Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma

Table 1 The baseline characteristics of patients

Variables	All (n = 20)
Age, yr	68.6 ± 8.4
Gender, male : female	19:1
BMI, kg/m2	22.2 ± 4.2
ECOG PS, 0:1:	18:2
Etiology, HBV:HCV:alcohol:others	7:7:3:3
AST, IU/L	52.2 ± 38.1
ALT, IU/L	45.1 ± 26.3
T.Bil, mg/dL	0.7 ± 0.4
Alb, g/dL	3.4 ± 0.5
PT, %	82.2 ± 15.2
Plt, × 104/μL	19.7 ± 6.1
Child–Pugh score, 5:6 points	8:12
Median AFP, ng/mL (range)	268 (4.5-53000)
Intrahepatic tumor size, cm	6.6 ± 6.3
Number of intrahepatic tumors, single : multiple	3:17
Portal vein invasion, n (%)	9 (45.0)
Extrahepatic metastasis, n (%)	15 (75.0)
Previous treatment, n (%)	19 (95.0)
Initial dose of lenvatinib, 8:12 mg/d	16:4

The values represent the mean ± SD or the median (range). BMI: Body mass index; ECOG: Eastern Cooperative Oncology Group; PS: Performance Status; T.Bil: Total bilirubin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; Alb: Albumin; PT: Prothrombin time; Plt: Platelet count; AFP: Alpha-fetoprotein.

Table 2 Distribution of changes in time-intensity curve parameters in tumors from day 0 to day 7 for 20 hepatocellular carcinoma patients according to modified Response Evaluation Criteria in Solid Tumors response at 2 mo

	Responders (n = 9)		Non-responders (n = 11)
	Day 0	Day 7	Day 0	Day 7
Slope	1.51 [1.31, 1.68]	1.09 [0.84, 1.23]	1.52 [1.22, 1.62]	1.33 [0.86, 1.71]
P value	0.018		0.511
TTP	10.56 [9.33, 12.13]	12.43 [11.94, 13.94]	11.02 [8.53, 12.51]	11.84 [10.15, 13.82]
P value	0.003		0.247
AUC	266.51 [225.38, 296.67]	156.44 [123.05, 178.91]	258.14 [191.61, 299.51]	229.65 [176.10, 269.50]
P value	0.001		0.322

The values represent the median [25^th-75^th percentile]. HCC: Hepatocellular carcinoma; TTP: Time to peak; AUC: Area under the curve.

Table 3 The performance characteristics of the rate of change of time-intensity curve parameters for the prediction of responders

	Slope (95%CI)	TTP (95%CI)	AUC (95%CI)
AUROC	0.818 (0.602-0.944)	0.869 (0.728-0.975)	0.939 (0.812-0995)
Cut-off value (%)	-11.765	+9.495	-25.714
Sensitivity	0.889 (0.540-0.978)	0.889 (0.540-0.978)	0.896 (0.616-0.989)
Specificity	0.545 (0.304-0.786)	0.818 (0.510-0.917)	0.909 (0.648-0.995)
PPV	0.615 (0.583-0.793)	0.800 (0.611-0.907)	0.833 (0.727-0.918)
NPV	0.857 (0.731-0.922)	0.878 (0.741-0.962)	0.900 (0.747-0.992)

TIC: Time-intensity curve; CI: Confidence interval; TTP: Time to peak; AUC: Area under the curve; AUROC: Area under receiver operating curve; PPV: Positive predictive value; NPV: Negative predictive value.