The impact of a genomic sequencing classifier (GSC) on clinical decision making in patients with a high-risk lung nodule.

Abstract

8549 Background: Current guidelines recommend that patients who have lung nodules with high risk of malignancy (ROM) ( > 65%) should undergo surgical and other ablative therapies. However, prior studies have shown that clinicians may opt for more conservative management in these high-risk patients. Percepta Genomic Sequencing Classifier (GSC), a RNA-seq based classifier derived from bronchial epithelial cells to assess risk of lung cancer, was designed to risk stratify lung nodules by both down classifying ROM as a “rule -out“ test with high sensitivity as well as up-classifying ROM as a “rule- in” test with high specificity for malignancy. This study assesses the impact of up-classification of high ROM to very high- risk (ROM > 90%) by Percepta GSC in increasing the number of ablative therapies recommended for high-risk lung nodules. Methods: This prospective randomized decision impact survey included 37 patients from the AEGIS I/ II cohorts and the Percepta Registry who were undergoing work up of a lung nodule and had a high ROM that was up-classified to very high ROM by Percepta GSC. 97 physicians assessed 10 randomly assigned patient cases. They then responded to a survey designed to test the hypothesis that including a Percepta GSC result will increase the recommendation for surgical or other ablative therapy in very high- risk patients as well as their level of confidence of this recommendation. Physicians were first presented with the patient’s clinical information without Percepta GSC and then with Percepta GSC. Results: 97 physicians provided a total of 682 evaluations of 37 patients. In this study, the recommendation for surgical or other ablative therapy increased from 19/341 (5.6%) prior to the Percepta GSC result to 157/341 (46%) after the Percepta GSC result (odds ratio of 4.76, p-value < 0.001). The number of extremely confident recommendations increased from 72/341 (21%) without Percepta GSC to 106/341 (31%) with Percepta GSC. Significantly more physicians had increased confidence in their recommended next step post-Percepta GSC when collapsing the confidence level responses into increased confidence (n = 93) and decreased confidence (n = 44) (p-value = 0.002). Conclusions: Percepta GSC had a quantifiable impact on clinical decision making. It increased the number of surgical and other ablative therapies recommended when patients were re-classified from high to very high- risk of lung cancer with a higher confidence in the recommended next step. By up-classifying nodules from high to very high ROM, Percepta GSC will improve the likelihood and timeliness of appropriate therapies and assist clinicians more effectively manage patients to improve patient outcomes.