Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
of America, 7 University of California Davis School of Medicine, Sacramento/AL/
United States of America, 8 Guardant Health, Inc., Redwood City/CA/United States
of America, 9 Division of Hematology & Oncology, University of California Davis
Comprehensive Cancer Center, Sacramento/CA/United States of America
Background: Next generation sequencing (NGS) has been increasingly used
in oncology practice but proven practically difficult when serial tumor
specimens are needed. The objectives of this study were to determine
feasibility and explore clinical utility of serial NGS analyses of circulating
tumor DNA (ctDNA) in patients (pts) with advanced solid tumors undergoing
treatment. Methods: ctDNA digital NGS was performed by a CLIA-certified
lab (70-gene panel with mutant allele fraction (MAF) quantification). ctDNA
results were retrospectively analyzed and decreases/increases/stability of
molecular tumor load (MTL) defined here as MAFs of truncal driver mutations
were correlated with clinical and radiographic response to treatment
(response, progression, or stable disease, respectively). Results: From Jan
2015 to July 2016, 38 consecutive pts with advanced lung tumors (84% LUAD,
5% LUSC, 5% SCLC, 5% NOS) receiving treatment (Table) had serial ctDNA
analyses (median 2, range 2-7). ctDNA alterations were detected at least once
in 37 (97.4%) pts. Changes in MTL correlated with or predicted all (95% CI,
82.0-99.8%) radiological and/or clinical responses except for the patient with
no genomic alteration detected. MTL results clarified response status when
radiographic responses were difficult to assess in 9 (28%) of pts with either
complex pleural disease (n=6), pneumonitis during PD-1 inhibitor therapy (2).
Two MTL change patterns were observed: 1) clonal changes while receiving
targeted therapy, including EGFR (12), ALK (3), MET (2), ERBB2 (2); 2) global
changes to PD-1 inhibitors, chemotherapy or radiation. Representative tumor
response maps will be presented. Table. Summary of tumor types and cancer
treatment.
Cancer Type
Targeted
Therapy
Immunotherapy
Chemotherapy
Radiation
LUAD 14 8 7 3 32
LUSC 1 1 0 0 2
SCLC 0 0 2 0 2
NOS 1 0 1 0 2
All 16 9 10 3 38
TOTAL
Conclusion: Serial liquid biopsies and ctDNA digital NGS are feasible and
clinically useful in monitoring MTL and genomic alterations during cancer
treatment, especially in situations when radiographic responses are
equivocal. Prospective evaluation of impact on clinical decision making is
warranted.
Keywords: plasma, Circulating Tumor DNA, lung cancer, digital next
generation sequencing
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
ANALYSIS OF RNA –
TUESDAY, DECEMBER 6, 2016
P2.01-010 DOWNREGULATION OF PFTK1 BY SHRNA INHIBITS
MIGRATION AND INVASION OF HUMAN NON-SMALL CELL LUNG
CANCER CELL LINES
Wentao Yue 1 , Xiaoting Zhao 2 , Mei Jiang 1 , Yu Teng 1 , Lina Zhang 1 , Li Ma 1
1 Beijing TB and Thoracic Tumor Research Institute/beijing Chest Hospital, Capital
Medical University, Beijing/China, 2 Department of Cellular Biology, Beijing TB
and Thoracic Tumor Research Institute/beijing Chest Hospital, Capital Medical
University, Beijing/China
Background: PFTK1, a novel cyclin-dependent kinases, plays pivotal roles
in cell proliferation, differentiation and cell cycle regulation. It has been
reported that cell motility and invasiveness could be enhanced by PFTK1
in kinds of tumors. However, the function of PFTK1 in NSCLC metastasis is
not clear. The aim of this study was to explore the potential role of PFTK1
in NSCLC metastasis. Methods: Expression of protein PFTK1 was assessed
by immunohistochemistry staining in tissue microarrays, containing
paired tumor tissue and adjacent NSCLC tissue from 119 cases of human
lung cancer. PFTK1 was knocked down by shRNA interference method both
in human H1299 and 95C cells. Then we applied H1299 and 95C cells that
PFTK1 expression was inhibited into the next study. The effect of PFTK1 on
cell migration and invasion was explored by cell wound healing assay and
transwell assay. Western blot was used to detect whether PFTK1 influences
the expression of EMT related proteins β-catenin, vimentin and ZEB1.
Cytoskeleton preotein F-actin was observed using cell immunofluorescence
test. Results: Immunohistochemistry staining of 119 NSCLC patients showed
that a high level of PFTK1 expression was correlated with lymph node
metastasis and T stage(P