Quality of life as a prognostic factor of overall survival in patients with advanced hepatocellular carcinoma: results from two French clinical trials.
ABSTRACT The aims of our study were to assess quality of life (QoL) as a prognostic factor of overall survival (OS) and to determine whether QoL data improved three prognostic classifications among French patients with advanced hepatocellular carcinoma (HCC).
We pooled two randomized clinical trials conducted by the Fédération Francophone de Cancérologie Digestive in a palliative setting. In each trial QoL was assessed at baseline using the Spitzer QoL Index (0-10). Three prognostic classifications were calculated: Okuda, Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer group (BCLC) scores. To explore whether the scores could be improved by including QoL, univariate Cox analyses of all potential baseline predictors were performed. A final multivariate Cox model was constructed including only significant multivariate baseline variables likely to result in improvement of each scoring system. In order to retain the best prognostic variable to add for each score, we compared Akaike information criterion, likelihood ratio, and Harrell's C-index. Cox analyses were stratified for each trial.
Among 538 included patients, QoL at baseline was available for 489 patients (90%). Longer median OS was significantly associated with higher Spitzer scores at baseline, ranging from 2.17 months (Spitzer=3) to 8.93 months (Spitzer=10). Variables retained in the multivariate Cox model were: jaundice, hepatomegaly, hepatalgia, portal thrombosis, alphafetoprotein, bilirubin, albumin, small HCC, and Spitzer QoL Index (hazard ratio=0.84 95% CI [0.79-0.90]). According to Harrell's C-index, QoL was the best prognostic variable to add. CLIP plus the Spitzer QoL Index had the most discriminating value (C=0.71).
Our results suggest that QoL is an independent prognostic factor for survival in HCC patients with mainly alcoholic cirrhosis. The prognostic value of CLIP score could be improved by adding Spitzer QOL Index scores.
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ABSTRACT: Hepatocellular carcinoma (HCC) is a common and rapidly fatal cancer ranking third among the leading causes of cancer-related deaths. Potentially curative therapies like surgery, transplant and ablation are not an option for most patients as they are often diagnosed when the disease is advanced. Liver directed therapy and oral targeted therapies are used in these patients to prolong life and palliate symptoms of the cancer and associated liver failure. Overall survival remains poor and hence health-related quality of life (HRQoL) is of paramount importance in these patients. As novel therapies are developed to improve outcomes, a comprehensive knowledge of available tools to assess impact on QoL is needed. Hence we reviewed all the studies in HCC patients published within the last 13 years from 2001-2013 which assessed HRQoL as a primary or secondary endpoint. A total of 45 studies and 4 meta-analysis were identified. Commonly used tools were European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (15 studies) and the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep) (14 studies). Of the 45 publications which incorporated HRQoL as end-point only 24 were clinical trials, 17/24 (71%) assessed systemic therapies while 7/24 (29%) assessed liver-directed therapies. Majority of the publications (trials + retrospective reviews) that had HRQoL as an endpoint in HCC patients were studies evaluating liver-directed therapies (23/45 or >50%). We discuss the measures included in the tools, their interpretation, and summarize existing QoL data that will help design future HCC trials.Journal of gastrointestinal oncology 08/2014; 5(4):296-317. DOI:10.3978/j.issn.2078-6891.2014.046
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ABSTRACT: Background Prior studies assessing quality of life (QOL) in patients with hepatocellular carcinoma (HCC) primarily included patients with preserved liver function and/or early HCC, leading to overestimation of QOL. Our study’s aim was to evaluate the association of QOL with survival among a cohort of cirrhotic patients with HCC that was diverse with respect to liver function and tumor stage. Methods We conducted a prospective cohort study among cirrhotic patients with HCC from a large urban safety-net hospital between April 2011 and September 2013. Patients completed two self-administered surveys, the EORTC QLQ-C30 and QLQ-HCC18, prior to the treatment. We used generalized linear models to identify correlates of QOL. Survival curves were generated using Kaplan–Meier analysis and compared using log rank test to determine whether QOL is associated with survival. Results A total of 130 treatment-naïve patients completed both surveys. Patients reported high cognitive and social function (median scores 67) but poor global QOL (median score 50) and poor role function (median score 50). QOL was associated with cirrhosis-related (p = 0.02) and tumor-related (p = 0.02) components of Barcelona Clinic Liver Cancer (BCLC) tumor stage. QOL was associated with survival on univariate analysis (HR 0.37, 95 % CI 0.16–0.85) but became nonsignificant (HR 0.82, 95 % CI 0.37–1.80) after adjusting for BCLC stage and treatment. Role functioning was significantly associated with survival (HR 0.40, 95 % CI 0.20–0.81), after adjusting for Caucasian race (HR 0.31, 95 % CI 0.16–0.59), BCLC stage (HR 1.51, 95 % CI 0.21–1.89), and treatment (HR 0.57, 95 % CI 0.33–0.97). Conclusions Role function has prognostic significance and is important to assess in patients with HCC.Quality of Life Research 12/2014; DOI:10.1007/s11136-014-0895-1 · 2.86 Impact Factor
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ABSTRACT: Health-related quality of life (QoL) has been validated as a prognostic factor for cancer patients; however, to be used in routine practice, QoL scores must be dichotomized. Cutoff points are usually based on arbitrary percentile values. We aimed to identify optimal cutoff points for six QoL scales and to quantify their added utility in the performance of four prognostic classifications in patients with hepatocellular carcinoma (HCC). We reanalyzed data of 271 patients with advanced HCC recruited between July 2002 and October 2003 from 79 institutions in France in the CHOC trial, designed to assess the efficacy of long-acting octreotide. QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30). The scores ranged from 0 to 100. Identification of optimal cutoff points was based on the method of Faraggi and Simon [Stat Med 1996;15:2203-2213]. Improvement in the performance of prognostic classifications was studied with Harrell's C-index, the net reclassification improvement (NRI), and integrated discrimination improvement (IDI). We found that optimal cutoff points were 50 for global health, 58.33 for physical functioning, 66.67 for role functioning, 66.67 for fatigue, 0 for dyspnea, and 33.33 for diarrhea. The addition of QoL and clinical factors improved the performance of all four prognostic classifications, with improvement in the range of 0.02-0.09 for the C-index, 0.24-0.78 for 3-month NRI, and 0.02-0.10 for IDI. These cutoff values for QoL scales can be useful to identify HCC patients with very poor prognosis and thus improve design of clinical trials and treatment adjustment for these patients. ©AlphaMed Press.The Oncologist 12/2014; 20(1). DOI:10.1634/theoncologist.2014-0175 · 4.54 Impact Factor