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Y.T. Kim

Moderator of

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    MS06 - Surgeons as Drivers of NSCLC Research (ID 23)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Surgery
    • Presentations: 4
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      MS06.1 - How Do I Contribute to the IASLC Staging Projects? (ID 481)

      14:00 - 15:30  |  Author(s): R. Rami-Porta

      • Abstract
      • Presentation
      • Slides

      Abstract
      The IASLC Staging Projects The International Association for the Study of Lung Cancer (IASLC) now has four staging projects. The first one, for lung cancer, originated during an international workshop on intrathoracic staging organized at the Royal Brompton Hospital, London, UK, in 1996. (1) It is an ongoing project with two phases: a retrospective phase, during which 81,495 analyzable lung cancer patients diagnosed between 1990 and 2000 were registered: 68,463 non-small cell lung cancers (NSCLC) and 13,032 small cell lung cancers (SCLC) (2); and a prospective phase, that includes 78,640 analyzable cases of NSCLC and 5,912 cases of SCLC diagnosed between 1999 and 2010. The retrospective database was used to revise the 6[th] edition of the tumour, node and metastases (TNM) classification and prepare for the 7[th] edition; (3, 4, 5) the data of the prospective phase will be used to inform the 8[th] edition of the TNM classification due to be published in 2016. This writer chairs the Lung Cancer Domain. In 2008, mesothelioma was incorporated into the activities of the IASLC Staging Project lead by Dr. Valerie Rusch as chair of the Mesothelioma Domain. As with lung cancer, a call was made to collect retrospective series from around the world and, at the same time, an online registration system was created for prospective collection of data. The retrospective mesothelioma database contains 3,101 surgically treated patients. This population was first analysed to assess the existing TNM classification and staging system for mesothelioma. (6) These analyses showed that more data are needed to refine the classification beyond what the retrospective database can do. In essence, more detailed data on the T, N and M descritpors is needed. The prospective collection of data is an ongoing project that collects surgically and non-surgically treated patients and is intended to inform the 8[th] edition of the TNM classification. In 2009, thymic malignancies were incorporated into the IASLC Staging and Prognostic Factors Committee (SPFC). So far, more than 10,000 retrospective cases have been collected and are now being analysed by the statistitians at Cancer Research And Biostatistics (CRAB), in Seattle, WA, USA. The main objective of these analyses is to establish a TNM classification for thymomas and thymic carcinomas. The Thymic Domain of the Committee is chaired by Dr. Frank Detterbeck. (7) Finally, also in 2009, oesophageal cancer was incorporated into the activities of the IASLC SPFC under the leadership of Dr. Tom Rice, who is the chair of the Oesophageal Cancer Domain of the SPFC. More than 10,000 cases are registered in a database stored and analysed at the Cleveland Clinic, Cleveland, OH, USA. The surgical cases were used to inform the 7[th] edition. Plans are made to analyse the non-surgical series and validate data to inform the 8[th] edition of the TNM classification. How to contribute Individuals, institutions, cooperative groups and proprietors of registries can contribute by submitting their databases directly to CRAB, provided their databases include the information that is essential for the IASLC Staging Projects, i.e. clinical and pathological data on the different T, N and M descriptors, treatment modality and survival. CRAB statisticians have to be informed about the characteristics of the databases to assess if they are useful for the project prior to submission. This is, indeed, the easiest way to contribute: to submit your database. CRAB accepts databases on lung cancer and mesothelioma. Databases of thymic malignancies can be submitted either to CRAB or to the International Thymic Malignancies Interest Group (ITMIG). ITMIG will assess the data and will forward the specific staging data to CRAB for analysis. Those wishing to contribute oesophageal cancer cases should get in touch with the chair of the Oesophageal Cancer Domain of the SPFC, Dr. Tom Rice, at the Cleveland Clinic, Cleveland, OH, USA. Contribution is best through the Worldwide Esophageal Cancer Collaboration (WECC). Those who want to contribute prospective cases can use the on-line registration system that CRAB has established for lung cancer and mesothelioma. There also is an on-line registration system for thymic tumours provided by the ITMIG. Submitting retrospective databases and on-line registration of prospective cases take time and may cost money. In order to facilitate grant application to those who need the assistance of a data manager, CRAB has prepared a document describing the project that can be used to complete the grant application forms. This document can be accessed through the IASLC website at www.iaslc.org. Go to ‘Staging’ and there you will find all the necessary information about the IASLC Staging Projects. Those who cannot participate submitting cases can participate analysing data not directly related to the main staging projects. An outline of the research project has to be sent to the Chair of the IASLC SPFC stating the objectives and the variables needed for the study. Approval will be granted based on the availability of data, the relevance of the project and the willingness of the applicant to pay for the CRAB statisticians’ work required for the extraction and analysis of data. (9) References 1. Goldstraw P. Report on the international workshop on intrathoracic staging, London, October 1996. Lung Cancer 1997;18:107-111. 2. Goldstraw P, Crowley JJ. The International Association for the Study of Lung Cancer international staging project on lung cancer. J Thorac Oncol 2006;1:281-286 3. Goldstraw P, ed. Staging manual in thoracic oncology. Orange Park, FL: Editorial Rx Press; 2009. 4. Sobin L et al., eds. TNM classification of malignant tumours. 7[th] edition. Oxford: Wiley-Blackwell; 2009;138-146. 5. Edge SB et al., eds. Cancer staging manual. 7[th] edition. New York: Springer; 2010;253-270. 6. Rusch VW et al. Initial analysis of the International Association for the Study of Lung Cancer mesothelioma database. J Thorac Oncol 2012;7:1631-1639. 7. Detterbeck FC, Huang J. Overview. J Thorac Oncol 2011;6(Suppl 3):s1689-1690. 8. Rice TW et al. 7[th] edition of the AJCC Cancer Staging Manual: esophageal and esophagogastric junction. Ann Surg Oncol 2010;17:1721-1724. 9. Goldstraw P et al. We probably have the answer: now what is the question? J Thorac Oncol 2009:4:939-940.

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      MS06.2 - Clinical Trial and Research Cooperation (ID 482)

      14:00 - 15:30  |  Author(s): W.Z. Zhong, Y. Wu

      • Abstract
      • Presentation
      • Slides

      Abstract
      Clinical research in non-small-cell lung cancer is a rapidly evolving field. We conducted a survey of lung cancer surgical clinical trials listed on clinicaltrials.gov. 658 records were found, which were mainly consisted of trials studying the surgical procedure and (neo) adjuvant therapy. Phase III trials account for 15.5%. Only 34.9 %( 230 records) trials were completed, and 43 studies present results in clinicaltrials.gov. The median time to completion (MTC) of Ph III surgical procedure trials was 9.4 years. The MTC of Ph III neo-adjuvant and adjuvant trials had not been reached but are longer than 10 years. In comparison, the MTC of Ph III trials in first line setting were only 4.5 years. We summarized the characteristics of these trials with real-world case examples. Our analyses reveal that it is critically needed for regulatory authorities, clinical trial sponsors, collaborative research groups, and academic institutions to work together to build the infrastructure and research cooperation for clinical trials with surgical components. In 2007, a national collaborative clinical research group, Chinese Thoracic Oncology Group (CTONG), was established. CTONG is a network of researchers, physicians and healthcare professionals in public institutions across China. Currently, there are 22 member hospitals in the group. A CTONG-sponsored trial (CTONG1104) is discussed to illustrate our experience with surgical clinical trials. In summary, to expedite clinical research in early stage lung cancer, it is necessary for investigators to collaborate in cooperative clinical trials. As cancer treatment is multidisciplinary, while retaining a surgical focus, surgical trials require multidisciplinary collaboration.

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      MS06.3 - Randomized Trial of VATS vs Axillary Thoracotomy for Lobectomy (ID 483)

      14:00 - 15:30  |  Author(s): L. Hao

      • Abstract
      • Presentation
      • Slides

      Abstract
      Background: Since video-assisted thoracoscopic surgery (VATS) was first reported in the 1990s, this approach has been rapidly gaining popularity worldwide because of its less morbidity and expedited patient recovery. As a milestone, VATS lobectomy was first introduced into NCCN Guidelines in 2006, and then has been recommended as a reasonable and acceptable alternative in the treatment of non-small cell lung cancer (NSCLC) since 2007. However, whether VATS’s superiority really exists in the domain of NSCLC has raised unprecedented dispute in the past two decades, especially when compared to other minimally invasive approaches like axillary thoracotomy. Major debates have involved surgical trauma, post-operative neuralgia, shoulder dysfunction, influence on respiratory function/quality of life (QOL), and finally oncologic outcomes. So far, strong evidence demonstrating decreased morbidity and equivalent long-term survival of the new technique is lacking. In an attempt to obtain a better answer, we designed and initiated this multicenter randomized controlled trial (RCT) in China, which compared VATS and axillary approaches in terms of various surgical and oncologic outcomes for early stage NSCLC. Methods: 400 patients were planned to be recruited in this study since 2008, and then randomized into VATS group (Experimental group) and axillary thoracotomy group (Control group). The Inclusion Criteria include: ①Clinical early stage NSCLC, no hilar and mediastinal lymphadenopathy (short diameter ≤ 1 cm assessed on computed tomography scan); ②No medical contraindications to lung resection; ③Age ≤ 75 years old and ≥18 years old; ④Ability to give informed consent. And the Exclusion Criteria are: ①Evidence of invasion into neighboring organs; ②Extensive pleura symphysis; ③Central tumors; ④Inability to tolerate single-lung ventilation; ⑤Previous thoracotomy or high-dose radiation on the chest ; ⑥Pregnant or lactating female patients; ⑦Inability to sign the informed consent form because of psychological, family and society factors; ⑧History of other malignancies in the past 5 years except for non-melanoma skin cancer, cervix cancer in situ or early-stage prostate cancer; ⑨Other uncontrolled factors (like intra-operative conversion to thoracotomy). Surgery criteria would be a radical lobectomy plus hilar and mediastinal lymph node dissection. Also, the VATS lobectomy was defined by the avoidance of rib-spreading and use of the thoracoscope for visualization. The total number of ports is not relevant in this definition, but is typically 3 and 4. Five-year overall survival (OS) and disease-free survival (DFS), as the primary endpoints will be evaluated. Peri-operative parameters, including post-operative chest pain, cytokines response, post-operative respiratory reserve, Karnofsky performance status and QOL would be explored. In addition, operation time, intra-operative blood loss, chest tube drainage, indwelling period of chest tube, etc. would be documented and compared between two groups. Lung Cancer Symptom Scale (LCSS) was adopted to estimate the QOL before operation and at post-operative standpoints of 1, 3, 6, 9 and 12 months. Post-operative respiratory function would be measured in first three months, while Karnofsky performance status and chest pain at the standpoint of 1 year after surgery. Cytokines response, to be exact, serum levels of IL-2, IL-4, IL-6, IL-10, TNF and IFN-r, would be analyzed in first 48 hours after surgery. Randomization was done via an interactive web response system with computer-generated randomization codes. This study has been registered in Clinicaltrials.gov (NCT01102517) and sponsored by Sun Yat-sen University Clinical Research 5010 plan as well as Guangdong provincial high-tech projects. Result: Five leading hospitals throughout China contributed to this RCT. 425 patients was recruited up to May 2013; nonetheless, 336 patients were finally analyzed in the study. The latest DMC review happened on May 2013 and our RCT was regarded to be strictly adhering to the protocol with good quality control. No surgery-related mortality was documented in both VATS and axillary thoracotomy groups. Unfortunately, four patients in the study group were excluded because of intra-operative conversion to axillary thoracotomy. The conversion rate was 0.94% (4/425) in our study. Another fact needs to be clarified that the remaining 85 patients were excluded due to a variety of reasons, which included extensive pleura symphysis (9 patients), benign pulmonary lesions (35 patients), small cell lung cancer (3 patients), accidental pleural metastasis (2 patients), Age > 75 years old (2 patients), invalid case report forms (13 patients), and inability to adhere to the randomized surgical approaches (21 patients). As a result, 175 patients in VATS group and 161 patients in axillary thoracotomy group were finalized and analyzed by the database. No significant difference between the two groups in terms of the anatomical location of the tumors, histological subtypes and clinical stages. Impressively, the operation time for the VATS lobectomy group was significantly shorter than that of the control group (150 min vs. 170 min, P<0.05). There was also remarkably less intra-operative blood loss in the study group (100 ml vs. 150 ml, P<0.001). Another important finding was that no significant differences were identified regarding the number of cleared lymph nodes and number of lymph node regions (10 vs 12; 5 vs 5, respectively). The peri-operative complication rates, once again, showed no significant difference between the two groups. Patients who undertook VATS lobectomy experienced significantly better post-operative QOL, and the superiority was showed in all the aspects of LCSS. When looking at cytokines response which may reflect the acute surgical injuries or trauma, IL-2, IL-4, IL-6, IL-10, TNF and IFN-r consistently demonstrated lower expression levels throughout the time in the VATS group. However, only the patients who recruited in Sun Yat-sen University Cancer Center underwent the evaluation of cytokines response (180 patients). Regarding the primary endpoints, although longer follow-up is still needed before drawing a clear conclusion, initial analyze did show no significant difference was seen between the two groups regarding OS and DFS. We considered these results were premature, but we also believed current data tended to demonstrate a statistical non-inferiority result. Conclusions: Our multicenter RCT has illustrated that VATS approach is a safe approach for the treatment of early stage NSCLC, and may be superior to axillary thoracotomy approach in terms of intra-operative blood loss, acute surgical injuries and post-operative QOL. However, we also realized that longer follow-up is necessary to determine its oncologic equivalency.

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      MS06.4 - Into the Lab: The Surgeon as Translational Researcher (ID 484)

      14:00 - 15:30  |  Author(s): G.M. Wright

      • Abstract
      • Presentation
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      Abstract
      Introduction Building translational research capacity is a daunting task if a thoracic surgeon has not inherited a fully set up laboratory. It is possible, however, for a thoracic surgeon to be involved in and even drive translational research. Given that surgeons are the major procurers of tissue and data in lung cancer, it should actually be more commonplace. It requires passion, organization, the understanding and assistance of colleagues, and the ability to seize what opportunities exist and create new ones with strategic collaboration. Creating this capacity also involves modifying surgical practice to facilitate research then building the relationships, funding and infrastructure. In this article, these building blocks are explored. A translational research project is presented as a successful application of this formula. Building Blocks As a principle, the pillars research capacity-building are: ~ Research-Based Surgical Practice ~ Relationships ~ Infrastructure ~ Funding Sources For individual surgeons and circumstances, these may differ. Some components may already exist and some may seem unattainable. It is often overlooked that simple changes to standard practice can make research a natural activity. For example, focusing audits on the procedures that are the subject of potential research, aligning timing of routine follow-up so that outcome assessment becomes automatic, or a policy that all tissue excess to diagnostic needs is routinely stored in a tissue bank. A research coordinator, at least part-time, is essential for any sustainable research activity. Beyond that, key relationships may differ. For me, the most important initial relationship is an anatomical pathologist with a keen interest in lung. Without such a person to review and precisely classify tumors, the power and applicability of any study is seriously diminished. However, a relationship with a laboratory-based clinician or scientist is necessary in order to have access, training and conduct of the benchtop component of research. The surgeon should be active in these endeavours (at least initially) to promote goodwill and a free-flowing exchange of ideas. Other clinicians or specialist scientists may then need to be involved depending on the scope of the potential research projects. Whatever infrastructure is available for research will often need to be augmented. Many useful research tests are already available in a diagnostic pathology laboratory (e.g. advanced immunohistochemistry, mutation screening, PCR). Some facilities may be shared with researchers in other specialties, resulting in synergies for both groups. This may be the way to acquire part time bench space, for example. After determining what capabilities are required to conduct the projected range of research, funding will be the next concern. It is not usually possible to get large project and infrastructure support without a track record and without the funds it is difficult to get a good track record. Therefore preliminary work needs to be funded from a range of more modest resources to pay for direct research costs and services outside any collaborative effort. Local organizations such as Rotary, Apex etc. are often keen to donate to research with a potential impact on their community. This could, for example, fund the construction of tissue microarrays or purchase of essential equipment. Anything that a name can be attached to is usually fair game for such donors. Hospital research foundations are the easiest target for competitive grants. Specialist societies commonly have foundations for distributing grants-in-aid. Participation in capitation-funded clinical trials may provide the salary for a research coordinator, allowing their spare time to be dedicated to translational projects. An Example of Surgeon Driven Translational Research After several years of building relationships, collaborations, infrastructure and funding, our group was able to assess our core research advantages. Figure 1 plots the gradual ascent to critical mass for research funding in our thoracic unit.Figure 1 Our example project investigated the genomic/transcriptomic landscape of the recently classified subtypes of lung adenocarcinoma.[1] Other than one gene expression study[2] using outdated array-based platforms and subtype classifications, no molecular signature has been reported to correlate to the morphology seen by the pathologist under the microscope. It is debated whether these subtypes are genetically different or just a spectrum of the same tumour. Inter-observer differences in classifying these subtypes are particularly problematic for the new micropapillary subtype; therefore a molecular marker is an important goal. To investigate these new subtypes (table 1), we carefully selected tumors with classical morphological regions of the differing subtypes. From this group, 29 tumours were selected with known mutations in one or more of EGFR, KRAS, BRAF and TP53. These would be the most likely cases to prove our hypothesis that there are differential genomic aberrations within subtypes of the same tumor.

      Table 1. Subtypes of lung adenocarcinoma investigated, as classified in the 2011 IASLC/ATS/ERS pathological classification of lung adenocarcinoma.
      Subtype Description
      Lepidic
      Minimal metastatic potential. Malignant cells growing along but not invading airway walls
      Acinar
      Moderate metastatic potential. Glandular structures in invasive stroma
      Papillary
      Moderate metastatic potential. Branching structures with fibrovascular stromal cores covered by malignant cells.
      Solid with/without mucin
      High metastatic potential. Sheets or nests of malignant cells with or without intracellular mucin.
      Micropapillary
      High metastatic potential. Papillary tufts of tumor cells without fibrovascular cores either lying apparently free in alveolar spaces or surrounded by thin fibrous septa, often at a tumor’s edge.
      After marking the subtypes in areas of tumor purity > 50%, punches of formalin-fixed paraffin embedded tumor were deparaffinized and DNA was extracted. High resolution melting was then used to screen for mutations in all selected subtypes of each tumor. In 3 out of 11 KRAS mutant tumors and 2 out of 4 BRAF mutant tumors, heterogeneity was found in mutation status between subtypes of lesser and higher metastatic potential. No differences were seen between subtypes for EGFR mutant tumors, however we did find a single case of very high copy number of the EGFR mutant allele mapping only to the micropapillary subtype in the tumor. The significance of this finding is far-reaching. It provides a genetic basis to support the new pathological classification and may inform its next revision. It also brings into question the accuracy of small biopsies in detecting mutations other than EGFR. It has the potential to unravel the biological evolution of lung adenocarcinoma, with EGFR apparently an early event, whereas KRAS and BRAF may be acquired later and result in a transition to a more malignant subtype phenotype within a given tumor. Conclusion This example demonstrates that surgeons can drive important translational research as well as advancing other researchers’ goals. Although it takes years to develop such programs, once critical mass is achieved the results create further opportunities to sustain future research and incorporate advances in sequencing platforms and knowledge in lung cancer biology. References
      1 Travis, W. D. et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6, 244–285 (2011).
      2 Bryant, C. M. et al. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study. PLoS One 5, e11712 (2010).

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Author of

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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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      MO10.11 - Genetic polymorphisms of TERT and TP63 genes are associated with exon 18 and exon 21 mutations of EGFR in adenocarcinoma of the lung. (ID 3046)

      16:15 - 17:45  |  Author(s): Y.T. Kim

      • Abstract
      • Presentation
      • Slides

      Background
      The presence of mutations of epidermal growth factor receptor (EGFR) is related to phenotypical characteristics such as ethnicity, gender and smoking status. Such observations led us to explore associations between genetic polymorphisms and EGFR mutational status.

      Methods
      We set up a set of samples from 677 primary pulmonary adenocarcinoma. We tested two genetic polymorphisms (rs2736100 and rs10937405), which were discovered previously as to be associated with the risk of lung adenocarcinoma. The association between EGFR mutational status and genetic polymorphisms were evaluated using logistic regression analysis.

      Results
      In 673 patients, four exons (18, 19, 20, 21) of EGFR were completely evaluated. Presence of EGFR mutations were found in 382 (56.8%) patients. In logistic regression analysis, female gender (aOR, 1.7 with 95% CI, 1.0-2.9) and smoking status (ex-smoker, aOR, 0.6 with 95% CI, 0.4-1.1; current smoker aOR, 0.4 with 95% CI, 0.2-0.8) were associated with presence of EGFR mutations. None of two single nucleotide polymorphism (SNP) sites showed significant association. In the analysis of individual type of EGFR mutations, however, we found a significant association between EGFR exon 18 mutations and a SNP rs27366100T/G located in TERT. The G/G genotype showed a 2.8-fold increase in the occurrence of the EGFR exon 18 mutations compared to T/T+G/T genotypes (aOR, 2.8 with 95% CI, 1.2-8.7). Additionally, C/T+T/T genotypes of rs10937405C/T SNP in TP63 showed frequnt occurrences of EGFR exon 21 mutations compared to CC genotype (aOR, 1.5 with 95% CI, 1.0-2.3).

      Conclusion
      Our findings suggest that the somatic mutations of EGFR may be closely associated with genetic polymorphisms. Further investigation of this field may enable us to identify patients who may get a benefit from EGFR inhibitors.

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    MTE15 - Surgery for Complications of Surgery (ID 59)

    • Event: WCLC 2013
    • Type: Meet the Expert (ticketed session)
    • Track: Surgery
    • Presentations: 1
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      MTE15.1 - Surgery for Complications of Surgery (ID 608)

      07:00 - 08:00  |  Author(s): Y.T. Kim

      • Abstract
      • Presentation

      Abstract
      Although recent development of minimally invasive procedures contributed significantly to reduce of postoperative complications, as the population continues to age, as more patients receive induction therapies, and as more patients are immunocompromised, complications will continue to increase. Although many complications can be treated medically, some complications require another round of surgery. Postoperative complications after lung cancer surgery can take place both in early and late postoperative periods. As a matter of fact, major surgical errors during the surgery can result in mortality or major morbidity. Hence, the surgery for complications of surgery should begin with prevention of the intraoperative event during the initial surgery. Intraoperative complications During the major lung resection, various kinds of errors can take place. Poor surgical technique can cause injuries of the pulmonary vasculature as well as of the bronchus. The risk of intraoperative technical complication can occur either during VATS or thoracotomy procedures. However, it is more difficult to control in VATS. Minor bleeding can be easily controlled trough VATS. However, once a major vascular injury occurs, the bleeding focus should be compressed, and a prompt thoracotomy should be made. Any bronchial injuries should be detected during the surgery and appropriately fixed. Bleeding can also occur from the pulmonary parenchyma, especially after wedge resection in patients whose pulmonary arterial pressure is increased. For such patients, the staple lines should be oversewed meticulously as the elevated pulmonary arterial pressure may cause postoperative bleeding. Sometimes, lack of understanding of variations of intrathoracic anatomy can cause serious complications. Such structural variations should be acknowledged preoperatively by carefully reviewing the CT scans. According to a report from a dedicated thoracic surgical center, the catastrophic complications took place in 1% of patients, including main pulmonary arterial and main pulmonary venous transection requiring reanastomosis, unplanned pneumonectomies, unplanned bilobectomy, tracheoesophageal fistula, membranous airway injury to the bronchus intermedius, complete staple line disruption of the inferior pulmonary vein, injury to the azygos/superior vena cava junction, and splenectomy. The third and perhaps the most important cause of intraoperative complication is negligence. Thus, establishment of standardized surgical protocol is mandatory in training hospital. Postoperative complications Common postoperative complications such as prolonged air leak, atrial fibrillation, aspiration and pneumonia can be treated by medical methods. The early postoperative course is often compromised by chylothorax. The initial treatment is to give nothing by mouth and wait until the chest tube drainage decreases. However, if the chylothorax persists, reoperation with duct ligation should be considered. Empyema is an uncommon complication after pulmonary resection. The key treatment principle is control of the pleural space, which can be established by lung expansion. If there is any question of a BPF, repeat thoracotomy with muscle or omental harvesting is mandatory to drain the empyema and to decorticate the lung, and to buttress the open bronchus. Superficial wound infections are managed with antibiotics, drainage, and local wound care. Management options of deep sternal infection include sternal debridement or sternectomy, prolonged open wound care or irrigation, muscle flap reconstruction, or some combination of these. Postpneumonectomy bronchopleural fistula (BPF) is difficult-to-manage. Management is determined by the timing of complication, the condition of the patient, and the presence or absence of empyema. Patients should be positioned with their operated side down. Chest tube drainage of the empyema should be performed. For repair of the bronchus, a long stump can be resected and closed primarily if the BPF took place in the early postoperative period. In some cases, primary closure of postpneumonectomy BPF may not be tenable. In such situations, the bronchial leak point can be closed with a vascularized flap. Sterile or minimally contaminated cavities can be irrigated, filled with antibiotic solution, and then closed. Eloesser flaps are ideal for long-term open drainage and irrigation. Alternatively, after the pleural cavity is granulating and healthy, it can be filled with antibiotic solution and closed. Rarely, BPFs have been managed nonoperatively with endoscopic techniques combined with antibiotics. Residual space after lobectomy can also occur. Intraoperative maneuvers to lessen the risk for space problems include pleural tents, phrenic nerve crush, muscle or omental transposition, thoracoplasty, and pneumoperitoneum. If a patient is clinically well, continued observation and antibiotics are appropriate while the space fills. Lobar torsion is one of the most serious complications and commonly affects the right middle lobe after right upper lobectomy. Visual confirmation of anatomic position and proper lung inflation allows detection of twisted or ischemic lung before closure. The lung may be salvageable if the torsion is recognized early, before infarction occurs. However, usually the diagnosis is late, and resection is required. Postpneumonectomy syndrome is caused by displacement and rotation of the mediastinum into the operated chest. The remaining main stem bronchus is stretched and compressed over the spine or aorta. Surgical treatment principle is to reposition the mediastinum by placing intrathoracic prosthetic implants, which will relieve the airway compromise. Sleeve lobectomy or other bronchoplastic procedures may result in late airway stenosis. Repeated dilations sometimes stabilize strictures but usually the effect is temporarily. In some cases, reoperation is necessary. If the stenosis resulted from kinking of the anastomosis, resection and re-anastomosis may fix the problem. Usually, a completion pneumonectomy may be necessary. A fistula between the airway and pulmonary artery occur after bronchoplasty or tracheal resection. If a fistula is apparent, emergency surgery should be performed. The mortality rate of bronchovascular fistulas is high. Tracheoesophageal fistula can develop with prolonged intubation and mechanical ventilation. Surgical repair should be attempted after the patient's condition is optimized, and the patient is breathing spontaneously. Chest wall graft infection can happen even several years after chest wall resection and reconstruction. When chronic, often times, soft tissue flap support may be sufficient to obviate skeletal reconstruction. Conclusions An appropriate patient selection and meticulous surgery are the best prophylaxis against postoperative surgical complications. When complications arise, they require an experienced surgeon for identification and correction. Furthermore, training of surgical techniques, sound knowledge of anatomical variations, as well as stringent observances of surgical principle are mandatory to overcome intraoperative complications.

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    O09 - General Thoracic Surgery (ID 100)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      O09.06 - Prognostic factors for long-term survival in non-small cell lung cancer patients with interstitial lung disease (ID 3453)

      16:15 - 17:45  |  Author(s): Y.T. Kim

      • Abstract
      • Presentation
      • Slides

      Background
      There is little information about prognosis after pulmonary resections for non-small cell lung cancer (NSCLC) in patients with interstitial lung disease (ILD). In this study, we examined the long-term outcome and the factors that affect long-term survival after resection for NSCLC in patients with ILD.

      Methods
      Between September 1996 and May 2011, 71 NSCLC patients were diagnosed as having ILD based on the CT and pathological findings. The extent of ILD on CT was scored visually at the level of 3 cm above the diaphragm as follows: minimal, <2 cm from the subpleura at the base of the lungs; moderate, >2 cm from the subpleura, but less than one-third of the lung area at the base of the lungs; severe, more than one-third of the lung area at the base of the lungs. Various clinical values such as gender, age, preoperative chemotherapy, severity of ILD on CT, preoperative pulmonary function test results, arterial blood gas studies, operative procedure, pathologic stage, cell type, and adjuvant treatment were evaluated using univariate and multivariate analysis.

      Results
      The mean age was 65.9 years, and the majority of patients were male(65:91.5%). In-hospital mortality was 9.9% (7/71). The causes of early mortality included pneumonia (n=4), acute respiratory distress syndrome (n=2), and acute exacerbation of ILD (n=1). The 5-year overall survival rate was 43.1% (stage I: 59.4%, stage II: 41.3%, stage III: 35.0%, respectively). In univariate analysis, the risk factors for long-term mortality were lower preoperative FEV~1~, FVC, severe ILD on CT, presence of pathologic pulmonary fibrosis, and non-squamous cell type. In multivariate analysis, severity of ILD on CT and non-squamous cell type remained as poor prognostic factors.Figure 1

      Conclusion
      Although patients with ILD undergoing pulmonary resection for NSCLC has resulted in a high in-hospital mortality, long-term survival can be expected in highly selected patients. NSCLC patients with severe ILD on CT findings and those with non-squamous cell type should be carefully selected for major pulmonary resection.

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    P1.19 - Poster Session 1 - Imaging (ID 179)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P1.19-015 - Clinical application of thin section chest CT with computer-aided detection system for the detection of small metastatic nodules in pulmonary metastasectomy. (ID 3428)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      It is important to identify possible metastatic nodule prior to metastasectomy, in order to perform complete resection. Thin section chest CT (TSCT) can detect small metastatic nodules more accurately than conventional chest CT. Conventional CT is known to miss metastatic nodules that are manually palpable by up to 40%. Reported sensitivity of helical CT cannot exceed 90%, also. We adopted TSCT and applied computer-aided detection (CAD) system for the search of small metastatic nodules to improve the detection power of TSCT.

      Methods
      From March 2009 to February 2013, 333 patients were referred to thoracic surgeon for pulmonary metastasectomy. TSCT with CAD was performed in every candidate for pulmonary metastasectomy. Every nodule detected by TSCT and CAD was annotated by radiologists and the whole map and annotation numbers of nodules were reported before operation. Intraoperatively, bi-manual palpation in open metastasectomy and finger palpation in video assisted thoracoscopic surgery (VATS) were used to detect the nodules. Only operations with complete available data were included in the study and 251 operations from 239 patients were analyzed.

      Results
      A total of 1021 nodules were identified by TSCT with CAD, while 115 nodules (11.3%) were additionally detected by CAD. Among the annotated nodules, 742 nodules were palpable during operation. Including intraoperatively detected 49 nodules, a total of 824 nodules were resected. Of 527 pathologically proven malignant nodules, 518 (62.9%) nodules were metastatic lesions. Among metastatic lesions, 496 were detected by TSCT (95.8%), 9 by CAD (1.7%) and 13 by manual palpation (2.5%). Also, 11 metastatic nodules were no palpated during operation but resected according to the annotation on CT. The overall sensitivity of thin section chest CT with CAD was 97.5%. Though overall specificity of TSCT with CAD was very low as 12.1% because that of radiologist’s reading was 14.2%, specificity only for CAD was 45.6%.

      Conclusion
      TSCT could detect small subcentimetre nodules and CAD enabled detecting additional small nodules. With help of TSCT with CAD, even the metastatic nodules, which were not palpable during operation, could successfully be resected. Furthermore, TSCT with CAD could detect tiny nodules with rather high specificity compare to radiologist’s reading only. Although the number of true metastatic nodules was small and several metastatic nodules were undetected, the TSCT with CAD system increased the detection sensitivity and would be helpful in complete metastasectomy.

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    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P2.09-015 - Role of postoperative radiotherapy after curative resection and adjuvant chemotherapy for patients with pathological stage N2 non-small cell lung cancer: A propensity score matching analysis (ID 2953)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      To evaluate the role of postoperative radiotherapy (PORT) after curative resection and adjuvant chemotherapy for patients with pathological stage N2 non-small cell lung cancer (NSCLC).

      Methods
      We performed a retrospective review of 219 consecutive patients who underwent curative surgery followed by adjuvant chemotherapy between 2000 and 2011. Among 219 patients, 41 received PORT additionally. Propensity scores for PORT receipt were calculated for each patient and used for matching to patients without PORT. 118 patients in non-PORT group and 39 patients in PORT group were matched. Clinical and pathologic characteristics were well-balanced after matching. PORT was delivered using conventional technique (n=13) or three-dimensional conformal technique (n=26) with median dose of 54 Gy (range, 50-60). The median follow-up duration for matched patients was 47 months.

      Results
      During the follow-up, 58 patients (49.2%) experienced loco-regional failure in the non-PORT group and 12 patients (30.8%) in the PORT group. Distant metastasis occurred in 68 patients (57.6%) in non-PORT group and 22 patients (56.4%) in PORT group. PORT was associated with improved loco-regional control rate (LRC) (5yr LRC 67.0% vs. 48.4%, p = 0.047), but not disease-free survival (DFS) (5yr DFS 43.3% vs. 32.3%, p = 0.257). An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple stations of mediastinal lymph node metastasis (5yr DFS 42.8% vs. 16.6%, p = 0.023). Grade 3 radiation pneumonitis and esophagitis was seen in only one patient, respectively.

      Conclusion
      In pathological stage N2 NSCLC patients, more than half eventually developed distant metastasis despite adjuvant chemotherapy. PORT increased LRC in these propensity-matched patients, but did not DFS. However, patients with multiple stations of mediastinal lymph node metastasis appear to benefit from PORT.

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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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      P3.07-028 - Long-term result of robot-assisted esophagectomy for esophageal cancer: Technical feasibility and oncological reliability. (ID 2229)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      Whether robot-assisted esophagectomy is a technically feasible and oncologically reliable operation for esophageal cancer has not been proven. This study aimed to evaluate short-term and long-term outcomes of robot-assisted esophagectomy.

      Methods
      Robot-assisted esophagectomy was performed in prone position for cervical anastomosis or lateral position for intrathoracic anastomosis. Thoracic procedures were performed by totally robotic technique and abdominal procedures were performed by robot or laparotomy. Two field lymph node dissection was performed in all patients and dissection along both recurrent laryngeal nerves was performed in the patients with T1b or more stages. Retrospective review on short-term and long-term outcomes for robot-assisted esophagectomy was performed.

      Results
      Robot-assisted esophagectomy was performed in 46 patients between 2008 and 2013, which was 16% of total esophagectomy cases during the same period. There were 43 men and 3 women and mean age was 63.9 ± 8.2 years. Preoperative clinical stages were IA in 19 patients (41%), IB in 8 (17%), IIA in 6 (13%), IIB in 9 (20%), and IIIA in 4 (9%). Neoadjuvant chemoradiation was performed in 5 patients (11%). Abdominal procedures were performed by robot in 29 patients (63%) and by laparotomy in 16 (35%). R0 resection was accomplished in 45 patients (98%) and mean operation time including robot docking time were 512 ± 104 minutes. Total 2-field lymph node dissection along bilateral recurrent laryngeal nerve was performed in 32 patients (70%) and mean number of dissected lymph nodes were 29.1 ± 14.1. Cell types of esophageal cancer were squamous cell carcinoma in 45 patients (98%) and melanoma in 1 patient (2%). Pathologic stages were IA in 9 patients (20%), IB in 19 (41%), IIA in 2 (4%), IIB in 11 (24%), IIIA in 4 (9%), and IIIB in 1 (2%). There were one 30-day mortality (2%) and postoperative complication occurred in 15 patients (33%); respiratory complication in 5 patients (11%), anastomosis site leakage in 5 (11%), and vocal cord palsy requiring treatment in 3 (7%). Overall 5-year survival was 88% and 5-year freedom from recurrence was 73%. Locations of recurrence were regional in 4 patients (9%), distant in 4 (9%), and there was no local recurrence.

      Conclusion
      Robot-assisted esophagectomy was technically feasible and oncologically reliable surgery in this study. Further studies based on large series of data are necessary to prove advantages of robot-assisted esophagectomy.

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    P3.18 - Poster Session 3 - Pathology (ID 177)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 2
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      P3.18-016 - The usefulness of frozen section diagnosis as for the decision making milestone during the surgery for pulmonary ground glass nodules: embedding medium inflation technique (ID 2946)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      The appropriate intraoperative decision making of surgical resection for the pulmonary ground glass nodules (GGN) is often difficult. We aimed to evaluate the role of frozen section diagnosis (FSD) as for the intraoperative decision making milestone and compared its accuracy to that of preoperative CT based practice as an interim result.

      Methods
      We retrospectively reviewed FSD of 171 consecutive pulmonary GGN from February 2005 to June 2013 and compared the diagnostic accuracy. Initially, we used only conventional method (Group A) but recently, we adapted a embedding medium inflation method (Group B) for FSD. The qualities of FSD were compared with the final pathologic diagnoses of corresponding permanent paraffin sections. Also, we calculated the sensitivity, specificity, and predictive values of assessing the size of invasive portion in GGN between FSD using the inflation method and preoperative CT based practice.

      Results
      There were no differences in nodule sizes between two groups (1.45±0.6 versus 1.51±0.5, p=0.63). In group A, a correct differential diagnosis between malignancies and benign lesions were made in 138 nodules. Thirteen nodules were erroneously classified and reported as false-positive or false-negative frozen section diagnoses (Sensitivity 95.6%, Specificity 53.8%). Three nodules were under-diagnosed in FSD. One patient required a secondary operation because of false-negative frozen diagnosis at the time of initial surgery. In group B, all of 17 nodules were correctly classified by frozen section. There were no false-positive or false-negative diagnoses in terms of making a diagnosis of malignancy, resulting in 100%-sensitivity and -specificity. (Figure 1) Thirteen nodules were correctly classified as being either minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma. Three nodules were diagnosed as MIA by frozen section through measuring invasive tumor size (<5mm) concomitantly. With regards to the estimating the size of invasive components of GGN, FSD in group B was superior to measurement of solid component in GGO nodules on HRCT. (Table 1)Figure 1

      Conclusion
      The accuracy of FSD using the embedding medium inflation method in GGO nodules was outstanding compared to the conventional frozen method. Furthermore, this method can help surgeons plan the appropriate surgical treatment after wedge resection of a GGO nodule by providing accurate size estimation of the invasive components of the GGN.

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      P3.18-020 - The mutational profile of lung adenocarcinoma in Korean population (ID 3097)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      Recent development of molecular target agents encouraged us to investigate the presence of driver mutations in patients with non-small cell lung cancer. As the prevalence of individual driver mutation is different in each ethnic group, understanding of mutational profiles of a specific country is important for clinical practice as well as for decision-making process of health care. Hence, we investigated the genetic profile of lung adenocarcinoma in Korean population.

      Methods
      Among the patients who underwent surgical resection for lung adenocarcinoma between 2001 and 2011, we set up a total of 477 patients whose fresh frozen lung cancer tissues and paraffin blocks were available. We retrospectively searched medical records of the EGFR exons 18-21 mutation tests results. Then, we selected patients who did not harbor EGFR mutations or who had not tested for EGFR mutations. DNA was extracted from those patients’ samples, and EGFR exons 18-21 and KRAS mutation test were performed by Sanger sequencing method. Tissue microarray was made for all 477 patients, and the EML4-Alk fusion was tested by a break-apart FISH method. We also tested KIF5B-RET fusion by using a break-apart FISH method and also by inversion specific long-range PCR. We investigated any correlation between mutational status and clinical variables, such as age, gender, smoking status, stage, and long term survivals.

      Results
      Among 477 patients, 321 patients (67.3%) were harboring at least one of four driver mutations. The EGFR mutations were the most frequently detected (270, 56.6%), followed by KRAS mutations (37, 7.8%), and EML4-Alk fusion (19, 4.0%). We also found five patients who had KIF5B-RET fusion mutations (1.0%). There were 10 patients who had more than two driver mutations; EGFR and KRAS mutations in 4, EGFR and EML4-Alk fusion in 4, KRAS and EML4-Alk fusion in one, and EGFR and KIF5B-RET fusion in one patient. The presences of EGFR mutations were frequently observed in patients with female gender (p=0.000). Although the EGFR mutations were associated with longer overall survival in univariate analysis (log-rank test rank test p=0.007), the presence of EGFR mutation was not a prognostic factor in multivariate analysis (Cox’s regression test p=0.469). The mutational statuses were associated with neither the disease-free survival nor fthe reedom from recurrence.

      Conclusion
      Based on our work, we found as high as 67.3% of lung adenocarcinoma patients in Korean populations were harboring at least one driver mutation, which may get a benefit from target agents. We also found as high as 2% of patients harbored multiple driver mutations. As the target agent will eventually develop resistance, it is recommended to test each driver mutation thoroughly even if one driver mutation was detected. Furthermore, our observation suggests future molecular testing should be based on the next generation sequencing platform.

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    P3.19 - Poster Session 3 - Imaging (ID 181)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P3.19-014 - CT Morphologic Patterns, Pathologic Subtypes, and Genetic Phenotypes: A Correlation Study in 600 Nodular Lung Adenocarcinomas (ID 2094)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      Genotype manifests itself as phenotype and that the one may inform the other. In terms of phenotype, imaging has the potential to assist in noninvasively characterizing the tumor, however, there are very few investigators who have pursued that potential connection between imaging features and the genetic characteristics of lung cancer. The purpose of this study was to retrospectively correlate the CT morphologic patterns of nodular lung adenocarcinomas (ADs) with pathological and molecular phenotypes in an East-Asian cohort of patients.

      Methods
      The institutional review board approved this retrospective study, and all patients provided informed consent. 600 primary lung ADs smaller than 3 cm in diameter that were surgically resected from 592 patients (M:F=257:335; mean age, 63) were included. CT morphologic pattern of ADs was evaluated by three board-certified thoracic radiologists and was classified into four patterns: pure GGN, GGO dominant part-solid nodule (PSN), solid dominant PSN, and pure solid nodule. EGFR mutation, ALK rearrangement, and KRAS mutation were evaluated using PCR-based direct DNA sequencing and FISH. Histologic subtype was classified according to IASLC/ATS/ERS classification of lung AD. The Fisher exact test and student t-test were used to assess statistical significance.

      Results
      Figure 1 In terms of CT morphologic patterns, 17.2%,15.2%, 31.8%, and 35.8% of tumors manifested as pure GGN, GGO dominant PSNs, solid dominant PSNs, and pure solid nodules, respectively. EGFR mutation was significantly more often found in ADs that manifested as subsolid nodules (69.9%, 269/385) than in ADs presented as pure solid nodules (46.7%, 100/214) (P<.0001). ALK rearrangement was more frequent in ADs that manifested as pure solid nodule (8.5%, 13/153) than in tumors presented as subsolid nodule (1.8%, 5/281) (P=.001). KRAS mutation showed no significant difference between subsolid nodules (6.6%, 8/121) and pure solid nodules (8.5%, 5/59) (P=.760). The ratio of subsolid nodule vs pure solid nodule was 72.7% vs 27.3% in ADs with EGFR mutation and was 27.8% vs 72.2% in ADs with ALK rearrangement. EGFR mutation was more frequent in minimally invasive ADs (P=.004) and lepidic predominant ADs (P=.018). ALK rearrangement was more frequent in solid predominant ADs (P=.002) and invasive mucinous ADs (P=.030). KRAS mutation was more frequent in invasive mucinous ADs (P=.001).

      Conclusion
      EGFR mutation was significantly more often found in ADs that manifested as subsolid nodules, and ALK rearrangement was more frequent in ADs that manifested as pure solid nodule.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 2
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      P3.21-005 - Clinical characteristics of non-small cell lung cancer with EGFR mutations in never smokers (ID 1755)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      EGFR mutations are highly associated with pulmonary adenocarcinoma in East Asian never-smoker population. The aim of this study is to evaluate the clinical characteristics of non-small cell lung cancer (NSCLC) with EGFR mutations in never smokers.

      Methods
      From June 2011 to Dec 2012, consecutive NSCLC patients who admitted for initial diagnosis of lung cancer without smoking habit were recruited in Seoul National University Hospital.

      Results
      Among 979 of lung cancer patients, 342 never smokers with NSCLC (38.6%) were analyzed. Mean age was 62.7 ± 10.6 years old and mean BMI was 23.8 ± 3.0 kg/m[2]. Adenocarcinoma (307, 89.8%) was the major pathologic diagnosis. The most common clinical stage was IV (134, 39.2%), followed by stage Ia (115, 33.6%). Among 303 patients who underwent EGFR mutation test, 180 (59.4%) patients had EGFR mutations. The never smokers with NSCLC-EGFR (+) showed better performance status (P=0.006), lower uptake of SUV in main mass (8.9 ± 5.9 vs. 11.4 ± 6.8, P=0.003), early clinical stage (≤ II, P=0.009), and higher proportion of curative lung resection (63.3% vs. 41.2%, P=0.005) compared to the patients with NSCLC-EGFR (-).

      Conclusion
      EGFR mutations are associated with early stage of non-small cell lung cancer in never smokers.

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      P3.21-006 - The N-classification Based on the Number of Metastatic Lymph Node is Superior to Regional N-classification in Predicting Outcomes After Surgical Resection for Non-small Cell Lung Cancer. (ID 1764)

      09:30 - 16:30  |  Author(s): Y.T. Kim

      • Abstract

      Background
      In many cancers, the N-classification of current TNM stage is categorized by the number of positive lymph nodes. However, for non-small cell lung cancer (NSCLC), it is classified by the involvement of specific regional node groups. The aim of this study is to make a new N-classification grouping (nN stage) based upon the number of metastatic lymph nodes and to evaluate its prognostic significance in predicting outcome after resection of NSCLC.

      Methods
      Between January 2000 and April 2011, 2319 patients underwent surgery for NSCLC in our hospital. A total of 1982 patients was selected by excluding patients who received preoperative induction therapy or did not get curative resection and those with pN3 metastatic lymph nodes. Prospectively collected clinical information as well as pathologic variables were retrospectively analyzed. The recursive partitioning analysis was applied to define the most significant cut-off number of metastatic lymph nodes. We then analyzed overall and disease-free survival using the new nN stage grouping to test if it can provide more accurate classification compared to the conventional N stage grouping.

      Results
      Recursive partitioning analysis identified patients could be divided into three distinct groups according to the number of metastatic lymph nodes: nN0 (none), nN1 (1-7), nN2 (>7). Among 1982 patients, 1371 patients were nN0, 538 were nN1, and 73 were nN2. The 5-year overall survival rates were 79.8%, 62.1% and 36.1% for nN0, nN1, and nN2, respectively, and they were statistically different (p < 0.001, log-rank test). For conventional N stage, 1371 patients were pN0, 284 were pN1, and 327 were pN2. The 5-year survival rates were 79.8%, 63.8%, and 54.8% for pN0, pN1, and pN2 stages, respectively (p < 0.001, log-rank test). The chi-square value of nN stage was superior to that of pN stage (141.02 vs. 117.16). When we further analyzed those with pN2 patients, the nN1/pN2 group showed a significantly better survival rate than nN2/pN2 group (p < 0.001, log-rank test). Moreover, the overall survival of nN1/pN2 patients was not different from that of nN1/pN1 patients. (p = 0.074, log-rank test) Figure 1

      Conclusion
      The nN-classification seemed to predict long-term survival more accurately compared to conventional N stage grouping. Our result suggested the new N stage grouping based on the number of metastatic lymph node should be considered for the next revision of the TNM classification system for NSCLC.