Gene signature may identify which lung cancer patients will benefit from chemotherapy, research finds

01 June 2008

Dr Ming Tsao

A study funded in part by the Canadian Cancer Society has identified a set of 15 genes that may predict the aggressiveness of an early-stage non-small cell lung cancer and identify those patients who might benefit from chemotherapy after surgery.

The findings suggest that patients without this set of genes – also described as a “gene expression signature” – have a less aggressive cancer and could be spared chemotherapy and its side effects. These preliminary results were presented at the 2008 American Society of Clinical Oncology (ASCO) meeting in Chicago.

“This research suggests that we can target treatment and potentially give each patient the most effective treatment for their situation,” says Dr Ming Tsao, a senior scientist at the Ontario Cancer Institute. “Knowing that a patient has this genetic signature gives both patients and their doctors a clearer picture of post-operative treatment.”

This study is a follow-up analysis of a clinical trial led by the NCIC Clinical Trials Group and conducted in collaboration with the U.S. National Cancer Institute. The original study showed a significant survival benefit from treatment with vinorelbine and cisplatin in patients with early-stage (stage I and II) non-small cell lung cancer who had their tumours surgically removed. The discovery was recognized by ASCO as one of the world’s most important breakthroughs in clinical cancer research.

For this investigation, the researchers performed a genetic analysis of tumor tissue from 133 of the 482 patients from the original study who had banked frozen tumour samples available. They identified a group of 15 genes that together predicted patient outcome. Some of these genes are known to play important roles in cell growth and death or regulate other genes involved in cancer.

The researchers first identified this 15-gene expression signature in 62 patients with early-stage non-small cell lung cancer who did not receive adjuvant chemotherapy and used it to predict which patients had aggressive cancers with a high risk of recurrence and death (33 patients) and which had less aggressive disease and a low risk of recurrence (29 patients). They then applied the signature to 71 patients who were randomized to receive chemotherapy in the original clinical trial. Patients predicted to have aggressive disease experienced the greatest benefit of chemotherapy — with a 73% reduction in the risk of death — while chemotherapy did not reduce the risk of death in patients designated as low risk.

The study was coordinated by the NCIC Clinical Trials Group, which is funded by the Canadian Cancer Society and is based at Queen’s University in Kingston, Ontario.