— A new gene test can predict how people with lung cancer will fare, say researchers, allowing aggressive chemotherapy to be targeted to only those who need it.
Patients whose tests reveal a high risk signature of gene activity are three times as likely to experience a cancer recurrence in the five years after surgery. The test may relieve the frustration doctors feel with the current lack of tools to predict which patients cancer will relapse and spread.
The new test provides a prognosis specific to non-small cell lung cancer, the most common form of lung cancer. The relapse rate among these patients is 40% within five years after treatments such as surgery to remove the tumour.
To develop the test, Pan-Chyr Yang of the National Taiwan University College of Medicine in Taipei and colleagues analysed samples of lung tumours removed from 125 patients, whose post-operative medical history was known. None of these patients received chemotherapy following their operations because such post-surgery treatment has only become a common practice in the past few years.
The team used DNA microarray (gene chip) technology to pick out abnormal gene activity in the tumour samples. The process involves extracting messenger RNA from cells and translating this into DNA fragments that fluoresce. When these DNA fragments bind to matching sequences on a specialised gene chip, it confirms that the related gene is active.
The DNA microarray analysis pointed to 672 genes potentially linked to non-small cell lung cancer. Of these, the researchers linked four genes to an increased chance of survival and 12 genes with increased risk of cancer recurrence.
Based on these findings, the team developed an algorithm that focused on only five genes to predict whether a patient is at high or low risk of a fatal cancer relapse. In the next step, they tested their algorithm on lung tumour samples from another 101 patients.
The median survival time for those patients classified as high risk was 20 months. By comparison, the median survival time for those indicated as low risk was 40 months.
The test is very easy. You can do all of these measurements over one or two days, says Yang.
Doctors could use this test in the future to determine which patients are at highest risk of relapse and therefore need aggressive chemotherapy, says lung cancer specialist Roy Herbst of the University of Texas M.D. Anderson Cancer Center in Houston, US.
He says current decisions to give chemotherapy after surgery or not often depend on the size of the tumour: But why should arbitrary size determine if they get this treatment? Its not quantity; its quality. Some smaller tumours could in fact be more likely to spread, he notes.
The chemotherapy given following lung cancer surgery can have serious side effects partly because it slows cell division. As a result, patients given this treatment can experience anything from hair loss to anaemia and increased susceptibility to infection.
Herbst says that the findings of the new study could also help guide the future development of lung cancer drugs. One of the five genes examined in the test is ERBB3, a gene that codes for receptors on the outside of cells. These receptors bind to proteins in the blood that promote tumour proliferation. Patients with certain versions of this gene might greatly benefit from compounds that block such receptors, Herbst suggests.
Scientists note that tests similar to the one developed by Yangs team have helped give a more accurate prognoses for breast cancers and lymphomas.
Journal reference: New England Journal of Medicine (vol 356, p 11)