) baseline at 12 weeks and 24 weeks(Specific Aim III) | Measures co-occurring symptom severity and interference with function | Change from baseline to 12 weeks and 24 weeks | 
| Change from Research And Development (RAND) Short Form-12 (SF-12) from baseline to 12 and 24 weeks (Specific Aim III) | Measures physical and mental functional status | Change from baseline to 12 weeks and 24 weeks | 
| Change from Functional Assessment of Cancer Therapy- Cognitive (FACT-COG) at baseline to 12 and 24 weeks (Specific Aim III) | Self-perceives cognitive function | Change from baseline to12 weeks and 24 weeks | 
| Change from Beck Depression Inventory (BDI) from baseline to 12 and 24 weeks (Specific Aim III) | Assesses depressive symptoms | Change from baseline to 12 and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from logMAR visual acuity baseline at 12 weeks and 24 weeks | Measures visual acuity. Relatively lower logMAR values are interpreted as better visual acuity (estimated as log transformed estimate of visual acuity with respect to deviation from standard 20/20) | Change from baseline to 12 and 24 weeks | 
| Change from logMAR contrast sensitivity baseline at 12 weeks and 24 weeks | Measures contrast sensitivity. Relatively lower logMAR values are interpreted as better contrast sensitivity. | Change from baseline to 12 and 24 weeks | 
| Change from Frequency Doubling Technology baseline at 12 weeks and 24 weeks | Measures visual field loss. A binary (yes/no) variable where presence of visual field defect is coded as evidence of visual field loss | Change from baseline to 12 and 24 weeks | 
| Change from Optical Coherence Tomography baseline at 12 weeks and 24 weeks | Measure of retinal nerve fiber layer (RNFL) thickness | Change from baseline to 12 and 24 weeks |