Value of quality of life analysis in liver cancer: A clinician’s perspective

Table 2 Clinical studies in hepatocellular carcinoma that involved health related quality of life assessment

Ref.	Year	Study type	n	HCC status	Intervention(s)	HRQOL instruments used	HRQOL assessment time point(s)	Remarks
Poon et al[34]	2001	Cohort	76	Resectable and unresectable	Resection (66) vs TACE (10)	FACT-G	Baseline, 3, 6, 7, 12, 18 and 24 mo	Observational study with QOL assessment during treatment
Brans et al[40]	2002	Cohort	26	Unresectable	SIRT (14) vs TACE (14)	EORTC QLQ-C30	Baseline, 1 and 3 mo	Observational study with QOL assessment during treatment
Bianchi et al[32]	2002	Case-control	101	Any stage	NA	SF-36	Baseline	To describe symptomatology and/or HRQOL of HCC patients -HRQOL of HCC patients compared to 202 matched cirrhotic patients
Chow et al[59]	2002	Phase III trial	329	Unresectable	Tamoxifen 120 mg/d (121) vs tamoxifen 60 mg/d (76) vs placebo (132)	Global QOL domain of EORTC QLQ-C30	Baseline, then every 1 mo	Phase III trial with HRQOL endpoint
Steel et al[46]	2004	Cohort	28	Allocated to SIRT or TACE	SIRT (14) vs TACE (14)	FACT-Hep, HepCS, TOI, FHSI8	Baseline, 3, 6 and 12 mo	Observational study with QOL assessment during treatment. Included in[97]
Poon et al[47]	2004	Randomized phase II trial	88	Allocated to TACE	Branched chained amino acid vs control	FACT-G	Baseline, 3, 6, 9 and 12 mo	Phase II trial with HRQOL endpoint
Steel et al[84]	2005	Cohort	82	Any stage	Various treatments	FACT-Hep, HepCS, TOI, FHSI8	Baseline, 3 and 6 mo	To describe symptomatology and/or HRQOL of HCC patients -Compared HRQOL between patients and proxy-raters. Included in[97]
Steel et al[96]	2005	Case-control	21	TNM stage III or IV	NA	FACT-Hep, Sexual History Questionnaire	Baseline	To describe symptomatology and/or HRQOL of HCC patients - Included 23 patients with chronic liver disease
Barbare et al[58]	2005	Phase III trial	420	Not eligible for resection or local treatment	Tamoxifen (210) vs control (210)	Spitzer QoL index	Baseline, then every 3 mo	Phase III trial with HRQOL endpoint
Kirchhoff et al[48]	2005	Randomized phase II trial	70	Eligible for TACE	TACE with microspheres (35) vs TACE (35)	Global QOL of EORTC QLQ-C30	Baseline, then every 6 mo	Phase II trial with HRQOL endpoint
Steel et al[97]	2006	Combined analysis of 3 studies	157	Mixed patient populations from 3 studies	Various treatments	FACT-Hep, HepCS, TOI, FHSI8	Baseline, 3 and 6 mo	Observational study with QOL assessment during treatment - evaluates minimally important difference in HRQOL
Eid et al[36]	2006	Cohort	7	Allocated to hepatic ablation or resection	Hepatic ablation (3) vs resection (4)	EORTC QLQ-C30, FACT-Hep, FHSI8, Profile of Mood States (POMS)	Baseline, postoperative visit, 1.5, 3 and 6 mo	Observational study with QOL assessment during treatment. Study included other liver tumor types (33 patients)
Yeo et al[65]	2006	Combined analysis of 2 phase III trials	233	Unresectable or metastatic	Chemotherapy, hormonal therapy	EORTC QLQ-C30	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC
Wang et al[98]	2006	Cohort	83	Non-metastatic, 3 nodules or less	TACE + RFA (43) vs TACE (40)	FACT-G	Baseline, 3 mo	Observational study with QOL assessment during treatment
Cebon et al[49]	2006	Phase I/II trial	63	Not eligible for standard therapies	Octreotide long acting release	FACT-Hep, patient disease and treatment assessment form (Pt DATA form), patient benefit form	Baseline, then every 1 mo	Phase I/II trial with HRQOL endpoint
Llovet et al[12]	2006	Phase III trial	602	Not eligible for local treatment or had disease progression after surgery or local treatment	Sorafenib (299) vs placebo (303)	FHSI-8	Baseline then every 3 wk	Phase III trial with HRQOL endpoint
Lee et al[31]	2007	Case control	161	Any stage	Surgical, TACE, percutaneous ethanol injection, supportive care	EORTC QLQ-C30, WHOQOL-BREF	Cross sectional one-time assessment	To describe symptomatology and/or HRQOL of HCC patients - compared with national matched healthy controls
Kondo et al[37]	2007	Case-control	97	Non-metastatic, 3 nodules or less	Percutaneous ablation	SF-36	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL compared to 97 matched chronic liver disease controls, and normal population values
Steel et al[33]	2007	Case-control	83	Any stage	NA	FACT-Hep	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL compared to 51 matched chronic liver disease controls, and 138 controls from general population
Martin et al[35]	2007	Cohort	4	Resectable	Resection	EORTC QLQ-C30, FACT-Hep, FHSI-8	Baseline, discharge, postoperative visit, 1.5, 3, 6 and 12 mo	Observational study with QOL assessment during treatment. Included 28 patients with other liver tumors
Becker et al[50]	2007	Randomized phase II trial	120	Not eligible for resection or local treatment	Octreotide (61) vs placebo (59)	EORTC QLQ-C30	Baseline, 1, 3 mo, then every 3 mo	Phase II trial with HRQOL endpoint
Dimitroulopoulos et al[51]	2007	Randomized phase II trial	127	Advanced stage. Somatostatin receptor overexpression for randomisation	Octreotide (31) vs placebo (30) observation (66)	EORTC QLQ-C30	Baseline then every 1 mo	Phase II trial with HRQOL endpoint
Sun et al[99]	2008	Cohort	22	Mainly advanced disease	Various treatments	FACT-Hep, Functional assessment of chronic illness therapy spirituality subscale (FACIT-Sp-12 )	Baseline, 1, 2 and 3 mo	Observational study with QOL assessment during treatment. Included 23 patients with pancreatic cancer
Méndez Romero et al[52]	2008	Phase I/II trial	9	Not eligible for other local treatments	SBRT	EORTC QLQ-C30 EQ-5D VAS	Baseline, 1, 3 and 6 mo	Observational study with QOL assessment during treatment. Included 19 patients with liver metastases. Phase I/II trial with HRQOL endpoint
Bonnetain et al[66]	2008	Combined analysis of 2 phase III trials[59,101]	538	Not eligible for resection, transplantation or percutaneous ablation	Tamoxifen vs supportive care; TACE + tamoxifen vs tamoxifen	Spitzer QoL index	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC
Doffoël et al[100]	2008	Phase III trial	138	Eligible for TACE	TACE + tamoxifen (70) vs tamoxifen (68)	Spitzer QoL index	Baseline, then every 2 mo during treatment, every 3 mo after treatment	Phase III trial with HRQOL endpoint
Barbare et al[60]	2009	Phase III trial	272	Not eligible for curative treatment	Octreotide (135) vs placebo (137)	EORTC QLQ-C30	Baseline, then every 1 mo during treatment, every 3 mo after treatment	Phase III trial with HRQOL endpoint
Cheng et al[13]	2009	Phase III trial	271	Unresectable or metastatic, no prior systemic therapy	Sorafenib (150) vs placebo (76)	FHSI-8. Physical well being domain of FACT-Hep	Baseline then every 3 wk	Phase III trial with HRQOL endpoint
Wible et al[44]	2010	Cohort	73	Allocated to TACE	TACE	SF-36	Baseline, 4, 8 and 12 mo	Observational study with QOL assessment during treatment
Dollinger et al[101]	2010	Phase III trial	135	Locally advanced or metastatic	Thymostimulin (67) vs placebo (68)	FACT = Hep	Baseline then every 3 mo	Phase III trial with HRQOL endpoint
Chow et al[61]	2011	Phase III trial	204	Advanced disease, not eligible for standard therapies	Megestrol acetate (195) vs placebo (69)	EORTC QLQ-C30	Baseline, then every 1 mo during treatment, then every 3 mo after treatment completed	Phase III trial with HRQOL endpoint
Shun et al[102]	2012	Cohort	89	Allocated to TACE	TACE	SF-12, Symptom Distress Scale, Hospital Anxiety and Depression Scale	3 d before discharge, 1 and 2 mo	Observational study with QOL assessment during treatment
Qiao et al[103]	2012	Observational	140	Any stage	NANANAdadsdfsaNA	FACT-epHHep	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL worsens with advancing stage
Eltawil et al[45]	2012	Cohort	48	Allocated to TACE	TACE	WHOQOL-BREF	Baseline then every 3-4 mo	Observational study with QOL assessment during treatment
Fan et al[104]	2012	Cross sectional	286	Any stage		EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL compared with population norms. Correlation between HRQOL and coping and illness perception
Diouf et al[67]	2013	Reanalysis of a phase III trial[61]	215	Not eligible for curative treatment, baseline HRQOL data available	Octreotide vs placebo	EORTC QLQ-C30	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC. HRQOL data may improve existing staging systems
Soliman et al[53]	2013	Phase II trial	21	Not eligible for or refractory to standard therapies, symptomatic	Liver radiotherapy	EORTC QLQ-C30, FACT-Hep, HepCS, TOI, FACT-G	Baseline, 1, 3 and 6 mo	Phase II trial with HRQOL endpoint. Included 20 patients with liver metastasis
Salem et al[41]	2013	Cohort	56	Allocated to SIRT or TACE	SIRT (29), TACE (27)	FACT-Hep	Baseline, 2 and 4 wk	Observational study with QOL assessment during treatment
Brunocilla et al[105]	2013	Cohort	36	Allocated to sorafenib	Sorafenib	FACT-Hep, FHSI-8, FACT-G	Baseline, 1 wk, 1 and 2 mo	Observational study with QOL assessment during treatment
Johnson et al[62]	2013	Phase III trial	1150	Not eligible for resection or local treatment, no prior systemic treatment	Brivanib (577) vs sorafenib (578)	Physical function and role function of EORTC QLQ-C30	Baseline then every 6 wk	Phase III trial with HRQOL endpoint
Meyer et al[63]	2013	Phase II/III trial	86	Unresectable, non-metastatic	TACE vs TAE	EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline, 1.5, 3 and 6 mo	Phase II trial with HRQOL endpoint
Mise et al[106]	2014	Cohort	69	Allocated to resection	Resection	SF-36	Baseline then every 3 mo	Observational study with QOL assessment during treatment
Huang et al[38]	2014	Cohort	388	Solitary HCC ≤ 3 cm	Resection, radiofrequency ablation	FACT-Hep, HepCS, TOI, FACT-G	Baseline, 3, 6, 12, 24 and 36 mo	Observational study with QOL assessment during treatment
Zhu et al[64]	2014	Phase III trial	564	Progressive disease during or after sorafenib	Everolimus (362) vs placebo (184)	Global QOL and physical function of EORTC QLQ-C30	Baseline, then multiple reassessments	Phase III trial with HRQOL endpoint
Palmieri et al[107]	2015	Case control	24	Any stage	NA	SF-36	Baseline	To describe symptomatology and/or HRQOL of HCC patients - evaluates relationship between psychological profile and HRQOL in HCC. Included 22 cirrhotic patients without HCC, 20 control subjects
Chie et al[108]	2015	Cohort	171	Allocated to respective treatments	Surgery (53), ablation (53), TACE (65)	EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline, then 4-6 wk for post-ablation/post-TACE, 12-15 wk post-operation	Observational study with QOL assessment during treatment
Heits et al[109]	2015	Cross sectional	173	Allocated to liver transplanation	liver transplantation	EORTC QLQ-C30	At one variable time point post-transplantion	To describe symptomatology and/or HRQOL of HCC patients
Xie et al[110]	2015	Cohort	102	Allocated to resection or TACE	resection (58), TACE (44)	SF-36	Baseline, 1, 3, 6, 12 and 24 mo	Observational study with QOL assessment during treatment
Xing et al[111]	2015	Cohort	118	Allocated to TACE	TACE with doxorubicin eluted beads	SF-36	Baseline, 1-3, 6 and 12 mo	Observational study with QOL assessment during treatment
Kolligs et al[54]	2015	Randomized phase II trial	28	Allocated to SIRT or TACE	SIRT (13), TACE (15)	FACT-Hep	Baseline, then every 6 wk	Phase II trial with HRQOL endpoint
Klein et al[42]	2015	Combined analysis of prior phase I/II trials	98	Allocated to SBRT	SBRT	EORTC QL-C30, FACT-Hep	Baseline, 1, 3, 6 and 12 mo	Phase I/II trial with HRQOL endpoint
Kensinger et al[48]	2016	Case-control	139	Allocated to priority liver transplantation	Liver transplantation	SF-36	Baseline, post transplantation	Observational study with QOL assessment during treatment - included 362 subjects without HCC
Lei et al[39]	2016	Cohort	205	Allocated to resection or transplantation	Liver transplantation (110), resection (95)	SF-36	Baseline, then every 1-2 mo for the first 6 mo, then every 2-3 mo for the next 6 mo, then every 6 mo	Observational study with QOL assessment during treatment
Yang et al[112]	2016	Cohort	17	Portal vein thrombosis	TACE and transarterial ethanol ablation	EORTC QLQ-C30	Baseline then every 1 mo	Observational study with QOL assessment during treatment
Anota et al[55]	2016	Phase I trial	21	Not eligible for curative treatment	TACE with idaurubicin eluted beads	EORTC QLQ-C30	Baseline, 15, 30 and 60 d	Phase I trial with HRQOL endpoint
Chie et al[88]	2016	Case-control	227	Any stage	Various treatments	EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline, post-treatment	Observational study with QOL assessment during treatment - Compared HRQOL between Asian and European HCC patients
Lv et al[56]	2016	Randomized phase II trial	120	Allocated to TACE	COX2 inhibitor (60) vs placebo (60)	Locally developed questionnaire	Baseline, 24 and 48 h	Phase II trial with HRQOL endpoint
Koeberle et al[57]	2016	Randomized phase II trial	106	Unresectable or metastatic	Sorafenib + everolimus (60) vs sorafenib (46)	FACT-HepCS, EQ-VAS	Baseline, then every 2 wk until week 12	Phase II trial with HRQOL endpoint
Shomura et al[113]	2016	Cohort	54	TNM stage IV	Sorafenib	SF-36	Baseline, then every 3 mo	Observational study with QOL assessment during treatment
Bruix et al[14]	2016	Phase III trial	573	Progressive disease during sorafenib	Regorafenib (379) vs placebo (193)	FACT-Hep, TOI, FACT-G, EQ-5D, EQ-VAS	Baseline, then multiple reassessments	Phase III trial with HRQOL endpoint
Li et al[69]	2017	Cohort	472	Any stage	Various treatments	EORTC QLQ-C30, EORTC QLQ-HCC18, C30 index score, HCC18 index score	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC. QOL derived scoring system resembles a staging system

EORTC: European Organisation for Research and Treatment of Cancer; EQ-5D: EuroQoL-5D; FACT-G: Functional Assessment of Cancer Therapy - General; FACT-Hep: Functional Assessment of Cancer Therapy - Hepatobiliary; FHSI-8: Functional Assessment of Cancer Therapy - Hepatobiliary Symptom Index; HCC: Hepatocellular carcinoma; HepCS: Hepatobiliary cancer subscale; HRQOL: Health related quality of life; n: Sample size; NA: Not applicable; RFA: Radiofrequency ablation; SBRT: Stereotactic body radiation therapy; SF-12: Short Form 12; SF-36: Short Form 36; SIRT: Selective internal radiation therapy; Spitzer QoL Index: Spitzer Quality of Life Index; TACE: Transarterial chemoembolization; TOI: Trial Outcome Index; VAS: Visual analogue scale; WHOQOL-BREF: World Health Organization Quality of Life Assessment abbreviated version.