Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

Table 1 Baseline characteristics of adolescent and young adult and older hepatocellular carcinoma patients

Characteristic		Total	AYA	Older	P value
		n = 12721	n = 366 (2.9%)	n = 12355 (97.1%)
Sex					< 0.001
	Male	10075	249 (68.0%)	9826 (79.5%)
	Female	2646	117 (32.0%)	2529 (20.5%)
Race					< 0.001
	White	8323	190 (51.9%)	8133 (65.8%)
	Black	1990	59 (16.1%)	1931 (15.6%)
	Other	2408	117 (32.0%)	2291 (18.5%)
Marital status					< 0.001
	Not married	2818	197 (53.8%)	2621 (21.2%)
	Married	9903	169 (46.2%)	9734 (78.0%)
SEER stage					< 0.001
	Localized	7264	178 (48.6%)	7086 (57.4%)
	Regional	3476	107 (29.2%)	3396 (27.3%)
	Distant	1981	81 (22.1%)	1900 (15.4%)
AJCC stage					< 0.001
	I	5063	118 (32.2%)	4945 (40.0%)
	II	2744	68 (18.6%)	2676 (21.7%)
	III	3036	105 (28.7%)	2931 (23.7%)
	IV	1878	75 (20.5%)	1803 (14.6%)
Grade					0.158
	I	3913	114 (31.3%)	3799 (30.7%)
	II	5719	141 (38.5%)	5578 (45.1%)
	III	2848	102 (27.9%)	2746 (22.2%)
	IV	241	9 (2.5%)	232 (1.9%)
Surgery					< 0.001
	No	6622	130 (35.5%)	6492 (52.5%)
	Yes	6099	236 (64.5%)	5863 (47.5%)
Radiation					0.319
	No	11862	346 (94.5%)	11516 (93.2%)
	Yes	859	20 (5.5%)	839 (6.8%)
Chemotherapy					0.306
	No	8074	223 (60.9%)	7851 (63.5%)
	Yes	4647	143 (39.1%)	4504 (36.5%)

AYA: Adolescent and young adult; HCC: Hepatocellular carcinoma; SEER: Surveillance, Epidemiology, and End Results; AJCC: American Joint Committee on Cancer; Grade I: Well differentiated; Grade II: Moderately differentiated; Grade III: Poorly differentiated; Grade IV: Undifferentiated.

Table 2 Univariate and multivariate analyses of overall survival in patients with hepatocellular carcinoma

Characteristic		Univariate analysis, HR (95%CI)	P value	Multivariate analysis, HR (95%CI)	P value
Age
	AYA	Reference		Reference
	Older	1.504 (1.307-1.732)	< 0.001	1.405 (1.218-1.621)	< 0.001
Sex
	Male	Reference		Reference
	Female	0.817 (0.775-0.861)	< 0.001	0.898 (0.851-0.947)	< 0.001
Race
	White	Reference		Reference
	Black	1.293 (1.223-1.368)	< 0.001	1.109 (1.048-1.174)	< 0.001
	Other	0.812 (0.767-0.860)	< 0.001	0.871 (0.823-0.923)	< 0.001
Marital status
	Not married	Reference		Reference
	Married	0.805 (0.767-0.846)	< 0.001	0.931 (0.885-0.980)	0.006
AJCC stage
	I	Reference		Reference
	II	1.028 (0.967-1.093)	0.376	1.116 (1.049-1.188)	< 0.001
	III	2.810 (2.662-2.966)	< 0.001	2.138 (2.021-2.262)	< 0.001
	IV	5.629 (5.290-5.990)	< 0.001	3.128 (2.925-3.345)	< 0.001
Grade
	I	Reference		Reference
	II	1.068 (1.016-1.123)	0.010	1.214 (1.154-1.277)	< 0.001
	III	1.856 (1.754-1.964)	< 0.001	1.708 (1.612-1.811)	< 0.001
	IV	2.270 (1.974-2.610)	< 0.001	1.998 (1.735-2.300)	< 0.001
Surgery
	No	Reference		Reference
	Yes	0.223 (0.213-0.234)	< 0.001	0.239 (0.226-0.252)	< 0.001
Radiation
	No	Reference		Reference
	Yes	1.428 (1.321-1.544)	< 0.001	0.712 (0.658-0.771)	< 0.001
Chemotherapy
	No	Reference		Reference
	Yes	1.053 (1.009-1.099)	0.018	0.598 (0.571-0.626)	< 0.001

OS: Overall survival; HCC: Hepatocellular carcinoma; HR: Hazard ratio; CI: Confident interval; AYA: Adolescent and young adult; AJCC: American Joint Committee on Cancer; Grade I: Well differentiated; Grade II: Moderately differentiated; Grade III: Poorly differentiated; Grade IV: Undifferentiated.

Table 3 Baseline characteristics of adolescent and young adult and older hepatocellular carcinoma patients after propensity score matching

Characteristic		Total, n = 690	AYA, n = 345 (50%)	Older, n = 345 (50%)	P value
Sex					0.934
	Male	475	238 (69.0%)	237 (68.7%)
	Female	215	107 (31.0%)	108 (31.3%)
Race					0.985
	White	371	185 (53.6%)	186 (53.9%)
	Black	117	58 (16.8%)	59 (17.1%)
	Other	202	102 (29.6%)	100 (29.0%)
Marital status					1.000
	No married	356	178 (51.6%)	178 (51.6%)
	Married	334	167 (48.4%)	167 (48.4%)
AJCC stage					0.974
	I	230	115 (33.3%)	115 (33.3%)
	II	127	64 (18.6%)	63 (18.3%)
	III	197	98 (28.4%)	99 (28.7%)
	IV	136	68 (19.7%)	68 (19.7%)
Grade					0.887
	I	217	109 (31.6%)	108 (31.3%)
	II	271	136 (39.4%)	135 (39.1%)
	III	188	93 (27.0%)	95 (27.5%)
	IV	14	7 (2.0%)	7 (2.0%)
Surgery					1.000
	No	250	125 (36.2%)	125 (36.2%)
	Yes	440	220 (63.8%)	220 (63.8%)
Radiation					1.000
	No	666	333 (96.5%)	333 (96.5%)
	Yes	24	12 (3.5%)	12 (3.5%)
Chemotherapy					0.937
	No	437	219 (63.5%)	218 (63.2%)
	Yes	253	126 (36.5%)	127 (36.8%)

AYA: Adolescent and young adult; HCC: Hepatocellular carcinoma; PSM: Propensity score matching; AJCC: American Joint Committee on Cancer; Grade I: Well differentiated; Grade II: Moderately differentiated; Grade III: Poorly differentiated; Grade IV: Undifferentiated.

Table 4 Comparison of overall survival between adolescent and young adult and older groups

	Characteristics	Survival months (Median, IQR)	P value
Before PSM	AYA	20.00 (5.00-62.50)	< 0.001
	Older adults	15.00 (4.00-40.00)
After PSM	AYA	21.00 (5.00-64.50)	< 0.001
	Older adults	18.00 (6.00-53.00)

OS: Overall survival; AYA: Adolescent and young adult; PSM: Propensity score matching; IQR: Interquartile range.

Table 5 Subgroup multivariate analysis stratified by American Joint Committee on Cancer stage

	Characteristics (AYA vs Older adults)	Multivariate analysis HR (95%CI)	P value
Before PSM	AJCC stage I/II	1.749 (1.352-2.263)	< 0.001
	AJCC stage III/IV	1.186 (0.997-1.410)	0.054
After PSM	AJCC stage I/II	1.891 (1.356-2.637)	< 0.001
	AJCC stage III/IV	1.192 (0.934-1.521)	0.157

Incorporating “age, sex, race, marital status, AJCC stage, grade, surgery, radiation, and chemotherapy” into Cox proportional hazard regression model, with AYA group as the reference. AJCC: American Joint Committee on Cancer; AYA: Adolescent and young adult; HR: Hazard ratio; CI: Confident interval; PSM: Propensity score matching.