Rajesh Shah, MD, director of interventional radiology and associate chief of radiology at the VA Palo Alto Healthcare System and clinical associate professor of radiology at Stanford University
PALO ALTO, Calif. — The VA Palo Alto Health Care System stepped up to be the first testing site for an early detection study in lung cancer that uses a blood assay as a screening mechanism. The VA is a logical location to initiate a test program, as veterans have substantially greater risk of lung cancer than the general population.
Lung cancer is the second most common and by far the most deadly form of cancer in the U.S., killing more than 130,000 people each year. The incidence is 76% higher in veterans than individuals who have never been in the Armed Forces because of much higher rates of smoking among those who have served and greater exposure to environmental risks during military operations. More than 8,000 veterans receive a diagnosis of lung cancer each year and 900,000 veterans are eligible for lung cancer screening.
Based on the latest recommendations of the U.S. Preventive Services Task Force, anyone aged 50 to 80 who has smoked the equivalent of 20 pack-years and currently smokes or quit smoking within the last 15 years should receive an annual low-dose computed tomography (LDCT) scan. Pack years are calculated as the number of packs of cigarettes smoked each day times the number of years smoked, so 20 pack-years could be two packs a day for 10 years or one pack each day for 20 years.
LDCT can identify nodules in the lungs that need additional investigation, an important first step in diagnosing lung cancer. The investigators involved in the Palo Alto study hope that a liquid biopsy can provide even more information and reduce the need for additional testing in many patients.
Improving Screening Outcomes
Early diagnosis of lung cancer— before it spreads to lymph nodes or other organs—increases the likelihood of surviving five years by 51%, according to the American Lung Association. “Lung cancer is more prevalent among veterans, but outcomes are better if cancer is detected earlier. There is a significant unmet need for a cost-effective, noninvasive assay to better identify patients with lung cancer, especially among veterans,” said Rajesh Shah, MD, director of interventional radiology and associate chief of radiology at the VA Palo Alto Healthcare System and clinical associate professor of radiology at Stanford University.
Currently, individuals who have nodules detected during screening proceed to invasive testing, such as percutaneous biopsy, bronchoscopy or surgical procedure. As early screening has increased, the number of patients with false positives who then undergo painful and potentially complicating tissue biopsies has also risen. A sensitive and specific, non-invasive blood test could reduce both costs and adverse effects associated with unnecessary biopsies.
A more comprehensive screening test could also help the VA overcome some challenges with adherence to recommended next steps, whether follow-up testing for screening-detected findings or continued annual screening. A retrospective study at the Bedford VA Healthcare System reviewed records of 28,294 veterans who had lung cancer screening (LCS) and time to act on recommendations based on that screening. The researchers found that 21,557 veterans had low-risk findings (Lung-RADS 1 or 2), 4,0001 had indeterminate results (Lung-RADS 3), and 2,736 had findings with a high suspicion of cancer (Lung-RADS 4).1
More than one in seven veterans (4,439) had no follow-up testing or subsequent screening. That number included 292 with the highest risk findings. The study, “which captured follow-up testing from VHA and Medicare systems, illustrates the challenges of providing timely, recommended next steps after LCS in real-world practice,” the authors concluded. Even in an integrated health system like the VA with low or no-cost care, delays and skipped follow up can erode the mortality benefits of screening seen in national trials.
The Study
Shah is the principal investigator of the prospective, observational study, Liquid Biopsy in Combination with PET/CT Versus PET/CT alone in Diagnosis of Small Lung Nodules, which aims to enroll 50 veterans. The liquid biopsy involves drawing a sample of blood that is then tested for the presence of DNA that has been released by tumors into the bloodstream or circulating tumor DNA (ctDNA).
The study will compare the sensitivity and specificity of positron emission tomography/computed tomography (PET/CT) in combination with liquid biopsy in detecting lung cancer in nodules that are six to 20 millimeters in size compared to using PET/CT alone to predict the presence of cancer in those nodules. The study will enroll veterans at high-risk of lung cancer who have at least one lung nodule considered suspicious for cancer. Secondary endpoints include sensitivity and specificity of circulating tumor DNA (ctDNA) genotyping and sensitivity and specificity of DNA methylation in detecting lung cancer. As part of the study, the researchers will also validate a machine learning model for predicting lung cancer that combines data from PET/CT imaging and clinical data, including the liquid biopsy results.
“A non-invasive liquid biopsy screening test that enables physicians to eliminate unnecessary invasive tests could both improve outcomes and the patient experience while reducing costs,” said Min-Han Tan, MBBS, PhD, founding CEO of Lucence, which makes the assay being studied. “We are excited to initiate this study—the first study examining the use of Lucence’s AmpliMark technology for early detection of cancer in the United States—with the VA Palo Alto Health Care System to continue to develop evidence for liquid biopsy’s utility across the patient journey. We are proud to be partnering with Dr. Shah and the VA Palo Alto to serve such an important population.”
- Núñez ER, Caverly TJ, Zhang S, et al. Adherence to Follow-up Testing Recommendations in US Veterans Screened for Lung Cancer, 2015-2019. JAMA Netw Open. 2021;4(7):e2116233. doi:10.1001/jamanetworkopen.2021.16233
