Background
Methods
Training cohort
Treatment
Validation cohort
Statistical analysis
Results
Patient characteristics and survival
Characteristic | Number (%) | Training cohort |
P-value | Validation cohort Number (%) | |
---|---|---|---|---|---|
SMAD | |||||
Absent | Present | ||||
Age, years | 0.379 | ||||
< 45 | 1404 (52.3%) | 1311 (93.4%) | 93 (6.6%) | 679 (51.1%) | |
≥ 45 | 1281 (47.7%) | 1185 (92.5%) | 96 (7.5%) | 650 (48.9%) | |
Sex | 0.025 | ||||
Male | 2131 (79.4%) | 1969 (92.4%) | 162 (7.6%) | 986 (74.2%) | |
Female | 554 (20.6%) | 527 (95.1%) | 27 (4.9%) | 343 (25.8%) | |
Smoking Status | 0.055 | ||||
Absent | 1708 (63.3%) | 1600 (93.7%) | 108 (6.3%) | 795 (59.8%) | |
Present | 977 (36.4%) | 896 (91.7%) | 81 (8.3%) | 534 (40.2%) | |
Drinking Status | 0.873 | ||||
Absent | 2382 (88.7%) | 2215 (93.0%) | 167 (7.0%) | 1117 (84.0%) | |
Present | 303 (11.3%) | 281 (92.7%) | 22 (7.3%) | 212 (16.0%) | |
Family history | 0.566 | ||||
Absent | 1926 (71.7%) | 1787 (92.8%) | 139 (7.2%) | 967 (72.8%) | |
Present | 759 (28.3%) | 709 (93.4%) | 50 (6.6%) | 362 (27.2%) | |
Calcium, mmol/L | 0.932 | ||||
< 2.4 | 1370 (51.0%) | 1273 (92.9%) | 97 (7.1%) | 501 (37.7%) | |
≥ 2.4 | 1315 (49.0%) | 1223 (93.0%) | 92 (7.0%) | 828 (62.3%) | |
Phosphorus, mmol/L | 0.587 | ||||
< 1.15 | 1398 (52.1%) | 1296 (92.7%) | 102 (7.3%) | 676 (50.9%) | |
≥ 1.15 | 1287 (47.9%) | 1200 (93.2%) | 87 (6.8%) | 653 (49.1%) | |
Magnesium, mmol/L | 0.308 | ||||
< 0.93 | 1410 (52.2%) | 1304 (92.5%) | 106 (7.5%) | 919 (69.1%) | |
≥ 0.93 | 1275 (47.5%) | 1192 (93.5%) | 83 (6.5%) | 410 (30.9%) | |
CRP, mg/L | < 0.001 | ||||
< 1.91 | 1345 (50.1%) | 1283 (95.4%) | 62 (4.6%) | 722 (54.3%) | |
≥ 1.91 | 1340 (49.9%) | 1213 (90.5%) | 127 (9.5%) | 607 (45.7%) | |
WBCs, ×109
| 0.137 | ||||
< 6.9 | 1376 (51.2%) | 1289 (93.7%) | 87 (6.3%) | 677 (50.9%) | |
≥ 6.9 | 1309 (48.8%) | 1207 (92.2%) | 102 (7.8%) | 652 (49.1%) | |
Neutrophils, ×109
| 0.001 | ||||
< 4.2 | 1356 (50.5%) | 1283 (94.6%) | 73 (5.4%) | 691 (52.0%) | |
≥ 4.2 | 1329 (49.5%) | 1213 (91.3%) | 116 (8.7%) | 638 (48.0%) | |
HGB, g/L | |||||
< 145 | 1379 (51.4%) | 1264 (91.7%) | 115 (8.3%) | 0.007 | 758 (57.0%) |
≥ 145 | 1306 (48.6%) | 1232 (94.3%) | 74 (5.7%) | 571 (43.0%) | |
Platelets, ×109
| 0.013 | ||||
< 229 | 1343 (50.0%) | 1265 (94.2%) | 78 (5.8%) | 638 (48.0%) | |
≥ 229 | 1342 (50.0%) | 1231 (91.7%) | 111 (8.3%) | 691 (52.0%) | |
ALT, U/L | 0.392 | ||||
< 22.2 | 1345 (50.1%) | 1256 (93.4%) | 89 (6.6%) | 725 (54.6%) | |
≥ 22.2 | 1340 (49.9%) | 1240 (92.5%) | 100 (7.5%) | 604 (45.4%) | |
AST, U/L | 0.092 | ||||
< 21 | 1366 (50.9) | 1281 (93.8%) | 85 (6.2%) | 675 (50.8%) | |
≥ 21 | 1319 (49.1%) | 1215 (92.1%) | 104 (7.9%) | 654 (49.2%) | |
ALP, U/L | < 0.001 | ||||
< 70 | 1357 (50.5%) | 1304 (96.1%) | 53 (3.9%) | 744 (56.0%) | |
≥ 70 | 1328 (49.5%) | 1192 (89.8%) | 136 (10.2%) | 585 (44.0%) | |
LDH, U/L | < 0.001 | ||||
< 172.2 | 1344 (50.1%) | 1287 (95.8%) | 57 (4.2%) | 706 (53.1%) | |
≥ 172.2 | 1341 (49.9%) | 1209 (90.2%) | 132 (9.8%) | 623 (46.9%) | |
ALB, g/L | 0.003 | ||||
< 44.9 | 1351 (50.3%) | 1236 (91.5%) | 115 (8.5%) | 576 (43.3%) | |
≥ 44.9 | 1334 (49.7%) | 1260 (94.5%) | 74 (5.5%) | 753 (56.7%) | |
GLB, g/L | 0.507 | ||||
< 30.5 | 1341 (49.9%) | 1251 (93.3%) | 90 (6.7%) | 793 (59.7%) | |
≥ 30.5 | 1344 (50.1%) | 1245 (92.6%) | 99 (7.4%) | 536 (40.3%) | |
Cholesterol, mmol/L | 0.054 | ||||
< 5.12 | 1353 (50.4%) | 1245 (92.0%) | 108 (8.0%) | 576 (43.3%) | |
≥ 5.2 | 1332 (49.6%) | 1251 (93.9%) | 81 (6.1%) | 753 (56.7%) | |
T lymphocytes, ×109
| 0.289 | ||||
< 1.8 | 1392 (51.8%) | 1287 (92.5%) | 105 (7.5%) | 622 (46.8%) | |
≥ 1.8 | 1293 (48.2%) | 1209 (93.5%) | 84 (6.5%) | 707 (53.2%) | |
Monocytes, ×109
| 0.005 | ||||
< 0.4 | 1385 (51.6%) | 1306 (94.3%) | 79 (5.7%) | 462 (34.8%) | |
≥ 0.4 | 1300 (48.4%) | 1190 (91.5%) | 110 (8.5%) | 867 (65.2%) | |
Pathology | 0.852 | ||||
Undifferentiated | 2592 (96.5%) | 2410 (93.0%) | 182 (7.0%) | 1300 (97.8%) | |
Differentiated | 93 (3.5%) | 86 (92.5%) | 7 (7.5%) | 29 (2.2%) | |
Cranial nerve injury | 0.730 | ||||
Absent | 2498 (93.0%) | 2321 (92.9%) | 177 (7.1%) | 1234 (92.9%) | |
Present | 187 (7.0%) | 175 (93.6%) | 12 (6.4%) | 95 (7.1%) | |
EBV-DNA, copies/ml | < 0.001 | ||||
< 1000 | 1130 (42.1%) | 1092 (96.6%) | 38 (3.4%) | 526 (39.6%) | |
1000–9999 | 585 (21.8%) | 555 (94.9%) | 30 (5.1%) | 265 (19.9%) | |
10,000–99,999 | 599 (22.3%) | 555 (92.7%) | 44 (23.3%) | 325 (24.5%) | |
100,000–999,999 | 290 (10.8%) | 245 (84.5%) | 45 (15.5%) | 156 (11.7%) | |
≥ 1,000,000 | 81 (3.0%) | 49 (60.5%) | 32 (39.5%) | 57 (4.3%) | |
T category | 0.804 | ||||
1 | 167 (6.2%) | 158 (94.6%) | 37 (5.4%) | 81 (6.1%) | |
2 | 525 (19.6%) | 488 (93.0%) | 37 (7.0%) | 328 (24.7%) | |
3 | 1374 (51.2%) | 1278 (93.0%) | 96 (7.0%) | 630 (47.4%) | |
4 | 619 (23.1%) | 572 (92.4%) | 47 (7.6%) | 290 (21.8%) | |
N category | < 0.001 | ||||
0 | 319 (11.9%) | 312 (97.8%) | 7 (2.2%) | 250 (18.8%) | |
1 | 921 (34.3%) | 887 (96.3%) | 34 (3.7%) | 449 (33.8%) | |
2 | 775 (28.9%) | 697 (89.9%) | 78 (10.1%) | 370 (27.8%) | |
3 | 549 (20.4%) | 494 (90.0%) | 55 (10.0%) | 243 (18.3%) | |
4 | 121 (4.5%) | 106 (87.6%) | 15 (12.4%) | 17 (1.3%) | |
Radiotherapy technique | 0.451 | ||||
IMRT +3DCRT | 1341(49.9%) | 1252 (93.4%) | 89 (6.6%) | 705(65.9%) | |
CRT | 1344(51.1%) | 1244 (92.6%) | 100 (7.4%) | 624(34.1%) | |
Treatment method |
P < 0.001 | ||||
Radiotherapy | 505(18.8%) | 481 (95.2%) | 24 (4.8%) | 318 (24.1%) | |
CCRT | 1136 (42.3%) | 1086 (95.6%) | 50(4.4%) | 425 (32.2%) | |
Neo + radiotherapy | 483 (18.0%) | 419 (86.7%) | 64 (13.3%) | 265 (20.1%) | |
Neo + CCRT | 561(20.9%) | 510 (90.9%) | 51(9.1%) | 311 (23.5%) | |
SMAD | |||||
Absent | 2496 (93.0%) | 1231 (92.6%) | |||
Present | 189 (7%) | 98 (7.4%) |
Univariate and multivariate analyses
Characteristic | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95% CI |
P-value | HR | 95% CI |
P-value | |
Age (≥ 45 vs. < 45 years) | 1.142 | 0.850–1.535 | 0.379 | |||
Gender (Male vs. Female) | 0.623 | 0.410–0.946 | 0.027 | |||
Smoking Status (Present vs. Absent) | 1.139 | 0.993–1.807 | 0.056 | |||
Drinking Status (Present vs. Absent) | 1.038 | 0.655–1.647 | 0.873 | |||
Family history (Present vs. Absent) | 0.907 | 0.649–1.267 | 0.566 | |||
Calcium, mmol/L (≥ 2.4 vs. < 2.4) | 0.987 | 0.734–1.327 | 0.932 | |||
Phosphorus, mmol/L (≥ 1.15 vs. < 1.15) | 0.921 | 0.685–1.239 | 0.587 | |||
Magnesium, mmol/L (≥ 0.93 vs. < 0.93) | 0.857 | 0.636–1.154 | 0.308 | |||
CRP, mg/L (≥ 1.91 vs. < 1.91) | 2.167 | 1.583–2.965 | < 0.001 | |||
WBCs, ×109 (≥ 6.9 vs. < 6.9) | 1.252 | 0.931–1.684 | 0.137 | |||
Neutrophils, ×109 (≥ 4.2 vs. < 4.2) | 1.681 | 1.241–2.276 | 0.001 | |||
HGB, g/L (≥ 145 vs. < 145) | 0.660 | 0.488–0.893 | 0.007 | 0.672 | 0.477–0.948 | 0.023 |
Platelets, ×109 (≥ 229 vs. < 229) | 1.462 | 1.083–1.974 | 0.013 | |||
ALT, U/L (≥ 22.2 vs. < 22.2) | 1.138 | 0.846–1.530 | 0.392 | |||
AST, U/L (≥ 21 vs. < 21) | 1.290 | 0.958–1.736 | 0.093 | |||
ALP, U/L (≥ 70 vs. < 70) | 2.807 | 2.024–3.893 | < 0.001 | 2.148 | 1.509–3.056 | < 0.001 |
LDH, U/L (≥ 172.2 vs. < 172.2) | 2.465 | 1.789–3.396 | < 0.001 | 1.512 | 1.069–2.139 | 0.019 |
ALB, g/L (≥ 44.9 vs. < 44.9) | 0.631 | 0.466–0.854 | 0.003 | |||
GLB, g/L (≥ 30.5 vs. < 30.5) | 1.105 | 0.822–1.486 | 0.507 | |||
Cholesterol, mmol/L (≥ 5.12 vs. < 5.12) | 0.746 | 0.554–1.006 | 0.055 | |||
T lymphocytes, ×109 (≥ 1.8 vs. < 1.8) | 0.852 | 0.632–1.147 | 0.290 | |||
Monocytes, ×109 (≥ 0.4 vs. < 0.4) | 1.528 | 1.133–2.062 | 0.006 | |||
Pathology (Differentiated vs. Undifferentiated | 1.078 | 0.492–2.363 | 0.852 | |||
Cranial nerve injury (Absent vs. Present) | 0.899 | 0.491–1.646 | 0.899 | |||
EBV-DNA, copies/ml | < 0.001 | < 0.001 | ||||
< 1000 | 1.000 | 1.000 | 1.000 | 1.000 | ||
1000–9999 | 1.553 | 0.952–2.534 | 0.078 | 1.293 | 0.784–2.131 | 0.314 |
10,000–99,999 | 2.278 | 1.459–3.558 | < 0.001 | 1.588 | 0.998–2.530 | 0.051 |
100,000–999,999 | 5.278 | 3.354–8.307 | < 0.001 | 3.234 | 1.982–5.279 | < 0.001 |
≥ 1,000,000 | 18.767 | 10.822–32.544 | < 0.001 | 10.703 | 5.876–19.498 | < 0.001 |
T category | 0.805 | |||||
1 | 1.000 | 1.000 | ||||
2 | 1.331 | 0.629–2.818 | 0.455 | |||
3 | 1.319 | 0.653–2.663 | 0.440 | |||
4 | 1.443 | 0.692–3.007 | 0.328 | |||
N category | < 0.001 | 0.002 | ||||
0 | 1.000 | 1.000 | 1.000 | 1.000 | ||
1 | 1.708 | 0.750–3.893 | 0.202 | 1.292 | 0.559–2.984 | 0.549 |
2 | 4.988 | 2.276–10.933 | < 0.001 | 2.924 | 1.304–6.557 | 0.009 |
3 | 4.962 | 2.232–11.035 | < 0.001 | 2.299 | 0.996–5.306 | 0.051 |
4 | 6.307 | 2.504–15.887 | < 0.001 | 2.606 | 0.983–6.905 | 0.054 |
Characteristic | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95% CI |
P-value | HR | 95% CI |
P-value | |
Age (≥ 45 vs. < 45 years) | 1.288 | 1.008–1.647 | 0.043 | |||
Gender (Male vs. Female) | 0.867 | 0.635–1.184 | 0.371 | |||
Smoking Status (Present vs. Absent) | 1.120 | 0.871–1.440 | 0.376 | |||
Drinking Status (Present vs. Absent) | 0.911 | 0.615–1.349 | 0.642 | |||
Family history (Present vs. Absent) | 0.831 | 0.627–1.010 | 0.198 | |||
Calcium, mmol/L (≥ 2.4 vs. < 2.4) | 0.927 | 0.725–1.186 | 0.548 | |||
Phosphorus, mmol/L (≥ 1.15 vs. < 1.15) | 0.927 | 0.725–1.185 | 0.545 | |||
Magnesium, mmol/L (≥ 0.93 vs. < 0.93) | 0.804 | 0.552–1.172 | 0.257 | |||
CRP, mg/L (≥ 1.91 vs. < 1.91) | 2.092 | 1.618–2.706 | < 0.001 | 1.450 | 1.108–1.897 | 0.007 |
WBCs, ×109 (≥ 6.9 vs. < 6.9) | 1.050 | 0.822–1.342 | 0.694 | |||
Neutrophils, ×109 (≥ 4.2 vs. < 4.2) | 1.177 | 0.921–1.504 | 0.193 | |||
HGB, g/L (≥ 145 vs. < 145) | 0.835 | 0.653–1.068 | 0.150 | 0.023 | ||
Platelets, ×109 (≥ 229 vs. < 229) | 1.134 | 0.887–1.449 | 0.315 | |||
ALT, U/L (≥ 22.2 vs. < 22.2) | 0.971 | 0.760–1.241 | 0.814 | |||
AST, U/L (≥ 21 vs. < 21) | 1.283 | 1.003–1.641 | 0.047 | |||
ALP, U/L (≥ 70 vs. < 70) | 2.023 | 1.570–2.606 | < 0.001 | 1.654 | 1.275–2.145 | < 0.001 |
LDH, U/L (≥ 172.2 vs. < 172.2) | 1.951 | 1.514–2.514 | < 0.001 | 1.424 | 1.098–1.847 | < 0.001 |
ALB, g/L (≥ 44.9 vs. < 44.9) | 0.694 | 0.542–0.889 | 0.004 | |||
GLB, g/L (≥ 30.5 vs. < 30.5) | 1.594 | 1.242–2.047 | < 0.001 | |||
Cholesterol, mmol/L (≥ 5.12 vs. < 5.12) | 0.955 | 0.747–1.220 | 0.710 | |||
T lymphocytes, ×109 (≥ 1.8 vs. < 1.8) | 0.913 | 0.714–1.167 | 0.468 | |||
Monocytes, ×109 (≥ 0.4 vs. < 0.4) | 1.431 | 1.118–1.832 | 0.004 | |||
Pathology (Differentiated vs. Undifferentiated | 0.410 | 0.153–1.101 | 0.077 | |||
Cranial nerve injury (Absent vs. Present) | 1.075 | 0.666–1.736 | 0.767 | |||
EBV-DNA, copies/ml | < 0.001 | < 0.001 | ||||
< 1000 | 1.000 | 1.000 | 1.000 | 1.000 | ||
1000–9999 | 1.955 | 1.349–2.832 | < 0.001 | 1.521 | 1.045–2.215 | 0.029 |
10,000–99,999 | 2.757 | 1.959–3.881 | < 0.001 | 1.822 | 1.277–2.601 | 0.001 |
100,000–999,999 | 4.569 | 3.147–6.631 | < 0.001 | 2.706 | 1.829–4.004 | < 0.001 |
≥ 1,000,000 | 7.451 | 4.221–13.151 | < 0.001 | 4.764 | 1.829–8.533 | < 0.001 |
Treatment method | 0.040 | |||||
Radiotherapy | 1.000 | 1.000 | ||||
CCRT | 1.064 | 0.639–1.773 | 0.811 | |||
Neo + Radiotherapy | 0.188 | 0.834–2.521 | 0.188 | |||
Neo + CCRT | 0.752 | 0.426–1.325 | < 0.001 | |||
Radiotherapy technology (IMRT + 3DCRT vs. CRT) | 0.745 | 0.378–1.471 | 0.397 | |||
T category | 0.021 | |||||
1 | 1.000 | 1.000 | ||||
2 | 3.190 | 1.269–8.020 | 0.014 | |||
3 | 3.752 | 1.538–9.157 | 0.004 | |||
4 | 3.966 | 1.596–9.856 | 0.003 | |||
N category | < 0.001 | < 0.001 | ||||
0 | 1.000 | 1.000 | 1.000 | 1.000 | ||
1 | 1.731 | 0.928–3.230 | 0.085 | 1.432 | 0.765–2.681 | 0.262 |
2 | 3.017 | 1.638–5.558 | < 0.001 | 2.149 | 1.156–3.995 | 0.016 |
3 | 5.987 | 3.281–10.925 | < 0.001 | 3.613 | 1.947–6.704 | < 0.001 |
4 | 6.310 | 3.079–12.933 | < 0.001 | 3.629 | 1.742–7.559 | 0.001 |
Nomograms for predicting SMAD and SMFS
Model | Training set | Validation set | ||||
---|---|---|---|---|---|---|
C-index | 95% CI |
P-value | C-index | 95% CI |
P-value | |
Nomograms (SMAD) | 0.83 | 0.78–0.87 | 0.005 | 0.76 | 0.71–0.79 | < 0.001 |
TNM classification (SMAD) | 0.73 | 0.70–0.77 | 0.64 | 0.60–0.67 | ||
Nomograms (SMFS) | 0.70 | 0.67–0.74 | < 0.001 | 0.61 | 0.55–0.0.66 | 0.005 |
TNM classification (SMFS) | 0.59 | 0.56–0.63 | 0.58 | 0.54–0.63 |