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Y.M. Shim



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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 - 16:20  |  Author(s): Y.M. Shim

      • 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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    O23 - Imaging and Screening (ID 125)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      O23.03 - Metabolic Imaging Based Prognostic Model for Predicting Survival of Patients with Stage I Non-Small Cell Lung Cancer (ID 1841)

      16:35 - 16:45  |  Author(s): Y.M. Shim

      • Abstract
      • Presentation
      • Slides

      Background
      The objective of this study was to develop a pretreatment prognostic model based on metabolic imaging biomarkers that could be used to predict overall survival (OS) in patients with stage I non–small cell lung cancer (NSCLC).

      Methods
      We evaluated 198 patients with pathologic stage I NSCLC who underwent pretreatment FDG PET/CT. Metabolic imaging biomarkers included maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and coefficient of variation (COV) for primary tumors. SUV is a semiquantitative index of metabolic activity. TLG is a volumetric measurement of tumor glycolytic activity. COV is an index of tumor uptake heterogeneity. The prognostic significance of clinical variables and imaging biomarkers (age, sex, histologic cell type, tumor size, SUVmax, TLG, COV) was assessed by Cox proportional hazards regression model. Statistically significant clinical variables and imaging biomarkers in the multivariable analysis were used to construct a prognostic model for predicting survival. The predictive accuracy of the prognostic model was evaluated by Harrell's concordance index (C-index).

      Results
      Median follow-up for surviving patients was 7.5 years with a range of 5.2 to 9.9. At the time of analysis, 52 (26.3%) patients had died. Age (HR = 1.05 for 1-year increase, P = 0.007), histologic cell type (HR = 0.54 for adenocarcinoma, P = 0.027), SUVmax (HR = 1.08 for 1-unit increase, P = 0.002), and TLG (HR = 1.23 for a doubling of TLG, P = 0.021) were significantly associated with OS by univariable analysis, whereas only age (HR = 1.07 for 1-year increase, P = 0.005) and SUVmax (HR = 1.04 for 1-unit increase, P = 0.012) were significantly associated with OS by multivariable analysis. The final prognostic model included age as a clinical variable and SUVmax as a metabolic imaging biomarker to predict OS. The predictive performance of the prognostic model for OS was not improved by addition of TLG or COV. The C-index was 0.694 for the final model with age and SUVmax. Kaplan-Meier survival curves stratified by risk score showed high-risk group of patients (n = 58, SUVmax > 12 and age > 60) and low-risk group of patients (n = 48, SUVmax ≤ 12 and age ≤ 60). Figure 1

      Conclusion
      A new prognostic model based on pretreatment metabolic imaging may have potential clinical utility for risk stratification of stage I NSCLC patients.

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-012 - Pulmonary Resection for Stage I Non-Small Cell Lung Cancer in Elderly Patients (ID 1282)

      09:30 - 09:30  |  Author(s): Y.M. Shim

      • Abstract

      Background
      With the increase in life expectancy, surgical treatment of non-small cell lung cancer (NSCLC) in elderly patients became more frequent. The aim of this study is to evaluate the risk factors for short and long-term outcomes after pulmonary resection in the elderly patients with stage I NSCLC.

      Methods
      From October 1994 to December 2011, the patients who were surgically treated with curative intent and pathologically diagnosed as stage I NSCLC were included. The patients were divided into two groups; elderly group (≥70 years) and younger group (<70 years). Comorbidity and surgical factors were analyzed for thirty-day mortality, hospital stay and overall survival in both groups.

      Results

      The Risk factors for short and long term outcome after pulmonary resection in elderly patients with stage I NSCLC
      Risk factor 30-day mortality (Pearson’s Chi-Square Test) Hospital stay (Linear Regression Model) 5-year survival (Cox Hazard Model)
      HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
      DLCO less than 70% 12.9 (1.8-93.6) 0.001 5.0 (2.7-7.3) < 0.001 3.4 (1.5-8.0) 0.004
      FEV~1~/FVC less than 70% NS 2.5 (0.8-4.3) 0.005 NS
      Open thoracotomy NS 3.6 (2.3-4.8) < 0.001 NS
      Pulmonary tuberculosis NS NS 3.3 (1.5-7.5) 0.004
      Interstitial pulmonary fibrosis NS NS 5.0 (1.4-18.0) 0.015
      Creatinine higher than 1.5mg/dL NS NS 5.7 (1.3-25.3) 0.022
      Extensive resection NS NS 4.4 (1.4-14.0) 0.012
      Total 1,340 patients were enrolled and 285 patients (21.3%) were classified as the elderly group and 1,055 patients (78.7%) as the younger group. The thirty-day mortality was 8 of 1,340 patients (0.6%) and all of the patients were elderly. The only independent factor for thirty-day mortality in elderly group was diffusing capacity for carbon monoxide (DLCO) less than 70% of predicted (hazard ratio, 12.9; p = 0.001). The elderly group had significantly longer hospital stay (11.2 12.2 vs. 8.0 6.7 days, p < 0.001). Open thoracotomy (p < 0.001), DLCO less than 70% of predicted (p < 0.001) and percentage of one second forced expiratory volume over forced vital capacity (FEV~1~/FVC) less than 70% (p = 0.005) were significantly associated with longer hospital stay. In-hospital complication rate in elderly patients was also significantly higher (47.7 vs. 26.9%, p < 0.001). 5-year overall survival rates were 91.1% in the younger group and 66.2% in the elderly group. In the elderly group, previous history of tuberculosis (p = 0.004) and interstitial pulmonary fibrosis (IPF; p = 0.015), DLCO less than 70% of predicted (p = 0.004), preoperative creatinine higher than 1.5 mg/dL (p = 0.022), and more extensive pulmonary resection (p = 0.012) were the independent risk factors for overall survival. On the other hand, previous history of IPF (p < 0.001) and pathologic stage IB over IA (p < 0.001) were the independent risk factors in the younger group.

      Conclusion
      Pulmonary resection for the elderly patient requires caution, particularly in case of low diffusing capacity (DLCO < 70%) or airflow limitation (FEV1/FVC < 70%).

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    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 2
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      P3.09-013 - Outcomes and predictors for recurrence and survival after neoadjuvant concurrent chemoradiation followed by operation in patients with clinical stage III-N2 non-small-cell lung cancer (ID 2053)

      09:30 - 09:30  |  Author(s): Y.M. Shim

      • Abstract

      Background
      This study assessed the impact of imaging, surgical, histopathologic and patient-related factors on the risks of local and distant recurrence and overall survival for patients with stage III-N2 non small cell lung carcinoma (NSCLC) undergoing definitive resection after neoadjuvant concurrent chemoradiation (neoCCRT).

      Methods
      We retrospectively examined 129 consecutive patients with stage III-N2 NSCLC received neoCCRT followed by curative surgery between 2008 and 2011. We reviewed clinical data and operation method. We also analyzed histopathologic factors such as subtype, pathologic invasive tumor characteristics, differentiation, residual tumor size, or the number of residual LNs as well as imaging characteristics on chest CT and PET/CT. Disease free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and predictive factors for recurrence and survival were identified by univariate and multivariate Cox-proportional analyses.

      Results
      112 (87%) patients were pathologically staged for N2-positive status (82 patients by mediastinoscopic biopsy and 30 patients by EBUS). The 5-year recurrence rate was 28.3 %, and the 5-year survival rate was 43.4 %. Five-year OS for patients with recurrence compared with those without was 29.5 versus 59.1 % (P = 0.028). Based on the multivariate Cox-proportional analysis and log-rank test, history of adjuvant therapy was the only significant prognostic predictor for prolonged OS (HR 0.134, 95 % CI 0.039–0.455, P = 0.001). As for recurrence, less size decrease on CT (HR 1.030, 95 % CI 1.005–1.056, P = 0.017), higher T stage (HR 2.450, 95 % CI 1.322–4.540, P = 0.004), larger residual tumor size on the pathologic specimen (HR 1.124, 95 % CI 1.010–1.252, P = 0.016), and presence of lymphovascular invasion (HR 4.180, 95 % CI 1.093–15.984, P = 0.037) were the significant predictors in both the multivariate Cox-proportional analysis and the log-rank test. Figure 1

      Conclusion
      Recurrence remains high in resected stage III-N2 NSCLC patients after neoCCRT and nodal downstaging, and patients who received adjuvant therapy had longer overall survival rate than patients who did not. Size decrease on CT, T stage, residual tumor size on the pathologic specimen, and presence of lymphovascular invasion would be predictive for higher recurrence and may necessitate more aggressive adjuvant treatment.

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      P3.09-015 - The role of adjuvant treatment in N2 positive non-small cell lung cancer patients treated with neoadjuvant chemoradiation followed by surgery: A retrospective single center experience. (ID 2673)

      09:30 - 09:30  |  Author(s): Y.M. Shim

      • Abstract

      Background
      The optimal management of locally advanced N2 positive non-small cell lung cancer (NSCLC) is still controversial. Some studies have shown promising results of neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection in terms of survival benefit without increasing morbidity and mortality. However, the role of adjuvant treatment after completion of neoadjuvant CCRT followed by surgery in N2 positive NSCLC patients has not defined yet.

      Methods
      From March 2006 to December 2011, 249 N2 positive NSCLC patients received neoadjuvant CCRT (weekly docetaxel/cisplatin with 45Gy/25Fx of thoracic radiotherapy) followed by curative surgery. Patients who died with post-operative complications within a month after surgery (n=5) were excluded to minimize selection bias.

      Results
      Among 244 patients, 80 patients (32.8%) receieved adjuvant radiotherapy alone, 26 patients (10.7%) received adjuvant chemotherapy alone, 57 patients (23.4%) received both of adjuvant radiotherapy/chemotherapy, and 80 patients (32.8%) did not receive adjuvant treatment. Survival was compared according to adjuvant treatment (any kind of adjuvant treatment [n=164, 67.2%] vs. no adjuvant treatment [n=80, 32.8%]). There was no significant differences between two groups in age over 60 years, ECOG performance, initial T stage, initial multistation N2 disease, completion of neoadjuvant CCRT, R0 resection, and pathologic down staging of N2 disease. In the univariate analysis, median overall survival (OS) and progression-free survival (PFS) were 54.1 months vs. 37.9 months (P=0.016) and 23.4 months vs. 17.7 months (P=0.239) in adjuvant treatment group and no adjuvant treatment group, respectively. In subgroup analysis, adjuvant treatment group showed significantly better OS than no adjuvant treatment group in patients who achieved N2 down staging by neoadjuvant CCRT (n=146, 59.8%) (78.1 months vs. 44.7 months, P=0.027) but not in patients who did not achieve pathologic N2 down staging (n=98, 40.2%) (32.3 months vs. 21.6 months, P=0.125).

      Conclusion
      This results suggest that adjuvant treatment may contribute survival benefit even after completion of neoadjuvant CCRT following curative surgery in N2 positive NSCLC. The role of adjuvant treatment should be seeked further in carefully selected patients who benefit most, such as CCRT sensitive patients who achieved pathologic N2 down staging.