AADN score: Predicting response to transarterial chemoembolization, sintilimab and lenvatinib in patients with hepatocellular carcinoma

Table 1 Comparison of clinicopathological characteristics of two groups patients, mean ± SD/median (interquartile range)

Parameter	Total patients (n = 188)	Training cohort (n = 101)	Validation cohort (n = 87)	P value
Gender: Female/male	24/164	14/87	10/77	0.790
Age (years)	57.76 ± 11.40	57.74 ± 12.44	57.78 ± 10.16	0.808
BMI	21.81 ± 2.72	21.96 ± 2.66	21.62 ± 2.77	0.415
Family history: No/yes	173/15	94/7	79/8	0.763
Alcohol abuse: No/yes	119/69	63/38	56/31	0.896
Smoking: No/yes	133/55	69/32	64/23	0.530
HBsAg: Negative/positive	37/151	24/77	13/74	0.183
Tumor size (cm)	8.31 ± 3.90	8.27 ± 3.97	8.35 ± 3.82	0.896
TBS	8.42 ± 3.71	8.33 ± 3.80	8.52 ± 3.59	0.735
PVTT: No/yes	125/63	73/28	52/35	0.098
EHS	141/47	75/26	66/21	0.933
Child stage: A/B	132/56	67/34	65/22	0.275
BCLC stage: B/C	104/84	59/42	45/42	0.439
ECOG-PS: 0/1-2	134/54	74/27	60/27	0.516
WBC (× 109/L)	6.04 ± 2.23	6.11 ± 2.41	5.95 ± 2.01	0.994
NEUT (× 109/L)	3.76 ± 1.74	3.72 ± 1.73	3.81 ± 1.75	0.736
LYMPH (× 109/L)	1.41 ± 0.55	1.49 ± 0.61	1.33 ± 0.46	0.085
Platelets (× 109/L)	179.61 ± 92.69	180.05 ± 91.57	179.09 ± 93.97	0.994
Albumin (g/L)	36.48 ± 6.44	36.50 ± 5.31	36.45 ± 7.54	0.316
Globulin (g/L)	35.28 ± 7.53	34.74 ± 8.04	35.92 ± 6.85	0.155
TBIL (μmol/L)	18.55 ± 12.69	18.50 ± 12.06	18.61 ± 13.39	0.545
DBIL (μmol/L)	10.12 ± 9.99	9.94 ± 9.74	10.33 ± 10.28	0.791
ALT (U/L)	30.65 (21.3-50.58)	28.9 (18.5-52.65)	31.9 (24.1-50.1)	0.185
AST (U/L)	47.3 (33.06-79.95)	47 (32.25-78.9)	48.4 (33.22-87.2)	0.844
GGT (U/L)	113 (69.64-214.9)	122.4 (78-223)	107 (64-189)	0.192
ALP (U/L)	116.42 (89-164)	116.84 (89-166.5)	115 (87-151)	0.526
AFP (ng/mL)	105.97 (6.76-1207.5)	96.5 (5.96-1210)	115.4 (7.16-1098.3)	0.808
ALBI score (1/2/3)	52/123/13	32/61/8	20/62/5	0.317
BUN (mmol/L)	5.17 ± 1.92	5.11 ± 1.89	5.24 ± 1.95	0.721
Cr (μmol/L)	72.91 ± 20.48	72.05 ± 19.81	73.91 ± 21.19	0.450
PT (seconds)	12.75 ± 1.63	12.79 ± 1.75	12.70 ± 1.47	0.877
INR	1.11 ± 0.15	1.11 ± 0.16	1.11 ± 0.14	0.539
NLR	2.92 ± 1.52	2.78 ± 1.50	3.08 ± 1.54	0.117

BMI: Body mass index; HBsAg: Hepatitis B surface antigen; TBS: Tumor burden score; PVTT: Portal vein tumor thrombus; EHS: Extrahepatic spread; BCLC: Barcelona Clinic Liver Cancer; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; WBC: White blood cell; NEUT: Neutrophilic granulocyte; LYMPH: Lymphocyte; TBIL: Total bilirubin; DBIL: Direct bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin; BUN: Blood urea nitrogen; Cr: Creatinine; PT: Prothrombin time; INR: International normalized ratio; NLR: Neutrophil to lymphocyte ratio.

Table 2 Univariate Cox regression analyses of overall survival in the training cohort

Variable	HR	95%CI	P value
Gender (male vs female)	1.348	0.481-3.778	0.571
Age, years (> 55 vs ≤ 55)	0.996	0.538-1.845	0.990
BMI (> 22 vs ≤ 22)	0.923	0.495-1.721	0.802
Alcohol abuse (present vs absent)	0.783	0.407-1.507	0.465
HBsAg (positive vs negative)	1.029	0.434-2.443	0.948
Tumor size, cm (> 6 vs ≤ 6)	1.092	0.505-2.361	0.822
Tumor number (multiple vs single)	1.330	0.636-2.781	0.448
TBS (> 8 vs ≤ 8)	1.637	0.891-3.008	0.113
PVTT (present vs absent)	2.216	1.205-4.077	0.011
EHS (present vs absent)	1.382	0.708-2.700	0.339
Child stage (B vs A)	2.519	1.345-4.718	0.004
ECOG-PS (1-2 vs 0)	1.446	0.776-2.697	0.246
DBIL, μmol/L (> 7.3 vs ≤ 7.3)	3.629	1.875-7.025	< 0.001
ALP, U/L (> 120 vs ≤ 120)	2.892	1.544-5.416	0.001
AFP, ng/mL (> 100 vs ≤ 100)	2.798	1.451-5.395	0.002
NLR (> 2.5 vs ≤ 2.5)	3.363	1.606-7.044	0.001

BMI: Body mass index; HBsAg: Hepatitis B surface antigen; TBS: Tumor burden score; PVTT: Portal vein tumor thrombus; EHS: Extrahepatic spread; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; DBIL: Direct bilirubin; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; NLR: Neutrophil to lymphocyte ratio; HR: Hazard ratio; CI: Confidence interval.

Table 3 Multivariable Cox regression analyses of overall survival in the training cohort

Variable	β estimate (95%CI)	HR (95%CI)	P value
PVTT (present vs absent)		1.005 (0.481-2.099)	0.844
Child stage (B vs A)		0.857 (0.400-1.835)	0.481
AFP, ng/mL (> 100 vs ≤ 100)	0.947 (0.229-1.665)	2.579 (1.258-5.285)	0.010
ALP, U/L (> 120 vs ≤ 120)	0.804 (0.120-1.149)	2.234 (1.127-4.430)	0.021
DBIL, μmol/L (> 7.3 vs ≤ 7.3)	1.075 (0.297-1.853)	2.931 (1.346-6.382)	0.007
NLR (> 2.5 vs ≤ 2.5)	1.140 (0.325-1.955)	3.127 (1.384-7.063)	0.006

PVTT: Portal vein tumor thrombus; AFP: Alpha-fetoprotein; ALP: Alkaline phosphatase; DBIL: Direct bilirubin; NLR: Neutrophil to lymphocyte ratio; HR: Hazard ratio; CI: Confidence interval.