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Gareth Rivalland
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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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P3.02-038 - Diagnosis of Leptomeningeal Disease and Clonal Heterogeneity with Digital Droplet PCR (ddPCR) in EGFR Mutated NSCLC (ID 8929)
09:30 - 09:30 | Presenting Author(s): Gareth Rivalland
- Abstract
Background:
Non-small cell lung cancer (NSCLC) spread to the central nervous system (CNS) is associated with universally poor outcomes. Diagnosis of leptomeningeal (LM) disease is particularly challenging, with radiological and cytological assessment of CSF often negative. Examination of cell-free DNA (cfDNA) is promising method for the assessment of tumour mutation status and disease monitoring. We examine its utility in the diagnosis and management of LM disease.
Method:
Patients with EGFR mutated NSCLC with symptoms suggestive of LM disease underwent cerebrospinal fluid (CSF) sampling and ddPCR assessment. Matched plasma and/or tumour biopsy samples were obtained. Clinical data was collected retrospectively. Genomic DNA was extracted from 1 mL of CSF and 4 mL of plasma using the Qiagen QIAamp Circulating Nucleic Acid kit and T790M and L858R mutations were assessed by using the QX200 ddPCR assays. Survival was calculated from diagnosis and diagnosis of LM disease.
Result:
Seven patients (pts) were included in the analysis. Most pts, 6/7 (86%) developed LM either during or after EGFR tyrosine kinase inhibitor (TKI) therapy. EGFR mutations were demonstrated in CSF in 6 (86%) pts, but only 2 (29%) demonstrated the same mutation profile in both CSF and plasma. Causes of discrepancy were between CSF and plasma/tissue were: two cases were CSF positive but had no extrathoracic disease to biopsy, 1 case was negative in the CSF for T790M but positive in plasma and on biopsy and one case was wild type in CSF but positive on plasma and biopsy for G719A+T790M mutation. Six pts (86%) received therapy after diagnosis of LM disease and OS from LM diagnosis ranged from 1.0 -15.8 months.Sex/ Age Therapy at diagnosis of CNS disease Duration of response to prior TKI (months) Therapy after diagnosis of CNS disease OS from diagnosis (months) OS from diagnosis of LM (months) Baseline EGFR mutation Tissue biopsy mutation profile CSF EGFR mutation profile (ddPCR) Plasma EGFR mutation profile (ddPCR) CSF cytology M/64 Nivolumab Erlotinib: 12.4 Gefitinib: 2.5 AZD3759 WBRT Osimertinib 52.7* 15.8* L858R L858R L858R + T790M L858R + T790M Positive - carcinoma F/68 Osimertinib Erlotinib: 18.2 Osimertinib: 7.2 Nil 28.6 1.7 L858R L858R + T790M Sample 1: L858R Sample 2: L858R + T790M N/A Sample 1 - negative Sample 2 - positive F/50 Osimertinib Erlotinib: 6.4 Osimertinib: 6.1 Erlotinib (1500mg weekly) 15.7 1.0 L858R L858R + T790M L858R L858R + T790M + C797S Positive - carcinoma F/79 Nil N/A Erlotinib (1500mg weekly) 74.5* 9.5* Exon 19 deletion No site for biopsy Exon 19 deletion Wild type Positive - carcinoma M/64 Erlotinib Erlotinib: 10.5 Erlotinib (1500mg weekly) 15.0 9.1 L858R No site for biopsy L858R Wild type Not performed F/63 Erlotinib Erlotinib: 5.9 Osimertinib 7.8* 1.3* G719A G719A + T790M WT G719A Not performed M/60 Erlotinib Erlotinib: 22.0 Erlotinib (1500mg weekly) 31.0* 7.4* Exon 19 deletion No site for biopsy Exon 19 deletion Exon 19 deletion Negative
Conclusion:
ddPCR is able to detect cfDNA in CSF, where other diagnostic modalities may be negative, and demonstrates both initial and resistance mutations. Heterogeneous mutation status may guide therapy when LM disease remains sensitive to targeted therapy.
