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T. Ohira
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-082 - The Feasibility of Cell-Free DNA Sequencing for Mutation Detection in Non–Small Cell Lung Cancer Was Detemined by Tumor Volume (ID 6001)
14:30 - 14:30 | Author(s): T. Ohira
- Abstract
Background:
Targeted therapeutics such as tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) have recently been introduced into clinical practice for individuals with NSCLC positive for actionable mutations of EGFR or ALK fusions, respectively. Molecular profiling that is able to predict the response to such drugs has thus become an important therapeutic strategy, allowing selection of the most appropriate treatment for individual patients.
Methods:
Matched lung cancer tissue and serum specimens were collected from 150 patients who underwent surgery at Tokyo Medical University Hospital from January 2013 to July 2014. All tissue samples were stored at –80°C until analysis. Tumor DNA and cfDNA samples were subjected to analysis with next-generation sequencing (NGS) panels for mutation detection.
Results:
All tumor DNA samples were successfully sequenced with the Ion Proton platform. The median read number per amplicon was 15,632. We identified TP53 mutations in 58 cases (38.7%); EGFR mutations in 56 (37.3%); KRAS mutations in 15 (10.0%); CTNNB1 mutations in 7 (4.7%); ERBB2, PIK3CA, BRAF, and PTEN mutations in 3 each (2.0%); and ERBB4, MET, ALK, FGFR2, NRAS, AKT1, and FBXW7 mutations in 1 each (0.7%). No mutation was detected in 22.0% (33/150) of the samples. Serum cfDNA was extracted for all 150 patients, with a median yield (copy number) of 4936 (range, 572 to 373,658). A total of 149 of the 150 (99.3%) cfDNA samples were successfully sequenced with the Ion Proton platform, with sequencing failure being due to an insufficient read number per amplicon in the one unsuccessful case. The median read number per amplicon for the 149 successfully sequenced cfDNA samples was 33,982.
Conclusion:
These results suggested that detection of mutations in cfDNA of patients with disease at stage IA or IB or at T2a or lower is difficult, and that the feasibility of mutation detection with cfDNA may depend on the T factor rather than the N factor. Tumor volume in the cfDNA mutation–positive group was significantly greater than that in the cfDNA mutation–negative group (159.1 ± 58.0 versus 52.5 ± 9.9 cm[3], p = 0.014). The maximum tumor diameter calculated at diagnosis was also larger in the cfDNA mutation–positive group than in the cfDNA mutation–negative group (5.3 ± 0.7 versus 4.1 ± 0.3 cm, p = 0.050). These results suggested that tumor volume is a determining factor for the feasibility of mutation detection with cfDNA.