Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
with superior results to conventional cytotoxic chemotherapy. At this time,
there is no approved targeted therapy for SCLC. In order to develop targeted
therapies we need to identify and characterize molecular targets
(alterations). This study aims to report our experience with genomic
sequencing of SCLC Methods: We performed a retrospective analysis of a
dataset of 54 cases of SCLC, who underwent genomic sequencing. Patients
were treated at 5 tertiary referral centers, between October 2012 and June
2016. The recorded data included: age at diagnosis, date of the genomic
sequencing, genomic alteration (affected genes and the type of molecular
alteration identified). For genomic profiling we used a platform commercially
available (FoundationOne). Results: We obtained 54 samples from 54
patients. Age range is 42 to 75 years, mean 60 and median 61 years old. All
cases had a histologic diagnosis of SCLC. The genomic analysis found 88
affected genes with 230 alterations. The most common affected genes: Tp53
alteration, 45 cases (83%) and Rb1 33 cases (61%). There were an average of 4.3
mutations per patient; with a median of 4 mutations per patient, with a
minimum of 0 and a maximum of 13.
cannot induce enough ADCC activity. Delivery of a cytotoxic agent DM1 to the
inside of cells via HER2-mediated internalization is expected and crucial to
exert antitumor effect in such ADCC-lacking SCLC cells.
Keywords: HER2, trastuzumab emtansine, SCLC, T-DM1
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
MOLECULAR CHANGES –
MONDAY, DECEMBER 5, 2016
Conclusion: Sustained investigations and sequencing of larger numbers of
SCLC are aiming to identify potential actionable mutations in these tumors.
The ultimate goal is to determine new therapies and optimal treatment
strategy based on the genomic profile.
Keywords: small cell, genomic alteration
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
MOLECULAR CHANGES –
MONDAY, DECEMBER 5, 2016
P1.07-033 TRASTUZUMAB EMTANSINE (T-DM1) SUPPRESSES
THE GROWTH OF HER2-POSITIVE SMALL-CELL LUNG CANCER IN
PRECLINICAL MODELS
Osamu Morimura 1 , Toshiyuki Minami 2 , Takashi Kijima 1 , Shohei Koyama 3 ,
Tomoyuki Otsuka 1 , Yuhei Kinehara 1 , Akio Osa 1 , Masayoshi Higashiguchi 1 ,
Kotaro Miyake 1 , Izumi Nagatomo 1 , Haruhiko Hirata 1 , Kota Iwahori 1 , Takayuki
Takimoto 2 , Yoshito Takeda 1 , Hiroshi Kida 1 , Atsushi Kumanogoh 1
1 Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka
University Graduate School of Medicine, Suita/Japan, 2 Department of Oncology
Center, Osaka University School of Medicine, Suita/Japan, 3 Department of
Immunopathology, Immunology Frontier Research Center, Osaka University, Suita/
Japan
Background: To overcome chemoresistance is indispensable to bring about
better prognosis in small-cell lung cancer (SCLC). We have reported that
HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance.
Moreover, HER2-upregulated cisplatin- or etoposide-resistant SCLC cells
were sensitive to trastuzumab-mediated antibody-dependent cell-mediated
cytotoxicity (ADCC). However, irinotecan-resistant SCLC cells, e.g. SBC-3/SN-
38, were refractory to trastuzumab despite high HER2 expression. To address
this issue, we studied the antitumor efficacy of trastuzumab emtansine
(T-DM1) on trastuzumab-resistant HER2-positive SCLC. Methods: SBC-3/
SN-38 (HER2-positive) or OS2RA (HER2-negative) SCLC cells were inoculated
subcutaneously in the flank of six-week-old male nude mice. Tumor size was
measured with a caliper two or three times per week. When tumor volume
reached about 150-200 mm 3 , mice were randomly assigned to three treatment
groups. Each group was treated with intravenous injection of T-DM1 15 mg/
kg, intraperitoneal injection of trastuzumab 30 mg/kg, or saline as control. To
confirm the HER2-specific delivery of T-DM1, in vivo imaging was performed.
Namely, several tumor-bearing mice were intravenously administered with
fluorescence-labeled T-DM1. Fluorescence images of mice were captured
with IVIS® Lumina II system (PerkinElmer). Results: Treatment with T-DM1
significantly suppressed the growth of SBC-3/SN-38 xenografts compared
with trastuzumab and saline groups. Histological analysis revealed that T-DM1
remarkably induced apoptosis and inhibited proliferation. Fluorescencelabeled
T-DM1 definitely accumulated to the xenografts in a HER2-selective
fashion. Conclusion: T-DM1 treatment could be an attractive therapeutic
option in trastuzumab-resistant HER2-positive SCLC where trastuzumab
P1.07-034 SOMATOSTATIN RECEPTORS EXPRESSION IN SMALL
CELL LUNG CANCER PATIENTS
Efimia Boutsikou 1 , George Gerasimou 2 , Dionisios Spyratos 1 , Ellada
Eleptheriadou 1 , Anna Gotzamani 2 , Konstantinos Zarogoulidis 1
1 Pulmonary Department, G.Papanikolaou Hospital, Aristotle University of
Thessaloniki, Thessaloniki/Greece, 2 2 nd Clinical Laboratory of Nuclear Medicine,
Ahepa Hospital, Thessaloniki/Greece
Background: Somatostatin receptors have been described on the membrane
of neoplastic cells and their expression has also been demonstrated on
small cell lung cancer (SCLC). In this study we examined if the expression of
somatostatin receptors at the time of disease progression correlated with
survival and time to progression (TTP) of SCLC patients. Methods: 10 patients
with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy
at diagnosis and disease progression. Scintigraphic examinations were
performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with
whole-body scintigraphy and planar scintigraphy of the thorax as well as the
SPECT technique .The scintigraphic results were expressed in comparison with
soft tissue intake (normal prices