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H.R. Kim



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    O13 - Limited Resections (ID 101)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      O13.05 - Outcomes of Sublobar Resection Versus Lobectomy for Non small cell Lung Cancer (NSCLC) with IPF (ID 3074)

      11:15 - 11:25  |  Author(s): H.R. Kim

      • Abstract
      • Presentation
      • Slides

      Background
      The patients for NSCLC with IPF are having at a high risk of pulmonary resection. The objective of this study was to compare the survival rate after sublobar resection and lobectomy or more resection for NSCLC among patients with IPF.

      Methods
      The total 80 patients with IPF from 1995 to 2012 at Asan Medical Center had received pulmonary resection for NSCLC. Predictors of overall survival and disease-free survival were evaluated. Statistical analyses included Kaplan-Meier estimates of survival, log-rank tests of survival differences and multivariate Cox proportional hazards models.

      Results
      Lobectomy or more resection (lobectomy group) was performed in 65 patients and sublobar resection (sublobar group) in 15 patients. The median age was 66 years (range, 42 to 86 years), The median follow-up was 17 months (range, 0.4 to 96.5 months). The postoperative early mortality rate was higher at lobectomy group than sublobar group (15.4% versus 6.7%, p<0.3), but there was no difference in postoperative late mortality between sublobar group and lobectomy group. (60.0% versus 56.9%, P<0.8) Lung cancer related death rate was higher at sublobar group than lobectomy group. (50.0% versus 23.4%, p=0.089), but the respiratory problem related death rate was higher at lobectomy group than sublobar group. (76.6% versus 50.0%, p=0.089) There was no difference in local recurrence between two groups (20.0% versus 7.7% P=0.15) Distant metastasis was higher at sublobar group than lobectomy group. (46.7% versus 10.9%, p<0.001) There was no difference in overall survival between two groups with a hazard ratio of 0.51 (95% confidence interval, 0.21 to 1.2). A disease-free survival of sublobar group was significantly lower than lobectomy group, with an increased hazard ratio of 4.7 (95% confidence interval, 1.1 to 20.2, p=0.03).

      Conclusion
      Although sublobar group was associated with increased incidence of distant metastasis compared with lobectomy group but there is no difference in overall survival. Therefore, sublobar resection might be considered as one of the strategy for lung cancer with IPF.

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    P1.05 - Poster Session 1 - Preclinical Models of Therapeutics/Imaging (ID 156)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.05-008 - The HSP 90 inhibitors suppress cell growth by suppression of ALK and TGF-beta1 signaling in crizotinib-resitant H2228 cells by Epithelial to mesenchymal transition (ID 2544)

      09:30 - 09:30  |  Author(s): H.R. Kim

      • Abstract

      Background
      Epithelial to mesenchymal transition (EMT) is related with reduced sensitivity to many chemotherapeutic drugs including EGFR tyrosine kinase inhibitors. We investigated whether EMT also could contribute to the resistance to crizotinib and there are other therapeutic options overcoming EMT-mediated resistance.

      Methods
      We established a crizotinib-resistant subline (H2228/CR), which was derived from the parental H2228 cell line by long-term exposure to increasing concentration of crizotinib. Characteristics related with EMT including morphology, EMT marker proteins and cellular mobility were analyzed. We examined whether the induction of EMT affect sensitivity to Hsp90 inhibitors.

      Results
      Compared with the H2228 cell, the growth of H2228/CR cells was independent on EML4-ALK, and they showed cross-resistance to TAE-684 (a 2[nd]-generation ALK inhibitor). Phenotypic change of a spindle-cell shape was found in H2228/CR, which was accompanied by a decrease of E-cadherin and an increase of vimentin and AXL. In addition, they showed the increased secretion and expression of TGF-β1. The capability of invasion and migration was dramatically increased in H2228/CR cells. TGF-b1 treatment for 72 h in parental H2228 cells induced reversible EMT leading to crizotinib-resistance while this was reversed through the removal of TGF-β1. Suppression of vimentin by siRNA treatment in H2228/CR cells restored the sensitivity to crizotinib. Furthermore, these resistant cells remained highly sensitive to the Hsp90 inhibitors similar to parental cells, H2228. HSP90 inhibition resulted in downregulation of TGF-β receptor II in addition to ALK.

      Conclusion
      EMT should be considered as one of possible acquired resistant mechanisms to crizotinib and HSP90 inhibitors can be a promising therapeutic option for EMT-mediated resistance.

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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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      P1.12-006 - Predictive risk factors for mediastinal lymph node metastasis in patients with clinical stage I adenocarcinoma of the lung (ID 1241)

      09:30 - 09:30  |  Author(s): H.R. Kim

      • Abstract

      Background
      The standard operation for patients with stage I lung adenocarcinoma is considered as a lobectomy. Recently, some researchers have reported that patients with tumors tend to show less aggressive nature which it could be candidates for thoracoscopic limited resection. In regard to mediastinal nodal metastasis, however, the precise criteria as an index for planning limited resection are obscure. Therefore, we have attempted to determine low-risk or high-risk populations for mediastinal nodal metastasis in patients with clinical stage I adenocarcinoma of the lung.

      Methods
      A retrospective analysis was made of 617 patients who underwent curative pulmonary resection with mediastinal lymph node dissection by video-assisted thoracoscopic surgery (VATS) between Jan 2006 and Nov 2012 for clinical stage I adenocarcinoma of the lung. Preoperative computed tomography (CT) and positron emission tomography (PET) were performed in all patients. Additionally, endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) was performed in 12 patients, mediastinoscopic lymph node biopsy in one patient, and endoscopic ultrasound (EUS) was performed in one patient. The patients had received the treatment with wedge resection or the patients who had other malignancies were excluded in this study.

      Results
      Among 617 patients, mediastinal nodal metastasis was found in 47 patients (7.6%), consisted of N1 disease in 24 patients (3.9%), N2 disease in 23 patients (3.7%), and skipped N2 disease in 6 patients (0.9%). Five year survival rate of the patients with N0 disease, N1 disease, and N2 disease was 90.3%, 55.6%, 54.8%, respectively (p<0.001). A univariate analysis identified the following four variables as significant predictors for mediastinal nodal metastasis: tumor size (p=0.003), consolidation/tumor ratio (p<0.001), maximal standardized uptake value (SUVmax) of tumor (p=0.002), and differentiation of tumor (p < 0.001). The optimal cutoff points of continuous variables were determined as: 1.7cm for the tumor size, 84.0% for consolidation/tumor ratio, and 3.3 for SUVmax. A multivariate analysis revealed that following three significant predictors for mediastinal nodal metastasis as shown in the next statement: the consolidation/tumor ratio of 84% or more (OR: 4.097, p=0.001), maximal SUV of 3.3 and more (OR: 3.662, p=0.002), moderate or poorly differentiation of histology (OR: 3.794, p=0.016). The prevalence of nodal metastasis was 0% in patients who had none of these three predictors. 2.1% in patients with one of the three predictors, 10.8% in patients with two of the three predictors, and 21.0% in patients with all of the three predictors (p<0.001).

      Conclusion
      Among the patients with clinical stage I adenocarcinoma of the lung, low-risk population for mediastinal nodal metastasis could be predicted by following the three predictors (84% of consolidation/tumor ratio, 3.3 of SUVmax, ‘moderate’ and ‘poorly’ differentiation of tumor). These predictive parameters may provide detailed criteria for thoracoscopic limited resection in regard to mediastinal nodal metastasis.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-030 - The Role of Mediastinal Lymph Node Dissection during Pulmonary Metastasectomy in Patients with No Evidence of Mediastinal Lymph Node Metastasis Based on Preoperative Computed Tomography and Positron Emission Tomography (ID 2616)

      09:30 - 09:30  |  Author(s): H.R. Kim

      • Abstract

      Background
      The clinical impact of mediastinal lymph node dissection (MLND) during pulmonary metastasectomy remains controversial. Especially the prognostic contribution of MLND on the prevention of tumor recurrence in patients with no evidence of mediastinal lymph node metastasis has not been clearly defined. We aimed to clarify the role of MLND during pulmonary metastasectomy in this population.

      Methods
      We retrospectively reviewed 632 patients who underwent pulmonary metastasectomy from January 2006 to December 2010 in Asan Medical Center. Among them, two hundred nine patients were identified to meet the following criteria and comprised the current study population: the presence of preoperative computed tomography (CT) and positron emission tomography (PET) within 2 months before pulmonary metastasectomy, definite control of the primary tumor, and no evidence of mediastinal lymph node metastasis. Of 209 patients, sixty-seven patients underwent MLND during pulmonary metastasectomy (MLND group), whereas 142 patients underwent pulmonary resection only (non-MLND group). Between-group recurrence-free survival was compared, and risk factors for tumor recurrence were evaluated. The data on tumor recurrence were obtained through a median follow-up duration of 42 months (range 2-83 months).

      Results
      The study population was composed of 119 male and 90 female, and the age at the first pulmonary metastasectomy ranged from 13 to 82 years (median, 56 years). Primary tumor pathologies included colorectal cancer (n=104, 49.8%), hepatobiliary cancer (n=38, 18.2%), kidney cancer (n=17, 8.1%), sarcoma (n=14, 6.7%), and the others (n=36, 17.2%). Disease-free interval from initial primary tumor treatment to the first metastasis ranged from 1 to 94 months (median, 25 months). Overall 5 year recurrence-free survival rate was 30.1%. There was no difference in recurrence rates between the MLND group and the non-MLND group (5 year recurrence-free survival: 30.0% vs. 24.5%, p=0.927). On multivariable analysis, primary tumor histopathology (p<0.001), disease-free interval (p=0.016), and the number of nodules (p<0.001) emerged as significant and independent prognostic factors for recurrence. After adjustment by these three significant variables, mediastinal lymph node dissection did not affect recurrence-free survival (hazard ratio, 0.924; 95% confidence interval, 0.641-1.333; p=0.672).

      Conclusion
      Tumor recurrence after pulmonary metastasectomy was affected by the histopathology of the primary tumor, disease-free interval, and the number of metastatic nodules. However, the role of mediastinal lymph node dissection as a part of pulmonary metastasectomy is obscure in patients with no evidence of mediastinal lymph node metastasis based on CT and PET.

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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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      P2.09-012 - Prognostic Value of Tumor Survivin Expression in Stage III Non-small Cell Lung Cancer Patients Treated with Platinum-based Chemoradiation Therapy Followed by Surgery (ID 2473)

      09:30 - 09:30  |  Author(s): H.R. Kim

      • Abstract

      Background
      The potential prognostic value of survivin is variably reported in various stage of lung cancer. This study evaluated the correlation between tumor survivin expression before and after chemoradiation therapy (CRT) and prognosis in stage III non-small cell lung cancer (NSCLC) patients treated with platinum-based chemoradiation therapy followed by surgery

      Methods
      Medical records from 53 patients whose tissues were suitable for study were reviewed. Tissues were stained by immunohistochemistry and were estimated the degree of stain with scoring for survivin. Clinicopathologic parameters and survivin expression score were evaluated for a prognostic relationship with overall survival (OS) and time to recurrence (TTR).

      Results
      Pathologic complete response, residual nodal involvement and radiologic response after CRT were not related with OS or TTR. Tumor survivin expression on pre-treatment tissues was presented in 47 patients (88.7%). Pre-treatment survivin score was not related with TTR and OS (p = 0.249 and p = 0.601, respectively). There was no correlation between pre-treatment and post-treatment survivin score (p = 0.309). Downregulation of survivin and post-treatment survivin score (0 – 1) after chemoradiation showed significant improvement in OS (p = 0.04 and p = 0.033, respectively). Age, downregulation of survivin score, and post-treatment survivin score (0 – 1) were significant prognostic factors for survival by multivariate analysis.

      Conclusion
      Downregulation of survivin score and post-treatment low survivin score in stage III NSCLC treated with platinum-based chemoradiation therapy followed by surgery has a value of prognostic factor regardless pre-treatment survivin score. Further studies to evaluate the relation of survivin expression and platinum-based chemoradiation therapy are warranted in NSCLC.

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    P2.15 - Poster Session 2 - Thymoma (ID 191)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P2.15-005 - Long-term survival after the multimodal treatment of thymic carcinomas: A single center experiences in 90 cases. (ID 1245)

      09:30 - 09:30  |  Author(s): H.R. Kim

      • Abstract

      Background
      Thymic carcinomas are rare aggressive tumors. We reviewed our experiences to evaluate the long-term prognosis regarding the multimodal treatment of thymic carcinoma.

      Methods
      A retrospective analysis was made of a total number of 90 patients who diagnosed with thymic carcinomas between December 1997 and July 2012. Among patients, 33 patients were treated with surgical resection followed by radiotherapy with or without chemotherapy. Of the remaining 57 patients treated initially with chemotherapy with or without radiotherapy for advanced thymic carcinoma, 24 patients could have surgical resections. The survival rate was compared between the groups. Stage was measured according to the Masaoka-Koga system.

      Results
      The study group was composed of 57 men and 33 women, with a mean age of 51.5 (±1.2 years). At the time of diagnosis, 10 patients (11.1%) had stage I disease, 14 (15.6%) stage II, 21 (23.3%) stage III, and 45 (50.0%) stage IV. Histologic subtypes included 50 squamous cell carcinoma (55.6%), 10 poorly-differentiated neuroendocrine carcinoma (11.1%), 5 well-differentiated neuroendocrine carcinoma (carcinoid tumors, 5.6%), and 4 other types (4.4%) among 69 patients whose histologic classification were made by pathologic study. Overall survival rates were 55.1% at 5 years and 32.3% at 10 years. Five year survival rates were 100% in stage I or II, 68.8% in stage III, and 39.8% in stage IV (p=0.012). Five year survival rates of the patients had treated with complete resection, the patients with incomplete resection, and the patients with unresectable tumors were 95.0%, 84.4%, 10.4%, respectively (p<0.001). In regard to the role of chemoradiotherapy, the survival rate of 24 patients had treated with initial chemotherapy followed by surgical resection, consisted of 13 cases of complete resection and 11 cases of incomplete resection and 4 cases of exploration, was better than those of 33 patients who were received chemotherapy with or without radiotherapy alone (5 year survival rate, 84.8% vs. 10.4%, p<0.001). On multivariate analysis, the extent of surgical resection (complete resection vs. unresectable tumors: hazard ratio [HR] =0.117; 95% CI 0.038-0.365; p<0.001, incomplete resection vs. unresectable tumors: HR=0.200; 95% CI 0.075-0.536; p=0.001) was the sole independent prognostic factor in this study.

      Conclusion
      The prognosis of patients with thymic carcinoma is distinct according to the extent of surgical resection. Initial chemoradiotherapy followed by surgical resection may produce long-term survival even at advanced stages of disease. Surgical resection of regressed tumors at loco-regional disease after initial chemotherapy with or without radiotherapy should have attempted.