Table 1.
Original cohort Erasmus MC Cancer Institute | External validation cohort MSKCC | Randomised patient cohort EORTC 40983 trial | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Preoperative chemotherapy | Preoperative chemotherapy | Treatment arm | ||||||||
No | Yes | No | Yes | Rx arm | CTx arm | |||||
n = 462 (%) | n = 415 (%) | P value* | n = 410 (%) | n = 793 (%) | P value* | n = 40 (%) | n = 30 (%) | P value* | ||
Age at resection CRLM (median [IQR]) | 66.0 [59.2–73.0] | 63.0 [56.0–69.0] | <0.001 | 62.0 [52.0–72.0] | 57.0 [48.0–66.0] | <0.001 | 67.5 [59.8–72.0] | 65.0 [58.5–71.8] | 0.536 | |
Gender | Male | 298 (65) | 270 (65) | 0.863 | 228 (56) | 452 (57) | 0.645 | 22 (55) | 19 (63) | 0.484 |
Female | 164 (35) | 145 (35) | 182 (44) | 341 (43) | 18 (45) | 11 (37) | ||||
Primary tumour location | Right‐sided | 80 (18) | 65 (16) | 0.655 | 141 (36) | 204 (27) | 0.003 | 8 (20) | 8 (27) | 0.768 |
Left‐sided | 195 (43) | 175 (43) | 175 (44) | 331 (45) | 15 (38) | 11 (37) | ||||
Rectal | 175 (39) | 170 (41) | 80 (20) | 207 (28) | 16 (40) | 11 (37) | ||||
Missing | 12 (3) | 5 (1) | 14 (3) | 51 (6) | 1 † (2) | 0 (0) | ||||
Adjuvant CTx for primary | No | 369 (80) | 383 (93) | <0.001 | 140 (56) | 256 (56) | 0.967 | 30 (75) | 23 (77) | 0.872 |
Yes | 92 (20) | 28 (7) | 109 (44) | 198 (44) | 10 (25) | 7 (23) | ||||
Missing | 1 (0) | 4 (1) | 161 (39) | 339 (43) | — | — | ||||
(y)pT‐stage | 0 | 6 (1) | 15 (4) | 0.004 | 0 (0) | 7 (1) | <0.001 | 0 (0) | 0 (0) | 0.823 |
1 | 11 (2) | 4 (1) | 21 (5) | 10 (1) | 1 (3) | 0 (0) | ||||
2 | 74 (16) | 47 (12) | 46 (12) | 65 (9) | 4 (10) | 4 (13) | ||||
3 | 327 (72) | 259 (69) | 263 (67) | 462 (66) | 30 (77) | 23 (77) | ||||
4 | 38 (8) | 51 (14) | 60 (15) | 153 (22) | 4 (10) | 3 (10) | ||||
Missing | 6 (1) | 39 (9) | 20 (5) | 96 (12) | 1 (2) | 0 (0) | ||||
(y)pN‐stage | 0 | 196 (43) | 139 (37) | 0.202 | 185 (46) | 246 (32) | <0.001 | 17 (44) | 13 (43) | 0.893 |
1 | 170 (38) | 151 (40) | 155 (38) | 307 (40) | 17 (44) | 12 (40) | ||||
2 | 87 (19) | 83 (22) | 64 (16) | 213 (28) | 5 (13) | 5 (17) | ||||
Missing | 9 (2) | 42 (10) | 6 (1) | 27 (3) | 1 (2) | 0 (0) | ||||
Differentiation grade | pCR | 5 (2) | 13 (4) | 0.189 | — | — | 0 (0) | 0 (0) | 0.733 | |
G1 | 6 (2) | 6 (2) | — | — | 9 (23) | 7 (23) | ||||
G2 | 267 (93) | 266 (89) | — | — | 28 (72) | 20 (67) | ||||
G3 | 9 (3) | 15 (5) | — | — | 2 (5) | 3 (10) | ||||
Missing | 175 (38) | 115 (28) | 410 (100) | 793 (100) | 1 (2) | 0 (0) | ||||
Disease‐free interval in months (median [IQR]) | 11.0 [0.0–22.8] | 0.0 [0.0–0.5] | <0.001 | 12.0 [0.0–24.8] | 0.0 [0.0–5.0] | <0.001 | 5.8 [0.0–14.5] | 0.0 [0.0–14.8] | 0.334 | |
Number of CRLM (median [IQR]) | 1.0 [1.0–2.0] | 3.0 [1.0–5.0] | <0.001 | 1.0 [1.0–2.0] | 2.0 [1.0–4.0] | <0.001 | 1.0 [1.0–2.0] | 2.0 [1.0–3.0] | 0.096 | |
Diameter of largest CRLM in cm (median [IQR]) | 3.2 [2.1–4.8] | 2.2 [1.3–3.7] | <0.001 | 3.0 [2.1–5.0] | 2.5 [1.6–4.2] | <0.001 | 3.0 [2.5–4.6] | 2.5 [2.0–3.6] | 0.100 | |
Preoperative CEA in μg/l (median [IQR]) | 11.0 [4.1–29.0] | 19.0 [5.3–74.0] | <0.001 | 9.8 [3.8–31.2] | 9.5 [3.9–35.3] | 0.577 | 7.4 [2.3–23.9] | 17.2 [4.8–58.5] | 0.078 | |
Clinical risk score | Low risk (0–2) | 331 (75) | 177 (48) | <0.001 | 286 (74) | 346 (47) | <0.001 | 27 (69) | 15 (52) | 0.142 |
High risk (3–5) | 111 (25) | 190 (52) | 100 (26) | 393 (53) | 12 (31) | 14 (48) | ||||
Missing | 20 (4) | 48 (12) | 24 (6) | 54 (7) | 1 (2) | 1 (3) | ||||
Extrahepatic disease | No | 429 (93) | 350 (84) | <0.001 | 362 (88) | 651 (82) | 0.005 | 38 (95) | 27 (90) | 0.421 |
Yes | 33 (7) | 65 (16) | 48 (12) | 142 (18) | 2 (5) | 3 (10) | ||||
Resection margin status | R0 | 410 (90) | 329 (80) | <0.001 | 368 (91) | 675 (86) | 0.009 | 37 (92) | 29 (97) | 0.457 |
R1 | 48 (10) | 84 (20) | 35 (9) | 109 (14) | 3 (8) | 1 (3) | ||||
Missing | 4 (1) | 2 (0) | 7 (2) | 9 (1) | — | — | ||||
HGP | Desmoplastic | 85 (18) | 125 (30) | <0.001 | 53 (13) | 185 (23) | <0.001 | 7 (18) | 8 (27) | 0.355 |
Non‐desmoplastic | 377 (82) | 290 (70) | 357 (87) | 608 (77) | 33 (82) | 22 (73) | ||||
APC | Wildtype | 11 (46) | 8 (24) | 0.075 | 21 (15) | 53 (16) | 0.737 | — | — | |
Mutant | 13 (54) | 26 (76) | 118 (85) | 271 (84) | — | — | ||||
Missing | 438 (95) | 381 (92) | 271 (66) | 469 (59) | 40 (100) | 30 (100) | ||||
KRAS | Wildtype | 42 (63) | 65 (56) | 0.345 | 151 (58) | 360 (56) | 0.633 | — | — | |
Mutant | 25 (37) | 52 (44) | 109 (42) | 279 (44) | — | — | ||||
Missing | 395 (85) | 298 (72) | 150 (37) | 154 (19) | 40 (100) | 30 (100) | ||||
NRAS | Wildtype | 36 (95) | 65 (97) | 0.558 | 204 (96) | 510 (95) | 0.791 | — | — | |
Mutant | 2 (5) | 2 (3) | 9 (4) | 25 (5) | — | — | ||||
Missing | 424 (92) | 348 (84) | 197 (48) | 258 (33) | 40 (100) | 30 (100) | ||||
BRAF | Wildtype | 56 (95) | 102 (100) | 0.022 | 226 (96) | 563 (96) | 0.663 | — | — | |
Mutant | 3 (5) | 0 (0) | 10 (4) | 21 (4) | — | — | ||||
Missing | 403 (87) | 313 (75) | 174 (42) | 209 (26) | 40 (100) | 30 (100) | ||||
MSI status | MSS | 62 (97) | 71 (95) | 0.523 | 116 (97) | 284 (98) | 0.314 | — | — | |
MSI | 2 (3) | 4 (5) | 4 (3) | 5 (2) | — | — | ||||
Missing | 398 (86) | 340 (82) | 290 (71) | 504 (64) | 40 (100) | 30 (100) |
Percentages of categorical variables are reported across valid cases only (i.e. missing are not considered).
CTx, chemotherapy; G, grade; MSS, microsatellite stable; pCR, pathological complete response; R0, negative resection margin (>0 mm margin); R1, positive resection margin; Rx, resection.
P values are calculated across valid cases only (i.e. missing are not considered).
Multiple primary tumours.