Lymphocyte-to-C Reactive Protein Ratio is an Independent Predictor of Survival Benefits for Hepatocellular Carcinoma Patients Receiving Radiotherapy

Figures & data

Table 1 Patient Baseline Characteristics

	Total (N=35, %)	RT for Primary Liver Lesions (N=25, %)	RT for Metastatic Bone Lesions (N=10, %)
Age (years)
Median (range)	58 (33–77)	62 (34–77)	54 (33–77)
<65	23 (65.7)	14 (56.0)	9 (90.0)
≥65	12 (34.3)	11 (44.0)	1 (10.0)
Sex
Male	29 (82.9)	21 (84.0)	8 (80.0)
Female	6 (17.1)	4 (16.0)	2 (20.0)
ECOG PS
0	21 (60.0)	19 (76.0)	2 (20.0)
1	14 (40.0)	6 (24.0)	8 (80.0)
Cirrhosis
Yes	21 (60.0)	16 (64.0)	5 (50.0)
No	14 (40.0)	9 (36.0)	5 (50.0)
Viral infection
Hepatitis B	32 (91.4)	23 (92.0)	9 (90.0)
Hepatitis C	3 (8.6)	2 (8.0)	1 (10.0)
Hypertension
Yes	12 (34.3)	9 (36.0)	3 (30.0)
No	23 (65.7)	16 (64.0)	7 (30.0)
Diabetes
Yes	6 (17.1)	4 (16.0)	2 (20.0)
No	29 (82.9)	21 (84.0)	8 (80.0)
BCLC class
B	10 (28.6)	10 (40.0)	0 (0)
C	25 (71.4)	15 (60.0)	10 (100.0)
PVT
Yes	11 (31.4)	11 (44.0)	0 (0)
No	24 (68.6)	14 (56.0)	10 (100.0)
Tumor size (cm)
<5.0	10 (28.6)	10 (40.0)	–
≥5.0	15 (42.9)	15 (60.0)	–
AFP (ng/mL)
<400	19 (54.3)	14 (56.0)	5 (50.0)
≥400	16 (45.7)	11 (44.0)	5 (50.0)

Abbreviations: RT, radiotherapy; ECOG PS, Eastern Cooperative Oncology Group Performance Status; BCLC, Barcelona clinical liver cancer; PVT, portal vein thrombosis; AFP, alpha-fetoprotein.

Figure 1 Flowchart of the recruitment process. ^aPTV 50 Gy in 25 fractions, five consecutive days per week; ^bPTV 15–24 Gy in 3 fractions, three consecutive days; ^cPTV 18 Gy/6 fractions, or 45 Gy/3 fractions.

Abbreviations: ICC, intrahepatic cholangiocarcinoma; cHCC-CCA, combined hepatocellular-cholangiocarcinoma; HCC, hepatocellular carcinoma; TT, targeted therapy; TACE, transarterial chemoembolization; LDRT, low-dose radiotherapy; SBRT, stereotactic body radiation therapy; PTV, planning target volume; PGTV, planning gross tumor volume.

Table 2 Uni- and Multivariate Analyses for PFS

Characteristics		Univariate Analysis			Multivariate Analysis
		HR	95% CI	P	HR	95% CI	P
Age, years	<65	1.0		0.851			NA
	≥65	1.084	0.465–2.527
Sex	Male	1.0		0.761			NA
	Female	1.188	0.392–3.595
ECOG PS	0	1.0		0.066			NA
	1	2.518	0.942–6.729
Cirrhosis	No	1.0		0.048	1.0		0.124
	Yes	0.397	0.158–0.993		0.374	0.107–1.309
Hypertension	No	1.0		0.208			NA
	Yes	0.545	0.212–1.402
Diabetes	No	1.0		0.078			NA
	Yes	2.775	0.898–8.576
BCLC class	B	1.0		0.366			NA
	C	1.527	0.610–3.820
PVT	No	1.0		0.788			NA
	Yes	1.126	0.475–2.672
Tumor size, cm	<5.0	1.0		0.396			NA
	≥5.0	1.483	0.597–3.686
AFP	<400	1.0		0.034	1.0		0.297
	≥400	2.742	1.078–6.974		1.955	0.555–6.887
PLR	<97.34	1.0		0.945			NA
	≥97.34	1.030	0.444–2.390
NLR	<1.95	1.0		0.298			NA
	≥1.95	1.592	0.663–3.823
LCR	<2361.11	1.0		0.002	1.0		0.000
	≥2361.11	0.229	0.088–0.595		0.154	0.054–0.439
LMR	<4.74	1.0		0.504			NA
	≥4.74	0.388	0.148–1.016
CAR	<0.10	1.0		0.061			NA
	≥0.10	2.311	0.962–5.552
SII	<348.87	1.0		0.711			NA
	≥348.87	1.188	0.478–2.955

Notes: P value in bold indicated a statistically significant difference in the univariate or multivariate Cox regression analyses (P<0.05).

Abbreviations: PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; BCLC, Barcelona clinical liver cancer; PVT, portal vein thrombosis; AFP, alpha-fetoprotein; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; LCR, lymphocyte-to-C reactive protein ratio; LMR, lymphocyte-to-monocyte ratio; CAR, C-reactive protein-to-albumin ratio; SII, systemic immune-inflammation index.

Figure 2 Kaplan–Meier curves for PFS (A), and stratified by LCR (B).

Abbreviations: PFS, progression-free survival; LCR, lymphocyte‐to-C reactive protein ratio.

Table 3 Uni- and Multivariate Analyses for OS

Characteristics		Univariate Analysis			Multivariate Analysis
		HR	95% CI	P	HR	95% CI	P
Age, years	<65	1.0		0.655			NA
	≥65	0.806	0.314–2.071
Sex	Male	1.0		0.235			NA
	Female	2.029	0.631–6.531
ECOG PS	0	1.0		0.119			NA
	1	2.397	0.798–7.196
Cirrhosis	No	1.0		0.037	1.0		0.363
	Yes	0.358	0.136–0.942		0.531	0.136–2.076
Hypertension	No	1.0		0.473			NA
	Yes	0.684	0.243–1.929
Diabetes	No	1.0		0.019	1.0		0.000
	Yes	4.258	1.273–14.245		1156.287	10.179–2399.684
BCLC class	B	1.0		0.358			NA
	C	1.577	0.597–4.166
PVT	No	1.0		0.897			NA
	Yes	1.061	0.430–2.621
Tumor size, cm	<5.0	1.0		0.603			NA
	≥5.0	1.295	0.488–3.434
AFP	<400	1.0		0.014	1.0		0.001
	≥400	4.148	1.336–12.878		42.078	4.184–423.210
PLR	<97.34	1.0		0.664			NA
	≥97.34	1.223	0.493–3.038
NLR	<1.95	1.0		0.344			NA
	≥1.95	1.563	0.620–3.940
LCR	<2361.11	1.0		0.022	1.0		0.013
	≥2361.11	0.310	0.114–0.844		0.182	0.048–0.695
LMR	<4.74	1.0		0.041	1.0		0.143
	≥4.74	0.330	0.114–0.958		0.382	0.105–1.385
CAR	<0.10	1.0		0.069			NA
	≥0.10	2.414	0.935–6.234
SII	<348.87	1.0		0.710			NA
	≥348.87	1.208	0.446–3.270

Notes: P value in bold indicated a statistically significant difference in the univariate or multivariate Cox regression analyses (P<0.05).

Abbreviations: OS, overall survival; HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; BCLC, Barcelona clinical liver cancer; PVT, portal vein thrombosis; AFP, alpha-fetoprotein; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; LCR, lymphocyte-to-C reactive protein ratio; LMR, lymphocyte-to-monocyte ratio; CAR, C-reactive protein-to-albumin ratio; SII, systemic immune-inflammation index.

Figure 3 Kaplan–Meier curves for OS (A), and stratified by LCR (B), AFP (C), and diabetes (D).

Abbreviations: OS, overall survival; LCR, lymphocyte‐to-C reactive protein ratio; AFP, alpha-fetoprotein.