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S. Jheon



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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 - 09:30  |  Author(s): S. Jheon

      • 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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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-003 - Alteration of the E-cadherin/β-catenin complex predicts poor response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (ID 161)

      09:30 - 09:30  |  Author(s): S. Jheon

      • Abstract

      Background
      Epidermal growth factor receptor (EGFR) mutation alone may be insufficient to predict clinical outcomes in the response to EGFR-tyrosine kinase inhibitor (TKI) therapy. The secondary mutation T790M and MET amplification are mechanisms of acquired resistance to EGFR-TKI in approximately 50% of patients, but the remaining mechanisms are unknown.

      Methods
      Eight metastatic lesions and specimens from 41 non-small cell lung carcinoma (NSCLC) patients harbouring activating EGFR mutations who underwent surgical resection and EGFR-TKI therapy were available. Immunohistochemistry was used to evaluate E-cadherin, β-catenin, and PTEN. Chromogenic in situ hybridisation and silver-enhanced in situ hybridisation were used to evaluate EGFR and MET amplification.

      Results
      Patients with E-cadherin/β-catenin alteration showed a poor objective response rate (ORR) (p=0.005) and shorter overall survival (p=0.059). Additionally, β-catenin alteration was associated with a poor ORR (p=0.012). In the metastatic tumours, 3 cases (37.5%) showed the acquisition of altered E-cadherin/β-catenin and PTEN loss, and 2 cases (25.0%) demonstrated MET/EGFR amplification.

      Conclusion
      Altered E-cadherin/β-catenin expression in NSCLC harbouring EGFR mutations was associated with a poor response to EGFR-TKI. During metastatic progression, changes in E-cadherin/β-catenin were found. These results may suggest that E-cadherin/β-catenin alteration is related to poor TKI response and resistance.

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    P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.11-015 - The prognostic value of total number of harvested lymph nodes and nodal ratio in node positive Non-small cell lung cancer (ID 1379)

      09:30 - 09:30  |  Author(s): S. Jheon

      • Abstract

      Background
      The purpose of this study is to evaluate the prognostic value of nodal ratio (NR) and total number of harvested lymph nodes (HLN) in postoperatively node positive Non-small-cell lung cancer (NSCLC).

      Methods
      Between June 2003 and December 2010, 1192 NSCLC patients had undergone surgical resection at Seoul National University Bundang Hospital. In this study, we excluded patients who had preoperative adjuvant treatments and were revealed to have pathologic T4, N3 or M1. Total 240 patients with N1 or N2 disease were analyzed in this study. According to the number of HLN and NR, we evaluated disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS).

      Results
      The median follow-up time was 36 months for the surviving patients and median total number of HLN was 23 (range, 6-64). On univariate analysis, patients with more than 20 HLN showed better 3-year DFS (55.6% vs 46.4% p = 0.045) and OS (78.2% vs 61.1%, p = 0.058), respectively. Patients who had NR > 0.1 showed worse 3-year DFS (39.3% vs 64.4%, p = 0.045), LRRFS (72.8% vs 84.0%, p = 0.037), DMFS (45.5% vs 69.6%, p < 0.001) and OS (62.9% vs 79.8%, p = 0.067), respectively. On multivariate analysis, NR > 0.1 showed statistical significance in 3-year LRRFS (p = 0.009) and marginal statistical significance in DFS (p = 0.083) and OS (p = 0.068).

      Conclusion
      The current nodal classification system does not include the total number of HLN and NR. The results of this study suggest that the total number of HLN and NR could be regarded as important prognostic factors and these factors might be used as decision criteria to postoperative adjuvant radiotherapy for patients with operable NSCLC.

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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 - 09:30  |  Author(s): S. Jheon

      • 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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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-009 - Clinicopathologic and Radiologic Characteristics of Lung Cancer Patients with Epidermal Growth Factor Receptor (EGFR), K-ras Mutation and Anaplastic Lymphoma Kinase (ALK) Rearrangement Presented as Nodular Ground-glass Opacity (ID 1388)

      09:30 - 09:30  |  Author(s): S. Jheon

      • Abstract

      Background
      Nodular ground-glass opacity (nGGO) lesion at computed tomography (CT) is a pattern of lung cancer at early stage, and a few studies revealed the characteristics of lung cancer presented as nGGO. Recently, several driver mutations of lung adenocarcinoma such as epidermal growth factor receptor (EGFR), K-ras mutation and anaplastic lymphoma kinase (ALK) rearrangement were found, and EGFR mutation is considered to play a role in early tumorigenesis of nGGO lesion, but the role of ALK rearrangement and K-ras mutation in nGGO lesion is still unknown.

      Methods
      We studied 217 nGGO lesions of 215 patients with lung cancer presented as nGGO, who had undergone surgical resection, retrospectively. We measured sizes of nGGO lesions at chest CT and calculated tumor disappearance rate (TDR). Pathologic analysis and molecular biomarker examination of surgical specimens were performed. Correlation between clinicopathologic and radiologic characteristics and molecular biomarker status was investigated.

      Results
      EGFR mutations were found in 119 among 217 cases (54.8%), positive ALK FISH in 6 among 217 cases (2.8%), and K-ras mutations in 7 among 154 cases (4.5%). Progressed disease stage (p=0.018), larger tumor size (p=0.035-0.037) were observed in ALK-positive group. Lower TDR, i.e. more solid portion in nGGO were observed in ALK-positive group, but it was not statistically significant (TDR 0.533 vs. 0.700, p=0.209). Female (p=0.004) and non-smoker or less smoker (p<0.001) were characteristics of EGFR-positive group, but tumor size and TDR revealed no significant difference. K-ras-positive group revealed no meaningful clinicopathologic and radiologic difference compared to K-ras-negative group. Histologic invasiveness was associated with advanced disease stage (p<0.001), lower TDR (p<0.001), and tumor size (p<0.001), but could not predict molecular biomarkers status. Low TDR was associated with nodal involvement (p<0.001), advanced disease stage (p<0.001), but not with molecular biomarkers status.

      Conclusion
      ALK rearrangement is not common in lung cancer presented as nGGO lesion, and associated with progressive stage and larger tumor size, suggestive of aggressive feature in the progression of lung adenocarcinoma. Role of K-ras mutation in nGGO lesion is indefinite. The status of three molecular biomarkers was not associated with histologic invasiveness or proportion of GGO portion itself.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 2
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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 - 09:30  |  Author(s): S. Jheon

      • 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.

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      P2.07-014 - Intrapleural Perfusion Hyperthermic Chemotherapy in Malignant Pleural Effusion and Pleural Seeding (ID 2580)

      09:30 - 09:30  |  Author(s): S. Jheon

      • Abstract

      Background
      Malignant pleural effusion or pleural seeding is detected in advanced non-small cell lung cancer (NSCLC) patients, and they are generally associated with poor prognosis. Systemic chemotherapy is the mainstay modality in these patients. However, it is not enough to improve the survival. Intrapleural perfusion hyperthermic chemotherapy (IPHC) provides direct effect to pleural seeding cancer cells. This study attempted to evaluate the efficacy and safety of IPHC.

      Methods
      From 2003 to 2012, 41 patients who underwent IPHC for malignant pleural effusion or pleural seeding for NSCLC in our institute. The IPHC was performed with cisplatin (dose:150-200mg/m[2]) for 90 minutes after resection of primary tumor. Efficacy was determined by computed tomography and Positron Emission Tomographic (PET) standardized uptake value (SUV) postoperatively.

      Results
      The IPHC group consisted of 25 males and 16 females. The mean age was 60.98±9.80 year ranging from 33 to 78. Preoperative pleural mean SUV was 1.46±1.88 (R: 0-6) and postoperative pleural mean SUV was 1.58±1.72 (R: 0-5) (p= 0.933). Sixteen patients were received adjuvant systemic chemotherapy. The 2-year and 5-year survival rate were 82.1% and 44.9%, respectively. Major post-IPHC complications are acute renal insufficiency (n=4, 9.76%) and arrhythmia (n=2, 4.88%). There were no difference in sex, age, adjuvant systemic chemotherapy, tumor size, nodal statues between the patients who survived more than 2 years and less than 2 years. There was no difference in SUV of preoperative main mass and pleura between the patients who survived more than 2 years and less than 2 years. However, the SUV of postoperative pleura in the patients who survived more than 2 years (SUV: 2.92±1.98) was less than that of the patients who survived less than 2 years (SUV: 1.16±1.45) (p=0.031).

      Conclusion
      IPHC would be safety procedure for malignant pleural effusion or pleural seeding. IPHC may provide better survival compared with the systemic chemotherapy only in the highly selected patients. Low post-IPHC SUV uptake would be provide longer survivor.

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    P2.17 - Poster Session 2 - Bronchoscopy, Endoscopy (ID 183)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      P2.17-007 - Misclassification of mediastinal lymph nodes by endobronchial ultrasound (EBUS) (ID 2478)

      09:30 - 09:30  |  Author(s): S. Jheon

      • Abstract

      Background
      Endobronchial ultrasound-guided transbronchial aspiration(EBUS-TBNA) is reported to show relatively high sensitivity and specificity in mediastinal node staging of non-small cell lung cancer (NSCLC). But discrepancies exist between bronchoscopic, radiologic, and surgical classification of mediastinal lymph nodes and thus can lead to misclassification. However, the impact of the misclassification on diagnostic performance of EBUS-TBNA has never been evaluated.

      Methods
      Medical records of NSCLC patients who underwent surgery after EBUS-TBNA for mediastinal staging from November 2010 until March 2013 in a tertiary hospital were reviewed. Of those, only lymph nodes which have been aspirated by EBUS-TBNA and removed by surgery were analyzed. Patients who received neoadjuvant chemotherapy between EBUS-TBNA and surgery were excluded. Detailed review of medical records and radiological imaging was done to infer the causes for false negative or positive results.

      Results
      A total of 105 lymph nodes from 96 patients were included in our analysis. Median interval between EUB-TBNA and surgery was 11 days. A total of 8 lymph nodes(7.6%) showed false negative results and only one lymph node (0.9%) showed false positive result. Sensitivity, specificity, accuracy, positive and negative predictive value (PPV and NPV) of EBUS-TBNA for malignancy were 65.2%, 97.5%, 88.5%, 88.5%, 90.6%, respectively. After detailed review of cases who had false positive or negative results, 3 false negative lymph nodes and 1 false positive lymph node (44%) were recognized to be due to misclassification. Other false negative cases were due to sampling errors.

      Conclusion
      Misclassification of lymph nodes can cause false positive or false negative results of EBUS-TBNA.