Background
Methods
Participants and procedure
Neuropsychological tests and self-report questionnaires
Biomarkers
Statistical analyses
Results
Participants
Neuropsychological tests
Patients VEGFR TKI (n = 30) | Patient controls (n = 20) | Healthy controls (n = 30) |
P
| ||||
---|---|---|---|---|---|---|---|
Characteristics | |||||||
Age, years | |||||||
Mean | 60 | 62 | 58 | 0.456e
| |||
Range | 38-81 | 30-75 | 45-73 | ||||
Sex (%) | |||||||
Male | 27 | (90) | 15 | 75 | 26 | (87) | 0.329f
|
Female | 3 | (10) | 5 | 25 | 4 | (13) | |
Median education level (SD)d
| 4 | (1.21) | 5 | (1.12) | 5 | (0.80) | 0.546g
|
Estimation IQ (SD) | 102.30 | (10.37) | 106.20 | (10.55) | 106.37 | (8.09) | |
Median free testosteronec pmol/L (IQR 25-75) | 165.00 | (129,5-238.00) | 237.50 | (200.75-299.25) | - | - | 0.005a
|
Median estradiol pmol/l† (IQR 25-75) | 48.00 | (42-55) | 78.50 | (78.5-112.5) | - | - | 0.000 a
|
Median albumin g/l (IQR 25-75) | 39.00 | (34.50-40.25) | 37.50 | (35.25-40.00) | - | - | 0.599a
|
Median CRP mg/l (IQR 25-75) | 10.00 | (4.00-21.75) | 5.00 | (4.00-38.25) | - | - | 0.849a, b
|
Median absolute neutrophil count 109/l (IQR 25-75) | 2.95 | (2.08-3.66) | 3,89 | (3.43-5.64) | - | - | 0.009a
|
Median ESR mm/hour (IQR 25-75) | 20.00 | (8.75-34.50) | 19.00 | (7.00-31.00) | - | - | 0.767a, b
|
Median glucose mmol/l (IQR 25-75) | 5.6 | (4.9-5.98) | 5.8 | (5.35-7.55) | - | - | 0.010a
|
Median TSH mE/l (IQR 25-75) | 2.29 | (1.49-3.63) | 1.12 | (0.78-2.04) | - | - | 0.003a, b
|
Median LDH U/l (IQR 25-75) | 463.50 | (402.25-526.50) | 346.50 | (314.50-458.00) | - | - | 0.008a, b
|
Median VEGF ng/ml (IQR 25-75) | 1.62 | (1.09-2.18) | 1.48 | (1.21-2.00) | - | - | 0.221a
|
Patients VEGFR TKI | Patient controls | Healthy controls | ||||
---|---|---|---|---|---|---|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
| |
Learning & memory
| ||||||
Working memory
| -0.26 | 0.93 | 0.11 | 0.95 | 0.19 | 0.79 |
Digit span backwards WAIS-III | 5.67 | 1.77 | 6.40 | 1.98 | 6.37 | 1.75 |
Letter-number sequencing WAIS-III | 9.47 | 2.27 | 10.15 | 2.08 | 10.50 | 1.59 |
Episodic memory
| -0.31*** | 0.89 | -0.11* | 0.74 | 0.38 | 0.56 |
RAVLT total score | 33.70 | 8.01 | 37.55 | 8.25 | 39.77 | 5.76 |
RAVLT delayed recall | 5.87 | 2.57 | 7.00 | 2.32 | 7.37 | 2.50 |
RAVLT delayed recognition | 26.33 | 3.02 | 27.70 | 1.59 | 28.03 | 1.45 |
RBMT story (Immediate Recall) | 9.62 | 2.75 | 9.42 | 3.14 | 11.75 | 2.51 |
RBMT story (Delayed Recall) | 8.43 | 3.51 | 7.85 | 3.30 | 10.38 | 2.56 |
Semantic memory
| -0.36*** | 0.97 | -0.26** | 0.89 | 0.53 | 0.88 |
Semantic fluency (Animal) | 22.47 | 5.49 | 22.95 | 4.39 | 26.73 | 5.22 |
Semantic fluency (Profession) | 16.30 | 4.65 | 16.80 | 5.19 | 20.70 | 4.21 |
Attention & concentration
| ||||||
Alertness
| -0.17 | 0.88 | 0.17 | 0.68 | 0.06 | 0.59 |
Digit span forwards WAIS-III | 8.23 | 2.05 | 9.20 | 1.94 | 8.47 | 1.28 |
TAP 2.1 alertnessa
| 256.28 | 51.96 | 248.40 | 35.52 | 240.75 | 27.45 |
Sustained attention
| -0.22 | 0.93 | 0.18 | 1.16 | 0.10 | 0.94 |
d2 test | 138.63 | 30.93 | 151.60 | 38.33 | 149.03 | 31.25 |
Executive functions
| ||||||
Response generation
| -0.26* | 0.91 | -0.13 | 1.23 | 0.35 | 0.83 |
Letter fluency (COWAT) | 32.97 | 9.28 | 34.25 | 12.58 | 39.17 | 8.46 |
Response inhibition
| -0.04 | 1.05 | 0.01 | 1.05 | 0.04 | 0.95 |
Stroop color word test (Interference)a
| 0.70 | 0.30 | 0.73 | 0.47 | 0.65 | 0.21 |
Mental flexibility
| -0.29 | 0.98 | 0.11 | 1.13 | 0.22 | 0.88 |
TAP flexibility (Alternation)a
| 900.37 | 353.23 | 824.40 | 405.37 | 732.03 | 177.52 |
Problem solving
| -0.19* | 0.88 | -0.18* | 0.85 | 0.31 | 0.74 |
Raven APM (Set I) | 8.00 | 2.23 | 8.10 | 2.02 | 9.50 | 1.93 |
Brixton spatial anticipation Test | 36.97 | 6.06 | 36.90 | 6.31 | 38.83 | 5.43 |
Self-report questionnaires
Patients VEGFR TKI | Patient controls | Healthy controls | ||||
---|---|---|---|---|---|---|
Mean
|
SD
|
Mean
|
SD
|
Mean
|
SD
| |
SCL-90-R
| ||||||
Anxiety | 13.07** | 3.10 | 12.75* | 3.06 | 11.10 | 1.71 |
Depression | 23.87*** | 6.31 | 22.55** | 5.32 | 18.20 | 2.68 |
Sleep disturbance | 4.93 | 2.57 | 5.00 | 2.03 | 4.10 | 1.40 |
Agoraphobia | 7.90 | 2.01 | 8.10 | 2.20 | 7.40 | 0.77 |
Somatization | 19.23*** | 5.73 | 17.40* | 6.07 | 14.17 | 3.18 |
Cognitive-performance difficulty | 14.77** | 4.68 | 14.75** | 4.82 | 11.43 | 2.13 |
Interpersonal sensitivity and paranoid ideation | 20.90 | 3.63 | 22.50 | 5.69 | 20.87 | 3.15 |
Anger-hostility | 6.90 | 1.27 | 6.90 | 1.12 | 6.43 | 0.86 |
Total score | 123.10*** | 24.13 | 121.80** | 26.81 | 103.67 | 11.88 |
CFQ
| ||||||
Total score | 93.37 | 13.20 | 89.55 | 10.13 | 91.80 | 9.64 |
BDI-II
| ||||||
Total score | 9.87*** | 5.76 | 8.25** | 5.78 | 3.60 | 2.98 |
CIS20r
| ||||||
Total score | 67.67*** | 26.75 | 61.05* | 21.11 | 46.60 | 16.24 |
Biomarkers
Patients VEGFR TKI | Patient controls | Patients VEGFR TKI | Patient controls | Patients VEGFR TKI | Patient controls | Patients VEGFR TKI | Patient controls | |||||||||
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Neuropsychological tests
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Learning & memory
| -0.427 | 0.019 | -0.410 | 0.030 | ||||||||||||
Working memory
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Episodic memory
| -0.432 | 0.017 | ||||||||||||||
Semantic memory
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Attention & concentration
| -0.440 | 0.019 | ||||||||||||||
Alertness
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Sustained attention
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Executive functions
| -0.376 | 0.049 | ||||||||||||||
Response generation
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Response inhibition
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Mental flexibility
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Problem solving
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Self-reported questionnaires
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SLC90-R total score
| -0.626 | 0.004 | ||||||||||||||
Anxiety | -0.526 | 0.021 | ||||||||||||||
Depression | -0.518 | 0.023 | ||||||||||||||
Sleep disturbance | ||||||||||||||||
Agoraphobia | ||||||||||||||||
Somatization | -0.476 | 0.039 | ||||||||||||||
Cognitive-performance difficulty | -0.540 | 0.017 | ||||||||||||||
Interpersonal sensitivity and paranoid ideation | -0.638 | 0.003 | ||||||||||||||
Anger-hostility | -0.729 | 0.000 | ||||||||||||||
CFQ total score
| -0.754 | 0.000 | ||||||||||||||
BDI-II total score
| 0.379 | 0.039 | 0.378 | 0.047 | 0.464 | 0.010 | -0.622 | 0.004 | ||||||||
CIS20r total score
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CIS fatigue | ||||||||||||||||
CIS motivation | ||||||||||||||||
CIS concentration | -0.466 | 0.045 | ||||||||||||||
CIS activation |