Pretreatment Neutrophil-to-Lymphocyte Ratio as Prognostic Biomarkers in Patients with Unresectable Hepatocellular Carcinoma Treated with Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab

Figures & data

Table 1 Demographic Characteristics of the Patients

Characteristics	ALL (n = 88)
Sex (male/female), n	75/13
Age, median [IQR], (years)	53.0, (46.3–62.0)
ECOG PS (0/1), n	86/2
mALBI (1/2a/2b/3), n	18/23/43/4
Child-Pugh classification (A/B), n	77/11
Aetiology of HCC (hepatitis B/non-B, non-C), n	81/7
Platelet count, median [IQR], (×10^9/L)	165 (102.3–237.5)
Neutrophils, median [IQR], (×10^9/L)	3.10 (2.30–4.47)
Lymphocytes, median [IQR], (×10^9/L)	1.04 (0.80–1.49)
Albumin, median [IQR], (g/L)	35.2 (32.7–39.0)
Total bilirubin, median [IQR], (µmol/L)	17.4 (10.9–26.7)
Alanine aminotransferase, median [IQR], (U/L)	39.7 (22.5–51)
Aspartate aminotransferase, median [IQR], (U/L)	53.9 (37.3–92.9)
γ-glutamyl transpeptidase, median [IQR], (U/L)	140.5 (67.3–277.5)
Alkaline phosphatase, median [IQR], (U/L)	143.1 (103.0–221.6)
AFP (≥400/<400), n (ng/mL)	49/39
Tumor Number (1/2/3/≥4), n	23/5/1/59
Maximum diameter of tumor, median [IQR], (cm)	9.90, (6.64–12.44)
Macrovascular invasion (yes/no), n	45/43
PVTT (0/Vp2/Vp3/Vp4), n	45/6/22/15
HVTT (0/Vv2/Vv3), n	84/2/2
Extrahepatic Spread (yes/no), n	20/68
BCLC Stage (A/B/C), n	6/25/57
NLR, median, [IQR]	3.46, (1.96–4.40)
Follow-up duration, median [IQR], (months)	11.4 (7.0–15.7)
HAIC regimen (FOLFOX/RALOX), n	74/14

Abbreviations: IQR, interquartile range; AFP, alpha-fetoprotein; ECOG PS, Eastern Cooperative Oncology Group performance status; mALBI, modified albumin-bilirubin; HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; NLR, neutrophil-to-lymphocyte ratio; HAIC, hepatic arterial infusion chemotherapy; FOLFOX, 5-fluorouracil, oxaliplatin, and leucovorin; RALOX, raltitrexed, and oxaliplatin; PVTT, portal vein tumor thrombosis; HVTT, hepatic vein tumor thrombus.

Table 2 Therapeutic Response to HAIC Combined with Lenvatinib and Camrelizumab

Evaluation (RECIST v1.1)	All Patients (n = 88)	NLR<3.46 (n = 44)	NLR≥3.46 (n = 44)	p-value	Evaluation (mRECIST)	All Patients (n = 88)	NLR<3.46 (n = 44)	NLR≥3.46 (n = 44)	i-value
CR, n (%)	0 (0)	0 (0)	0 (0)	–	CR, n (%)	5 (5.7)	4 (9.1)	1 (2.3)	0.360
PR, n (%)	22 (25.0)	11 (25.0)	11 (25.0)	–	PR, n (%)	42 (47.7)	20 (45.5)	22 (50.0)	0.671
SD, n (%)	54 (61.4)	30 (68.2)	24 (54.5)	0.192	SD, n (%)	29 (33.0)	17 (38.6)	12 (27.3)	0.260
PD, n (%)	12 (13.6)	3 (6.8)	9 (20.5)	0.062	PD, n (%)	12 (13.6)	3 (6.8)	9 (20.5)	0.062
ORR, %	25	25	25	–	ORR, %	53.4	54.5	52.3	0.831
DCR, %	86.4	93.2	79.5	0.062	DCR, %	86.4	93.2	79.5	0.062

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progression disease; ORR, objective response rate; DCR, disease control rate; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; mRECIST, modified Response Evaluation Criteria in Solid Tumors; NLR, neutrophil-to-lymphocyte ratio.

Figure 1 Kaplan-Meier curve for progression-free survival (a) and overall survival (b) for all patients receiving combination therapy of HAIC and lenvatinib plus camrelizumab. Kaplan-Meier curves of progression-free survival (c) and overall survival (d) for patients stratified by NLR.

Abbreviation: NLR, neutrophil-to-lymphocyte ratio.

Figure 2 Forest plot for univariate and multivariate analysis of factors that influenced overall survival.

Abbreviations: HR, hazard ratio; CI, confidence interval; mALBI, modified albumin-bilirubin; AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; NLR, neutrophil-to-lymphocyte ratio.

Figure 3 Forest plot for univariate and multivariate analysis of factors that influenced progression-free survival.

Abbreviations: HR, hazard ratio; CI, confidence interval; mALBI, modified albumin-bilirubin; AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; NLR, neutrophil-to-lymphocyte ratio.

Table 3 Sequential Therapy After Progression

Sequential Therapy	All (n = 45)
Regorafenib, n	6
HAIC/TACE, n	13
Ablation, n	3
Radiotherapy, n	3
BSC, n	11
Surgery, n	1
Unknown, n	8

Abbreviations: HAIC, hepatic arterial infusion chemotherapy; TACE, transarterial chemoembolization; BSC, best supportive care.