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

10578 General Poster Session (Board #47C), Mon, 1:15 PM-5:15 PM
Preoperative detection of circulating tumor cells in patients with colorectal
carcinoma: Correlation with clinicopathologic variables and recurrence.
Presenting Author: Hideyasu Sakihama, Gastroenterological Surgery 1,
Hokkaido University Graduate School of Medicine, Sapporo, Japan
Background: The role of circulating tumor cells (CTC) in the management of
colorectal cancer patients has not fully established. The aims of this study
are to investigate the relationship between the presence of CTC with
clinicopathological variables and recurrence by magnetic activated cell
sorting (MACS) system. Methods: Peripheral blood samples were collected
from 80 patients. Enrichment of CTC was performed by direct immunomagnetic
labeling of EpCAM positive cells in peripheral blood. Subsequently,
double immunofluorescence for cytokeratin and CD45 was performed to
detect CTC. Peripheral blood samples from twenty healthy volunteers were
used as controls. Results: Preoperative positive rate of CTC was 35% while
specificity was 100%. No CTC was found in peripheral blood from healthy
volunteers. No correlation was found between the presence of CTC and
location of tumors, grade of differentiation, vessel invasion, lymph node
metastasis or TNM stages. On the other hand, the depth of invasion (0% in
Tis, 11.1% in T1, 18.2% in T2 and 34.7% in T3�T4, P�0.05) and tumor
recurrence (28.2% for initial operation and 88.9% for reoperative surgery
for tumor recurrence, P�0.001) closely correlated with the presence of
CTC. Preoperative positive rate of CTC among patients who have recurred
postoperatively was 75%. Conclusions: Our results indicate that detections
of CTCs correlate with the depth of invasion and tumor recurrence.
Preoperative presence of CTCs might be a strong predictor for tumor
recurrence.
10580 General Poster Session (Board #47E), Mon, 1:15 PM-5:15 PM
Defining a FISH chromosomal aneusomy panel for predicting lung cancer in
the setting of CT-detected lung nodules. Presenting Author: Wilbur A.
Franklin, University of Colorado Denver, Denver, CO
Background: Early detection of lung cancer by CT is supported by the
National Lung Screening Trial; but while sensitivity of CT is high, specificity
is low. Biomarkers to predict the malignant nature of CT detected lung
nodules would have great clinical utility. We previously found in a nested
case-control study that a 4-target chromosomal aneusomy (CA) FISH panel
exhibited sensitivity/specificity of 76%/88% in sputum samples of heavy
smokers obtained within 18 months of lung cancer diagnosis. We hypothesized
that CA-FISH may be an effective biomarker to assist with clinical
decisions in the setting of CT detected lung nodules of indeterminate
etiology and attempted to identify a more effective reagent. Methods:
Homebrew probes encompassing genomic sequences of EGFR, NXK2-1,
PIK3CA, MYC, BRF2, SOX2, PPMID, FGFR1 and the commercial reagent
LSI D5S721/D5S23 (Abbott Molecular) were combined in 2-4-target FISH
assays to investigate tissue copy number in early stage lung squamous cell
carcinoma (SCC, N�19) and adenocarcinoma (AC, N�20). Logistic
regression models were used to estimate predictive discrimination [sensitivity,
specificity, area under the ROC curve (AUC)]. Results: Copy number
gain was largely detected for all markers (mean range 3.39 - PPMID to 4.67
- MYC). Mean copy number of PI3CA, BRF2, SOX2 and FGFR1 were
significantly higher in SCC than AC, while NKX2 and MYC were marginally
higher in AC than SCC. Gene amplification was detected for all 9 markers,
most frequently for SOX2 and FGFR1 (6 and 5 cases) with significant
overlap between FGFR1/BRF2 and SOX2/PIK3CA. Based on the AUC
results and the existence of targeted inhibitors, the probe set EGFR/FGFR1/
MYC/PIK3CA was selected as a candidate for further development as an
adjunct to CT screening for early detection. For this selected set,the
optimal cutoff based in the linear predictor from logistic regression yields a
sensitivity and specificity of 0.85. Conclusions: A highly sensitive/specific
CA-FISH probe set was identified which may well complement CT screening
in the early diagnosis of lung cancer. This probe set will be tested in the
setting of CT detected lung nodules. (Supported by LUNGevity and
NCI-Lung Cancer SPORE grants).
Tumor Biology
675s
10579 General Poster Session (Board #47D), Mon, 1:15 PM-5:15 PM
Retrospective analysis of gene expression profiling and TTF-1 staining in
cancer of unknown primary (CUP). Presenting Author: Wendy M. Chiang,
Tufts Medical Center, Boston, MA
Background: CUP involves extensive use of immunohistochemical (IHC)
stains because no individual marker is highly both site specific or sensitive.
IHC algorithms lack standardization and may even eliminate actual primary
sites. Extensive validation studies with gene expression profiling (GEP) has
shown it be a new diagnostic technique that further contributes tumor site
location in CUP. Thyroid transcription factor-1 (TTF-1) IHC stain is
commonly used to identify the pulmonary origin of CUP (particularly
adenocarcinoma) and is often used to exclude lung primary in CUP
patients. This study evaluates the utility of TTF-1 staining in lung primaries
(specifically non-small cell lung carcinoma - NSCLC) of CUP to GEP
testing. Methods: This retrospective study contains data obtained from a
registry of physicians who received the GEP-based Tissue of Origin (TOO)
test (Pathwork Diagnostic, Sunnyvale, CA) between 07/2009 and 12/2009
on CUP cases. Sixty-six physicians contributed 111 TOO test cases. Only
cases that had TTF-1 done were included for analysis and these were
compared to TOO NSCLC results. Results: Out of 111 cases, there were 73
analyzable TTF-1 results with 12 cases of NSCLC and 61 cases of
non-NSCLC by TOO (see TABLE). Assuming that the results of TOO testing
accurately indicated the true primary site, the sensitivity and specificity of
TTF-1 was 50% and 90%, respectively. The false negative rate was 50%,
indicating that half of the identified NSCLC cases in this series had
negative TTF-1. On the other hand, 10% of the 61 cases with primaries
other than NSCLC (none of whom had thyroid cancer), had positive TTF-1.
The “false positive” TTF-1 cases comprised 4 ovarian, 1 breast and 1
colorectal as the site of origin. Conclusions: TTF-1 has limited utility in
identifying NSCLC in the setting of CUP. Half of NSCLCs identified by TOO
testing had negative TTF-1, and 10% of non-lung primaries were TTF-1
positive. Negative TTF-1 should not be used to exclude NSCLC in the
workup of CUP.
NSCLC by TOO Non- NSCLC by TOO Total
TTF-1 stain positive 6 (TP) 6 (FP) 12
TTF-1 stain negative 6 (FN) 55 (TN) 61
Total 12 61 73
Sensitivity 0.50
Specificity 0.90
False negative rate (1-sensitivity) 0.50
False positive rate (1-specificity) 0.10
10581 General Poster Session (Board #47F), Mon, 1:15 PM-5:15 PM
89 Zr-bevacizumab PET imaging in metastatic renal cell carcinoma patients
before and during antiangiogenic treatment. Presenting Author: Sjoukje
Oosting, Department of Medical Oncology, University Medical Center
Groningen, Groningen, Netherlands
Background: Renal cell cancer (RCC) is characterized by high VEGF
production leading to excessive angiogenesis. To visualize VEGF, we
performed serial 89Zr-bevacizumab-PET scans before and during antiangiogenic
treatment in RCC patients. Methods: Metastatic (m) RCC patients
who received sunitinib (50 mg once daily, 4 out of 6 weeks) or bevacizumab
(10 mg/kg every 2 weeks) plus interferon (IFN 3-9 MU 3x/week), underwent
89Zr-bevacizumab-PET scans at baseline and after 2 and 6 weeks, and CT
scans at baseline and every 3 months. Tracer uptake in tumor lesions was
quantified with maximum Standardized Uptake Value (SUVmax). Relationship
between baseline and � SUVmax and time to progression (TTP) was
analyzed. Wilcoxon test was used to compare scans, Kaplan-Meier method
for survival analysis. Results: 22 out of 26 patients were evaluable, 11 per
treatment. On 89Zr-bevacizumab-PET, 131 out of 231 lesions � 10 mm
(detection limit) were visible and 125 quantifiable. Mean SUVmax at
baseline was 10.1 (SD 8.4; range 2.3 - 46.9). During bevacizumab/IFN
treatment, SUVmax consistently decreased (mean decrease 47.0% 95% CI
39.1-54.9, P�0.0001) at 2 weeks with a further decrease of 9.7% (95%
CI 0.86-18.5, P�0.016) at 6 weeks. After 2 weeks sunitinib, there was
only a modest decrease in mean SUVmax (14.6%, 95% CI 1.57-27.63,
P�0.0064) with a wide range (-80.4% to �269.9%) and an overshoot of
84.4% (95% CI 47.8-120.9, P�0.0001) after 2 drug free weeks. TTP was
longer in (n�15) patients with baseline SUVmax � 11.1 (highest normal
tissue uptake) in the 3 most intense lesions than in those with a lower value
(median 89.7 vs 22.8 weeks, HR 0.16, 95% CI 0.04 - 0.70). TTP was
longer in patients (n�11) with an absolute � SUVmax �6.00 in the most
intense lesion at 2 weeks (HR 0.25, 95% CI 0.06-0.98). Conclusions:
89Zr-bevacizumab-PET visualizes tumor lesions in mRCC patients. Different
changes in tumor tracer uptake after start of bevacizumab/IFN versus
sunitinib indicate that these drugs induce different angiogenic responses.
High baseline SUVmax and large change in SUVmax corresponded with
longer TTP, suggesting that 89Zr-bevacizumab-PET may help to identify
patients who benefit the most from antiangiogenic treatment.
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