Elsevier

Journal of Hepatology

Volume 58, Issue 3, March 2013, Pages 509-521
Journal of Hepatology

Research Article
The added value of quality of life (QoL) for prognosis of overall survival in patients with palliative hepatocellular carcinoma

https://doi.org/10.1016/j.jhep.2012.11.019Get rights and content

Background & Aims

Several prognostic classifications (PCs) have been developed for use in palliative care in patients with hepatocellular carcinoma (HCC). We have recently suggested that CLIP combined with WHO PS has the greatest discriminative power. We evaluated the prognostic value of quality of life (QoL) data and whether the latter could improve classification of palliative HCC patients.

Methods

This was a reanalysis from the CHOC trial with an evaluation of the discriminative power for overall survival (OS) of the established CLIP/GRETCH/BCLC/BoBar prognostic systems alone and then in association with each of the following groups of parameters: selected clinical factors, QoL as continuous variables, dichotomized QoL, selected clinical factors and continuous QoL, selected clinical factors and dichotomized QoL.

Baseline QoL was assessed using the EORTC QLQ-C30. Discriminative power was evaluated with the Harrell’s C-index and net reclassification improvement.

Results

Quality of life was available in 79% of the patients (n = 271). Univariate analysis revealed that better role functioning (HR = 0.991 [0.987–0.995]) and better physical functioning (0.991 [0.984–0.997]) scores were associated with longer survival. In contrast, poorer score for fatigue (1.011 [1.006–1.015]) and diarrhoea (1.008 [1.002–1.013]) were associated with shorter survival. After adjustment for clinical and sociodemographic variables, only better role functioning score (0.993 [0.988–0.998]) was associated with longer survival. Adding oedema, hepatomegaly, fatigue and diarrhoea QoL scales to CLIP resulted in the best performance.

Conclusions

Our results confirm that QoL scales are independent prognostic factors of OS in palliative HCC patients. Incorporation of QoL data improved all the studied PCs.

Introduction

Primary liver cancer is the fifth most common cancer and the third most common cause of cancer-related death in the world [1]. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer [2] and about 70% of HCC patients are cared for in a palliative setting. In France, the main aetiology of HCC is alcohol abuse. Overall survival (OS) is poor, but can be improved by administration of one of the most recently developed treatments [3]. For patients in palliative care, the standard treatments are chemoembolization [4] and sorafenib [3]. Despite recent research results [5], the benefits of chemoembolization in HCC patients remain subject to debate. Hence, optimizing the treatment of HCC on the basis of the patient’s characteristics is an important goal in a palliative setting and more generally.

One of the main objectives of a prognostic classification is to guide the selection of a therapeutic strategy according to the patient clinical, biochemical, and oncological characteristics. A classification can also be used to define eligibility criteria in randomized clinical trials and stratification criteria for randomization. Several prognostic classifications for HCC patients have been developed, including the Okuda staging system [6], the Cancer of the Liver Italian Program (CLIP) [7], [8], the Barcelona Clinic Liver Cancer (BCLC) system [9] and the Groupe d’Étude et de Traitement du Carcinome Hépatocellulaire (GRETCH) system [10]. Several recent studies have emphasized the limitations of these scores in terms of discriminative power and OS prediction in a palliative setting (Colette et al. [11] and Tournoux-Facon et al. [12]). Hence, improving the quality and capabilities of these prognostic classifications remains an important challenge, since most patients have palliative HCC. To this end, Tournoux-Facon et al. suggested adding the World Health Organization’s performance status (WHO PS) score to CLIP and further proposed a new prognostic classification (BoBar) that included metastasis, portal vein thrombosis, ascites status, tumour morphology, WHO PS, serum alpha-fetoprotein (AFP), jaundice and alkaline phosphatase [12]. These classifications were selected according to their discriminative ability (according to the C-index [13]) and the accuracy of the prognosis for the patient’s individual outcome (according to the Schemper statistic [14]). As is the case for cancers in other sites (Quinten et al. [15]), we hypothesized that health-related quality of life (QoL) could improve the prediction of OS in palliative HCC.

Improving existing prognostic classifications by adding QoL could help physician optimize treatment for a given patient, in accordance with the goal of providing targeted, personalized therapy. A preliminary study by Bonnetain et al. [16] demonstrated the independent, prognostic value of self-reported QoL (assessed according to the Spitzer QoL Index) for HCC patients in a palliative setting and QoL’s capability to improve HCC prognostic classifications, when compared with biochemical and/or clinical parameters.

In a population with a hepatitis B virus (HBV) aetiology, Yeo et al. [17] found that QoL scales rated with the EORTC QLQ-C30 were independent prognostic factors for OS in patients with unresectable HCC.

The objective of our present study was to confirm the prognostic value of QoL and to establish whether it could improve the performance of the CLIP, BCLC, GRETCH and BoBar classifications. In other words, the present study was designed to provide external validation of the results reported by Bonnetain et al. [16].

Section snippets

Patients

Individual patient data were extracted from a phase III randomized, controlled trial (the CHOC trial) on the efficacy of long-acting octreotide in palliative HCC [18]. Between July 2002 and October 2003, 271 patients were randomized to receive either long-acting octreotide (n = 134) or placebo (n = 137). The CHOC trial failed to demonstrate the efficacy of octreotide in palliative HCC. The trial’s inclusions criteria and results have been extensively described in detail elsewhere [18].

Quality of life assessment

Quality of

Patients’ characteristics

The patients’ baseline characteristics are summarized in Table 2A. Most of the patients were male (75%) and were aged ⩾65 years (66%). Cirrhosis was present in 78% of the patients and 23% had extrahepatic metastasis. Eighty percent of the subjects have a good WHO PS (score 0–1). Most of the patients were Child-Pugh class A (67%), CLIP class 0–1–2 (52%), BCLC class C (68%) and GRETCH class B (71%).

Of the 271 patients randomized into the CHOC trial, 215 (79%) had a full set of baseline QoL data

Discussion

We established that role functioning, fatigue and diarrhoea QoL scales (as assessed by the EORTC QLQ-C30) were independent prognostic factors of OS in patients with palliative HCC. In multivariable Cox analysis, in which QoL scores were treated as continuous variables, role functioning was the main independent prognostic factor (in addition to clinical variables). Moreover, addition of QoL scales improved all prognostic classifications: fatigue and diarrhoea were frequently selected when QoL

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

References (37)

  • D. Osoba

    What has been learned from measuring health-related quality of life in clinical oncology?

    Eur J Cancer

    (1999)
  • C.H. Köhne et al.

    Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients

    Ann Oncol

    (2002)
  • P. Solal-Céligny et al.

    Follicular lymphoma international prognostic index

    Am Soc Hematol

    (2004)
  • J.M. Blazeby et al.

    Development of a questionnaire module to supplement the EORTC QLQ-C30 to assess quality of life in patients with hepatocellular carcinoma, the EORTC QLQ-HCC18

    Eur J Cancer

    (2004)
  • D.M. Parkin et al.

    Estimating the world cancer burden: Globocan 2000

    Int J Cancer

    (2001)
  • J.M. Llovet et al.

    Sorafenib in advanced hepatocellular carcinoma

    N Engl J Med

    (2008)
  • K. Okuda et al.

    Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients

    Cancer

    (1985)
  • The Cancer of Liver Italian Program Investigators

    A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: The Cancer of the Liver Italian Program (CLIP) investigators

    J Hepatol

    (1998)
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