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R. Meguid

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    MINI 06 - Quality/Prognosis/Survival (ID 111)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 15
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      MINI06.01 - Prognostic Impact of Visceral Pleural Invasion and Its Degrees in Non-Small Cell Lung Cancer: A SEER Database Analysis (ID 2256)

      16:45 - 18:15  |  Author(s): L. Zhao, J. Zha, F. Zhou, K. Fei, C. Chen

      • Abstract
      • Presentation
      • Slides

      Background:
      Visceral pleural invasion (VPI) is reported to be associated with poor prognosis in non-small cell lung cancer (NSCLC). However, whether a tumor size larger than 3cm with VPI should be upgraded to the next T stage remains unclear. In addition, few studies have clarified the impact of VPI according to nodal status, and whether degree of VPI (PL1, PL2) affects survival is controversial. The objective of this study was to evaluate the influence of VPI and also develop a prognostic nomogram.

      Methods:
      We retrospectively reviewed the SEER database from 2004 to 2011. Inclusion criteria were defined as: first and only primary NSCLC treated with lobectomy; staging as T1-3N0-2M0, no other non-size-based T factors except VPI. Tumors were divided into 10 groups: A, 0-2cm, non-VPI; B, 0-2cm, VPI; C, 2-3cm, non-VPI; D, 2-3cm, VPI; E, 3–5cm, non-VPI; F, 3–5cm, VPI; G, 5–7cm, non-VPI; H, 5–7cm, VPI; I, >7cm, non-VPI; J, >7cm, VPI. Kaplan-Meier overall survival (OS) curves were compared using the log-rank test. A Cox proportional hazard model was used, and identified independent prognostic factors were entered into the nomogram.

      Results:
      A total of 26,315 patients were finally identified, 5,941 patients (22.6%) had VPI. VPI showed an adverse impact in all tumor size groups in N0 status (p<0.001). Cox regression showed that VPI is an independent risk factor (HR 1.25; 95%CI 1.19-1.31). In N0 status, the survival rates were significantly different between B with C and D with E groups (p<0.001), whereas not significantly between F with G (p=0.405) and H with I (p=0.506). In N1 and N2 status, only the A and B groups showed a distinct survival impact (p=0.001). Between 2010 and 2011, 5,632 patients performed the elastic stain for differentiating the degrees of VPI, and survival was not significantly different between PL1 and PL2 (p=0.568). The C-index of the nomogram was 0.68. The calibration curves showed optimal agreement between nomogram prediction and actual observation of OS.Figure 1



      Conclusion:
      The presence of VPI, rather than the extent (PL1, PL2) has an adverse impact on NSCLC patients and N0 status. In a future TNM staging system, VPI should lead to upstaging to the next T category in current 3-7cm tumors. VPI is more aggressive in early-stage tumors, while its prognostic impact in node positive and locally invasive tumors is less significant. We further established and validated a nomogram to provide individual prediction of OS. The nomogram could be helpful for clinicians in decision making.

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      MINI06.02 - T1a Lung Adenocarcinomas: Presence of Spread of Tumor through Alveolar Spaces (STAS), Micropapillary and Solid Patterns Determines Outcomes (ID 3068)

      16:45 - 18:15  |  Author(s): T. Eguchi, K. Kadota, N.P. Rizk, K.M. Woo, C.S. Sima, B.J. Park, D.R. Jones, W.D. Travis, P.S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Background:
      Our previous reports highlighting the significance of presence of micropapillary (MIP) (JNCI 2013), STAS- spread of tumor through alveolar spaces (JTO 2015), and predominant solid (SOL) (Modern Pathol 2011) histological subtype as poor prognostic markers in stage I lung adenocarcinomas (ADC) are reproduced by others. In this study, we hypothesized that presence of STAS, MIP or SOL patterns (≥5%) in small stage I lung ADC (≤2 cm) is a marker of invasion and poor prognosis, and can influence the recurrence patterns based on the type of surgical resection – lobectomy (LO) versus limited resection (LR).

      Methods:
      All available tumor slides from patients with therapy-naive, surgically resected small (≤ 2cm), solitary stage I lung ADC were reviewed (1995-2011; n = 909). STAS was defined as isolated tumor cells within alveolar spaces separate from the main tumor. MIP and SOL patterns were considered present in the tumor when it comprised ≥5% of the overall tumor. Cumulative incidence of recurrence (CIR; any types, locoregional or distant) was estimated using a cumulative incidence function. Differences in CIR between groups were assessed using Gray’s method.

      Results:
      Figure 1 The association of outcomes with the presence of STAS, MIP, or SOL patterns is shown in the table. The risk of developing any types of recurrence was significantly higher in patients with both STAS and MIP positive tumors than others (P < 0.001); and the risk of developing any types of recurrence was significantly lower in patients with both STAS and SOL negative tumors than others (P < 0.001). In the LR group, STAS, MIP and SOL patterns were independent prognostic factors for any types of recurrence (HR: 4.5, 1.4, and 1.3, respectively), locoregional recurrence (HR: 5.2, 1.3, and 1.3, respectively), and distant recurrence (HR: 3.1, 1.4, and 1.2, respectively).



      Conclusion:
      Tumor STAS, presence of MIP and SOL patterns are independent risk factors of recurrence especially in the LR group of small stage I lung ADC patients. Importantly, of these factors, tumor STAS was the strongest predictor of locoregional recurrence in this group. These results suggest that the identification of STAS in small lung ADC may identify LR patients who need further management, one of which may be completion lobectomy.

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      MINI06.03 - Improved Survival in Patients with Stage I-II NSCLC Treated with Surgery or Radiotherapy in the Department of Veterans Affairs (ID 1276)

      16:45 - 18:15  |  Author(s): J.K. Salama, C.D. Williams, D. Moghanaki, M.J. Kelley

      • Abstract
      • Presentation
      • Slides

      Background:
      Recent advancements in surgical and radiotherapy techniques for early stage NSCLC have demonstrated improved outcomes in clinical trials and case series. However, their impact on large populations remains poorly studied. We therefore analyzed Department of Veterans Affairs (VA) data to evaluate temporal trends in survival within a large integrated healthcare system during the decade these techniques were introduced.

      Methods:
      Using VA Central Cancer Registry and vital status data, patients diagnosed with stage I-II NSCLC between 1/1/2001-12/31/2010 were identified. Patient characteristics assessed included age, race, stage, histology, Charlson comorbidity index, specific comorbid conditions, and smoking status. Descriptive and chi-square statistics were used to compare patient characteristics and outcomes.

      Results:
      18,442 patients were identified with stage I-II NSCLC. The primary modality of treatment was surgery in 10,754 (58%), radiotherapy in 3,708 (20%), and another or no therapy in 3,980 (22%). Patients treated with surgery were younger (median age 66 vs 72%, p<0.0001), were more likely to have a comorbidity index of 0 (28% vs 18%, p<0.0001), and were less likely to have COPD (41% vs 58%, p<0.0001), diabetes (22% vs 25%, p=0.0026), peripheral vascular disease (16% vs 20%,P<0.0001), and coronary vascular disease (9 vs 12%,p<0.0001). Surgery patients were more likely to be current (52% vs 45%, p<0.0001) and less likely to be former (39% vs 45%,p<0.0001) smokers. Equal percentages of surgery and radiation patients were black (14% vs 15%) and white (86% vs 85%). Compared to radiotherapy, surgery patients were more likely to have earlier stage disease (stage I: 79% vs 70%, p<0.0001), and adenocarcinoma (45% vs 22%, p<0.0001). The number of stage I-II NSCLC patients treated with radiotherapy or surgery increased by 50% (667 to 1,001) and 35% (1,845 to 2,496), respectively. The percentage treated each year with surgery increased from 56% in 2001 to a peak of 61% in 2004-2005, decreasing back to 56% in 2010. Inversely, the percentage treated each year with radiation decreased from 21% in 2001, to 17% in 2005 and increased to 24% in 2010. The use of other/no therapy remained unchanged. The Southern region comprised almost half of all treated lung cancer diagnoses (46%), followed by the Midwest (21%), the West (17%), and the Northeastern Region (14%). Between 2001-2010, the number of patients receiving therapy (radiation or surgery) increased each year (p=0.0017). The 4-year survival rate was 54% for surgery patients and 19% for radiotherapy patients (p<0.0001), which varied based on stage (stage I: 58% vs 22%; stage II: 41% vs 13%, respectively). Between 2001-2010, patients treated with either surgery or radiotherapy had a 12% absolute improvement in 4 year OS, representing a 100% survival improvement with radiotherapy (12% to 24%) and a 24% improvement with surgery (49% to 61%).

      Conclusion:
      The Department of Veterans Affairs is treating increasing numbers of patients with stage I-II NSCLC. Following a decade when advanced technologies were introduced for surgery and radiotherapy, survival rates have improved significantly for both treatment modalities. The largest gains were observed among patients treated with radiotherapy with a doubling of 4-year survival.

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      MINI06.04 - Impact of Attainment of the American College of Surgeons Commission on Cancer Quality Measure on Patient Survival After Lung Cancer Resection (ID 2177)

      16:45 - 18:15  |  Author(s): X. Yu, N. Faris, R. Eke, M.P. Smeltzer, G. Relyea, F.E. Rugless, C. Fehnel, N. Chakraborty, C. Houston-Harris, F. Lu, E.T. Robbins, R.S. Signore, L. McHugh, B. Wolf, C. Mutrie, L. Deese, P. Levy, E. Crocker, L. Wiggins, R.U. Osarogiagbon

      • Abstract
      • Presentation
      • Slides

      Background:
      Institution-driven survival disparities persist among non-small cell lung cancer (NSCLC) patients who receive curative-intent surgical resection. Recently, the Commission on Cancer (CoC) established an institutional quality surveillance measure: the proportion of resected stage IA–IIB NSCLC with examination of ≥10 lymph nodes. We examined the potential impact of this measure on long-term patient survival.

      Methods:
      We analyzed all stage IA-IIB NSCLC resections in the Mid-South Quality of Surgical Resection cohort, a patient-level database of all lung cancer resections performed in 11 institutions in 5 Dartmouth Hospital Referral Regions in Eastern Arkansas, Northern Mississippi, and Western Tennessee from 2004-2013. We recorded pathologic staging details. Patients receiving pre-operative therapy were excluded. A trend analysis of quality and survival disparities was performed based on a Cox proportional hazard model, adjusted for age and pathologic stage.

      Results:
      Of 1,877 eligible patients, 77% were stage I and 23% stage II. The median number of lymph nodes retrieved during surgery was 6 (interquartile range [IQR]: 3-10). The CoC quality measure was achieved in 27.8% of cases. Conversely, 11% of resections had no lymph nodes examined (pNX). The proportion of cases meeting the CoC criteria increased from 18.8% in 2004 to 50% in 2013 (p<0.001). Large variations among institutions existed, ranging from 14% to 55% of institutional cases meeting the CoC measure. Compared to pNX resections, resections with at least one lymph node examined yielded some survival benefit (Hazard ratio (HR): 0.71, 95%CI: 0.54-0.93, p=0.014). Likewise, Patients with 10-12 lymph nodes examined had 43% overall survival benefit (HR: 0.57, 95%CI: 0.40-0.81, p=0.002), but survival did not significantly improve compared with 4-6 (the median) lymph nodes harvested (p=0.48). However, the survival benefit improved as more lymph nodes were examined, reaching an optimal point of a 72% benefit when 19-21 lymph nodes were harvested (HR: 0.28, 95%CI: 0.11-0.68, p=0.005). Compared with 4-6 lymph nodes, the survival benefit was 17% (p=0.06) (Figure 1). Furthermore, for those with any mediastinal lymph nodes sampled during the surgery, the survival benefit was 17% (HR: 0.82, 95%CI: 0.71-0.96, p=0.015). Figure 1



      Conclusion:
      Only 28% of NSCLC resections achieved the CoC measure, with large variations among institutions, but the overall rate of attainment has increased over time. Compared with no lymph nodes examined, meeting the CoC criteria provided a 43% overall survival benefit. However, more stringent measures, such as examining 20 lymph nodes (72%) or requiring mediastinal lymph node examination (17%), will have even greater survival impact.

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      MINI06.05 - Discussant for MINI06.01, MINI06.02, MINI06.03, MINI06.04 (ID 3398)

      16:45 - 18:15  |  Author(s): D. Harpole

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MINI06.06 - Early-Stage Lung Cancer Treatment and Survival: Impact of Race (ID 727)

      16:45 - 18:15  |  Author(s): C.D. Williams, M.J. Kelley

      • Abstract
      • Presentation
      • Slides

      Background:
      Lower rates of surgical resection for early-stage lung cancer among blacks compared to whites are well-documented and have persisted for decades. It is suggested that the survival disparity is largely due to lower rates of surgery among blacks and that equivalent outcomes are possible for blacks and whites with similar treatment. The objectives of this work were to utilize a decade of data to evaluate trends in receipt of treatment among blacks and whites and examine the impact of race on survival outcomes.

      Methods:
      We used data from a national cohort of patients in the Veterans Administration diagnosed with Stage I-II non-small cell lung cancer (NSCLC) between 2001 and 2010. Chi-square statistics were used to compare treatment and outcomes by race. Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (95%CI).

      Results:
      Among 18,442 patients with stage I-II NSCLC, the proportion of blacks and whites receiving surgery was 54% and 59% (p ≤ 0.0001), respectively. The black-white difference in surgery rates was 8% in 2001 and 1% in 2010. There was no racial difference in receipt of nonsurgical therapy; however, blacks were more likely than whites to have no treatment (22% vs. 18%, p ≤ 0.0001). Among surgical patients, type of surgical resection was similar by race, the 30-day mortality rate was 2% in both race groups, but 90-day mortality was significantly higher in whites than blacks (6% vs. 3%, p=0.0008). Also, 31% of blacks were diagnosed at the time of surgery compared to 27% of whites (p<0.0001). There was no racial difference in type of nonsurgical treatment, with 86% of all patients who did not have surgery receiving radiation therapy. Among all patients, the 4-year survival rate was 40% in blacks and 39% in whites (p=0.38), and the adjusted HR for blacks compared to whites was 0.91 (95%CI 0.84-0.98) among all patients. Corresponding HRs and 95% CI among patients receiving surgical treatment, nonsurgical treatment, or no treatment were 0.90 (0.83-0.97), 0.83 (0.76-0.91), and 0.91 (0.82-0.996), respectively.

      Conclusion:
      The racial disparity in receipt of surgery for early-stage lung cancer decreased between 2001 and 2010, with similar rates observed at the end of the study period. Previously reported racial differences in survival outcomes were not observed in this cohort. Despite overall lower surgery rates among blacks, the proportion of black and white patients surviving 4 years was similar although overall survival was slightly better among blacks, and this finding was consistent among patients with and without treatment.

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      MINI06.07 - High Incidence of PD-L1 Expression in Surgically Resected Pulmonary Lymphoepithelioma-Like Carcinoma Is Linked to Prognosis (ID 1495)

      16:45 - 18:15  |  Author(s): Y. Yang, S. Hong, W. Fang, H. Zhao, Y. Huang, X. Wang, L. Zhang

      • Abstract
      • Presentation
      • Slides

      Background:
      Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare and distinct type of primary lung cancer which is characterized by Epstein-Barr virus (EBV) infection. The prognostic significance of programmed cell death ligand 1 (PD-L1) in pulmonary LELC remains poorly understood.

      Methods:
      A total of 113 surgically resected pulmonary LELC in Sun Yat-sen University Cancer Center between January 2008 and December 2012 were included. Paraffin-embedded tumor sections were stained with PD-L1 antibody. H score were calculated by multiplying the percentage of positively stained cells by an intensity score. Tumors with >5% PD-L1 expression were deemed PD-L1 positive. The mRNA level of latent membrane protein 1 (LMP1) were determined by RT-PCR. Univariate and multivariate analyses were performed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS).

      Results:
      The positive rate of PD-L1 was 74.3%. Patients with PD-L1 (+) tumor were significantly younger than those with PD-L1 (-) (median age, 50 vs 58 years; p = 0.008). High PD-L1 expression (H-score > 30) was associated with impaired DFS (median: 33.8 months vs not reached; p = 0.008) compared with low PD-L1 expression (Figure 1). Multivariate analysis shows that PD-L1 expression level (p = 0.014), N stage (p = 0.039) and M stage (p= 0.024) were independent prognostic factors for DFS. N stage and M stage but not PD-L1 expression level were significantly associated with OS (Figure 2). Also, LMP1 mRNA level was significantly associated with PD-L1 expression level (p < 0.001).Figure 1Figure 2





      Conclusion:
      Our results reveal higher incidence of PD-L1 expression in pulmonary LELC than common lung cancer, which may be linked to EBV burden. PD-L1 was a negative prognostic factor for DFS but was not associated with OS in surgically resected pulmonary LELC. These findings may provide a rationale for immunotarget therapy in this virus-associated lung cancer.

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      MINI06.08 - Recognition Of 'Aggressive' Nodal Metastatic Behavior In 'Indolent' Ground Glass Opacity Lesions (ID 2345)

      16:45 - 18:15  |  Author(s): J. Zha, L. Zhao, D. Xie, K. Fei, C. Chen

      • Abstract
      • Presentation
      • Slides

      Background:
      Radiologically characteristic ground-glass opacity (GGO) represents a special cohort of pulmonary adenocarcinomas that has been unanimously defined as biologically inert. Lymph node metastasis, however, occurs occasionally in these biologically "indolent" cancers. The incidence and underlying risk factors of nodal metastasis remain unknown.

      Methods:
      All surgically removed GGO lesions between Jan. 2008 and Dec. 2014 were reviewed from a single treatment institution. Pathologically-confirmed adenocarcinomas with systemic lymph node dissection or sampling were enrolled into the present study. All the lesions were classified into three groups according to the proportion of solid densities: Group I, pure GGO; Group II, 1% to 50%; and Group III, 50% to 100%. Risk factors analysis of lymph node involvement was performed by multivariate logistic regression.

      Results:
      Of the 867 patients eligible for this study, there were 566 (65.3%) females and 301 (34.7 %) males. 553 (63.7%) presented as pure GGOs (Group I) and 314 (36.2%) were mixed GGOs, of which 160 (18.5%) were in Group II and 154 (17.8%) group III. Lymph node metastasis was confirmed in 25 patients, including 12 pN1 and 13 pN2 cases. Among these 25 cases, 11 were Group II and 14 were Group III; 13 (13/367) had1-2cm tumors and 12 (12/136) had 2-3cm tumors, which also showed a significant statistical difference (p=0.016). Two of the 25 patients were deceased from lung cancer metastases at postoperative 23rd and 36thmonths, respectively. Statistical analysis revealed three predictors for lymph nodal metastasis: tumor size, preoperative serum carcinoembryonic antigen level, and proportion of the mix density. The ROC curves show cutoff values at 1.1cm, 2.75ng/ml and 21%, respectively.Figure 1

      Table1. Independent predictors of lymph node involvement by multivariate analysis
      Variables Odds Ratio 95%CI P
      Tumor size 2.544 1.271-5.092 0.008
      GGO status(Ratio) 3.272 1.759-6.089 <0.001
      CEA level 9.672 3.805-24.584 <0.001




      Conclusion:
      Among the majority of "indolent" GGO lesions, lymph node metastasis occurs occasionally at 2.9%. A larger size, mixed GGOs with a higher proportion of solid component, and elevated serum CEA level were associated with a higher preference for nodal metastasis.

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      MINI06.09 - Aerogeneous Spread Is a Predictive Factor of Recurrence in Stage I Lung Adenocarcinoma (ID 248)

      16:45 - 18:15  |  Author(s): S. Shiono, N. Yanagawa

      • Abstract
      • Presentation
      • Slides

      Background:
      Previously, aerogeneous spread with floating cancer cell clusters (ASFC) was a prognostic factor and significantly related with local recurrence of the surgical margin after metastatic lung tumor (Shiono, Ann Thorac Surg 2005). However, ASFC in surgically resected lung cancer has not been investigated well. Since our institute examined ASFC in resected lung cancer specimens prospectively, we assessed the prognostic impact of ASFC and local recurrence in stage I lung adenocarcinoma cases.

      Methods:
      From July 2004 to November 2014, a total of 877 lung cancer patients underwent a surgery. Among them, 318 patients with pathological stage I adenocarcinoma cases were reviewed. We investigated the characteristics of ASFC and analyzed the relationship between ASFC and prognosis. The patients who received preoperative treatment or had multiple lung cancers were excluded.

      Results:
      Median follow-up time was 28 months. Of the 318 patients, 47 (14.8%) patients had ASFC. The local recurrence rate was 11 of 47 (23.4%) cases with ASFC and 10 of 271 (3.7%) cases without (p < 0.01). All 4 cases developing surgical stump recurrence had an ASFC. In patients with ASFC, the ratio of male, smoker, EGFR mutation negative, lymphovascular and pleural invasion were significantly high (p < 0.01). Standardized uptake value (SUV) (p < 0.01) was also significantly higher in ASFC positive cases. Surgical procedure did not influence development of ASFC. Multivariate analysis revealed that the ASFC were significantly related with EGFR negative mutation and lymphovascular invasion. As preoperative predictive factors for ASFC, SUV was a significant predictive factor (p = 0.01). Univariate analysis showed that overall 5-year survival of cases with ASFC was 62.7% and without was 91.1% (p < 0.01) and recurrence free 5-year survival of cases with ASFC was 54.4% and without 87.8% (p < 0.01). Multivariate analysis showed that age, pleural invasion and ASFC were significant prognostic factors for overall survival, and that these factors were significantly related to cancer recurrence after surgery.Figure 1



      Conclusion:
      In p-stage-I lung adenocarcinoma patients, ASFC was frequently found in invasive lung adenocarcinoma cases. Therefore, characteristics of these lung cancers may develop a poor prognosis. PET scan might have effective radiological examinations to find a lung adenocarcinoma with ASFC.

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      MINI06.10 - Discussant for MINI06.06, MINI06.07, MINI06.08, MINI06.09 (ID 3545)

      16:45 - 18:15  |  Author(s): O.T. Brustugun

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MINI06.11 - The Influence of Body Mass Index on Overall Survival following Surgical Resection of Non-Small Cell Lung Cancer (ID 2722)

      16:45 - 18:15  |  Author(s): K.A. Gold, B. Sepesi, A.M. Correa, X. Liu, J.V. Heymach, A.A. Vaporciyan, E. Dmitrovsky

      • Abstract
      • Presentation
      • Slides

      Background:
      Population studies suggest that high body mass index (BMI) correlates with a reduced risk of death from lung cancer. The aim of our study was to evaluate the influence of BMI on long term overall survival (OS) in surgical patients with non-small cell lung cancer (NSCLC).

      Methods:
      Study population consisted of 1935 patients who underwent surgical resection for lung cancer at MD Anderson Cancer Center between 2000-2014. Patients with perioperative mortality, 90-day mortality, intraoperative transfusion, postoperative ICU days, postoperative pneumonia, and postoperative transfusion were excluded. Study variables included both patient and treatment related characteristics. Univariable and multivariable Cox regression analyses were performed to identify variables associated with overall survival. Propensity matching was performed to compare patients with BMI <25 and BMI≥30 matching on type of surgery, age, gender, histology, and pathological stage.

      Results:
      On univariable analysis, significant predictors of improved survival were higher BMI, pathologic tumor stage (stage I vs II, III, or IV), type of surgery (lobectomy/pneumonectomy vs wedge resection/segmentectomy), younger age, female gender, and adenocarcinoma histology (vs squamous) (all p<0.05). Patients considered morbidly obese (BMI≥35) had a trend towards better outcomes than those classified as obese (BMI ≥30 and <35), overweight (BMI ≥25 and <30), or healthy weight (BMI<25) (HR 0.727, 0.848, 0.926, and 1, respectively, p=NS). On multivariate analysis, BMI remained an independent predictor of survival (p=0.02, see Table). Propensity matching analysis demonstrated significantly better OS (p=0.008) in patients with BMI≥30 compared to BMI <25 (Figure).

      Multivariate Cox Regression Model
      N (%) Overall Survival HR (95% CI)
      BMI <25 (Reference) ≥25 646 (33.4%) 1289 (66.7%) 1.000 0.833(0.713-0.975)
      Age Continuous variable Median 66 (13-88) 1.024 (1.015-1.032)
      Gender Female (Reference) Male 984 (50.9%) 951 (49.1%) 1.000 1.236 (1.061-1.441)
      Stage I (Reference) II III IV 1149 (59.4%) 431 (22.3%) 299 (15.5%) 56 (2.9%) 1.000 1.839 (1.570-2.271) 2.653 (2.182-3.225) 2.737 (1.934-3.873)
      Surgery Wedge/Segmentectomy (Reference) Lobectomy/Pneumonectomy 198 (10.2%) 1737 (89.8%) 1.000 0.602 (0.479-0.755)
      Pre-op therapy No (Reference) Yes 1604 (82.9%) 331 (17.2%) 1.000 1.399 (1.160-1.686)
      Histology Adenocarcinoma (Reference) Squamous Other 1252 (64.7%) 472 (24.4%) 211 (10.9%) 1.000 1.225 (1.035-1.451) 0.959 (0.747-1.231)
      Figure 1



      Conclusion:
      In a large, single center series, after controlling for disease stage and other variables, higher BMI was associated with improved OS following surgical resection of NSCLC. Further studies are necessary to define the complex relationship between BMI and treatment outcomes.

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      MINI06.12 - Prognostic Impact of Cancer-involved Lymph Node Ratio in Resected NSCLC Differ between 'N1' or 'N2' Disease (ID 3209)

      16:45 - 18:15  |  Author(s): W. Liang, J. He

      • Abstract
      • Slides

      Background:
      The extent of lymph nodes (LN) involvement and the adequacy of systematic LN sampling are significantly correlated with the prognosis of cancer patients. The index combing these two factors, cancer-involved LN ratio (LNR), has been proved a strong prognostic factor by extensive previous studies, including non-small cell lung cancer (NSCLC). However, intrapulmonary or mediastinal LNs associate with different examination strategy. It might not be appropriate to apply the LNR indistinguishably to all patients. Therefore, we sought to examine the performance of LNR separately.

      Methods:
      A consecutive cohort of patients who underwent radical resection with systematic lymph node sampling for NSCLC between Sep 2009 and Dec 2011 were collected. LNR for intrapulmonary and hilar LNs was recorded as LNR1, and LNR for mediastinal LNs was recorded as LNR2. LNR was incorporated in the Cox regression model as a continuous variable. Disease free survival (DFS) was the primary endpoint.

      Results:
      A total of 681 cases were included for analysis. Overall LNR was a significant prognostic factor in overall population (HR 11.75, 95% CI 6.99 to 19.75; P<0.001). For patients with ‘N2’ disease, overall LNR remained a prognostic factor (HR 3.07, 95% CI 1.22 to 7.74; P=0.02). However, further explorations revealed that LNR2 has prognostic impact (HR 3.59, 95% CI 1.68 to 7.67; P<0.01) but not LNR1 (HR 0.99, 95% CI 0.48 to 2.06; P= 0.99). For those with ‘N1’ disease, LNR1 was not a significant prognostic factor (HR 3.19, 95% CI 0.87 to 11.66; P=0.08) but the prognostic value of overall LNR is strong (HR 36.17, 95% CI 6.23 to 210.13; P<0.01).

      Conclusion:
      This study suggests that for pathological ‘N1’ NSCLC, overall LNR should be considered a prognostic value while for ‘N2’ disease, only medialstinal LNR should be included in prognostic stratification.

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      MINI06.13 - Multiple Lung Cancers: Is Their Survival Better or Worse Then Other Lung Cancers? (ID 3058)

      16:45 - 18:15  |  Author(s): J. Naidoo, K. Woo, C.S. Sima, W.D. Travis, M. Arcila, D.J. Finley, V. Rusch, D.R. Jones, M.G. Kris, M.G. Zauderer

      • Abstract
      • Presentation
      • Slides

      Background:
      Multiple lung cancers (MLCs) are determined using the Martini-Melamed clinical criteria, and comprehensive pathologic assessment. The prognosis of MLCs is not known. Herein, we evaluate the prognosis of patients with MLCs, one resected LC, and recurrent LC, to ascertain whether patients with MLCs have a distinct natural history compared to the other two groups.

      Methods:
      After IRB approval, we conducted a retrospective review of all patients who underwent an R0 resection for stage IA-IIIA LC from 2008-2013 in our institution. Patients with carcinoid tumors, adenocarcinoma-in-situ, multiple ground-glass opacities, intrapulmonary metastases and cancers not originating from the lung, were excluded. MLCs were defined using Martini-Melamed criteria and comprehensive pathologic assessment. Clinicopathologic data was collected. We used the Kaplan-Meier method and log-rank test to assess overall survival (OS) of patients with MLCs, one LC, or recurrent LC, from the time of surgery/pathologic confirmation of their MLC, one LC, or recurrent LC, respectively.

      Results:
      2352 patients were identified: one LC (n=2238), recurrent LC (n=348), MLC (n=113).Median OS and 2-year OS for patients in these subgroups stratified by stage, is depicted in Table 1. In patients with one LC, never smokers (p<0.001), adenocarcinoma histology (p<0.001), and surgery type (p<0.001) were associated with improved OS. In patients with recurrent LC, never smokers (p=0.015), and adenocarcinoma histology (p=0.009) were associated with favorable OS, compared to smokers and squamous histology respectively. In patients with MLCs, adenocarcinoma histology was associated with improved OS when compared to squamous histology (p=0.049).

      Pathologic Stage (n) Median Overall Survival (months, 95% CI) Two-Year Overall Survival p value
      One Lung Cancer (n=2238) All Not Reached (75.2-NA) 0<0.001
      IA 0.914
      IB 0.841
      IIA 0.789
      IIB 0.755
      IIIA 0.691
      Multiple Lung Cancers(n=113) All 55.5 (49.4-NA) 0.32
      IA 0.810
      IB 0.806
      II/III 0.830
      Recurrent Lung Cancer (n=348) All 10.4 (9.1-12.3) 0.077
      IA 0.263
      IB 0.180
      IIA 0.273
      IIB 0.351
      IIA 0.083


      Conclusion:
      Martini-Melamed criteria and comprehensive pathologic assessments successfully identify patients with MLCs. Prognostic data for patients with MLCs, one LC and recurrent LC, highlight that these patients have a long natural history. MLCs have a long survival stage for stage, which underscores a definitive therapeutic approach where possible, based on favorable prognosis of these patients.

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      MINI06.14 - The Impact of Serum EGFR Levels on Survival of Resected Patients with Non-Small Cell Lung Cancer (ID 3237)

      16:45 - 18:15  |  Author(s): E. Hekimoglu, Y. Oltulu, I. Yaylım, K. Kaynak, A. Turna

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung cancer is an important cause of cancer mortality. Mutations of the EGFR gene may cause deranged activation leading to cell proliferation and the inhibition of apoptosis and metastases. Screening for EGFR mutation plays a key role for managements of lung cancer cases. The aim of our study is to determine a possible relationship between EGFR gene mutations in exon 19,20,21, along with serum EGFR levels and non small cell lung cancer.

      Methods:
      A total of 35 patients; 29 (%82.9) male and 6 (%17.1) female with non small cell lung cancer who underwent surgical resection between February 2011 and July 2013 were analyzed.Mean age of the patients was 60.1(41-79) Mediastinoscopy was performed to all patients prior to the resection. Lobectomy, pneumonectomy and bilobectomy were performed to 30(%85.7), 4(%11.4) and 1 (%2.9) patients respectively. The most common tumour histopathology was adenocarcinoma(%55.6). EGFR gene mutations were analyzed for exon 19,20 and 21 by direct sequencing. In addition, serum EGFR levels were determined by ELISA in non small cell lung cancer patients and control group

      Results:
      Exon 19,20 and 21 aminoacid substitutions that could cause significant mutations were detected.At exon 19,20 and 21, totally 17 mutations were detected in 10 different regions.One of these mutations were (2237-MT) E746- T751>V, E746-T751VA, E746-S752>V on exon 19. In one sample 5 different regions of exon 20 mutations were detected. On exon 21 two mutations that cause aminoacid changes were detected which includes Leu 861 Gln ve Leu 861 Arg. In our study there was no significant difference in survival rates between the cases who have EGFR mutations or who have not(p=0.21). Serum EGFR average levels of non small cell lung cancer patients and healthy control groups were calculated respectively as, 341,49±125,41 pg/ml ve 574,9±125,96 pg/ml and the difference was found statistically significant (p<0,001). According to the EGFR levels survival rate at 3 years was %45 and mean survival time is 19 (%95 confidence interval :14-29 months)and 23 (%95 confidence interval 18-29 months)month in patients with serum EGFR levels higher and lower than 400 pg/ml respectively. The patients with high serum EGFR levels (>400 pg/ml) have better survival time than the ones who had low serum EGFR levels (p=0.04).

      Conclusion:
      EGFR mutation did not lead to survival difference in resected patients with lung adenocarcinoma.. However, survival of patients with higher serum EGFR levels seems better. The modus operandi of this effect and validation of the data need further studies.

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      MINI06.15 - Discussant for MINI06.11, MINI06.12, MINI06.13, MINI06.14 (ID 3471)

      16:45 - 18:15  |  Author(s): G. Wright

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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