Evidence map›Paper›PMID 22374331›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2012

Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma.

Josep M Llovet, Carol E A Peña, Chetan D Lathia, Michael Shan, Gerold Meinhardt, Jordi Bruix, SHARP Investigators Study Group

Abstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 287 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
287citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

287 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  6. Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase III REFLECT Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
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  8. A Phase II and Biomarker Study of Sorafenib Combined with Modified FOLFOX in Patients with Advanced Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
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  20. CXCR2 expression is associated with prostate-specific membrane antigen expression in hepatocellular carcinoma: reappraisal of tumor microenvironment and angiogenesis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article

227 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Josep M LlovetBarcelona Clínic Liver Cancer Group, Liver Unit, CIBERehd, Institut d'Investigacions Biomèdiques, August Pi i Sunyer, Hospital Clínic Barcelona, Barcelona, Spain. jmllovet@clinic.ub.es
Carol E A Peña
Chetan D Lathia
Michael Shan
Gerold Meinhardt
Jordi Bruix
SHARP Investigators Study Group

Funding

Integrative genomic analysis in hepatocellular carcinomaR01DK076986 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI LLOVET, JOSEP M · 2007 to 2011
$1.3M
NIDDK NIH HHS 1R01DK076986-01NIDDK NIH HHS R01 DK076986
6 · The paper itself

Abstract

purposeValidated biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma (HCC). One of the objectives of the phase III, randomized, controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy. EXPERIMENTAL

designIn SHARP, 602 patients with advanced HCC were randomized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis. Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment. The candidate biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib.

resultsIn both the entire patient population and the placebo cohort, baseline angiopoietin 2 (Ang2) and VEGF concentrations independently predicted survival. Clinical variables such as macroscopic vascular invasion, Eastern Cooperative Oncology Group (ECOG) performance status, and baseline α-fetoprotein and alkaline phosphatase concentrations also independently predicted survival in these groups. In the sorafenib cohort, trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline (P of interaction = 0.081 and 0.073, respectively).

conclusionsThe angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC. In contrast, none of the biomarkers tested significantly predicted response to sorafenib.

Indexed as

Alkaline Phosphatasealpha-FetoproteinsAngiopoietin-2BenzenesulfonatesBiomarkers, TumorCarcinoma, HepatocellularCohort StudiesDisease-Free SurvivalFemaleHepatocyte Growth FactorHumansLiver NeoplasmsMaleNiacinamidePhenylurea CompoundsProto-Oncogene Proteins c-kitAlkaline Phosphatasealpha-FetoproteinsAngiopoietin-2BenzenesulfonatesBiomarkers, TumorHepatocyte Growth FactorNiacinamidePhenylurea CompoundsProto-Oncogene Proteins c-kitPyridinesSorafenibVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID22374331
PMCPMC12268944

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.