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

10528 Poster Discussion Session (Board #21), Tue, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
New microRNA-based diagnostic test for lung cancer classification. Presenting
Author: Ranit Aharonov, Rosetta Genomics, Rehovot, Israel
Background: Lung cancer is the leading cause of cancer deaths in the US.
Treatment options are determined by tumor subtyping, for which there is
lack of standardized, objective, and highly accurate techniques. In 20%-
30% of cases significant limitations of tumor quantity and quality prevent
full classification of the tumor using traditional diagnostic methods. Using
microRNA microarray data generated from over a hundred formalin-fixed,
paraffin-embedded (FFPE) primary lung cancer samples, we have identified
microRNA expression profiles that differ significantly for the main lung
cancer types. Based on these findings, we have developed and validated a
microRNA-based qRT-PCR assay that differentiates primary lung cancers
into four types: squamous cell carcinoma, non-squamous non-small cell
lung cancer, carcinoid and small cell carcinoma. Methods: Over 700
primary tumor samples from different histological types of lung cancer were
collected. Samples included FFPE blocks from resection or biopsies and
cell blocks from cytology specimens including fine needle aspiration,
bronchial brushing and bronchial washing. High-quality RNA was extracted
from the samples using proprietary protocols. Expression levels of potential
microRNA biomarkers were profiled using microarrays followed by a
sensitive and specific qRT-PCR platform. An assay for lung tumors
classification using 8 microRNAs on qRT-PCR was developed based on
data from 261 samples. This assay was validated on an independent
blinded set of 451 cytological and pathological samples. Results: Using the
expression levels of 8 microRNAs measured in qRT-PCR, accurate classification
of the primary lung tumors into the four main cancer types is
obtained. The microRNA-based assay reached an accuracy of 94%.
Moreover, cytological samples composed over 50% of the validation set
and reached an accuracy of 95%. Conclusions: We present here a new
microRNA-based assay for the classification of the four main types of lung
cancer based only on the expression of 8 microRNAs. This assay displays
very high levels of accuracy for both pathological and cytological samples.
The assay comprises a standardized, well-tested and objective tool which
can assist physicians in the diagnosis of lung cancer.
10530 Poster Discussion Session (Board #23), Tue, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Molecular gene expression profiling to predict the tissue of origin and direct
site-specific therapy in patients (pts) with carcinoma of unknown primary
site (CUP): Results of a prospective Sarah Cannon Research Institute
(SCRI) trial. Presenting Author: Frank A. Greco, SCRI/Tennessee Oncology,
PLLC, Nashville, TN
Background: Tumor profiling is an emergent technique to determine tissue
of origin in CUP patients. However, the value of these predictions in
improving treatment efficacy is unknown. In this prospective trial, we used
tumor profiling results to direct site-specific therapy for CUP pts. Methods:
A 92-gene RT-PCR assay (CancerTYPE ID; bioTheranostics, Inc.) was
performed on tumor biopsies from previously untreated CUP pts who
consented. When a tissue of origin was predicted, pts who were treatment
candidates were assigned standard site-specific first-line therapy. Results:
Between 10/08 and 12/11, 289 pts were enrolled, 252 had successful
assays performed, and 247 (98%) had a tissue of origin predicted. 224 pts
were eligible for treatment; 197 pts received assay-directed treatment.
120 of 224 treated pts (54%) had assay diagnoses of tumor types known to
derive substantial benefit from standard site-specific treatment (bladder
27, colorectal 26, NSCLC 24, breast 10, ovary 10, kidney 9, prostate 4,
germ cell 4, others 6 (3 sites), while 104 pts (46%) had assay diagnoses of
relatively resistant tumors (biliary tract 45, pancreas 12, gastroesophageal
10, liver 7, sarcoma 5, cervix 5, others 20 (8 sites). Median OS for all
treated pts was 10.8 months (mos); OS for 197 pts with assay-directed
treatment was 12.2 mos (versus 6.0 mos for 27 pts receiving empiric
therapy). Median OS was better in the 120 pts with assay diagnoses of more
responsive tumor types (12.8 vs 7.4 mos; p � .027). Median OS (mos) in
specific subgroups: pancreas 9, kidney 12, colon 12, NSCLC 16, ovary 30.
Conclusions: This is the first prospective trial in which molecular profiling
has directed site-specific therapy in CUP pts. Assay-directed therapy in
197 pts produced a median OS (12.2 mos) that compares favorably with
previous empiric CUP therapy. CUP pts predicted to have more responsive
tumor types had longer survival compared to less responsive types,
suggesting accurate identification by the assay. These results strengthen
the rationale for molecular profiling in CUP management.
Tumor Biology
663s
CRA10529 Poster Discussion Session (Board #22), Tue, 8:00 AM-12:00 PM
and 11:30 AM-12:30 PM
Regional screening network for characterization of the molecular epidemiology
of non-small cell lung cancer (NSCLC) and implementation of
personalized treatment. Presenting Author: Thomas Zander, Lung Cancer
Group Cologne, Center for Integrated Oncology, University Hospital Cologne,
Cologne, Germany
The full, final text of this abstract will be available at
abstract.asco.org at 12:01 AM (EDT) on Monday, June 4,
2012, and in the Annual Meeting Proceedings online
supplement to the June 20, 2012, issue of Journal of
Clinical Oncology. Onsite at the Meeting, this abstract will
be printed in the Monday edition of ASCO Daily News.
10531 General Poster Session (Board #41D), Mon, 1:15 PM-5:15 PM
Homeobox B9: A potential surrogate marker for bevacizumab in combination
with chemotherapy in colorectal cancer. Presenting Author: Yoshinori
Hoshino, Department of Surgery, Keio University School of Medicine,
Tokyo, Japan
Background: Homeobox B9 (HOXB9) is known to be overexpressed in
human breast cancer and profoundly related to tumorigenicity, lung
metastasis and radio-resistance. (Hayashida, PNAS 2010, and Chiba,
PNAS 2011). However, little is known about the relation between the
expression of HOXB9 and angiogenesis in colorectal cancer (CRC). We
aimed to clarify the impact of HOXB9 in CRC and evaluate the importance
for bevacizumab treatment. Methods: The expression of HOXB9 in human
CRC specimens was analyzed. Then, we introduced HOXB9 construct into
human CRC cell lines and examined TGF� signaling and angiogenic
factors. Xenograft model was established by these cell lines either with or
without the administration of bevacizumab (5mg/kg, weekly) intraperitoneally.
Finally, we examined the mRNA levels of consecutive patients who
were treated by chemotherapy with bevacizumab in our institute and
calculated the Kaplan- Meier curve with log-rank test. Results: 47 of 69
surgical specimens (67%) showed positive expression of HOXB9 mRNA.
The high HOXB9 mRNA levels significantly correlated with poor differentiation
and liver metastasis. The HOXB9-overexpressed cell lines showed
significantly higher expression of TGF� signaling target genes and angiogenic
factors. HOXB9 overexpression significantly increased tumor volume
and burden with higher microvessel density in vivo, even though the cell
proliferation decreased in vitro. Notably, HOXB9-overexpressed tumor was
dramatically shrunk by administration of bevacizumab (tumor shrinkage
rate; 93% vs. 42% in HT29, 83% vs. 27% in HCT116). Patients with high
expression of HOXB9 in tumor showed significantly longer progression free
and overall survival periods (n�39). Conclusions: Our results demonstrated
that patients with high expression of HOXB9 in tumor had better prognosis
with bevacizumab treatment but worse without. In vivo and in vitro
experiments revealed that HOXB9 might orchestrate angiogenesis and
establish positive feedback between cancer cells and microenvironment.
Bevacizumab might inhibit the feedback to reduce tumor growth dramatically.
Therefore, HOXB9 may work as a potential surrogate marker of
bevacizumab treatment in CRC.
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