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Biomarkers: a novel tool to improve lung nodule classification

Presented by
Dr Michael Pritchett
ERS 2020
Current clinical management of lung nodule patients is inefficient and causes patient misclassification, which increases healthcare expenses. According to a real-world study, the addition of blood-based biomarkers leads to a distinct shift from nodules being assessed as low-to-moderate risk to a very-low risk category, thus saving invasive procedures [1].

Currently, a physician-assessed probability of malignancy drives care decisions for patients with solitary pulmonary nodules. The American College of Chest Physicians has published recommendations on how to deal with patients with these nodules (see Figure) [2]. However, a subgroup of the PANOPTIC trial has shown that 38% of biopsies and 20% of surgeries are performed on benign nodules [3]. Results from the PANOPTIC trials have recently indicated that the use of a biomarker-driven lung nodule classifier can be a useful addition to physician-assessed probability of malignancy. The authors suggest that it could lead to 40% fewer invasive procedures compared with physician-assessed probability only [3].

Figure: ACCP guidelines for solitary pulmonary nodules in patients with low surgical risk [2]

The was the motivation for the real-world, observational ORACLE study to evaluate the impact of a blood-based test on the management of patients with solitary pulmonary nodules. The study assessed whether the additional performance of biomarkers is of clinical use and can lead to a change in the malignancy assessment of the physician.

Physician-assessed and Mayo calculated-based probability of malignancy were used to define the pre-test risk score of patients based on age, smoking status, nodule size, location, spiculation, and history of cancer. In addition, the blood-based Nodify XL2TM test (XL2) was performed in every patient meeting the following criteria: ≥40 years of age, nodule size between 8-30 mm, physician-assessed probability and Mayo ≤50%.

The use of the Nodify XL2 TM test resulted in a re-classification of 46% of all nodules from low-to-moderate risk into the very-low risk category per ACCP guidelines. This shift in risk distribution by use of the blood-based proteomic test led to a substantial increase in benign nodules routed to CT surveillance instead of invasive procedures. The authors conclude that the addition of biomarkers to a physician-based evaluation may result in a substantial reduction of unnecessary invasive procedures.


    1. Pritchett M, et al. First Look at the Distribution of Risk of Malignancy Pre and Post-Test Using a Blood-Based Biomarker in Patients with Pulmonary Nodules in a Real-World Observational Study. Poster 323. ATS 2020 Virtual, 5-10 Aug.
    2. Gould MK, et al. Chest 2013;143 (5 Suppl):e93S-e120S.
    3. Silvestri GA, et al. Chest 2018:154: 491-500.


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