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1Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
2Department of Public Health, Yonsei University, Seoul, Korea
3Department of Surgery, Ajou University School of Medicine, Suwon, Korea
4Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
5Department of Medicine, University of California, San Francisco, CA, USA
© 2021, Korean Society of Epidemiology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare for this study.
FUNDING
This study was supported by a National Research Foundation of Korea grant funded by the Ministry of Science and ICT (grant number 2020R1C1C1003502).
AUTHOR CONTRIBUTIONS
Conceptualization: KK, SJJ. Data curation: KK, SJJ. Formal analysis: KK. Funding acquisition: SJJ. Methodology: KK, SJJ. Project administration: KK. Visualization: KK, SJJ. Writing – original draft: KKH, SJJ. Writing – review & editing: KK, CWK, AS, HK, SJJ.
Values are presented as hazard ratio (95% confidence interval).
Overall, chemotherapy and radiotherapy were not significantly associated with cognitive impairment in colorectal cancer. Folate therapy was negatively associated with cognitive impairment. When analyzed by regimen, FOLFOX and FOLFOXIRI decreased the risk of cognitive impairment, while the CapeOx and capecitabine-only regimens were positively associated with cognitive impairment.
FOLFOX, folate, 5-fluorouracil (5-FU). oxaliplatin; FOLFIRI, folate, 5-FU, irinotecan; FOLFOXIRI, folate, 5-FU, oxaliplatin, irinotecan; CapeOx: capecitabine, oxaliplatin.
1 All models are adjusted for age, sex, Charlson comorbidity index, and monthly insurance premium.
Characteristics | Colon cancer (n=66,733) | Rectal cancer (n=28,570) | ||||
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Primary resection only (n=52,587) | Resection with chemotherapy (n=14,146) | Primary resection only (n=14,707) | Resection with chemotherapy (n=2,604) | Resection with radiotherapy (n=8,098) | Resection with concurrent chemoradiotherapy (n=3,161) | |
Age | 64.52±11.99 | 61.31±11.05 | 65.10±11.55 | 61.52±10.78 | 60.56±11.16 | 59.34±10.99 |
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Male | 30,588 (58.2) | 8,474 (59.9) | 8,940 (60.8) | 1,726 (66.3) | 5,282 (65.2) | 2,185 (69.12) |
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Charlson comorbidity index | ||||||
2 | 1,243 (2.4) | 552 (3.9) | 323 (2.2) | 92 (3.5) | 335 (4.1) | 161 (5.1) |
3 | 3,235 (6.2) | 1,376 (29.8) | 830 (5.6) | 273 (10.5) | 818 (10.1) | 424 (13.4) |
4 | 5,218 (9.9) | 2,069 (28.4) | 1,419 (9.7) | 407 (15.6) | 1,205 (14.9) | 532 (16.8) |
5 | 7,094 (13.5) | 2,440 (17.3) | 1,928 (13.1) | 467 (18.0) | 1,359 (16.8) | 566 (17.9) |
6 | 7,999 (15.2) | 2,255 (15.9) | 2,295 (15.6) | 428 (16.4) | 1,317 (16.3) | 509 (16.1) |
7 | 7,886 (15.0) | 1,940 (13.7) | 2,377 (16.2) | 358 (13.8) | 1,090 (13.5) | 377 (11.9) |
8 | 6,848 (13.0) | 1,456 (17.5) | 1,952 (13.3) | 246 (9.5) | 790 (9.8) | 259 (8.2) |
9 | 5,222 (9.9) | 997 (7.1) | 1,446 (9.8) | 151 (5.8) | 531 (6.6) | 176 (5.6) |
≥10 | 7,842 (14.9) | 1,061 (7.5) | 2137 (14.5) | 182 (7.0) | 653 (8.1) | 157 (5.0) |
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Insurance premium, percentile (KRW/mo) | ||||||
0 | 2,361 (4.5) | 545 (3.8) | 744 (5.1) | 115 (4.4) | 290 (3.6) | 115 (3.6) |
<20th (<18,700) | 9,910 (18.8) | 2,832 (20.0) | 2,876 (19.6) | 547 (21.0) | 1,531 (18.9) | 680 (21.5) |
20th–40th (18,700–31,109) | 9,314 (17.7) | 2,682 (19.0) | 2,669 (18.1) | 520 (20.0) | 1,561 (19.3) | 655 (20.7) |
40–60th (31,110–44,169) | 10,280 (19.5) | 2,743 (19.4) | 2,882 (19.6) | 516 (19.8) | 1,656 (20.4) | 596 (18.8) |
60th–80th (44,170–63,749) | 10,671 (20.3) | 2,841 (20.1) | 2,969 (20.2) | 482 (18.5) | 1,657 (20.5) | 604 (19.1) |
≥80th (≥63,750) | 10,051 (19.1) | 2,503 (17.7) | 2,567 (17.4) | 424 (16.3) | 1,403 (17.3) | 511 (16.2) |
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Observed person-years | 5.57±3.95 | 3.21±2.79 | 6.08±4.14 | 3.07±2.81 | 6.36±3.82 | 3.52±2.59 |
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Incidence rate of cognitive impairment, per 1,000 person-years | 22.17 | 14.48 | 23.16 | 12.65 | 13.12 | 10.69 |
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All-cause mortality rate, per 1,000 person-years | 49.05 | 96.52 | 47.5 | 107.33 | 54.75 | 123.66 |
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Chemotherapy regimen combination | ||||||
FOLFOX | - | 4,508 (31.9) | - | 776 (29.8) | - | 659 (20.8) |
FOLFIRI | - | 891 (6.3) | - | 205 (7.9) | - | 212 (6.7) |
FOLFOXIRI | - | 1,287 (9.1) | - | 284 (10.9) | - | 334 (10.6) |
CapeOx | - | 563 (4.0) | - | 114 (4.4) | - | 105 (3.3) |
Capecitabine only | - | 2,343 (16.6) | - | 436 (16.7) | - | 749 (23.7) |
5-fluorouracil only | - | 718 (5.1) | - | 223 (8.6) | - | 480 (15.2) |
Oxaliplatin only | - | 3,311 (23.4) | - | 462 (17.7) | - | 317 (10.0) |
Others | - | 1,088 (7.7) | - | 104 (4.0) | - | 305 (9.6) |
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Radiotherapy | ||||||
Single port | - | - | - | - | 4,775 (59.0) | 1,023 (32.4) |
Parallel port | - | - | - | - | 4,970 (61.4) | 1,013 (32.0) |
Rotation radiation | - | - | - | - | 29 (0.4) | 2 (0.1) |
3D radiotherapy | - | - | - | - | 3,860 (47.7) | 1,985 (62.9) |
Brachytherapy | - | - | - | - | 33 (0.4) | 8 (0.2) |
Density-modulated radiotherapy | - | - | - | - | 320 (3.9) | 685 (21.7) |
Proton therapy | - | - | - | - | 11 (0.1) | 16 (0.5) |
Variables | Colon cancer (n=66,733) | Rectal cancer (n=28,570) |
---|---|---|
Surgical resection only | 1.00 (reference) | 1.00 (reference) |
| ||
Chemotherapy, overall | 0.92 (0.83, 1.03) | 0.88 (0.75, 1.04) |
| ||
Folate therapy, overall | 0.66 (0.45, 0.97) | 0.52 (0.31, 0.88) |
| ||
Chemotherapy, by regimen | ||
FOLFOX | 0.44 (0.32, 0.60) | 0.53 (0.34, 0.82) |
FOLFIRI | 1.22 (0.77, 1.94) | 1.43 (0.87, 2.35) |
FOLFOXIRI | 0.85 (0.58, 1.27) | 0.49 (0.26, 0.91) |
CapeOx | 1.33 (0.82, 2.18) | 1.60 (0.93, 2.76) |
Capecitabine only | 1.37 (1.16, 1.62) | 1.01 (0.76, 1.34) |
5-FU only | 0.86 (0.54, 1.37) | 0.71 (0.47, 1.05) |
Oxaliplatin only | 0.73 (0.60, 0.89) | 0.91 (0.65, 1.29) |
Values are presented as mean±standard deviation or number (%). FOLFOX, folate, 5-fluorouracil and oxaliplatin; FOLFIRI, folate, 5-fluorouracil and irinotecan; FOLFOXIRI, folate, 5-fluorouracil, oxaliplatin and irinotecan; CapeOx, capecitabine and oxaliplatin; KRW, Korean won.
Values are presented as hazard ratio (95% confidence interval). Overall, chemotherapy and radiotherapy were not significantly associated with cognitive impairment in colorectal cancer. Folate therapy was negatively associated with cognitive impairment. When analyzed by regimen, FOLFOX and FOLFOXIRI decreased the risk of cognitive impairment, while the CapeOx and capecitabine-only regimens were positively associated with cognitive impairment. FOLFOX, folate, 5-fluorouracil (5-FU). oxaliplatin; FOLFIRI, folate, 5-FU, irinotecan; FOLFOXIRI, folate, 5-FU, oxaliplatin, irinotecan; CapeOx: capecitabine, oxaliplatin. All models are adjusted for age, sex, Charlson comorbidity index, and monthly insurance premium.