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S. Cho



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    MO10 - Molecular Pathology II (ID 127)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO10.01 - Integrative and comparative genomic analysis of East-Asian lung squamous cell carcinomas (ID 2667)

      16:15 - 17:45  |  Author(s): S. Cho

      • Abstract
      • Presentation
      • Slides

      Background
      Lung squamous cell carcinoma (SqCC) is the second most prevalent type of lung cancer. Currently, no targeted-therapeutics are approved for treatment of this cancer, largely due to a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SqCC, we probed somatic genome alterations of lung SqCC cases from Korean patients.

      Methods
      We performed whole-exome sequencing of DNA from 104 lung SqCC samples from Korean patients and matched normal DNA. In addition, copy number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.

      Results
      This cancer cohort is characterized by a very high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of cigarette-smoke exposure. Seven genes demonstrated statistical enrichment for mutation (TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2 and PIK3CA). Comparative analysis between Korean and North American lung SqCC demonstrated similar spectrum of alterations in these two populations, in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SqCC.

      Conclusion
      These findings provide new steps towards the identification of genomic target candidates for precision medicine in lung SqCC, a disease with a significant unmet medical need.

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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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      P1.07-025 - Long-term Survival of Patients with cN2/pN2 Non-Small-Cell Lung Cancer (ID 2026)

      09:30 - 16:30  |  Author(s): S. Cho

      • Abstract

      Background
      Optimal management of stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. However, surgery is used increasingly for stage IIIA NSCLC. We believe that surgical outcome of NSCLC patients with clinical N2 and pathological N2 (cN2/pN2) is worst among the NSCLC patients with cN2 disease. Analysis aimed at evaluating survival rates of patients with cN2/pN2 stage, and at studying prognostic factors for long-term survival.

      Methods
      This is a retrospective study of 72 NSCLC patients with cN2/pN2 stage who underwent surgery with neoadjuvant or adjuvant treatment from 2003 to 2011. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier methods. A multivariate analysis for prognostic factors was performed by the Cox proportional hazards regression model.

      Results
      The median follow-up time was 24.5 months (range, 1 to 110 months) for 72 NSCLC patients. Neoadjuvant treatment was administered to 32 patients (44.4%), and adjuvant therapy was given to 40 patients (55.6%). Pneumonectomies were performed more frequently in patients who were treated with neoadjuvant therapy (25% vs. 15%). Complete resection was achieved more commonly in patients who underwent surgery followed adjuvant treatment (95% vs. 75%). Five year OS was 40.5% and 3-year DFS was 34.3%. In a multivariate analysis, incomplete resection was prognostic for a worse OS (hazard ratio: 3.07, 95% CI: 1.20 to 7.86). The more advanced pathological T stage was prognostic factor for a worse DFS (hazard ratio: 3.21, 95% CI: 1.42-7.24). Number of metastatic lymph node is important prognostic factor for OS and DFS.

      Conclusion
      Favorable survival can be achieved in cN2/pN2 NSCLC patients after resection with neoadjuvant therapy or adjuvant therapy. Survival is more favorable for complete resection than incomplete resection.

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    P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.12-022 - Predictive value of SUV max/invasive size ratio in the subtypes of lung adenocarcinoma (ID 3186)

      09:30 - 16:30  |  Author(s): S. Cho

      • Abstract

      Background
      In lung adenocarcinoma, prognostic importance of maximum standardized uptake (SUV max) value on positron emission tomography (PET) has been well observed. Different subtypes had different 18F-fluorodeoxyglucose (FDG) uptake, and it was also related with tumor size. The ratio of SUV max and tumor size was supposed to be different depending on the subtypes of lung adenocarcinoma.

      Methods
      Medical records of the lung adenocarcinoma patients who underwent surgery in Seoul National University Bundang Hospital between 2003 and 2012 were reviewed. Ratio of SUV max and invasive tumor sizes was calculated and categorized into two groups. Group 1 included patients of ratio < 1.5, and Group 2 included the rest. The subtypes of lung adenocarcinoma were categorized into 4 groups; solid, acinar, lepidic, papillary according to their pathologic reports. Overall survival and disease-free survival rates of Group 1 and 2 were compared in each predominant subtype patients.

      Results
      Total number of patients was 680. The average ratio of SUV max/invasive size was 1.63. The ratio of SUV max/invasive size of solid subtype was 2.48 and it was significantly higher than acinar and lepidic subtypes. (p<0.000) Overall survival (OS) and disease-free (DF) survival of lepidic subtype were 39.3 months and 41.4 months each, and were significantly higher than solid and acinar subtypes. OS and DF of Group 1 were 36.4 and 32.8 each. Those of Group 2 were 29.8 and 21.6 months. Group 1 had significantly longer OS and DF than Group 2. (p<0.000, and p=0.001 each) In solid subtype, OS and DF of Group 1 were 32.8 and 27.7 months and those of Group 2 were 22.7 and 17.6. But there were no significant differences. (p=0.117 and p=0.123 each) In acinar subtype, OS and DF of Group 1 were 38.2 and 34.4 months, those of Group 2 were 32.9 and 24.3 months. The differences were statistically significant. (p<0.000, p=0.023, each) Three-year overall survival rates and 3-year disease-free survival of Group 1 were 45.2% and 39.1%. Those survival rates of Group 2 were 32.2% and 19.2% respectively. Recurrence hazard ratio of Group 2 was 1.68. (p<0.000, 95% confidence interval 1.379-2.061) In acinar subtype, recurrence hazard ratio of Group 2 was 1.83 and there was significant difference. (95% confidence interval: 1.410-2.381, p< 0.000) In other subtypes, recurrence hazard ratio showed no significant differences.

      Conclusion
      Ratio of SUV max and invasive tumor size had limited prognostic value in subtypes of lung adenocarcinoma. It could be used as a prognostic factor for recurrence in acinar predominant subtype category.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-013 - Risk factors for locoregional failure in completely resected N1 non-small cell lung cancer without postoperative radiotherapy (ID 1316)

      09:30 - 16:30  |  Author(s): S. Cho

      • Abstract

      Background
      N1 disease is a subset of non-small cell lung cancer (NSCLC) with a different prognosis than other subsets. Although the NCCN guideline recommends adjuvant chemotherapy alone in completely resected N1 disease, locoregional failure, which could have been prevented by postoperative radiotherapy (PORT), may not be uncommon. Using PORT with modern techniques has resulted in significantly higher rates of local control, disease-free survival, and overall survival. Therefore, this study aimed to evaluate the actuarial rates of locoregional failure in patients with pathologic N1 NSCLC and to identify the risk factors associated with an increased risk of locoregional failure, which could have been potentially prevented by PORT after complete resection.

      Methods
      Between 2003 and 2010, we enrolled 136 patients who underwent complete resection with pathologically confirmed N1 disease through the prospective lung cancer database of Seoul National University Bundang Hospital. Patients who underwent neoadjuvant therapy, adjuvant radiotherapy, or operative mortality were excluded. Multiple factors potentially related to outcomes including patient-related factors, surgery-related factors, and pathologic factors were extensively evaluated. Locoregional failure, which could have been potentially prevented by PORT, was defined as recurrence at either a bronchial stump, or a resected margin of the lung, hilum, and mediastinum. Other failures were ipsilateral lung recurrence, pleural seeding, and metastasis of distant organs. Univariate analysis by a log rank test and multivariate analysis by the Cox proportional hazards model were performed to identify risk factors independently associated with a higher risk of locoregional failure.

      Results
      The median follow-up duration was 45 months (6-114) and recurrence developed in 54 (40%) patients. The actuarial 5-year rates of disease-free survival and overall survival were 56% and 66%, respectively. From the perspective of first site recurrence, 23 (17%) locoregional failures, which could have been potentially prevented by PORT, included recurrence in the mediastinum in 10, bronchial stump in 5, regional lymph nodes in 4, and mediastinum + others in 4. The 31 (23%) other failures included a distant organ in 17, ipsilateral lung in 12, and pleural seeding in 2. The median survival time from locoregional failure and other failures was 41 and 57 months, respectively; however, there was no significant difference. Risk factors of locoregional failure were squamous cell carcinoma, number of involved node (>1), pathologic stage (IIIA), interlobar node involvement, more than 2 node stations of involvement, and a lymph node ratio greater than 10% by univariate analysis. Pathologic stage (HR=4.768, 95% CI=1.641-13.859, p=0.01), interlobar node involvement (HR=2.783, 95% CI=1.057-7.327, p=0.04), and squamous cell carcinoma (HR=2.449, 95% CI=0.929-6.454, p=0.07) were independent risk factors by multivariate analysis.

      Conclusion
      Locoregional failure was more common than expected, and pathologic stage, interlobar node involvement, and cell type were independent risk factors for locoregional failure after complete resection of N1 NSCLC. A prospective clinical trial may be necessary to evaluate the effectiveness of adjuvant radiotherapy in patients with these risk factors.