Methods
Study Design and Patients
Results
Patient Characteristics
Missing data n (%) | dHGP | non-dHGP | |||||
---|---|---|---|---|---|---|---|
HAIP (n = 75) | no HAIP (n = 216) | p value | HAIP (n = 247) | no HAIP (n = 695) | p value | ||
Age, median [IQR] | – | 53.0 [47.0, 61.0] | 63.0 [52.0, 70.0] | < 0.001 | 54.0 [46.0, 65.0] | 62.0 [53.0, 69.0] | < 0.001 |
Female gender, n (%) | – | 50 (67) | 140 (65) | 0.772 | 159 (64) | 411 (59) | 0.148 |
ASA > II, n (%) | 9 (1) | 38 (51) | 80 (37) | 0.044 | 150 (61) | 281 (42) | < 0.001 |
Location primary tumor, n (%) | 55 (4.5) | – | – | 0.099 | – | – | 0.812 |
Right-sided | – | 23 (32) | 55 (27) | – | 58 (25) | 166 (25) | – |
Left-sided | – | 37 (51) | 90 (44) | – | 115 (49) | 315 (47) | – |
Rectum | – | 12 (17) | 61 (30) | – | 62 (26) | 191 (28) | – |
Disease-free Interval > 1 year, n (%) | – | 7 (9) | 32 (15) | 0.230 | 87 (31) | 54 (21) | 0.008 |
Number of CRLM, median [IQR] | 9 (1) | 3.0 [2.0, 5.0] | 1.0 [1.0, 2.0] | < 0.001 | 3.0 [1.0, 4.0] | 2.0 [1.0, 3.0] | < 0.001 |
Diameter of CRLM, median [IQR] | 33 (3) | 2.2 [1.2, 3.2] | 1.7 [1.1, 3.0] | 0.433 | 2.9 [2.0, 4.9] | 2.6 [1.7, 4.2] | 0.011 |
Preoperative CEA, median [IQR] | 148 (12) | 7.0 [3.1, 19.0] | 8.0 [3.1, 28.0] | 0.699 | 12.1 [5.1, 47.0] | 15.3 [4.6, 52.7] | 0.567 |
Involvement of locoregional lymph nodes (N+) | 12 (1) | 10 (14) | 22 (10) | 0.446 | 214 (87) | 566 (84) | 0.260 |
Fong clinical risk score, n (%) | – | – | – | 0.778 | – | – | 0.009 |
Low (0–2) | – | 33 (44) | 91 (42) | – | 113 (46) | 385 (55) | – |
High (3–5) | – | 33 (44) | 91 (42) | – | 134 (54) | 310 (45) | – |
KRAS mutation, n (%) | 652 (53) | 25 (41) | 32 (42) | 0.927 | 76 (37) | 133 (45) | 0.055 |
Preoperative systemic CTx | – | 63 (84) | 195 (90) | 0.140 | 168 (68) | 547 (79) | 0.001 |
Involvement resection margin (R1), n (%) | 12 (1) | 10 (14) | 22 (10) | 0.446 | 36 (13) | 35 (14) | 0.152 |
Major hepatectomy, n (%) | 80 (7) | 30 (45) | 71 (34) | 0.108 | 117 (53) | 272 (42) | 0.004 |
Treatment center MSKCC, n (%) | 0 | 75 (100) | 111 (51) | < 0.001 | 247 (100) | 417 (60) | < 0.001 |
Survival Outcomes of the Whole Cohort
Survival Outcomes in dHGP Group
Endpoint | dHGP | non-dHGP | ||
---|---|---|---|---|
HAIP | no HAIP | HAIP | no HAIP | |
5-year OS | 79% (95% CI 69–90%) | 61% (95% CI 54–69%) | 60% (95% CI 53–67%) | 49% (95% CI 44–66%) |
5-year PFS | 50% (95% CI 40–64%) | 36% (95% CI 30–43%) | 30% (95% CI 25–37%) | 16% (95% CI 14–20%) |
5-year hPFS | 61% (95% CI 50–74%) | 44% (95% CI 38–52%) | 48% (95% CI 41–56%) | 27% (95% CI 23–31%) |
Survival Outcomes in Non-dHGP Group
Multivariable Regression Analysis
Univariable | p value | Multivariable | p value | |
---|---|---|---|---|
Overall survival (n = 496) | ||||
Age < 65 years | 0.73 [0.62–0.86] | < 0.001 | 1.01 [0.73–1.39] | 0.95 |
ASA > II | 0.95 [0.80–1.13] | 0.56 | 1.08 [0.79–1.46] | 0.63 |
Location primary tumor | ||||
Right-sided | Reference | – | Reference | – |
Left-sided | 0.84 [0.69–1.03] | 0.10 | 0.83 [0.59–1.18] | 0.31 |
Rectum | 0.83 [0.66–1.04] | 0.11 | 0.86 [0.57–1.29] | 0.46 |
Preoperative systemic CTx | 1.75 [1.40–2.19] | < 0.001 | 1.67 [1.13–2.47] | < 0.01 |
Number of CRLM | 1.09 [1.06–1.12] | < 0.001 | 1.10 [1.04–1.16] | < 0.01 |
Diameter of largest CRLM (cm) | 1.04 [1.02–1.07] | < 0.01 | 1.08 [1.03–1.14] | < 0.001 |
Preoperative CEA (before chemo) | 1.00 [1.00–1.00] | 0.76 | 1.00 [1.00–1.00] | 0.63 |
Disease-free interval (months) | 1.00 [0.99–1.00] | 0.54 | 1.00 [0.98–1.01] | 0.51 |
Nodal status primary tumor | 1.45 [1.22–1.73] | < 0.001 | 2.01 [1.42–2.83] | < 0.001 |
R1 resection | 1.68 [1.36–2.07] | < 0.001 | 1.53 [1.01–2.31] | 0.04 |
KRAS mutated | 1.71 [1.32–2.21] | < 0.001 | 1.63 [1.20–2.22] | < 0.01 |
dHGP (vs. non-dHGP) | 0.67 [0.54–0.82] | < 0.001 | 0.49 [0.32–0.73] | < 0.001 |
HAIP chemotherapy | 0.62 [0.50–0.76] | < 0.001 | 0.61 [0.45–0.82] | < 0.001 |
Progression-free survival | ||||
Age < 65 years | 0.97 [0.84–1.13] | 0.73 | 1.29 [0.98–1.70] | 0.07 |
ASA >II | 0.92 [0.80–1.07] | 0.29 | 1.32 [1.02–1.71] | 0.04 |
Location primary tumor | ||||
Right-sided | Reference | – | Reference | – |
Left-sided | 1.08 [0.90–1.28] | 0.43 | 1.14 [0.84–1.54] | 0.39 |
Rectum | 1.07 [0.87–1.30] | 0.52 | 1.25 [0.88–1.76] | 0.21 |
Preoperative systemic CTx | 1.83 [1.51–2.22] | < 0.001 | 1.34 [0.97–1.85] | 0.08 |
Number of CRLM | 1.13 [1.10–1.15] | < 0.001 | 1.16 [1.10–1.21] | < 0.001 |
Diameter of largest CRLM (cm) | 1.01 [0.99–1.04] | 0.31 | 1.05 [1.00–1.10] | 0.05 |
Preoperative CEA (before chemo) | 1.00 [1.00–1.00] | 0.86 | 1.00 [1.00–1.00] | 0.36 |
Disease-free interval (months) | 0.99 [0.99–1.00] | < 0.001 | 0.99 [0.98–1.01] | 0.28 |
Nodal status primary tumor | 1.36 [1.17–1.58] | < 0.001 | 1.75 [1.33–2.31] | < 0.001 |
R1 resection | 1.56 [1.29–1.89] | < 0.001 | 1.19 [0.82–1.73] | 0.36 |
KRAS mutated | 1.40 [1.14–1.73] | < 0.01 | 1.41 [1.09–1.82] | < 0.01 |
dHGP (vs. non-dHGP) | 0.64 [0.53–0.76] | < 0.001 | 0.72 [0.52–0.99] | 0.05 |
HAIP chemotherapy | 0.53 [0.45–0.64] | < 0.001 | 0.47 [0.36–0.60] | < 0.001 |
Hepatic progression-free survival | ||||
Age < 65 years | 0.73 [0.62–0.86] | < 0.001 | 1.01 [0.73–1.39] | 0.95 |
ASA >II | 0.95 [0.80–1.13] | 0.56 | 1.08 [0.79–1.46] | 0.63 |
Location primary tumor | ||||
Right-sided | Reference | – | Reference | – |
Left-sided | 0.84 [0.69–1.03] | 0.10 | 0.83 [0.59–1.18] | 0.31 |
Rectum | 0.83 [0.66–1.04] | 0.11 | 0.86 [0.57–1.29] | 0.46 |
Preoperative systemic CTx | 1.75 [1.40–2.19] | < 0.001 | 1.67 [1.13–2.47] | < 0.01 |
Number of CRLM | 1.09 [1.06–1.12] | < 0.001 | 1.10 [1.04–1.16] | < 0.01 |
Diameter of largest CRLM (cm) | 1.04 [1.02–1.07] | < 0.01 | 1.08 [1.03–1.14] | < 0.001 |
Preoperative CEA (before chemo) | 1.00 [1.00–1.00] | 0.76 | 1.00 [1.00–1.00] | 0.63 |
Disease-free interval (months) | 1.00 [0.99–1.00] | 0.54 | 1.00 [0.98–1.01] | 0.51 |
Nodal status primary tumor | 1.45 [1.22–1.73] | < 0.001 | 2.01 [1.42–2.83] | < 0.001 |
R1 resection | 1.68 [1.36–2.07] | < 0.001 | 1.53 [1.01–2.31] | 0.04 |
KRAS mutated | 1.71 [1.32–2.21] | < 0.001 | 1.63 [1.20–2.22] | < 0.01 |
dHGP (vs. non-dHGP) | 0.67 [0.54–0.82] | < 0.001 | 0.49 [0.32–0.73] | < 0.001 |
HAIP chemotherapy | 0.62 [0.50–0.76] | < 0.001 | 0.61 [0.45–0.82] | < 0.001 |
Univariable | p value | Multivariable | p value | |
---|---|---|---|---|
Overall survival (n = 496) | ||||
Age < 65 years | 0.73 [0.62–0.86] | < 0.001 | 1.01 [0.73–1.39] | 0.95 |
ASA > II | 0.95 [0.80–1.13] | 0.56 | 1.08 [0.80–1.47] | 0.62 |
Location primary tumor | ||||
Right-sided | Reference | – | Reference | – |
Left-sided | 0.84 [0.69–1.03] | 0.10 | 0.83 [0.59–1.18] | 0.30 |
Rectum | 0.83 [0.66–1.04] | 0.11 | 0.86 [0.57–1.29] | 0.46 |
Preoperative systemic CTx | 1.75 [1.40–2.19] | < 0.001 | 1.67 [1.13–2.47] | < 0.01 |
Number of CRLM | 1.09 [1.06–1.12] | < 0.001 | 1.10 [1.04–1.16] | < 0.01 |
Diameter of largest CRLM (cm) | 1.04 [1.02–1.07] | < 0.01 | 1.08 [1.03–1.14] | < 0.001 |
Preoperative CEA (before chemo) | 1.00 [1.00–1.00] | 0.76 | 1.00 [1.00–1.00] | 0.63 |
Disease-free interval (months) | 1.00 [0.99–1.00] | 0.54 | 1.00 [0.98–1.01] | 0.50 |
Nodal status primary tumor | 1.45 [1.22–1.73] | < 0.001 | 2.01 [1.42–2.83] | < 0.001 |
R1 resection | 1.68 [1.36–2.07] | < 0.001 | 1.52 [1.01–2.30] | 0.05 |
KRAS mutated | 1.71 [1.32–2.21] | < 0.001 | 1.64 [1.21–2.22] | < 0.01 |
dHGP (vs. non-dHGP) | 0.71 [0.56–0.89] | < 0.01 | 0.47 [0.27–0.82] | < 0.01 |
HAIP chemotherapy | 0.66 [0.52–0.83] | < 0.001 | 0.60 [0.44–0.83] | < 0.01 |
Interaction term: dHGP*HAIP | 0.77 [0.44–1.32] | 0.34 | 1.06 [0.47–2.36] | 0.90 |
Progression-free survival | ||||
Age < 65 years | 1.01 [0.88–1.16] | 0.84 | 1.32 [1.02–1.69] | 0.03 |
ASA >II | 0.95 [0.83–1.09] | 0.46 | 1.11 [0.88–1.40] | 0.38 |
Location primary tumor | ||||
Right-sided | Reference | – | Reference | – |
Left-sided | 1.07 [0.90–1.27] | 0.43 | 1.29 [0.97–1.70] | 0.08 |
Rectum | 1.12 [0.93–1.35] | 0.21 | 1.40 [1.02–1.91] | 0.04 |
Preoperative systemic CTx | 1.65 [1.39–1.96] | < 0.001 | 1.50 [1.12–1.99] | < 0.01 |
Number of CRLM | 1.11 [1.08–1.13] | < 0.001 | 1.15 [1.10–1.20] | < 0.001 |
Diameter of largest CRLM (cm) | 1.04 [1.02–1.06] | < 0.001 | 1.08 [1.03–1.12] | < 0.001 |
Preoperative CEA (before chemo) | 1.00 [1.00–1.00] | 0.04 | 1.00 [1.00–1.00] | 0.99 |
Disease-free interval (months) | 0.99 [0.99–1.00] | < 0.01 | 0.99 [0.98–1.00] | 0.22 |
Nodal status primary tumor | 1.38 [1.20–1.59] | < 0.001 | 1.58 [1.24–2.02] | < 0.001 |
R1 resection | 1.51 [1.26–1.82] | < 0.001 | 1.27 [0.91–1.77] | 0.16 |
KRAS mutated | 1.63 [1.35–1.97] | < 0.001 | 1.73 [1.37–2.18] | < 0.001 |
dHGP (vs. non-dHGP) | 0.58 [0.48–0.70] | < 0.001 | 0.47 [0.32–0.70] | < 0.001 |
HAIP chemotherapy | 0.65 [0.55–0.78] | < 0.001 | 0.50 [0.39–0.64] | < 0.001 |
Interaction term: dHGP*HAIP | 1.01 [0.67–1.52] | 0.95 | 1.29 [0.72–2.32] | 0.40 |
Hepatic progression-free survival | ||||
Age < 65 years | 0.97 [0.84–1.13] | 0.73 | 1.29 [0.98–1.71] | 0.07 |
ASA >II | 0.92 [0.80–1.07] | 0.29 | 1.33 [1.03–1.73] | 0.03 |
Location primary tumor | ||||
Right-sided | Reference | – | Reference | – |
Left-sided | 1.08 [0.90–1.28] | 0.43 | 1.14 [0.85–1.55] | 0.38 |
Rectum | 1.07 [0.87–1.30] | 0.52 | 1.26 [0.89–1.78] | 0.20 |
Preoperative systemic CTx | 1.83 [1.51–2.22] | < 0.001 | 1.34 [0.97–1.85] | 0.08 |
Number of CRLM | 1.13 [1.10–1.15] | < 0.001 | 1.15 [1.10–1.21] | < 0.001 |
Diameter of largest CRLM (cm) | 1.01 [0.99–1.04] | 0.31 | 1.05 [1.00–1.10] | 0.05 |
Preoperative CEA (before chemo) | 1.00 [1.00–1.00] | 0.86 | 1.00 [1.00–1.00] | 0.36 |
Disease-free interval (months) | 0.99 [0.99–1.00] | < 0.001 | 0.99 [0.98–1.00] | 0.26 |
Nodal status primary tumor | 1.36 [1.17–1.58] | < 0.001 | 1.76 [1.33–2.32] | < 0.001 |
R1 resection | 1.56 [1.29–1.89] | < 0.001 | 1.17 [0.80–1.71] | 0.41 |
KRAS mutated | 1.40 [1.14–1.73] | < 0.01 | 1.42 [1.10–1.83] | < 0.01 |
dHGP (vs. non-dHGP) | 1.67 [1.37–2.04] | < 0.001 | 1.53 [1.01–2.32] | 0.05 |
HAIP chemotherapy | 0.63 [0.42–0.94] | 0.02 | 0.57 [0.32–1.01] | 0.05 |
Interaction term: dHGP*HAIP | 0.80 [0.51–1.24] | 0.31 | 0.79 [0.42–1.49] | 0.46 |