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Guest Column

Molecular signatures determine lung cancer care

By Dr. V. Upender Rao
Published October 16, 2006


Expression of genes and their proteins in a given tissue determine the disease state, its prognosis and the likelihood of response or resistance to drugs.

The present standard is to assess prognosis and determine treatment based on surgical staging, which includes tumor size, grade and lymph node involvement, among other things.

Based upon these criteria, some 10 percent to 20 percent of stage I, non-small cell lung cancer patients will present with recurrent disease and succumb to their illness.

According to Anil Potti, MD, assistant professor of medicine and assistant professor at the Institute of Genome Sciences and Policy at Duke University, gene expression micro array assay (lung metagene mode) can distinguish stage I lung cancer patients who are destined to experience a recurrence from those who will enjoy long-term remission following surgical resection alone.

Dr. Potti and colleagues from Duke applied the lung metagene model to 84 samples of non-small cell lung cancer from patients diagnosed a few years ago and whose remission and recurrence patterns are known.

In this study, published in the New England Journal of Medicine, the lung metagene model was 80 percent accurate in identifying recurrence patterns.

Based on these results, Cancer and Acute Leukemia Group B will conduct a lung metagene model trial of 500 to 1,000 non-small cell lung cancer samples in a prospective fashion.

The CALGB study is tentatively approved by the National Cancer Institutes Cancer Therapy Evaluation Program.

Robert A. Kratzke, MD, associate professor of medicine at the University of Minnesota and CALGB's Respiratory Committee chairman said, "The cure rate from surgery alone is far from 100 percent."

In this study, patients whose risk of recurrence is 50 percent or greater will be given chemotherapy after surgery, and those with less than 50 percent risk will be spared chemotherapy.

Both groups will be followed prospectively. If this study bears positive results, metagene analysis can help improve the outcome of early lung cancer patients by identifying those who will need chemotherapy and those who can be followed without further therapy.

Similar gene analysis is currently available for node negative breast cancer patients. The Oncotype DX recurrence score and the 70-gene profile that gives a recurrence score, based on which node negative breast cancer patients who are likely to recur, can be identified.

These two and an additional three similar models were tested on 295 breast cancer samples. There was an overall good concordance in most of these models. This study appeared in the Aug. 10, 2006, issue of the New England Journal of Medicine.

Dr. Potti visited the Cancer and Blood Disease Center in Lecanto recently. He said, "From a technical standpoint, the lung metagene model is ready for clinical use, but the question is whether it will stand the test of time in a large prospective validation."

He also demonstrated expression micro array-based chemotherapy drug sensitivity and resistance analysis that he developed. His work will be published in Nature in the near future.

By this analysis, oncologists can choose drugs that are likely to be effective and eliminate those that will only add to the toxicities of cancer therapy.

V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified October 15, 2006, 20:18:52]


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