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T. Yung
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-032 - Detection of EGFR, ALK and Other Driver Oncogenes from Plasma cfDNA by Single Molecule Amplification and Re-sequencing Technology (cSMART) (ID 8603)
09:30 - 09:30 | Author(s): T. Yung
- Abstract
Background:
All patients with advanced stage NSCLC should have their EGFR and ALK mutation status known prior to initiation of first line therapy. Multiple plasma-based technologies such as ARMS and ddPCR are available for rapid detection of EGFR mutation, while only the more laborious Next Generation Sequencing (NGS) may cover EGFR, ALK and other uncommon mutations in a single blood test. cSMART is a novel NGS-based technology with rapid turnaround time that can detect EGFR, ALK and KRAS mutations plus others less common lung cancer specific driver oncogenes (BRAF, ROS-1, HER-2, PIK3CA, RET, MET14skipping).
Method:
Objectives of this study is to investigate the clinical application of cSMART on patients with advanced NSCLC. In cSMART assay, each cfDNA single allelic molecule is uniquely barcoded and universally amplified to make duplications. The amplified products are circularized and re-amplified with target-specific back-to-back primers. These DNA are then ligated with sequencing adapters and pair-end sequenced (>40,000x) with illumine sequencers. The original cfDNA molecules are reconstituted by multi-step bioinformatics pipeline for censor and correction. The final products are quantified for calculation of allele frequencies
Result:
Out of the 1664 samples tested, total of 1469 were of advanced stage NSCLC. We detected EGFR mutations in 758 (51.6%), ALK translocation in 34 (2.3%) and KRAS mutation in 78 (5.8%) patients. Among the patients with activating EGFR mutations, 301(39.7%) have exon 19 deletion and 279 (36.8%) have exon 21 point-mutation. Total of 6 (0.8%) patients with EGFR mutation have concurrent presence of ALK translocation. Incidence and mean allele frequency of the less common target mutation is summarized in Table. Median sample turnaround time is 7 days.Incidence (%) Median Mutation Allele frequency (%) BRAF 29 (1.97%) 0.08% ROS1 2 (0.14%) 0.77% HER-2 19 (1.29%) 0.20% PIK3CA 70 (4.77%) 0.17% RET 14 (0.95%) 0.57% MET14skipping 63 (4.29%) 0.08%
Conclusion:
cSMART is a novel plasma cfDNA-based technology that can detect the actionable target oncogenes for patients with advanced NSCLC. This is a sensitive method with capacity of detecting the uncommon targets at relatively low allele frequency.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-031 - Detection of Activating EGFR Mutations and Resistant T790M Mutation from cfDNA in Malignant Pleural Effusion(MPE-DNA) (ID 8389)
09:30 - 09:30 | Author(s): T. Yung
- Abstract
Background:
Analysis of activating EGFR and resistant T790M mutations from plasma cfDNA is now recognized as one of the standard testing methods in clinical practice.(Mok et al CCR 2015, Oxnard et al JCO 2016) Sensitivity varies from 60 to 80% while specificity is above 90%. Malignant pleural effusion (MPE) is an alternative rich source of cfDNA and efficacy of mutation testing from this sample source remains unclear.
Method:
Objectives of this study is to study the feasibility of testing EGFR mutations using MPE-DNA and to compare the diagnostic utilities with plasma cfDNA in lung cancer patients with known EGFR mutation status established by tumor tissue. 10 ml of blood and 10 ml of pleural fluid were collected after consent. DNA was extracted and tested by digital PCR (Sanomics Inc. Hong Kong, China).
Result:
We enrolled 45 patients between November 2016 and May 2017. Patient demographics are summarized as follows: male (n=21) vs female (n=24); tissue EGFR wild type (n=13) vs mutation (n=24) vs unknown (n=8); treatment naïve (n=26) vs progression of TKI (n=19). Diagnostic utilities are summarized in table below. 9 plasma samples were positive for T790M compared to 14 samples of MPE-DNA being positive. (Detection rate: 0.20 vs 0.31, respectively) Total of 6 negative T790M plasma samples were tested positive in MPE-DNA, and vice versa, 2 samples. Concordance rate of T790M testing between plasma cfDNA and MPE-DNA is 0.82.EGFR mutation Plasma cfDNA vs tumor MPE-DNA vs tumor Sensitivity 0.83 0.92 Specificity 0.92 0.92 Concordance 32/37=0.86 34/37= 0.92 Mean allele frequency of cfDNA only (range) 13.43% (0.10%-58.66%) 31.77% (1.21%-83.40%)
Conclusion:
It is feasible to detect activating EGFR and resistant T790M mutations from MPE-DNA. Sensitivity of testing MPE-DNA is similar if not better than plasma cfDNA. Further investigation is warranted.
