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