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M. Kang



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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P1.07-038 - Surgical Treatment for T4 Non-small Cell Lung Cancer Invading Mediastinal Structures (ID 2642)

      09:30 - 16:30  |  Author(s): M. Kang

      • Abstract

      Background
      Non-small cell lung cancer (NSCLC) with invasion of mediastinal structures is now classified as stage IIIA or IIIB according to N stages, and has been considered surgically unfavorable. However, in a selected group of these patients, better results have been reported after surgical resection compared to non-surgical group. The aim of this study is to evaluate the role of surgical resection in treatment of mediastinal T4 NSCLC and risk factors that should be considerated.

      Methods
      Among 2215 patients who underwent surgical intervention for non-small cell lung cancer from Aug 1987 to Dec 2011 in Korea cancer center hospital, 119 patients had an invasion of T4 mediastinal structures. Their medical records in Data Base were reviewed, and they were followed up completely until Apr 2013. Surgical results and prognostic factors of NSCLC invading mediastinal structures were evaluated retrospectively.

      Results
      Lung cancer was resected completely in 83 patients (69.7%, 83/119). Lobectomy was performed in 25 patients and pneumonectomy in 58. The mediastinal structures invaded by primary tumor were great vessels (44.6%), heart (15.7%), vagus nerve (12.1%), carina (8.4%), esophagus (9.6%), and vertebral body (9.6%). Nodal status was N0 in 16, N1 in 28, and N2 in 39. Neoadjuvant therapy was executed in 11 (13.25%) and adjuvant therapy was added in 53 (63.9%) out of complete resection group (n=83). Complication rate was 30.1% and operative mortality was 8.4% in complete resection group. Median and 5 year overall survival including operative mortality was 20.1 months and 22.7% in complete resection group (n=83), and 6.1months and 0% in exploration only group (n=36, p=.001). Overall 5year survival rates of N2(-) and N2(+) group were 32.8% and 9.3% respectively (p=.002). There was no survival difference between T4 N2(-) group and other IIIA stage group. Mediastinal structure invaded, old age, gender, neoadjuvant and adjuvant chemotherapy showed no significant prognostic difference.

      Conclusion
      The operative risk of NSCLC invading mediastinal structures was high because of high rate of pneumonectomy and wider range of resection, however it can be acceptable. Long-term result of complete resection was favorable in selected group. Aggressive surgical approach is recommended in well selected patients with good performance and N2(-) in mediastinal T4 group. Stage grouping of T4N2(-) patients in AJCC 7th edition is thought to be adequate when complete resection was likely.

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    P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.02-012 - Cysteine dioxygenase 1 (CDO1) : A novel tumor suppressor gene regulated by hypermethylation. (ID 2207)

      09:30 - 16:30  |  Author(s): M. Kang

      • Abstract

      Background
      Lung cancer is one of the most common causes of cancer-related deaths worldwide. Effective early diagnosis and targeted therapies for lung cancer to reduce mortality and incidence would benefit from in-depth study on molecular mechanism of lung carcinogenesis, but these are largely unknown. In our previous study, we reported a novel hyper-methylated gene, CDO1, encoding cysteine dioxygenase 1 that involved in the conversion of cysteine to cysteine sulfinate, and plays a key role in taurine biosynthesis. In this study, we evaluated the functional characteristics of CDO1 in Lung squamous cell carcinoma (LSCC).

      Methods
      We analyzed expression levels of CDO1 mRNA and protein in tumor and normal tissue pairs from 12 LSCC patients were determined by RT-PCR and Western blot analysis. In order to determine whether high levels of CDO1 expression contributed to the LSCC cell proliferation, migration, invasion and colony formation, we employed a CDO1-expressing vector pEGFP_C3_CDO1 to transfect CDO1 into LSCC cell lines (HCC-95, HCC-1588). Furthermore, we performed gene expression profile analysis using human whole genome oligonucleotide chip (Agilent).

      Results
      Downregulation of CDO1 mRNA level was observed in LSCC cell lines and tumors derived from patient tissues. In cell proliferation assay, the number of HCC-95 and HCC-1588 cells transfected with pEGFP_C3_CDO1 decreased to 58-70% compared with pEGFP_C3 (p<0.05). Moreover, the forces expression of CDO1 in two different types of LSCC cell lines significantly decreased the cell migration, invasion, and colony formation ability (p<0.05). Furthermore, we showed that overexpression of CDO1 make change of several signal molecules in lung cancer cells using microarray analysis.

      Conclusion
      In this study, we found that CDO1 expression was regulated by DNA methylation, and this epigenetic regulated CDO1 might be a novel tumor suppressor gene and potentially valuable biomarker for lung squamous cell carcinoma.

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    P3.21 - Poster Session 3 - Diagnosis and Staging (ID 171)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P3.21-011 - Proposal of an alternative prognosis prediction method - Hazard Ratio scoring system based on well-suited nomogram. (ID 3310)

      09:30 - 16:30  |  Author(s): M. Kang

      • Abstract

      Background
      The prediction of prognosis has been essential for programing cancer treatment strategies. In NSCLC, the TNM staging system is a worldwide standard form and there have been considerate improvements in its accuracy. However, the TNM staging system still has many limitations. It cannot reflect all the detailed pronostic parameters. In the AJCC system, prognostic factors are used to make a mutually exclusive partitioning of patients and ordering of patients assumes that all the patients receive surgery only. Therefore, treatment-specific prognosis cannot be predicted in the AJCC system. The prognoses of TNM stages may be different between institutes, however the same hazard ratio represents the same prognosis. So we propose a hazard ratio scoring system as an alternative prognosis predition method which can be used for specific clinical purposes.

      Methods
      A nomogram was developed and validated using clinical data of 2,115 patients who received surgery for NSCLC. Patients were randomly divided into the training set (n=1,060) and validation set (n=1,055). Nomogram predictions for 3- and 5-year overall survival were calculated for each patient in training set by using Cox proportional hazard model and compared with actual survival. Validation set was used for evaluating nomogram and AJCC staging.

      Results
      The median overall survival was 55.6 months for the training set and 58.1 months for validation set. In the prediction of 5-year survival, the nomogram showed an area under the receiver operating characteristic curve of 0.78 (95% CI, 0.76-0.79) in the training set. The validation set showed a good discrimination with an AUC of 0.85 (95% CI, 0.82-0.89). AJCC TNM staging system showed an AUC of 0.74 (95% CI, 0.70-0.79) with a training set.

      Conclusion
      The nomogram represented the survival results of a single institute more accurately than AJCC TNM staging system. The hazard scoring system cannot replace the position of the AJCC TNM system, however it can be used for programing treatment strategies concerning new or site-specific treatment methods, biomarkers and future clinical parameters.