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Journal Thoracic Oncology

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Abstracts <strong>Journal</strong> of <strong>Thoracic</strong> <strong>Oncology</strong> • Volume 12 Issue S1 January 2017<br />

POSTER SESSION 2 – P2.02: LOCALLY ADVANCED NSCLC<br />

BIOLOGY –<br />

TUESDAY, DECEMBER 6, 2016<br />

P2.02-002 ASSOCIATION BETWEEN VEGF GENE FUNCTIONAL<br />

POLYMORPHISMS AND CLINICAL AND PATHOLOGICAL<br />

CHARACTERISTICS OF NON-SMALL CELL LUNG CANCER<br />

Anna Shchayuk 1 , Evelina Krupnova 1 , Michael Shapetska 2 , Alena Mikhalenka 1 ,<br />

Natalia Chebotaryova 1 , Svetlana Pissarchik 3<br />

1 Institute of Genetics and Cytology, National Academy of Sciences of Belarus,<br />

Minsk/Belarus, 2 Belarusian State Medical University, Minsk/Belarus, 3 City Clinical<br />

Pathologoanatomic Bureau, Minsk/Belarus<br />

Background: Vascular endothelial growth factor (VEGF) is one of the most<br />

important angiogenic factor, which promotes endothelial cell growth and<br />

tumor neovascularization. VEGF expression is a marker of invasiveness and<br />

tumor progression in various cancers including in NSCLC. The aim of this study<br />

was to analyze association between VEGF gene functional polymorphisms<br />

and clinical and pathological characteristics of NSCLC. Methods: A total of<br />

276 people with histological diagnosis of squamous cell carcinoma (SCC)<br />

and adenocarcinoma (AC) were included in this study. All patients gave their<br />

informed consent. VEGF gene polymorphisms were determined by PCR-RFLP<br />

analysis. Statistical analysis of the material was carried out using SNPStats<br />

online program. Results: Analysis of rs699947 polymorphism association with<br />

clinical and pathological characteristics of the tumor showed that patients<br />

with -2578CC genotype are more likely to have a greater extent of the primary<br />

tumor (T2-T4) than a small non-invasive cancer (T1): p = 0.005; OR = 2.54, 95%<br />

CI: 1.35-4.77. Association between this polymorphism and regional lymph<br />

node metastasis and the stage of the disease was found. A-allele is protective<br />

against a more aggressive course of the disease: in patients with -2578AA<br />

genotype regional lymph node metastases (N1-3) occur less frequently as<br />

compared to -2578CC genotype carriers (p = 0.0098; OR = 0.34, 95% CI: 0.17-<br />

0.69). -2578A-allele carriers are less likely to have stages of the disease III and<br />

IV (p = 0.012 and 0.015 respectively). A tendency of rs3025039 polymorphism<br />

influence on the histological type of the tumor was identified. + 936TT<br />

genotype is more common in patients with SCC as compared to AC (p = 0.055;<br />

OR = 4.78, 95% CI: 1.01-22.71). For rs2010963 polymorphism the association<br />

with clinical and pathological characteristics of NSCLC was not identified.<br />

Haplotype analysis of three studied polymorphisms of VEGF gene showed a<br />

significant association between -634C/-2578C/+936C haplotype and a small<br />

non-invasive cancer (p = 0.0068). -634G/-2578C/+936C haplotype carriers<br />

showed high aggressiveness of the disease (stage - p = 0.0061; regional lymph<br />

node metastasis - p= 0.0014). Conclusion: -2578CC genotype of rs699947<br />

polymorphism VEGF gene is associated with a large size of the primary tumor<br />

focus, the occurrence of regional lymph node metastasis and a greater stage<br />

of the disease. High aggressiveness of the disease was revealed in -634G/-<br />

2578C/+936C haplotype carriers. A significant association between -634C/-<br />

2578C/+936C haplotype and small non-invasive cancer was showed.<br />

Keywords: VEGF gene polymorfisms, vascular endothelial growth factor, nonsmall<br />

cell lung cancer, angiogenesis<br />

POSTER SESSION 2 – P2.02: LOCALLY ADVANCED NSCLC<br />

BIOLOGY –<br />

TUESDAY, DECEMBER 6, 2016<br />

P2.02-003 INCREASED CIRCULATING CYTOKERATIN-19 (CYFRA<br />

21-1) IS PREDICTIVE OF POOR OUTCOME OF LOCALLY ADVANCED<br />

SQUAMOUS CELL CARCINOMA IN LUNG<br />

Jingbo Wang 1 , Zhe Ji 1 , Jianzhong Cao 2 , Yan Ma 3 , Wei Jiang 1 , Lipin Liu 1 , Yu Men 1 ,<br />

Cai Xu 1 , Xiaozhen Wang 1 , Zhou Guang Hui 1 , Jun Liang 1 , Jima Lv 1 , Zongmei Zhou 1 ,<br />

Zefen Xiao 1 , Qinfu Feng 1 , Dongfu Chen 1 , Hongxing Zhang 1 , Weibo Yin 1 , Luhua<br />

Wang 1<br />

1 Radiation <strong>Oncology</strong>, Cancer Hospital, Chinese Academy of Medical Sciences,<br />

Beijing/China, 2 Cancer Hospital of Shanxi Cancer Hospital, Taiyuan/China,<br />

3 Radiology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing/China<br />

Background: Our goal was to evaluate the prognostic significance of<br />

circulating tumour markers in locally advanced squamous cell carcinoma of<br />

lung (LA-SCCL). Methods: Eligible patients included those with histologically<br />

proven LA-SCCL, available baseline tumour marker panel analysis (carcinoembryonic<br />

antigen [CEA], carcinoma antigen 125 [CA125], squamous cell<br />

carcinoma antigen [SCC], cytokeratin-19 [Cyfra 21-1] and neuron-specific<br />

enolase [NSE]) and receiving definitive radiotherapy. Age, gender, radiation<br />

dose, baseline KPS, smoking history, weightless, TNM stage, PET staging,<br />

RT technique and treatment modality (radiotherapy alone vs. sequential<br />

chemoradiotherapy vs. concurrent chemoradiotherapy) were also<br />

retrospectively collected. To dichotomise the continuous values of tumour<br />

markers into categorical variables, ROC analysis was adopted to identify the<br />

optimal cutoff values using the progression within 2 years after diagnosis as<br />

the endpoint. Cox regression based multivariate analyses were used to select<br />

independent factors correlated with various survival endpoints. Overall<br />

survival (OS), local regional progression free survival (LRPFS) and distant<br />

metastasis free survival (DMFS) were defined as the time from diagnosis<br />

until the first occurrence of specific event: death, local-regional recurrence or<br />

distant metastasis, respectively. Progression free survival (PFS) was defined<br />

as the duration between the cancer diagnosis and the date of any progression<br />

or cancer related death. Results: A total of 216 patients with LA-SCCL were<br />

analyzed. The optimal discriminative values for CEA, CA125, SCC, Cyfra 21-1<br />

and NSE in predicting 2-y progression were 5.3 ng/ml, 17.0 U/ml, 2.5 ng/ml,<br />

5.2 ng/ml and 17.8 ng/ml, respectively. Univariate analyses showed that<br />

increased Cyfra 21-1 was associated with inferior OS, LRPFS, DMFS and PFS.<br />

Increased NSE was predictive of poor OS, DMFS and PFS. CEA also presented<br />

significant correlation with OS. Under multivariate analysis involving all<br />

clinical and tumour markers, IIIA stage, better performance status, CEA ≤<br />

5.3 ng/ml and Cyfra 21-1 ≤ 5.2 ng/ml were independently associated with<br />

improved OS. IMRT technique, RT dose ≥ 60Gy and Cyfra 21-1 ≤ 5.2 ng/ml were<br />

correlated with better LRPFS. None-smoker, IIIA stage, NES ≤ 17.8 ng/ml were<br />

favourable predictors for DMFS. IIIA stage, KPS ≥ 80 and Cyfra 21-1 ≤ 5.2 ng/ml<br />

were advantageous factors related with favourable PFS. Conclusion: Baseline<br />

tumour marker panel including Cyfra 21-1, NSE and CEA can be prognostic of<br />

OS, local and distant tumor control for LA-SCCL, and should be recommended<br />

for baseline evaluation of tumour burden.<br />

Keywords: Non-small cell lung cancer, squamous cell carcinoma, serum tumor<br />

marker, prognosis<br />

POSTER SESSION 2 – P2.02: LOCALLY ADVANCED NSCLC<br />

BIOLOGY –<br />

TUESDAY, DECEMBER 6, 2016<br />

P2.02-004 REAL-TIME MONITORING OF CIRCULATING<br />

TUMOR CELLS TO EVALUATE RESPONSE OF NEOADJUVANT<br />

CHEMOTHERAPY IN LOCALLY ADVANCED NSCLC<br />

Miao Huang, Yuanyuan Ma, Yue Yang<br />

Peking University Cancer Hospital and Institute, Beijing/China<br />

Background: Enumeration and karyotyping of circulating tumor cells (CTCs)<br />

in therapeutic cancer patients is of particular clinical significance. The aim<br />

of this study is to evaluate therapeutic effect of neoadjuvant chemotherapy<br />

(NAC) by means of real-time monitoring of CTCs in locally advanced nonsmall<br />

cell lung cancer (NSCLC). Methods: Real-time monitoring of CTCs in the<br />

course of 2 cycles of platinum-based NAC was conduct in 34 locally advanced<br />

NSCLC patients. The integrated subtraction enrichment and immunostaining<br />

fluorescence in situ hybridization (SE-iFISH) method was applied to detect<br />

and characterize CTCs in peripheral venous blood. Chest CT was used to<br />

evaluate therapeutic response with RECIST 1.1 as the evaluation criterion.<br />

Results: Of the 34 patients enrolled, 13 acquired partial response (PR) and<br />

21 were stable diseases (SD) after NAC. The numbers of CTCs were found<br />

decrease in 70% of PR patients and only 25% of SD patients. The changes of<br />

CTC count were significantly different between PR and SD group (p=0.009).<br />

The positive rate of CTCs with triploidy of chromosome 8 increased after 2<br />

cycles platinum-based NAC, and the elevation was even more remarkable in<br />

SD group. Conclusion: The changes of CTC count after NAC were in accordance<br />

with CT responses. Triploidy of chromosome 8 CTC was correlated with<br />

primary resistance to platinum-based chemotherapy. Real-time monitoring<br />

of CTC count and karyotype may be of clinical value in rapid evaluation of<br />

therapeutic effect and monitoring occurrence of chemo-resistance.<br />

Keywords: non-small cell lung cancer, neoadjuvant chemotherapy, Circulating<br />

tumor cell, Therapeutic response<br />

POSTER SESSION 2 – P2.02: LOCALLY ADVANCED NSCLC<br />

BIOLOGY –<br />

TUESDAY, DECEMBER 6, 2016<br />

P2.02-005 A RARE CLINICAL PRESENTATION OF EGFR-MUTANT<br />

NON-SMALL CELL LUNG CANCER WITH OLIGO-ACROMETASTASIS<br />

Pınar Akın Kabalak 1 , Tuba Inal Cengiz 1 , Ugur Yılmaz 1 , Derya Kızılgöz 1 , Metehan<br />

Karaca 2 , Fatma Canbay 1 , Inci Uslu 3 , Yetkin Ağaçkıran 4 , Kyle Wang 5<br />

1 Chest Disease, Ankara Atatürk Chest Disease and <strong>Thoracic</strong> Surgery Training and<br />

Research Hospital, Ankara/Turkey, 2 Radiation <strong>Oncology</strong>, Ankara Atatürk Chest<br />

Disease and <strong>Thoracic</strong> Surgery Training and Research Hospital, Ankara/Turkey,<br />

3 Nuclear Medicine, Ankara Atatürk Chest Disease and <strong>Thoracic</strong> Surgery Training and<br />

Research Hospital, Ankara/Turkey, 4 Ankara Atatürk Training and Research Hospital,<br />

Ankara/Turkey, 5 Radiation <strong>Oncology</strong>, University of North Carolina Hospitals,<br />

Chapel Hill/NC/United States of America<br />

Background: 44% of acrometastasis are originated from primary lung tumors<br />

and metastasis to digits is seen in 0.2% of patients with lung cancer. After<br />

Copyright © 2016 by the International Association for the Study of Lung Cancer<br />

S443

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