New Gene-Expression Test Improves Diagnostic Yield of Bronchoscopy

ATLANTA – The combined use of a novel bronchial airway gene-expression test and bronchoscopy improves the ability to rule out lung cancer in patients with benign disease, compared with bronchoscopy alone, according to findings from the prospective case-controlled AEGIS-1 trial.

Because bronchoscopy, which plays a central role in lung cancer diagnosis, has varying diagnostic yield based on factors such as the size and location of the lesion, the method used to collect cells, and pathological processing methods, the findings suggest that the test (BronchoGen) could minimize the need for additional invasive procedures in these patients, Duncan Whitney, Ph.D., said at the annual meeting of the American College of Chest Physicians.

The AEGIS-1 (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer 1) trial included more than 700 current or former smokers undergoing bronchoscopy for suspicion of lung cancer. It was designed to evaluate the diagnostic accuracy of the genomic test, which detects gene expression of cytologically normal bronchial airway epithelial cells.

The investigators collected mainstem bronchial airway brushings from 330 patients, including 240 with confirmed primary lung cancer and 90 controls, and performed microarray analysis. The sample set was then split into an independent training sample of 220 cases and a test set of 110 cases, and the gene-expression prediction model was optimized.

Next, reverse transcription polymerase chain reaction (RT-PCR) assays were developed for candidate biomarker genes, and a multivariate test algorithm was reoptimized using the RT-PCR data generated by a reanalysis of 153 of the samples from cancer patients and 64 of the samples from controls, explained Dr. Whitney.

The test, which ultimately focused on 30 genes, yielded a sensitivity of 77%, compared with 74% for bronchoscopy alone. The combined use of the test and bronchoscopy yielded a sensitivity of 96% and a specificity of 73%.

The negative predictive value of the combined test also was better than that of bronchoscopy alone (0.85 vs. 0.65, respectively), said Dr. Whitney.

"So in essence, we’re reducing the false negative rate from 26% down to 4%," he said.

The BronchoGen test was developed based on the airway "field of injury" principle, which refers to the common molecular response that occurs throughout the respiratory tract in current and former smokers with lung cancer, Dr. Whitney explained.

These changes are detected in a gene-expression signature from normal airway cells, even decades after smoking cessation, he noted.

Despite tremendous work done in this area, which has dramatically improved the diagnostic yield and sensitivity of bronchoscopy in the past few years, the procedure is either inconclusive or not diagnostic in up to 50% of cases, he said.

Thus, a "fairly large need" exists in the medical community, given that about 300,000 bronchoscopy procedures are performed each year for suspicion of lung cancer, he added.

Complete results from AEGIS-1, as well as clinical validation of the BronchoGen test, are expected to be released later this year. An additional 1,300 patients have been enrolled in the ongoing AEGIS-II trial.

Allegro Diagnostics, which developed the BronchoGen test, reports that it plans to commercialize it for use with bronchoscopy beginning in 2013.

This study was sponsored by Allegro Diagnostics. Dr. Whitney is an employee of the company, and had no other disclosures to report.

ATLANTA – The combined use of a novel bronchial airway gene-expression test and bronchoscopy improves the ability to rule out lung cancer in patients with benign disease, compared with bronchoscopy alone, according to findings from the prospective case-controlled AEGIS-1 trial.

Because bronchoscopy, which plays a central role in lung cancer diagnosis, has varying diagnostic yield based on factors such as the size and location of the lesion, the method used to collect cells, and pathological processing methods, the findings suggest that the test (BronchoGen) could minimize the need for additional invasive procedures in these patients, Duncan Whitney, Ph.D., said at the annual meeting of the American College of Chest Physicians.

The AEGIS-1 (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer 1) trial included more than 700 current or former smokers undergoing bronchoscopy for suspicion of lung cancer. It was designed to evaluate the diagnostic accuracy of the genomic test, which detects gene expression of cytologically normal bronchial airway epithelial cells.

The investigators collected mainstem bronchial airway brushings from 330 patients, including 240 with confirmed primary lung cancer and 90 controls, and performed microarray analysis. The sample set was then split into an independent training sample of 220 cases and a test set of 110 cases, and the gene-expression prediction model was optimized.

Next, reverse transcription polymerase chain reaction (RT-PCR) assays were developed for candidate biomarker genes, and a multivariate test algorithm was reoptimized using the RT-PCR data generated by a reanalysis of 153 of the samples from cancer patients and 64 of the samples from controls, explained Dr. Whitney.

The test, which ultimately focused on 30 genes, yielded a sensitivity of 77%, compared with 74% for bronchoscopy alone. The combined use of the test and bronchoscopy yielded a sensitivity of 96% and a specificity of 73%.

The negative predictive value of the combined test also was better than that of bronchoscopy alone (0.85 vs. 0.65, respectively), said Dr. Whitney.

"So in essence, we’re reducing the false negative rate from 26% down to 4%," he said.

The BronchoGen test was developed based on the airway "field of injury" principle, which refers to the common molecular response that occurs throughout the respiratory tract in current and former smokers with lung cancer, Dr. Whitney explained.

These changes are detected in a gene-expression signature from normal airway cells, even decades after smoking cessation, he noted.

Despite tremendous work done in this area, which has dramatically improved the diagnostic yield and sensitivity of bronchoscopy in the past few years, the procedure is either inconclusive or not diagnostic in up to 50% of cases, he said.

Thus, a "fairly large need" exists in the medical community, given that about 300,000 bronchoscopy procedures are performed each year for suspicion of lung cancer, he added.

Complete results from AEGIS-1, as well as clinical validation of the BronchoGen test, are expected to be released later this year. An additional 1,300 patients have been enrolled in the ongoing AEGIS-II trial.

Allegro Diagnostics, which developed the BronchoGen test, reports that it plans to commercialize it for use with bronchoscopy beginning in 2013.

This study was sponsored by Allegro Diagnostics. Dr. Whitney is an employee of the company, and had no other disclosures to report.

ATLANTA – The combined use of a novel bronchial airway gene-expression test and bronchoscopy improves the ability to rule out lung cancer in patients with benign disease, compared with bronchoscopy alone, according to findings from the prospective case-controlled AEGIS-1 trial.

Because bronchoscopy, which plays a central role in lung cancer diagnosis, has varying diagnostic yield based on factors such as the size and location of the lesion, the method used to collect cells, and pathological processing methods, the findings suggest that the test (BronchoGen) could minimize the need for additional invasive procedures in these patients, Duncan Whitney, Ph.D., said at the annual meeting of the American College of Chest Physicians.

The AEGIS-1 (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer 1) trial included more than 700 current or former smokers undergoing bronchoscopy for suspicion of lung cancer. It was designed to evaluate the diagnostic accuracy of the genomic test, which detects gene expression of cytologically normal bronchial airway epithelial cells.

The investigators collected mainstem bronchial airway brushings from 330 patients, including 240 with confirmed primary lung cancer and 90 controls, and performed microarray analysis. The sample set was then split into an independent training sample of 220 cases and a test set of 110 cases, and the gene-expression prediction model was optimized.

Next, reverse transcription polymerase chain reaction (RT-PCR) assays were developed for candidate biomarker genes, and a multivariate test algorithm was reoptimized using the RT-PCR data generated by a reanalysis of 153 of the samples from cancer patients and 64 of the samples from controls, explained Dr. Whitney.

The test, which ultimately focused on 30 genes, yielded a sensitivity of 77%, compared with 74% for bronchoscopy alone. The combined use of the test and bronchoscopy yielded a sensitivity of 96% and a specificity of 73%.

The negative predictive value of the combined test also was better than that of bronchoscopy alone (0.85 vs. 0.65, respectively), said Dr. Whitney.

"So in essence, we’re reducing the false negative rate from 26% down to 4%," he said.

The BronchoGen test was developed based on the airway "field of injury" principle, which refers to the common molecular response that occurs throughout the respiratory tract in current and former smokers with lung cancer, Dr. Whitney explained.

These changes are detected in a gene-expression signature from normal airway cells, even decades after smoking cessation, he noted.

Despite tremendous work done in this area, which has dramatically improved the diagnostic yield and sensitivity of bronchoscopy in the past few years, the procedure is either inconclusive or not diagnostic in up to 50% of cases, he said.

Thus, a "fairly large need" exists in the medical community, given that about 300,000 bronchoscopy procedures are performed each year for suspicion of lung cancer, he added.

Complete results from AEGIS-1, as well as clinical validation of the BronchoGen test, are expected to be released later this year. An additional 1,300 patients have been enrolled in the ongoing AEGIS-II trial.

Allegro Diagnostics, which developed the BronchoGen test, reports that it plans to commercialize it for use with bronchoscopy beginning in 2013.

This study was sponsored by Allegro Diagnostics. Dr. Whitney is an employee of the company, and had no other disclosures to report.