Integrated Diagnostics today announced the e-publication of full results of a large prospective clinical trial validating its Xpresys Lung 2® in the peer-reviewed medical journal CHEST.
Lung nodules are a diagnostic challenge with an estimated yearly incidence of 1.6 million in the United States. The majority of these patients have benign lung nodules, however, there are significant costs, morbidity and mortality associated with the invasive biopsies needed to determine which nodules are cancerous.
These avoidable procedures are most common in patients with nodules that are low to moderate risk for cancer.
“Integrated Diagnostics pioneered the liquid biopsy approach to lung nodules based on proteomic (protein) analyses of blood plasma samples from hundreds of patients with nodules,” stated CEO Dr. Albert Luderer.
“This research resulted in the discovery of several lung cancer-associated changes in a patient’s plasma proteome.” The original findings were published in Science Translational Medicine and the Journal of Thoracic Oncology, and collectively demonstrated that specific protein changes could be detected in early stage lung cancer and utilized to exclude cancer in patients with benign nodules.
The newly published clinical validation represents the performance of the second generation diagnostic test of Integrated Diagnostic’s original published work and is termed Xpresys Lung 2 (‘XL2’).
This new test combines five standard-of-care clinical factors such as patient age and nodule size in combination with the measurement of two proteins into a single risk assessment.
The validation study confirmed the high accuracy of XL2 in identifying benign nodules in patients with a pretest probability of malignancy of 50% and less.
Co-authors Paul Kearney, PhD and Steven Springmeyer, MD commented that:
To establish a high level of evidence, we conducted two prospective studies, one for discovery and the other for validation that focused only on Stage 1A lung nodules. This is incredibly important as these are the lung nodules that are the hardest to assess. We integrated clinical risk factors and found that the proteomic signal was additive to the clinical risk factors. So in a real sense, XL2 is providing physicians with a molecular insight that they have never had before.
“The outcomes of the PANOPTIC prospective, multi-center, observational trial are significant as they validate a new approach leveraging the proteome –– to accurately distinguish between benign and malignant nodules to rule out early stage lung cancer,” added senior author Dr. Peter Mazzone, Director of the Lung Cancer Program and Lung Cancer Screening Program for the Respiratory Institute.
“Through this large-scale research, we have shown that this may provide the needed objective assessment of lung nodules to better determine the best treatment path forward, which could reduce or avoid invasive biopsy or surgery procedures and create improved patient outcomes.”
State-of-art instrumentation used multiple reaction monitoring mass spectrometry to measure the relative abundance of two plasma proteins, LG3BP and C163A. These proteins were integrated into a ratio that is associated with the malignant condition - LG3BP is elevated and C163A is diminished.
The low to moderate risk subgroup of 178 patients with a clinician assessed pCA≤50% had a 16% prevalence of lung cancer. XL2 demonstrated a sensitivity of 97% (CI 82%-100%), a specificity of 44% (CI 36%-52%) and a negative predictive value (NPV) of 98% (CI 92%-100%) in distinguishing benign from malignant nodules.
When XL2 performance was contrasted to other standard-of-care diagnostic modalities performed on these patients, the classifier performed better than all other modalities including positron emission tomography (PET), validated lung nodule risk models and physician estimated cancer probability (p<0.001).
If the integrated classifier results were used to direct care, 40% fewer procedures would be performed on benign nodules while only 3% of malignant nodules would be misclassified. This low XL2 error rate contrasts dramatically to the trial’s observed standard of care misclassification of cancers (45%).