Significance of Physical Status and Liver Function Reserve for Outcome of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib Treatment

Figures & data

Table 1 Clinical Characteristics of Patients Receiving Lenvatinib Treatment for Advanced-Stage Hepatocellular Carcinoma

Characteristics	n= 143 (%)
Age (years), median (range)	63.7 (14.7–90.5)
Gender
Male	108 (75.5)
Female	35(24.5)
Body weight (Kg)
≥ 60	96 (67.1)
< 60	47 (32.9)
Hepatitis status
HBV(+)	90 (62.9)
HCV(+)	25 (17.5)
HBV and HCV(+)	3 (2.1)
None	25 (17.5)
Tumor Burden (>50% liver)
Yes	35 (24.5)
No	108 (75.5)
Major vascular invasion
Vp2+3	36 (25.2)
Vp4	19 (13.3)
Hepatic veins	9 (6.3)
Extrahepatic metastasis
Yes	81 (56.6)
No	62 (43.4)
AFP
Range, Median	58.2 (2.0–413,017)
Child-Pugh score
5	113 (79.0)
6	24 (16.8)
7	6 (4.2)
ALBI grade
1	75 (52.4)
2	66 (46.2)
3	2 (1.4)
Therapy before lenvatinib treatment
TACE	44 (30.8)
Proton therapy or radiotherapy	2 (1.4)
Systemic therapy*	20 (14.0)
No	77 (53.8)
Additional TACE
0	95 (66.4)
1–3	42 (29.4)
≥ 4	6 (4.2)
Additional ICIs
Yes	64 (44.8)
No	79 (55.2)
Outcomes
Died of HCC	70 (49.0)
Alive without lenvatinib	38 (26.6)
Alive with lenvatinib	35 (24.4)

Note: *Systemic therapy other than lenvatinib.

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; Vp, extent of portal vein tumor thrombosis; AFP, alpha-fetoprotein; ALBI grade, albumin-bilirubin grade; TACE, Trans-arterial Chemoembolization; ICI, immune checkpoint inhibitor; HCC, hepatocellular carcinoma.

Table 2 Univariate and Multivariate Analyses of Prognostic Factor Affecting Progression-Free Survival of Patients with Hepatocellular Carcinoma Under Lenvatinib Treatment

Factors	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	p value	HR (95% CI)	p value
Age (years), ≥60 / <60	0.93 (0.63–1.37)	0.717
Sex, Female / Male	1.27 (0.83–1.95)	0.268
BMI (kg/m^2), >25 / ≤25	1.02 (0.70–1.50)	0.886
Body weight (Kg), ≥60 / <60	0.95 (0.63–01.44)	0.838
HBV, Yes / No	1.01 (0.68–1.50)	0.946
HCV, Yes / No	0.86 (0.52–1.40)	0.546
Maximum tumor size (cm), ≥5 / <5	1.18 (0.79–1.75)	0.409
Tumor Burden (>50% liver), Yes / No.	1.48 (0.96–2.27)	0.070	1.22 (0.78–1.92)	0.371
Major vascular invasion, Yes / No.	1.41 (0.91–2.07)	0.073	1.22 (0.82–1.81)	0.320
Extra-hepatic metastasis, Yes / No.	0.97 (0.66–1.42)	0.877
AFP (ng/mL), >400 / ≤ 400	1.07 (0.71–1.60)	0.738
Up-to-seven, Beyond / Within	1.34 (0.89–2.00)	0.156
ALBI grade, 2.3 / 1	1.33 (0.91–1.94)	0.139
Child-Pugh score, >5 / 5	2.66 (1.71–4.12)	<0.001	2.43 (1.55–3.80)	0.001
Platelet count (10^3/μL), >100 / ≤100	0.73 (0.43–1.26)	0.267
Creatinine, ≥1.3 / <1.3	0.99 (0.51–1.91)	0.992
Therapy before Lenvatinib treatment, Yes / No	1.06 (0.72–1.55)	0.762
Additional TACE, Yes / No	0.68 (0.45–1.04)	0.076	0.71 (0.47–1.08)	0.111
Additional ICIs, Yes / No	0.99 (0.68–1.45)	0.987

Abbreviations: BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; AFP, alpha-fetoprotein; ALBI grade, albumin-bilirubin grade; TACE, Trans-arterial Chemoembolization; ICI, immune checkpoint inhibitor; HCC, hepatocellular carcinoma.

Table 3 Univariate and Multivariate Analyses of Prognostic Factor Affecting Overall Survival of Patients with Hepatocellular Carcinoma Under Lenvatinib Treatment

Factors	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	p value	HR (95% CI)	p value
Age (years), ≥60 / <60	1.33 (0.78–2.26)	0.285
Sex, Female / Male	1.67 (0.98–2.86)	0.058	1.41 (0.79–2.49)	0.235
BMI (kg/m^2), >25 / ≤25	0.90 (0.54–1.49)	0.689
Body weight (Kg), ≥60 / <60	0.59 (0.35–0.98)	0.044	0.54 (0.32–0.90)	0.020
HBV, Yes / No	1.14 (0.67–1.95)	0.619
HCV, Yes/ No	0.84 (0.43–1.62)	0.609
Maximum tumor size (cm), ≥5 / <5	1.36 (0.79–2.32)	0.257
Tumor Burden (>50% liver), Yes / No.	1.61 (0.93–2.79)	0.084	1.41 (0.80–2.50)	0.232
Major vascular invasion, Yes / No.	1.40 (0.85–2.32)	0.186
Extra-hepatic metastasis, Yes / No	0.95 (0.57–1.58)	0.871
AFP (ng/mL), >400 / ≤ 400	1.28 (0.76–2.16)	0.347
Up-to-seven, Beyond / Within	1.44 (0.83–2.50)	0.191
ALBI grade, 2.3 / 1	1.39 (0.84–2.30)	0.199
Child-Pugh score, >5 / 5	2.23 (1.27–3.92)	0.005	2.12 (1.20–3.74)	0.009
Platelet count (10^3/μL), >100 / ≤100s	0.75 (0.36–1.52)	0.427
Creatinine, ≥1.3 / <1.3	0.64 (0.23–1.77)	0.394
Therapy before lenvatinib treatment, Yes / No	0.98 (0.59–1.63)	0.953
Additional TACE, Yes / No	0.38 (0.20–0.71)	0.002	0.38 (0.21–0.70)	0.003
Additional ICIs, Yes / No	0.85 (0.51–1.41)	0.546

Abbreviations: BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; AFP, alpha-fetoprotein; ALBI grade, albumin-bilirubin grade; TACE, Trans-arterial Chemoembolization; ICI, immune checkpoint inhibitor; HCC, hepatocellular carcinoma.

Figure 1 Kaplan–Meier survival curves in patients with advanced hepatocellular carcinoma following lenvatinib treatment. (A) Progression-free survival curve, and the median time was 7.1 months. (B) Overall survival curve, and the median time was 17.7 months.

Figure 2 Comparison of cumulative survival curves according to AFP >10% reduction within the first 4 weeks of treatment for patients with baseline serum AFP ≥10 ng/mL (n = 97). (A) Progression-free survival curve. (B) Overall survival curve.

Figure 3 Comparison of cumulative survival curves according to AFP >10% reduction within the first 4 weeks of treatment for patients with baseline serum AFP >400 ng/mL (n = 46). (A) Progression-free survival curve. (B) Overall survival curve.

Figure 4 Comparison of cumulative survival curves according to neutrophil-lymphocyte ratio (NLR). Patients with pre-treatment NLR > 4.07 (n = 55) showed a significant worse outcome than those patients with NLR ≤ 4.07 (n = 88). (A) Progression-free survival curve. (p = 0.014) (B) Overall survival curve. (p = 0.010).

Figure 5 Comparison of cumulative survival curves according to platelet-lymphocyte ratio (PLR). No significant differences were observed for patients with lenvatinib treatment based on the PLR. (A) Progression-free survival curve. (p = 0.497) (B) Overall survival curve. (p = 0.821).