A two-year study to validate a test to detect early-stage liver cancer has been initiated by the National Cancer Institute (NCI), part of the National Institutes of Health, at six centers* across the United States. This test, conceived with the assistance of NCI's Early Detection Research Network (EDRN), looks at whether a substance called des-gamma carboxyprothrombin (DCP) can identify those at risk for liver cancer.

Validation -- proving that the measurement of a substance accurately signifies the risk for or presence of cancer -- is the critical step to create a truly useful test. "It's the first study testing a marker for liver cancer, and the first Phase II EDRN-supported study," said Sudhir Srivastava, Ph.D., who heads EDRN as chief of the Cancer Biomarkers Research Group in NCI's Division of Cancer Prevention.

Liver cancer, or hepatocellular carcinoma, with over 20,000 estimated new cases this year in the United States, is both one of the more common cancers worldwide and one of the few cancers in the United States in which the number of new cases is rising, and expected to continue to rise over the next two decades. Frequent surveillance of patients with liver cirrhosis is recommended, but current procedures have shortcomings. Alpha-fetoprotein, a blood test currently used for surveillance of liver cancer, suffers from poor sensitivity and specificity (ability to determine if someone actually has, or does not have, liver cancer). Liver ultrasound is dependent on the skills and knowledge of the technician and can lead to false-negative results. This EDRN-supported study looks to improve upon these negatives.

DCP is a protein precursor of prothrombin, one of the factors produced by the liver to help the blood clot. In patients with liver cancer, this protein seems to be elevated compared to those without liver cancer. Early studies have shown that DCP is better than alpha-fetoprotein for the diagnosis of liver cancer and has close to 90 percent accuracy.

The investigators conducting the validation study, headed by Jorge A. Marrero, M.D., of the University of Michigan, and Paul Wagner, Ph.D., program director in NCI's Cancer Biomarkers Research Group, plan to enroll 450 patients diagnosed with liver cancer, of which at least 170 will be early stage. Four hundred fifty patients with cirrhosis and no cancer will serve as controls. The participating institutions will collect samples from patients in this study, and the samples will be analyzed for DCP using an assay manufactured by Eisai Company, Teaneck, N.J. The primary goal of the study is to determine whether DCP can lead to improved accuracy in the detection of early-stage hepatocellular carcinoma.

This trial will run for two years and final results are expected in early 2007. If successful, this study will provide a much-needed tool for the early detection of liver cancer. Additionally, EDRN's gastrointestinal collaborative group is working on two other early novel detection tests for liver cancer for future validation.

EDRN, established by NCI in early 2000, is a broad, interdisciplinary consortium whose work is aimed at both identifying and validating cancer biomarkers for use in early cancer detection, and is divided among collaborative groups studying specific tumors. Numerous proteins and genes have been linked with a variety of cancers, which can make them targets for therapy, as well as targets for identifying the risk of cancer onset, progression, or recurrence.

For more information about the Early Detection Research Network (EDRN), visit the EDRN home page at http://www3.cancer.gov/prevention/cbrg/edrn

For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

• University of Michigan; Ann Arbor, Mich. (Jorge A. Marrero, M.D.)
• Mount Sinai Hospital, New York, N.Y. (Myron Schwartz, M.D.)
• University of Pennsylvania, Philadelphia, Pa. (Rajender Reddy, M.D.)
• Mayo Clinic, Rochester, Minn. (Lewis Roberts, M.D., Ph.D.)
• St. Louis University; St Louis, Mo. (Alex Befeler, M.D.)
• Stanford University; Stanford, Calif. (Mindie Nguyen, M.D.)

In addition, the Data Management and Coordinating Center for the study is headed by Ziding Feng, Ph.D., at the Fred Hutchinson Cancer Research Center in Seattle, Wash.

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