USE OF TWO BLOOD-BASED BIOMARKER TESTS IN SERIES TO RECLASSIFY RISK OF INDETERMINATE PULMONARY NODULES

Abstract

SESSION TITLE: Lung Cancer Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Assessing the risk of malignancy of indeterminate pulmonary nodules (IPN) is imprecise. Misclassification of risk can potentially delay the diagnosis of lung cancer or lead to unnecessary invasive procedures. The Nodify XL2 (XL2) and Nodify CDT (CDT) tests are independently validated, blood-based lung nodule tests that help reclassify risk of malignancy. Performing CDT first to identify high risk patients quickly and then performing XL2 following a CDT negative (CDT-N) result may lead to more effective risk stratification and diagnostic plans. Using banked samples from the PANOPTIC study (NCT01752114), we evaluated the utility of combining these two tests in series to increase the negative predictive power of the XL2 test. METHODS: CDT-N plasma samples from PANOPTIC were retrospectively evaluated with XL2. A total of 317 patients were eligible for analysis based on sample availability; 150 patients (33% cancer prevalence) met the clinical use (CU) criteria for both tests: 8-30mm diameter, age ≥40 years, pCA≤65% by physician and Mayo calculated and no cancer history. Following testing, the post-test risk of malignancy can be calculated using positive and negative likelihood ratios for CDT and XL2, respectively. RESULTS: Analysis of the overall CU cohort identified 16 patients as CDT positive and 134 as CDT-N, of which 93 patients (18% cancer prevalence) met the XL2 analysis criteria (XL2-CU, pCA <50% by Mayo and physician assessed risk). In the CDT-N and XL2 eligible patients, 41 (44%) patients had a post-test pCA <5% with 41/41 (100%) being benign. The test performance of XL2 in XL2-CU population was: sensitivity 100% (CI 82-100%), specificity 54% (CI 43-65%) and negative predictive value (NPV) 100% (CI 91-100%). 42 (32%) of the IPN in the low/moderate risk category (N=132, pCA 5-65%) were reclassified into either the high risk category (pCA >65%) by CDT (N=12/132 [9%]) or the very low risk category (pCA <5%) by XL2 (N=30/78 [38%]). Thus, this testing strategy could have reclassified 3 malignant nodules that were routed to CT surveillance and 6 benign nodules that underwent invasive procedures. CONCLUSIONS: Performing CDT first identifies patients with a high risk of malignancy that should be evaluated quickly and reduces the prevalence of cancer in the subsequent population analyzed by XL2. Performing XL2 on these remaining patients identifies those who can be more confidently monitored with surveillance with a high level of accuracy. CLINICAL IMPLICATIONS: This combined testing strategy shifts 32% of patients into risk groups with different, guideline recommended diagnostic plans. Reclassifying the risk of malignancy by incorporating biomarkers with traditional risk assessment may help reduce unnecessary procedures on benign nodules and reduce delays in diagnosis of malignant nodules. DISCLOSURES: Consultant relationship with Biodesix Please note: $1001 - $5000 Added 06/02/2020 by Kevin Doubleday, source=Web Response, value=Consulting fee Consultant relationship with Biodesix Please note: $20001 - $100000 Added 05/31/2020 by James Jett, source=Web Response, value=Consulting fee Employee relationship with Biodesix, Inc. Please note: >$100000 Added 06/02/2020 by Laura Peek, source=Web Response, value=Salary Employee relationship with Biodesix Please note: >$100000 Added 06/01/2020 by Trevor Pitcher, source=Web Response, value=Salary Removed 06/01/2020 by Trevor Pitcher, source=Web Response Employee relationship with Biodesix Please note: >$100000 Added 06/01/2020 by Trevor Pitcher, source=Web Response, value=Salary Employee relationship with Biodesix Please note: >$100000 Added 06/02/2020 by Steven Springmeyer, source=Web Response, value=Salary