BLOOD TEST FOR NSCLC SCREENING

The use of low-dose CT (LDCT) as a screening tool for lung cancer has been criticized for its high cost and its feasibility, given the large number of long-time heavy smokers and ex-smokers and the complexity of the process.

What if a less expensive and more easily administered test could refine who is at highest risk for lung cancer, and therefore identify the top candidates for LDCT?

A team of Italian researchers believe they have developed such a tool — an experimental blood test that detects genetic material associated with lung tumors.

They suggest that the tool could make LDCT a lot more attractive to health systems and patients.

"The availability of blood-detectable markers for selecting a high-risk population for subsequent LDCT screening could help reduce screening costs and increase compliance," write Pier Paolo Di Fiore, MD, from the European Institute of Oncology in Milan, and colleagues.

Their report on the tool, known as the miR-Test, was published online March 20 in the Journal of the National Institute of Cancer.

The 13 micro (mi)RNA signature in the miR-Test involves short noncoding RNAs that are normally involved in cellular regulation but are often deregulated in tumors. Cancer often leads to alterations in miRNA profiles in bodily fluids, which might be useful in the early detection of disease.

Dr Di Fiore and colleagues like the early results they have seen with the potential pre-LDCT screening tool. "Our miR-Test possesses the characteristics of accuracy and robustness required for such a first-line tool," they write.

In their report, the team describes a multitiered study designed to validate the miR-Test in high-risk individuals (heavy smokers older than 50 years) enrolled in the Continuous Observation of Smoking Subjects (COSMOS) trial and in lung cancer patients diagnosed outside of the screening initiative.

But more sophisticated data on the test are on the way, Dr Di Fiore told Medscape Medical News.

Because the COSMOS trial only looked at the miR-Test, another study, COSMOS 2, is underway with 10,000 high-risk subjects who will be screened with both CT and the miR-Test at eight different health institutions.

COSMOS 2 will follow participants for 5 years, with intermediate results after 3 years. "The accrual of individuals was completed in July 2014, which means we will have initial results of the screening in 2017," he said.

In their study, Dr Di Fiore and his colleagues analyzed results from a validation set of 1115 patients.

Table. Performance of the miR-Test 

Measure	Result	95% Confidence Interval
Area under the curve	0.85	0.78–0.92
Accuracy, %	74.90	72.2–77.6
Sensitivity, %	77.80	64.2–91.4
Specificity, %	74.80	72.1–77.5

The team also assessed the ability of the miR-Test to distinguish between nonmalignant lung diseases and lung cancer. For this analysis, they used an independent, smaller cohort of individuals with at least 5 years of follow-up who had chronic obstructive pulmonary disease, CT-determined stable pulmonary nodules, benign (histologically negative) tumors, or pneumonia.

They found that the negative predictive value of the test was greater than 99%, which means that "negative-risk individuals can safely avoid subsequent LDCT scan."

Furthermore, the sensitivity and negative predictive value of the miR-Test are "comparable" with LDCT alone, which means that "the miR-Test could be used as a first-line screening tool," the team writes.

They also trumpet the fact that miR-Test results were negative for most of the 164 individuals with nonmalignant lung diseases (76.8%). "This is relevant because in LDCT screening trials there is a high rate of false-positive findings," they write. "Therefore, a first-line screening miR-Test could considerably reduce unnecessary LDCTs for individuals without lung cancer."

Another blood test that uses plasma microRNAs is also at an advanced stage of validation, Dr Di Fiore reported. But the competition is friendly and collaborative, he explained.

The other test was developed by a research group working at the Istituto Nazionale dei Tumori, also located in Milan. Dr Fiore said that the two groups are now "collaborating to see whether a combination of the two tests can improve lung cancer early detection," he said.

Both tests were recently licensed to Gensignia Ltd., a company focused on microRNA research for cancer early diagnosis.

The study was supported by grants from Associazione Italiana per la Ricerca sul Cancro, the Monzino Foundation, and the Umberto Veronesi Foundation. Dr Di Fiore's research is supported in part by Gensignia.

J Natl Cancer Inst. Published online March 20, 2015. Abstract