Genomic test to predict who needs chemotherapy

Duke University Medical Center scientists have developed a genomic test to predict which patients with early-stage lung cancer will need chemotherapy to live and which patients can avoid the toxic regimen of drugs.

The test has the potential to save thousands of lives each year by recommending chemotherapy for patients who are currently advised against it, said the test's developers at Duke's Institute for Genome Sciences & Policy.

The test's promising results have initiated a multi-centre clinical trial, to be led by Duke investigators next year. Patients with early-stage non-small cell lung cancer, the most common and fatal form of cancer, will receive the genomic test and its results will determine their treatment.

The test, called the Lung Metagene Predictor, scans thousands of genes to identify patterns of gene activity in individual tumours that indicate a patient is likely to suffer a recurrence of disease. Recurrent tumours are typically fatal, so identifying at-risk patients is critical to properly treating them, said the Duke researchers.

"Using the unique genomic signatures from each tumour, our new test predicted with up to 90% accuracy which early-stage lung cancer patients would suffer a recurrence of the their cancer and which patients would not," said Anil Potti, MD, an assistant professor of medicine and lead author of the study. "We now have a tool that can be used to move these high-risk patients from the "no chemotherapy' group into the aggressive treatment group."

The researchers published their findings in the 10 August 2006 issue of the New England Journal of Medicine. The research was funded by the National Institutes of Health.

The genomic test can theoretically apply to any cancer, but the Duke team focused its effort on lung cancer because the survival rate is just 15%.

The Duke researchers developed the test by analysing the activity of genes from early-stage lung cancer patients whose disease outcomes were known. The Duke scientists then validated the genomic test in 129 patients by comparing the test's predictions with the patient's actual outcomes. The test predicted their risk of recurrence with 90% accuracy, the study showed.

If proven to be effective in the clinical trial, the test may replace the current method of assessing risk, which is imprecise and provides only a broad estimate of a patient's risk, said Joseph Nevins, PhD, a professor of molecular genetics at Duke and senior author of the study being reported.

To employ the test, physicians take a sample of the tumour as it is removed during surgery. They extract its messenger RNA, which represents the activity of thousands of genes in the tumour.

Scientists label the messenger RNA with fluorescent tags. The fluorescent RNA is then placed on a gene chip. There, it binds to its complementary DNA sequence on the gene chip.

When scanned with special light, the fluorescent RNA emits a telltale luminescence that demonstrates how much RNA is present on the chip " and thus which genes are most active in a given tumour. The physicians then use a rigorous statistical analysis to assess the relative risk of large groupings of genes, called metagenes, which have similar characteristics.

The test generates a risk "number' for each patient. If their risk exceeds 50%, the patient is advised to get chemotherapy.

"This genomic test is a clear example of personalised medicine, where we use the unique molecular characteristics of each patient's tumour to guide treatment decisions," said Geoffrey Ginsburg, MD, PhD, a professor of medicine and co-author of the study.