Early recurrence risk stratification of hepatocellular carcinoma receiving preoperative radiotherapy: Incorporating clinical and imaging features across treatment phases

doi:10.3748/wjg.v32.i23.118308

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jun 21, 2026; 32(23): 118308
Published online Jun 21, 2026. doi: 10.3748/wjg.v32.i23.118308

Table 1 Baseline clinical characteristics and imaging features of patients, n (%) or median (interquartile range)

Characteristics	Total (n = 81)	ER group (n = 37)	Non-ER group (n = 44)	P value
Clinical factors
Age (years)	55 (46.5-62)	55 (46.5-63.5)	53.5 (46.3-62)	0.456
Sex (male)	71 (87.7)	34 (91.9)	37 (84.1)	0.332
Child-Pugh class A	81 (100)	37 (100)	44 (100)
Cirrhosis	65 (80.2)	33 (89.2)	32 (72.7)	0.064
Hepatitis B	60 (74.1)	29 (78.4)	31 (70.5)	0.418
Hepatitis C	5 (6.2)	2 (5.4)	3 (6.8)	1.000
BCLC stage				0.877
A	51 (63.0)	23 (62.2)	28 (63.6)
B	3 (3.7)	1 (2.7)	2 (4.5)
C	27 (33.3)	13 (35.1)	14 (31.8)
AFP > 400 ng/mL	40 (49.4)	20 (54.1)	20 (45.5)	0.441
PLT < 100 × 10⁹/L	3 (3.7)	1 (2.7)	2 (4.5)	1.000
ALT > 40 U/L	28 (34.6)	15 (40.5)	13 (29.5)	0.300
AST > 40 U/L	30 (37.0)	16 (43.2)	14 (31.8)	0.289
GGT > 60 U/L	41 (50.6)	26 (70.3)	15 (34.1)	0.001^a
TBIL > 21 μmol/L	17 (21.0)	8 (21.6)	9 (20.5)	0.898
Albumin < 40 g/L	8 (9.9)	4 (10.8)	4 (9.1)	1.000
ALBI grade 2	12 (14.8)	6 (16.2)	6 (13.6)	0.764
Imaging features
Tumor size > 5 cm	59 (72.8)	30 (81.1)	29 (65.9)	0.142
Tumor number 2-3	6 (7.4)	4 (10.8)	2 (4.5)	0.404
Satellite tumors	6 (7.4)	4 (10.8)	2 (4.5)	0.404
Tumor in vein	25 (30.9)	12 (32.4)	13 (29.5)	0.779
PVTT I	15 (60.0)	10 (83.3)	5 (38.5)
PVTT II	8 (32.0)	1 (8.3)	7 (53.8)
PVTT III	1 (4.0)	0 (0.0)	1 (7.7)
IVCTT	1 (4.0)	1 (8.3)	0 (0.0)
Nonrim APHE	51 (63.0)	21 (56.8)	30 (68.2)	0.289
Nonperipheral washout	70 (86.4)	32 (86.5)	38 (86.4)	0.987
Enhancing capsule	73 (90.1)	35 (94.6)	38 (86.4)	0.279
Mild-moderate T2 hyperintensity	79 (97.5)	37 (100)	42 (95.5)	0.498
Corona enhancement	48 (59.3)	24 (64.9)	24 (54.5)	0.346
Nonenhancing capsule	4 (4.9)	1 (2.7)	3 (6.8)	0.621
Nodule-in-nodule	12 (14.8)	5 (13.5)	7 (15.9)	0.762
Mosaic architecture	38 (46.9)	18 (48.6)	20 (45.5)	0.774
Blood products in mass	32 (39.5)	16 (43.2)	16 (36.4)	0.528
Fat in mass	33 (40.7)	16 (43.2)	17 (38.6)	0.674
Rim APHE	30 (37.0)	16 (43.2)	14 (31.8)	0.289
Peripheral washout	8 (9.9)	5 (13.5)	3 (6.8)	0.459
Delayed central enhancement	9 (11.1)	2 (5.4)	7 (15.9)	0.170
Targetoid restriction	12 (14.8)	4 (10.8)	8 (18.2)	0.352
Necrosis or severe ischemia	69 (85.2)	31 (83.8)	38 (86.4)	0.745
Nonsmooth tumor margin	69 (85.2)	32 (86.5)	37 (84.1)	0.762
APHE portion ≥ 50%	38 (46.9)	13 (35.1)	25 (56.8)	0.051
Intratumoral artery	45 (55.6)	22 (59.5)	23 (52.3)	0.517
Complete capsule	26 (32.1)	13 (35.1)	13 (29.5)	0.591
Tumor ADC (× 10^-3 mm²/second)	1.15 (1.04-1.26)	1.15 (1.02-1.24)	1.15 (1.06-1.32)	0.544
Tumor-to-liver ADC ratio	0.95 (0.85-1.06)	0.93 (0.86-1.02)	0.96 (0.84-1.09)	0.310

^aP < 0.05.

ER: Early recurrence; BCLC: Barcelona Clinic Liver Cancer; AFP: Alpha-fetoprotein; PLT: Platelet count; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transpeptidase; TBIL: Total bilirubin; ALBI: Albumin-bilirubin; PVTT: Portal vein tumor thrombus; IVCTT: Inferior vena cava tumor thrombus; APHE: Arterial phase hyperenhancement; ADC: Apparent diffusion coefficient.

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Table 2 Preoperative and postoperative characteristics of patients, n (%) or median (interquartile range)

Characteristics	Total (n = 81)	ER group (n = 37)	Non-ER group (n = 44)	P value
Preoperative clinical factors
TACE prior to RT	5 (6.2)	3 (8.1)	2 (4.5)	0.656
Concurrent systemic therapy	41 (50.6)	18 (48.6)	23 (52.3)	0.745
Targeted therapy	34 (82.9)	13 (72.2)	21 (91.3)
Targeted therapy plus immunotherapy	4 (9.8)	3 (16.7)	1 (4.3)
Immunotherapy	3 (7.3)	2 (11.1)	1 (4.3)
TACE after RT	8 (9.9)	5 (13.5)	3 (6.8)	0.459
Preoperative AFP > 400 ng/mL	9 (11.1)	8 (21.6)	1 (2.3)	0.010^a
Preoperative PLT count < 100 × 10⁹/L	20 (24.7)	11 (29.7)	9 (20.5)	0.335
Preoperative ALT > 40 U/L	17 (21.0)	6 (16.2)	11 (25.0)	0.334
Preoperative AST > 40 U/L	20 (24.7)	7 (18.9)	13 (29.5)	0.269
Preoperative GGT > 60 U/L	50 (61.7)	24 (64.9)	26 (59.1)	0.594
Preoperative TBIL > 21 μmol/L	6 (7.4)	1 (2.7)	5 (11.4)	0.212
Preoperative albumin < 40 g/L	28 (34.6)	14 (37.8)	14 (31.8)	0.570
Preoperative ALBI grade 2	26 (32.1)	11 (29.7)	15 (34.1)	0.675
Imaging features
Early response by RECIST				0.370
CR + PR	26 (32.1)	10 (27.0)	16 (36.4)
SD + PD	55 (67.9)	27 (73.0)	28 (63.6)
Early response by mRECIST				0.264
CR + PR	47 (58.0)	19 (51.4)	28 (63.6)
SD + PD	34 (42.0)	18 (48.6)	16 (36.4)
Preoperative response by RECIST				0.842
CR + PR	36 (44.4)	16 (43.2)	20 (45.5)
SD + PD	45 (55.6)	21 (56.8)	24 (54.5)
Preoperative response by mRECIST				0.213
CR + PR	56 (69.1)	23 (62.2)	33 (75.0)
SD + PD	25 (30.9)	14 (37.8)	11 (25.0)
Preoperative CR by mRECIST	18 (22.2)	4 (10.8)	14 (31.8)	0.023^a
Tumor ADC (× 10^-3 mm²/second)	1.47 (1.31-1.69)	1.47 (1.27-1.65)	1.48 (1.31-1.72)	0.513
Tumor-to-liver ADC ratio	1.20 (1.09-1.46)	1.20 (1.01-1.44)	1.21 (1.10-1.46)	0.431
ΔADC%	28.3 (13.4-42.2)	28.3 (12.4-40.7)	28.2 (17.2-46.5)	0.615
Pathological factors
Major pathological response	32 (39.5)	13 (35.1)	19 (43.2)	0.461
Pathological complete response	8 (9.9)	2 (5.4)	6 (13.6)	0.279
Poor tumor differentiation	39 (48.1)	18 (48.6)	21 (47.7)	0.934
MVI	22 (27.2)	14 (37.8)	8 (18.2)	0.048^a
Satellite nodules	8 (9.9)	6 (16.2)	2 (4.5)	0.133
Invasion of liver surface	25 (30.9)	13 (35.1)	12 (27.3)	0.445

^aP < 0.05.

ER: Early recurrence; RT: Radiotherapy; TACE: Transarterial chemoembolization; AFP: Alpha-fetoprotein; PLT: Platelet count; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transpeptidase; TBIL: Total bilirubin; ALBI: Albumin-bilirubin; RECIST: Response Evaluation Criteria in Solid Tumor; mRECIST: Modified Response Evaluation Criteria in Solid Tumor; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; ADC: Apparent diffusion coefficient; MVI: Microvascular invasion.

Full Size Table

Table 3 Multivariable Cox regression analysis for early recurrence-free survival

Variables	Baseline model		Baseline-preoperative model		Preoperative model		Pre-postoperative model		Postoperative combined model
Variables	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Baseline variables
Cirrhosis	2.39 (0.84-6.77)	0.101	3.27 (1.09-9.83)	0.035	NA	NA	NA	NA	4.85 (1.59-14.74)	0.005
GGT > 60 U/L	3.31 (1.62-6.78)	0.001	4.29 (1.96-9.42)	< 0.001	NA	NA	NA	NA	4.67 (2.17-10.07)	< 0.001
Tumor size > 5 cm	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
APHE portion ≥ 50%	0.49 (0.25-0.96)	0.037	0.36 (0.18-0.72)	0.004	NA	NA	NA	NA	0.29 (0.14-0.59)	< 0.001
Preoperative variables
Preoperative AFP > 400 ng/mL	NA	NA	1.93 (0.82-4.52)	0.129	3.59 (1.63-7.94)	0.002	3.12 (1.38-7.04)	0.006	NA	NA
Preoperative CR by mRECIST	NA	NA	0.15 (0.05-0.45)	< 0.001	0.32 (0.11-0.91)	0.032	0.34 (0.12-0.97)	0.043	0.15 (0.05-0.45)	< 0.001
Pathological variables
MVI	NA	NA	NA	NA	NA	NA	1.77 (0.89-3.53)	0.102	2.36 (1.14-4.88)	0.021

HR: Hazard ratio; CI: Confidence interval; GGT: Gamma-glutamyl transpeptidase; APHE: Arterial phase hyperenhancement; AFP: Alpha-fetoprotein; CR: Complete response; mRECIST: Modified Response Evaluation Criteria in Solid Tumor; MVI: Microvascular invasion; NA: Not applicable.

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Table 4 C-index of the prognostic models and major staging systems

Models	C-index	Bootstrap C-index	P value	P value
Baseline model	0.707 (0.627-0.787)	0.686 (0.600-0.770)	0.010	0.011
Baseline-preoperative model	0.779 (0.714-0.844)	0.751 (0.675-0.824)	Reference	0.704
Preoperative model	0.634 (0.563-0.705)	0.631 (0.552-0.696)	< 0.001	< 0.001
Pre-postoperative model	0.673 (0.593-0.753)	0.660 (0.627-0.784)	0.018	0.007
Postoperative combined model	0.786 (0.717-0.855)	0.758 (0.678-0.834)	0.704	Reference
BCLC stage	0.508 (0.430-0.585)	0.530 (0.497-0.607)	< 0.001	< 0.001
TNM stage	0.526 (0.450-0.602)	0.512 (0.428-0.540)	< 0.001	< 0.001
CNLN stage	0.548 (0.462-0.634)	0.516 (0.476-0.554)	< 0.001	< 0.001

BCLC: Barcelona Clinic Liver Cancer; TNM: Tumor-node-metastasis; CNLC: China liver cancer.

Full Size Table

Citation: Cong R, Chen B, Cheng SN, Zhai YR, Wu F, Feng B, Wang LY, Chen ZW, Zhu YJ, Ma XH, Zhao XM. Early recurrence risk stratification of hepatocellular carcinoma receiving preoperative radiotherapy: Incorporating clinical and imaging features across treatment phases. World J Gastroenterol 2026; 32(23): 118308
URL: https://www.wjgnet.com/1007-9327/full/v32/i23/118308.htm
DOI: https://dx.doi.org/10.3748/wjg.v32.i23.118308

Cong R, Chen B, Cheng SN, Zhai YR, Wu F, Feng B, Wang LY, Chen ZW, Zhu YJ, Ma XH, Zhao XM. Early recurrence risk stratification of hepatocellular carcinoma receiving preoperative radiotherapy: Incorporating clinical and imaging features across treatment phases. World J Gastroenterol 2026; 32(23): 118308 [DOI: 10.3748/wjg.v32.i23.118308]

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