Lenvatinib and pembrolizumab plus FOLFOX-hepatic arterial infusion chemotherapy in locally advanced, potentially resectable hepatocellular carcinoma

Table 1 Criteria for defining successful conversion and surgical decision-making

Category	Criterion	Definition/threshold	Assessment method and timing
Overall requirement	MDT consensus	Agreement by hepatobiliary surgery, interventional radiology, and oncology	MDT review after every 2 cycles of therapy
Radiological response	Objective tumor response	Achieve complete or partial response according to RECIST 11 and/or modified RECIST	Contrast-enhanced CT/magnetic resonance imaging every 6 weeks; response must be confirmed on two consecutive scans ≥ 4 weeks apart
	Technical resectability	Tumor downstaging to allow for a potential R0 resection. Regression of major vascular involvement (e.g., portal vein tumor thrombus)	Volumetric and anatomical assessment via imaging
Liver function and volume	FLR volume	FLR > 40% of standardized total liver volume	CT volumetry prior to surgical decision
	Liver function reserve	Child-Pugh score ≤ 7	Laboratory and clinical evaluation every 3 weeks
		ICG 15-minute retention rate ≤ 20%	ICG clearance test prior to surgical decision
Patient general status	Performance status	Eastern Cooperative Oncology Group Performance Status score: 0-1	Clinical assessment every 3 weeks
Systemic disease control	Extrahepatic metastasis	Absence of new or progressive extrahepatic metastases	Chest CT and baseline extrahepatic imaging every 6 weeks
Surgical safety	Major organ function	No severe, uncontrolled comorbidities precluding major surgery (cardiopulmonary, renal insufficiency, etc.)	Comprehensive preoperative anesthesiology evaluation

CT: Computed tomography; FLR: Future liver remnant; ICG: Indocyanine green; MDT: Multidisciplinary team; RECIST: Response Evaluation Criteria in Solid Tumors.

Table 2 Baseline characteristics of 38 patients who had primary unresectable hepatocellular carcinoma

Clinical characteristic	Data
Sex
Male	36
Female	2
Age (years)
≤ 65	32
> 65	6
Hepatitis B
Yes	34
No	4
Cirrhosis
Yes	18
No	20
Antiviral treatment
Yes	8
No	30
China Liver Cancers stage
Ia	1
Ib	5
IIa	3
IIb	1
IIIa	28
Barcelona Clinic Liver Cancer stage
Early (A)	6
Intermediate (B)	4
Advanced (C)	28
Number of cancer lesions
1	16
≥ 2	22
Sum of longest diameter of target lesions (cm)
≥ 10	23
< 10	15
Alpha-fetoprotein (μg/L)
≥ 400	21
< 400	17

Table 3 Evaluation of effectiveness of conversion therapy (number of cases/percentage)

Assessment indicators	RECIST	Modified RECIST
CR	3/38 (7.9%)	5/38 (13.1%)
Partial response	16/38 (42.1%)	15/38 (39.5%)
Stable disease	18/38 (47.4%)	17/38 (44.7%)
Progressive disease	1/38 (2.6%)	1/38 (2.6%)
Objective response rate	19/38 (50.0%)	20/38 (52.6%)
Disease control rate	37/38 (97.4%)	37/38 (97.4%)
Pathological CR	3/38 (7.9%)	3/38 (7.9%)
Conversion success rate	19/38 (50.0%)	20/38 (52.6%)
Surgical conversion rate	17/38 (44.7%)	17/38 (44.7%)

CR: Complete response; RECIST: Response Evaluation Criteria in Solid Tumors.

Table 4 Univariate analysis of survival factors in 38 patients with initially unresectable hepatocellular carcinoma, n (%)

Factors	Survival	Death	Hazard ratio (95%CI)	P value
Gender				0.114
Male	19 (52.8)	17 (47.2)	Reference
Female	2 (100)	0 (0)	3.297 (0.751-14.479)
Age (years)				0.725
≤ 65	18 (56.3)	14 (43.7)	Reference
> 65	3 (50.0)	3(50.0)	0.802 (0.236-2.734)
Hepatitis B				0.189
Negative	1 (25.0)	3 (75.0)	Reference
Positive	20 (58.8)	14 (41.2)	3.872 (0.514-29.169)
Liver cirrhosis				0.935
Negative	11 (55.0)	9 (45.0)	Reference
Positive	10 (55.6)	8 (44.4)	0.965 (0.41-2.274)
Antiviral therapy				0.093
Negative	14 (46.7)	16 (53.3)	Reference
Positive	7 (87.5)	1 (12.5)	2.179 (0.879-5.402)
China Liver Cancers stage				0.734
Ia	1 (100.0)	0	Reference
Ib	2 (40.0)	3 (60.0)	2.863 (0.362-22.623)	0.319
IIa	2 (66.7)	1 (33.3)	0.495 (0.113-2.172)	0.351
IIb	0	1 (100.0)	1.031 (0.236-4.498)	0.968
IIIa	16 (57.1)	12 (42.9)	0	0.983
Barcelona Clinic Liver Cancer stage				0.337
A	2 (33.3)	4 (66.7)	Reference
B	3 (75.0)	1 (25.0)	0.397 (0.09-1.746)	0.222
C	16 (57.1)	12 (42.9)	1.538 (0.442-5.353)	0.499
Hepatocellular carcinoma lesions				0.181
1	7 (43.7)	9 (56.3)	Reference
≥ 2	14 (63.6)	8 (36.4)	1.886 (0.745-4.776)
Alpha-fetoprotein (μg/L)				0.696
< 400	9 (52.9)	8 (47.1)	Reference
≥ 400	12 (57.1)	9 (42.9)	1.188 (0.5-2.823)
Conversion rate				0.011
Fail	9 (42.9)	12 (57.1)	Reference
Succes	12 (70.6)	5 (29.4)	0.272 (0.099-0.745)

Table 5 Multivariate analysis of survival factors in 38 patients with initially unresectable hepatocellular carcinoma

Factors	β	Wald	Hazard ratio	P value	95%CI
Gender				0.060	0.937-24.376
Male	-	-	Reference
Female	1.564	3.541	4.780
Hepatitis				0.107	0.691-44.754
Negative	-	-	Reference
Positive	1.715	2.599	5.559
Antiviral therapy				0.691	0.448-3.359
Negative	-	-	Reference
Positive	0.205	0.159	1.227
Lesion numbers				0.461	0.518-4.275
1	-	-	Reference
≥ 2	0.397	0.544	1.488
Conversion rate
Fail	-	-	Reference
Success	-1.609	8.263	0.200	0.004	0.067-0.599