Prognosis Prediction of CRAFITY Score in HCC Undergoing TACE Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapy

Figures & data

Figure 1 Flowchart of the patient selection process.

Abbreviations: uHCC, unresectable hepatocellular carcinoma; PS, performance status.

Table 1 Baseline Demographic and Clinical Characteristics of Enrolled Patients

Characteristics	CRAFITY 0 Points (n=32)	CRAFITY 1 Points (N=31)	CRAFITY 2 Points (n=22)	Entire Cohort	p value
Age	64+8.4	59+9.6	57+10.9	61+9.9	0.02
Gender					0.352
Male	30(93.8)	26(83.9)	18(81.8)	74(87.1)
Female	2(6.2)	5(16.1)	4(18.2)	11(12.9)
Etiology					0.584
Hepatitis B	26(81.3)	28(90.3)	19(86.4)	73(85.9)
Non	6(18.7)	3(9.7)	3(13.6)	12(14.1)
ECOG PS					0.352
0	17(53.1)	21(67.7)	11(50)	49(57.6)
1	15(36.9)	10(32.3)	11(50)	36(42.4)
Cirrhosis					0.997
Yes	25(78.1)	24(77.4)	17(77.3)	66(77.6)
No	7(11.9)	7(12.6)	5(12.7)	19(12.4)
Child-Pugh stage
A	28(87.5)	22(71.0)	13(59.1)	63(74.1)	0.057
B	4(12.5)	9(29.0)	9(40.9)	22(15.9)
ALBI stage
1	10(31.3)	7(22.6)	3(13.6)	20(23.5)	0.321
2	22(68.7)	24(67.4)	19(86.4)	65(76.5)
BCLC stage					0.013
B	18(56.3)	19(61.3)	5(22.7)	42(49.4)
C	14(43.7)	12(38.7)	17(77.3)	43(50.6)
EHS					0.373
Yes	5(15.6)	4(12.9)	6(27.3)	16(18.8)
No	27(84.6)	27(87.1)	16(72.7)	69(71.2)
Distribution					0.248
Unilobar	22(68.8)	15(48.4)	12(54.5)	50(58.8)
Bilobar	10(31.2)	16(51.6)	10(45.5)	35(41.2)
Tumor diameter	5.4(3.1~8.5)	7.3(4.5~9.2)	10.3(7.2~13.5)	7.2(4.4~10.0)	0.001
AFP ≥100 ng/mL	0	21(67.7)	22(100)	43	0.001
CRP≥1 mg/dl	0	10(32.3)	22(100)	32	0.001
Circle of TACE	3 (1~4)	3 (2~4)	3 (2~4)	3 (2~4)	0.707

Notes: Continuous variables with abnormal distribution were expressed as median (interquartile ranges). Categorical variables were expressed as number (percentage).

Abbreviations: CRAFITY, C-reactive protein and alpha-fetoprotein in immunotherapy; ECOG-PS, Eastern Cooperative Oncology Group performance status; ALBI grade albumin-bilirubin grade; BCLC, Barcelona Clinic Liver Cancer; EHS, extrahepatic spread; AFP, alpha-fetoprotein; CRP, C-reactive protein; TACE transarterial chemoembolization.

Figure 2 (A) Kaplan–Meier curve for overall survival among the three groups. (B) Kaplan–Meier curve for progression-free survival among the three groups.

Figure 3 (A) Kaplan–Meier curve for overall survival between CRAFITY<2 group and CRAFITY 2 group. (B) Kaplan–Meier curve for progression-free survival between CRAFITY<2 group and CRAFITY 2 group.

Table 2 Tumor Response for Each Group

	Entire Cohort	CRAFITY 0 Score	CRAFITY 1 Score	CRAFITY 2 Score	p value
CR	10	5	3	2	0.690
PR	49	20	18	11	0.658
SD	13	5	5	3	0.968
PD	13	2	5	6	0.107
ORR	69.4%	78.1%	67.7%	59.1%	0.040
DCR	84.7%	93.8%	83.9%	72.7%	0.318

Notes: The bold values highlighted the tumor response with significant difference.

Abbreviations: CRAFITY, C-reactive protein and alpha-fetoprotein in immunotherapy; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate.

Table 3 Treatment-Related Adverse Events

Adverse Events	Grade 1/2				Grade 3/4
	CRAFITY 0 Score	CRAFITY 1 Score	CRAFITY 2 Score	p value	CRAFITY 0 Score	CRAFITY 1 Score	CRAFITY 2 Score	p value
Abdominal pain	14	16	13	0.536	1	NA	NA	0.433
Liver injury	22	20	16	0.816	NA	NA	3	0.012
Fever	15	18	8	0.292	NA	1	NA	0.414
Fatigue	3	3	7	0.044	NA	NA	1	0.235
AE related to MTT	13	15	10	0.823	4	3	3	0.895
AE related to ICIs	10	8	5	0.772	2	4	2	0.663

Notes: The bold values highlighted the treatment-related adverse events with significant difference.

Abbreviations: CRAFITY, C-reactive protein and alpha-fetoprotein in immunotherapy; NA, not applicable.

Table 4 Multivariate Analyses Factors Associated with OS and PFS

Variables	Multivariable Analysis		Multivariable Analysis
	OS	p value	PFS	p value
	HR (95% CI)		HR (95% CI)
Cirrhosis	1.560(0.799–3.046)	0.192	1.629(0.731–3.631)	0.233
BCLC stage	1.526(0.760–3.062)	0.235	2.013(1.159–3.496)	0.013
Tumor diameter	1.052(0.976–1.134)	0.182	1.012(0.913–1.121)	0.821
Tumor distribution	0.997(0.533–1.865)	0.991	1.369(0.624–3.004)	0.434
ALBI grade	2.248(0.869–5.819)	0.095	2.118(0.814–5.510)	0.124
CRAFITY		0.038		0.007
0	Reference		Reference
1	1.255(0.536–1.842)	0.524	0.994(0.536–1.842)	0.985
2	2.610(1.281–4.564)	0.014	2.419(1.281–4.564)	0.006

Notes: The bold values highlighted the factors with significant difference.

Abbreviations: ALBI, albumin-bilirubin; BCLC, Barcelona Clinic Liver Cancer; CRAFITY, C-reactive protein and alpha-fetoprotein in immunotherapy.