CT scans measuring blood flow in the lungs can detect early emphysema-related changes that occur in smokers Image source: Eric Hoffman, PhD, University of Iowa Carver College of Medicine

A gene-based test that estimates lung cancer risk may help identify which smokers are most likely to benefit from CT screening for lung cancer, according to a study presented at the American Association of Cancer Research (AACR) annual conference on Nov. 9.

“The medical challenge to understand who is most likely to develop lung cancer has become even more urgent with the recent evidence that a regular screening program with CT scans of smokers can save lives,” said Robert Young, MD, associate professor of medicine and molecular genetics at the University of Auckland in New Zealand.

“Now that the broad benefit of screening for lung cancer has been confirmed, there’s a pressing need to better target screening resources on those individuals who are most at risk from this disease,” he added.

Current screening models based on age and pack year exposure may be problematic. Yearly detection rates for CT screening using this approach range from 0.5 to 1 percent, and the false positive rates can stretch as high as nearly 25 percent, which results in additional downstream testing and costs.

The radiology community and clinicians involved in early diagnosis of lung cancer “are going to have to think about how best to use the results of National Lung Cancer Screening Trial (NLST) to provide a useful service to patients. It may not be feasible to screen 50 million Americans,” offered Young in an interview with Health Imaging News.

A number of critical unknowns regarding screening CT remain, said Young, including:

• Reimbursement for screening;
• Target candidates for screening; and
• When and how often to screen.

Strategies such as gene-based testing to target screening may help mitigate some of the economic and clinical challenges posed by screening. Young’s study suggests the merit of the approach.

The prospective study followed 1,212 confirmed lung cancer cases and 1,200 controls gathered from smokers in New Zealand, Spain and the United Kingdom for four to ten years.

Researchers administered a gene-based predisposition test that incorporates 20 genetic markers associated with smoking-related lung damage and propensity to lung cancer along with clinical factors including age, family history and diagnosis of chronic obstructive pulmonary disease to derive a risk score on a 1 to 12 scale with higher scores correlating with higher risk.

According to the researchers, current or former smokers with scores of 6 or higher, comprising 20 percent of the at-risk population, accounted for more than 50 percent of those with lung cancer. In the study, the test demonstrated specificity of 80 percent.

“At scores of 6 or more … only 25 percent of otherwise eligible smokers would be screened but over half of lung cancers would potentially be detected, many in a treatable stage,” concluded Young and colleagues, who suggested that increasing the detection rate of lung cancer per number of patients screened could improve the cost-effectiveness of CT screening.

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