Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy

Figures & data

Figure 1 Flow diagram of the study selection process.

Table 1 Univariate Analysis for Objective Response Rates in the High-AFP Group (n=77)

Variables	Univariate
	OR (95% CI)	p-value
Sex (male)	0.857 (0.162–4.529)	0.856
Age (≥65 years)	1.860 (0.475–7.293)	0.373
PS (1)	1.083 (0.306–3.834)	0.901
ALBI grade (II)	0.508 (0.175–1.474)	0.213
BCLC (C)	0.629 (0.199–1.993)	0.431
Tumor size (mm) (≥50)	0.900 (0.220–3.682)	0.883
Tumor number (multiple)	0.464 (0.071–3.008)	0.420
Macrovascular invasion (yes)	0.471 (0.150–1.483)	0.198
AFP (ng/mL) (≥400)	1.493 (0.516–4.322)	0.460
AFP reduction >50% (yes)	13.542 (3.991–45.950)	0.000

Note: Bold values are statistically significant (p<0.05).

Abbreviations: OR, odds ratio; CI, confidence interval; PS, performance status; ALBI, albumin–bilirubin; BCLC, Barcelona Clinic Liver Cancer staging; AFP, alpha-fetoprotein.

Table 2 Univariate and Multivariate Analysis for Objective Response Rates in the High-DCP Group (n=76)

Variables	Univariate		Multivariate
	OR (95% CI)	p-value	OR (95% CI)	p-value
Sex (male)	1.933 (0.164–22.781)	0.600
Age (≥65 years)	2.130 (0.431–10.529)	0.354
PS (1)	0.973 (0.236–4.006)	0.970
ALBI grade (II)	0.373 (0.120–1.164)	0.089	0.322 (0.081–1.289)	0.109
BCLC (C)	1.295 (0.410–4.085)	0.659
Tumor size (mm) (≥50)	0.600 (0.160–2.245)	0.448
Tumor number (multiple)	0.237 (0.032–2.273)	0.198
Macrovascular invasion (yes)	0.840 (0.270–2.613)	0.763
DCP (mAU/mL) (≥400)	3.000 (0.731–12.304)	0.127
DCP reduction >50% (yes)	16.657 (4.456–62.269)	0.000	17.853 (4.478–71.179)	0.000

Note: Bold values are statistically significant (p<0.05).

Abbreviations: OR, odds ratio; CI, confidence interval; PS, performance status; ALBI, albumin–bilirubin; BCLC, Barcelona Clinic Liver Cancer staging; DCP, des-gamma-carboxyprothrombin.

Figure 2 The survival curves of patients with uHCC receiving triple therapy for progression-free survival (PFS). (A) After 6 weeks of triple therapy, patients with AFP reduction >50% have significantly longer PFS than those with AFP reduction ≤50%. (B) Similarly, patients with DCP reduction >50% also had better PFS.

Table 3 Univariate and Multivariate Analysis for Overall Survival in the High-AFP Group (n=77)

Variables	Univariate		Multivariate
	HR (95% CI)	p-value	HR (95% CI)	p-value
Sex (male)	1.769 (0.231–13.546)	0.583
Age (≥65 years)	0.995 (0.276–3.583)	0.994
PS (1)	2.235 (0.689–7.245)	0.180
ALBI grade (II)	4.030 (1.123–14.458)	0.032	3.250 (0.886–11.928)	0.076
BCLC (C)	1.932 (0.539–6.932)	0.312
Tumor size (mm) (≥50)	2.519 (0.328–19.341)	0.374
Tumor number (multiple)	1.393 (0.174–11.119)	0.755
Macrovascular invasion (yes)	2.090 (0.660–6.616)	0.210
AFP (ng/mL) (≥400)	1.960 (0.546–7.043)	0.302
AFP reduction >50% (yes)	0.263 (0.094–0.733)	0.011	0.327 (0.116–0.922)	0.034

Note: Bold values are statistically significant (p<0.05).

Abbreviations: HR, hazard ratio; CI, confidence interval; PS, performance status; ALBI, albumin–bilirubin; BCLC, Barcelona Clinic Liver Cancer staging; DCP, des-gamma-carboxyprothrombin.

Table 4 Univariate and Multivariate Analysis for Overall Survival in the High-DCP Group (n=76)

Variables	Univariate		Multivariate
	HR (95% CI)	p-value	HR (95% CI)	p-value
Sex (male)	0.299 (0.037–2.432)	0.259
Age (≥65 years)	0.600 (0.134–2.688)	0.504
PS (1)	4.371 (1.504–12.701)	0.007	6.310 (1.984–20.069)	0.002
ALBI grade (II)	3.606 (1.139–11.423)	0.029	3.794 (1.096–13.135)	0.035
BCLC (C)	2.917 (0.652–13.044)	0.161
Tumor size (mm) (≥50)	1.082 (0.240–4.885)	0.918
Tumor number (multiple)	0.833 (0.174–3.983)	0.819
Macrovascular invasion (yes)	1.613 (0.545–4.771)	0.388
DCP (mAU/mL) (≥400)	0.637 (0.137–2.957)	0.565
DCP reduction >50% (yes)	0.175 (0.061–0.498)	0.001	0.221 (0.074–0.664)	0.007

Note: Bold values are statistically significant (p<0.05).

Abbreviations: HR, hazard ratio; CI, confidence interval; PS, performance status; ALBI, albumin–bilirubin; BCLC, Barcelona Clinic Liver Cancer staging; DCP, des-gamma-carboxyprothrombin.

Figure 3 The survival curves of patients with uHCC receiving triple therapy for overall survival (OS). (A) After 6 weeks of triple therapy, patients with AFP reduction>50% have significantly improved OS compared to those without. (B) Likewise, the OS of patients with DCP reduction >50% was significantly longer.