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

674s Tumor Biology
10574 General Poster Session (Board #46G), Mon, 1:15 PM-5:15 PM
Correlation of ERCC1 expression on circulating tumor cells with progressionfree
survival in metastatic non-small cell lung cancer patients treated with
platinum-based chemotherapy. Presenting Author: Jonathan Riess, Stanford
University School of Medicine, Stanford, CA
Background: Biomarkers predicting efficacy of chemotherapy are highly
desirable. Fiber array scanning technology (FAST) is a novel method of
detecting circulating tumor cells (CTCs) that does not employ an EpCam
enrichment step. The purpose of this study was to use FAST to evaluate
ERCC1 expression on CTCs to determine whether ERCC1 expression
correlates with progression-free survival (PFS) in patients who received
platinum-based chemotherapy for metastatic non-small-cell lung cancer
(NSCLC). Methods: Peripheral blood from one hundred enrolled patients
with metastatic NSCLC was collected by two institutions (Stanford Cancer
Institute and Billings Clinic Cancer Center). FAST was used to identify
individual CTCs on immunofluorescence by pancytokeratin antibodies.
Nuclear localization of ERCC1 expression by immunofluorescence was
quantified on individual CTCs. Total patient ERCC1 levels were determined
from the average expression of all the CTCs in each patient sample.
Fifty-seven of the one hundred patients enrolled received platinum chemotherapy.
Seventeen of those fifty-seven patients (30%) had � 2 evaluable
intact CTCs and were analyzed retrospectively. Linear regression (F-test)
was used to evaluate the correlation between ERCC1 expression and PFS.
Kaplan-Meier survival analysis (log-rank test) was used to compare PFS in
patients with CTCs with no detectable ERCC1 expression versus patients
with CTCs that expressed any level of ERCC1. Results: PFS decreased with
increasing ERCC1 expression (P�0.04 F-test, linear regression). Lack of
ERCC1 expression was associated with longer PFS (266 days vs. 172 days,
log-rank test P�0.02). The difference in survival was statistically significant
with a hazard ratio of 4.20 (95% CI 1.25-14.1, p�0.02, log-rank
test). Conclusions: In this small study, using FAST to isolate CTCs, low
expression of ERCC1 on evaluable CTCs correlated with increased PFS in
patients with metastatic NSCLC who received platinum chemotherapy. A
larger, prospective study to validate these retrospective results is warranted.
10576 General Poster Session (Board #47A), Mon, 1:15 PM-5:15 PM
A gene expression profile test that distinguishes ovarian from endometrial
cancers. Presenting Author: Anita Lal, Pathwork Diagnostics, Redwood
City, CA
Background: The differential diagnosis between primary epithelial ovarian
and endometrial cancers is often unresolved because the histologic
subtypes of these two tumor types can have very similar histology and
immunohistochemical appearance. Here we report the development and
validation of a gene expression profile (GEP) diagnostic test (Pathwork
Tissue of Origin Endometrial Test) that distinguishes ovarian and endometrial
cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using
a 316–gene classification model. Methods: The test was clinically validated
in a blinded study using a pre-specified algorithm and microarray
data files for 75 metastatic, poorly differentiated or undifferentiated
primary FFPE tumor specimens that had either a known clinical diagnosis
of ovarian or endometrial cancer and belonged to one of the 14 ovarian and
endometrial WHO histologic subtypes on the test panel. Results: Classification
biomarkers, empirically selected by machine learning, included
several genes such as homeobox transcription factors and kallikrein
peptidases with known function in the biology of ovarian and endometrial
cancers. The Tissue of Origin Endometrial Test accurately identified the
primary site for 94.7% (95% CI, 87% to 99%) of ovarian and endometrial
cancers. Other measures of test performance include an area under the
ROC curve of 0.997 and a diagnostic odds ratio of 406. Test performance
did not change significantly when stratified by specimens from metastases
(90.5%) or by poorly differentiated and undifferentiated primary tumors
(96.3%). All stages of ovarian and endometrial cancers were included in
the validation study and had agreements of 85% to 100% with the clinical
diagnosis. In a precision study, concordance in test results was 100%.
Reproducibility in test results between three laboratories had a concordance
of 94.3%. Conclusions: The GEP test identified specific ovarian and
endometrial cancer morphologies even when a clear distinction could not
be made by histologic criteria. The GEP test can aid in resolving an
important differential diagnostic question in gynecologic oncology and may
impact clinical management of these patients as well as entry opportunities
into clinical trials.
10575 General Poster Session (Board #46H), Mon, 1:15 PM-5:15 PM
Accuracy of microRNA-based classification of metastases of unknown
primary. Presenting Author: Nicholas Pavlidis, Ioannina University Hospital,
Ioannina, Greece
Background: Identification of the tissue of origin of metastatic tumors is
important for estimation of prognosis and patient management. Carcinoma
of unknown primary (CUP) is not uncommon in oncology, representing
3-5% of all newly found malignancies. We used a microarray-based test
that uses the expression of 64 microRNAs to retrospectively evaluate
tumors from CUP patients. Methods: A cohort of resected metastatic lesions
from patients diagnosed with CUP was studied blindly on the microRNAbased
test. The cohort included 93 samples (from 92 patients) with tissue
adequate for the test. Eight samples failed due to inadequate RNA quality;
85 samples (84 patients) were processed successfully. Test results were
compared with clinical presentation including imaging, pathological data
(histology and IHC) at initial CUP diagnosis and with clinical management
and outcome data at the completion of each patient�s follow up. Results:
The test results were fully concordant with the diagnosis based on all the
clinical and pathological information available including follow-up and
outcome in 92% of patients compared to ~70% agreement with the
patients’ diagnosis at initial presentation, before additional data gathered
throughout patient management. Two different metastases from the same
patient yielded the same result. The microRNA test assigned a single tissue
of origin for 51 patients and two tissues of origin in 33 patients, with the
first being the more likely diagnosis. When comparing only the first (or
single) diagnosis, a concordant level of 88% was achieved. Conclusions: In
a retrospective, well studied cohort of metastases from CUP patients, a
previously developed test based on the expression profile of 64 microRNAs
allowed accurate identification of tissue of origin in 92% of the cases. This
study validates the high accuracy of the test on real CUP patients. The high
concordance of the test results to the final tissue of origin diagnosis of the
patient, even in cases where the initial diagnosis at CUP presentation was
discordant, demonstrates the importance of the test in yielding additional
data valuable for patient management at an early stage of the patient’s
treatment plan.
10577 General Poster Session (Board #47B), Mon, 1:15 PM-5:15 PM
Use of early 18f-fluorodeoxyglucose-positron emission tomography to
predict clinical outcome of patients with advanced non-small cell lung
cancer on gefitinib treatment versus carboplatin plus paclitaxel. Presenting
Author: Masaki Kanazu, National Hospital Organization Kinki-Chuo Chest
Medical Center, Sakai, Japan
Background: Early prediction of clinical efficacy is of great value in cancer
patients in avoiding unnecessary toxicities and giving them another chance
for different treatments. This study aimed to assess the 18F-fluorodeoxyglu cose-positron emission tomography (FDG-PET) at 3 days on treatment as an
early predictor of clinical outcome in patients with advanced non-small cell
lung cancer (NSCLC) treated with gefitinib and in those treated with
cytotoxic chemotherapy. Methods: This study comprised two groups:
patients with stage IIIB or IV NSCLC were treated with gefitinib (250mg)
once daily (gefitinib group) or with carboplatin (AUC 6, day 1) plus
paclitaxel (200mg/m2 , day 1) q21 days (CP group) according to the
physicians’ choice. FDG-PET was performed before, 3 days on and 28 days
on each treatment. Reduction of tumor FDG uptake was assessed by using
standardized uptake value (SUV). Metabolic response was defined as
reduction of FDG uptake in the tumor � 25% according to the criteria of
the European Organization for Research and Treatment of Cancer. Metabolic
response was correlated with clinical outcomes. Results: This study
included 38 patients: 19 in gefitinib group and 19 in CP group. Reduction
of SUV at 3days on treatment preceded tumor shrinkage more closely in
gefitinib group. Metabolic response was significantly correlated with longer
progression-free survival (PFS) in gefitinib cohort (median PFS 15.8
months [95% CI 13.2-18.4] vs. 3.7 months [95% CI 0.1-8.0], p �
0.001), but not in CP group (median PFS 5.7 months vs. 2.9 months, p �
0.054). Furthermore, metabolic response was significantly correlated with
longer overall survival (OS) in gefitinib group (median OS 28.7 months
[95%CI 23.5-33.9] vs. 9.8 months [95% CI 2.1-17.5], p � 0.009), but
not in CP group (median OS 13.9 months vs. 10.5 months, p � 0.56). In
multivariate analysis using Cox hazards models, metabolic response was a
significant predictive factor of PFS and OS. Conclusions: Reduction of SUV
levels on FDG-PET at 3 days on treatment may predict response and
survival in gefitinib-treated patients with advanced NSCLC.
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