Table 1.
The results of subgroups analysis based on clinical variables in different GI cancers
| OS | PFS | OS | PFS | OS | PFS | |||
|---|---|---|---|---|---|---|---|---|
| NO | HR (95%CI) | NO | HR (95%CI) | NO | HR (95%CI) | |||
| A) Hepatocellular carcinoma | ||||||||
| Age | 0.783 | 0.145 | ||||||
| ≥ 65 yr | 4 | 0.80 (0.71, 0.91) | 0.0% (0.454) | 2 | 0.65 (0.52, 0.82) | 0.0% (0.795) | ||
| < 65 yr | 4 | 0.82 (0.72, 0.94) | 0.0% (0.892) | 1 | 0.89 (0.63, 1.26) | NA | ||
| Sex | 0.647 | 0.629 | ||||||
| Male | 4 | 0.77 (0.69, 0.86) | 0.0% (0.457) | 2 | 0.66 (0.55, 0.80) | 30.3% (0.231) | ||
| Female | 4 | 0.82 (0.64, 1.07) | 0.0% (0.442) | 2 | 0.60 (0.40, 0.89) | 0.0% (0.968) | ||
| ECOG performance status | 0.689 | 0.614 | ||||||
| 0 | 5 | 0.77 (0.68, 0.88) | 0.0% (0.474) | 3 | 0.60 (0.50, 0.72) | 0.0%, (0.592) | ||
| 1 | 5 | 0.74 (0.65, 0.86) | 44.6% (0.124) | 3 | 0.64 (0.53, 0.78) | 24.3%, (0.267) | ||
| Location | 0.078 | 0.171 | ||||||
| Asia | 7 | 0.75 (0.67, 0.84) | 0.0% (0.534) | 4 | 0.63 (0.54, 0.75) | 44.9% (0.142) | ||
| Rest of the world | 6 | 0.86 (0.78, 0.96) | 0.0% (0.557) | 3 | 0.74 (0.63, 0.87) | 0.0% (0.872) | ||
| AFP at baseline | 0.368 | 0.021 | ||||||
| ≥ 400 ng/mL | 5 | 0.66 (0.57, 0.77) | 0.0% (0.942) | 2 | 0.64 (0.53, 0.78) | 35.5% (0.213) | ||
| < 400 ng/mL | 5 | 0.75 (0.60, 0.93) | 59.8% (0.041) | 2 | 0.46 (0.37, 0.56) | 0.0%, (0.541) | ||
| Barcelona liver stage | 0.332 | 0.843 | ||||||
| B | 6 | 0.89 (0.63, 1.24) | 50.7% (0.071) | 3 | 0.63 (0.45, 0.89) | 48.0% (0.146) | ||
| C | 6 | 0.74 (0.66, 0.84) | 34.5%, (0.177) | 3 | 0.61 (0.53, 0.70) | 0.0% (0.682) | ||
| Macrovascular invasion at study entry | 0.365 | 0.598 | ||||||
| Yes | 5 | 0.71 (0.60, 0.84) | 0.0%, (0.425) | 3 | 0.58 (0.46, 0.74) | 0.0% (0.546) | ||
| No | 5 | 0.78 (0.70, 0.87) | 29.0% (0.228) | 3 | 0.63 (0.54, 0.73) | 6.4% (0.344) | ||
| Extrahepatic spread at study entry | 0.06 | 0.213 | ||||||
| Yes | 5 | 0.70 (0.62, 0.78) | 49.7% (0.093) | 3 | 0.58 (0.50, 0.67) | 0.0% (0.440) | ||
| No | 5 | 0.84 (0.72, 0.98) | 0.0%, (0.811) | 3 | 0.70 (0.54, 0.89) | 0.0% (0.368) | ||
| MVI and/or extrahepatic spread at study entry | 0.017 | 0.103 | ||||||
| Yes | 6 | 0.72 (0.66, 0.80) | 15.8%, (0.312) | 3 | 0.55 (0.47, 0.65) | 0.0% (0.932) | ||
| No | 6 | 0.91 (0.78, 1.08) | 46.4%, (0.097) | 3 | 0.73 (0.54, 0.98) | 15.7% (0.305) | ||
| Etiology | 0.001 | 0.028 | ||||||
| Hepatitis B | 7 | 0.65 (0.57, 0.74) | 0.0%, (0.514) | 4 | 0.54 (0.46, 0.64) | 0.0%, (0.508) | ||
| Hepatitis C | 6 | 0.92 (0.77, 1.09) | 42.1%, (0.125) | 3 | 0.60 (0.43, 0.84) | 0.0%, (0.633) | ||
| Nonviral | 6 | 0.87 (0.77, 0.98) | 0.0%, (0.502) | 3 | 0.78 (0.63, 0.96) | 0.0%, (0.658) | ||
| B) Gastric cancer | ||||||||
| Age | 0.844 | 0.987 | ||||||
| ≥ 65 yr | 9 | 0.84 (0.77, 0.93) | 39.3%, (0.106) | 2 | 1.06 (0.64, 1.74) | 75.3%, (0.044) | ||
| < 65 yr | 9 | 0.85 (0.79, 0.93) | 13.0%, (0.326) | 2 | 1.07 (0.32, 3.52) | 96.5%, (0.000) | ||
| Sex | 0.046 | 0.688 | ||||||
| Male | 9 | 0.82 (0.76, 0.88) | 33.9%, (0.147) | 2 | 1.03 (0.48, 2.18) | 93.6%, (0.000) | ||
| Female | 9 | 0.94 (0.84, 1.06) | 0.0%, (0.517) | 2 | 1.40 (0.38, 5.18) | 94.3%, (0.000) | ||
| ECOG performance status | 621 | 0.700 | ||||||
| 0 | 8 | 0.89 (0.77, 1.03) | 43.0%, (0.092) | 2 | 1.29 (0.46, 3.67) | 93.4%, (0.000) | ||
| 1 | 8 | 0.84 (0.74, 0.97) | 54.4%, (0.032) | 2 | 0.99 (0.41, 2.39) | 94.1%, (0.000) | ||
| Location | 0.884 | 0.372 | ||||||
| Asia | 8 | 0.85 (0.75, 0.97) | 32.1%, (0.171) | 2 | 1.91 (1.38, 2.64) | 12.3%, (0.286) | ||
| Rest of the world | 7 | 0.86 (0.80, 0.93) | 0.0%, (0.732) | 1 | 1.57 (1.19, 2.08) | NA | ||
| Lauren histological type | 0.449 | 0.09 | ||||||
| Diffuse type | 6 | 0.85 (0.76, 0.96) | 43.7%, (0.114) | 1 | 0.84 (0.62, 1.14) | NA | ||
| Intestinal type | 6 | 0.80 (0.71, 0.90) | 12.9%, (0.332) | 1 | 0.56 (0.39, 0.80) | NA | ||
| Primary sites | 0.986 | 0.666 | ||||||
| Gastric cancer | 9 | 0.87 (0.78, 0.97) | 51.1%, (0.037) | 2 | 1.16 (0.44, 3.09) | 95.9%, (0.000) | ||
| Gastroesophageal junction cancer | 9 | 0.87 (0.76, 0.99) | 0.0%, (0.641) | 2 | 0.89 (0.44, 1.81) | 65.8%, (0.087) | ||
| Liver metastasis | 0.344 | 0.204 | ||||||
| Yes | 3 | 0.72 (0.63, 0.84) | 0.0%, (0.899) | 1 | 0.59 (0.42, 0.83) | NA | ||
| No | 3 | 0.82 (0.66, 1.03) | 72.2%, (0.027) | 1 | 0.79 (0.59, 1.05) | NA | ||
| Lymph node metastasis | 0.405 | 0.559 | ||||||
| Yes | 1 | 0.94 (0.77, 1.15) | NA | 1 | 0.73 (0.58, 0.92) | NA | ||
| No | 1 | 0.77 (0.50, 1.18) | NA | 1 | 0.61 (0.35, 1.06) | NA | ||
| Peritoneal metastasis | 0.130 | 0.002 | ||||||
| Yes | 2 | 0.98 (0.61, 1.56) | 72.1%, (0.058) | 1 | 1.04 (0.76, 1.43) | NA | ||
| No | 2 | 0.66 (0.55, 0.79) | 0.0%, (0.687) | 1 | 0.51 (0.37, 0.70) | NA | ||
| Number of organs with metastases | 0.245 | 0.014 | ||||||
| < 2 | 4 | 0.72 (0.60, 0.85) | 0.0%, (0.672) | 1 | 0.42 (0.26, 0.69) | NA | ||
| ≥ 2 | 4 | 0.84 (0.68, 1.04) | 78.4%, (0.003) | 1 | 0.84 (0.66, 1.07) | NA | ||
| Microsatellite status | 0.000 | |||||||
| Stable | 5 | 0.87 (0.79, 0.95) | 42.1%, (0.178) | |||||
| Unstable (Instability-high) | 3 | 0.33 (0.20, 0.52) | 0.0%, (0.988) | |||||
| Prior gastrectomy | 0.924 | 0.956 | ||||||
| Yes | 4 | 0.89 (0.73, 1.08) | 0.0%, (0.913) | 1 | 0.71 (0.46, 1.10) | NA | ||
| No | 4 | 0.90 (0.80, 1.00) | 0.0%, (0.826) | 1 | 0.70 (0.54, 0.90) | NA | ||
| Disease status | 0.313 | |||||||
| Metastatic | 2 | 0.91 (0.77, 1.07) | 0.0%, (0.633) | |||||
| Locally advanced | 1 | 2.84 (0.31,25.74) | NA | |||||
| C) Esophageal cancer | ||||||||
| Age | 0.175 | 0.133 | ||||||
| ≥ 65 yr | 9 | 0.67 (0.60, 0.75) | 0.0% (0.701) | 6 | 0.58 (0.51, 0.66) | 37.9%, (0.154) | ||
| < 65 yr | 9 | 0.74 (0.68, 0.81) | 0.0%,(0.623) | 6 | 0.66 (0.60, 0.73) | 44.3%, (0.110) | ||
| Sex | 0.029 | 0.588 | ||||||
| Male | 10 | 0.72 (0.67, 0.77) | 26.6%, (0.199) | 6 | 0.63 (0.54, 0.75) | 67.2%, (0.009) | ||
| Female | 10 | 0.90 (0.75, 1.08) | 9.1%, (0.359) | 6 | 0.69 (0.54, 0.89) | 0.0%, (0.655) | ||
| ECOG performance status | 0.623 | 0.674 | ||||||
| 0 | 10 | 0.74 (0.66, 0.83) | 0.0%, (0.449) | 6 | 0.61 (0.50, 0.76) | 34.6%, (0.177) | ||
| 1 | 10 | 0.71 (0.66, 0.78) | 0.0%, (0.739) | 6 | 0.65 (0.56, 0.75) | 53.5%, (0.056) | ||
| Location | 0.145 | 0.889 | ||||||
| Asia | 4 | 0.71 (0.62, 0.80) | 18.8% (0.296) | 2 | 0.68 (0.51, 0.91) | 69.6%, (0.070) | ||
| Rest of the world | 4 | 0.84 (0.69, 1.02) | 54.6%, (0.086) | 1 | 0.70 (0.56, 0.88) | NA | ||
| Histology | 0.240 | 0.239 | ||||||
| Adenocarcinoma | 2 | 0.92 (0.61, 1.38) | 73.3%, (0.053) | 1 | 0.63 (0.46, 0.87) | NA | ||
| Squamous cell carcinoma | 11 | 0.72 (0.67, 0.77) | 0.0%, (0.860) | 10 | 0.79 (0.65, 0.95) | 84.9%, (0.000) | ||
| Liver metastasis | 0.358 | 0.451 | ||||||
| Yes | 4 | 0.64 (0.51, 0.80) | 0.0%, (0.792) | 3 | 0.75 (0.48, 1.15) | 67.0%, (0.048) | ||
| No | 4 | 0.72 (0.63, 0.83) | 0.0%, (0.738) | 3 | 0.62 (0.48, 0.79) | 61.8%, (0.073) | ||
| Lymph node metastasis | 0.319 | |||||||
| Yes | 2 | 0.80 (0.65, 0.98) | 0.0%, (0.540) | |||||
| No | 2 | 0.68 (0.55, 0.86) | 0.0%, (0.702) | |||||
| Number of organs with metastases | 0.169 | 0.138 | ||||||
| < 2 | 5 | 0.79 (0.69, 0.91) | 0.0%, (0.923) | 2 | 0.70 (0.56, 0.86) | 0.0%, (0.350) | ||
| ≥ 2 | 5 | 0.70 (0.62, 0.79) | 0.0%, (0.454) | 2 | 0.56 (0.46, 0.68) | 44.0%, (0.181) | ||
| Disease status | 0.063 | 0.408 | ||||||
| Metastatic | 6 | 0.66 (0.60, 0.74) | 0.0%, (0.802) | 4 | 0.58 (0.52, 0.65) | 0.0%, (0.409) | ||
| Locally advanced | 6 | 0.80 (0.68, 0.95) | 0.0%, (0.833) | 4 | 0.65 (0.50, 0.85) | 0.0%, (0.847) | ||
| Smoking history | 0.806 | 0.852 | ||||||
| Never | 5 | 0.77 (0.62, 0.95) | 0.0%, (0.565) | 2 | 0.79 (0.47, 1.32) | 58.8%, (0.119) | ||
| Current or former | 5 | 0.75 (0.67, 0.83) | 0.0%, (0.867) | 2 | 0.73 (0.39, 1.36) | 85.8%, (0.008) | ||
| D) Colorectal cancer | ||||||||
| Age | 0.570 | 0.804 | ||||||
| ≥ 65 yr | 3 | 0.89 (0.52, 1.54) | 69.1%, (0.039) | 3 | 1.07 (0.81, 1.40) | 0.0%, (0.539) | ||
| < 65 yr | 3 | 1.06 (0.85, 1.32) | 0.1%, (0.368) | 3 | 1.11 (0.91, 1.35) | 47.8%, (0.147) | ||
| Sex | 0.963 | 0.080 | ||||||
| Male | 2 | 0.73 (0.55, 0.95) | 0.0%, (0.383) | 1 | 0.77 (0.57, 1.05) | NA | ||
| Female | 2 | 0.72 (0.50, 1.03) | 39.0%, (0.200) | 1 | 1.21 (0.81, 1.80) | NA | ||
| ECOG performance status | 0.926 | 0.806 | ||||||
| 0 | 4 | 0.91 (0.55, 1.50) | 75.0%, (0.007) | 3 | 1.24 (0.66, 2.32) | 86.2%, (0.001) | ||
| 1 | 4 | 0.88 (0.71, 1.09) | 13.0%, (0.327) | 3 | 1.14 (0.90, 1.44) | 0.0%, (0.623) | ||
| Location | 0.753 | |||||||
| Asia | 1 | 0.65 (0.27, 1.56) | NA | |||||
| Rest of the world | 1 | 0.76 (0.52, 1.09) | NA | |||||
| BRAF status | 0.507 | |||||||
| Wild type | 3 | 0.61 (0.39, 0.95) | 0.0%, (0.720) | |||||
| Variant | 2 | 0.71 (0.52, 0.96) | 0.0%, (0.375) | |||||
| KRAS/NRAS status | 0.569 | |||||||
| Wild type | 2 | 0.61 (0.39, 0.95) | 0.0%, (0.720) | |||||
| Variant | 2 | 0.71 (0.52, 0.96) | 0.0%, (0.375) | |||||
| Liver metastasis | 0.044 | 0.751 | ||||||
| Yes | 1 | 1.14 (0.72, 1.81) | NA | 2 | 0.86 (0.69, 1.09) | 0.0%, (0.512) | ||
| No | 1 | 0.33 (0.11, 1.00) | NA | 2 | 0.80 (0.51, 1.24) | 0.0%, (0.523) | ||
| Site of primary tomur | 0.358 | 0.519 | ||||||
| Right | 3 | 0.78 (0.58, 1.06) | 0.0%, (0.715) | 3 | 1.00 (0.71, 1.39) | 0.0%, (0.947) | ||
| Left | 3 | 0.95 (0.71, 1.28) | 0.0%, (0.812) | 3 | 1.13 (0.92, 1.40) | 26.0%, (0.259) | ||
| Microsatellite status | 0.402 | 0.622 | ||||||
| Stable | 3 | 0.91 (0.64, 1.28) | 68.9%, (0.040) | 3 | 1.07 (0.71, 1.61) | 77.2%, (0.012) | ||
| Unstable (Instability-high) | 1 | 0.74 (0.53, 1.03) | NA | 2 | 0.84 (0.35, 2.01) | 60.5%, (0.111) | ||
| Number of organs with metastases | 0.668 | |||||||
| < 2 | 1 | 0.98 (0.68, 1.41) | NA | |||||
| ≥ 2 | 1 | 0.88 (0.63, 1.22) | NA | |||||
| E) Pancreatic cancer | ||||||||
| Age | 0.491 | 0.177 | ||||||
| ≥ 65 yr | 2 | 0.92 (0.67, 1.25) | 0.0%, (0.837) | 1 | 0.73 (0.48, 1.11) | NA | ||
| < 65 yr | 2 | 0.72 (0.39, 1.34) | 69.6%, (0.070) | 1 | 0.48 (0.31, 0.75) | NA | ||
| Sex | 0.486 | 0.234 | ||||||
| Male | 2 | 0.72 (0.52, 0.99) | 42.7%, (0.187) | 1 | 0.52 (0.35, 0.77) | NA | ||
| Female | 2 | 0.85 (0.60, 1.20) | 0.0%, (0.947) | 1 | 0.76 (0.47, 1.23) | NA | ||
| ECOG performance status | 0.444 | 0.056 | ||||||
| 0 | 2 | 0.72 (0.32, 1.65) | 75.4%, (0.044) | 1 | 0.47 (0.31, 0.71) | NA | ||
| 1 | 2 | 1.01 (0.81, 1.26) | 0.0%, (0.461) | 1 | 0.87 (0.54, 1.41) | NA | ||
| F) Biliary tract cancer | ||||||||
| Age | 0.949 | 0.211 | ||||||
| ≥ 65 yr | 1 | 0.79 (0.60, 1.04) | NA | 1 | 0.84 (0.66, 1.07) | NA | ||
| < 65 yr | 1 | 0.80 (0.61, 1.04) | NA | 1 | 0.68 (0.54, 0.85) | NA | ||
| Sex | 0.797 | 0.696 | ||||||
| Male | 1 | 0.78 (0.60, 1.01) | NA | 1 | 0.73 (0.58, 0.92) | NA | ||
| Female | 1 | 0.82 (0.62, 1.08) | NA | 1 | 0.78 (0.62, 0.99) | NA | ||
| ECOG performance status | 0.255 | 0.938 | ||||||
| 0 | 1 | 0.90 (0.68, 1.20) | NA | 1 | 0.77 (0.61, 0.98) | NA | ||
| 1 | 1 | 0.72 (0.56, 0.93) | NA | 1 | 0.76 (0.60, 0.96) | NA | ||
| Location | 0.290 | 0.127 | ||||||
| Asia | 1 | 0.72 (0.56, 0.93) | NA | 1 | 0.67 (0.54, 0.84) | NA | ||
| Rest of the world | 1 | 0.89 (0.66, 1.20) | NA | 1 | 0.87 (0.68, 1.12) | NA | ||
| Disease status | 0.108 | 0.012 | ||||||
| Metastatic | 1 | 0.49 (0.27, 0.90) | NA | 1 | 0.42 (0.26, 0.68) | NA | ||
| Locally advanced | 1 | 0.83 (0.68, 1.02) | NA | 1 | 0.81 (0.68, 0.97) | NA | ||