Metabolic Tumor Volume Measured by ¹⁸F-FDG PET/CT is Associated with the Survival of Unresectable Hepatocellular Carcinoma Treated with PD-1/PD-L1 Inhibitors Plus Molecular Targeted Agents

Figures & data

Table 1 Characteristics of Patients with Unresectable Hepatocellular Carcinoma

Characteristics (n=77)	Value (%)
Age (years), median (range)	55 (21–76)
Male, n (%)	65 (84.4)
AFP ≥ 400 ng/mL, n (%)	34 (44.2)
Cirrhosis, n (%)
Presence	53 (68.8)
Absence	24 (31.2)
ECOG-PS, n (%)
0	49 (63.6)
1	21 (27.3)
2	7 (9.1)
Confirmed by
Histology	55 (71.4)
Clinically	22 (28.6)
Tumor differentiation, n (%)
Well	5 (6.5)
Moderate	16 (20.8)
Poor	16 (20.8)
Undifferentiated	2 (2.6)
Unknown	38 (49.3)
BCLC stage, n (%)
B	8 (10.4)
C	69 (89.6)
Child–Pugh grade, n (%)
A	72 (93.5)
B	3 (3.9)
C	2 (2.6)
Macrovascular invasion, n (%)
Presence	32 (41.6)
Absence	45 (58.4)
Extra hepatic spread, n (%)
Presence	60 (77.9)
Absence	17 (22.1)
Bone metastasis, n (%)
Presence	14 (18.2)
Absence	63 (81.8)
Numbers of involved organs
≥3	10 (13.0)
<3	67 (87.0)
Prior local treatment, n (%)	50 (64.9)
Lines of previous systemic therapy, n (%)
0	60 (77.9)
1	11 (14.3)
2 or more	6 (7.8)
Combination of immunotherapy with target therapy, n (%)
PD-1 inhibitors	70 (90.9)
PD-L1 inhibitors	7 (9.1)
Follow up (months), median (IQR)	16.8 (5.8–25.4)

Abbreviations: AFP, alpha-fetoprotein; ECOG-PS, Eastern Cooperative Oncology Group Performance Status; BCLC stage, Barcelona Clinic Liver Cancer stage.

Figure 1 Flow chart of the data selection process.

Abbreviations: HCC, hepatocellular carcinoma; SUV_max, maximum standardized uptake value; MTV, metabolic tumor volume; TLG, total lesion glycolysis; ECOG-PS, Eastern Cooperative Oncology Group Performance Status; PFS, progression-free survival, OS; overall survival.

Figure 2 Kaplan–Meier curves for overall survival in relation to (A) SUV_max, (B) MTV, and (C) TLG (p values for Log rank test).

Abbreviations: MTV, metabolic tumor volume; SUV_max, maximum standardized uptake value; TLG, total lesion glycolysis; OS, overall survival.

Table 2 Univariate Analysis of Prognostic Factors Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma

Variables	HR	95% CI	P value
Age
≥65 years	0.886	0.603–1.303	0.539
<65 years	1 (Reference)
Gender
Male	1.037	0.706–1.524	0.854
Female	1 (Reference)
Prior local treatment
Presence	0.957	0.505–1.812	0.891
Absence	1 (Reference)
Previous lines of treatment
≥2	0.952	0.639–1.416	0.807
≤1	1 (Reference)
Current treatment
PD-1 based	1.974	0.689–5.652	0.205
PD-L1 based	1 (Reference)
AFP, ng/mL
≥400	1.185	0.878–1.599	0.266
<400	1 (Reference)
ECOG-PS
≥1	2.807	1.791–4.400	<0.001*
0	1 (Reference)
Child–Pugh grade
B-C	3.663	2.174–6.173	<0.001*
A	1 (Reference)
BCLC stage
B	1.173	0.730–1.883	0.510
C	1 (Reference)
Vascular invasion
Presence	0.994	0.544–1.817	0.984
Absence	1 (Reference)
Extra hepatic spread
Presence	1.095	(0.551–2.176)	0.796
Absence	1 (Reference)
Bone metastasis
Presence	3.093	1.528–6.258	0.002*
Absence	1 (Reference)
Numbers of involved organs
≥3	0.925	0.363–2.359	0.870
<3	1 (Reference)
Cirrhosis
Presence	0.858	0.619–1.189	0.357
Absence	1 (Reference)
SUVmax
≥7.12	1.148	0.849–1.553	0.370
<7.12	1 (Reference)
MTV, cm^3
≥39.65	1.862	1.009–3.437	0.047*
<39.65	1 (Reference)
TLG, g
≥159.2	1.342	0.989–1.823	0.059*
<159.2	1 (Reference)

Note: Bold*: p<0.1.

Abbreviations: AFP, alpha-fetoprotein; ECOG-PS, Eastern Cooperative Oncology Group Performance Status; BCLC stage, Barcelona Clinic Liver Cancer stage; SUV_max, maximum standardized uptake value; MTV, metabolic tumor volume; TLG, total lesion glycolysis.

Table 3 Multivariate Analysis of Prognostic Factors Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma

Variables	HR	95% CI	P value
ECOG-PS
≥1	3.730	1.925–7.231	<0.001*
0	1 (Reference)
Child–Pugh grade
B-C	15.384	4.292–55.556	<0.001*
A	1 (Reference)
Bone metastasis
Presence	2.994	1.425–6.289	0.004*
Absence	1 (Reference)
MTV, cm^3
≥39.65	1.371	1.001–1.878	0.049*
<39.65	1 (Reference)
TLG, g
≥159.2	0.678	0.251–1.832	0.444
<159.2	1 (Reference)

Note: Bold*: p<0.05.

Abbreviations: ECOG-PS, Eastern Cooperative Oncology Group Performance Status; MTV, metabolic tumor volume; TLG, total lesion glycolysis.

Figure 3 Kaplan–Meier curves for overall survival in three risk groups stratified according to MTV combined with the ECOG-PS (A), Child-Pugh grade (B), and bone metastasis (C). Illustration of high, moderate, and low risk using maximal intensity projection on ¹⁸F-FDG PET images of three patients (D).