Gene test could identify early stage lung cancer patients who may benefit from extra chemo

In collaboration with the Press Association

Researchers in the US have developed a gene test that could predict which patients with non-small cell lung cancer (NSCLC) still have a low chance of surviving despite having their disease diagnosed early (stage 1).

The findings, published in the Lancet, will allow new trials to find out whether these patients could benefit from additional (‘adjuvant’) chemotherapy after surgery, as although chemotherapy after surgery is an extra option for patients with later stages of the disease, it has not been shown to improve survival in early stage patients, and can cause considerable side effects, especially for older patients.

Treatment for lung cancer - the second most common cancer in the UK after breast cancer - varies depending on how advanced the disease is when it is diagnosed.

About 12 per cent of people diagnosed with NSCLC are diagnosed with stage I cancer, which is defined as a cancer smaller than five cm that has not spread to any other part of the body.

For patients with stage I NSCLC, the routine treatment is surgery only, and this cures around two-thirds of patients.

While additional chemotherapy is an extra option for patients with later stages of the disease, it has not been shown to improve survival in early stage patients, and can cause considerable side effects, especially for older patients.

This study by Dr Michael J Mann and Professor David M Jablons, of the University of California, San Francisco (UCSF) Thoracic Surgery Division, measured the activity of 14 genes in tumour tissue taken from 361 patients diagnosed with stage I NCSLC.

The pattern of gene activity levels was then analysed, and compared to the patients' outcomes. From this, the researchers were able to find genetic 'fingerprints' for people at high, medium and low risk of the cancer coming back.

To confirm these findings, the researchers then repeated the test on a further 433 stage I NCSLC patients from hospitals around California, and on 1,006 patients from hospitals around China, who were diagnosed with stage I, II or III disease.

The authors found that the test was the "strongest predictor" of patients' fates compared with standard criteria such as age and smoking status. It also outperformed guidelines used to identify high-risk patients with early stage disease.

Professor Siow Ming Lee, Cancer Research UK's lung cancer expert, said the findings were "encouraging".

"If this finding is confirmed in larger studies, a test to detect this profile could be used to carry out new clinical trials to find out whether adjuvant chemotherapy would help treat such poor prognosis early stage patients.

But he cautioned that the test needed to be shown to work in much larger groups of patients, and that questiones remained over some aspects of the study.

"It isn't clear whether the patients in the validation arms of the study had the stage of their tumour accurately measured by the current standard of care - PET-CT scanning and/or endobronchial ultrasound," he added.

"It's also possible that this gene profile is an indication of more aggressive disease, and that these patients would be unlikely to benefit from chemotherapy. To find out, it would be useful to look at people with later stage disease who have this profile, and who received chemotherapy after surgery, and see whether it actually affects survival.

"Chemotherapy can be too harsh for many elderly lung cancer patients, who often have other problems besides cancer. It's too early to recommend adjuvant chemotherapy for stage I patients until this gene signature is shown to lead to improved treatment in randomised trials," he said.

In an accompanying comment article in the same issue of the Lancet, Dr Yang Xie and Professor John Minna, from the Southwestern Medical Center in Texas, also called for more research. "Further studies will tell whether the genes in this new assay are of functional relevance and whether they also will provide information on how a lung cancer patient will respond to adjuvant therapy," they wrote.

Copyright Press Association 2012

References

  • Kratz, J. R. et al. A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies. Lancet doi:10.1016/S0140-6736(11)61941-7