Introduction
Methods and materials
Patients
Non-cancer controls
Measures
Neuropsychological test | Description/cognitive domain |
---|---|
Hopkins verbal learning test-revised (HVLT-R) | Verbal memory test (12 target words, 6 parallel versions) |
1. HVLT-R immediate recall | Short-term verbal memory span |
2. HVLT-R delayed recall | Longer-term verbal memory |
3. HVLT-R recognition | Delayed verbal recognition (correct responses minus semantically related and unrelated false-positive errors) |
Trail making test (TMT) | Test of visual conceptual and visuomotor tracking |
4. TMT A | Psychomotor speed |
5. TMT B | Cognitive flexibility (aspect of executive functioning) |
Controlled oral word association test 6. COWA | Speeded verbal fluency test (requires aspects of executive functioning; 2 parallel versions) |
WAIS digit span | Forward and backward repetitions of series of digits |
7. Digit span forward | Immediate attention |
8. Digit span backward | Working memory |
WAIS digit symbol 9. Digit symbol | Symbol substitution test of information processing speed (requires visuomotor coordination and sustained attention) |
Lafayette grooved pegboard (GP) | A manipulative dexterity test |
10. GP dominant hand | Motor dexterity dominant hand |
11. GP non-dominant hand | Motor dexterity non-dominant hand |
Questionnaire | Description |
Hospital and Anxiety and Depression Scale (HADS) | Symptoms of anxiety and depression |
Multidimensional Fatigue Inventory (MFI) | Symptoms of general fatigue, physical fatigue, reduced activation, reduced motivation and mental fatigue |
Functional assessment of cancer therapy-brain (FACT-Br) | General quality of life (QOL) questionnaire that reflects symptoms or problems associated with brain malignancies across five scales |
Statistical analyses
Results
Participants’ characteristics
No. of patients (%) | No. of controls (%) | Test statistic | p value | |
---|---|---|---|---|
Number of participants | 92 | 104 | ||
Sex | χ2 = 0.18A | 0.67 | ||
Male | 47 (51) | 50 (48) | ||
Female | 45 (49) | 54 (52) | ||
Age in years, mean ± SD (range) | 62 ± 10 (31–80) | 59 ± 11 (31–87) | t = 1.53B | 0.13 |
Educational level | χ2 = 4.63A | 0.10 | ||
Low | 28 (31) | 25 (24) | ||
Middle | 37 (40) | 33 (32) | ||
High | 27 (29) | 46 (44) | ||
KPS | ||||
70–80 | 33 (36) | |||
90–100 | 59 (64) | N/A | ||
DS-GPA | ||||
Class I (3.5–4 points) | 8 (9) | N/A | ||
Class II (2.5–3 points) | 33 (35) | |||
Class III (1.5–2 points) | 44 (48) | |||
Class IV (0–1 points) | 7 (8) | |||
Primary cancer | ||||
Lung (NSCLC) | 55 (60) | N/A | ||
Renal | 15 (16) | |||
Melanoma | 12 (13) | |||
Other | 10 (11) | |||
Number of BM | ||||
1 | 32 (35) | |||
2–4 | 29 (31) | N/A | ||
5–10 | 31 (34) | |||
BM volume by patient (cm3) | ||||
Median (range) | 5.64 (0.02–31.15) | N/A | ||
Timing of BM diagnosis | ||||
Synchronous | 28 (30) | |||
Metachronous | 64 (70) | |||
Extracranial metastasesa | ||||
Yes | 66 (72) | |||
No | 26 (28) | N/A | ||
BM Symptoms at diagnosis | ||||
Symptomatic | 64 (70) | |||
Asymptomatic | 28 (30) | N/A | ||
Systemic therapy | ||||
No | 39 (42) | N/A | ||
Yes | 53 (58) | |||
Chemotherapyb | 37 (40) | |||
HADS scoresc, mean ± SD | ||||
Anxiety subscale | 7.3 ± 4.4 | 4.4 ± 2.8 | t = 5.36B | < 0.001 |
Depression subscale | 5.7 ± 4.1 | 3.5 ± 2.9 | t = 4.37B | < 0.001 |
Group-level cognitive performance
Test variables | Group level | Individual level | ||||||
---|---|---|---|---|---|---|---|---|
Mean Z scores of patients versus controlsa | Impaired performance per test variableb | |||||||
z score d | z test | p value | Effect sizee | Patients (%) | Controls (%) | χ2A | p value | |
HVLT-R immediate recall | − 0.52 | − 4.95 | < 0.001* | − 0.52 (medium) | 27.2 | 4.9 | 18.60 | < 0.001* |
HVLT-R delayed recall | − 0.27 | − 2.59 | 0.010* | − 0.27 (small) | 15.2 | 4.8 | 6.04 | 0.014* |
HVLT-R recognition | − 0.21 | − 1.99 | 0.047* | − 0.21 (small) | 14.3 | 8.7 | 1.54 | 0.215 |
TMT A | − 0.99 | − 9.21 | < 0.001* | − 0.99 (large) | 25.3 | 7.7 | 11.08 | 0.001* |
TMT B|Ac | − 1.49 | − 13.35 | < 0.001* | − 1.49 (large) | 28.8 | 5.8 | 17.99 | < 0.001* |
COWA | − 0.63 | − 6.06 | < 0.001* | − 0.63 (medium) | 27.2 | 7.7 | 13.23 | < 0.001* |
Digit span forward | − 0.43 | − 4.10 | < 0.001* | − 0.43 (small) | 10.9 | 5.8 | 1.64 | 0.200 |
Digit span backward | − 0.78 | − 7.51 | < 0.001* | − 0.78 (medium) | 22.8 | 6.8 | 10.15 | 0.001* |
Digit symbol | − 1.49 | − 13.78 | < 0.001* | − 1.49 (large) | 55.3 | 6.7 | 54.05 | < 0.001* |
GP dominant hand | − 1.43 | − 13.42 | < 0.001* | − 1.43 (large) | 27.3 | 6.9 | 14.41 | < 0.001* |
GP non-dominant hand | − 1.63 | − 15.25 | < 0.001* | − 1.63 (large) | 43.2 | 5.9 | 36.94 | < 0.001* |
Individual cognitive performance
No. of tests | Patients (%) (n = 76) | Controls (%) (n = 99) | χ2b | p value |
---|---|---|---|---|
≥ 1 test | 76.3 | 43.4 | 19.05 | < 0.001c |
≥ 2 tests | 61.8 | 18.2 | 35.10 | < 0.001c |
≥ 3 tests | 46.1 | 3.0 | 46.81 | < 0.001c |
≥ 4 tests | 36.8 | 3.0 | 33.72 | < 0.001c |
≥ 5 tests | 23.7 | 0 | 26.14 | < 0.001c |
≥ 6 tests | 14.5 | 0 | 15.29 | < 0.001c |
≥ 7 tests | 11.8 | 0 | 12.36 | < 0.001c |
≥ 8 tests | 6.6 | 0 | 6.71 | 0.010c |
≥ 9 tests | 0 | 0 | N/A | N/A |
≥ 10 tests | 0 | 0 | N/A | N/A |
11 tests | 0 | 0 | N/A | N/A |
Predictors of baseline cognitive performance
Test variable | Model | Predictor | B | SE B | p* | F(df) | R2 | ∆R2 | p* (∆R2) |
---|---|---|---|---|---|---|---|---|---|
HVLT-R immediate recall | Model 1 | 0.220 | 1.50 (3,88) | 0.049 | |||||
Number of BMSingle | − 0.635 | 0.363 | 0.084 | ||||||
Number of BM5–10 | 0.023 | 0.366 | 0.949 | ||||||
Total volume of BM | 0.002 | 0.020 | 0.922 | ||||||
Model 2 | 0.011* | 2.96 (6,85) | 0.173 | 0.124 | 0.008* | ||||
Number of BMSingle | − 0.554 | 0.353 | 0.120 | ||||||
Number of BM5–10 | − 0.081 | 0.352 | 0.818 | ||||||
Total volume of BM | 0.014 | 0.020 | 0.474 | ||||||
Chemotherapy | − 0.402 | 0.319 | 0.211 | ||||||
Symptomatic (y/n) | − 0.743 | 0.318 | 0.022* | ||||||
Timing of BM diagnosis | − 0.472 | 0.343 | 0.173 | ||||||
HVLT-R delayed recall | Model 1 | 0.046 | 2.77 (3,88) | 0.086 | |||||
Number of BMSingle | − 0.540 | 0.323 | 0.098 | ||||||
Number of BM5–10 | 0.326 | 0.754 | |||||||
Total volume of BM | 0.103 | 0.017 | 0.102 | ||||||
Model 2 | 0.013* | 3.10 (5,86) | 0.153 | 0.066 | 0.039* | ||||
Number of BMSingle | − 0.388 | 0.320 | 0.229 | ||||||
Number of BM5–10 | 0.095 | 0.319 | 0.766 | ||||||
Total volume of BM | − 0.030 | 0.017 | 0.079 | ||||||
Chemotherapy | − 0.291 | 0.290 | 0.319 | ||||||
Timing of BM diagnosis | − 0.533 | 0.308 | 0.087 | ||||||
HVLT-R recognition | Model 1 | 0.426 | 0.94 (3,87) | 0.031 | |||||
Number of BMSingle | − 0.166 | 0.356 | 0.642 | ||||||
Number of BM5–10 | 0.071 | 0.359 | 0.844 | ||||||
Total volume of BM | − 0.028 | 0.019 | 0.149 | ||||||
Model 2 | 0.014* | 3.04 (5,85) | 0.151 | 0.120 | 0.004* | ||||
Number of BMSingle | − 0.049 | 0.345 | 0.888 | ||||||
Number of BM5–10 | − 0.049 | 0.342 | 0.887 | ||||||
Total volume of BM | − 0.019 | 0.019 | 0.313 | ||||||
Symptomatic (y/n) | − 0.568 | 0.308 | 0.068 | ||||||
Timing of BM diagnosis | − 0.790 | 0.300 | 0.010* | ||||||
TMT A | Model 1 | 0.135 | 1.91 (3,82) | 0.065 | |||||
Number of BMSingle | − 0.425 | 0.458 | 0.356 | ||||||
Number of BM5–10 | 0.541 | 0.459 | 0.242 | ||||||
Total volume of BM | − 0.025 | 0.025 | 0.302 | ||||||
Model 2 | 0.005* | 3.42 (6,79) | 0.206 | 0.141 | 0.005* | ||||
Number of BMSingle | − 0.172 | 0.438 | 0.695 | ||||||
Number of BM5–10 | 0.504 | 0.433 | 0.249 | ||||||
Total volume of BM | − 0.020 | 0.023 | 0.389 | ||||||
Chemotherapy | − 0.572 | 0.398 | 0.154 | ||||||
Timing of BM diagnosis | − 0.299 | 0.434 | 0.492 | ||||||
Mental fatigue | − 0.109 | 0.046 | 0.021* | ||||||
TMT B|A | Model 1 | 0.683 | 0.501 (3,76) | 0.019 | |||||
Number of BMSingle | − 0.567 | 0.723 | 0.435 | ||||||
Number of BM5-10 | − 0.466 | 0.709 | 0.513 | ||||||
Total volume of BM | − 0.028 | 0.038 | 0.455 | ||||||
COWA | Model 1 | 0.289 | 1.27 (3,87) | 0.042 | |||||
Number of BMSingle | − 0.515 | 0.315 | 0.106 | ||||||
Number of BM5-10 | − 0.058 | 0.318 | 0.856 | ||||||
Total volume of BM | − 0.006 | 0.017 | 0.708 | ||||||
Model 2 | 0.091 | 1.97 (5,85) | 0.104 | 0.062 | 0.059 | ||||
Number of BMSingle | − 0.419 | 0.312 | 0.183 | ||||||
Number of BM5–10 | − 0.036 | 0.311 | 0.908 | ||||||
Total volume of BM | − 0.010 | 0.017 | 0.562 | ||||||
Timing of BM diagnosis | − 0.360 | 0.275 | 0.195 | ||||||
Reduced motivation | − 0.059 | 0.033 | 0.078 | ||||||
Digit span forward | Model 1 | 0.741 | 0.417 (3,88) | 0.014 | |||||
Number of BMSingle | 0.015 | 0.240 | 0.950 | ||||||
Number of BM5–10 | 0.069 | 0.242 | 0.777 | ||||||
Total volume of BM | − 0.014 | 0.013 | 0.276 | ||||||
Digit span backward | Model 1 | 0.163 | 1.75 (3,88) | 0.083 | |||||
Number of BMSingle | − 0.128 | 0.267 | 0.632 | ||||||
Number of BM5–10 | − 0.144 | 0.269 | 0.594 | ||||||
Total volume of BM | − 0.029 | 0.014 | 0.046 | ||||||
Model 2 | 0.108 | 1.96 (4,87) | 0.083 | 0.026 | 0.118 | ||||
Number of BMSingle | − 0.167 | 0.266 | 0.532 | ||||||
Number of BM5–10 | − 0.188 | 0.268 | 0.486 | ||||||
Total volume of BM | − 0.022 | 0.015 | 0.138 | ||||||
Symptomatic (y/n) | − 0.379 | 0.240 | 0.118 | ||||||
Digit symbol | Model 1 | 0.518 | 0.764 (3,80) | 0.028 | |||||
Number of BMSingle | 0.063 | 0.343 | 0.855 | ||||||
Number of BM5–10 | − 0.033 | 0.353 | 0.925 | ||||||
Total volume of BM | − 0.028 | 0.019 | 0.150 | ||||||
Model 2 | 0.010* | 3.03 (6,77) | 0.191 | 0.163 | 0.003* | ||||
Number of BMSingle | 0.226 | 0.324 | 0.488 | ||||||
Number of BM5–10 | − 0.058 | 0.328 | 0.859 | ||||||
Total volume of BM | − 0.023 | 0.018 | 0.210 | ||||||
Timing of BM diagnosis | − 0.625 | 0.295 | 0.037* | ||||||
Mental fatigue | − 0.041 | 0.038 | 0.281 | ||||||
Symptoms of depression | − 0.068 | 0.037 | 0.072 | ||||||
GP dominant hand | Model 1 | 0.511 | 0.78 (3,83) | 0.027 | |||||
Number of BMSingle | − 0.720 | 0.771 | 0.353 | ||||||
Number of BM5–10 | − 0.558 | 0.787 | 0.480 | ||||||
Total volume of BM | − 0.038 | 0.041 | 0.361 | ||||||
Model 2 | 0.194 | 1.56 (4,82) | 0.070 | 0.043 | 0.054 | ||||
Number of BMSingle | − 0.602 | 0.761 | 0.431 | ||||||
Number of BM5–10 | − 0.555 | 0.774 | 0.475 | ||||||
Total volume of BM | − 0.030 | 0.041 | 0.466 | ||||||
Mental fatigue | − 0.152 | 0.078 | 0.054 | ||||||
GP non-dominant hand | Model 1 | 0.977 | 0.07(3,84) | 0.002 | |||||
Number of BMSingle | − 0.238 | 0.601 | 0.693 | ||||||
Number of BM5–10 | − 0.238 | 0.609 | 0.697 | ||||||
Total volume of BM | − 0.002 | 0.032 | 0.961 | ||||||
Model 2 | 0.018* | 2.73(6, 81) | 0.168 | 0.166 | 0.002* | ||||
Number of BMSingle | − 0.137 | 0.576 | 0.813 | ||||||
Number of BM5–10 | − 0.312 | 0.571 | 0.587 | ||||||
Total volume of BM | − 0.002 | 0.030 | 0.949 | ||||||
KPS | 0.031 | 0.029 | 0.284 | ||||||
Timing of BM diagnosis | − 1.03 | 0.526 | 0.054 | ||||||
Reduced activity | − 0.117 | 0.062 | 0.062 |