Background
Methods
Study setting and population
Data sources and data collection
Chemotherapy regimens
RDI
Primary outcome measures
Statistical analysis
Results and discussion
Study population
Characteristic | VA Chemotherapy | 5-FU/LV | Oxaliplatin plus 5-FU/LV | Oxaliplatin plus Capecitabine | Capecitabine Monotherapy | Other | p-valuea |
---|---|---|---|---|---|---|---|
N = 367, N (col%) | N = 126, N (col%) | N = 152, N (col%) | N = 30, N (col%) | N = 48, N (col%) | N = 11, N (col%) | ||
Age (mean, SD)
| 66.4 (9.9) | 67.2 (9.3) | 63.7 (9.6) | 65.6 (9.2) | 73.1 (8.5) | 66.3 (12.8) | <0.001 |
Age
| <0.001 | ||||||
<55 | 39 (10.6) | 11 (8.7) | 23 (15.1) | 3 (10.0) | 0 (0.0) | 2 (18.2) | |
55-64 | 131 (35.7) | 41 (32.5) | 66 (43.4) | 13 (43.3) | 8 (16.7) | 3 (27.3) | |
65-74 | 110 (30.0) | 45 (35.7) | 38 (25.0) | 7 (23.3) | 17 (35.4) | 3 (27.3) | |
75+ | 87 (23.7) | 29 (23.0) | 25 (16.4) | 7 (23.3) | 23 (47.9) | 3 (27.3) | |
Male
| 360 (98.1) | 124 (98.4) | 148 (97.4) | 30 (100.0) | 47 (97.9) | 11 (100.0) | 0.86 |
Married
| 0.92 | ||||||
No | 181 (49.3) | 62 (49.2) | 75 (49.3) | 16 (53.3) | 24 (50.0) | 4 (36.4) | |
Yes | 184 (50.1) | 64 (50.8) | 75 (49.3) | 14 (46.7) | 24 (50.0) | 7 (63.6) | |
Missing | 2 (0.5) | 0 (0.0) | 2 (1.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Race/Ethnicity
| <0.001 | ||||||
Hispanic | 58 (15.8) | 18 (14.3) | 32 (21.1) | 1 (3.3) | 2 (4.2) | 5 (45.5) | |
Black (non-Hispanic) | 59 (16.1) | 20 (15.9) | 25 (16.4) | 3 (10.0) | 7 (14.6) | 4 (36.4) | |
White (non-Hispanic) | 237 (64.6) | 83 (65.9) | 90 (59.2) | 23 (76.7) | 39 (81.3) | 2 (18.2) | |
Other/missing | 13 (3.5) | 5 (4.0) | 5 (3.3) | 3 (10.0) | 0 (0.0) | 0 (0.0) | |
Charlson Comorbidity Index
b
(mean, SD)
| 1.1 (1.7) | 1.3 (1.8) | 1.1 (1.9) | 0.8 (1.4) | 1.2 (1.2) | 1.1 (1.0) | 0.14 |
Tumor
| 0.52 | ||||||
T1 | 16 (4.4) | 4 (3.2) | 7 (4.6) | 1 (3.3) | 3 (6.3) | 1 (9.1) | |
T2 | 45 (12.3) | 15 (11.9) | 16 (10.5) | 5 (16.7) | 9 (18.8) | 0 (0.0) | |
T3 | 275 (74.9) | 94 (74.6) | 119 (78.3) | 23 (76.7) | 31 (64.6) | 8 (72.7) | |
T4 | 31 (8.4) | 13 (10.3) | 10 (6.6) | 1 (3.3) | 5 (10.4) | 2 (18.2) | |
Node
| 0.51 | ||||||
N1 | 235 (64.0) | 87 (69.0) | 96 (63.2) | 18 (60.0) | 28 (58.3) | 6 (54.5) | |
N2 | 132 (36.0) | 39 (31.0) | 56 (36.8) | 12 (40.0) | 20 (41.7) | 5 (45.5) | |
Histologic type
| <0.001 | ||||||
Adenocarcinoma | 340 (92.6) | 118 (93.7) | 147 (96.7) | 21 (70.0) | 45 (93.8) | 9 (81.8) | |
Unknown | 24 (6.5) | 8 (6.3) | 3 (2.0) | 9 (30.0) | 3 (6.3) | 1 (9.1) | |
Other | 3 (0.8) | 0 (0.0) | 2 (1.3) | 0 (0.0) | 0 (0.0) | 1 (9.1) | |
Histologic grade
| 0.68 | ||||||
Well differentiated | 35 (9.5) | 15 (11.9) | 10 (6.6) | 2 (6.7) | 7 (14.6) | 1 (9.1) | |
Moderately differentiated | 247 (67.3) | 81 (64.3) | 107 (70.4) | 23 (76.7) | 29 (60.4) | 7 (63.6) | |
Poorly differentiated | 68 (18.5) | 25 (19.8) | 27 (17.8) | 4 (13.3) | 10 (20.8) | 2 (18.2) | |
Undifferentiated | 4 (1.1) | 0 (0.0) | 4 (2.6) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Unknown | 13 (3.5) | 5 (4.0) | 4 (2.6) | 1 (3.3) | 2 (4.2) | 1 (9.1) | |
Number of lymph nodes evaluated
| 0.03 | ||||||
<12 | 132 (36.0) | 53 (42.1) | 48 (31.6) | 8 (26.7) | 19 (39.6) | 4 (36.4) | |
12+ | 229 (62.4) | 68 (54.0) | 104 (68.4) | 22 (73.3) | 29 (60.4) | 6 (54.5) | |
Missing | 6 (1.6) | 5 (4.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (9.1) | |
Number of lymph nodes evaluated (mean, SD)
| 15.6 (8.9) | 14.3 (8.5) | 16.6 (9.2) | 16.5 (10.0) | 15.1 (8.8) | 15.3 (7.0) | 0.11 |
Number of positive lymph nodes (mean, SD) (N = 366)
| 3.8 (4.0) | 3.4 (3.8) | 3.9 (3.9) | 4.8 (5.2) | 3.6 (3.5) | 6.0 (5.7) | 0.10 |
Preoperative CEA
| 0.68 | ||||||
<5 ng/ml | 178 (48.5) | 60 (47.6) | 78 (51.3) | 14 (46.7) | 20 (41.7) | 6 (54.5) | |
≥5 ng/ml | 84 (22.9) | 32 (25.4) | 36 (23.7) | 6 (20.0) | 8 (16.7) | 2 (18.2) | |
Missing | 105 (28.6) | 34 (27.0) | 38 (25.0) | 10 (33.3) | 20 (41.7) | 3 (27.3) | |
Preoperative CEA (mean, SD) (N = 262)
| 8.0 (15.2) | 9.4 (18.8) | 7.8 (14.2) | 4.8 (6.3) | 7.1 (11.5) | 5.2 (6.3) | 0.48 |
Lymphovascular invasion
| 0.003 | ||||||
Yes | 134 (36.5) | 41 (32.5) | 62 (40.8) | 10 (33.3) | 17 (35.4) | 4 (36.4) | |
No | 103 (28.1) | 26 (20.6) | 41 (27.0) | 17 (56.7) | 17 (35.4) | 2 (18.2) | |
Unknown | 130 (35.4) | 59 (46.8) | 49 (32.2) | 3 (10.0) | 14 (29.2) | 5 (45.5) | |
Perineural invasion
| 0.01 | ||||||
Yes | 38 (10.4) | 8 (6.3) | 17 (11.2) | 4 (13.3) | 6 (12.5) | 3 (27.3) | |
No | 102 (27.8) | 28 (22.2) | 45 (29.6) | 15 (50.0) | 13 (27.1) | 1 (9.1) | |
Unknown | 227 (61.9) | 90 (71.4) | 90 (59.2) | 11 (36.7) | 29 (60.4) | 7 (63.6) | |
Bowel obstruction
| 0.89 | ||||||
Yes | 75 (20.4) | 27 (21.4) | 26 (17.1) | 7 (23.3) | 13 (27.1) | 2 (18.2) | |
No | 168 (45.8) | 56 (44.4) | 73 (48.0) | 14 (46.7) | 21 (43.8) | 4 (36.4) | |
Unknown | 124 (33.8) | 43 (34.1) | 53 (34.9) | 9 (30.0) | 14 (29.2) | 5 (45.5) | |
Perforation
| 0.19 | ||||||
Yes | 21 (5.7) | 13 (10.3) | 5 (3.3) | 2 (6.7) | 0 (0.0) | 1 (9.1) | |
No | 229 (62.4) | 74 (58.7) | 94 (61.8) | 20 (66.7) | 34 (70.8) | 7 (63.6) | |
Unknown | 117 (31.9) | 39 (31.0) | 53 (34.9) | 8 (26.7) | 14 (29.2) | 3 (27.3) | |
Margins
| 0.003 | ||||||
All margins histologically negative | 307 (83.7) | 100 (79.4) | 138 (90.8) | 20 (66.7) | 39 (81.3) | 10 (90.9) | |
1 or more margins included | 25 (6.8) | 9 (7.1) | 10 (6.6) | 2 (6.7) | 4 (8.3) | 0 (0.0) | |
Unknown | 35 (9.5) | 17 (13.5) | 4 (2.6) | 8 (26.7) | 5 (10.4) | 1 (9.1) | |
ECOG performance status
c
| 0.006 | ||||||
0 | 96 (26.2) | 26 (20.6) | 52 (34.2) | 7 (23.3) | 6 (12.5) | 5 (45.5) | |
1 | 44 (12.0) | 19 (15.1) | 14 (9.2) | 2 (6.7) | 8 (16.7) | 1 (9.1) | |
2 -4 | 20 (5.4) | 8 (6.3) | 3 (2.0) | 1 (3.3) | 7 (14.6) | 1 (9.1) | |
Missing or unknown | 207 (56.4) | 73 (57.9) | 83 (54.6) | 20 (66.7) | 27 (56.3) | 4 (36.4) | |
Days between surgery and start of chemotherapy
| 0.053 | ||||||
≤30 | 12 (3.3) | 5 (4.0) | 4 (2.6) | 0 (0.0) | 3 (6.3) | 0 (0.0) | |
31-60 | 232 (63.2) | 95 (75.4) | 85 (55.9) | 19 (63.3) | 27 (56.3) | 6 (54.5) | |
61-90 | 90 (24.5) | 21 (16.7) | 45 (29.6) | 7 (23.3) | 13 (27.1) | 4 (36.4) | |
91-120 | 33 (9.0) | 5 (4.0) | 18 (11.8) | 4 (13.3) | 5 (10.4) | 1 (9.1) |
Adjuvant chemotherapy
Relative dose intensity
Outcomes | Total | 5-FU/LV | Oxaliplatin plus 5-FU/LV | Oxaliplatin plus Capecitabine | Capecitabine Monotherapy | Mixed/Othera |
---|---|---|---|---|---|---|
N = 367 | N = 113 | N = 126 | N = 20 | N = 46 | N = 62 | |
Patients completing ≤70% of RDI, n (col%)
| 122 (33.2) | 35 (31.0) | 25 (19.8) | 11 (55.0) | 30 (65.2) | 21 (33.9) |
Patients completing >70% of RDI, n (col%)
| 206 (56.1) | 70 (61.9) | 90 (71.4) | 8 (40.0) | 14 (30.4) | 24 (38.7) |
Missing or unknown,
b
n (col%)
| 39 (10.6) | 8 (7.1) | 11 (8.7) | 1 (5.0) | 2 (4.3) | 17 (27.4) |
RDI (%), median (IQR)
| 82.3 (49.7, 97.5) | 96.7 (52.0, 100) | 86.1 (70.9, 96.3) | 62.2 (46.9, 81.4) | 51.2 (29.2, 72.1) | 68.8 (42.8, 90.2) |
Patients completing all cycles (N = 348), n (row%)
| 191 (54.9) | 79 (73.8) | 71 (58.2) | 6 (30.0) | 18 (40.0) | 17 (31.5) |
Months of chemotherapy, median (IQR)
| 5.4 (4.3, 6.2) | 5.2 (4.5, 6.6) | 5.6 (4.9, 6.1) | 4.5 (3.1, 5.6) | 4.9 (2.1, 5.6) | 5.5 (3.6, 6.4) |
Adverse drug events
Overall survival and disease-free survival
Overall survival (5 years)b | Disease free survivalc(3 years) | |||
---|---|---|---|---|
HR (95% CI) | P values | HR (95% CI) | P values | |
Chemotherapy regimens
| ||||
5-FU/ LV | Reference | Reference | ||
Oxaliplatin plus 5-FU/LV | 0.55 (0.34,0.91) | 0.02 | 0.65 (0.41,1.05) | 0.08 |
Oxaliplatin plus Capecitabine | 1.15 (0.42,3.16) | 0.79 | 1.07 (0.42,2.70) | 0.89 |
Capecitabine Monotherapy | 0.80 (0.43,1.50) | 0.50 | 0.91 (0.50,1.64) | 0.75 |
Mixed/Other | 0.89 (0.50,1.59) | 0.70 | 1.20 (0.70,2.05) | 0.51 |
Relative dose intensity
| ||||
≤70% | Reference | Reference | ||
>70% | NAd | 0.75 (0.50,1.11) | 0.15 | |
At year 1 | 0.58 (0.37,0.89) | 0.01 | ||
At year 2 | 0.74 (0.47,1.18) | 0.21 | ||
At year 3 | 0.86 (0.52,1.44) | 0.57 | ||
At year 4 | 0.96 (0.54,1.68) | 0.88 | ||
At year 5 | 1.04 (0.56,1.91) | 0.90 | ||
Unknown or Missing | 0.95 (0.51,1.78) | 0.88 | 0.97 (0.53,1.77) | 0.91 |
Age (years)
| ||||
<55 | 0.68 (0.30, 1.52) | 0.34 | 1.00 (0.50, 1.97) | 0.99 |
55-64 | Reference | Reference | ||
65-74 | 0.99 (0.61,1.62) | 0.96 | 1.14 (0.72,1.82) | 0.57 |
75+ | 2.06 (1.25,3.40) | 0.005 | 1.98 1.21,3.23) | 0.006 |
Male
| 1.70 (0.39,7.52) | 0.48 | 1.67 (0.39,7.27) | 0.49 |
Race/Ethnicity
| ||||
White (non-Hispanic) | Reference | Reference | ||
Hispanic | 0.56 (0.17,1.80) | 0.33 | 0.27 (0.08,0.93) | 0.04 |
Black (non-Hispanic) | 0.75 (0.37,1.50) | 0.41 | 0.76 (0.40,1.44) | 0.40 |
Other/Missing | 1.42 (0.58,3.48) | 0.44 | 1.35 (0.59,3.11) | 0.48 |
Charlson Comorbidity Index (per unit)
| 1.17 (1.06,1.30) | 0.002 | 1.15 (1.04,1.27) | 0.007 |
Married
| 0.66 (0.45,0.97) | 0.03 | 0.86 (0.59,1.24) | 0.42 |
Tumor
| ||||
T1/T2e | Reference | Reference | ||
T3 | 1.62 (0.83,3.14) | 0.15 | 1.63 (0.88,3.02) | 0.12 |
T4 | 5.88 (2.69,12.9) | <0.001 | 5.84 (2.82,12.1) | <0.001 |
Node
| ||||
N1 | Reference | Reference | ||
N2 | 1.68 (1.12,2.50) | 0.01 | 1.89 (1.30,2.77) | 0.001 |
Lymphovascular invasion
| ||||
No | Reference | Reference | ||
Yes | 1.69 (0.90,3.17) | 0.10 | 1.95 (1.10,3.45) | 0.02 |
Unknown or Missing | 1.09 (0.57,2.07) | 0.79 | 1.20 (0.66,2.16) | 0.55 |
Bowel obstruction
| ||||
No | Reference | Reference | ||
Yes | 2.32 (1.36,3.95) | 0.002 | 2.12 (1.28,3.51) | 0.003 |
Unknown or Missing | 1.05 (0.57,1.95) | 0.88 | 1.19 (0.67,2.10) | 0.56 |
Days between surgery and start of chemotherapy
| ||||
≤30 | Reference | Reference | ||
31-60 | 1.44 (0.40,5.22) | 0.58 | 1.14 (0.37,3.49) | 0.82 |
61-90 | 1.65 (0.43,6.25) | 0.47 | 1.35 (0.42,4.33) | 0.61 |
91-120 | 1.84 (0.46,7.41) | 0.39 | 1.56 (0.46,5.32) | 0.47 |