Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
prognostic for lung squamous cell carcinoma (SCC) under a NCI/SPECS
(Strategic Partnerships fo Evaluating Cancer Signatures) award. The study
design specifies a primary validation cohort comprising institutional cases,
and additional validation cohorts of Cooperative Group cases, all profiled via
a common pipeline. Methods: Completely resected SCC (confirmed by central
pathology review) meeting clinical (Stage I-II; complete 3-year follow-up)
and specimen quality criteria (Tumor cellularity ≥ 50%;necrosis ≤ 20%) were
submitted by 6 institutions. Clinical, pathological and outcome data were
uploaded to a central database. Lysates from 5 um sections of FFPE SSC tumor
samples were run on the HTG EdgeSeq Processor (HTG Molecular Diagnostics,
Tucson, AZ) using the miRNA whole transcriptome assay in which an excess of
nuclease protection probes (NPPs) complimentary to each miRNA hybridize
to their target. S1 nuclease then removes un-hybridized probes and RNA
leaving behind only NPPs hybridized to their targets in a 1-to-1 ratio. Samples
were individually barcoded (using a 16-cycle PCR reaction to add adapters and
molecular barcodes), individually purified using AMPure XP beads (Beckman
Coulter, Brea, CA) and quantitated using a KAPA Library Quantification
kit (KAPA Biosystems, Wilmington, MA). Libraries were sequenced on
the Illumina HiSeq platform (Illumina, San Diego, CA) for quantification.
Standardization and normalization was provided to the project statistical
core for validation of two pre-existing signatures and generation of new
models (MCP clustering). Results: Among 224 cases with miRNA data, median
age was 70 (43-92), 143 (64%) male, with 67% former (67%) and current (26%)
smokers. All patients were completely resected stage I or II. . At follow-up, 59
(26%) had documented recurrence and 129 (58%) were deceased. To date, we
have been unable to validate the previous models, but have created a novel
signature of three miRNAs (see Figure) that is being validated in the second
phase of the project using an independent, blinded multi-institutional cohort.
Conclusion: The Squamous Lung Cancer SPECS Consortium has established
well-annotated and quality-controlled resources for validation of prognostic
miRNA signatures. A new candidate 3-miRNA signature has been identified for
further development as a clinically useful biomarker.
Keywords: Squamous cell lung cancer, gene expression signature
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
TRANSLATIONAL RESEARCH & BIOMARKERS –
MONDAY, DECEMBER 5, 2016
P1.05-002 THE PROGNOSTIC IMPACT OF EGFR MUTATION STATUS
AND MUTATION SUBTYPES IN PATIENTS WITH SURGICALLY
RESECTED LUNG ADENOCARCINOMAS
Kazuya Takamochi, Shiaki Oh, Takeshi Matsunaga, Kenji Suzuki
Juntendo University School of Medicine, Tokyo/Japan
Background: EGFR mutation status is a well-established predictor of the
efficacy of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer.
Recently, the differences in EGFR mutation subtypes were also reported to be
associated with the efficacy of EGFR TKIs. However, the prognostic impact of
EGFR mutation status and mutation subtypes remains controversial. Methods:
We retrospectively reviewed 945 consecutive patients with surgically resected
adenocarcinomas who had their EGFR mutation status analyzed between
January 2010 and December 2014. Overall survival (OS) and recurrence-free
survival (RFS) were analyzed in three cohorts (all patients, pathological stage I
patients, and patients with exon 21 L858R point mutation or exon 19 deletions)
using Kaplan-Meier methods and Cox regression models. Results: The median
follow-up time was 42 months. The results for EGFR mutation status, mutation
subtype, and the comparison data of OS/RFS are summarized in the attached
Table. Positive EGFR mutation status was significantly associated with longer
OS/RFS in all patients and was also associated with longer OS in pathological
stage I patients. However, no significant differences were observed in OS/
RFS between patients with exon 21 L858R point mutation and those with
exon 19 deletions. In a Cox regression model for OS, the EGFR mutation status
was a significant prognostic factor that was independent of well-established
prognostic factors such as age, pathological stage, vascular invasion,
lymphatic permeation, and serum CEA level.
3y-RFS 5y-RFS P 3y-OS 5y-OS P
All Pts 0.009 < 0.001
EGFR mut+
(N = 423)
EGFR mut-
(N = 522)
84.6% 76.7% 95.2% 89.0%
78.8% 71.2% 84.9% 76.5%
p stage I Pts 0.102 < 0.001
EGFR mut-
(N = 392)
90.6% 82.8% 92.6% 85.9%
Subtypes 0.385 0.507
Ex 21 L858R
(N = 224)
Ex 19 del
(N = 164)
84.8% 79.6% 95.2% 90.0%
84.7% 74.3% 97.5% 95.8%
Conclusion: Positive EGFR mutation status is a favorable prognostic factor
in patients with surgically resected lung adenocarcinomas. However, EGFR
mutation subtypes (exon 21 L858R point mutation or exon 19 deletions) have
no prognostic impact.
Keywords: progonostic factor, EGFR, lung adenocarcinoma
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
TRANSLATIONAL RESEARCH & BIOMARKERS –
MONDAY, DECEMBER 5, 2016
P1.05-003 COEXPRESSION OF CD8A AND PD-L1 FREQUENTLY
OBSERVED IN RESECTED NSCLC TUMORS FROM SMOKERS
Aaron Lisberg 1 , Robert Mckenna 2 , Judy Dering 1 , Hsiao-Wang Chen 1 , Naeimeh
Kamranpour 1 , Dongmei Hou 1 , Maria Velez 1 , Robert Cameron 3 , Jay Lee 3 , Steven
Dubinett 3 , Dennis Slamon 1
1 Translational Oncology Research Laboratory, UCLA Medical Center, Santa Monica/
CA/United States of America, 2 St John’s Health Center, Santa Monica/CA/United
States of America, 3 David Geffen School of Medicine at UCLA, Los Angeles/CA/
United States of America
Background: With the approval of anti-programmed cell death-1 (PD-1)
therapy in advanced non-small cell lung cancer (NSCLC), identifying patients
with early stage disease most likely to benefit from therapy has become a
priority. It has been hypothesized that patients whose tumors show evidence
of PD-1 mediated T cell exhaustion, via the presence of both tumor infiltrating
lymphocytes (TILs) and PD-L1 expression, are more likely to respond to
anti-PD-1 therapy (Teng et al, 2015). The current study utilized microarray
analysis to evaluate the relationship between both clinicopathologic features
and overall survival (OS) with tumor microenvironment (TME) composition.
Methods: Gene expression microarray analysis was performed using the
Agilent Whole Human Genome 4x44K 2-color platform for 319 NSCLC and 15
normal resection specimens. The reference sample was an equal mixture of
258 of the NSCLC samples. Rosetta Resolver and Statistica 13.0 were used
for analysis. Samples with PD-L1 expression levels greater or unchanged from
reference level were classified as positive, while those significantly lower [log
(ratio)