Immune checkpoint inhibitors (ICIs) are a group of novel immunotherapies that boost the body's own defense against the cancer by improving the immune system's ability to recognize and destroy cancer cells. While it is relatively well-documented that conventional cancer treatments (e.g., chemotherapy) are associated with cognitive impairment, virtually nothing is yet known about effects on cognition during and after ICI treatment. Due to significantly improved survival rates after ICI treatments, it becomes important to map possible adverse effects associated with these treatments. The investigators therefore investigate possible changes in cognitive function in a group of cancer patients from prior to ICI treatment to nine months later. A gender- and age- matched healthy control group will serve as a comparison. The study has the potential to broaden our understanding of associations between cognition, the brain, and the immune system and to provide clinically relevant knowledge about possible cognitive impairments associated with immunotherapy.
This controlled prospective observational study will include two groups with a total of 84 participants. A total of 42 patients diagnosed with melanoma, referred to treatment with ICI will be enrolled in the study and examined prior to treatment with ICI (baseline), at eight weeks following baseline (T2), at 24 weeks following baseline (T3) and 12 weeks after treatment completed (T4). A total of 42 gender- and age- matched healthy controls will be included and assessed at similar time points. Assessments will include a battery of neuropsychological tests, questionnaires, blood samples, and Magnetic Resonance Imaging (MRI). The main objectives of the study are to investigate: 1. Changes in cognitive functions over the course of treatment with ICIs. 2. Possible associations between changes in cognitive function and immune markers during and following ICI treatment. 3. Possible associations between changes in cognitive function and changes in brain morphology. 4. Changes over time in other possible adverse effects of ICI treatment, including psychological distress, sleep disturbances, and fatigue.
Study Type
OBSERVATIONAL
Enrollment
100
Aarhus University Hospital
Aarhus, Denmark
Attention
Changes in attention as measured with WAIS-IV The Digit Span Forwards (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Attention
Changes in attention as measured with Paced Auditory Serial Addition Test (scores ranging from a minimum of 0 and a maximum of 60 with higher scores indicating a better outcome)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Processing Speed
Changes in processing speed as measured with WAIS-IV The Digit Symbol coding (scores ranging from a minimum of 0 and a maximum of 135 with higher scores indicating a better outcome)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Processing Speed
Changes in processing speed as measured with Trail Making Test A (outcome is time in seconds)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Working memory
Changes in working memory as measured with WAIS-IV The Digit Span Backwards (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Working memory
Changes in working memory as measured with WAIS-IV The Digit Span Ranking (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Learning and memory
Changes in learning and memory as measured with the Hopkins Verbal Learning Test - Revised (part 1 include a minimum score of 0 and a maximum score of 36 with higher score indicating a better outcome, part 2 include a minimum score of 0 and a maximum score of 12 with higher scores indicating better outcomes)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Learning and memory
Changes in learning and memory as measured with Brief Visuospatial Memory Test - Revised (part 1 include a minimum score of 0 and a maximum score of 18 with a higher score indicating a better outcome, part 2 include a minimum score of 0 and a maximum score of 6 with higher scores indicating better outcomes)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Visuospatial ability
Changes in visuospatial ability as measured with WAIS-IV Matrix Reasoning (scores with a minimum of 0 and a maximum of 26 with higher scores indicating better outcomes)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Verbal fluency
Changes in verbal fluency as measured with the Controlled Oral Word Association Test, letter and animal (as many words as possible, more words indicating a better outcome. No maximum value)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Executive function
Changes in executive function as measured with the Trail Making Test B (outcome is time in seconds)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Cancer-related fatigue
Changes in fatigue severity as measured with The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT fatigue) scale (range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Sleep quality
Changes in sleep quality as measured with the Insomnia Severity Index (ISI) (scores ranging from a minimum of 0 and a maximum of 28 with higher scores indicating higher levels of insomnia)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Sleep quality
Changes in sleep quality as measured with the Pittsburgh Sleep Quality Index (PSQI) (scores ranging form a minimum of 0 indicating no difficulty and a maximum of 21 indicating severe difficulties in all areas related to sleep)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Perceived cognitive functioning
Changes in perceived cognitive functioning as measured with The Patient Assessment of Own Functioning Inventory (PAOFI) (outcome is scores ranging from a minimum of 35 to a maximum of 210)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Depression/Anxiety
Changes in depression/anxiety as measured with the Hospital Anxiety and Depression Scale (HADS) (range from a minimum score of 0 to a maximum score of 21 in which a higher scores mean higher levels of depression/anxiety)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Sickness behavior
Changes in subjective sickness behavior as measured with the Sickness Questionnaire (SicknessQ) (scores ranging from a minimum of 0 and a maximum of 30 with higher scores indicating worse outcome)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
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Health-related quality of life
Changes in health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life questionnaire for cancer patients (EORTC QLQ-C30) (all of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.)
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Moderator: genotype
Genotype of COMT and APOE4 Genotype of COMT
Time frame: Baseline
Inflammatory immune markers
TNF-α, IL-6, IL-8, IL-21, CRP, IP-10 and MCP-1 extracted from blood samples
Time frame: Baseline, and week 8, 24 and 12 weeks after completed treatment
Brain grey matter
Changes in brain grey matter as measured with T1-weighted MRI
Time frame: Baseline and week 24.
Brain white matter
Changes in brain white matter as measured with T1-weighted MRI
Time frame: Baseline and week 24.