Clinical Benefits of Neoadjuvant Radiotherapy on the Postoperative Recurrence of Centrally Located Hepatocellular Carcinoma: A Real-World Evidence Based on Phase II Clinical Trial

Figures & data

Table 1 Comparisons of Baseline Demographics and Clinicopathological Characteristics in Patients Undergoing neoRT + LR or LR Alone Before and After Propensity Score Matching Analysis

Characteristic	Before Matching			After Matching
	neoRT+LR (n=38)	LR (n=130)	Standardized Mean Difference^a	neoRT+LR (n=36)	LR (n=36)	Standardized Mean Difference^a
Age (years)			0.30			0.06
≤60	25 (65.8%)	103 (79.2%)		25 (69.4%)	26 (72.2%)
>60	13 (34.2%)	27 (20.8%)		11 (30.6%)	10 (27.8%)
Sex			0.40			0
Male	37 (97.4%)	113 (86.9%)		35 (97.2%)	35 (97.2%)
Female	1 (2.6%)	17 (13.1%)		1 (2.8%)	1 (2.8%)
Alcoholism			0.31			0.06
Yes	16 (42.1%)	36 (27.7%)		15 (41.7%)	14 (38.9%)
No	22 (57.9%)	94 (72.3%)		21 (58.3%)	22 (61.1%)
Preoperative liver function
ALT level	29.9 ± 16.8	37.1 ± 39.5	0.24	30.4 ± 17.1	32.9 ± 21.1	0.13
ALB level	42.1 ± 2.9	44.1 ± 3.9	0.58	42.1 ± 3.0	42.0 ± 3.8	0.04
TBIL level	12.4 ± 4.6	13.2 ± 5.1	0.16	12.4 ± 4.6	12.2 ± 4.5	0.04
Tumor
Preoperative AFP level^b	2.2 ± 1.4	1.8 ± 1.3	0.30	2.3 ± 1.4	2.2 ± 1.3	0.05
Satellite nodule			0.24			0.08
Yes	5 (13.2%)	29 (22.3%)		5 (13.9%)	6 (16.7%)
No	33 (86.8%)	101 (77.7%)		31 (86.1%)	30 (83.3%)
Diaphragmatic invasion			0.10			0
Yes	3 (7.9%)	7 (5.4%)		3 (8.3%)	3 (8.3%)
No	35 (92.1%)	123 (94.6%)		33 (91.7%)	33 (91.7%)
Tumor size (cm)	6.5 ± 2.8	6.0 ± 3.6	0.14	6.6 ± 2.8	6.7 ± 4.0	0.01
Number			0.08			0
Single	34 (89.5%)	113 (86.9%)		32 (88.9%)	32 (88.9%)
Multiple	4 (10.5%)	17 (13.1%)		4 (11.1%)	4 (11.1%)

Notes: ^aStandardized differences of ≥ 0.1 represent meaningful differences in covariates between groups. ^bVariables are transformed as log10. Variables are expressed as the mean±SD (median with range) or N (%) (number with percentages), unless otherwise indicated.

Abbreviations: neoRT, neoadjuvant radiotherapy; LR, liver resection.

Figure 1 Flow chart for patient screening.

Table 2 Associations Between neoRT + LR and LR Alone Group in the Crude Analysis, Multivariable Analysis and Propensity-Score Analysis

Analysis	Hazard Ratio (95% CI)
Crude analysis	0.52 (0.32, 0.84)
Multivariable analysis^a	0.42 (0.25, 0.69)
Propensity-score analyses
With matching^b	0.43 (0.24, 0.76)
With GenMatching^c	0.32 (0.23, 0.43)
Adjusted for propensity score^d	0.41 (0.23, 0.73)
With inverse probability weighting^e	0.38 (0.22, 0.65)

Notes: ^aShown is the hazard ratio from the multivariable Cox proportional-hazards model, with stratification according to neoadjuvant radiotherapy, and with additional adjustment for confounders sex, albumin, tumor number, tumor size and satellite nodule. The analysis included all patients. ^bShown is the hazard ratio from a multivariable Cox proportional-hazards model with the same strata and covariates with matching according to the propensity score (Confounders or Covariates included sex, age, albumin, alanine aminotransferase, tumor number, tumor size, satellite nodule and alpha-fetoprotein; caliper 0.02). The analysis included 72 patients (36 who received neoRT + LR and 36 who received LR alone). ^cMatching was performed using a genetic matching algorithm (Diamond & Sekhon, 2013) as implemented in the R Matching package. ^dShown is the hazard ratio from a Cox proportional-hazards model with the same strata and covariates, with additional adjustment for the propensity score. The analysis included 72 patients (36 who received neoRT + LR and 36 who received LR alone). ^eShown is the primary analysis with a hazard ratio from the multivariable Cox proportional-hazards model with the same strata and covariates with inverse probability weighting according to the propensity score. The analysis included all the patients.

Figure 2 Cox proportional-hazards regression in DFS.

Abbreviations: NeoRT, neoadjuvant radiotherapy; LR, liver resection; Cm, centimetre; AFP, Alpha-fetoprotein; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; TBIL, Total bilirubin.

Figure 3 Kaplan–Meier curve of DFS before matching in neoRT+LR and LR groups.

Abbreviations: NeoRT, neoadjuvant Radiotherapy; LR, liver resection.

Figure 4 Kaplan–Meier curve of DFS after matching in neoRT+LR and LR groups.

Abbreviations: NeoRT, neoadjuvant Radiotherapy; LR, liver resection.

Table 3 Comparisons of Early Recurrence in Patients Undergoing LR+neoRT or LR

	NeoRT+LR	LR	Standardized Difference (95% CI)	P-value
Early Recurrence (12 months)			0.65 (0.17, 1.12)	0.009
Yes	10	21
No	26	15
Early Recurrence (24 months)			0.78 (0.30, 1.26)	0.002
Yes	13	26
No	23	10

Abbreviations: NeoRT, neoadjuvant radiotherapy; LR, liver resection.