Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

Table 1 Summary of the prognostic scoring systems (points)

Prognostic system	Constituents		Risk stratification		Candidates
HAP	Albumin < 36 g/L	1	HAP A	0	Yes
	AFP > 400 ng/mL	1	HAP B	1
	Tumor diameter > 7 cm	1	HAP C	2	No
	Bilirubin > 17 μmol/L	1	HAP D	3-4
mHAP	Albumin < 36 g/L	1	mHAP A	0	Yes
	AFP > 400 ng/dL	1	mHAP B	1
	Tumor diameter > 7 cm	1	mHAP C	2	No
			mHAP D	3
mHAP2	Albumin < 36 g/L	1	mHAP2 A	0	Yes
	AFP > 400 ng/mL	1	mHAP2 B	1
	Tumor diameter > 7 cm	1	mHAP2 C	2	No
	Tumor number ≥ 2	1	mHAP2 D	3-5
	Bilirubin > 0.9 mg/dL	1
mHAP3	The prognostic index (PI) formula: (0.104 × size in cm) + [0.3089 × number (single nodule = 1; 2-3 nodules = 2; more than three nodules = 3)] + (0.2185 × Log10AFP in ng/mL) - (0.4049 × Albumin in g/dL) + (0.1506 × Bilirubin in mg/dL)		< Median PI		Yes
			≥ Median PI		No
6&12	Score = Tumor size in cm + Tumor number		< Median Score		Yes
			≥ Median Score		No
ART	Absence of radiologic response	1	0-1.5		Yes
	AST increase >25 %	4
	Child-Pugh increase: 1 point	1.5	≥ 2.5		No
	≥ 2 points	3
ABCR	Presence of radiologic response	-3	≤ 2		Yes
	AFP ≥ 200 ng/mL	1
	BCLC B	2
	BCLC C	3	≥ 3		No
	Child-Pugh increase: ≥ 2 points	2

BCLC: Barcelona Clinic Liver Cancer; HAP: Hepatoma Arterial-embolization Prognostic; mHAP: Modified HAP; 6&12: Six-and-twelve criteria; ART: Assessment for re-treatment with TACE; ABCR: Alpha-fetoprotein, BCLC stage, Child-Pugh and Response.

Table 2 Baseline characteristics of patients treated with first TACE and before repeated TACE, n (%) / Median [IQR]

Characteristics	Study cohort
	TACE (n = 1107)	Re-TACE (n = 912)
Gender
Male	971 (87.7)	801 (87.8)
Female	136 (12.3)	111 (12.2)
Age (year)	57 [47-65]	57 [47-65]
Etiology
HBV	1004 (90.7)	832 (91.2)
Non-HBV	103 (9.3)	80 (8.8)
Largest tumor diameter, cm
≤ 7	459 (41.5)	389 (42.7)
> 7-≤ 10	309 (27.9)	247 (27.1)
> 10	339 (30.6)	276 (30.2)
Number of tumors
1	556 (50.2)	444 (48.7)
2	244 (22.0)	212 (23.2)
≥ 3	307 (27.7)	256 (28.1)
Alpha-fetoprotein, ng/mL
< 400	626 (56.5)	523 (57.3)
≥ 400	481 (43.5)	389 (42.7)
Child-Pugh score
A5	823 (74.3)	688 (75.4)
A6	217 (19.6)	174 (19.1)
B7	67 (6.1)	50 (5.5)
ECOG score
0	639 (57.7)	529 (58.0)
1	468 (42.3)	383 (42.0)
White blood cells, 109/L	5.9 [4.4-8.2]	5.7 [4.3-7.5]
Platelets, 109/L	140 [95-199]	140 [94-197]
International normalized ratio	1.1 [1-1.1]	1.1 [1-1.1]
Alanine aminotransferase, U/L	46 [28-57]	45 [28-59]
Aspartate aminotransferase, U/L	50 [34-73]	50 [34-72]
Albumin, g/L	39.4 [36.1-43.2]	39.5 [36.2-43.3]
Total bilirubin, μmol/L	16.4 [12.0-22.9]	16.3 [12.0-22.4]
Blood urea nitrogen, mmol/L	5.6 [4.6-6.2]	5.6 [4.5-6.3]
Serum creatinine, μmol/L	72 [63-83]	72 [63-83]
Sessions of TACE	3 [2-4]	3 [2-4]

TACE: Transarterial chemoembolization; re-TACE: Repeated TACE; HBV: Hepatitis B virus; ECOG: Eastern Cooperative Oncology Group.

Table 3 Correlations between radiological response and prognostic systems for first transarterial chemoembolization

Prognostic system	Score, median [IQR]	Grade	Radiological response, n					Spearman R (P value)	Kappa (P value)
			CR	PR	SD	PD	Total
HAP	2 [1-2]	A	42	55	26	10	133	0.27 (0.028)	0.10 (0.020)
		B	50	157	83	42	332
		C	39	157	109	92	397
		D	18	72	81	74	245
mHAP	1 [1-2]	A	56	101	43	15	215	0.29 (0.028)	0.10 (0.020)
		B	64	198	116	80	458
		C	25	126	120	96	367
		D	4	16	20	27	67
mHAP2	2 [2-3]	A	13	11	7	2	33	0.27 (0.028)	0.07 (0.017)
		B	50	91	53	19	213
		C	50	180	98	58	386
		D	36	159	141	139	475
mHAP3	0.41 [0.05-0.83]	A	68	129	61	18	276	0.27 (0.028)	0.10 (0.020)
		B	48	119	65	46	278
		C	26	122	72	56	276
		D	7	71	101	98	277
6&12	9.7 [7.5-12.9]	A	70	114	51	22	257	0.39 (0.026)	0.14 (0.019)
		B	58	145	56	46	305
		C	18	114	85	54	271
		D	3	68	107	96	274

HAP: Hepatoma Arterial-embolization Prognostic; mHAP: Modified HAP; 6&12: Six-and-twelve criteria; ART: Assessment for re-treatment with transarterial chemoembolization; ABCR: Alpha-fetoprotein, BCLC stage, Child-Pugh and Response.

Table 4 Comparison of prognostic performance of the predicting systems

Predicting systems	Candidates/non-candidates		Predicting performance
	Number of patients	Median survival (mo)	Cox Regression		C-index (95%CI)	LRχ2
			HR (95%CI)	P value
For first TACE
HAP	465/642	33.8/19.3	0.56 (0.47-0.67)	< 0.001	0.59 (0.56-0.61)	43.71
mHAP	673/434	30.8/16.1	0.58 (0.49-0.68)	< 0.001	0.59 (0.56-0.61)	40.85
mHAP 2	632/475	30.8/17.2	0.60 (0.51-0.71)	< 0.001	0.58 (0.56-0.60)	35.24
mHAP 3	554/553	33.8/17.2	0.52 (0.44-0.62)	< 0.001	0.60 (0.57-0.62)	57.51
6&12	562/545	31.3/18.5	0.61 (0.51-0.72)	< 0.001	0.58 (0.56-0.60)	33.82
For re-TACE
ART	646/266	27.0/23.7	0.88 (0.72-1.08)	0.226	0.52 (0.49-0.54)	1.56
ABCR	600/312	33.1/16.4	0.47 (0.39-0.57)	< 0.001	0.61 (0.59-0.63)	57.36

TACE: Transarterial chemoembolization; HR: Hazard ratio; CI: Confidence interval; LR: Likelihood ratio; HAP: Hepatoma Arterial-embolization Prognostic; mHAP: Modified HAP; 6&12: Six-and-twelve criteria; ART: Assessment for re-treatment with TACE; ABCR: Alpha-fetoprotein, BCLC stage, Child-Pugh and Response.