Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Keywords: non-small cell lung cancer, survival, variants of invasive
adenocarcinoma, gene abnormality
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
P1.02-013 CLINICOPATHOLOGICAL CHARACTERISTICS AND
SURVIVAL OF ALK, ROS1 AND RET ARRANGEMENTS IN NON-
ADENOCARCINOMA NON-SMALL CELL LUNG CANCER PATIENTS
Zhengbo Song 1 , Xinmin Yu 2 , Yiping Zhang 2
1 Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer
Hospital, Hangzhou/China
Background: ALK, ROS1 and RET rearrangements represent three
most frequency of fusion genes in non-small cell lung cancer (NSCLC).
Rearrangements of the three genes are predominantly found in lung
adenocarcinoma, while,rare in non-adenocarcinoma. The aim of this study
was to investigate the frequency, clinicopathological characteristics and
survival of ALK, ROS1 and RET arrangements in non-adenocarcinoma
NSCLC patients. Methods: We screened ALK,ROS1 and RET arrangements in
patients with completely resected non-adenocarcinoma NSCLC using reverse
transcriptase polymerase chain reaction (PCR). All positive samples were
confirmed with fluorescence in situ hybridization (FISH). Survival analysis
was performed with Kaplan-Meier method and log-rank for comparison.
Results: Totally, 385 patients, who underwent complete resection, including
245 with squamous cell carcinoma, 85 with adenosquamous carcinoma and
55 with large cell carcinoma were enrolled. Twelve patients were identified
as harboring fusion genes,including seven with ALK, three with ROS1 and
two with RET rearrangements. The frequencies of fusions in adenosquamous
carcinoma, squamous cell carcinoma, and large cell carcinoma were 8.2%,1.6%
and 1.8%, respectively. The median age of 12 patients was 49.5 years and
three patients had smoking history. No survival difference existed between
fusion genes positive and negative patients (36.7 vs.50.2 months,P=0.21).
Conclusion: The frequencies of ALK, ROS1 and RET rearrangements are low
in non-adenocarcinoma NSCLC patients, and the clinical characteristics are
similar with those in lung adenocarcinoma. Fusions of the three genes are not
prognostic marker for non-adnocarcinoma NSCLC patients.
Keywords: fusion gene, frequency, survival, non-small cell lung cancer
P1.02-015 A MULTICENTER STUDY OF EGFR AND EML4-ALK
DETECTION IN NON-SQUAMOUS, NON-SMALL-CELL LUNG CANCER
PATIENTS WITH MALIGNANT PLEURAL EFFUSION
Xun Shi 1 , Zhengbo Song 2 , Xinmin Yu 1 , Yiping Zhang 1
1 Zhejiang Cancer Hospital, Hangzhou/China, 2 Medical Oncology, Zhejiang Cancer
Hospital, Hangzhou/China
Background: Currently, multicenter studies involving a large number of
patients have not been not undertaken to detect the frequencies of EGFR
mutations and ALK rearrangement in malignant pleural effusion (MPE)
samples of patients with non-squamous, non-small-cell lung cancer (NSCLC),
we undertook a multicenter, observational study of Asian patients with
untreated stage IV NSCLC. Methods: Eligible patients had untreated of EGFR
and ALK inhibitor stage IV non-squamous NSCLC patients with MPE. The EGFR
and ALK status of MPE and partially paired tumor tissue was determined with
reverse transcription polymerase chain reaction (RT-PCR). Results: Among 210
patients with pleural effusion samples confirmed as malignant, 16 had EML4-
ALK fusion gene rearrangements and 89 had EGFR mutations. No ALK/EGFR
coaltered gene was found. Tumor tissue of 56 patients were collected. EGFR
and ALK concordance rates between MPE samples and matched tumor tissue
samples from 56 patients were 87.5% (49/56) and 96.1% (49/51), respectively.
There was a tendency for a longer progression free survival in patients with
EGFR accordance in comparison with those with EGFR discordance between
tumor tissue and MPE samples (9.8 vs 6.2 months, respectively; p = 0.078).
A same trend was found in patients with ALK accordance and discordance
(10.0 vs 3.2 months, respectively; p = 0.004) . Conclusion: These results
demonstrate that MPE can be substituted for tumor tissues for EGFR and ALK
gene detection. Patients with gene mutations or arrangement discordance
between tumor tissue and MPE samples showed a inferior efficacy of targeted
therapy than those with accordance.
Keywords: Epidermal growth factor receptor, Anaplastic lymphoma kinase,
malignant pleural effusion, Non-small-cell lung cancer
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
P1.02-014 HER2 MUTATIONS IN CHINESE PATIENTS WITH NON-
SMALL CELL LUNG CANCER
Zhengbo Song, Yiping Zhang
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China
Background: ERBB2 (HER2) is a driver gene identified in non-small cell
lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability
and treatment of HER2-positive NSCLC in Chinese population are unclear.
Methods: Eight hundred and fifty-nine patients with pathologically
confirmed NSCLC were screened for HER2 mutations using Sanger
sequencing. Next-generation sequencing (NGS) was performed in positive
cases. HER2 amplification was detected with FISH. Overall survival (OS) was
evaluated using Kaplan-Meier methods and compared with log-rank tests.
Results: Twenty-one cases carrying HER2 mutations were identified with
a prevalence of 2.4%. HER2 mutations were more frequently encountered
in females, non-smokers and adenocarcinoma. NGS was performed in 19
out of 21 patients, The results showed 16 cases with additional genetic
aberrations, most commonly associated with TP53 (n = 6), followed by EGFR
(n = 3), NF1 (n = 3), KRAS (n = 2) and other mutations. One patient harbored
HER2 amplification(figure 1). Four patients with stage IV received afatinib
treatment, and three showed stable disease with a median progression-free
survival of 4 months and one patient was diagnosed with progressive disease.
No survival difference existed between HER2 positive and negative patients(
(49.3 months vs.45.0 months, P = 0.150). Conclusion: HER2 mutations
represent a distinct subset of NSCLC. NGS showed that HER2 mutations
commonly co-existed with other driver genes. Afatinib treatment displayed
moderate efficacy in patients with HER2 mutations.
Keywords: PREVALENCE, treatment, HER2 mutation, genetic variability
P1.02-016 HER4 EXPRESSION WAS RELATED TO THE SENSITIVITY
OF EGFR-TKI IN NON-SMALL CELL LUNG CANCER
Masaaki Inoue, Junichi Yoshida, Takashi Iwanami, Yusuke Nabe, Masatoshi
Kanayama, Daisei Yasuda
Chest Surgery, Shimonoseki City Hospital, Shimonoseki/Japan
Background: EGFR-TKIs show significant therapeutic effects against nonsmall
cell lung cancer (NSCLC) with EGFR-activating mutations, however
20-30% of them have no response to EGFR-TKIs. HER-family receptors play
a critical role in tumor progression, differentiation and survival in lung
cancer. Recent studies suggest that the overexpression of HER-family
receptors have a potential risk of EGFR-TKIs resistance. The aims of this
study were to investigate the association between EGFR-mutation and the
expression of HER-family receptor in regard to clinical outcomes. Methods:
We invested EGFR mutation by direct PCR analysis and HER2-4 expression
by immunohistochemistry (IHC) of 231 consecutive non-small cell lung
cancers, who had undertaken an operation from January 2007 to July 2012.
The intensity of HER2-4 was graded (score: 0-3) from negative (score: 0-1) to
positive (score: 2-3). The observed protein expression levels were analyzed
for correlation to EGFR mutation status, clinicopathological parameters and
the responses of EGFR-TKI treatment. Results: EGFR mutation was observed
in 40% of lung cancer, 61% of p.[Leu858Arg]and 31% of exon 19 deletion.
Positive expression rates of HER2, HER3 and HER4 were 22.9%, 1.2%, 38.5%,
respectively. HER4 positive rare of EGFR positive group was significantly
higher than that of EGFR negative group (52% vs 30%, P