Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
negative. ADx, cobas, ddPCR, and firefly NGS uncovered 73, 69, 70, and 68
EGFR wild-type loci, respectively. The concordance and negative coincidence
rates between any two platforms were over 90%. Conclusion: The detection
rate and concordance were probably affected by the abundance of EGFR
mutations and the sensitivity of different platforms. Three platforms,
including cobas, ddPCR, and firefly NGS, exhibited higher positive coincidence
and detection rates when the allele frequency was lower than 1%.
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
JCES01.23 EGFR MUTATION STATUS ANALYSIS IN CEREBROSPINAL
FLUID AND PLASMA OF ADVANCED LUNG ADENOCARCINOMA
WITH BRAIN METASTASES
Liang Shi 1 , Zhe Liu 2 , Jungfang Tang 1 , Hongbo Wu 1 , Lili Guo 1 , Mingzhi Li 1 , Li
Tong 1 , Wei Wu 3 , Hong Tao 1 , Weihua Wu 1 , Hongxia Li 3 , Qiyi Meng 1 , Liyan Xu 1 ,
Yunzhong Zhu 1
1 Oncology, Beijing Chest HospitaL, Capital Medical University, Beijing/China,
2 Oncology, Beijing Chest Hospital, Capital Medical University, Beijing/China,
3 Beijing Chest Hospital, Beijing/China
Background: We aimed to investigate the feasibility of droplet digital PCR
(ddPCR) for the detection of epidermal growth factor receptor (EGFR)
mutations in circulating free DNA (cfDNA) from cerebrospinal fluid (CSF) and
plasma of advanced Lung Adenocarcinoma (ADC) with brain metastases (BM).
Methods: Fourteen advanced ADC patients with BM carrying activating EGFR
mutations in tumour tissues were enrolled in this study, and their matched
CSF and plasma samples were collected. EGFR mutations were detected by
the Amplification Refractory Mutation System (ARMS) in tumour tissues.
EGFR mutations, including 19del, L858R, and T790M were examined in cfDNA
isolated from 2milliliter CSF or plasma by ddPCR assay. The clinical response
was assessed according to Response Evaluation Criteria in Solid Tumors
(RECIST) version 1.1 guidelines. Overall survival (OS) and progression free
survival (PFS) after the diagnosis of BM were also evaluated. Results: Out of
14 patients, eleven were females and three males aged from 34 to 74 years
old (median age of 55 years old). In all of cases, CSF cytology were negative.
In ddPCR assays, EGFR mutations were detected in CSF of three patients
(21.4%; one of 19del and two of L858R), and in plasma of six patients (42.9%;
one of 19del, one of L858R, one of T790M, two of L858R&T790M, and one of
19del&T790M). All EGFR T790M mutations were found during or after EGFR-
TKIs treatments. The three patients with activating EGFR mutations in CSF
achieved partial response (PR) of BM after treated with combination of WBRT
and EGFR-TKIs. The median OS and PFS after the diagnosis of BM were 18.0
months and 9.0 months, respectively.
Patient
Tissue
EGFR
CSF
EGFR
Plasma
EGFR
Systematic Treatment
1 19del WT T790M Erotinib
+Chemotherapy
2 19del WT 19del
Erotinib
+Chemotherapy
3 L858R L858R L858R
Gefitinib
+Chemotherapy
4 L858R WT WT
Gefitinib
+Chemotherapy
5 19del WT WT
Gefitinib
+Chemotherapy
6 L858R WT
L858R/
T790M
Erotinib
+Chemotherapy
BM Treatment
WBRT
+Gamma knife
WBRT
WBRT
WBRT
WBRT
WBRT
7 L858R WT WT Gefitinib WBRT
8 19del 19Del
19Del/
T790M
Gefitinib WBRT
9 L858R WT WT
Erotinib
+Chemotherapy
NONE
10 19del WT WT
Erotinib
+Chemotherapy
WBRT
11 19del WT WT
Icotinib
+Chemotherapy
WBRT
12 L858R WT
L858R/
T790M
Chemotherapy WBRT
13 L858R L858R WT Icotinib WBRT
14 19del WT WT
Gefitinib
+Chemotherapy
WBRT
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
JCES01.24 MOLECULAR MECHANISM OF TRANSFORMATION FROM
ADENOCARCINOMA TO SMALL-CELL LUNG CANCER AFTER EGFR-
TKI
Jiefei Han 1 , Qiuyi Zhang 2 , Binchao Wang 3 , Qing Zhou 2 , Lixu Yan 3 , Zhou Zhang 3 ,
Huajun Chen 3 , Jian Su 4 , Zhi Xie 5 , Feiyu Niu 3 , Yi Long Wu 6 , Shannon Chuai 7 , Jinji
Yang 8 , Zhong-Yi Dong 5
1 Guangdong Lung Cancer Institute, Guangzhou/China, 2 Guangdong Lung Cancer
Institute; Guangdong General Hospital(GGH)& Guangdong Academy of Medical
Sciences, Guangzhou/China, 3 Guangdong Lung Cancer Institute, Guangdong
General Hospital & Guangdong Academy of Medical Sciences, Guangdong Key
Laboratory of Lung Cancer Translational Medicine, Guangzhou/China, 4 Guangdong
Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational
Medicine in Lung Cancer, Guangdong General Hospital & Guangdong Academy
of Medical Sciences, Guangzhou/China, 5 Guangdong Lung Cancer Institute,
Guangdong General Hospital, Guangzhou/China, 6 /, 7 Burning Rock Dx Ltd,
Guangzhou/China, 8 Guangdong Lung Cancer Institute, Institution: Guangdong
General Hospital and Guangdong Academy of Medical Sciences, Guangzhou/China
Background: In patients with advanced non–small-cell lung cancer (NSCLC)
harboring epidermal growth factor receptor (EGFR) activating mutations,
EGFR-tyrosine kinase inhibitors (TKIs) are recommended as first-line
treatment due to favorable clinical efficacy. However, acquired resistance
inevitably develops after median progression-free survival (PFS) of 9-14
months. Among the mechanisms of acquired resistance, small-cell lung cancer
(SCLC) transformation was reported to account for nearly 5%. However,
the molecular details underlying this histological change and resistance to
EGFR-TKI therapy remain unclear. Methods: 15 out of 233 (6.4%) patients
were confirmed to develop SCLC transformation after failure to EGFR-TKI.
We analyzed the clinical parameters of these patients by using chi-square
test and Kaplan-Meier analysis. To explore gene alterations that might
contribute to SCLC transformation, next generation sequencing (NGS) was
performed on four pairs of matched pre- and post-transformation tumor
tissue samples. We further performed NGS on 11 matched circulating tumor
DNA (ctDNA) to explore the potential mechanism of resistance to EGFR-TKI.
Results: The median age of SCLC transformed patients was 53 years. 93.3%
(14/15) patients harbored EGFR exon19 deletion. The median PFS and overall
survival (OS) of SCLC-transformed patients treated with EGFR-TKI compared
to those without transformation were 11.7 versus 11.9 months (P=0.473) and
29.4 versus 24.3 months (P=0.664), respectively. All 4 patients developed
loss of heterozygosity of TP53/RB1 after transformation. Besides, increased
copy number of five proto-oncogenes were identified in post-transformation
tissue samples. Three patients developed EGFR T790M mutation in the
post-transformation ctDNA rather than their tissue samples. Conclusion:
SCLC transformation was commonly seen in patients harboring EGFR exon 19
deletion. The clinical outcomes of TKI and OS in SCLC transformed patients
were similar to non-transformed patients. The loss of heterozygosity of TP53
and RB1along with increased copy number of proto-oncogenes may lead to
the SCLC transformation. The mechanisms of acquired resistance to TKI
during SCLC transformation might be the emergence of classic drug resistance
mutations, which was undetectable due to the intra-tumor heterogeneity.
Conclusion: It was feasible to test EGFR mutation in CSF. CSF may serve as
liquid biopsy of advanced ADC with BM by enabling measurement of cfDNA
within CSF to characterize EGFR mutations.
S124 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017