Gene set shows which patients benefit from chemotherapy after surgery

Scientists have identified a genetic signature that can help doctors determine which patients with early-stage non-small cell lung cancer are at high risk for developing disease recurrence and therefore may benefit from chemotherapy after surgery.

The study, advances the 2005 findings of the NCIC Clinical Trials Group study JBR.10, conducted in collaboration with the US National Cancer Institute.

The JBR.10 findings showed significant survival benefit from the anti-cancer drugs vinorelbine and cisplatin in patients with early-stage (stage I and II) non-small cell lung cancer whose tumors had been surgically removed.

Principal investigator Dr. Ming Tsao, pathologist at the Princess Margaret Hospital (PMH) Cancer Program, University Health Network (UHN), and Professor of Laboratory Medicine and Pathobiology at the University of Toronto research team and collaborators at NCIC Clinical Trials Group at Queen's University performed a genetic analysis of tumor tissue from 133 of the 482 patients from the JBR.10 study who had banked frozen tumor samples.

The Tsao team identified a set of 15 genes that, in 62 patients who did not receive chemotherapy after surgery, predicted which patients had aggressive cancers with high risk of recurrence and death (31 patients), and which had less aggressive disease and low risk of recurrence (31 patients).

They then applied the signature to 71 patients who were randomized to receive chemotherapy in the JBR.10 trial. Patients predicted to have aggressive disease experienced the greatest benefit from chemotherapy - with a 67 percent reduction in the risk of death - while chemotherapy did not reduce the risk of death in patients designated as low risk.

While a previous JBR.10 analysis showed that overall only patients with stage II disease benefited from chemotherapy after surgery, Dr. Tsao's study demonstrates that the 15 gene signature may identify patients with both stage I and II cancers who may benefit from post-operative chemotherapy.

The study has been published online in the Journal of Clinical Oncology (JCO 64325).