Efficacy of salvage surgery for hepatocellular carcinoma following conversion therapy

Table 1 Demographic and baseline characteristics of patients, n (%)

Characteristics	Total cohort (n = 28)
Age (year), mean ± SD	57.18 ± 12.46
Age, years
< 65	19 (67.9)
≥ 65	9 (32.1)
Gender
Male	25 (89.3)
Female	3 (10.7)
Etiology
HBV	22 (78.6)
HCV	1 (3.6)
Non-viral	5 (17.9)
ECOG-PS
0	25 (89.3)
1	3 (10.7)
Child-Pugh class
A	23 (82.1)
B	5 (17.9)
Pre-treatment AFP (ng/mL)
< 400	7 (25.0)
≥ 400	21 (75.0)
BCLC staging system
A	1 (3.6)
B	10 (35.7)
C	17 (60.7)
Vascular invasion
Present	17 (60.7)
Absent	11 (39.3)
Maximum tumor diameter (cm), mean ± SD	7.38 ± 3.67
Number of tumors
1	9 (32.1)
2	4 (14.3)
3	2 (7.1)
≥ 4	13 (46.4)
irAEs
Yes	6 (21.4)
No	22 (78.6)
Post-operative complications
Yes	4 (14.3)
No	24 (85.7)
Post-operative adjuvant therapy
Yes	16 (57.1)
No	12 (42.9)
ALT level (IU/L)
< 40	20 (71.4)
≥ 40	8 (28.6)
AST level (IU/L)
< 40	15 (53.6)
≥ 40	13 (46.4)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; ECOG-PS: Eastern Cooperative Oncology Group performance status; Child-Pugh: Child-Pugh score; AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; irAEsA: Immune-related adverse events; ALT: Alanine transaminase; AST: Aspartate transaminase.

Table 2 Treatment regimens and hepatic tumor response, n (%)

Variable	Patients (n = 28)
Anti-PD-antibody treatment cycle, median (IQR)	1 (1-1)
Number of TACE treatments, median (IQR)	4 (3-5.75)
Anti-PD-1 antibody class
Tislelizumab	6 (21.4)
Sintilimab	12 (42.9)
Camrelizumab	7 (25.0)
Pembrolizumab	3 (10.7)
TKI class
Lenvatinib	19 (67.9)
Donafenib	5 (17.9)
Apatinib	3 (10.7)
Sorafenib	1 (3.6)
Optimal tumor response according to mRECIST
PR	14 (50.0)
CR	14 (50.0)

PD-1: Programmed cell death protein 1; TACE: Transarterial chemoembolization; IQR: Interquartile range; ICI: Immune checkpoint inhibitor; TKI: Tyrosine kinase inhibitor; mRECIST: Modified Response Evaluation Criteria in Solid Tumors; PR: Partial response; CR: Complete response.

Table 3 Perioperative clinical data, n (%)

Salvage operation	Patients (n = 28)
Type of surgery
Laparoscopy	7 (25.0)
Open	21 (75.0)
Operative time, median (IQR), minutes	245 (182.5-370.0)
Intraoperative blood loss, median (IQR), mL	200 (100.0-475.0)
Intraoperative blood transfusion
Yes	13 (46.4)
No	15 (53.6)
Pathological reaction
PCR	14 (50.0)
Non-PCR	14 (50.0)
Post-operative hospitalization days, median (IQR), days	16 (7.5-23.8)
Post-operative complication
Present	20 (71.4)
Absent	8 (28.6)
Clavien-Dindo class
I-II	16 (57.1)
III-V	4 (14.3)
Post-operative complication
Liver failure	6 (21.4)
Abdominal fluid	13 (46.4)
Bile leakage	4 (14.3)
Abdominal infection	7 (25.0)
Abdominal hemorrhage	1 (3.6)
Pleural effusion	15 (53.6)

IQR: Interquartile range; PCR: Pathological complete response.

Table 4 Outcomes of salvage surgery, n (%)

Treatment outcome	Patients (n = 28)
Follow-up time, median (range), months	14.6 (1.3-42.1)
Number of relapsed patients	13 (46.4)
Recurrence
Intrahepatic	7 (25.0)
Extrahepatic	2 (7.1)
Intrahepatic combined with extrahepatic	4 (14.3)
Therapeutic measures after relapse
Microwave	1 (3.6)
Systemic therapy + targeted therapy	7 (25.0)
Systemic therapy + targeted therapy + TACE	2 (7.1)

TACE: Transcatheter arterial chemoembolization.

Table 5 Analysis of postoperative recurrence-free survival-related risk factors

Risk factor	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age (≥ 65 years)	3.475 (0.889-13.586)	0.073	-	-
HBsAg (positive)	1.117 (0.237-5.272)	0.889	-	-
EOCG-PS (1)	11.943 (2.310-61.743)	0.003	0.406 (0.027-6.115)	0.515
Child-Pugh class (B)	5.810 (1.521-22.185)	0.010	3.748 (0.390-35.980)	0.252
Vascular invasion (present)	1.676 (0.433-6.487)	0.455	-	-
Conversion therapy cycle (≥ 5 times)	1.567 (0.436-5.637)	0.491	-	-
Number of TACE (≥ 2 times)	2.326 (0.481-11.245)	0.294	-	-
irAEs (present)	0.446 (0.056-3.566)	0.446	-	-
Surgical type (open)	4.256 (0.533-34.003)	0.172	-	-
Surgery time (≥ 200 minutes)	1.580 (0.335-7.448)	0.563	-	-
Intraoperative blood loss (≥ 500 mL)	0.821 (0.174-3.869)	0.803	-	-
Intraoperative blood transfusion (yes)	0.917 (0.257-3.278)	0.894	-	-
Clavien-Dindo class (IIIa-V)	0.037 (0.000-71.508)	0.394	-	-
Post-operative pathology (PCR)	0.171 (0.036-0.811)	0.026	0.073 (0.009-0.571)	0.013
Maximum tumor diameter (≥ 10 cm)	1.537 (0.392 -6.028)	0.537	-	-
Number of tumors (≥ 3)	1.088 (0.306-3.861)	0.897	-	-
WBC count (≥ 4 × 109/L)	1.201 (0.310-4.653)	0.791	-	-
HGB level (≥ 120 g/L)	0.072 (0.009-0.571)	0.013	0.51 (0.018-14.854)	0.701
RBC count (≥ 4.3 × 1012/L)	0.194 (0.041-0.916)	0.038	1.816 (0.190-17.317)	0.604
PLT count (≥ 100 × 109/L)	2.200 (0.650-40.842)	0.120	-	-
ALB level (≥ 35 g/L)	0.052 (0.007-0.412)	0.005	0.022 (0.001-0.594)	0.023
ALT level (≥ 40 IU/L)	0.602 (0.127-2.860)	0.523	-	-
AST level (≥ 40 IU/L)	0.777 (0.219-2.756)	0.696	-	-
AFP level (≥ 400 ng/mL)	1.415 (0.365-5.477)	0.615	-	-
Postoperative adjuvant therapy (present)	0.746 (0.213-2.606)	0.646	-	-

HR: Hazard ratio; CI: Confidence interval; HbsAg: Hepatitis B surface antigen; ECOG-PS: Eastern Cooperative Oncology Group performance status; TACE: Transcatheter arterial chemoembolization; irAEs: Immune-related adverse events; PCR: Pathological complete response; WBC: White blood cell count; HGB: Hemoglobin; RBC: Red blood cell count; PLT: Platelet count; ALB: Albumin; ALT: Alanine transaminase; AST: Aspartate transaminase; AFP: Alpha-fetoprotein.

Table 6 Postoperative complications in the pathological complete response group vs non-pathological complete response group.

Postoperative complications	PCR group (n = 14)	Non-PCR group (n = 14)	P value
Liver failure, no/yes	12/2	10/4	0.645
Abdominal fluid, no/yes	7/7	8/6	0.705
Bile leakage, no/yes	11/3	13/1	0.589
Abdominal infection, no/yes	11/3	10/4	1.000
Abdominal hemorrhage, no/yes	13/1	14/0	1.000
Pleural effusion, no/yes	6/8	7/7	0.705

PCR: Pathological complete response.