New noninvasive screening technologies are poised to improve the diagnostic yield of advanced imaging in lung cancer and, by so doing, improve patient outcomes, according to Dr. Paul A. Bunn.
A blood test for detecting genetic mutations in circulating tumor cells of lung cancer specimens and a colorimetric sensor array that identifies cancerous compounds in exhaled human breath are among the technologies that could lead to earlier diagnosis and treatment, said Dr. Bunn, executive director of the International Association for the Study of Lung Cancer (IASLC).
Paul A. Bunn Jr.
Lung cancer treatment has been hampered in the past by late diagnoses, typically achieved using invasive procedures only after symptoms have presented, said Dr. Bunn, the James Dudley Professor of Lung Cancer Research at the University of Colorado at Denver.
"But this is changing quickly," he said. "Major breakthroughs are leading to interventions that make a huge difference and make it an exciting time for lung cancer."
The first such breakthrough has been the use of low-dose helical computed tomography, which can identify early-stage disease in asymptomatic individuals while exposing them to a fraction of the radiation emitted by a standard diagnostic chest CT or x-ray, Dr. Bunn said in a press briefing on research presented at a joint conference of the American Association for Cancer Research and the IASLC.
"Spiral CT scans reduced lung cancer mortality by 20% [among current or former heavy smokers] and increased the 7-year survival rate by 20% compared with standard chest x-rays," he said, citing preliminary results of the National Lung Screening Trial (NLST) (N. Engl. J. Med. 2011;365:395-409).
"The low-dose CT screening also increased the diagnosis of stage I cases and surgical cures while they decreased the number of stage IV diagnoses because patients were diagnosed earlier and cured," he said.
Unfortunately, the value of CT scans as a routine screening tool is limited by the technology’s low specificity. In the NLST study, approximately 24% of the participants screened positive based on abnormal CT scan findings, but only 4% of the abnormalities were confirmed as lung cancer. This has led to controversy over whether smokers should be routinely screened for lung cancer.
"The remaining 96% were false positives," said Dr. Bunn, who maintained that the technology, on its own, is currently not cost effective enough to recommend for routine annual screening. "Working up those nodules is incredibly expensive and complicated, and often leads to surgery for something that is benign, not malignant," he said.
The cost/benefit ratio stands to improve substantially, however, as some of the noninvasive screening technologies presented at the conference come to fruition, Dr. Bunn predicted.
For example, Heidi S. Erickson, Ph.D., and her colleagues at the University of Texas M.D. Anderson Cancer Center in Houston have developed a highly sensitive method for detecting cancer mutations in DNA isolated from circulating tumor cells of non–small cell lung cancer (NSCLC). They use the mass spectrometry–based technology to look for any of 135 mutations among 13 genes representing multiple pathways known to be involved in lung cancer.
The methodology requires a simple blood test, which makes it less intrusive than a biopsy. The information will ultimately help investigators understand the molecular characteristics of lung cancer treatment and progression, Dr. Erickson said in an interview. When perfected, it will also complement the information attained via spiral CT scans by providing important insight into diagnostic, prognostic, and predictive markers of disease, thus aiding management decisions, she said.
Similarly, a test identifying lung cancer biomarkers through exhaled breath may also help clinicians and researchers identify which patients with abnormal CT scans need more aggressive follow-up, according to Dr. Bunn.
Dr. Nir Peled of the Sheba Medical Center in Tel Hashomer, Israel, presented data from a cross-sectional comparative survey using breath analyses, in which investigators captured the "metabolic biosignatures" – the pattern of volatile organic compounds (VOCs) – of 74 patients with solitary pulmonary nodules to determine the VOC profiles for malignant and benign lung nodules.
For the analyses, a patient’s breath is drawn across an array of nanomaterial-based sensors, and the patterns are captured using digital cameras. Of the 74 high-risk patients, 53 had malignant nodules and 21 had benign growths, Dr. Peled reported. Within the malignant group, 47 samples were NSCLC and 6 were small cell lung cancer. Further, 30 of the patients had early-stage (I/II) disease and 23 had advanced disease (stage III/V), he said.
"On analysis, two [VOCs] in patients’ exhaled breath showed statistically significant differences in concentration for benign and malignant lung nodules, and the sensor array distinguished between the corresponding collective VOC patterns with nearly 90% accuracy," Dr. Peled said in an interview.