1Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
2Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
3Pancreatobiliary Cancer Clinic, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
4Biostatistics Collaboration Unit, Medical Research Center, Yonsei University College of Medicine, Seoul, Korea
5Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
6Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea
Copyright © 2017 by the Korean Cancer Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Characteristic | Total (n=482) | Investigation dataset (n=340) | Validation dataset (n=142) | p-value |
---|---|---|---|---|
Age (yr) | ||||
< 67 | 235 (48.8) | 163 (47.9) | 72 (50.7) | 0.58 |
≥ 67 | 247 (51.2) | 177 (52.1) | 70 (49.3) | |
Sex | ||||
Male | 281 (58.3) | 201 (59.1) | 80 (56.3) | 0.573 |
Female | 201 (41.7) | 139 (40.9) | 62 (43.7) | |
Disease status | ||||
Recurrent | 158 (32.8) | 117 (34.4) | 41 (28.9) | 0.238 |
Metastatic | 324 (67.2) | 223 (65.6) | 101 (71.1) | |
ECOG | ||||
0-2 | 418 (86.7) | 296 (87.1) | 122 (85.9) | 0.736 |
3-4 | 64 (13.3) | 44 (12.9) | 20 (14.1) | |
Primary site | ||||
Intrahepatic CC | 123 (25.5) | 87 (25.6) | 36 (25.4) | 1.00 |
Hilar CC | 79 (16.4) | 56 (16.5) | 23 (16.2) | |
Non-hilar CC | 87 (18.0) | 61 (17.9) | 26 (18.3) | |
Gallbladder | 146 (30.3) | 103 (30.3) | 43 (30.3) | |
Ampullary | 47 (9.8) | 33 (9.7) | 14 (9.9) | |
BMI | 22.8 (20.6-25.0) | 22.7 (20.4-24.9) | 23.2 (21.0-25.1) | 0.223 |
Complete blood count | ||||
WBC count (/μL) | 7,090 (5,525-9,615) | 7,070 (5,555-9,650) | 7,130 (5,328-9,563) | 0.881 |
Hemoglobin (g/dL) | 12.2 (11.1-13.4) | 12.1 (11.1-13.4) | 12.3 (11.1-13.4) | 0.771 |
Platelet (×103/μL) | 243 (189-319) | 241 (186-314) | 250 (200-326) | 0.398 |
NLR | 3.2 (2.0-5.8) | 3.3 (2.0-5.7) | 3.2 (2.1-6.1) | 0.738 |
PLR | 171 (122-251) | 165 (120-234) | 181 (123-275) | |
Blood chemistry profile | ||||
Protein (g/dL) | 6.9 (6.5-7.4) | 6.9 (6.5-7.4) | 7.0 (6.5-7.4) | 0.804 |
Albumin (g/dL) | 3.9 (3.4-4.3) | 3.9 (3.4-4.3) | 3.9 (3.4-4.3) | 0.775 |
BUN (mg/dL) | 14.7 (11.5-19.2) | 14.8 (11.6-19.3) | 14.4 (11.3-18.9) | 0.671 |
AST (IU/L) | 36 (22-75) | 37 (23-81) | 35 (22-68) | 0.433 |
ALT (IU/L) | 30 (17-74) | 30 (17-72) | 29 (18-76) | 0.850 |
Bilirubin (mg/dL) | 0.8 (0.5-3.4) | 0.8 (0.5-3.6) | 0.8 (0.5-2.7) | 0.650 |
ALP (IU/L) | 146 (89-321) | 146 (88-321) | 141 (91-312) | 0.599 |
Cholesterol (mg/dL) | 167 (134-198) | 168 (134-194) | 165 (132-202) | 0.900 |
Tumor marker | ||||
CEA (ng/mL) | 3.6 (1.9-16.0) | 3.2 (1.8-15.1) | 4.2 (2.4-18.9) | 0.056 |
CA 19-9 (U/mL) | 160 (26-1,472) | 166 (25-1,587) | 145 (27-1,298) | 0.567 |
Palliative Tx | ||||
No | 148 (30.7) | 106 (31.2) | 42 (29.6) | 0.809 |
Gem/Cis | 168 (34.9) | 120 (35.3) | 48 (33.8) | |
Othersa) | 166 (34.4) | 114 (33.5) | 52 (36.6) |
Values are presented as number (%) or median (interquartile range). The Mann-Whitney U test was used for comparisons of continuous values. ECOG, Eastern Cooperative Oncology Group; CC, cholangiocarcinoma; BMI, body mass index; WBC, white blood cell; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CEA, carcinoembryonic antigen; CA 19-9, carbohydrate antigen 19-9; Tx, treatment; Gem/Cis, combination chemotherapy with cisplatin and gemcitabine.
a) Fluorouracil or gemcitabine-based (excluding Gem/Cis) chemotherapy.
Characteristic |
Investigation dataset |
Validation dataset |
||||
---|---|---|---|---|---|---|
HR | 95% CI | p-value | HR | 95% CI | p-value | |
Age (yr) | ||||||
< 67 | 1 | 0.02 | 1 | 0.249 | ||
≥ 67 | 1.311 | 1.043-1.649 | 1.231 | 0.865-1.754 | ||
Sex | ||||||
Male | 1 | 0.515 | 1 | 0.937 | ||
Female | 0.926 | 0.735-1.167 | 1.014 | 0.713-1.443 | ||
Disease status | ||||||
Recurrent | 1 | < 0.001 | 1 | 0.057 | ||
Metastatic | 1.584 | 1.24-2.023 | 1.462 | 0.989-2.161 | ||
ECOG | ||||||
0-2 | 1 | < 0.001 | 1 | < 0.001 | ||
3-4 | 4.499 | 3.205-6.316 | 5.276 | 3.102-8.972 | ||
Primary site | ||||||
Intrahepatic CC | 1 | 0.045 | 1 | 0.187 | ||
Hilar CC | 0.802 | 0.563-1.144 | 0.834 | 0.479-1.451 | ||
Non-hilar CC | 0.91 | 0.643-1.289 | 0.592 | 0.349-1.004 | ||
Gallbladder cancer | 0.94 | 0.692-1.276 | 0.895 | 0.56-1.431 | ||
Ampullary cancer | 0.514 | 0.331-0.8 | 0.519 | 0.255-1.057 | ||
BMI | ||||||
≥ 18.5 | 1 | 0.001 | 1 | 0.024 | ||
< 18.5 | 2 | 1.332-3.002 | 2.225 | 1.111-4.459 | ||
WBC count (/μL) | ||||||
Normal (< 10,800) | 1 | < 0.001 | 1 | < 0.001 | ||
Abnormal (≥ 10,800) | 1.779 | 1.327-2.383 | 3.177 | 2.014-5.012 | ||
Hemoglobin (g/dL) | ||||||
Normal (≥ 12) | 1 | 0.005 | 1 | 0.209 | ||
Abnormal (< 12) | 1.391 | 1.107-1.748 | 1.254 | 0.881-1.784 | ||
Platelet (×103/μL) | ||||||
Normal (≥ 150) | 1 | 0.086 | 1 | 0.814 | ||
Abnormal (< 150) | 1.375 | 0.955-1.98 | 0.935 | 0.535-1.634 | ||
Protein (g/dL) | ||||||
Normal (≥ 6.9) | 1 | 0.013 | 1 | 0.006 | ||
Abnormal (< 6.9) | 1.337 | 1.064-1.681 | 1.635 | 1.149-2.325 | ||
Albumin (g/dL) | ||||||
Normal (≥ 3.4) | 1 | < 0.001 | 1 | 0.011 | ||
Abnormal (< 3.4) | 2.216 | 1.698-2.892 | 1.699 | 1.132-2.552 | ||
BUN (mg/dL) | ||||||
Normal (< 23) | 1 | 0.058 | 1 | 0.01 | ||
Abnormal (≥ 23) | 1.401 | 0.988-1.988 | 1.956 | 1.178-3.25 | ||
AST (IU/L) | ||||||
Normal (< 30) | 1 | 0.151 | 1 | 0.176 | ||
Abnormal (≥ 30) | 1.187 | 0.94-1.501 | 1.279 | 0.895-1.826 | ||
ALT (IU/L) | ||||||
Normal (< 33) | 1 | 0.773 | 1 | 0.237 | ||
Abnormal (≥ 33) | 1.034 | 0.823-1.299 | 1.239 | 0.869-1.768 | ||
Bilirubin (mg/dL) | ||||||
Normal (< 1.2) | 1 | 0.435 | 1 | 0.198 | ||
Abnormal (≥ 1.2) | 1.099 | 0.867-1.394 | 1.277 | 0.88-1.853 | ||
ALP (IU/L) | ||||||
Normal (< 123) | 1 | 0.043 | 1 | 0.043 | ||
Abnormal (≥ 123) | 1.27 | 1.007-1.6 | 1.439 | 1.011-2.05 | ||
Cholesterol (mg/dL) | ||||||
Normal (< 139) | 1 | 0.005 | 1 | 0.022 | ||
Abnormal (≥ 139) | 1.437 | 1.114-1.854 | 1.586 | 1.068-2.353 | ||
CEA (ng/mL) | ||||||
< 9 | 1 | < 0.001 | 1 | 0.016 | ||
≥ 9 | 1.812 | 1.414-2.321 | 1.604 | 1.094-2.353 | ||
CA 19-9 (U/mL) | ||||||
< 120 | 1 | < 0.001 | 1 | 0.441 | ||
≥ 120 | 1.668 | 1.323-2.104 | 1.149 | 0.807-1.637 | ||
NLR | ||||||
< 3 | 1 | < 0.001 | 1 | < 0.001 | ||
≥ 3 | 2.04 | 1.616-2.575 | 2.96 | 2.042-4.29 | ||
PLR | ||||||
< 150 | 1 | < 0.001 | 1 | 0.057 | ||
≥ 150 | 1.719 | 1.355-2.181 | 1.43 | 0.99-2.066 | ||
Palliative Tx | ||||||
No | 1 | < 0.001 | 1 | < 0.001 | ||
Gem/Cis | 0.484 | 0.364-0.643 | 0.284 | 0.180-0.448 | ||
Othersa) | 0.492 | 0.372-0.650 | 0.305 | 0.198-0.471 |
HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; CC, cholangiocarcinoma; BMI, body mass index; WBC, white blood cell; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CEA, carcinoembryonic antigen; CA 19-9, carbohydrate antigen 19-9; NLR, neutrophillymphocyte ratio; PLR, platelet-lymphocyte ratio; Tx, treatment; Gem/Cis, combination chemotherapy with cisplatin and gemcitabine.
a) Fluorouracil or gemcitabine-based (excluding Gem/Cis) chemotherapy.
Characteristic | Total (n=482) | Investigation dataset (n=340) | Validation dataset (n=142) | p-value |
---|---|---|---|---|
Age (yr) | ||||
< 67 | 235 (48.8) | 163 (47.9) | 72 (50.7) | 0.58 |
≥ 67 | 247 (51.2) | 177 (52.1) | 70 (49.3) | |
Sex | ||||
Male | 281 (58.3) | 201 (59.1) | 80 (56.3) | 0.573 |
Female | 201 (41.7) | 139 (40.9) | 62 (43.7) | |
Disease status | ||||
Recurrent | 158 (32.8) | 117 (34.4) | 41 (28.9) | 0.238 |
Metastatic | 324 (67.2) | 223 (65.6) | 101 (71.1) | |
ECOG | ||||
0-2 | 418 (86.7) | 296 (87.1) | 122 (85.9) | 0.736 |
3-4 | 64 (13.3) | 44 (12.9) | 20 (14.1) | |
Primary site | ||||
Intrahepatic CC | 123 (25.5) | 87 (25.6) | 36 (25.4) | 1.00 |
Hilar CC | 79 (16.4) | 56 (16.5) | 23 (16.2) | |
Non-hilar CC | 87 (18.0) | 61 (17.9) | 26 (18.3) | |
Gallbladder | 146 (30.3) | 103 (30.3) | 43 (30.3) | |
Ampullary | 47 (9.8) | 33 (9.7) | 14 (9.9) | |
BMI | 22.8 (20.6-25.0) | 22.7 (20.4-24.9) | 23.2 (21.0-25.1) | 0.223 |
Complete blood count | ||||
WBC count (/μL) | 7,090 (5,525-9,615) | 7,070 (5,555-9,650) | 7,130 (5,328-9,563) | 0.881 |
Hemoglobin (g/dL) | 12.2 (11.1-13.4) | 12.1 (11.1-13.4) | 12.3 (11.1-13.4) | 0.771 |
Platelet (×103/μL) | 243 (189-319) | 241 (186-314) | 250 (200-326) | 0.398 |
NLR | 3.2 (2.0-5.8) | 3.3 (2.0-5.7) | 3.2 (2.1-6.1) | 0.738 |
PLR | 171 (122-251) | 165 (120-234) | 181 (123-275) | |
Blood chemistry profile | ||||
Protein (g/dL) | 6.9 (6.5-7.4) | 6.9 (6.5-7.4) | 7.0 (6.5-7.4) | 0.804 |
Albumin (g/dL) | 3.9 (3.4-4.3) | 3.9 (3.4-4.3) | 3.9 (3.4-4.3) | 0.775 |
BUN (mg/dL) | 14.7 (11.5-19.2) | 14.8 (11.6-19.3) | 14.4 (11.3-18.9) | 0.671 |
AST (IU/L) | 36 (22-75) | 37 (23-81) | 35 (22-68) | 0.433 |
ALT (IU/L) | 30 (17-74) | 30 (17-72) | 29 (18-76) | 0.850 |
Bilirubin (mg/dL) | 0.8 (0.5-3.4) | 0.8 (0.5-3.6) | 0.8 (0.5-2.7) | 0.650 |
ALP (IU/L) | 146 (89-321) | 146 (88-321) | 141 (91-312) | 0.599 |
Cholesterol (mg/dL) | 167 (134-198) | 168 (134-194) | 165 (132-202) | 0.900 |
Tumor marker | ||||
CEA (ng/mL) | 3.6 (1.9-16.0) | 3.2 (1.8-15.1) | 4.2 (2.4-18.9) | 0.056 |
CA 19-9 (U/mL) | 160 (26-1,472) | 166 (25-1,587) | 145 (27-1,298) | 0.567 |
Palliative Tx | ||||
No | 148 (30.7) | 106 (31.2) | 42 (29.6) | 0.809 |
Gem/Cis | 168 (34.9) | 120 (35.3) | 48 (33.8) | |
Others |
166 (34.4) | 114 (33.5) | 52 (36.6) |
Characteristic | Investigation dataset |
Validation dataset |
||||
---|---|---|---|---|---|---|
HR | 95% CI | p-value | HR | 95% CI | p-value | |
Age (yr) | ||||||
< 67 | 1 | 0.02 | 1 | 0.249 | ||
≥ 67 | 1.311 | 1.043-1.649 | 1.231 | 0.865-1.754 | ||
Sex | ||||||
Male | 1 | 0.515 | 1 | 0.937 | ||
Female | 0.926 | 0.735-1.167 | 1.014 | 0.713-1.443 | ||
Disease status | ||||||
Recurrent | 1 | < 0.001 | 1 | 0.057 | ||
Metastatic | 1.584 | 1.24-2.023 | 1.462 | 0.989-2.161 | ||
ECOG | ||||||
0-2 | 1 | < 0.001 | 1 | < 0.001 | ||
3-4 | 4.499 | 3.205-6.316 | 5.276 | 3.102-8.972 | ||
Primary site | ||||||
Intrahepatic CC | 1 | 0.045 | 1 | 0.187 | ||
Hilar CC | 0.802 | 0.563-1.144 | 0.834 | 0.479-1.451 | ||
Non-hilar CC | 0.91 | 0.643-1.289 | 0.592 | 0.349-1.004 | ||
Gallbladder cancer | 0.94 | 0.692-1.276 | 0.895 | 0.56-1.431 | ||
Ampullary cancer | 0.514 | 0.331-0.8 | 0.519 | 0.255-1.057 | ||
BMI | ||||||
≥ 18.5 | 1 | 0.001 | 1 | 0.024 | ||
< 18.5 | 2 | 1.332-3.002 | 2.225 | 1.111-4.459 | ||
WBC count (/μL) | ||||||
Normal (< 10,800) | 1 | < 0.001 | 1 | < 0.001 | ||
Abnormal (≥ 10,800) | 1.779 | 1.327-2.383 | 3.177 | 2.014-5.012 | ||
Hemoglobin (g/dL) | ||||||
Normal (≥ 12) | 1 | 0.005 | 1 | 0.209 | ||
Abnormal (< 12) | 1.391 | 1.107-1.748 | 1.254 | 0.881-1.784 | ||
Platelet (×103/μL) | ||||||
Normal (≥ 150) | 1 | 0.086 | 1 | 0.814 | ||
Abnormal (< 150) | 1.375 | 0.955-1.98 | 0.935 | 0.535-1.634 | ||
Protein (g/dL) | ||||||
Normal (≥ 6.9) | 1 | 0.013 | 1 | 0.006 | ||
Abnormal (< 6.9) | 1.337 | 1.064-1.681 | 1.635 | 1.149-2.325 | ||
Albumin (g/dL) | ||||||
Normal (≥ 3.4) | 1 | < 0.001 | 1 | 0.011 | ||
Abnormal (< 3.4) | 2.216 | 1.698-2.892 | 1.699 | 1.132-2.552 | ||
BUN (mg/dL) | ||||||
Normal (< 23) | 1 | 0.058 | 1 | 0.01 | ||
Abnormal (≥ 23) | 1.401 | 0.988-1.988 | 1.956 | 1.178-3.25 | ||
AST (IU/L) | ||||||
Normal (< 30) | 1 | 0.151 | 1 | 0.176 | ||
Abnormal (≥ 30) | 1.187 | 0.94-1.501 | 1.279 | 0.895-1.826 | ||
ALT (IU/L) | ||||||
Normal (< 33) | 1 | 0.773 | 1 | 0.237 | ||
Abnormal (≥ 33) | 1.034 | 0.823-1.299 | 1.239 | 0.869-1.768 | ||
Bilirubin (mg/dL) | ||||||
Normal (< 1.2) | 1 | 0.435 | 1 | 0.198 | ||
Abnormal (≥ 1.2) | 1.099 | 0.867-1.394 | 1.277 | 0.88-1.853 | ||
ALP (IU/L) | ||||||
Normal (< 123) | 1 | 0.043 | 1 | 0.043 | ||
Abnormal (≥ 123) | 1.27 | 1.007-1.6 | 1.439 | 1.011-2.05 | ||
Cholesterol (mg/dL) | ||||||
Normal (< 139) | 1 | 0.005 | 1 | 0.022 | ||
Abnormal (≥ 139) | 1.437 | 1.114-1.854 | 1.586 | 1.068-2.353 | ||
CEA (ng/mL) | ||||||
< 9 | 1 | < 0.001 | 1 | 0.016 | ||
≥ 9 | 1.812 | 1.414-2.321 | 1.604 | 1.094-2.353 | ||
CA 19-9 (U/mL) | ||||||
< 120 | 1 | < 0.001 | 1 | 0.441 | ||
≥ 120 | 1.668 | 1.323-2.104 | 1.149 | 0.807-1.637 | ||
NLR | ||||||
< 3 | 1 | < 0.001 | 1 | < 0.001 | ||
≥ 3 | 2.04 | 1.616-2.575 | 2.96 | 2.042-4.29 | ||
PLR | ||||||
< 150 | 1 | < 0.001 | 1 | 0.057 | ||
≥ 150 | 1.719 | 1.355-2.181 | 1.43 | 0.99-2.066 | ||
Palliative Tx | ||||||
No | 1 | < 0.001 | 1 | < 0.001 | ||
Gem/Cis | 0.484 | 0.364-0.643 | 0.284 | 0.180-0.448 | ||
Others |
0.492 | 0.372-0.650 | 0.305 | 0.198-0.471 |
Factor | Chi-square score | HR | 95% CI | p-value | Score |
---|---|---|---|---|---|
ECOG performance status | |||||
0-2 | 1.00 | 0.001 | 0 | ||
3-4 | 10.5 | 2.10 | 1.34-3.28 | +2 | |
Albumin (g/dL) | |||||
≥ 3.4 | 1.00 | 0.017 | 0 | ||
< 3.4 | 5.7 | 1.49 | 1.08-2.07 | +1 | |
CEA (ng/mL) | |||||
< 9 | 1.00 | 0.033 | 0 | ||
≥ 9 | 4.5 | 1.35 | 1.02-1.78 | +1 | |
CA 19-9 (U/mL) | |||||
< 120 | 1.00 | 0.032 | 0 | ||
≥ 120 | 4.6 | 1.32 | 1.02-1.70 | +1 | |
NLR | |||||
< 3 | 1.00 | < 0.001 | 0 | ||
≥ 3 | 14.5 | 1.64 | 1.27-2.11 | +3 |
Values are presented as number (%) or median (interquartile range). The Mann-Whitney U test was used for comparisons of continuous values. ECOG, Eastern Cooperative Oncology Group; CC, cholangiocarcinoma; BMI, body mass index; WBC, white blood cell; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CEA, carcinoembryonic antigen; CA 19-9, carbohydrate antigen 19-9; Tx, treatment; Gem/Cis, combination chemotherapy with cisplatin and gemcitabine. Fluorouracil or gemcitabine-based (excluding Gem/Cis) chemotherapy.
HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; CC, cholangiocarcinoma; BMI, body mass index; WBC, white blood cell; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CEA, carcinoembryonic antigen; CA 19-9, carbohydrate antigen 19-9; NLR, neutrophillymphocyte ratio; PLR, platelet-lymphocyte ratio; Tx, treatment; Gem/Cis, combination chemotherapy with cisplatin and gemcitabine. Fluorouracil or gemcitabine-based (excluding Gem/Cis) chemotherapy.
HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; CEA, carcinoembryonic antigen; CA 19-9, carbohydrate antigen 19-9; NLR, neutrophil-lymphocyte ratio.