Copyright
©The Author(s) 2020.
World J Gastrointest Oncol. Apr 15, 2020; 12(4): 405-423
Published online Apr 15, 2020. doi: 10.4251/wjgo.v12.i4.405
Published online Apr 15, 2020. doi: 10.4251/wjgo.v12.i4.405
Table 1 Patient characteristics before propensity score matching
LPTL1 | RPTL1 | |||||
Cetuximab (n = 164) | Bevacizumab (n = 679) | P value | Cetuximab (n = 84) | Bevacizumab (n = 385) | P value | |
Age at index date2, years | 0.727 | 0.801 | ||||
Median | 61.0 | 61.0 | 66.5 | 67.0 | ||
Sex, n (%) | 0.749 | 0.296 | ||||
Female | 59 (36.0) | 256 (37.7) | 36 (42.9) | 192 (49.9) | ||
Male | 105 (64.0) | 423 (62.3) | 48 (57.1) | 193 (50.1) | ||
Race, n (%) | 0.042 | 0.506 | ||||
Black or African American | 17 (10.4) | 61 (9.0) | 7 (8.3) | 43 (11.2) | ||
White | 114 (69.5) | 435 (64.1) | 57 (67.9) | 264 (68.6) | ||
Other race | 27 (16.5) | 109 (16.1) | 9 (10.7) | 46 (11.9) | ||
Missing | 6 (3.7) | 74 (10.9) | 11 (13.1) | 32 (8.3) | ||
Region, n (%) | 0.001 | 0.008 | ||||
Northeast | 38 (23.2) | 144 (21.2) | 20 (23.8) | 73 (19.0) | ||
Midwest | 14 (8.5) | 133 (19.6) | 12 (14.3) | 99 (25.7) | ||
South | 54 (32.9) | 246 (36.2) | 24 (28.6) | 140 (36.4) | ||
West | 40 (24.4) | 105 (15.5) | 15 (17.9) | 47 (12.2) | ||
Unknown | 18 (11.0) | 51 (7.5) | 13 (15.5) | 26 (6.8) | ||
Practice type, n (%) | 0.079 | 0.052 | ||||
Academic | 2 (1.2) | 31 (4.6) | 0 | 17 (4.4) | ||
Community | 162 (98.8) | 648 (95.4) | 84 (100) | 368 (95.6) | ||
Site of disease, n (%) | 1.000 | NA | ||||
Colon | 111 (67.7) | 460 (67.7) | 84 (100) | 385 (100) | ||
Rectum | 53 (32.3) | 219 (32.3) | 0 | 0 | ||
Side of colon, n (%) | 0.973 | 0.745 | ||||
Left side | 86 (52.4) | 364 (53.6) | 0 | 0 | ||
Rectosigmoid | 18 (11.0) | 79 (11.6) | 0 | 0 | ||
Rectum | 52 (31.7) | 206 (30.3) | 0 | 0 | ||
Splenic flexure | 8 (4.9) | 30 (4.4) | 0 | 0 | ||
Right side | 0 | 0 | 70 (83.3) | 329 (85.5) | ||
Transverse colon | 0 | 0 | 14 (16.7) | 56 (14.5) | ||
Group stage at initial diagnosis, n (%) | 0.199 | 0.001 | ||||
Stage I | 2 (1.2) | 26 (3.8) | 1 (1.2) | 5 (1.3) | ||
Stage II | 13 (7.9) | 73 (10.8) | 5 (6.0) | 40 (10.4) | ||
Stage III | 44 (26.8) | 145 (21.4) | 37 (44.0) | 87 (22.6) | ||
Stage IV | 101 (61.6) | 411 (60.5) | 41 (48.8) | 253 (65.7) | ||
Unknown | 4 (2.4) | 24 (3.5) | 0 | 0 | ||
ECOG PS at index date2, 3, n (%) | 0.176 | 0.026 | ||||
0 | 39 (23.8) | 192 (28.3) | 27 (32.1) | 80 (20.8) | ||
1 | 22 (13.4) | 117 (17.2) | 9 (10.7) | 83 (21.6) | ||
2+ | 5 (3.0) | 29 (4.3) | 3 (3.6) | 26 (6.8) | ||
Missing | 98 (59.8) | 341 (50.2) | 45 (53.6) | 196 (50.9) | ||
Modified CCI at index date2, 4, n (%) | 0.526 | 0.339 | ||||
0 | 136 (82.9) | 557 (82.0) | 64 (76.2) | 293 (76.1) | ||
1 | 20 (12.2) | 86 (12.7) | 17 (20.2) | 59 (15.3) | ||
2 | 7 (4.3) | 21 (3.1) | 3 (3.6) | 24 (6.2) | ||
3+ | 1 (0.6) | 15 (2.2) | 0 | 9 (2.3) | ||
NRAS tested, n (%) | 51 (31.1) | 281 (41.4) | 0.020 | 28 (33.3) | 160 (41.6) | 0.204 |
NRAS status among those tested5, n (%) | 0.112 | 0.373 | ||||
Mutation negative | 49 (96.1) | 256 (91.1) | 28 (100) | 144 (90.0) | ||
Mutation positive | 0 | 19 (6.8) | 0 | 14 (8.8) | ||
Results pending | 0 | 1 (0.4) | 0 | 1 (0.6) | ||
Unknown | 1 (2.0) | 1 (0.4) | 0 | 0 | ||
Unsuccessful/indeterminate | 1 (2.0) | 4 (1.4) | 0 | 1 (0.6) | ||
BRAF tested, n (%) | 46 (28.0) | 313 (46.1) | < 0.001 | 35 (41.7) | 176 (45.7) | 0.579 |
BRAF status among those tested5, n (%) | 0.075 | 0.072 | ||||
Mutation negative | 45 (97.8) | 288 (92.0) | 24 (68.6) | 103 (58.5) | ||
Mutation positive | 0 | 23 (7.3) | 10 (28.6) | 73 (41.5) | ||
Results pending | 0 | 1 (0.3) | 0 | 0 | ||
Unknown | 1 (2.2) | 1 (0.3) | 0 | 0 | ||
Unsuccessful/indeterminate | 0 | 0 | 1 (2.9) | 0 | ||
First-line chemotherapy backbone, n (%) | < 0.001 | < 0.001 | ||||
FOLFIRI | 105 (64.0) | 165 (24.3) | 64 (76.2) | 96 (24.9) | ||
FOLFOX | 59 (36.0) | 514 (75.7) | 20 (23.8) | 289 (75.1) | ||
History of adjuvant chemotherapy6, n (%) | 0.171 | < 0.001 | ||||
No/not documented | 114 (69.5) | 510 (75.1) | 44 (52.4) | 299 (77.7) | ||
Yes | 50 (30.5) | 169 (24.9) | 40 (47.6) | 86 (22.3) | ||
First-line therapy duration7, days | 0.076 | 0.969 | ||||
Median | 197.0 | 183.0 | 156.0 | 162.0 | ||
Length of follow-up8, days | 0.019 | 0.345 | ||||
Median | 501.5 | 442.0 | 323.5 | 350.0 |
Table 2 Patient characteristics after propensity score matching
Total (n = 792) | Cetuximab (n = 228) | Bevacizumab (n = 564) | P value | |
Age at index date1, years | 0.923 | |||
Median | 64.0 | 64.0 | 63.0 | |
Sex, n (%) | 0.914 | |||
Female | 334 (42.2) | 92 (40.4) | 242 (42.9) | |
Male | 458 (57.8) | 136 (59.6) | 322 (57.1) | |
Race, n (%) | 0.905 | |||
Black or African American | 71 (9.0) | 22 (9.6) | 49 (8.7) | |
White | 549 (69.3) | 158 (69.3) | 391 (69.3) | |
Other race | 111 (14.0) | 32 (14.0) | 79 (14.0) | |
Missing | 61 (7.7) | 16 (7.0) | 45 (8.0) | |
Region, n (%) | 0.620 | |||
Northeast | 185 (23.4) | 54 (23.7) | 131 (23.2) | |
Midwest | 113 (14.3) | 26 (11.4) | 87 (15.4) | |
South | 253 (31.9) | 75 (32.9) | 178 (31.6) | |
West | 158 (19.9) | 48 (21.1) | 110 (19.5) | |
Unknown | 83 (10.5) | 25 (11.0) | 58 (10.3) | |
Practice type, n (%) | <0.001 | |||
Academic | 35 (4.4) | 0 | 35 (6.2) | |
Community | 757 (95.6) | 228 (100) | 529 (93.8) | |
Site of disease, n (%) | 1.000 | |||
Colon | 630 (79.5) | 180 (78.9) | 450 (79.8) | |
Rectum | 162 (20.5) | 48 (21.1) | 114 (20.2) | |
Group stage at initial diagnosis, n (%) | 0.763 | |||
Stage I | 9 (1.1) | 3 (1.3) | 6 (1.1) | |
Stage II | 68 (8.6) | 18 (7.9) | 50 (8.9) | |
Stage III | 245 (30.9) | 79 (34.6) | 166 (29.4) | |
Stage IV | 458 (57.8) | 124 (54.4) | 334 (59.2) | |
Unknown | 12 (1.5) | 4 (1.8) | 8 (1.4) | |
ECOG PS at index date1, 2, n (%) | 0.379 | |||
0 | 197 (24.9) | 61 (26.8) | 136 (24.1) | |
1 | 130 (16.4) | 30 (13.2) | 100 (17.7) | |
2+ | 35 (4.4) | 6 (2.6) | 29 (5.1) | |
Missing | 430 (54.3) | 131 (57.5) | 299 (53.0) | |
Modified CCI at index date1, 3, n (%) | 0.861 | |||
0 | 650 (82.1) | 185 (81.1) | 465 (82.4) | |
1 | 104 (13.1) | 32 (14.0) | 72 (12.8) | |
2 | 34 (4.3) | 10 (4.4) | 24 (4.3) | |
3+ | 4 (0.5) | 1 (0.4) | 3 (0.5) | |
NRAS tested, n (%) | 274 (34.6) | 70 (30.7) | 204 (36.2) | 0.410 |
NRAS status among those tested4, n (%) | 0.908 | |||
Mutation negative | 268 (97.8) | 68 (97.1) | 200 (98.0) | |
Mutation positive | 0 | 0 | 0 | |
Results pending | 1 (0.4) | 0 | 1 (0.5) | |
Unknown | 1 (0.4) | 1 (1.4) | 0 | |
Unsuccessful/indeterminate | 4 (1.5) | 1 (1.4) | 3 (1.5) | |
BRAF tested, n (%) | 290 (36.6) | 76 (33.3) | 214 (37.9) | 0.955 |
BRAF status among those tested4, n (%) | 0.881 | |||
Mutation negative | 248 (85.5) | 64 (84.2) | 184 (86.0) | |
Mutation positive | 39 (13.4) | 10 (13.2) | 29 (13.6) | |
Results pending | 1 (0.3) | 0 | 1 (0.5) | |
Unknown | 1 (0.3) | 1 (1.3) | 0 | |
Unsuccessful/indeterminate | 1 (0.3) | 1 (1.3) | 0 | |
First-line chemotherapy backbone, n (%) | 0.485 | |||
FOLFIRI | 387 (48.9) | 149 (65.4) | 238 (42.2) | |
FOLFOX | 405 (51.1) | 79 (34.6) | 326 (57.8) | |
History of adjuvant chemotherapy5, n (%) | 0.789 | |||
No/not documented | 519 (65.5) | 140 (61.4) | 379 (67.2) | |
Yes | 273 (34.5) | 88 (38.6) | 185 (32.8) | |
First-line therapy duration6, days | 0.424 | |||
Median | 179.0 | 162.0 | 190.0 | |
Length of follow-up7, days | 0.533 | |||
Median | 434.0 | 428.5 | 434.5 | |
Side of colon, n (%) | 0.868 | |||
Left side | 283 (35.7) | 78 (34.2) | 205 (36.3) | |
Rectosigmoid | 62 (7.8) | 17 (7.5) | 45 (8.0) | |
Rectum | 154 (19.4) | 47 (20.6) | 107 (19.0) | |
Splenic flexure | 19 (2.4) | 5 (2.2) | 14 (2.5) | |
Right side | 231 (29.2) | 68 (29.8) | 163 (28.9) | |
Transverse colon | 43 (5.4) | 13 (5.7) | 30 (5.3) |
Table 3 Cox regression estimation in the propensity score–matched sample (n = 792)
Log (HR) | HR | SE [Log (HR)] | Robust SE [Log (HR)] | Z | P value | |
Cetuximab | 0 | 1.00 | 0.18 | 0.19 | 0 | 0.996 |
LPTL | -0.58 | 0.56 | 0.13 | 0.15 | -3.89 | < 0.001 |
Cetuximab × LPTL | -0.14 | 0.87 | 0.24 | 0.25 | -0.57 | 0.566 |
Table 4 Overall survival sensitivity analyses
Matched/weighted | HR (95%CI) of cetuximab vs bevacizumab, for LPTL | HR (95%CI) of cetuximab vs bevacizumab, for RPTL | |
mOS (mo) for cetuximab vs bevacizumab | |||
Main analysis with propensity score matching | 27.9 vs 25.4 | 0.87 (0.63-1.19) | 1.00 (0.68-1.46) |
Planned sensitivity analyses | |||
1:1 matching without a caliper (propensity score matching) | 27.9 vs 21.7 | 0.76 (0.55-1.06) | 0.91 (0.59-1.41) |
2:1 matching without a caliper (propensity score matching) | 27.9 vs 22.3 | 0.82 (0.61-1.11) | 0.87 (0.58-1.29) |
IPTW | 27.9 vs 25.6 | 0.87 (0.63-1.19) | 0.98 (0.65-1.49) |
LPTL only (propensity score matching) | 29.4 vs 30.5 | 0.88 (0.61-1.28) | NA |
RPTL only (propensity score matching) | 17.9 vs 20.4 | NA | 1.09 (0.74-1.63) |
Change definition of tumor location (IPTW) | |||
RPTL: C/A/HF; LPTL: transverse to rectum | 27.9 vs 25.6 | 0.89 (0.66-1.20) | 0.96 (0.61-1.53) |
RPTL: C/A/HF to transverse; LPTL: splenic flexure to rectosigmoid | 27.9 vs 26.6 | 0.98 (0.66-1.44) | 0.98 (0.64-1.50) |
RPTL: C/A/HF to transverse; LPTL: splenic flexure to descending/sigmoid | 27.4 vs 25.8 | 0.93 (0.61-1.43) | 0.98 (0.65-1.48) |
RPTL: C/A/HF; LPTL: transverse to rectosigmoid | 27.9 vs 26.6 | 1.02 (0.71-1.46) | 0.95 (0.60-1.52) |
RPTL: C/A/HF; LPTL: transverse to descending/sigmoid | 27.4 vs 25.8 | 0.98 (0.67-1.45) | 0.95 (0.60-1.50) |
RPTL: C/A/HF; LPTL: splenic flexure to rectum | 28.3 vs 25.8 | 0.88 (0.64-1.21) | 0.96 (0.60-1.51) |
RPTL: C/A/HF; LPTL: splenic flexure to rectosigmoid | 28.3 vs 26.6 | 1.00 (0.68-1.47) | 0.93 (0.59-1.48) |
RPTL: C/A/HF; LPTL: splenic flexure to descending/sigmoid | 28.3 vs 26.0 | 0.95 (0.62-1.46) | 0.94 (0.60-1.47) |
NRAS mutation–negative patients only (IPTW) | 28.9 vs 26.0 | 0.77 (0.40-1.50) | 1.03 (0.54-1.97) |
Restricted to patients with chemotherapy backbone of FOLFIRI (IPTW) | 24.6 vs 23.1 | 0.96 (0.64-1.44) | 1.05 (0.62-1.77) |
Restricted to patients with chemotherapy backbone of FOLFOX (IPTW) | Not reached vs 25.91 | 0.63 (0.37-1.08) | 0.52 (0.23-1.17) |
Change definition of index date (propensity score matching)2 | 27.8 vs 24.8 | 0.86 (0.61-1.20) | 0.96 (0.64-1.44) |
Restrict to stage IV patients (IPTW) | 29.7 vs 29.4 | 0.98 (0.61-1.57) | 0.99 (0.51-1.90) |
- Citation: Aggarwal H, Sheffield KM, Li L, Lenis D, Sorg R, Barzi A, Miksad R. Primary tumor location and survival in colorectal cancer: A retrospective cohort study. World J Gastrointest Oncol 2020; 12(4): 405-423
- URL: https://www.wjgnet.com/1948-5204/full/v12/i4/405.htm
- DOI: https://dx.doi.org/10.4251/wjgo.v12.i4.405