Genome-wide cell-free DNA (cfDNA) methylation signatures and effect on tissue of origin (TOO) performance.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3049-3049 ◽  
Author(s):  
Minetta C. Liu ◽  
Arash Jamshidi ◽  
Oliver Venn ◽  
Alexander P. Fields ◽  
M. Cyrus Maher ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Early Stage ◽  
Stage Iv ◽  
Stage I ◽  
Multiple Cancer ◽  
Isolated Cells ◽  
Genome Wide ◽  
Ffpe Tumor ◽  
Formalin Fixed Paraffin Embedded ◽  
Cancer Types

3049 Background: For multi-cancer detection using cfDNA, TOO determination is critical to enable safe and efficient diagnostic follow-up. Previous array-based studies captured < 2% of genomic CpGs. Here, we report genome-wide fragment-level methylation patterns across 811 cancer cell methylomes representing 21 tumor types (97% of SEER cancer incidence), and define effects of this methylation database on TOO prediction within a machine learning framework. Methods: Genomic DNA from 655 formalin-fixed paraffin-embedded (FFPE) tumor tissues and 156 isolated cells from tumors was subjected to a prototype 30x whole-genome bisulfite sequencing (WGBS) assay, as previously reported in the Circulating Cell-free Genome Atlas (CCGA) study (NCT02889978). Two independent TOO models, one with and one without the methylation database, were fitted on training samples; each was used to predict on the test set. A WGBS classifier was used to detect cancer at 98% specificity; reported TOO results reflect percent agreement between predicted and true TOO among those detected cancers (166 cases: 81 stage I-III, 69 stage IV, 16 non-informative). Results: Genome-wide methylation data generated from this database allowed fragment-level analysis and coverage of ~30 million CpGs across the genome (~60-fold greater than array-based approaches). Incorrect TOO assignments decreased by 35% (20% to 13%) after incorporating methylation database information into TOO classification. Improvement was observed across all cancer types and was consistent in early-stage cancers (stage I-III). Respective performances in breast cancer (n = 23) were 87% vs 96%; in lung cancer (n = 32) were 85% vs 88%; in hepatobiliary (n = 10) were 70% vs 90%; and in pancreatic cancer (n = 17) were 94% vs 100%. Results using an optimized approach informed by these results in a large cohort of CCGA participants will be reported. Conclusions: Incorporating data from a large methylation database improved TOO performance in multiple cancer types. This supports feasibility of this methylation-based approach as an early cancer detection test across cancer types. Clinical trial information: NCT02889978.

Generation and validation of a primary-tumor-derived four-gene prognostic signature for recurrence (R) of stages I/II colorectal cancer (CRC) following potentially curative resection

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4035-4035
Author(s):  
P. F. Lenehan ◽  
D. W. Fry ◽  
E. R. Heyman ◽  
J. F. Eliason ◽  
W. P. Worzel
Keyword(s):  
Early Stage ◽  
Low Risk ◽  
Stage I ◽  
Primary Adenocarcinoma ◽  
Prognostic Signature ◽  
Curative Intent ◽  
Prognostic Test ◽  
Nccn Guidelines ◽  
Ffpe Tumor ◽  
Formalin Fixed Paraffin Embedded

4035 Background: Current guidance for postoperative clinical management of stages I/II CRC patients (pts) is suboptimal. We hypothesized that a molecular prognostic test using primary CRC tissue would better predict the chances of tumor R within 3 years (y) than NCCN Clinical Practice Guidelines. Methods: Archival formalin-fixed paraffin-embedded (FFPE) primary adenocarcinoma tissues obtained at initial resection with curative intent were retrieved for 145 stage I/II (pT1–4 pN0 M0) CRC pts from multiple international sites; none had neoadjuvant or adjuvant therapy. Pts had tumor R by 36 months (mo) or confirmed non-recurrence (NR) for ≥36 mo after surgery. Pts were stratified by R/NR status and then randomized to a Training Set (TSet) (n=73; 34R, 39NR) or Validation Set (VSet) (n=72; 33R, 39NR). Tumor gene expression was quantified by DASL assay (Illumina, San Diego) using a custom 512-gene panel. Genetic programming (GP), a machine-learning technique, defined 15 TSet genes as key for differentiating pts with R versus NR. Results: Successive GP analyses of TSet data evolved a prognostic signature that mathematically combined 4 of the 15 key genes identified. This selected dichotomous rule correctly classified 28/33 R and 35/39 NR VSet pts (85% sensitivity, 90% specificity). ‘High risk’ pts had a significantly higher probability of R by 36 mo than ‘low risk’ pts: 88% PPV, 88% NPV; relative risk (RR) 7.0 (95% CI: 3.1, 16.1; p<0.0001). RR by stage (I/II) = 7.00/7.28 and tumor site (colon/rectum) = 8.75/4.50. Kaplan-Meier recurrence-free survival: hazard ratio 11.8 (95% CI: 4.5, 31.1; p<0.0001). NCCN Guidelines (V.2.2008) correctly classified 24/33 R and 15/39 NR VSet pts: 73% sensitivity, 38% specificity, 50% PPV, 63% NPV; RR 1.33 (95% CI: 0.74, 2.40; p=0.32). Conclusions: A GP derived 4-gene prognostic test using FFPE tumor tissue can differentiate early stage CRC pts at high versus low risk for R within 3y better than current NCCN Guidelines. [Table: see text] [Table: see text]

scholarly journals Serum Biomarker Signature-Based Liquid Biopsy for Diagnosis of Early-Stage Pancreatic Cancer

2018 ◽  
Vol 36 (28) ◽  
pp. 2887-2894 ◽  
Author(s):  
Linda D. Mellby ◽  
Andreas P. Nyberg ◽  
Julia S. Johansen ◽  
Christer Wingren ◽  
Børge G. Nordestgaard ◽  
...  
Keyword(s):  
Case Control Study ◽  
Early Stage ◽  
Stage Iv ◽  
The United States ◽  
Case Control ◽  
Stage I ◽  
Serum Biomarker ◽  
Patient Cohort ◽  
Biomarker Signature ◽  
Control Study

Purpose Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival of < 10% because of diffuse symptoms leading to late-stage diagnosis. That survival could increase significantly if localized tumors could be detected early. Therefore, we used multiparametric analysis of blood samples to obtain a novel biomarker signature of early-stage PDAC. The signature was derived from a large patient cohort, including patients with well-defined early-stage (I and II) PDAC. This biomarker signature was validated subsequently in an independent patient cohort. Patients and Methods The biomarker signature was derived from a case-control study, using a Scandinavian cohort, consisting of 16 patients with stage I, 132 patients with stage II, 65 patients with stage III, and 230 patients with stage IV PDAC, and 888 controls. This signature was validated subsequently in an independent case-control cohort in the United States with 15 patients with stage I, 75 patients with stage II, 15 patients with stage III, and 38 patients with stage IV PDAC, and 219 controls. An antibody microarray platform was used to identify the serum biomarker signature associated with early-stage PDAC. Results Using the Scandinavian case-control study, a biomarker signature was created, discriminating samples derived from patients with stage I and II from those from controls with a receiver operating characteristic area under the curve value of 0.96. This signature, consisting of 29 biomarkers, was then validated in an independent case-control study in the United States. The biomarker signature could discriminate patients with stage I and II PDAC from controls in this independent patient cohort with a receiver operating characteristic area under the curve value of 0.96. Conclusion This serum biomarker signature might represent a tenable approach to detecting early-stage, localized PDAC if these findings are supported by a prospective validation study.

XMAP230 is required for the assembly and organization of acetylated microtubules and spindles in Xenopus oocytes and eggs

1998 ◽  
Vol 111 (16) ◽  
pp. 2315-2327 ◽  
Author(s):  
B.J. Cha ◽  
B. Error ◽  
D.L. Gard
Keyword(s):  
Late Stage ◽  
Xenopus Oocytes ◽  
Early Stage ◽  
Polyclonal Antibodies ◽  
Stage Iv ◽  
Stage I ◽  
Meiotic Spindle ◽  
Heat Stable ◽  
Early Embryos ◽  
And Function

We used affinity-purified polyclonal antibodies to characterize the distribution and function of XMAP230, a heat-stable microtubule-associated protein isolated from Xenopus eggs, during oogenesis. Immunoblots revealed that XMAP230 was present throughout oogenesis and early development, but was most abundant in late stage oocytes, eggs, and early embryos. Immunofluorescence microscopy revealed that XMAP230 was associated with microtubules in oogonia, post-mitotic stage 0 oocytes, early stage I oocytes, and during stage IV-VI of oogenesis. However, staining of microtubules by anti-XMAP230 was not detectable during late stage I through stage III. In stage VI oocytes, anti-XMAP230 stained a large subset of microtubules that were also stained with monoclonal antibodies specific for acetylated (α)-tubulin. During oocyte maturation, XMAP230 was associated with the transient microtubule array that serves as the precursor of the first meiotic spindle, as well as both first and second meiotic spindles. The extensive array of cytoplasmic microtubules present throughout maturation was not detectably stained by anti-XMAP230. Microinjection of anti-XMAP230 locally disrupted the organization and acetylation of microtubules in stage VI oocytes, and reduced the re-acetylation of microtubules during recovery from cold-induced microtubule disassembly. Subsequent maturation of oocytes injected with anti-XMAP230 resulted in defects in the assembly of the transient microtubules array and first meiotic spindle. These observations suggest that XMAP230 is required for the stabilization and organization of cytoplasmic and spindle microtubules in Xenopus oocytes and eggs.

Stage at cancer diagnosis during the COVID-19 pandemic in western Washington state.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 145-145
Author(s):  
Catherine R. Fedorenko ◽  
Karma L. Kreizenbeck ◽  
Li Li ◽  
Laura Elizabeth Panattoni ◽  
Veena Shankaran ◽  
...  
Keyword(s):  
Medical Care ◽  
Early Stage ◽  
Stage Iv ◽  
Washington State ◽  
Stage I ◽  
Tumor Type ◽  
Stage At Diagnosis ◽  
Stage Iv Cancer ◽  
Using Data ◽  
The Impact

145 Background: The COVID-19 pandemic disrupted medical care, including routine cancer screening for breast, colorectal, lung and cervical cancers. We aimed to investigate the impact of the pandemic on stage at diagnosis for cancer patients. Methods: Using data from the Washington State SEER records we compared AJCC stage for patients diagnosed with cancer in 2017-2019 to 2020 for two time periods, March to June (initial pandemic months) and July to December (later pandemic months). Patients were included if they were age 18+, diagnosed with a solid tumor, and not diagnosed at autopsy. Results: In the early phase of the pandemic, March – June 2020, there was a shift to cancers being diagnosed at a later stage compared to the same time period in 2017-2019 (Stage III: 13.5% to 14.9%, Stage IV: 16.2% to 19.7%). There was also a decrease in cancer diagnoses for cancers that are often detected through routine screening. As a percentage of all cancer diagnoses, both melanoma (13.2% to 9.8%) and colon cancer diagnoses (7.2% to. 6.7%) decreased during the early pandemic. In the later phase of the pandemic, July to December 2020, the stage at diagnosis showed an indication of returning to pre-pandemic levels with an increase in the proportion of early stage cancers (In situ: 16.6% to 19.3%, Stage I: 38.8% to 41.1%). Stage at diagnosis trends varied by tumor type. For colorectal cancer, the overall number of diagnoses decreased during the initial pandemic months. Stage I diagnoses decreased and Stage IV cancer diagnoses increased in both early and late stages of the pandemic. Conclusions: In Washington State, the COVID-19 pandemic had an impact on stage at diagnosis potentially caused by delays or interruptions in medical care. Additional studies are needed to understand how this shift in stage at diagnosis impacted treatment and outcomes for patients.

An ultrasensitive method for noninvasive pan-cancer early detection based on targeted methylation sequencing of cell-free DNA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10544-10544
Author(s):  
Tiancheng Han ◽  
Yuanyuan Hong ◽  
Pei Zhihua ◽  
Song Xiaofeng ◽  
Jianing Yu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Detection ◽  
Real World ◽  
Early Stage ◽  
Validation Dataset ◽  
Cpg Sites ◽  
Free Dna ◽  
Cancer Types ◽  
Discovery Dataset ◽  
Pan Cancer

10544 Background: Screening the biomarkers from the cell-free DNA (cfDNA) of peripheral blood is a non-invasive and promising method for cancer diagnosis. Among diverse types of biomarkers, epigenetic biomarkers have been reported to be one of the most promising ones. Epigenetic modifications are widespread on the human genome and generally have strong signals due to the similar methylation patterns shared by adjacent CpG sites. Although some epigenetic diagnostic methods have been developed based on cfDNAs, few of them could be applied to pan-cancer and their sensitivities are barely satisfactory for early cancer detection. Methods: Targeted methylation sequencing was performed using our in-house-designed panel targeting regions with abundant cancer-specific methylation CpGs. The cfDNA samples from 80 healthy individuals and 549 cancer patients of 14 cancer types were separately sequenced. The dataset was randomly split into one discovery dataset and one validation dataset. Moreover, cfDNA samples from four cancer patients were diluted with the healthy cfDNAs to generate 12 in vitro simulated samples with low circulating tumor DNA (ctDNA) fraction. Additionally, DNAs extracted from 130 unmatched tumor formalin fixation and paraffin embedding (FFPE) samples of 10 cancer types were sequenced to screen the diagnostic biomarkers. Adjacent CpG sites were first merged into methylation-correlated blocks (MCB) according to their correlations of methylation levels in tumor DNAs. The MCBs with higher methylation levels in tumor DNAs than that of healthy cfDNAs (from the discovery dataset) were defined as our hypermethylation biomarkers. For each cfDNA sample, a hypermethylation score (HM-score) was computed to measure the overall methylation level difference of selected biomarkers. The performance of our method was evaluated with the real-world dataset, while the limit of detection was estimated using the simulated low-ctDNA samples. Results: Our model based on 37 hypermethylation MCB biomarkers achieved an area under the curve (AUC) of 0.89 and 0.86 in the real-world pan-cancer discovery and validation cfDNA datasets, respectively. Furthermore, the overall specificity and sensitivity are 100% and 76.19% in the discovery dataset, and 96.67% and 72.86% in the validation dataset. In the validation dataset, 28/40 (70%) of early-stage colorectal cancer patients and 10/20 (50%) of non-small-cell lung cancer patients were successfully diagnosed. Additionally, all the simulated samples with theoretical ctDNA factions over 0.5% were predicted as diseased, demonstrating the ability of our method to detect tumor signals at early stages. Conclusions: Our cfDNA-based epigenetic method outperforms currently available methods in various cancer types, and is promising to be applied to early-stage cancer detection and samples with low ctDNA fractions.

Treatment Outcomes in Completely Resected Stage I to Stage IV Uterine Carcinosarcoma With Rhabdomyosarcoma Differentiation

2013 ◽  
Vol 23 (9) ◽  
pp. 1635-1641 ◽  
Author(s):  
Vicky Makker ◽  
Sara J. Kravetz ◽  
Jacqueline Gallagher ◽  
Oana-Paula Orodel ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Group Versus ◽  
Stage Iv ◽  
Stage I ◽  
Cancer Center ◽  
Uterine Carcinosarcoma ◽  
Entire Cohort ◽  
Gynecology And Obstetrics ◽  
Resected Stage

ObjectiveTo evaluate overall survival (OS) and progression-free survival (PFS) after adjuvant therapy in stage I to stage IV uterine carcinosarcoma with rhabdomyosarcoma differentiation.MethodsMemorial Sloan-Kettering Cancer Center medical records from 1990 to 2012 were reviewed. Patients who received chemotherapy with or without radiation therapy (RT), or RT alone, for completely resected stage I to stage IV uterine carcinosarcoma with rhabdomyosarcoma differentiation were included.ResultsOf 53 patients, International Federation of Gynecology and Obstetrics stage distribution was as follows: I, 13 (24.5%); II, 8 (15.1%); III, 13 (24.5%); and IV, 19 (35.9%). Forty-one (77.4%) of 53 patients received adjuvant chemotherapy, and 34% of the patients who received chemotherapy also received pelvic RT or intravaginal brachytherapy (IVRT). Twelve (22.6%) of the 53 patients received only pelvic RT with/without IVRT. Paclitaxel-carboplatin was the most commonly used adjuvant chemotherapy treatment. The median PFS for the entire cohort was 13.4 months (95% confidence interval [CI], 10.5–17.0). The median OS for the entire cohort was 23.0 months (95% CI, 16.9–34.3). The median PFS periods by stage were 15.9 months for stages I/II versus 11.2 months for stages III/IV (P= 0.012). Median OS was not reached in the early-stage cohort. The median OS for the late-stage cohort was 20.9 months (P= 0.004). The median PFS periods by treatment were 10.4 months for pelvic RT with/without IVRT group versus 13.1 months for chemotherapy with/without pelvic RT with/without IVRT group (P= 0.498). The median OS periods by treatment were 23.6 months for chemotherapy with/without pelvic RT with/without IVRT group versus 16.9 months for pelvic RT with/without IVRT group (P= 0.501).ConclusionThe results suggest that chemotherapy alone or in combination with RT is associated with longer PFS and OS compared to RT alone. Only the stage of disease significantly affected PFS and OS.

scholarly journals International Study of Primary Mucinous Ovarian Carcinomas Managed at Tertiary Medical Centers

2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  
Keyword(s):  
Early Stage ◽  
Statistical Tests ◽  
Stage Iv ◽  
Stage I ◽  
Stage Iii ◽  
Oncologic Outcomes ◽  
Disease Stage ◽  
Ovarian Carcinomas ◽  
Early Stage Disease ◽  
Medical Centers

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.

Validation of a high performing blood test for multiple major cancer screenings.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10561-10561
Author(s):  
Linhao Xu ◽  
Jun Wang ◽  
Weifeng Ma ◽  
Xin Liu ◽  
Sihui Li ◽  
...  
Keyword(s):  
Cancer Screening ◽  
Blood Test ◽  
Retrospective Cohort ◽  
Early Stage ◽  
Stage I ◽  
Cancer Type ◽  
Data Set ◽  
Specificity And Sensitivity ◽  
Cancer Types ◽  
Stage Stage

10561 Background: Early detection at the localized stage is pivotal for the successful treatment of various cancer types. Although several cancers already have routine screening approaches, the comprehensive utilities are impeded for various reasons, e.g., low accuracy, high cost, limited availability of required facilities, especially in the developing countries. Therefore, an accurate, cost-effective, and non-invasive test for multiple major cancer screening is in high demand. We previously reported a cfDNA methylation test, which can detect five major cancer types with high specificity and sensitivity, especially at the early stage (stage I). These five major cancers, including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and esophageal cancer (EC), account for 56% of new cancer cases and 60% of cancer-related deaths yearly in China. Here, we report the result in an independent cohort as a further validation of this multi-cancer screening test. Methods: The high-throughput targeted methylation profiling platform, Aurora, was used to analyze the plasma samples from an independent retrospective cohort containing 505 healthy controls and ̃200 cases for each cancer type. A locked model based on our previous pilot study (reported in AACR 2020 and 2021) was applied to this data set to assess the overall performance. Results: The Area Under Curves (AUC) of the classifier for LC, BC, CRC, GC and EC are 97.3%, 96.2%, 92.0%, 94.0% and 93.5%, respectively. At a fixed specificity of 99%, the sensitivities for LC, BC, CRC, GC and EC are 84%, 75%, 82%, 85% and 78%, respectively. Conclusions: A methylation blood test for five major cancer screening has been validated in a large retrospective cohort. Its high sensitivity for each cancer type, especially at the early stage (stage I), and easy to use suggests it can be implemented in real clinical world. A large prospective clinical trial is undergoing to further validate this test in asymptomatic populations.

scholarly journals Pan-cancer subtyping in a 2D-map shows substructures that are driven by specific combinations of molecular characteristics

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Erdogan Taskesen ◽  
Sjoerd M. H. Huisman ◽  
Ahmed Mahfouz ◽  
Jesse H. Krijthe ◽  
Jeroen de Ridder ◽  
...  
Keyword(s):  
Therapy Response ◽  
Visual Exploration ◽  
Molecular Characteristics ◽  
Cancer Type ◽  
Breast Cancers ◽  
Data Types ◽  
Multiple Cancer ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Cancer Types

Abstract The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to move from single genome-wide measurements in a single cancer-type towards measuring several different molecular characteristics across multiple cancer-types. Although current approaches shed light on molecular characteristics of various cancer-types, detailed relationships between patients within cancer clusters are unclear. We propose a novel multi-omic integration approach that exploits the joint behavior of the different molecular characteristics, supports visual exploration of the data by a two-dimensional landscape, and inspection of the contribution of the different genome-wide data-types. We integrated 4,434 samples across 19 cancer-types, derived from TCGA, containing gene expression, DNA-methylation, copy-number variation and microRNA expression data. Cluster analysis revealed 18 clusters, where three clusters showed a complex collection of cancer-types, squamous-cell-carcinoma, colorectal cancers, and a novel grouping of kidney-cancers. Sixty-four samples were identified outside their tissue-of-origin cluster. Known and novel patient subgroups were detected for Acute Myeloid Leukemia’s, and breast cancers. Quantification of the contributions of the different molecular types showed that substructures are driven by specific (combinations of) molecular characteristics.

Predictive factors for metastasis in patients (pts) with gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15056-15056
Author(s):  
S. Kilickap ◽  
O. Dizdar ◽  
H. Harputluoglu ◽  
S. Aksoy ◽  
S. Yalcin
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Early Stage ◽  
Stage Iv ◽  
Stage I ◽  
Early Stage Disease ◽  
Increased Risk ◽  
Metastasis Development ◽  
The Mean

15056 Background: Determination of patients (pts) with early stage disease who have a high risk for developing metastatic disease is crucial. We investigated the risk factors associated with metastases development in pts with operable gastric cancer. Patients and Methods: In this retrospective study, pts with stage I-III and non-metastatic stage IV gastric cancer diagnosed between 1990 and 2006 were evaluated. The medical records of all pts including patient characteristics, laboratory results, histopathological examinations, were reviewed. Logistic regression methods were used to determine the risk factors for developing metastasis and to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: 184 pts (70% male, 30% female) were analyzed. The mean age ± standard deviation was 56.5±11.9. The mean age of female were higher than male (p=0.014). At the time of diagnosis, 13.6% of the pts had stage I, 19.0% had stage II, 53.3% had stage III, and 14.1% had non-metastatic stage IV disease. The tumors were distally localized in 80% of the cases. Median follow-up period was 35 months. During follow up, 51 pts developed metastases. Median time to metastases development was 14 months. Overall survival was shorter in pts who developed metastasis than those who did not. (20 months vs. not reached, respectively, p=0.002). In univariate analyses, stage (p=0.020), tumor localization (p=0.006), extracapsular lymphatic extension (ELE) (p<0.001), the number of metastatic lymph nodes (p=0.001), CEA level (p<0.001), lymphovascular invasion (LVI) (p=0.001), and perineural invasion (p=0.007) were associated with metastasis development. In multivariate analysis, elevated CEA levels (p=0.009; OR: 2.8; CI 95%: 1.29–6.19), LVI (p=0.041; OR: 2.2; CI 95%: 1.03–4.64) and ELE (p=0.029; OR: 2.3; CI 95%: 1.09–4.78) were associated with increased risk of metastasis development while distal localization (p=0.038; OR: 0.42; CI%: 0.18–0.95) was associated with decreased risk in pts with gastric cancer. Discussion: In pts with early stage or locally advanced gastric cancer, elevated CEA levels, LVI, proximal localization and ELE were associated with increased risk of developing metastasis. Aggressive treatment options and closer follow up should be considered for pts with these risk factors. No significant financial relationships to disclose.

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