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.