Kezhong Chen1, Jingbo Zhang2, Tian Guan1, Fan Yang1, Feng Lou2, Wei Chen2, Mingyu Zhao2, Jay Zhang2, Siyi Chen3, Jun Wang4. 1. Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China. 2. San Valley Biotechnology Inc, Beijing, China. 3. Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif. 4. Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China. Electronic address: wangjun@pkuph.edu.cn.
Abstract
OBJECTIVE: Noninvasive liquid biopsies of circulating tumor DNA (ctDNA) can be used to assess non-small cell lung cancer (NSCLC), but previous work focused on patients with advanced-stage cancer. Thus, we evaluated the feasibility and their potential clinical application of circulating tumor DNA approached for surgical patients with NSCLC. METHOD: Consecutive patients with suspected lung cancer who underwent curative-intent lung resection were enrolled prospectively in this study. Targeted DNA sequencing with a next-generation sequencing platform was used to identify a series of somatic mutations in matched tumor tissue DNA (tDNA) and plasma ctDNA samples. Plasma was collected before, during, and after surgery. Concordance was defined as matched tDNA and ctDNA with the same identified mutations or with no mutations. RESULTS: In the enrolled 76 patients with lung cancer who were included, 31 had concordant mutations and 21 had no mutation in both ctDNA and tDNA, yielding an overall concordance of 68.4%. ctDNA samples obtained before and during surgery had the same mutations with a low variance in mutation frequency (1.2%) that was reduced to an average of 0.28% after surgery (P < .001). More patients were positive as assayed by ctDNA (48; 63.2%) than with serum tumor protein markers (36; 49.3%). The area under the curve was greater in ctDNA (0.887, 95% confidence interval [CI], 0.788-0.986) than for the 2 prediction models (0.803, 95% CI, 0.647-0.959; 0.69, 95% CI, 0.512-0.869) for estimating malignancy of solitary pulmonary nodules. CONCLUSION: ctDNA mutation analysis for stage I-III surgical patients with NSCLC is feasible. More studies are needed to investigate its clinical application.
OBJECTIVE: Noninvasive liquid biopsies of circulating tumor DNA (ctDNA) can be used to assess non-small cell lung cancer (NSCLC), but previous work focused on patients with advanced-stage cancer. Thus, we evaluated the feasibility and their potential clinical application of circulating tumor DNA approached for surgical patients with NSCLC. METHOD: Consecutive patients with suspected lung cancer who underwent curative-intent lung resection were enrolled prospectively in this study. Targeted DNA sequencing with a next-generation sequencing platform was used to identify a series of somatic mutations in matched tumor tissue DNA (tDNA) and plasma ctDNA samples. Plasma was collected before, during, and after surgery. Concordance was defined as matched tDNA and ctDNA with the same identified mutations or with no mutations. RESULTS: In the enrolled 76 patients with lung cancer who were included, 31 had concordant mutations and 21 had no mutation in both ctDNA and tDNA, yielding an overall concordance of 68.4%. ctDNA samples obtained before and during surgery had the same mutations with a low variance in mutation frequency (1.2%) that was reduced to an average of 0.28% after surgery (P < .001). More patients were positive as assayed by ctDNA (48; 63.2%) than with serum tumor protein markers (36; 49.3%). The area under the curve was greater in ctDNA (0.887, 95% confidence interval [CI], 0.788-0.986) than for the 2 prediction models (0.803, 95% CI, 0.647-0.959; 0.69, 95% CI, 0.512-0.869) for estimating malignancy of solitary pulmonary nodules. CONCLUSION: ctDNA mutation analysis for stage I-III surgical patients with NSCLC is feasible. More studies are needed to investigate its clinical application.
Authors: Kezhong Chen; Heng Zhao; Fan Yang; Bengang Hui; Tianyang Wang; Lieu Tu Wang; Yanbin Shi; Jun Wang Journal: BMJ Open Date: 2018-02-06 Impact factor: 2.692
Authors: Frederik van Delft; Hendrik Koffijberg; Valesca Retèl; Michel van den Heuvel; Maarten IJzerman Journal: Cancers (Basel) Date: 2020-04-30 Impact factor: 6.639