Clinical utility of circulating genetically abnormal cells within low-dose computed tomography lung cancer screening: A correlative MCPND trial study.

Abstract

e15536 Background: Recent screening trial results using low-dose computed tomography (LDCT) have been shown to reduce lung cancer mortality in high-risk patients. However, high false-positive rates, inter-grader variability, and radiation injuries are challenging, and therefor highlight the necessity for complementary biomarkers. The diagnostic performance of circulating genetically abnormal cells (CACs) was respectively evaluated in samples collected from patients with pulmonary nodules before and after lung lobectomy within the Multicenter Chinese Pulmonary Nodule Detection (MCPND) trial. We also propose a deep learning that detects related genetically abnormal cells in excisions of symptomatic lesions to identify the source of CACs. Methods: 269 plasma samples (n = 179, before surgery; n = 90, after surgery) from 179 participants, including 125 patients with lung cancer and 54 donors with benign nodular lesions, were analyzed by using a FISH–based assay for 3p22.1, 3q29, 10q22_3 and CEP10. Diagnostic performance of CAC was evaluated in a blinded validation group. 109 paraffin-embedded specimens (45 benign nodular lesions, 64 malignancies) obtained from participants were tested in the same way to identify the genetically abnormal cells. Results: The diagnostic performance of CACs for lung cancer detection was 91% for sensitivity and 81% for specificity. For all participants, CACs had a positive predictive value of 92% and 80% for negative predictive value, respectively. Area under the ROC curve was 0.89 (P < 0.01; 95%CI (0.82, 0.96)). 90 plasma samples were drawn from patients within 10 days after surgery. Of these samples, 58 participants’ CACs level reduced and 25 of them remained stable. Moreover, of 64 malignant specimens, genetically abnormal cells were detected in 60 specimens. However, only 4 specimens were detected having genetically abnormal cells in 45 benign nodular lesions. Conclusions: This validation study indicated that the number of genetically abnormal cells in circulation decreased after surgical resection, which suggested CACs could be released from lung cancer. CACs have diagnostic and prognostic value and could assist to improve the diagnostic accuracy in early stage lung cancer after low-dose computed tomography. Clinical trial information: ChiCTR1900026233.