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Y.M. Shim



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    MINI 07 - ChemoRT and Translational Science (ID 110)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      MINI07.07 - Risk Factor of Morbidity and Mortality of Surgical Resection after Induction Therapy in Patients with Stage IIIA-N2 Lung Cancer (ID 1762)

      16:45 - 18:15  |  Author(s): Y.M. Shim

      • Abstract
      • Presentation

      Background:
      Surgical resection after neoadjuvant chemoradiation therapy for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) carries high postoperative complications. Careful selection of candidate for surgery should be based on analysis of proven risk factors.

      Methods:
      We retrospectively reviewed all consecutive patients with clinical stage IIIA-N2 non-small cell lung cancer who underwent surgical resection after neoadjuvant chemoradiation therapy from 1997 to 2013. Preoperative, perioperative, and outcome variables which related to the morbidity and mortality were assessed. Univariate and multivariate analysis was done to identify predictors of postoperative morbidity and mortality.

      Results:
      During the study period, 574 patients underwent major pulmonary resection after induction therapy. The median time interval between the end of induction therapy and surgery was 33 days (range, 5-79 days). Thirty-day and ninety-day postoperative mortality were 1.4% (8 patients), and 7.1% (41 patients), respectively. The most common cause of In-hospital mortality was acute respiratory distress syndrome (n=6, 4.5%). Morbidity rate was 34.7 % (199 patients). Median hospital stay was 8 days (interquartile range, 7-11 days). Significant predictors of morbidity by multivariable analysis included patient age more than 70 years (odds ratio- 1.82;p=0.040), low body mass index <18.5 (odds ratio - 2.62;p=0.022), and pneumonectomy (odds ratio – 1.8;p=0.026). Significant predictors of mortality by multivariable analysis included patient age more than 70 years (odds ratio – 1.82; p=0.022), and pneumonectomy (odds ratio – 3.256; p=0.003). Ninety-day mortality was 15.8 % (9/57) in patient age more than 70 years, and 17.8 % (13/73) in patients who underwent pneumonectomy.

      Conclusion:
      Surgical outcomes after neoadjuvant CCRT for patients who are older than 70 year or undergo pneumonectomy are relatively poor. For those patients, there should be extra concern about the respiratory complications. And for the elderly patients with limited pulmonary reserves, other possible alternative treatment options, such as definitive CCRT rather than surgery should be considered.

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    MINI 20 - Surgery (ID 137)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 2
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      MINI20.06 - The Importance of Sleeve Lobectomy after Induction Therapy for Patients with Stage IIIA-N2 Lung Cancer: The Avoidance of Pneumonectomy (ID 364)

      16:45 - 18:15  |  Author(s): Y.M. Shim

      • Abstract
      • Presentation

      Background:
      Outcomes of pneumonectomy after neoadjuvant chemoradiastion therapy (CCRT) for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) have been well-known as grave. Whenever possible, we have tried sleeve resection in patients to avoid pneumonectomy(PN). We evaluated whether the sleeve resection (SL) could have avoided the postoperative mortality/morbidity and achieved comparable long-term outcomes with pneumonectomy.

      Methods:
      We retrospectively reviewed medical records of 574 consecutive patients with clinical stage IIIA-N2 non-small cell lung cancer who underwent surgery after neoadjuvant CCRT from 1997 to 2013. Clinical outcomes were analyzed and compared in 98 consecutive patients who had either SL (n = 25) or PN (n = 73) after neoadjuvant CCRT in a single institution.

      Results:
      Thirty-day postoperative mortality were 0% (0/25) in SL group, and 5.5% (4/73) in PN group (p=0.120). Ninety-day postoperative mortality were 12.0% (3/25) in SL group, and 17.8% (13/73) in PN group (p=0.498). The most common cause of ninety-day mortality was acute respiratory distress syndrome (n=11). Morbidity rate was 48.0 % (12/25) in SL, and 49.3% (36/73) in PN. The 5-year survival was lower in the PN group (PN, 24.7 % versus SL, 45.1%, p=0.086). The recurrence pattern (locoregional versus distant) did not differ between two groups (p=0.726). When recurrences occurred (n = 50), the site of first recurrence was local (stump site) in 0 % (0/25) of patients with SL and in 4.1% (3/73) of patients with PN.

      Conclusion:
      Following neoadjuvant CCRT for patients with stage IIIA-N2 NSCLC, SL showed a comparable or even better early and long term clinical outcomes with PN. Therefore, SL should be considered, whenever possible.

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      MINI20.10 - Prognostic Impact of Lymph Node Ratio in Patients with Pathologic Stage N1 Non-Small Cell Lung Cancer (ID 3194)

      16:45 - 18:15  |  Author(s): Y.M. Shim

      • Abstract
      • Presentation
      • Slides

      Background:
      Current nodal staging for non-small cell lung cancer (NSCLC) only take into account the anatomic location of lymph node (LN). Although among patients with same pathologic N1 NSCLC, they are known to have heterogeneous prognosis and prognostic significance of extent of LN involvement is still uncertain. The objective of current study was to evaluate whether LN ratio (LNR) is a marker of prognostic factor for survival in patients with pathologic stage II/ N1 NSCLC after complete resection

      Methods:
      A total of 4,089 consecutive patients underwent curative surgical resection for NSCLC between 2004 and 2012. Of these, 413 patients who found to have pathologic stage II/N1 NSCLC after complete resection were retrospectively analyzed. For LNR, the optimal cutoff value was determined using chi square score, which were calculated using the Cox proportional hazards regression model. The prognostic value of the LNR was calculated by Cox regression hazard model analysis.

      Results:
      The study included 337 males and 76 females with a mean age of 62 years. The mean numbers of metastatic and dissected LN were 1.84 and 26 respectively and the mean LNR was 0.082. The number of the metastatic LN was significantly correlated to the LNR (r=721; p<0.0001). Based on the maximum chi square score and minimum p value approach, the optimal cutoff value of LNR was 0.1 and patients were classified into two groups according to LNR. Both 5-year overall survival rate and the lung cancer-specific survival rate in the high LNR group (LNR ≥0.1) were significantly lower than those in the low-LNR group (overall survival: 55.4.% vs 69.8%, p=0.003; lung cancer specific survival rate: 58.4% vs. 77.0%, p<0.0001) Also, disease free survival (DFS) rates according to LNR were 56.8% in low-LNR group (LNR<0.1) and 35.0% in high-LNR group (LNR≥0.1). DFS rate in the low-LNR group was significantly higher than that in the high-LNR group (p<0.001). LNR is an independently related prognostic factor with overall survival (OR=2.288; 95% CI=1.513~3.459; p<0.0001), lung cancer-specific survival (OR=2.740; 95% CI=1.709~4.395; p<0.0001) and DFS (OR=2.191; 95% CI=1.543~3.110; p<0.0001) after adjustments of clinical variables including sex, age, stage, surgical extent, histology and adjuvant treatment.

      Conclusion:
      LNR is an independent prognostic factor of survival in patients with pathologic N1 NSLC after complete surgical resection.

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    P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P1.08-037 - PD-L1 Expression in Surgically Resected Thymic Epithelial Tumor (ID 1488)

      09:30 - 17:00  |  Author(s): Y.M. Shim

      • Abstract

      Background:
      Blockade of the immune checkpoint programmed death receptor ligand-1 (PD-L1)/PD-1 pathway has recently shown clinical activity across many tumor types. PD-L1 protein expression by immunohistochemistry (IHC) is emerging as a predictive biomarker of response to these therapies. Hence, we studied PD-L1 expression in a thymic epithelial tumor (TET).

      Methods:
      Of the patients who previously underwent resection of TET at Samsung Medical Center between January 2000 and January 2013, 220 patients who had available tissue block for immunohistochemistry were included. Formalin-fixed paraffin embedded tumor samples were stained with murine monoclonal antibody (clone h5H1) to human PD-L1. PD-L1 staining was classified based on intensity and moderate or strong intensity in 5% or more of tumor tissues was considered as positive PD-L1 expression.

      Results:
      The median age was 52 years (range, 18-81), and 57.7% of patients were male. WHO histologic type was mostly B2 (N=96, 43.6%), followed by C (N=48, 21.8%), B3 (N=47, 21.4%) and neuroendocrine tumor (N=17, 7.7%). R0 resection was possible in 193 patients (87.7%). Positive PD-L1 expression was observed in 83 samples (37.7%). PD-L1 expression and histologic type was significantly correlated, with high PD-L1 expression in histologic type B2/B3/C (7.1% vs. 42.4% in type A/AB/neuroendocrine tumor vs. type B2/B3/C; P<0.001). PD-L1 expression did not affect overall survival both in univariate and multivariate survival analysis.

      Conclusion:
      In TET, PD-L1 expression was positive in 37.7% and it was more frequently observed in aggressive histology (B2/B3/C). PD-1/PD-L1 targeting agents could be a promising therapy for TET.

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    P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P2.03-004 - Surgical Outcomes of Locally Advanced Non-Small Cell Lung Cancer Invading Great Vessels and Heart (ID 3125)

      09:30 - 17:00  |  Author(s): Y.M. Shim

      • Abstract
      • Slides

      Background:
      The role of surgery has been debated in locally advanced lung cancer, especially in cases with great vessel or cardiac invasion. The aim of this study was to evaluate predictive factors and clarify whether surgical resection is beneficial in lung cancer with great vessels and heart involvement.

      Methods:
      Patients who were surgically treated and pathologically diagnosed as T4N0/1 non-small cell lung cancer (NSCLC) with great vessel or heart invasion were enrolled and evaluated for surgical outcomes. Patients with other structural invasion to trachea, carina, esophagus, and vertebrae were excluded. Patients with previous history of other malignant disease or double primary cancer were also excluded.

      Results:
      We included 50 patients and mean age was 63 9 years old. The structural involvement included main pulmonary artery (54%), pulmonary vein (38%), aorta (12%), superior vena cava (10%) and heart (10%). Complete resection was achieved in 45 patients (90%) and 5 patients underwent tumor resection under cardio-pulmonary bypass. In-hospital mortality was 12% and 5-year overall and disease-free survival rate was 44% and 40%, respectively. Multivariate analysis demonstrated that right sided cancer (p = 0.023), grossly incomplete resection (R2; p = 0.032), pneumonectomy (p = 0.029), and large cell neuroendocrine cancer (p < 0.001) were significant unfavorable prognostic factors for overall survival. NSCLC with heart invasion showed worse 5-year overall survival than NSCLC with great vessel involvement (53% vs. 20%), but did not show statistical significance (p = 0.143) due to small number of patients (Figure).Figure 1



      Conclusion:
      Surgical resection of locally advanced lung cancer involving great vessels or heart showed an important role with affordable outcomes.

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    P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P3.03-001 - Comparison of Adjuvant Therapy Modes Following Resection in Lung Cancer Patients with Clinically (-) but Pathologically (+) N2 Disease (ID 1298)

      09:30 - 17:00  |  Author(s): Y.M. Shim

      • Abstract
      • Slides

      Background:
      Mediastinal nodal staging is very important before recommending surgical resection in newly diagnosed non-small cell lung cancer patients. Following curative resection for having apparently clinically uninvolved mediastinal node (cN0-1), some proportion of patients, however, turns out to have pathologically involved mediastinal node (pN2). There have been controversies on optimal adjuvant therapy during past 2 decades in this clinical setting. Systemic chemotherapy, either followed by or concurrent with radiation therapy, has remained most important modality. This study is to evaluate clinical outcomes following similar, but different, 3 adjuvant therapy modalities, in all of which included systemic chemotherapy, at authors’ institute.

      Methods:
      Between 2006 and 2012, authors identified 240 cN0-1/pN2 patients who received adjuvant systemic chemotherapy following curative resection: chemotherapy alone in 85 patients (Group A); chemotherapy concurrent with thoracic radiation therapy (CCRT) in 68 (Group B); and CCRT followed by consolidation chemotherapy in 87 (Group C), respectively. Chemotherapy dose intensity was lower in CCRT setting than in upfront or consolidation chemotherapy settings, while thoracic radiation therapy dose schedule was the same (50 Gy/25 fractions). Clinical outcomes of loco-regional control (LRC), distant-metastasis free survival (DMFS) and overall survival (OS) were compared among Groups.

      Results:
      Median follow-up duration was 30 (5~93) months. Median age of all patients was 60 years and 149 patients (62.1%) were male. Majority of patients (224 patients, 93.3%) underwent lobectomy, while 16 (6.7%) did pneumonectomy. Adenocarcinoma was most common in 165 patients (68.8%) followed by squamous cell carcinoma in 53 (22.1%), and others in 22 (9.2%). There was no difference among Groups with respects to pretreatment and treatment characteristics except median age (Group A was older: 63 years vs. 58 years vs. 58 years, p=0.022). LRC, DMFS and OS rates at 5 years in all patients were 75.1%, 38.0% and 76.2%, respectively. Though no significant difference in OS at 5 years among Groups (76.8% vs. 68.4% vs. 82.5%, p=0.096), LRC rate at 5 years was significantly improved by addition of thoracic radiation therapy (62.9% vs. 78.9% vs. 82.9%, p=0.011), while DMFS rate at 5 years was significantly improved by delivering full dose chemotherapy (40.6% vs. 19.4% vs. 28.6%, p=0.018).

      Conclusion:
      Although in retrospective nature having potential selection bias, current observations support that maximal benefit could be achieved by thoracic radiation therapy concurrent with chemotherapy and consolidation full dose chemotherapy with respects to LRC and DMFS. Further prospective clinical trial would be desired.

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