A meta‐analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma†

Abstract

Knowing the spontaneous outcome of hepatocellular carcinoma (HCC) is important for designing randomized controlled trials (RCTs) of new therapeutic approaches; however, survival of patients in the absence of treatment is highly variable, and prognostic factors influencing outcomes are incompletely defined. The aims of this meta-analysis were to estimate the 1-year and 2-year survival rates of untreated HCC patients enrolled in RCTs of palliative treatments, and to identify prognostic factors. RCTs evaluating therapies for HCC with placebo or no-treatment arms were identified on MEDLINE through April 2009. Data were combined in a random effect model. Primary outcomes were 1-year and 2-year survival. Thirty studies met the inclusion criteria. The pooled estimates of the survival rates were 17.5% at 1 year (95% confidence interval [95%CI], 11%-27%; range, 0%-75%) and 7.3% at 2 years (95%CI, 3.9%-13%; range, 0%-50%). Heterogeneity among studies was highly significant (P < 0.0001) both for 1-year and 2-year survival, and persisted when RCTs were stratified according to all patient and study features. T he extensive application of surveillance programs for early detection of small (Ͻ5 cm) hepatocellular carcinoma (HCC) has increased the number of tumors detected within the Milan criteria 1 at Barcelona Clinic Liver Cancer (BCLC) stages 0 or A (very early or early), 2 and potentially responsive to curative treatments, such as liver transplantation and percutaneous or surgical ablation. 3,4 Nonetheless, most patients with HCC (approximately 70%) are diagnosed at BCLC B (intermediate) and C (advanced) stages (approximately 50%) or BCLC D (end stage, approximately 20%). 4 A previous systematic review 5 showed that the survival rates of untreated patients or of those who received placebo in randomized controlled trials (RCTs) of unresectable HCC vary among the studies, ranging from 10% to 72% at 1 year and from 8% to 50% at 2 years.In the setting of unresectable HCC, an accurate estimate of survival among untreated patients is essential for (1) evaluating the natural history and assessing the validity of biological or radiological surrogate markers, (2) controlling for confounding factors in observational studies, (3) calculating the sample size and stratifying subjects in RCTs, and (4) assessing treatment effect size to formulate therapeutic strategies. Knowledge of the factors influencing the outcome of untreated patients also may be important for interpreting the results of RCTs of different treatments.

Economic Evaluation and Budget Impact Analysis of the Surveillance Program for Hepatocellular Carcinoma in Thai Chronic Hepatitis B Patients

“…To calculate the transition probabilities, all values of average annual transition probabilities for one year-cycle length were changed to semi-annual probabilities by the survival curve function and put into six month-cycle length estimation. Transition probabilities were obtained from published studies (Lee et al, 2002;Chung, 2005;Yeung et al, 2005;Chen et al, 2006;2009;Fattovich et al, 2008;Bouza et al, 2009;Cheng et al, 2009;Kim et al, 2009;Cabibbo et al, 2010;Tong et al, 2010;Zhou et al, 2010a;2010b;Chun et al, 2011;Kao, et al, 2011;Sawhney et al, 2011;Thein et al, 2012).…”

Refining Sorafenib Therapy: Lessons from Clinical Practice

“…A meta-analysis of 30 clinical trials into which HCC patients were enrolled for palliative treatment reflects this heterogeneity. It demonstrated a high variability in survival among untreated patients and concluded that no single patient characteristic alone could predict outcome [2].The prognosis and treatment options for HCC are generally related to tumor stage and liver function at presentation [3,4]. In the west, approximately 30% of all patients with HCC are diagnosed in…”

Hepatocellular carcinoma with blood supply from parasitized omental artery: Angiographic appearance and chemoembolization

“…In our study, no cases with HCC rupture were found in A group, but 2 cases in B group, because usually OA was involved in the marginal part of the tumor, where part of rupture is often located, so chemoembolization via the POA may have potential effect for preventing HCC rupture. [22][23][24][25] . This is why we didn't perform statistical compassion of these patients' survival outcomes between A and B groups.…”