Anxiety, depression, and quality of life in hepatocellular carcinoma treated with drug-eluting microspheres plus lenvatinib: A prospective study

Table 1 Baseline characteristics of the study population (n = 126), n (%)

Characteristic	Value
Age (years), median (range)	56 (32-74)
Sex
Male	91 (72.2)
Female	35 (27.8)
Etiology
HBV	111 (88.1)
HCV	8 (6.3)
Non-viral	7 (5.6)
Child-Pugh class
A	102 (81.0)
B	24 (19.0)
ECOG PS
0	68 (54.0)
1	50 (39.7)
2	8 (6.3)
BCLC stage
B	47 (37.3)
C	79 (62.7)
Tumor diameter (cm), median (range)	7.2 (3.5-15.8)
Tumor number
Single	53 (42.1)
Multiple	73 (57.9)
Portal vein tumor thrombus	41 (32.5)
AFP (ng/mL), median (range)	386 (3.2-21450)
Number of TACE procedures, median (range)	2 (1-5)
Lenvatinib dose (mg/day)
12	78 (61.9)
8	48 (38.1)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; ECOG PS: Eastern Cooperative Oncology Group performance status; BCLC: Barcelona Clinic Liver Cancer; AFP: Alpha-fetoprotein; TACE: Transcatheter arterial chemoembolization.

Table 2 Changes in anxiety and depression over time (n = 126), mean ± SD/n (%)

Time point	Patients assessed	HADS-A score	Anxiety ≥ 8	HADS-D score	Depression ≥ 8
Baseline	126	9.8 ± 4.2	74 (58.7)	10.3 ± 3.9	77 (61.1)
3 months	126	7.1 ± 3.8a	54 (42.9)	7.3 ± 3.5a	57 (45.2)
6 months	119	5.9 ± 3.2a	42 (35.3)	6.1 ± 3.0a	39 (32.8)
12 months	97	5.2 ± 2.9a	30 (30.9)	5.4 ± 2.7a	28 (28.9)
P value1	-	< 0.001	< 0.001	< 0.001	< 0.001

^aP < 0.001 vs baseline (post-hoc analysis with Bonferroni correction).

¹P value from repeated-measures ANOVA for overall time effect.

HADS-A: Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale-Depression subscale.

Table 3 Changes in quality of life scores over time (n = 126), mean ± SD

Scale/domain	At baseline	At 3 months	At 6 months	At 12 months	P value1
EORTC QLQ-C30
Global health status/QoL	52.3 ± 15.7	65.8 ± 14.5a	69.4 ± 13.8a	71.2 ± 14.3a	< 0.001
Physical functioning	68.5 ± 18.3	75.9 ± 16.8a	78.6 ± 16.1a	81.2 ± 15.7a	< 0.001
Role functioning	65.2 ± 21.4	72.4 ± 18.9a	76.1 ± 17.5a	78.9 ± 17.8a	< 0.001
Emotional functioning	63.7 ± 19.5	72.8 ± 17.2a	76.9 ± 16.4a	79.6 ± 16.2a	< 0.001
Cognitive functioning	71.8 ± 17.2	77.3 ± 15.8a	80.2 ± 15.1a	82.4 ± 14.9a	< 0.001
Social functioning	64.9 ± 20.8	71.5 ± 18.6a	74.8 ± 17.9a	77.3 ± 18.5a	< 0.001
Fatigue	58.3 ± 22.1	45.2 ± 20.3a	40.8 ± 19.7a	35.7 ± 19.4a	< 0.001
Nausea and vomiting	28.4 ± 21.5	22.7 ± 17.8a	19.3 ± 16.2a	15.2 ± 14.8a	< 0.001
Pain	52.6 ± 24.3	39.8 ± 21.6a	34.2 ± 20.1a	28.9 ± 18.7a	< 0.001
EORTC QLQ-HCC18
Fatigue	61.2 ± 21.8	48.7 ± 20.5a	43.9 ± 20.1a	38.4 ± 20.3a	< 0.001
Jaundice	35.2 ± 28.4	27.8 ± 24.7a	23.5 ± 23.1a	18.7 ± 22.3a	< 0.001
Nutrition	54.7 ± 23.2	42.3 ± 21.5a	37.8 ± 20.3a	32.8 ± 19.5a	< 0.001
Pain	49.8 ± 26.1	37.9 ± 23.4a	32.6 ± 21.8a	27.5 ± 20.9a	< 0.001
Body image	48.9 ± 25.7	38.2 ± 23.4a	33.7 ± 22.1a	29.6 ± 21.4a	< 0.001

^aP < 0.01 vs baseline (post-hoc analysis with Bonferroni correction).

¹P value from repeated-measures ANOVA for overall time effect.

EORTC: European Organization for Research and Treatment of Cancer; QLQ-C30: Quality of Life Questionnaire-Core 30; QLQ-HCC18: Quality of Life Questionnaire-Hepatocellular Carcinoma 18; QoL: Quality of life.

Table 4 Correlation between the Hospital Anxiety and Depression Scale score and quality of life domains at baseline (n = 126)

QLQ-C30/QLQ-HCC18 domain	HADS-A score (r)	P value	HADS-D score (r)	P value
Global health status/QoL	-0.68	< 0.001	-0.71	< 0.001
Physical functioning	-0.61	< 0.001	-0.64	< 0.001
Role functioning	-0.59	< 0.001	-0.62	< 0.001
Emotional functioning	-0.72	< 0.001	-0.75	< 0.001
Social functioning	-0.57	< 0.001	-0.60	< 0.001
Fatigue	0.58	< 0.001	0.63	< 0.001
Pain	0.54	< 0.001	0.57	< 0.001
Nausea and vomiting	0.42	< 0.001	0.45	< 0.001
QLQ-HCC18 nutrition	0.56	< 0.001	0.61	< 0.001
QLQ-HCC18 fatigue	0.60	< 0.001	0.65	< 0.001
QLQ-HCC18 body image	0.52	< 0.001	0.55	< 0.001

HADS-A: Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale-Depression subscale; QLQ-C30: Quality of Life Questionnaire-Core 30; QLQ-HCC18: Quality of Life Questionnaire-Hepatocellular Carcinoma 18; QoL: Quality of life.

Table 5 Treatment-related adverse events (n = 126), n (%)

AEs	Any grade	Grade 1 or 2	Grade ≥ 3
Post-embolization syndrome	105 (83.3)	105 (83.3)	0 (0)
Hypertension	60 (47.6)	48 (38.1)	12 (9.5)
Reduced appetite	54 (42.9)	52 (41.3)	2 (1.6)
Fatigue	48 (38.1)	45 (35.7)	3 (2.4)
Diarrhea	44 (34.9)	43 (34.1)	1 (0.8)
Hand-foot skin reaction	40 (31.7)	38 (30.2)	2 (1.6)
Elevated AST/ALT	38 (30.2)	30 (23.8)	8 (6.3)
Nausea	36 (28.6)	36 (28.6)	0 (0)
Proteinuria	28 (22.2)	23 (18.3)	5 (4.0)
Thrombocytopenia	24 (19.0)	20 (15.9)	4 (3.2)
Dysphonia	22 (17.5)	22 (17.5)	0 (0)
Abdominal pain	20 (15.9)	20 (15.9)	0 (0)
Weight loss	18 (14.3)	18 (14.3)	0 (0)
Hypothyroidism	14 (11.1)	14 (11.1)	0 (0)

AE: Adverse event; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.