Background
Methods
Patients and methods
QOL assessment
QOL instrument | Description |
---|---|
European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) [32] | EORTC QLQ-C30 is a general cancer instrument containing multiple items, measured in multiple-point Likert scales, that reflect the multidimensionality of QOL construct [32]. It includes five functional domains (physical, role, cognitive, emotional and social), three symptom domains (fatigue, pain, nausea and vomiting), and a global health and QOL domain. Six single items assess common symptoms in cancer patients (dyspnea, appetite loss, sleep disturbance, constipation and diarrhea) and financial problem. All scales and domains are transformed to scores ranging from 0 to 100. A lower score for a functional or global QOL scale reflects a poorer functioning level or global QOL, while a lower score for a symptom/problem scale reflects less symptoms/problem (better QOL). |
European Organization for Research and Treatment of Cancer QLQ-HCC18 (EORTC QLQ-HCC18) [33] | EORTC QLQ-HCC18 includes eighteen multiple item scales organized into six domains (fatigue, body image, jaundice, nutrition, pain and fever) and two items (abdominal swelling and sex life) [33]. All scales are grouped and transformed to score ranging from 0 to 100. A lower score represents a less severe symptom/problem (better QOL). EORTC QLQ-HCC18 is used together with EORTC QLQ-C30. |
C30 index score [30] | ∑ [(100-Physical functioning), (100-Role functioning), (100-Emotional functioning), (100-Cognitive functioning), (100-Social functioning), (100-global QOL), scores of Fatigue, Nausea and vomiting, Pain, Dyspnoea, Insomnia, Appetite loss, Constipation, Diarrhea, Financial Diffculty] ÷ 15. (remarks: a lower score represents a less severe symptom/problem) |
HCC18 index score [30] | ∑(scores of Fatigue, Body Image, Jaundice, Nutrition, Pain, Fever, Sex life, Abdominal distension) ÷ 8. (remarks: a lower score represents a less severe symptom/problem) |
Clinical factors
ALBI score | −0.085 × albumin + 0.66 × log bilirubin (remarks: albumin in g/L, bilirubin in μmol/L) |
MELD score | [9.57 x ln(Creatinine ÷ 88.4)] + [3.78 x ln(Bilirubin ÷17.1)] + [11.2 x ln(INR)] + 6.43 (remarks: bilirubin in umol/L, creatinine in umol/L) |
Albumin-to-ALP ratio | albumin ÷ ALP (remark: albumin in g/L, ALP in iu/L) |
ALP-to-platelet ratio | ALP ÷ platelet (remarks: ALP in iu/L, platelet count in 109/L) |
Statistical analysis
Sample size estimation
Results
Patient characteristics
Variable | N | % | Mean ± SD |
Clinical data | |||
Age < = 65 | 328 | 69 | 60 ± 12 |
Male gender | 419 | 89 | |
ECOG | |||
0 | 144 | 31 | |
1 | 299 | 63 | |
≥ 2 | 29 | 6 | |
Cirrhosis (radiological) | 278 | 59 | |
Tumor morphology | |||
Uninodular | 122 | 26 | |
Multinodular | 143 | 30 | |
Diffuse | 207 | 44 | |
Extrahepatic metastasis (nodal or distant) | 108 | 23 | |
Portal vein thrombosis | 152 | 32 | |
Hepatitis B surface antigen + | 386 | 82 | |
Hepatitis C antibody + | 30 | 6 | |
α-feto protein ≥200 mg/ml | 250 | 53 | |
ALBI score | 472 | −2.29 ± 1.33 | |
Grade 1 | 155 | 32.8 | |
Grade 2 | 265 | 56.2 | |
Grade 3 | 52 | 11.0 | |
MELD score | 472 | 9.08 ± 4.05 | |
Grade 1 (< 10) | 319 | 67.6 | |
Grade 2 (10–14) | 109 | 21.4 | |
Grade 3 (> 14) | 52 | 11.0 | |
Child-Pugh class | |||
A | 319 | 67.6 | |
B | 130 | 27.5 | |
C | 23 | 4.9 | |
Albumin | 472 | 100 | 37.4 ± 15.2 |
Bilirubin | 472 | 100 | 32.8 ± 45.7 |
INR | 472 | 100 | 1.15 ± 0.17 |
ALP | 472 | 100 | 193.4 ± 155.8 |
ALT | 472 | 100 | 77.3 ± 69.4 |
Albumin-to-ALP ratio | 472 | 100 | 0.29 ± 0.22 |
ALP-to-platelet ratio | 472 | 100 | 1.20 ± 1.19 |
Presence of ascites | 122 | 25.8 | |
Hemoglobin < 10 g/dL | 27 | 6 | |
White cell count > 10 × 109/L | 64 | 14 | |
Platelet count < 100 × 109/L | 33 | 7 | |
1st line Treatment | |||
Surgical treatment | 54 | 12 | |
Local ablative therapies | 29 | 6 | |
Trans-arterial therapies | 116 | 25 | |
Systemic therapies | 91 | 19 | |
Best supportive care alone | 182 | 38 |
mean ± SD | ln(Albumin) | ln(Bilirubin) | ln(INR) | ln(ALP) | ln(ALT) | ln(Alb/ALP) | ln(ALP/plt) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
rho |
p
| rho |
p
| rho |
p
| rho |
p
| rho |
p
| rho |
p
| rho |
p
| ||
EORTC QLQ-C30 | |||||||||||||||
Physical functioning | 72.27 ± 23.74 | 0.404 | < 0.001 | − 0.235 | < 0.001 | −0.202 | < 0.001 | − 0.271 | < 0.001 | − 0.030 | 0.514 | 0.337 | < 0.001 | − 0.145 | 0.002 |
Role functioning | 74.61 ± 32.60 | 0.318 | < 0.001 | − 0.262 | < 0.001 | − 0.194 | < 0.001 | − 0.304 | < 0.001 | − 0.187 | < 0.001 | 0.350 | < 0.001 | − 0.141 | 0.002 |
Emotional functioning | 70.67 ± 25.48 | − 0.023 | 0.612 | − 0.055 | 0.232 | − 0.018 | 0.693 | − 0.076 | 0.099 | − 0.054 | 0.239 | 0.066 | 0.154 | −0.044 | 0.345 |
Cognitive functioning | 76.80 ± 24.68 | 0.133 | 0.004 | −0.115 | 0.013 | −0.146 | 0.002 | −0.072 | 0.120 | −0.029 | 0.533 | 0.094 | 0.041 | −0.071 | 0.121 |
Social functioning | 68.46 ± 30.33 | 0.151 | 0.001 | −0.147 | 0.001 | −0.116 | 0.012 | −0.235 | < 0.001 | − 0.069 | 0.135 | 0.241 | < 0.001 | −0.082 | 0.076 |
Global quality of life | 52.22 ± 26.34 | 0.257 | < 0.001 | −0.232 | < 0.001 | −0.167 | < 0.001 | − 0.230 | < 0.001 | −0.025 | 0.595 | 0.265 | < 0.001 | −0.070 | 0.131 |
Fatigue | 42.93 ± 30.23 | −0.321 | < 0.001 | 0.285 | < 0.001 | 0.246 | < 0.001 | 0.316 | < 0.001 | 0.127 | 0.006 | −0.354 | < 0.001 | 0.163 | < 0.001 |
Nausea & vomiting | 11.26 ± 21.41 | −0.114 | 0.013 | 0.180 | < 0.001 | 0.1406 | 0.002 | 0.178 | < 0.001 | 0.093 | 0.043 | −0.183 | < 0.001 | 0.017 | 0.721 |
Pain | 32.87 ± 31.97 | −0.106 | 0.022 | 0.066 | 0.152 | 0.084 | 0.069 | 0.238 | < 0.001 | 0.050 | 0.278 | −0.229 | < 0.001 | − 0.003 | 0.953 |
Dyspnoea | 29.73 ± 31.46 | −0.244 | < 0.0001 | 0.171 | < 0.001 | 0.153 | 0.001 | 0.166 | < 0.001 | 0.020 | 0.661 | −0.201 | < 0.001 | 0.111 | 0.016 |
Insomnia | 41.88 ± 36.41 | −0.165 | < 0.001 | 0.110 | 0.017 | 0.104 | 0.024 | 0.215 | < 0.001 | 0.111 | 0.016 | −0.228 | < 0.001 | 0.077 | 0.095 |
Appetite loss | 32.34 ± 35.88 | −0.200 | < 0.001 | 0.245 | < 0.001 | 0.134 | 0.004 | 0.300 | < 0.001 | 0.086 | 0.061 | −0.304 | < 0.001 | 0.071 | 0.121 |
Constipation | 16.67 ± 27.13 | −0.057 | 0.217 | 0.006 | 0.890 | −0.007 | 0.885 | −0.019 | 0.684 | 0.024 | 0.598 | 0.008 | 0.857 | −0.048 | 0.297 |
Diarrhea | 16.45 ± 26.87 | −0.164 | < 0.001 | 0.222 | < 0.001 | 0.146 | 0.001 | 0.126 | 0.006 | 0.119 | 0.009 | −0.158 | < 0.001 | 0.143 | 0.002 |
Financial difficulties | 51.20 ± 37.22 | −0.093 | 0.044 | 0.085 | 0.066 | 0.086 | 0.061 | 0.159 | < 0.001 | 0.062 | 0.178 | −0.163 | < 0.001 | 0.077 | 0.093 |
EORTC QLQ-HCC18 | |||||||||||||||
Fatigue | 35.23 ± 25.86 | −0.305 | < 0.001 | 0.258 | < 0.001 | 0.209 | < 0.001 | 0.295 | < 0.001 | 0.122 | 0.008 | −0.329 | < 0.001 | 0.148 | 0.001 |
Body Image | 25.35 ± 22.98 | −0.280 | < 0.001 | 0.255 | < 0.001 | 0.152 | 0.001 | 0.287 | < 0.001 | 0.064 | 0.164 | −0.320 | < 0.001 | 0.106 | 0.021 |
Jaundice | 23.41 ± 22.15 | −0.094 | 0.041 | 0.226 | < 0.001 | 0.110 | 0.017 | 0.096 | 0.038 | 0.082 | 0.074 | −0.101 | 0.027 | 0.126 | 0.006 |
Nutrition | 26.96 ± 21.35 | −0.225 | < 0.001 | 0.276 | < 0.001 | 0.149 | 0.001 | 0.341 | < 0.001 | 0.134 | 0.004 | −0.343 | < 0.001 | 0.136 | 0.003 |
Pain | 23.34 ± 24.57 | −0.077 | 0.096 | 0.144 | 0.002 | 0.094 | 0.042 | 0.182 | < 0.001 | 0.057 | 0.217 | −0.178 | < 0.001 | 0.038 | 0.407 |
Fever | 6.60 ± 14.39 | −0.220 | < 0.001 | 0.117 | 0.011 | 0.193 | < 0.001 | 0.097 | 0.036 | 0.016 | 0.735 | −0.131 | 0.004 | 0.041 | 0.378 |
Sex life | 28.74 ± 34.76 | −0.053 | 0.249 | 0.095 | 0.040 | 0.129 | 0.005 | 0.170 | < 0.001 | 0.041 | 0.379 | −0.157 | < 0.001 | 0.166 | < 0.001 |
Abdominal swelling | 33.33 ± 35.43 | −0.312 | < 0.001 | 0.325 | < 0.001 | 0.225 | < 0.001 | 0.299 | < 0.001 | 0.108 | 0.019 | −0.343 | < 0.001 | 0.175 | 0.001 |
Index-scores | |||||||||||||||
C30 index-score | 30.69 ± 19.61 | −0.272 | < 0.001 | 0.250 | < 0.0001 | 0.1927 | < 0.001 | 0.301 | < 0.0001 | 0.1245 | 0.007 | −0.329 | < 0.001 | 0.116 | 0.011 |
HCC18 index-score | 25.37 ± 17.21 | −0.304 | < 0.001 | 0.318 | < 0.0001 | 0.2229 | < 0.001 | 0.343 | < 0.0001 | 0.1188 | 0.010 | −0.371 | < 0.001 | 0.187 | < 0.001 |
Correlations between QOL and liver biochemistries
Correlation between QOL and albumin-to-ALP ratio
Correlation between QOL and ALP-to-platelet ratio
Correlation between QOL and child-Pugh class
Variable Name | Child’s classes B to C | ALBI grades 2 to 3 | Presence of ascites | MELD grades 2 to 3 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | 95% CI | p-value | OR | 95% CI | p-value | OR | 95% CI | p-value | OR | 95% CI | p-value | |
EORTC QLQ-C30 | ||||||||||||
Physical functioning | 0.972 | 0.964–0.981 | < 0.001 | 0.962 | 0.952–0.973 | < 0.001 | 0.974 | 0.965–0.982 | < 0.001 | 0.989 | 0.981–0.997 | 0.009 |
Role functioning | 0.982 | 0.976–0.987 | < 0.001 | 0.975 | 0.967–0.983 | < 0.001 | 0.982 | 0.976–0.988 | < 0.001 | 0.992 | 0.986–0.998 | 0.007 |
Emotional functioning | 0.997 | 0.990–1.005 | 0.508 | 0.997 | 0.989–1.004 | 0.396 | 0.995 | 0.988–1.003 | 0.262 | 1.002 | 0.994–1.010 | 0.597 |
Cognitive functioning | 0.988 | 0.980–0.996 | 0.002 | 0.987 | 0.979–0.996 | 0.003 | 0.991 | 0.980–1.001 | 0.082 | 0.993 | 0.985–1.000 | 0.064 |
Social functioning | 0.990 | 0.984–0.996 | 0.002 | 0.986 | 0.979–0.993 | < 0.001 | 0.989 | 0.982–0.996 | 0.001 | 0.995 | 0.989–1.001 | 0.124 |
Global quality of life | 0.980 | 0.972–0.987 | < 0.001 | 0.978 | 0.970–0.986 | < 0.001 | 0.979 | 0.970–0.987 | < 0.001 | 0.989 | 0.981–0.996 | 0.003 |
Fatigue | 1.022 | 1.015–1.029 | < 0.001 | 1.025 | 1.017–1.033 | < 0.001 | 1.025 | 1.017–1.032 | < 0.001 | 1.010 | 1.003–1.016 | 0.003 |
Nausea & vomiting | 1.014 | 1.005–1.023 | 0.002 | 1.019 | 1.007–1.031 | 0.001 | 1.013 | 1.004–1.022 | 0.004 | 1.009 | 1.001–1.018 | 0.037 |
Pain | 1.005 | 0.999–1.011 | 0.099 | 1.008 | 1.002–1.015 | 0.010 | 1.007 | 1.000–1.013 | 0.036 | 0.998 | 0.992–1.004 | 0.479 |
Dyspnoea | 1.016 | 1.009–1.022 | < 0.001 | 1.016 | 1.009–1.023 | < 0.001 | 1.017 | 1.010–1.024 | < 0.001 | 1.007 | 1.001–1.013 | 0.033 |
Insomnia | 1.009 | 1.004–1.015 | 0.001 | 1.010 | 1.005–1.016 | < 0.001 | 1.010 | 1.005–1.016 | 0.001 | 0.999 | 0.993–1.004 | 0.638 |
Appetite loss | 1.014 | 1.008–1.019 | < 0.001 | 1.016 | 1.010–1.023 | < 0.001 | 1.015 | 1.009–1.020 | < 0.001 | 1.007 | 1.002–1.012 | 0.010 |
Constipation | 1.004 | 0.998–1.011 | 0.205 | 1.002 | 0.995–1.010 | 0.508 | 1.007 | 0.999–1.014 | 0.072 | 0.998 | 0.991–1.005 | 0.586 |
Diarrhea | 1.017 | 1.009–1.024 | < 0.001 | 1.016 | 1.007–1.025 | 0.003 | 1.017 | 1.010–1.025 | < 0.001 | 1.012 | 1.005–1.019 | 0.001 |
Financial difficulties | 1.003 | 0.998–1.008 | 0.253 | 1.007 | 1.002–1.012 | 0.011 | 1.004 | 0.998–1.009 | 0.200 | 1.000 | 0.995–1.006 | 0.861 |
EORTC QLQ-HCC18 | ||||||||||||
Fatigue | 1.024 | 1.016–1.032 | < 0.001 | 1.030 | 1.020–1.040 | < 0.001 | 1.022 | 1.013–1.030 | < 0.001 | 1.008 | 1.001–1.016 | 0.027 |
Body Image | 1.029 | 1.020–1.038 | < 0.001 | 1.025 | 1.015–1.035 | < 0.001 | 1.034 | 1.024–1.044 | < 0.001 | 1.014 | 1.005–1.022 | 0.001 |
Jaundice | 1.024 | 1.015–1.033 | < 0.001 | 1.011 | 1.002–1.021 | 0.020 | 1.016 | 1.007–1.025 | 0.001 | 1.018 | 1.009–1.027 | < 0.0001 |
Nutrition | 1.027 | 1.017–1.037 | < 0.001 | 1.026 | 1.015–1.037 | < 0.001 | 1.024 | 1.014–1.033 | < 0.001 | 1.013 | 1.004–1.022 | 0.003 |
Pain | 1.012 | 1.004–1.020 | 0.003 | 1.013 | 1.004–1.022 | 0.004 | 1.013 | 1.005–1.022 | 0.001 | 1.001 | 0.993–1.009 | 0.802 |
Fever | 1.023 | 1.009–1.037 | 0.001 | 1.033 | 1.014–1.053 | 0.001 | 1.012 | 0.999–1.026 | 0.079 | 1.011 | 0.998–1.025 | 0.085 |
Sex life | 1.004 | 0.999–1.010 | 0.130 | 1.007 | 1.001–1.013 | 0.017 | 1.002 | 0.997–1.008 | 0.431 | 1.005 | 0.999–1.010 | 0.089 |
Abdominal swelling | 1.023 | 1.017–1.029 | < 0.001 | 1.019 | 1.012–1.026 | < 0.001 | 1.028 | 1.022–1.035 | < 0.001 | 1.009 | 1.004–1.015 | 0.001 |
Index-scores | ||||||||||||
C30 index-score | 1.029 | 1.019–1.040 | < 0.001 | 1.037 | 1.024–1.049 | < 0.001 | 1.031 | 1.020–1.042 | < 0.001 | 1.011 | 1.001–1.021 | 0.028 |
HCC18 index-score | 1.045 | 1.032–1.058 | < 0.001 | 1.044 | 1.029–1.058 | < 0.001 | 1.043 | 1.030–1.056 | < 0.001 | 1.020 | 1.009–1.032 | < 0.001 |
Child’s classes B to C | ALBI grades 2 to 3 | Presence of ascites | MELD grades 2 to 3 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | 95% CI | p-value | OR | 95% CI | p-value | OR | 95% CI | p-value | OR | 95% CI | p-value | |
EORTC QLQ-C30 Physical Functioning | 0.987 | 0.974–1.000 | 0.045 | 0.973 | 0.961–0.985 | < 0.001 | – | – | – | – | – | – |
EORTC QLQ-HCC18 Abdominal Swelling | 1.012 | 1.003–1.021 | 0.011 | – | – | – | 1.020 | 1.012–1.028 | < 0.001 | – | – | – |
CUPI | 4.239 | 2.357–7.626 | < 0.001 | 2.580 | 1.557–4.277 | < 0.001 | 10.538 | 5.944–18.681 | < 0.001 | – | – | – |
Bilirubin | 1.100 | 1.073–1.126 | < 0.001 | 1.089 | 1.058–1.121 | < 0.001 | 1.010 | 1.001–1.019 | 0.029 | 1.093 | 1.072–1.114 | < 0.001 |
ln(AFP) | 0.838 | 0.763–0.920 | 0.001 | – | – | – | 0.790 | 0.721–0.865 | < 0.001 | – | – | – |
Planned treatment modality | – | – | – | 2.149 | 1.162–3.972 | 0.015 | – | – | – | – | – | – |