1Department of Radiation Oncology, Soonchunhyang University College of Medicine, Bucheon, Korea
2Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3Department of Radiation Oncology, Korea University Ansan Hospital, Ansan, Korea
4Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
6Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
7Department of Radiation Oncology, Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
8Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, Korea
9Department of Radiation Oncology, Dong-A University College of Medicine, Busan, Korea
10Department of Radiation Oncology, Chonbuk National University Hospital, Jeonju, Korea
11Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
12Department of Radiation Oncology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
13Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
Copyright © 2019 by the Korean Cancer Association
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Characteristic | No. of patients (%) |
---|---|
Age, median (range, yr) | 58 (39-85) |
Sex | |
Male | 158 (85.9) |
Female | 26 (14.1) |
ECOG score | |
0 | 54 (29.3) |
1 | 80 (43.5) |
2 | 50 (27.2) |
Hepatitis | |
No | 11 (6.0) |
HBV | 135 (73.4) |
HCV | 25 (13.6) |
Alcoholic | 13 (7.0) |
Initial CP score | |
7 | 114 (62.0) |
8 | 57 (31.0) |
9 | 13 (7.0) |
Tumor size, median (range, cm) | 5.4 (1-21) |
No. of tumors | |
1 | 83 (45.1) |
2-3 | 54 (29.4) |
4-9 | 23 (12.5) |
≥ 10 | 24 (13.0) |
Tumor location | |
One lobe | 131 (71.2) |
Both lobes | 53 (28.8) |
Bile duct invasion | |
No | 150 (81.5) |
Yes | 34 (18.5) |
PVTT | |
No | 62 (33.7) |
Yes | 122 (66.3) |
Main PVTT | 54 (44.3) |
Branched PVTT | 68 (55.7) |
mUICC_T | |
1 | 10 (5.4) |
2 | 21 (11.4) |
3 | 61 (33.2) |
4 | 92 (50.0) |
mUICC_N | |
0 | 158 (85.9) |
1 | 26 (14.1) |
Previous liver-directed therapy | |
No | 79 (42.9) |
Yes | 105 (57.1) |
Combined treatment | |
No | 70 (38.0) |
Yes | 114 (62.0) |
Fraction size, median (range, Gy) | 2.5 (1.5-5) |
BED, median (range, Gy10) | 56.0 (40.4-89.6) |
RT completion | |
Yes | 179 (97.3) |
No | 5 (2.7)a) |
AFP, median (range, IU/mL) | 242.7 (0.7-1136990) |
Additional treatment | |
No | 95 (51.6) |
Yes | 89 (48.4) |
ECOG, Eastern Cooperative Oncology Group; HBV, hepatitis B virus; HCV, hepatitis C virus; CP, Child-Pugh; PVTT, portal vein tumor thrombosis; mUICC, the modified International Union Against Cancer stage; T, tumor; N, lymph nodes; BED, biologically effective dose when the α/β ratio was assumed to be 10 Gy; AFP, α-fetoprotein.
a) The cease of RT was due to patients’ refusal (n=2), decreased general performance (n=2); aggravation of hyperbilirubinemia (n=1).
Factor | No. of patients | 1-Year OS (%) | Median OS (mo) | UVA p-value | MVA HR (95% CI) | MVA p-value |
---|---|---|---|---|---|---|
Age (yr) | ||||||
≤ 60 | 107 | 30.8 | 8.3 | 0.154 | 0.722 | 0.104 |
> 60 | 77 | 51.3 | 12.2 | (0.487-1.069) | ||
Sex | ||||||
Male | 158 | 35.8 | 9.1 | 0.055 | 1.174 | 0.622 |
Female | 26 | 60.6 | 13.4 | (0.621-2.219) | ||
ECOG score | ||||||
0-1 | 134 | 40.2 | 9.4 | 0.817 | - | - |
2 | 50 | 37.2 | 9.7 | |||
Hepatitis | ||||||
No | 10 | 57.1 | 20.7 | 0.020 | Reference | 0.011 |
HBV/HCV | 160 | 40.0 | 9.5 | 1.970 (0.829-4.683) | 0.125 | |
Alcoholic | 14 | 19.0 | 5.3 | 4.559 (1.570-13.235) | 0.005 | |
Initial CP score | ||||||
7 | 114 | 43.2 | 10.7 | 0.381 | - | - |
8 | 57 | 35.5 | 9.1 | |||
9 | 13 | 23.1 | 5.6 | |||
Tumor size (cm) | ||||||
≤ 5 | 85 | 48.7 | 11.1 | 0.019 | - | - |
> 5 | 99 | 31.4 | 8.0 | |||
No. of tumors | ||||||
1-3 | 137 | 43.6 | 10.1 | 0.014 | - | - |
≥ 4 | 47 | 26.7 | 8.0 | |||
Tumor location | ||||||
One lobe | 131 | 42.1 | 10.1 | 0.052 | - | - |
Both lobes | 53 | 32.6 | 8.2 | |||
PVTT | ||||||
No | 62 | 55.1 | 13.2 | < 0.001 | 1.022 | 0.928 |
Yes | 122 | 31.6 | 8.0 | (0.636-1.643) | ||
mUICC_T | ||||||
1, 2 | 31 | 72.7 | 24.1 | < 0.001 | 3.277 | 0.002 |
3, 4 | 153 | 32.5 | 8.3 | (1.546-6.944) | ||
mUICC_N | ||||||
0 | 158 | 41.8 | 10.0 | 0.031 | 1.355 | 0.242 |
1 | 26 | 22.8 | 6.4 | (0.815-2.254) | ||
Initial AFP (IU/mL) | ||||||
≤ 200 | 87 | 47.1 | 11.1 | 0.003 | 1.875 | 0.005 |
> 200 | 92 | 29.2 | 8.0 | (1.207-2.911) | ||
RT aima) | ||||||
Curative | 99 | 43.2 | 10.1 | 0.044 | 0.876 | 0.486 |
Palliative | 85 | 34.8 | 8.3 | (0.604-1.271) | ||
BED (Gy10) | ||||||
≤ 53 | 75 | 31.4 | 8.3 | 0.029 | 0.946 | 0.760 |
> 53 | 109 | 45.1 | 10.1 | (0.664-1.349) | ||
AFP responseb) | ||||||
Yes | 79 | 44.4 | 9.8 | 0.012 | 0.593 | 0.013 |
No | 81 | 24.2 | 6.6 | (0.393-0.894) | ||
Classic RILD | ||||||
No | 162 | 41.2 | 9.7 | 0.582 | - | - |
Yes | 22 | 27.3 | 7.7 | |||
Non-classic RILD | ||||||
No | 118 | 51.3 | 12.2 | < 0.001 | 2.674 | < 0.001 |
Yes | 66 | 17.2 | 5.1 | (1.826-3.916) | ||
Additional treatment | ||||||
No | 95 | 27.0 | 7.0 | 0.001 | 2.159 | < 0.001 |
Yes | 89 | 51.7 | 12.2 | (1.479-3.152) |
OS, overall survival; UVA, univariate analysis; MVA, multivariate analysis; HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HBV, hepatitis B virus; HCV, hepatitis C virus; CP, Child-Pugh; PVTT, portal vein tumor thrombosis; mUICC, the modified International Union Against Cancer stage; T, tumor; N, lymph nodes; AFP, α-fetoprotein; RT, radiotherapy; BED, biologically effective dose when the α/β ratio was assumed to be 10 Gy; RILD, radiation-induced liver disease.
a) Curative intent means that RT field cover all viable tumors; palliative intent means that RT field cover a part of viable tumors,
b) Defined as AFP level reduction of > 20% from the initial level at 1 months after completion of RT in 160 patients who check follow-up AFP level.
Parameter | Mean±standard deviation | p-value | ROC AUC |
---|---|---|---|
GTV (mL) | 287.7±585.7 | 0.211 | 0.666 |
TLV (mL) | 1,555.8±758.7 | 0.311 | 0.571 |
NLV (mL) | 1,184.4±442.2 | 0.013 | 0.694 |
DTLV_mean EQD28 (Gy)a) | 18.1±8.8 | 0.041 | 0.593 |
TLV5Gy EQD28 (%)b) | 71.8±17.3 | 0.120 | 0.582 |
TLV10Gy EQD28 (%) | 58.9±18.3 | 0.082 | 0.607 |
TLV15Gy EQD28 (%) | 50.0±18.9 | 0.023 | 0.644 |
TLV20Gy EQD28 (%) | 43.2±19.6 | 0.019 | 0.648 |
TLV25Gy EQD28 (%) | 37.6±19.6 | 0.051 | 0.618 |
TLV30Gy EQD28 (%) | 32.7±19.9 | 0.051 | 0.594 |
TLV35Gy EQD28 (%) | 28.5±19.3 | 0.039 | 0.595 |
TLV40Gy EQD28 (%) | 21.8±19.5 | 0.003 | 0.635 |
DNLV_mean EQD28 (Gy) | 13.9±5.4 | 0.794 | 0.508 |
NLV5Gy EQD28 (%)c) | 68.7±17.4 | 0.203 | 0.582 |
NLV10Gy EQD28 (%) | 53.0±16.2 | 0.373 | 0.560 |
NLV15Gy EQD28 (%) | 42.0±15.2 | 0.190 | 0.592 |
NLV20Gy EQD28 (%) | 34.1±14.4 | 0.143 | 0.606 |
NLV25Gy EQD28 (%) | 27.7±13.4 | 0.495 | 0.551 |
NLV30Gy EQD28 (%) | 22.4±12.4 | 0.470 | 0.551 |
NLV35Gy EQD28 (%) | 17.9±11.3 | 0.205 | 0.577 |
NLV40Gy EQD28 (%) | 12.1±10.8 | 0.057 | 0.591 |
ROC, receiver operator characteristics; AUC, area under the curve; GTV, gross tumor volume; TLV, total liver volume; NLV, normal liver volume, which was defined as the total liver volume minus GTV in seven institutions and as the TLV minus the planning target volume in six institutions; EQD2, equivalent dose of 2 Gy per fraction.
a) Due to variations in the fractionation, all doses converted into the EQD2 using linear-quadratic model when the α/β ratio for the normal liver was assumed to be 8 Gy,
b) The percentage of the TLV ≥ X Gy,
c) The percentage of the NLV ≥ X Gy.
Characteristic | No. of patients (%) |
---|---|
Age, median (range, yr) | 58 (39-85) |
Sex | |
Male | 158 (85.9) |
Female | 26 (14.1) |
ECOG score | |
0 | 54 (29.3) |
1 | 80 (43.5) |
2 | 50 (27.2) |
Hepatitis | |
No | 11 (6.0) |
HBV | 135 (73.4) |
HCV | 25 (13.6) |
Alcoholic | 13 (7.0) |
Initial CP score | |
7 | 114 (62.0) |
8 | 57 (31.0) |
9 | 13 (7.0) |
Tumor size, median (range, cm) | 5.4 (1-21) |
No. of tumors | |
1 | 83 (45.1) |
2-3 | 54 (29.4) |
4-9 | 23 (12.5) |
≥ 10 | 24 (13.0) |
Tumor location | |
One lobe | 131 (71.2) |
Both lobes | 53 (28.8) |
Bile duct invasion | |
No | 150 (81.5) |
Yes | 34 (18.5) |
PVTT | |
No | 62 (33.7) |
Yes | 122 (66.3) |
Main PVTT | 54 (44.3) |
Branched PVTT | 68 (55.7) |
mUICC_T | |
1 | 10 (5.4) |
2 | 21 (11.4) |
3 | 61 (33.2) |
4 | 92 (50.0) |
mUICC_N | |
0 | 158 (85.9) |
1 | 26 (14.1) |
Previous liver-directed therapy | |
No | 79 (42.9) |
Yes | 105 (57.1) |
Combined treatment | |
No | 70 (38.0) |
Yes | 114 (62.0) |
Fraction size, median (range, Gy) | 2.5 (1.5-5) |
BED, median (range, Gy10) | 56.0 (40.4-89.6) |
RT completion | |
Yes | 179 (97.3) |
No | 5 (2.7) |
AFP, median (range, IU/mL) | 242.7 (0.7-1136990) |
Additional treatment | |
No | 95 (51.6) |
Yes | 89 (48.4) |
Factor | No. of patients | 1-Year OS (%) | Median OS (mo) | UVA p-value | MVA HR (95% CI) | MVA p-value |
---|---|---|---|---|---|---|
Age (yr) | ||||||
≤ 60 | 107 | 30.8 | 8.3 | 0.154 | 0.722 | 0.104 |
> 60 | 77 | 51.3 | 12.2 | (0.487-1.069) | ||
Sex | ||||||
Male | 158 | 35.8 | 9.1 | 0.055 | 1.174 | 0.622 |
Female | 26 | 60.6 | 13.4 | (0.621-2.219) | ||
ECOG score | ||||||
0-1 | 134 | 40.2 | 9.4 | 0.817 | - | - |
2 | 50 | 37.2 | 9.7 | |||
Hepatitis | ||||||
No | 10 | 57.1 | 20.7 | 0.020 | Reference | 0.011 |
HBV/HCV | 160 | 40.0 | 9.5 | 1.970 (0.829-4.683) | 0.125 | |
Alcoholic | 14 | 19.0 | 5.3 | 4.559 (1.570-13.235) | 0.005 | |
Initial CP score | ||||||
7 | 114 | 43.2 | 10.7 | 0.381 | - | - |
8 | 57 | 35.5 | 9.1 | |||
9 | 13 | 23.1 | 5.6 | |||
Tumor size (cm) | ||||||
≤ 5 | 85 | 48.7 | 11.1 | 0.019 | - | - |
> 5 | 99 | 31.4 | 8.0 | |||
No. of tumors | ||||||
1-3 | 137 | 43.6 | 10.1 | 0.014 | - | - |
≥ 4 | 47 | 26.7 | 8.0 | |||
Tumor location | ||||||
One lobe | 131 | 42.1 | 10.1 | 0.052 | - | - |
Both lobes | 53 | 32.6 | 8.2 | |||
PVTT | ||||||
No | 62 | 55.1 | 13.2 | < 0.001 | 1.022 | 0.928 |
Yes | 122 | 31.6 | 8.0 | (0.636-1.643) | ||
mUICC_T | ||||||
1, 2 | 31 | 72.7 | 24.1 | < 0.001 | 3.277 | 0.002 |
3, 4 | 153 | 32.5 | 8.3 | (1.546-6.944) | ||
mUICC_N | ||||||
0 | 158 | 41.8 | 10.0 | 0.031 | 1.355 | 0.242 |
1 | 26 | 22.8 | 6.4 | (0.815-2.254) | ||
Initial AFP (IU/mL) | ||||||
≤ 200 | 87 | 47.1 | 11.1 | 0.003 | 1.875 | 0.005 |
> 200 | 92 | 29.2 | 8.0 | (1.207-2.911) | ||
RT aim |
||||||
Curative | 99 | 43.2 | 10.1 | 0.044 | 0.876 | 0.486 |
Palliative | 85 | 34.8 | 8.3 | (0.604-1.271) | ||
BED (Gy10) | ||||||
≤ 53 | 75 | 31.4 | 8.3 | 0.029 | 0.946 | 0.760 |
> 53 | 109 | 45.1 | 10.1 | (0.664-1.349) | ||
AFP response |
||||||
Yes | 79 | 44.4 | 9.8 | 0.012 | 0.593 | 0.013 |
No | 81 | 24.2 | 6.6 | (0.393-0.894) | ||
Classic RILD | ||||||
No | 162 | 41.2 | 9.7 | 0.582 | - | - |
Yes | 22 | 27.3 | 7.7 | |||
Non-classic RILD | ||||||
No | 118 | 51.3 | 12.2 | < 0.001 | 2.674 | < 0.001 |
Yes | 66 | 17.2 | 5.1 | (1.826-3.916) | ||
Additional treatment | ||||||
No | 95 | 27.0 | 7.0 | 0.001 | 2.159 | < 0.001 |
Yes | 89 | 51.7 | 12.2 | (1.479-3.152) |
Parameter | Mean±standard deviation | p-value | ROC AUC |
---|---|---|---|
GTV (mL) | 287.7±585.7 | 0.211 | 0.666 |
TLV (mL) | 1,555.8±758.7 | 0.311 | 0.571 |
NLV (mL) | 1,184.4±442.2 | 0.013 | 0.694 |
DTLV_mean EQD28 (Gy) |
18.1±8.8 | 0.041 | 0.593 |
TLV5Gy EQD28 (%) |
71.8±17.3 | 0.120 | 0.582 |
TLV10Gy EQD28 (%) | 58.9±18.3 | 0.082 | 0.607 |
TLV15Gy EQD28 (%) | 50.0±18.9 | 0.023 | 0.644 |
TLV20Gy EQD28 (%) | 43.2±19.6 | 0.019 | 0.648 |
TLV25Gy EQD28 (%) | 37.6±19.6 | 0.051 | 0.618 |
TLV30Gy EQD28 (%) | 32.7±19.9 | 0.051 | 0.594 |
TLV35Gy EQD28 (%) | 28.5±19.3 | 0.039 | 0.595 |
TLV40Gy EQD28 (%) | 21.8±19.5 | 0.003 | 0.635 |
DNLV_mean EQD28 (Gy) | 13.9±5.4 | 0.794 | 0.508 |
NLV5Gy EQD28 (%) |
68.7±17.4 | 0.203 | 0.582 |
NLV10Gy EQD28 (%) | 53.0±16.2 | 0.373 | 0.560 |
NLV15Gy EQD28 (%) | 42.0±15.2 | 0.190 | 0.592 |
NLV20Gy EQD28 (%) | 34.1±14.4 | 0.143 | 0.606 |
NLV25Gy EQD28 (%) | 27.7±13.4 | 0.495 | 0.551 |
NLV30Gy EQD28 (%) | 22.4±12.4 | 0.470 | 0.551 |
NLV35Gy EQD28 (%) | 17.9±11.3 | 0.205 | 0.577 |
NLV40Gy EQD28 (%) | 12.1±10.8 | 0.057 | 0.591 |
ECOG, Eastern Cooperative Oncology Group; HBV, hepatitis B virus; HCV, hepatitis C virus; CP, Child-Pugh; PVTT, portal vein tumor thrombosis; mUICC, the modified International Union Against Cancer stage; T, tumor; N, lymph nodes; BED, biologically effective dose when the α/β ratio was assumed to be 10 Gy; AFP, α-fetoprotein. The cease of RT was due to patients’ refusal (n=2), decreased general performance (n=2); aggravation of hyperbilirubinemia (n=1).
OS, overall survival; UVA, univariate analysis; MVA, multivariate analysis; HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HBV, hepatitis B virus; HCV, hepatitis C virus; CP, Child-Pugh; PVTT, portal vein tumor thrombosis; mUICC, the modified International Union Against Cancer stage; T, tumor; N, lymph nodes; AFP, α-fetoprotein; RT, radiotherapy; BED, biologically effective dose when the α/β ratio was assumed to be 10 Gy; RILD, radiation-induced liver disease. Curative intent means that RT field cover all viable tumors; palliative intent means that RT field cover a part of viable tumors, Defined as AFP level reduction of > 20% from the initial level at 1 months after completion of RT in 160 patients who check follow-up AFP level.
ROC, receiver operator characteristics; AUC, area under the curve; GTV, gross tumor volume; TLV, total liver volume; NLV, normal liver volume, which was defined as the total liver volume minus GTV in seven institutions and as the TLV minus the planning target volume in six institutions; EQD2, equivalent dose of 2 Gy per fraction. Due to variations in the fractionation, all doses converted into the EQD2 using linear-quadratic model when the α/β ratio for the normal liver was assumed to be 8 Gy, The percentage of the TLV ≥ X Gy, The percentage of the NLV ≥ X Gy.