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NSCLC, metastatic

1728 - Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells

Date

10 Sep 2017

Session

NSCLC, metastatic

Presenters

Yang-Si Li

Citation

Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380

Authors

Y. Li1, B. Jiang1, W. Guo1, X. Zhang1, J. Yang1, Y. Shao2, B. Huang3, Y. Liu4, Y. Wu1

Author affiliations

  • 1 Guangdong General Hospital & Guangdong Academy Of Medical Sciences, Guangdong Lung Cancer Institute, 510080 - Guangzhou/CN
  • 2 Geneseeq Biotechnology, Geneseeq, Nanjing/CN
  • 3 Guangdong General Hospital & Guangdong Academy Of Medical Sciences, Department of Radiology, 510080 - Guangzhou/CN
  • 4 Guangdong General Hospital & Guangdong Academy Of Medical Sciences, Department of Pathology, 510080 - Guangzhou/CN
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Abstract 1728

Background

Leptomeningeal metastases (LM) are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of LM.

Methods

We compared the CellSearch Assay™, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected LM. Next-Generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTCs) of 19 patients.

Results

Twenty-one patients were diagnosed with LM, and CSFCTCs were captured by CellSearch in 20 patients (median, 969 CSFCTCs/7.5 mL; range, 27–14,888). CellSearch had a sensitivity of 95.2% for LM diagnosis, which was higher than that of TCT (12/21, 57.1%), MRI (10/21, 47.6%), and MRI plus TCT (19/21, 90.5%), respectively. CTCs were found only in 5 of 14 patients (median, 2 CTCs/7.5 mL; range, 2–4), which was a much lower ratio than CSFCTCs. Genetic profiles of CSFCTCs were highly concordant with molecular mutations identified in the primary tumor (17/19, 89.5%). The resistance gene EGFR T790M was detected in 7 of 9 patients with extracranial lesions, but was only detected in 1 of 14 CSFCTCs samples. Other potential resistant mutations such as MET amplification and ERBB2 mutation were also identified in CSFCTCs.Table:

1307PD

Patient No.Primary gene profileTargeted therapy before LMRebiopsy gene profileCSFCTCs gene profile (NGS)
1EGFR L858R (lung)ErlotinibEGFR L858R (lung, ARMS); MET(IHC):80% (3+)EGFR L858R
2bEGFR del19 (lymph node)IcotinibUAEGFR del19; EGFR T790M
3EML4-ALK (lung)CrizotinibEML4-ALK (pleural effusion)EML4-ALK; MET amplification
4EGFR 20INS (lung)NoneUAEGFR 20INS
5EGFR del19 (pleura)GefitinibEGFR del19 and T790M (lung)EGFR del19; EGFR amplification
6EGFR L858R (lung)ErlotinibEGFR L858R and T790M (lung)EGFR L858R
7EGFR, ALK (WT)NoneSnapshot, MET, KIT (WT)Common driver gene (WT)
9EGFR del19 (pleura)GefitinibEGFR del19 and T790M (liver);MET: 100% (3+) (liver)EGFR del19; ERBB2 exon8 T328fs; ROS1 exon7 W215X
10EGFR L858R (lung)Gefitini, erlotinibEGFR del19 and T790M (lung)EGFR del19
11EGFR L858R (lung)Gefitini, erlotinibUAEGFR L858R
12EGFR L858R (lung)GefitinibEGFR L858R and T790M (plasma)Common driver gene (WT)
13EML4-ALK (lung)CrizotinibUAEML4-ALK
14EGFR del19 (lung)Erlotinib, afatinibUAEGFR del19; MET amplification
15EGFR del19 (lung)IcotinibUAEGFR del19
16EGFR L858R (lung)NoneEGFR L858R (lymph node)EGFR and ALK (WT); RET exon4 V253E
17EGFR L861Q (lymph node)ErlotinibUAEGFR L861Q; EGFR del19
18cEGFR L858R (lung)GefitinibEGFR L858R and T790M (lung)EGFR L858R; PIK3CA exon2 N107S; MET exon11 F839L
19EGFR L858R (lung)GefitinibEGFR L858R and T790M (lung)EGFR L858R
21EGFR L858R (lung)GefitinibUAEGFR L858R

Conclusions

CellSearch could be a more sensitive method for detecting tumor cells in CSF, and potentially provides earlier diagnosis of LM. More importantly, CSFCTCs could be an important and new way of “liquid biopsy” for genetic profiles of metastatic tumor cells in LM patients of NSCLC.

Clinical trial identification

none

Legal entity responsible for the study

Yi-Long Wu

Funding

Geneseeq Biotechnology, Inc., Nanjing, China

Disclosure

All authors have declared no conflicts of interest.

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