S172
1S
the service of personalized medicine for lung
cancer. Oncotarget 2016; http://dx.doi.org/10.18632/
oncotarget.11717. 3. Nishino M, Giobbie-Hurder A,
Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a
common language for tumor response to immunotherapy:
immune-related response criteria using unidimensional
measurements. Clin Cancer Res 2013; 19: 3936-43. 4.Di
Maio M, Basch E, Bryce J, Perrone F. Patient-reported
outcomes in the evaluation of toxicity of anticancer
treatments. Nat Rev Clin Oncol 2016; 13: 319-25.
Keywords: clinical trials, Monitoring, treatment
outcome, oncology practice
MTE21.01
Next Generation Sequencing
Ignacio Wistuba,1 Xuefei Li2 1Translational
Molecular Pathology, The University of Texas MD
Anderson Cancer Center, Houston/United States of
America, 2Medical Oncology, Shanghai Pulmonary
Hospital, Shanghai/China
Non-small cell lung cancer (NSCLC) with sensitive
epidermal growth factor receptor (EGFR) mutations
invariably develop resistance to EGFR tyrosine kinase
inhibitors (TKIs). 20%-30% of NSCLC patients harboring
sensitive mutations have no good initial clinical response
to EGFR-TKIs, which is dened as having intrinsic
resistance to EGFR-TKIs; while the rest of patients with
activating mutations who are initially responsive to
EGFR-TKIs eventually develop acquired resistance after
10e12 months of consistent clinical benet, followed
by disease progression. The drug resistance is a really
tough and urgent clinical problem. Part of resistant
mechanisms have been reported, including BIM deletion
polymorphism, combined with other bypass signal
pathway activation, epithelial-mesenchymal transition
(EMT) for primary resistance; T790M, cMET amplica-
tion, SCLC transformation for acquired resistance. How-
ever, partial resistant mechanisms still unknown. In
contrast to acquired resistance to EGFR-TKIs, intrinsic
resistance is more complicated. Next-generation
sequencing (NGS) is a promising tool for analysis of tu-
mor mutations. We aimed to investigate the intrinsic
resistant mechanisms to EGFR-TKIs by NGS, further to
optimize treatment strategies and improve clinical
outcome in EGFR activating mutant patients having
intrinsic resistance to EGFR-TKIs. At present, the study
is underway, and the results will be presented at the
2016 WCLC.
Keywords: next-generation sequencing, NSCLC, EGFR-
TKIs, drug resistance
Journal of Thoracic Oncology Vol. 12 No.
MTE22.01
Perspectives in Lung Cancer Imaging
Thomas Henzler Institute of Clinical Radiology
and Nuclear Medicine, University Medical Center
Mannheim, Medical Faculty Mannheim, Heidelberg
University, Mannheim/Germany
Lung cancer is still the leading cause of cancer-related
death in both men and women with 80% to 85% of
cases being non-small-cell lung cancer (NSCLC).1 Over
the past years, the IASLC Staging and Prognostic Fac-
tors Committee has collected a new database of 94,708
cases of lung cancer as the backbone for the upcoming
8th edition of the TNM classication for lung cancer due
to be published late 2016.2,3 The 8th edition will
signicantly impact lung cancer staging with CT and/or
PET-CT due to the subclassication of T1 and T2 into
a,b and c categories, the reclassication of tumors more
than 5 cm but not more than 7 cm in greatest dimension
as T3, the reclassication of tumors more than 7 cm in
greatest dimension as T4, the grouping of the involve-
ment of the main bronchus as a T2 descriptor, regard-
less of distance from the carina, but without invasion of
the carina, the grouping of partial and total atelectasis
or pneumonitis as a T2 descriptor, the reclassication
of diaphragm invasion as T4 and the elimination of
mediastinal pleura invasion as a T descriptor.2,3 More-
over, the upcoming 8th edition will also lead to a novel
classication of distant metastasis, in which single
extrathoracic metastasis will be classied as M1b
whereas multiple extrathoracic metastasis are classied
as M1c. The changes made within the proposal of the
8th edition of the TNM will be discussed within the
presentation using clinical examples. Besides the accu-
rate staging of patients with lung cancer early detection
using CT screening with novel low radiation dose CT
technologies will also be discussed. Within this context,
a special focus will be given on novel methods that may
improve a more accurate characterization of detected
lung nodules using deep machine learning and Radio-
mics. Radiomics refers to the comprehensive quanti-
cation of lung nodule and tumor phenotypes by
applying a large number of quantitative image features
that are standardized collected with specic software
algorithms. Radiomics features have the capability to
further enhance imaging data regarding prognostic tu-
mor signatures, detection of tumor heterogeneity as
well as the detection of underlying gene expression
patterns which is of special interest in patients with
metastatic disease. The third part of the presentation
will focus on novel techniques in lung cancer imaging.
The past fteen years have brought signicant
January 2017
breakthroughs in the understanding of the molecular
biology of lung cancer. Signaling pathways and genetic
driver mutations that are vital for tumor growth have
been identied and can be effectively targeted by novel
pharmacologic agents, resulting in signicantly
improved survival of patients with lung cancer.4 Par-
allel to the progress in lung cancer treatment, imaging
techniques aiming at improving diagnosis, staging,
response evaluation, and detection of tumor recurrence
have also considerably advanced in recent years.5
However, standard morphologic computed tomography
(CT) and magnetic resonance imaging (MRI) as well as
uor-18-uorodeoxyglucose (18F-FDG) positron emis-
sion tomography CT (PET-CT) are still the currently
most frequently utilized imaging modalities in clinical
practice and most clinical trials.6,7 Novel state-of-the-
art functional imaging techniques such as dual-energy
CT (DECT), dynamic contrast enhanced CT (DCE-CT),
diffusion weighted MRI (DW-MRI), perfusion MRI, and
PET-CT with more specic tracers that visualize
angiogenesis, tumor oxygenation or tumor cell prolif-
eration have not yet been broadly implemented, neither
in clinical practice nor in phase IeIII clinical trials. In
this context, Nishino et al.4 published an article on
personalized tumor response assessment in the era of
molecular treatment in oncology. The authors showed
that the concept of personalized medicine with regard
to cancer treatment has been well applied in thera-
peutic decision-making and patient management in
clinical oncology. With regard to imaging techniques,
however, it was criticized that the developments in
tumor response assessment that should parallel the
advances in cancer treatment are not sufcient to
produce state-of-the-art functional information that
directly reect treatment targets. Functional informa-
tion on tumor response is highly required because
there is growing evidence that the current objective
criteria for treatment response assessment may not
reliably indicate treatment failure and do not
adequately capture disease biology. Molecular-targeted
therapies and novel immunotherapies induce effects
that differ from those induced by classic cytotoxic
treatment including intratumoral hemorrhage, changes
in vascularity, and tumor cavitation. Thus, conventional
approaches for therapy response assessment such as
RECIST or WHO criteria that exclusively focus on the
change in tumor size are of decreasing value for drug
response assessment in clinical trials.8,9 In summary,
the aim of this presentation is to provide an overview
on the changes made within the upcoming 8th of the
TNM classication as well as to provide an overview on
state-of-the-art imaging techniques for lung cancer
screening, staging, response evaluation as well as
Abstracts S173
surveillance in patients with lung cancer. The various
techniques will be discussed regarding their pros and
cons to further provide functional information that best
reects specic targeted therapies including anti-
angiogenetic treatment, immunotherapies and stereo-
tactic body radiation therapy.
References: 1. Rami-Porta R, Crowley JJ, Goldstraw P.
The revised TNM staging system for lung cancer. Ann
Thorac Cardiovasc Surg 2009;15:4-9. 2. Asamura H,
Chansky K, Crowley J, et al. The International Association
for the Study of Lung Cancer Lung Cancer Staging Proj-
ect: Proposals for the Revision of the N Descriptors in the
Forthcoming 8th Edition of the TNM Classication for
Lung Cancer. Journal of thoracic oncology: ofcial pub-
lication of the International Association for the Study of
Lung Cancer 2015;10:1675-84. 3. Rami-Porta R, Bolejack
V, Crowley J, et al. The IASLC Lung Cancer Staging
Project: Proposals for the Revisions of the T Descriptors
in the Forthcoming Eighth Edition of the TNM Classi-
cation for Lung Cancer. Journal of thoracic oncology :
ofcial publication of the International Association for
the Study of Lung Cancer 2015;10:990-1003. 4. Rengan
R, Maity AM, Stevenson JP, Hahn SM. New strategies in
non-small cell lung cancer: improving outcomes in che-
moradiotherapy for locally advanced disease. Clin Cancer
Res 2011;17:4192-9. 5. Miles K. Can imaging help
improve the survival of cancer patients? Cancer Imaging
2011;11 Spec No A:S86-92. 6. Nishino M, Jackman DM,
Hatabu H, Janne PA, Johnson BE, Van den Abbeele AD.
Imaging of lung cancer in the era of molecular medicine.
Acad Radiol 2011;18:424-36. 7. Nishino M, Jagannathan
JP, Ramaiya NH, Van den Abbeele AD. Revised RECIST
guideline version 1.1: What oncologists want to know
and what radiologists need to know. AJR Am J Roent-
genol 2010;195:281-9. 8. Oxnard GR, Morris MJ, Hodi FS,
et al. When progressive disease does not mean treatment
failure: reconsidering the criteria for progression. J Natl
Cancer Inst 2012;104:1534-41. 9. Stacchiotti S, Collini P,
Messina A, et al. High-grade soft-tissue sarcomas:
tumor response assessmentpilot study to assess the
correlation between radiologic and pathologic response
by using RECIST and Choi criteria. Radiology
2009;251:447-56.
Keywords: Imaging of lung cancer, lung cancer, Radio-
mics, functional imaging
MTE23.01
Biomarker Characterization: Challenges
and Perspectives
Leonhard Mllauer Institute of Pathology, Medical
University Vienna, Vienna/Austria