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e14557 Background: Circulating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or predicting tumor recurrence in early stage lung cancer patients. Methods: We analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing to detect somatic mutations and differential epigenomics patterns, including methylation signatures. Results: Using somatic mutation analysis alone, ctDNA was detected in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 71%. ctDNA detection rate also varied markedly between lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC);using combined analysis of somatic mutations and epigenomic patterns, ctDNA was detected in all SCC patients, while only 55% of ADC (12/22) were ctDNA-positive (p= 0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, pre-operative ctDNA status was correlated with tumor recurrence post-resection; three of eight (38%) ctDNA-positive stage I ADC patients recurred within 2 years of resection, while only one of nine (11%) ctDNA-negative stage I ADC patients recurred (p= 0.29). Conclusions: Taken together, we show that the combination of somatic mutation detection and epigenomic analysis outperforms each individual biomarker in the detection of ctDNA in early stage lung cancer. Importantly, we also demonstrate that pre-operative ctDNA detection may identify a high-risk population of early stage lung cancer patients that may benefit from (neo)adjuvant therapy.

e22033 Non-invasive and repeatable EGFR analysis using novel enrichment method for circulating tumor cells Background: The first-line treatment in confirmed NSCLC (non-small cell lung cancer) patie...

e22029 Background: Although many effective therapies improve the survival rate in breast cancer patients, a significant number of patients could not avoid recurrence and metastasis. Liquid biopsy u...

e21062 Background: In metastatic colorectal cancers tumor cells were already disseminated, prior to surgical resection of the primary tumors, but micrometastases remain dormant until proper colonization mechanisms are activated. Specific aims of this study are, 1) to examine the colonization pathways and genes newly activated in metastatic tumors by longitudinal pair-wise comparisons between primary-to-metastatic tumors and 2) to understand tropism between colon-to-liver and colon-to-lung metastases at gene expression level. Methods: Total 24 tumor samples were prepared as longitudinal pairs from 6 hepatic, and 6 pulmonary cases. In these samples mRNA levels were quantitatively determined for 215 genes that were previously reported to play roles in metastasis, cytokines signaling, or angiogenesis, as provided as RT2 Profiler TM PCR arrays (PAHS-022, 024, 028). Unsupervised hierarchical clustering of Ct values and heat map analyses of DCt values were carried out using web based data analysis program, and 17-gene tropism signature was selected for stratification of the hepatic and the pulmonary metastases. Results: Ct values of 23 duplicated genes and 5 house-keeping genes showed plate-to-plate correlation of 0.92. Unsupervised hierarchical clustering of the Ct values from the Metastasis Arrays revealed that the hepatic metastases were indistinguishable from the primary colorectal cancers (n=5/6), but the lung metastases were highly diversified (n=6/6). Cytokine Array data also showed the divergence of pulmonary metastases from the primary colorectal cancers (n=6/6). Heat map analyses of DCt values from the Metastasis Arrays identified 17-gene tropism signature that was sufficient not only to distinguish the liver and the lung metastases, but also reconstitute the clustering of primary tumors with the hepatic metastases. Conclusions: Intrinsic difference existed between the pulmonary and hepatic metastases of colorectal origins among the tested samples. 17-gene tropism signature was identified, and further genomic and clinical studies are in process to validate their potentials as therapeutic targets to treat pulmonary metastases of colorectal cancers.

7053 Background: The mutational profiles are crucial for cancer diagnosis and classification, which lead to tailoring the best therapeutic strategy to each patient. Here, we present target sequencing of 30 hot spot genes in lung adenocarcinoma to identify new hot spot mutations in never-smoker, female lung adenocarcinoma patients. Methods: We targeted 30 genes that are known to be mutated frequently in lung adenocarcinoma. The exome capture was done using selector technology and sequencing was done using Illumina GA IIx Genome Analyzer. Exomic short reads from Illumina Pipeline 1.4 were aligned to human genome (NCBI build 36) with BWA 0.5.0. Variations and small indels were called by Samtools 0.1.7 and filtered by custom R scripts. Potential effects of these identified alterations were assessed with sequence analysis. Results: On average, 1.5 billion bases were uniquely mapped, and mean depth and coverage of exon regions were 38X and 96%, respectively. Filtering of data against public SNP database (dbSNP130), resulted in ~2,000 novel genetic alterations per sample, including single nucleotide variations, and small insertion and deletions in protein-coding regions. Among them, there were novel variants in LTK and EPHA5 genes. Conclusions: Our results demonstrated the feasibility of high-throughput mutation profiling with lung adenocarcinoma samples. We identified novel variants in hot target genes, which may provide an insight into the tumorigenesis signaling of lung adenocarcinoma.

e18083 Background: Identical lung cancer cells may get diversified depending on tumor microenvironments. We hypothesized that diversity of cancer associated fibroblasts renders identical lung cancer cells various tumor characteristics such as drug responsiveness and proliferation rate. To test this hypothesis, we isolated cancer associated fibroblasts from 20 different lung cancers, and compared their effects on the proliferation and drug responsiveness of lung cell lines. Methods: Cancer associated fibroblasts were isolated from 20 solid tumors of NSCLCs, and treated with Mitomycin to control the overgrowth during cocultures. H358 and A549 cells were mixed with cancer associated fibroblasts in 1:1 ratio and co-cultured for 4-7 days. Cell number was scored by time-lapse photography, and cell morphology was observed under fluorescent microscope. Expression of cell type markers were examined. Responsiveness to Erlotinib was examined in coculture condistions. Results: Cancer associated fibroblasts stimulated cancer cell proliferation ranging from almost no effects to approximately 3 folds. Coculture in transwell with no direct contacts with cancer cells showed minimal stimulatory effects. Direct contacts induced dramatic changes in cancer cell morphology from cohesive epithelial colonies to dispersed fibroblastic single cells. EMT markers such as down-regulation of Cytokeratins and up-regulation of Vimentin were detected in GFP positive cells. A549 cells that were sensitive to 15 uM Erlotinib (IC50=7.5uM) became resistant when co-cultured with cancer associated fibroblasts. Conclusions: In this study, cancer associated fibroblasts isolated from different lung cancers induced significant changes in tumor cell characteristics such as proliferation, EMT, and drug responsiveness.

5584 Background: Adenoid cystic carcinoma is a rare malignancy, accounting for about 1% of head and neck cancer. We assessed clinical characteristics and prognostic factors affecting clinical outco...

e11565 Background: Breast cancer represent a heterogenous group of tumors that are diverse in behavior, outcome, and response to therapy. To reduce mortality from breast cancer, there is a desire t...

6548 Background: Myeloablative hematopoietic stem cell transplantation (HSCT) is the treatment of choice for several malignant hematologic disorders. Long-term survivors are increasing by the impro...

3609 Background: Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) are correlated with angiogenesis and involved in tumor growth and metastases. P53 gene mutation i...

6608 Background: Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by significant prognostic heterogeneity and a preleukemic condition with transformation into acute myeloid leukemia. However, the underlying genetic events remain poorly understood. Since aberrant DNA methylation might play a causative role in disease and prognosis, the study investigated the difference of DNA methylation profiles between refractory anemia with excess blast (RAEB) and refractory cytopenia with multilineage dysplasia (RCMD). Methods: Bone marrow samples from 20 patients with primary MDS (nine RAEB and 11 RCMD) and peripheral blood samples from four controls, were assessed using a commercial whole genome-wide methylation assay. Results: The microarray data revealed statistically significant hypermethylation of 69 genes in RAEB, but not in RCMD. The candidate genes mapped to five different networks, with network 1 being the top-scoring network with functions in gene expression, cancer...

14005 Background: We conducted a study to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1 plus weekly docetaxel in pts with metastatic gastric cancer (MGC), and to recommend a dose for phase II study Methods: Pts with MGC, age ≥ 18 yrs, ECOG PS 0–2, adequate organ function, and no or 1–2 prior chemotherapy were eligible. S-1 was given twice daily, p.o. on D1–14 and docetaxel i.v. on D1, 8, q 3 wks. Each cohort of 3 pts was treated with escalating doses of S-1/docetaxel at 60/25 (level I), 70/25 (level II), 70/30 (level III), 80/30 (level IV), 80/35 (level V), 90/35 (level VI), and 90/40 mg/m2 (level VII). The DLT pertaining to 1st cycle only was obtained. Results: Thirty pts with median age of 50 yrs (range: 27–71) with MGC received a median of 8 cycles (range: 1–12). A total of 222 cycles were administered. DLTs were; G3 elevated liver enzyme at level I (1/6 pts), gastric perforation at level V (1/6), G3 diarrhea and febrile neutropenia (FN) with G3 nausea/anorexia/fatigue at level VI (2/6), and FN and neutropenic infection (NI) with G3 stomatitis at level VII (2/3). After DLT occurred in 2 of 3 pts in level VII, 2 of additional 3 pts enrolled at level VI had DLT. Then, 1 pt developed DLT among additional 3 pts enrolled at level V. Therefore, MTD and recommended dose (RD) were level VI and V, respectively. There were 2 CRs, 17 PRs with response rate of 65.5% (95% CI 48.2–82.8%), 8 SDs and 2 PDs among 29 efficacy-evaluable pts. Conclusions: MTD for this regimen was S-1 90 mg/m2/d + docetaxel 35 mg/m2 and RD was S-1 80 mg/m2/d (D1–14) + docetaxel 35 mg/m2 (D1, 8). (Supported by National Cancer Center Grant; Docetaxel and S-1 were provided by Sanofi-Aventis Korea and Jeil Pharm. Co., respectively) [Table: see text] No significant financial relationships to disclose.

3607 Background: The aim of this study was to determine whether expressions of the excision cross-complementing (ERCC1), thymidylate synthase (TS) and glutathione S-transferase π (GSTπ) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy. Methods: The study population consisted of 70 advanced colorectal cancer patients (median age, 53 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at days 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU bolus 400 mg/m2 and 22 hour continuous infusion of 600 mg/m2 at day 1–2. Treatment was repeated in 2 week intervals. The expressions of ERCC1, TS and GSTπ of primary tumors were examined by immunohistochemistry. Results: The positive rates of ERCC1, TS, and GSTπ were 55.7%, 68.6%, and 71.4%, respectively. The patients without TS expression were more likely to respond to chemotherapy (p=0.009). There were no significant differences between response and ERCC1 or GSTπ expression pattern (p=0.768, p=0.589, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (p=0.0474). Patients with ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GSTπ positive had poor OS (p=0.0017, p=0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted on OS (Hazard ratio 1.72, p=0.023). Conclusions: Immunohistochemical studies for ERCC1 and TS may be useful in prediction of the clinical outcome of advanced colorectal cancer patients treated with 5-FU and oxaliplatin. No significant financial relationships to disclose.

8237 Background: We conducted this prospective study to assess the changes of quality of life, anxiety and depression in patients receiving palliative chemotherapy for solid cancers. Methods: Patie...

4074 Background: ECF has been regarded as a highly active regimen for the advanced gastric cancer. Capecitabine (X) is an oral fluoropyrimidine carbamate and may be less toxic and more active than ...

4193 Background: Paclitaxel and docetaxel has been shown to be effective in some patients with advanced gastric cancer. We used a randomized phase II design to prospectively compare the toxicity an...