Gene Patterns May Predict Recurrence for Early Stage Lung Cancer

Test May Help Decide Which Patients Need Chemotherapy

August 22, 2006 04:23:28 PM PST

Summary: Duke University researchers have discovered a set of gene patterns that they say can help predict recurrence in people with early stage non-small cell lung cancer. If their findings are confirmed, doctors could one day use these patterns to help decide which people need additional treatment with chemotherapy after surgery and which do not. The research appears in the New England Journal of Medicine.

Why it's important: Lung cancer is the deadliest cancer among US men and women, claiming more lives than breast, colon, and prostate cancer combined. Nearly 175,000 new cases and 163,000 deaths are expected in the US in 2006. Non-small cell lung cancer is the most common form of the disease. Refining treatment could give some patients a better chance at surviving the disease, and spare some people unnecessary chemotherapy.

What's already known: For most patients, chemotherapy after surgery is standard treatment. Because nearly everyone gets it, there are likely some people who are treated even though their cancer probably wouldn't come back after surgery. By the same token, patients with the earliest stage of lung cancer, stage IA, do not routinely get chemotherapy because they are thought to have a low risk of relapse. Yet about 25% of people with stage IA lung cancer do have a recurrence -- meaning they might benefit from additional treatment with chemotherapy.

The problem lies in identifying which patients would benefit from chemotherapy and which would not. Right now the only way to predict who might have a relapse is by looking at specific characteristics like tumor size and stage, the type of tumor, and the person's age and sex. These are called clinical factors. But clinical factors are not always accurate. The Duke researchers hoped their gene patterns would be a more accurate way of determining which patients are likely to relapse.

How this study was done: To test their idea, the researchers first identified a group of gene patterns that occurred among many different lung tumor samples. They called these patterns "metagenes." Then they used those metagenes to predict recurrence in groups of patients from 3 different studies of lung cancer. They compared the accuracy of the metagene predictions with the predictions calculated by using clinical factors.

What was found: The metagene model was significantly more accurate than clinical factors alone in predicting which patients had a high or low risk of relapse. In the first group of 89 patients, the metagenes were 93% accurate, while clinical factors were only 64% accurate. In the second group of 25 patients, the metagene was 72% accurate and in the third group of 84 patients, it was 79% accurate. The gene patterns were accurate for all early stages of non-small cell lung cancer, and for both the adenocarcinoma and squamous cell types of carcinoma. Using both the metagenes and clinical factors was even better at predicting who was likely to relapse. The metagene model also predicted survival more accurately than clinical factors. The people who had a high risk of recurrence according to the gene patterns also had lower survival than people with a low recurrence risk.

The bottom line: The study is an important first step toward more tailored treatment for lung cancer, said Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society. But it still isn't known whether giving patients chemotherapy based on these recurrence predictions will actually make a difference in their survival.

The Duke researchers lay out a plan for a clinical trial to test exactly that. People with stage IA lung cancer would first have surgery, then the metagene model would be used to determine who was at high risk and who was at low risk for recurrence. The high risk patients would be randomly assigned to either observation (the current standard of care) or chemotherapy to see if additional treatment could help them live longer.

This type of trial would be very important, Lichtenfeld said, especially if it showed that the high risk patients could, in fact, benefit from chemotherapy.

"Although this is a first step, it is an exciting entr茅e into a 'new world' where we will be able to continuously improve our practical understanding of tumor biology and tumor behavior, and more effectively target our treatment efforts to those circumstances where they will do the most good while sparing others the discomfort and harm of unneeded toxic therapies," he said.

Citation: "A Genomic Strategy to Refine Prognosis in Early-Stage Non-Small Cell Lung Cancer." Published in the Aug. 10, 2006, New England Journal of Medicine (Vol. 355, No. 6: 570-580). First author: Anil Potti, MD, Duke University.