Annual Meeting Proceedings Part 1 - American Society of Clinical ...

466s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7060 General Poster Session (Board #37C), Sat, 1:15 PM-5:15 PM
miRNA profiling in resectable NSCLC by multiplex next-generation sequencing.
Presenting Author: Sandra Gallach, Fundación para la Investigación
del Hospital General Universitario de Valencia, Valencia, Spain
Background: Early-stage NSCLC has a relapse rate around 40% within 5
years. With the advent of microRNA (miRNA), which seems to regulate
many genes critical for tumorigenesis, there is a growing interest in the
characterization of miRNAome in NSCLC specimens and to correlate them
with prognosis. Next generation sequencing is a useful tool to study the
miRNA content of solid tumors. Here, we applied high-throughput SOLiD
transcriptome sequencing to study miRNAs expression in a cohort of
early-stage NSCLC patients (tumor vs normal lung). Methods: RNA was
isolated from frozen lung specimens (tumor and normal lung) from
resectable NSCLC patients (n�35). Samples with a RIN � 7 were analyzed
and enriched in the miRNA fraction. miRNAs were sequencing using a
bar-code multiplex SOLiD protocol. Data normalization was carried out by
rescaling all data according to their counts. Readings were mapped against
mature and no-mature miRNAs using miRBase. Statistical analysis was
performed with CLCbio software and considered significant when padj�0.005.
Results: Using the SOLiD high throughput sequencing, we
performed a systemic miRNA expression profiling analysis of paired
samples (tumor vs normal lung). A total of 1268 miRNAs (mature and
no-mature) have been detected in at least one sample. The differential
expression between normal and tumor samples shown that 6 miRNAs
(miR-193b, miR-182, miR-96, miR-148a, miR-299, miR-590) were
upregulated and 7 (miR-145, miR-133a, miR-218, miR-125a, miR-30a,
miR-126 and miR-139) were down-regulated significantly in tumor samples
compared with normal lung tissues. We are performing studies using
qRT-PCR in an independent cohort to further validate these findings.
Conclusions: The deep sequencing technology used for differential miRNA
expression is useful and novel. The use of barcoding allows multiplexing
and lowers cost per sample. Several miRNAs were differentially expressed
between tumor and normal tissue, but this point needs to be further
validated in an independent cohort. Supported by grants TRA09-0132
(MICINN) and RD06/0020/1024 (ISCIII).
7062 General Poster Session (Board #37E), Sat, 1:15 PM-5:15 PM
Comparative effectiveness of five treatment strategies for early-stage
non-small cell lung cancer in the elderly. Presenting Author: Shervin
Shirvani, University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Early-stage lung cancer incidence among older adults is
expected to increase due to demographic trends and CT-based screening,
yet optimal treatment in the elderly remains controversial. Using the
SEER-Medicare cohort spanning 2001-2007, we determined survival
outcomes associated with five strategies used in contemporary practice.
Methods: Treatment strategy and covariates were determined in 10,923
patients age�66 with stage IA-IB non-small cell lung cancer. Cox regression,
adjusted for patient and tumor factors, compared overall and
disease-specific survival for lobectomy, sublobar resection, conventional
radiation, stereotactic body radiotherapy (SBRT) and observation. In a
second analysis, propensity-score matching was used for pairwise comparison
of SBRT with other strategies. Results: Median age was 75 years and
29% had substantial comorbidity. Treatment distribution was lobectomy
(59%), sublobar resection (11.7%), conventional radiation (14.8%),
observation (12.6%), and SBRT (1.1%). In unmatched Cox regression with
median follow up of 3.2 years, SBRT was associated with the lowest risk of
death within six months of diagnosis (HR 0.47; 95%CI 0.37-0.61; referent
is lobectomy). After six months, sublobar resection and SBRT were
associated with similar overall survival (P�0.51) and were both modestly
worse than lobectomy. With propensity-score matching, survival after SBRT
was similar to lobectomy (HR 0.90; 95%CI 0.64-1.27). Conventional
radiation and observation were associated with poor outcomes in all
analyses. Disease-specific survival outcomes followed similar trends.
Conclusions: This population-based experience provides strong support of
SBRT as an alternative to surgery or conventional radiation for select
patient populations. Evaluation of this new therapy in randomized trials is
urgently needed.
7061 General Poster Session (Board #37D), Sat, 1:15 PM-5:15 PM
SOX2 and FGFR1 gene copy number in surgically resected non-small cell
lung cancer (NSCLC). Presenting Author: Luca Toschi, Humanitas Cancer
Center, Rozzano, Italy
Background: SOX2 is a member of the SRY-related HMG-box family of
transcription factors and has been shown to be frequently amplified and
overexpressed in squamous cell lung cancer, with conflicting results
regarding its prognostic relevance. Similarly, FGFR1, a transmembrane
tyrosine kinase receptor belonging to the fibroblast growth factor receptor
family, has been recently reported to be amplified in squamous cell lung
carcinomas, suggesting a potential role for FGFR1 as a therapeutic target in
NSCLC. Aim of the present study is to evaluate SOX2 and FGFR1 gene copy
number in surgically resected NSCLCs, to investigate their prognostic
relevance and their association with clinico-pathological characteristics.
Methods: SOX2 and FGFR1 gene copy number was assessed by fluorescence
in situ hybridization (FISH) in tissue microarray cores from 447
surgically resected NSCLCs. Each patient was given a score ranging from 1
to 6 according to increasing mean copy number per cell of each gene, with
6 indicating true gene amplification. Results: SOX2 and FGFR1 FISH was
successfully performed in 445 patients (pts), which were grouped as �
(score 5-6) and - (score 1-4). Using this scoring system 105 (23.6%) pts
tested SOX2�, while 74 (16.6%) pts resulted FGFR1�. True gene
amplification for SOX2 and FGFR1 was observed in 19 (4.3%) and 37
(8.3%) cases, respectively. SOX2� and FGFR1� status was significantly
associated with squamous histology (p�.001). Additionally, SOX2� pts
had a significantly higher chance of being former/current smokers, male
and FGFR1�. FGFR1 gene status had no prognostic impact in the whole
population and in the squamous cell carcinoma subgroup. Conversely,
SOX2� pts had significantly longer overall survival compared with SOX2pts
(HR 0.68, p�.020). When restricting survival analysis to squamous cell
histology, stage I-II SOX2� pts had a significant survival advantage
compared with SOX2- group (HR 0.38, p�.006), while no difference was
observed in stage III-IV pts. Conclusions: Increased SOX2 and FGFR1 gene
copy number is a common event in lung cancer pts with squamous cell
histology. SOX2 gene gain is a favorable prognostic factor in surgically
resected pts, particularly in early stage squamous cell cancers.
7063 General Poster Session (Board #37F), Sat, 1:15 PM-5:15 PM
FGFR1 amplification in squamous cell lung cancers. Presenting Author:
Michele L. Cote, Karmanos Cancer Institute, Wayne State University,
Detroit, MI
Background: Squamous cell carcinoma of the lung (SqCCL) is the second
most common type of lung cancer. There are currently no established
targeted therapies that take advantage of SqCCL-specific genetic abnormalities.
Amplification of the fibroblast growth factor receptor type 1 gene
(FGFR1) has been identified as a driver event in breast cancers and in
SqCCL. The demographic characteristics and prognosis of patients with
these tumors remains to be defined. Methods: DNA from 123 surgically
resected, fresh frozen, and clinically annotated SqCCLs was extracted
using a resin-based or phenol-based methodology. DNA quantity and
quality was assessed using the Quantifiler kit (ABI). Specimen histology
was validated, and the proportion of tumor cells was �60%. Copy number
variation (CNV) analysis was performed using quantitative PCR with
primers specific for exons 12 and 16 of FGFR1 and data analysis using
CopyCaller (ABI). Samples with a predicted CNV of at 2 or greater in at least
one exon were scored as amplified. Chi-squared tests were used to examine
clinical and demographic differences between patients with and without
amplification of FGFR1. Survival differences were examined by Kaplan
Meier and Cox regression models. Results: Men comprised the majority of
the population (n�91, 74%) and most cases were pathological stage I
(n�75, 61%) or stage II (n�32, 26%). Thirty (24.4%) tumors showed
amplification of FGFR1. There was no association between amplification
and sex (p�0.18) or stage (p�0.37). The majority of the patients were
white (n�114, 92.7%), but the proportion of tumors that were amplified
was higher among non-whites (5/9, 55.5%) than whites (25/114, 21.9%,
p�0.02). Overall, median survival was 32.2 months. In univariate survival
analysis, amplification was associated with an increased hazard of death
(HR�1.55, Wilcoxon p�0.03). Tumor stage at diagnosis was also associated
with increased risk of death (HR�1.67, p�0.0009). Only stage
remained a significant predictor of death in the multivariate survival models
(HR�1.65, p�0.004). Conclusions: Somatic amplification of FGFR1 is a
relatively common event in SqCCL and may be associated with race and
overall survival.
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