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IMPROVING INDETERMINANT PULMONARY NODULE MANAGEMENT WITH THE PERCEPTA GENOMIC SEQUENCING CLASSIFIER

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Co-Author(s)
Hans Lee, Momen Wahidi, Peter Mazzone, David Feller-Kopman, Michael Bernstein, Daniel Pankratz, Lori Lofaro, Giulia Kennedy, Yoonha Choi, Jing Huang, Travis Dotson, Christina Bellinger, Patric WalshPresenting Author(s)
Sangeeta Bhorade
Purpose:
Guidelines recommend patients with intermediate-risk nodules undergo bronchoscopic workup, yet the diagnostic yield is only around 50%, underscoring the need for additional tools to inform patient management. We previously established the clinical accuracy of Percepta Bronchial Genomic Classifier, a molecular test that utilizes a brushing of bronchial epithelium to improve nodule management in smokers. We have since developed the second-generation Percepta Genomic Sequencing Classifier (GSC), which utilizes 1232 gene transcripts from whole-transcriptome RNA sequencing, as well as clinical factors, to achieve improved performance. Here we report the clinical validation and demonstrate improvement for nodule diagnosis.

Methods:
We utilized over 1600 patient samples to train the new Percepta GSC, which is an ensemble of four machine-learning models that incorporate genomic and clinical features as well as their interactions. We established diagnostic accuracy on an independent validation set consisting of 412 patient samples from three cohorts: AEGIS I and II (246 patients) and the Percepta Registry (166 patients)—all with nondiagnostic lung nodules from bronchoscopy. We measured positive predictive value (PPV) and negative predictive value (NPV) of Percepta GSC results in physician-reported pre-test risk categories of low, intermediate or high risk. In AEGIS I/II cohorts, where patients with diagnostic bronchoscopy results are available, we calculated the sensitivities of bronchoscopy and Percepta GSC alone, as well as in combination.

Results:
In the validation set, 80 patients (19%) had a low pre-test risk (cancer prevalence 5.0%), 188 (35%) had an intermediate pre-test risk (cancer prevalence 28.2%), and 144 (46%) had a high pre-test risk (cancer prevalence 73.6%). Percepta GSC down-classified patients with low pre-test risk with >99% NPV and intermediate pre-test risk with a 91.0% NPV. In addition, the classifier up-classified patients with intermediate pre-test risk with a 65.4% PPV and high pre-test risk with a 91.5% PPV. In total, 41.6% of intermediate pre-test risk patients were either down- or up-classified by the test. In the AEGIS cohorts, the sensitivity among low and intermediate pre-test risk patients was: 40.9% (bronchoscopy alone), 92.3% (Percepta GSC alone), and 95.5% (combined).

Conclusions:
Percepta GSC is clinically validated to accurately up-classify and down-classify the probability of malignancy for a substantial portion of lung nodule patients with nondiagnostic bronchoscopy. Percepta GSC significantly improves the sensitivity of bronchoscopy overall and demonstrates a combined 95%+ sensitivity for low/intermediate pre-test risk groups.

Clinical Implications:
Percepta GSC compliments bronchoscopy and when used together can enable improved management of pulmonary nodules.