Prognostic significance of pan-immune-inflammation value in hepatocellular carcinoma treated by curative radiofrequency ablation: potential role for individualized adjuvant systemic treatment

Figures & data

Figure 1. High PIV was associated with unfavorable recurrence-free survival (RFS) and overall survival (OS) in early-stage hepatocellular carcinoma treated by curative RFA in testing cohort B after propensity score matching. Kaplan-Meier curves for RFS (A) and OS (B) of patients with high or low PIV. PIV: pan-immune-inflammation value; RFA: radiofrequency ablation.

Figure 2. Prognostic role of PIV was validated in external validating cohort C after propensity score matching. The time-dependent receiver operating characteristic curve (A) of PIV cutoff derived from training cohort A to predict the 5-year overall survival (OS), and Kaplan-Meier curves for OS (B) and recurrence-free survival (C) in early-stage hepatocellular carcinoma treated by curative RFA in external validating cohort C. AUC: area under curve; PIV: pan-immune-inflammation value; RFA: radiofrequency ablation.

Figure 3. The PIV-based nomogram (A) and calibration curves for predicting the 2-year (B) and 5-year (C) OS in external validating cohort C after propensity score matching. PIV: pan-immune-inflammation value; OS: overall survival; BCLC: Barcelona clinic liver cancer.

Figure 4. The PIV-based nomogram (A) and calibration curves for predicting the 2-year (B) and 5-year (C) RFS in external validating cohort C after propensity score matching. PIV: pan-immune-inflammation value; RFS: recurrence-free survival; BCLC: Barcelona clinic liver cancer.

Table 1. Baseline characteristics of patients in the primary and PSM cohorts of external validating cohort C.

Characteristics	Primary cohort			PSM cohort
	PIV*<120 (N = 157) N (%)	PIV*≥120 (N = 108) N (%)	p value	PIV*<120 (N = 107) N (%)	PIV*≥120 (N = 107) N (%)	p value
Gender			0.05			0.810
Female	28 (10.6%)	10 (3.8%)		10 (4.7%)	9 (4.2%)
Male	129 (48.7%)	98 (37.0%)		97 (45.3%)	98 (45.8%)
Age (y)			0.914			0.767
<65	110 (41.5%)	75 (28.3%)		73 (34.1%)	75 (35.0%)
≥65	47 (17.7%)	33 (12.5%)		34 (15.9%)	32 (15.0%)
HBsAg			0.967			0.873
Negative	36 (13.6%)	25 (9.4%)		26 (12.1%)	25 (11.7%)
Positive	121 (45.7%)	83 (31.3%)		81 (37.9%)	82 (38.3%)
HBV-DNA (IU/mL)			0.479			0.763
<500	53 (20.0%)	32 (12.1%)		30 (14.0%)	32 (15.0%)
≥500	104 (39.2%)	76 (28.7%)		77 (36.0%)	75 (35.0%)
HCV infection			0.007^#			0.122^#
No	138 (52.1%)	105 (39.6%)		99 (46.3%)	104 (48.6%)
Yes	19 (7.2%)	3 (1.1%)		8 (3.7%)	3 (1.4%)
Alcoholic liver disease			0.082^#			0.246^#
No	152 (57.4%)	108 (40.8%)		104 (48.6%)	107 (50.0%)
Yes	5 (1.9%)	0 (0%)		3 (1.4%)	0 (0%)
Cirrhosis			0.005			0.057
No	36 (13.6%)	42 (15.8%)		28 (13.1%)	41 (19.2%)
Yes	121 (45.7%)	66 (24.9%)		79 (36.9%)	66 (30.8%)
Antiviral treatment			0.568			0.129
No	70 (26.4%)	52 (19.6%)		41 (19.2%)	52 (24.3%)
Yes	87 (32.8%)	56 (21.1%)		66 (30.8%)	55 (25.7%)
AFP (ng/mL)			0.151			0.663
<400	63 (23.8%)	34 (12.8%)		37 (17.3%)	34 (15.9%)
≥400	94 (35.5%)	74 (27.9%)		70 (32.7%)	73 (34.1%)
Tumor number			0.484			0.891
Solitary	94 (35.5%)	60 (22.6%)		59 (27.6%)	60 (28.0%)
Multiple	63 (23.8%)	48 (18.1%)		48 (22.4%)	47 (22.0%)
Tumor size (cm)			0.416			0.774
<2	94 (35.5%)	70 (26.4%)		71 (33.2%)	69 (32.2%)
≥2	63 (23.8%)	38 (14.3%)		36 (16.8%)	38 (17.8%)
BCLC stage			0.503			0.988
0	53 (20.0%)	44 (16.6%)		42 (19.6%)	43 (20.1%)
A	62 (23.4%)	39 (14.7%)		40 (18.7%)	39 (18.2%)
B	42 (15.8%)	25 (9.4%)		25 (11.7%)	25 (11.7%)
Child-Pugh class			0.636			0.508
A	141 (53.2%)	95 (35.8%)		97 (45.3%)	94 (43.9%)
B	16 (6.0%)	13 (4.9%)		10 (4.7%)	13 (6.1%)

^# Fisher’s exact test.

* ×10¹⁸/L.

PIV: pan-immune-inflammation value; HBsAg: hepatitis B surface antigen; HCV: hepatitis C virus; HBV-DNA: hepatitis B virus DNA; AFP: alpha-fetoprotein; BCLC: Barcelona clinic liver cancer; PSM: propensity score matching.

Table 2. Univariate and multivariate analysis with the cox proportional hazard model for OS and RFS of early-stage hepatocellular carcinoma treated by radiofrequency ablation in PSM cohort derived from external validating cohort C.

Variables	Univariate analysis				Multivariate analysis
	p	HR	95% CI for HR		P	HR	95% CI for HR
			Lower	Upper			Lower	Upper
OS
Sex (female vs. male)	0.755	0.907	0.491	1.675
Age (y) (≥65 vs. <65)	0.869	1.042	0.639	1.697
Cirrhosis (yes vs. no)	0.079	0.681	0.443	1.045
HBsAg (positive vs. negative)	0.508	0.848	0.521	1.381
Tumor size (≥2cm vs. <2cm)	0.005	1.846	1.202	2.835
Tumor number (multiple vs. single)	<0.001	3.821	2.383	6.126	0.026	1.814	1.223	3.827
BCLC stage
A vs. 0	<0.001	4.288	2.244	8.193	0.005	3.744	1.493	9.391
B vs. 0	<0.001	8.285	4.189	16.386	<0.001	6.320	2.318	17.237
PIV* (≥120 vs. <120)	<0.001	2.640	1.658	4.204	<0.001	2.777	1.735	4.446
RFS
Sex (female vs. male)	0.122	0.683	0.422	1.107
Age (y) (≥65 vs. <65)	0.887	0.975	0.685	1.388
Cirrhosis (yes vs. no)	0.917	0.982	0.704	1.371
HBsAg (positive vs. negative)	0.362	1.194	0.815	1.750
Tumor size (≥2cm vs. <2cm)	0.680	0.932	0.668	1.301
Tumor number (multiple vs. single)	<0.001	1.813	1.305	2.521	0.029	1.692	1.065	2.712
BCLC stage
A vs. 0	0.046	1.453	1.006	2.098
B vs. 0	<0.001	2.092	1.371	3.193	0.009	1.572	1.291	2.873
PIV *(≥120 vs. <120)	<0.001	1.828	1.305	2.561	<0.001	1.957	1.393	2.748

* ×10¹⁸/L.

PIV: pan-immune-inflammation value; OS: overall survival; RFS: recurrence-free survival; HBsAg: hepatitis B surface antigen; BCLC: Barcelona clinic liver cancer; PSM: propensity score matching; HR: hazard ratio; CI: confidence interval.

Figure 5. Adjuvant AA-ICI treatment following curative RFA exhibited more benefit in early-stage hepatocellular carcinoma patients in high-risk group in the pooled cohort D. Kaplan-Meier curves for RFS (A) and OS (B) of patients in low-risk group with adjuvant AA-ICI treatment or not. Kaplan-Meier curves for RFS (C) and OS (D) of patients in high-risk group with adjuvant AA-ICI treatment or not. RFA: radiofrequency ablation; RFS: recurrence-free survival; OS: overall survival; AA-ICI: anti-angiogenesis target therapy plus immune checkpoint inhibitor.

Table 3. Baseline characteristics of early-stage hepatocellular carcinoma patients with or without adjuvant AA-ICI treatment following curative RFA between low- and high-risk groups.

Characteristics	Low-risk			High-risk
	No AA-ICI (N = 152) N (%)	AA-ICI (N = 34) N (%)	p value	No AA-ICI (N = 153) N (%)	AA-ICI (N = 59) N (%)	p value
Gender			0.378^#			0.689
Female	20 (10.8%)	2 (1.1%)		25 (11.8%)	11 (5.2%)
Male	132 (71.0%)	32 (17.2%)		128 (60.4%)	48 (22.6%)
Age (y)			0.831			0.503
<65	109 (58.6%)	25 (13.4%)		107 (50.5%)	44 (20.8%)
≥65	43 (23.1%)	9 (4.8%)		46 (21.7%)	15 (7.1%)
HBsAg			0.113			0.113
Negative	23 (12.4%)	9 (4.8%)		38 (17.9%)	13 (6.1%)
Positive	129 (69.4%)	25 (13.4%)		115 (54.2%)	46 (21.7%)
Cirrhosis			0.699			0.337
No	36 (19.4%)	7 (3.8%)		52 (24.5%)	16 (7.5%)
Yes	116 (62.4%)	27 (14.5%)		101 (47.6%)	43 (20.3%)
Tumor number			–			0.443
Solitary	152 (81.7%)	34 (18.3%)		36 (17.0%)	11 (5.2%)
Multiple	–	–		117 (55.2%)	48 (22.6%)
Tumor size (cm)			0.219			0.289
<2	118 (63.4%)	23 (12.4%)		81 (38.2%)	36 (17.0%)
≥2	34 (18.3%)	11 (5.9%)		72 (34.0%)	23 (10.8%)
PIV*			0.836			0.708
<120	100 (53.8%)	23 (12.4%)		77 (36.3%)	28 (13.2%)
≥120	52 (28.0%)	11 (5.9%)		76 (35.8%)	31 (14.6%)
Child-Pugh class			0.261			0.975
A	143 (76.9%)	30 (16.1%)		132 (62.3%)	51 (24.1%)
B	9 (4.8%)	4 (2.2%)		21 (9.9%)	8 (3.8%)
AFP (ng/mL)			0.950			0.666
<400	35 (18.8%)	8 (4.3%)		65 (30.7%)	27 (12.7%)
≥400	117 (62.9%)	26 (14.0%)		88 (41.5%)	32 (15.1%)
BCLC stage			0.187			0.598^#
0	119 (64.0%)	23 (12.4%)		1 (0.5%)	0 (0%)
A	33 (17.7%)	11 (5.9%)		89 (42.0%)	31 (14.6%)
B	–	–		63 (29.7%)	28 (13.2%)

^# Fisher’s exact test.

* ×10¹⁸/L.

AA-ICI: anti-angiogenesis target treatment combined with immune checkpoint inhibitor; PIV: pan-immune-inflammation value; HBsAg: hepatitis B surface antigen; BCLC: Barcelona clinic liver cancer; AFP: alpha-fetoprotein; RFA: radiofrequency ablation.

Data availability statement

Data can not be shared publicly because the data from this study contain potentially sensitive private information. Data would be available from the corresponding authors upon reasonable request or on the research data deposit (RDD) platform of Sun Yat-sen University after the manuscript was published.