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G. Veronesi

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    MINI 20 - Surgery (ID 137)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 14
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      MINI20.01 - Do Secondary Lung Cancers Have the Same Disease-Specific Survival and Overall Survival as Primary Lung Cancers? (ID 2686)

      16:45 - 18:15  |  Author(s): C. Stock, J.M. Varlotto, S. Ali, J. Flickinger, M. Decamp, D. Maddox, K. Uy, J. Glanzman, J. Liebmann, S. Quadri, F. Gu, G. Graeber, V. Kasturi, W. Walsh, A. Yao

      • Abstract
      • Presentation
      • Slides

      Background:
      The risk of recurrent lung cancer decreases markedly after 4 years. It is unknown whether frequent surveillance after this time period would be beneficial in order to diagnose and treat secondary lung cancers. The purpose of investigation is to assess whether there is an increasing frequency of second lung cancers and whether the first primary reduces Overall Survival(OS)/Lung Cancer Specific Survival(LCSS) as compared to similar patients presenting with their first lung cancer (new primary, NP).

      Methods:
      The SEER databases were used to investigate incidence (1973-2010) and OS/LCSS (1998-2010) of secondary lung cancer. Incidence was examined by frequency and trend analyses. A SP population was chosen who was originally treated for Stage I-III NSCLC and developed a new primary at least four years after diagnosis of their original primary lung cancer (N=1,699). The OS/LCSS of their SP NSCLC were compared to patients presenting with a new primary (NP) NSCLC. OS/LCSS in NP and SP were analyzed by Kaplan-Meier estimation, multivariate proportional hazards modeling and log-rank tests in the overall group and in a favorable sub-group (stage I, < 4cm).

      Results:
      The annual incidence rates per 100,000 persons for SP NSCLC has increased almost 5 fold in last three decades (2.5 in 1973; 12 in 2010; p<0.001), more so in male patients. OS and LCSS in SP were higher than NP in the log rank tests (p<0.001). In the subgroup of NP and SP who had favorable tumor characteristics, OS/LCSS was significantly different between NP and SP (P=0.0032; P=0.0015), but did not remain so after accounting for treatment, tumor factors, and patient characteristics (HR=0.983, p=0.8493; HR=1.154, p=0.1770). Rates of OS and LCSS improved significantly with increasingly aggressive treatment in the SP group. Patient and tumor characteristics of the first primary NSCLC were not signantly linked to mortality.

      Conclusion:
      Patients presenting with a second primary lung cancer had a similar or better OS/LCSS as compared to patients presenting with a new primary lung cancer. The SP population also benefitted from increasingly aggressive treatment. Continued surveillance for new primary lung cancers after 4 years may be beneficial to lung cancer survivors.

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      MINI20.02 - Risk-Adjusted Margin Positivity (RAMP) Rate as a Surgical Quality Metric for Non-Small-Cell Lung Cancer in the US National Cancer Data Base (NCDB) (ID 1247)

      16:45 - 18:15  |  Author(s): C.C. Lin, M.P. Smeltzer, X. Yu, R.U. Osarogiagbon, A. Jemal

      • Abstract
      • Presentation
      • Slides

      Background:
      Surgical resection is the most important curative treatment modality for early-stage non-small-cell lung cancer (NSCLC). However, incomplete (margin-positive) resection is associated with inferior survival. We sought to develop a valid facility-based quality metric to measure surgical quality, adjusting related patient demographic and clinical characteristics.

      Methods:
      We identified facilities that performed cancer-directed surgery for patients diagnosed with AJCC stage I-IIIA NSCLC in the NCDB between 2004 and 2011. We used a multivariate logistic regression model, adjusting for patient risk-mix in each facility, to predict the expected number of risk-adjusted margin positivity (RAMP) cases for each facility. We divided the number of observed margin positivity (OMP) cases by the expected number of RAMP cases to obtain an observed: expected (O/E) ratio for each facility. We categorized facility performance as low outlier (O/E ratio<1 and p<.05), high outlier (O/E ratio>1 and p<.05), or non-outlier. Facility characteristics across performance categories were compared by chi-square test. Five-year unadjusted overall survival (OS) rates were estimated by Kaplan-Meier analyses and compared across categories with the log-rank test.

      Results:
      A total of 96,596 NSCLC stage I-IIIA patients underwent surgery in 941 facilities. The overall OMP rate was 4.6%. We identified 73 facilities as low outliers (mean O/E ratio=0.41), 755 as non-outliers (mean O/E ratio=1.28) and 113 as high outliers (mean O/E ratio=2.78). Compared to patients treated at high-outlier facilities, patients treated at low-outliers were more likely to be privately insured (34.7%[Low] vs. 32.9%[High]), reside in high-income neighborhoods, have no comorbidity (51.7% [Low] vs. 41.9 [High], p<.001), have adenocarcinoma (62.4%[Low] vs. 58.1%[High], p<.001), stage IA disease (41.6%[Low] vs. 39.6%[High], p<.001) and receive sub-lobectomy (11.7%[Low] vs. 9.9%[High], p<.001). Low-outlier facilities were more likely to be teaching/research or NCI-designated programs (54.8% [Low] vs. 18.5% [High], p<.001) and in the highest quartile of total cancer surgical volume (90.4% [Low] vs. 34.5% [High], p<.001) and lung cancer surgery volume (42.5% [Low] vs. 29.2% [High], p<.001) (Table 1). They also had smaller proportions of uninsured/Medicaid patients (45.2% [Low] vs. 36.2% [High], p=.006). The 5-year unadjusted OS estimates were: 0.62 (low-outliers), 0.58 (non-outliers), 0.57 (high-outliers); log-rank p<.001. Table 1. Facility characteristics across performance categories

      High-Outlier(N=113) Non-Outlier(N=755) Low-Outlier(N=73) p-value
      N(%)
      Census_region
      Northeast 18(15.9) 154(20.4) 19(26.0) 0.03
      Midwest 39(34.5) 223(29.5) 15(20.6)
      South 37(32.7) 257(34.0) 35(48.0)
      West 19(16.8) 121(16.0) 4(5.5)
      Facility_type
      Community_Cancer_Program 23(20.4) 164(21.7) 0(0.0) <0.001
      Comprehensive_Community_Cancer_Program 62(54.9) 419(55.5) 28(38.4)
      Teaching/Research 17(15.0) 128(17.0) 28(38.4)
      NCI_program 4(3.5) 17(2.3) 12(16.4)
      Other 7(6.2) 27(3.6) 5(6.9)
      Proportion_of_Medicaid/uninsure_patients
      Q1(low) 25(22.1) 206(27.3) 13(17.8) 0.006
      Q2 16(14.2) 204(27.0) 20(27.4)
      Q3 41(36.3) 174(23.1) 21(28.8)
      Q4(high) 31(27.4) 171(22.7) 19(26.0)
      Lung_cancer_surgery_as_a_proportion of_all_surgery
      Q1(low) 8(7.1) 73(9.7) 0(0.0) <0.001
      Q2 37(32.7) 224(29.7) 9(12.3)
      Q3 35(31.0) 226(29.9) 33(45.2)
      Q4(high) 33(29.2) 232(30.7) 31(42.5)
      Total_cancer_surgery_volume
      Q1(low) 12(10.6) 98(13.0) 0(0.0) <0.001
      Q2 32(28.3) 193(25.6) 0(0.0)
      Q3 30(26.6) 253(33.5) 7(9.6)
      Q4(high) 39(34.5) 211(28.0) 66(90.4)


      Conclusion:
      Facility performance in lung cancer surgery can be captured by using the RAMP rate. Low-outlier facilities delivered superior OS than high-outliers. RAMP metrics could allow facilities to understand their performance and serve as a quality improvement benchmark.

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      MINI20.03 - The Survival Impact of Missed Lymph Node Metastasis in Surgically Resected Non-Small Cell Lung Cancer (NSCLC) (ID 2204)

      16:45 - 18:15  |  Author(s): N. Faris, M.P. Smeltzer, C. Adair, A. Berry, X. Yu, L. McHugh, R.U. Osarogiagbon

      • Abstract
      • Presentation
      • Slides

      Background:
      Lymph node (LN) metastasis is an important prognostic factor for patients with surgically resected NSCLC. We have previously described the extent of missed N1 LN metastasis in a cohort of patients treated at metropolitan institutions. With long-term follow up, we now quantify the survival impact of missed LN metastasis.

      Methods:
      We conducted a prospective cohort study to retrieve intrapulmonary LNs from discarded NSCLC resection specimens after completion of routine pathology examination. Retrieved materials were histologically examined and classified as LNs with and without metastasis. Survival information was retrieved from institutional tumor registries. Survival distributions were plotted using the Kaplan-Meier method and evaluated with proportional hazards models controlling for gender, race, pathologic N-category, tumor size, margin status, and Charlson score.

      Results:
      We evaluated 111 patients who were 47% male with a median age of 66 years. Clinical characteristics are summarized in Table 1. Discarded LNs with metastasis were found after re-dissection in 25 (23%) patients. Patients with discarded LN metastasis had an increased risk of death (Figure 1) with an unadjusted hazard ratio (HR) of 2.0 (p-value=0.06) and an adjusted HR of 1.8 (p-value=0.23) compared to those with no discarded LNs with metastasis. When >2 discarded LNs with metastasis were found, patients had 4.8 (p-value=0.0002) times the hazard of death compared to those with no discarded LNs with metastasis (adjusted HR=4.4, p-value=0.0032).

      N(%) No LN Metastasis LN Metastasis Total
      Bi-lobectomy 8 2 10
      9% 8%
      Lobectomy 75 16 91
      87% 64%
      Pneumonectomy 3 7 10
      3% 28%
      N0 71 6 77
      83% 24%
      N1 6 12 18
      7% 48%
      N2 9 7 16
      10% 28%
      T1 45 3 48
      52% 12%
      T2 29 11 40
      34% 44%
      T3 10 8 18
      12% 32%
      T4 2 2 4
      2% 8%
      Margin Negative 83 22 105
      97% 88%
      Margin Positive 3 3 6
      3% 12%
      Mean(SD)
      Charlson Score 1.8 1.8 1.8
      1.6 1.7 1.6
      Tumor Size(cm) 3.2 5.0 3.6
      1.8 2.1 2.0
      Figure 1



      Conclusion:
      The presence of metastasis in inadvertently discarded LNs in NSCLC resection specimens has significant implications for patients’ post-operative clinical course. Additional LN metastasis found on re-dissection was associated with reduced survival. A more rigorous protocol for gross dissection of lung resection specimens is needed, and should prove beneficial to patients’ long-term survival.

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      MINI20.04 - Right-Sided vs Left-Sided Pneumonectomy after Induction Therapy for Non-Small Cell Lung Cancer (ID 3064)

      16:45 - 18:15  |  Author(s): C.J. Yang, D.Y. Chan, B.C. Gulack, D.N. Ranney, B.C. Tong, M.W. Onaitis, D. Harpole, T.A. D'Amico, M.G. Hartwig, M.F. Berry

      • Abstract
      • Presentation
      • Slides

      Background:
      A right-sided pneumonectomy after induction therapy for non-small cell lung cancer (NSCLC) has been shown to be associated with significant perioperative risk. We examined the impact of laterality on long-term survival using the National Cancer Data Base (NCDB).

      Methods:
      Perioperative and long-term outcomes of patients who underwent pneumonectomy following induction chemotherapy ± radiation from 2003-2011 in the NCDB were evaluated using Kaplan-Meier method, multivariable logistic regression analysis and multivariable Cox proportional hazards modeling.

      Results:
      During the study period, 1,652 patients met inclusion criteria, of whom 740 (45%) underwent right-sided pneumonectomies. Right-sided patients were more likely to have adenocarcinomas, cN2 disease and lower co-morbidity scores (Table). The 30-day mortality rate was higher for right-sided procedures in univariable (11% [84/740] vs 4% [39/912], p<0.001) and multivariable (OR 9.1 [1.8-50.0], p<0.01) analysis. However, 5-year overall survival between right and left pneumonectomy were not significantly different (figure) after a median follow up of 30.2 months. Right-sided procedure also did not impact overall survival in multivariable analysis (hazard ratio (HR), 1.41 [95% CI: 0.87-2.27], p=0.16), while increasing age (HR, 1.02 [95% CI: 1.01-1.03]), Charlson co-morbidity Score of 2 (HR, 1.42 [95% CI: 1.04-1.93]), adenosquamous histology (HR, 1.72 [95% CI: 1.18-2.51]), cN1 status (HR, 1.27 [95% CI: 1.02-1.58]), cN2 status (HR, 1.38 [95% CI: 1.14-1.66]), cN3 status (HR, 1.84 [95% CI: 1.19-2.83]), cM1 status (HR, 2.04 [95% CI: 1.42-2.92]) and incomplete resection (HR, 1.45 [95% CI: 1.14-1.84]) all predicted worse survival. Figure 1

      Table: Baseline characteristics.
      Variable Right-sided (n=740) Left-sided (n=912) p
      Induction chemoradiation 461 (62%) 584 (64%) 0.47
      Age (median, IQR) 59 (52-66) 60 (52-67) 0.07
      Charlson/Deyo Comorbidity Score 0.02
      0 518 (70%) 610 (66%)
      1 190 (26%) 243 (27%)
      2 32 (4%) 68 (7%)
      Histology 0.02
      Adenocarcinoma 227 (37%) 243 (32%)
      Squamous 310 (50%) 450 (59%)
      Large cell 28 (5%) 19 (2%)
      Adenosquamous 20 (3%) 21 (3%)
      Neuroendocrine/carcinoid 4 (1%) 7 (1%)
      BAC 28 (5%) 23 (3%)
      Clinical N < 0.01
      0 190 (27%) 269 (31%)
      1 134 (19%) 187 (21%)
      2 368 (52%) 381 (44%)
      3 16 (2%) 34 (4%)
      There were no significant differences between the groups with regards to sex, race, facility type, and clinical T and M status.



      Conclusion:
      In this population analysis, right-sided pneumonectomy after induction therapy was associated with a significantly higher perioperative but not worse long-term mortality compared to a left-sided procedure. These findings can be used in the risk/benefit analysis when considering patients for pneumonectomy following induction therapy.

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      MINI20.05 - Discussant for MINI20.01, MINI20.02, MINI20.03, MINI20.04 (ID 3420)

      16:45 - 18:15  |  Author(s): U. Pastorino

      • Abstract
      • Presentation

      Abstract not provided

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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): J.H. Cho, Y.S. Choi, J. Kim, H.K. Kim, J.I. Zo, Y.M. Shim, K. Kim

      • 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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      MINI20.07 - Extended Cervical Mediastinoscopy (ECM) for Biopsy of AortoPulmonary Window (APW) Lymph Nodes and an APW Index (APWI) Useful in Patient Selection (ID 565)

      16:45 - 18:15  |  Author(s): R.B. Cameron, S. Andaz, G. Hoal, L. Hua-Feng, M. Doyle, J. Benfield

      • Abstract
      • Slides

      Background:
      Biopsy of APW (levels 5/6) lymph nodes can be important for lung cancer staging, but the APW is not accessible by routine mediastinoscopy or EBUS. Although some consider ECM potentially dangerous, we reviewed our ECM experience to determine safety and accuracy and to define/validate parameters for patient selection.

      Methods:
      With IRB approval we reviewed two institutions' databases for patients undergoing ECM between 3/1/97 and 12/31/11. Physical parameters (PP) that were thought to impact on the difficulty and safety of ECM, ie., clavicular head (CH), thoracic inlet (TI), and anterior mediastinal (AM) dimensions, were measured using 55 CT scans available from the first 100 pts.

      Results:
      Of 190 patients, 128 (67.3%) were male and ages ranged 28-91 yrs. Indication for surgery was either cancer (>95% with lung cancer >80%) or adenopathy (<5%). All procedures were performed by a single surgeon during routine mediastinoscopy. There were no intraoperative complications and blood loss was <25 cc in all cases. Morbidity occurred in 15 (7.9%) with 1 (0.55%) major complication and no mortality. A pathologic diagnosis was obtained in 189 (99.5%). Postop pain was easily controlled with bupivicaine. PP were compared to those in an additional 12 control patients with failed procedures (Table). Although each PP alone was not useful, the APWI (TI X AM product) did predict degree of difficulty (p=0.015) and divided patients into 3 groups predictive of the degree of difficulty: Straightforward (APWI>17), Intermediate (APWI=6-17), and Prohibitive (APWI<6) (Figure). The APWI was then prospectively validated with excellent accuracy in the next 90 patients. The APWI can be helpful in the selection of patients for thoracic surgeons, particularly those learning ECM. A short video demonstrating the technique of ECM will be presented.

      Table: Physical Parameter Measurements (values were obtained from CT scans available on 55/100 initial patients comparing with a separate group of 12 patients with unsuccessful ECM
      Parameter Successful ECM (cms) UnSuccessful ECM (cms)
      Clavicular Head (CH) 2.3+0.36 2.28+0.36
      Thoracic Inlet (TI) 6.32+1.07 5.99+0.62
      Anterior Mediastinum (AM) 2.53+0.82 1.89+0.82
      APWI (TI X AM) 16.2+6.77 11.1+4.4*
      *p=0.015
      Figure 1



      Conclusion:
      ECM is straightforward, safe, and accurate in mediastinal staging. Our novel APWI helps to safely select patients for any thoracic surgeon's skill and comfort level.

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      MINI20.08 - Survival in Unexpected Multi-Station pN2 Following Surgical Resection of NSCLC (ID 1246)

      16:45 - 18:15  |  Author(s): M. Evison, S. Britton, H. Al-Najjar, R. Shah, P. Crosbie, R. Booton

      • Abstract
      • Presentation
      • Slides

      Background:
      In our cancer network, single station N2 NSCLC may be managed with surgical resection followed by adjuvant chemotherapy as meaningful survival has been shown in such circumstances. Multi-station N2 disease diagnosed pre-operatively is not considered a surgical entity. However, sometimes occult multi-station pN2 may only be identified during intra-operative nodal sampling. This study aimed to analyse the survival of such patients at a large thoracic surgical centre in the United Kingdom.

      Methods:
      A retrospective review of all pathological reports from NSCLC resections at the University Hospital South Manchester from 01/01/2011 to 31/12/2013. Based on the histological results from intra-operative nodal sampling, patients were stratified into nodal categories pN0, pN1, pN2 single station and pN2 multi-station. Survival data was obtained through national death registry data allowing a minimum of twelve months follow-up for all patients at the time of analysis in January 2015.

      Results:
      987 surgical resections for NSCLC were performed during the study period 2011 to 2013 at UHSM. A total of 132 patients had pN2 disease; 85 with single station pN2 and 47 with multi-station N2. The median survival time for those patients with multi-station pN2 was 798 days (95% CI 405-1191 days) and 762 days (95% CI 616-908 days) for those with single station pN2. Median survival times were not estimable for patients with pN0 and pN1 as only a small proportion of patients died. For pairwise comparisons between N categories, a Bonferroni adjustment for multiple comparisons used a critical value of 0.008 for significance. Patients with single station pN2 and multi station pN2 had significantly lower survival times than patients with N0, but there was no statistically significant difference in survival between patients with pN1, single station pN2 and multi-station pN2 (Figure 1).Figure 1



      Conclusion:
      Interestingly, patients with multi-station pN2 had a similar survival to those with single station pN2. This cohort of multistation pN2 patients is likely to represent those with microscopic nodal metastases and does not represent all multistation N2 disease. Although the numbers are small it does raise interesting questions about the exclusion of patients with radiologically-occult multi-station N2 disease, detected during the pre-operative systematic sampling of small mediastinal nodes through endoscopic or surgical techniques, being excluded from surgery as part of their multi-modality treatment in our network.

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      MINI20.09 - Discussant for MINI20.06, MINI20.07, MINI20.08 (ID 3549)

      16:45 - 18:15  |  Author(s): V. Rusch

      • Abstract
      • Presentation

      Abstract not provided

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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): S. Shin, H.K. Kim, Y.S. Choi, K. Kim, J. Kim, J.I. Zo, 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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      MINI20.11 - Lymph Node Impact on Conversion of VATs Lobectomy to Open Thoractomy (ID 75)

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

      • Abstract

      Background:
      Conversion to open thoracotomy occurs when thoracoscopic manipulation becomes difficult as a result of particular situations during complete thoracoscopic lobectomy after the surgeon starts to dissect blood vessels Based on special intra-operative situations, conversion to open thoracotomy can be divided into active and passive conversion. Active conversion to open thoracotomy implies that the surgeon gives up the thoracoscopic manipulation voluntarily and performs open surgery under direct vision as a result of the difficulty of thoracoscopic manipulation when encountering problems, such as adhesions of lymph nodes and difficulty of exposing huge tumors, which may result in massive bleeding, tumor rupture, and undue extension of the operative time. Passive conversion to open thoracotomy implies that the surgeon has to discontinue thoracoscopic manipulation and perform open surgery under direct vision because of urgent or serious intra-operative complications, including blood vessel breakage and bronchial membrane rupture, which are difficult to treat thoracoscopically. Lymph nodes are an important etiology affecting the conversion of complete thoracoscopic lobectomy to open thoracotomy.Five hundred consecutive patients with non-small cell lung cancer underwent complete thoracoscopic lobectomy at the Department of Thoracic Surgery of Peking University People’s Hospital, and the conversion to open thoracotomy was performed in 47 cases (9.4%). Lymph node interference means that a lymph node cannot be separated easily, and was the reason for conversion to open surgery in 31 cases (65.9% of 47 cases).The effect of lymph node interference on surgery has not been thoroughly addressed to date. We studied the data of patients who underwent complete thoracoscopic lobectomy in our hospital, and analyzed the effect of lymph nodes on the conversion to open thoracotomy and corresponding factors.

      Methods:
      Between September 2006 to April 2013, 1006 patients (545 men, 461women, median age 60 years, range from 13 to 86 years)received completly thoracoscopic lobectomy, including segmectomy(n=13), simple lobectomy(n=846), compound lobectomy(n=131), pneumonectomy (n=8), sleeve lobectomy(n=8). The main procedure was completely video-assisted anatomical lobectomy with mediastinal lymphadenectomy as we have reported.

      Results:
      All procedures were carried out smoothly without serious complication. 83 cases converted to thoracotomy(8.2%), including 70 cases of initiative conversion and 13 cases of passive conversion in which 59 cases was interference by doornail lymph nodes. Pathological result show 821 cases of malignant disease and 185 cases of benign disease. All patients recovered well.the average operative time in the conversion thoracotomy group was significantly longer (272.7 ± 67.2min versus186.9 ± 58.1min, P = 0.001)compared with completely endoscopic surgery group, the average blood loss was significantly increased(564.2 ± 507.7ml versus 158.0 ± 121.0ml, P = 0.001), the drainage time was significantly longer(8.9 ± 5.0d versus 6.6 ± 3.5d, P = 0.001) and the postoperative hospital stay was significantly longer(12.5 ± 7.7d versus 9.2 ± 5.8d, P = 0.001).

      Conclusion:
      Interference of lymph doeds was the main reason for conversion to thoracotomy on VATs lobectomy. It may prolonged the operative time, increase the blood loss in operation and delay the postoperative recovery of the patients. Select the proper indication of conversion thoracotomy may reduce the negative effects of conversion thoracotomy.

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      MINI20.12 - Advancements in Bronchoplasty as Treatments for Lung Cancer: Single Institutional Review of 213 Patients (ID 1331)

      16:45 - 18:15  |  Author(s): T. Nagayasu, N. Yamasaki, T. Tsuchiya, K. Matsumoto, T. Miyazaki

      • Abstract
      • Presentation
      • Slides

      Background:
      Bronchoplasty has become widely accepted as a reliable and safe lung-saving procedure for lung cancer. The purpose of this study was to evaluate the factors contributing to the outcomes of bronchoplasty for lung cancer by analyzing a single institution’s data for a 30-year period.

      Methods:
      In the 2416 patients who underwent lung resections for lung cancer at Nagasaki University Hospital from 1980 to 2010, there were 222 bronchoplastic procedures. After excluding patients who underwent carinoplasty, 213 patients (161 bronchoplasty and 52 broncho-angioplasty) were included. The patients were divided into two groups by the date of surgery: the 1[st] period was 1980 to 1995, and the 2[nd] period was 1996 to 2010.

      Results:
      Bronchoplasty and broncho-angioplasty were performed in 100 (75.8%) and 32 (24.2%) patients, respectively, in the first period and 61 (75.3%) and 20 (24.7%) patients, respectively, in the second period. Overall 90-day operative morbidity and mortality rates were 25.8 and 9.8%, respectively, in the first period and 45.7 and 2.5%, respectively, in the second period. Thirty-day mortality rates were 6.8% in the first period and 0% in the second period. Five-year survival was 41.1% (n = 132) in the first period and 61.5% (n = 81) in the second period (P = 0.0003). Comparing bronchoplasty and broncho-angioplasty, the 5-year survival was 45.6 and 26.5%, respectively, in the first period (P = 0.0048) and 60.9 and 62.1%, respectively, in the second period (P = 0. 8131). Using multivariate analysis to identify potential prognostic factors, the type of operation (broncho-angioplasty), postoperative complications and histology (non-squamous cell carcinoma) were significant factors affecting survival in the first period, but none of the factors significantly affected survival in the second period. When the rates of pN2 or N3 histological type disease were compared in each period, the rate of pN2 or N3 disease in non-squamous cell carcinoma was 51.4% in the first period and 45.5% in the second period; both were significantly higher than in squamous cell carcinoma (31.6 and 16.9%, respectively; P = 0. 0365 and 0.0073). Figure 1



      Conclusion:
      The present study suggests that progress in the preoperative staging system and perioperative medical management, as well as surgery, has contributed to current improvements in patients undergoing bronchoplasty and broncho-angioplasty. However, since nodal status in non-squamous cell carcinoma is not precisely evaluated before the operation, the indication for bronchoplasty should be considered carefully.

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      MINI20.13 - A Prospective Comparison of FDG-PET & EBUS for Determining the Extent of Mediastinal Lymph Node Involvement in NSCLC (ID 2323)

      16:45 - 18:15  |  Author(s): D.P. Steinfort, S. Siva, T. Leong, M. Rose, D. Gunawardana, P. Antippa, D. Ball, L.B. Irving

      • Abstract
      • Presentation
      • Slides

      Background:
      Non-small cell lung cancer (NSCLC) may be treated with curative intent using radiotherapy, either as single modality or in combination with systemic chemotherapy. Most commonly, radiation treatment is planned based on findings at 18-Fluorodeoxyglucose Positron Emission Tomography (PET), following pathologic confirmation of involvement at a single mediastinal site. We hypothesized that systematic mediastinal evaluation with EBUS-TBNA in NSCLC patients considered for radical radiation therapy may identify disease extent discrepant with that indicated by PET-CT.

      Methods:
      This prospective ethics board-approved multi-centre cohort study in three Austrailan tertiary centres consented patients prior to mediastinal evaluation with Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) for NSCLC,where non-invasive imaging indicated the likely treatment modality would include radical radiotherapy. EBUS evaluation was performed systematically with sampling of any lymph node (LN) exceeding 6mm diameter.

      Results:
      Thirty eligible patients with NSCLC form the basis of this report. No procedural complications occurred during performance of EBUS-TBNA. LN sampling was performed from a mean 2.5 lymph node stations per patient (median 3,range 1–5). Adequate samples were obtained from all sites examined by EBUS-TBNA. Mean long-axis size of sampled LN was 16+7.8mm (median 13mm,range 5–36mm). 24% of sampled LN were 10mm or less. Discordant findings were observed in 10 of 30 patients (33%) (Figure 1) EBUS-TBNA identified a greater extent of mediastinal involvement than PET in four patients, with invasive sampling resulting in upstaging in three patients. In one further patient, extent of disease was greater than noted on PET due to more proximal involvement of LN disease not resulting in stage advancement. Median size of LN upstaged by EBUS was 7.5mm (range 7–9). In eleven mediastinal LN in six patients, EBUS identified a lesser extent of mediastinal disease than PET, including two patients down-staged from N3 à N2. Median size of LN down-staged by EBUS was 12mm (range 6–21). FIGURE 1. Flowchart of patients Figure 1



      Conclusion:
      Our findings demonstrate clinically significant discrepancy between two modalities frequently used to stage mediastinal disease extent in NSCLC patients being considered for radiotherapy. PET-based radiotherapy planning alone may not be appropriate given the risk of excessively large, or insufficiently large, radiation fields where planning is not based on invasive LN sampling. These results suggest minimally invasive comprehensive/systematic mediastinal staging should be considered for all patients prior to radiotherapy to accurately assess pathologic stage and extent of disease, and to ensure treatment fields most accurately encompass all sites of disease.

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      MINI20.14 - Discussant for MINI20.10, MINI20.11, MINI20.12, MINI20.13 (ID 3479)

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

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MS 10 - Management of Screening Detected Lung Cancer (ID 28)

    • Event: WCLC 2015
    • Type: Mini Symposium
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MS10.04 - When to Intervene on Screening Detected Lung Nodules (ID 1892)

      14:15 - 15:45  |  Author(s): G. Veronesi

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The National Lung Screening Trial (1) largely resolved the dispute as to whether low-dose computed tomography (LDCT) screening can reduce lung cancer mortality. However the trial was characterized by a high recall rate and high rate of benign disease at surgery, probably because a diagnostic and management protocol for indeterminate nodules was not in place. Screening has improved the stage distribution of lung cancer at diagnosis and greatly increased the cure rate (2). It has also increased numbers of overdiagnosed cancers and of potentially harmful diagnostic procedures carried out for benign disease. It is therefore critical to establish quality criteria for screening programs to reduce the risks of these occurrences. Recommendations from the surgeon team at the 2011 WCLC workshop, Amsterdam (3) were that: (i) A formal diagnostic and surgical management protocol should be part of any screening program; surgeons should be involved drawing up protocols along with other members of the multidisciplinary team. (ii) A false positive rate of less than 15% should be aimed at. (iii) Screening should only be performed at centres with access to a full minimally invasive surgical program (VATS or robotic anatomical resection). (iv) For pure ground-glass or partially-solid LDCT-detected lung cancers below 2 cm, anatomical segmentectomy is adequate treatment provided intraoperative frozen section examination shows that lymph nodes at hilar and mediastinal stations are negative. The diagnostic algorithm of COSMOS (4) was non-invasive, with no routine CT-guided transthoracic biopsy, and indication for surgery based on nodule size, volume doubling time (VDT), and SUV on PET-CT. After 5 years, only 14% of surgical biopsies were for benign disease, one of the lowest in the literature. Around half the biopsied benign nodules had a VDT generally considered to indicate malignancy, and the other half were PET positive. Thus addition always of reducing false positives are needed and molecular markers appear promising in this respect. The false negative rate is a good indicator of screening program quality. In COSMOS we defined false negatives as stage II-IV cancers present on a previous annual scan but not considered to merit further workup: 16 of the 190 cancers (8%) were false negatives, similar to the I-ELCAP figure of 9%. Most false negatives were centrally located, rapidly-growing nodules, but a few were misinterpreted by radiologists. The role of PET-CT in the workup algorithm was investigated on 378 COSMOS volunteers with indeterminate nodules (5). PET-CT was found highly sensitive for nodules detected at baseline, nodules ≥15 mm, and solid nodules. Sensitivity was lower for partially solid and nonsolid nodules, and those discovered after baseline, for which other methods, e.g. VDT, should be used. The Danish Lung Cancer Screening Trial investigated both PET-CT and VDT, finding that the best predictor of malignant nodules was PET-CT and VDT combined (6). NELSON trial investigators were the first to introduce VDT as main the component of the diagnostic algorithm (7). As regards overdiagnosis, in a retrospective analysis of 175 COSMOS patients VDT was suggested as a marker of aggressiveness that could be used to estimate overdiagnosis and tailor treatment [8]. We divided nodules into: fast-growing (VDT <400 days) days), slow-growing (VDT 400-599 days), and indolent (VDT >600 days). Median VDT was significantly faster in new cancers than slow-growing and indolent cancers (52, 223 and 545 days, respectively). Median VDT (303 days) was significantly longer in adenocarcinomas than squamous cell carcinomas (77 days) and small cell cancers (70 days). The authors concluded that slow-growing nonsolid nodules, many of which are likely to be overdiagnosed, could be safely treated with minimally invasive (sublobar) surgery. If centrally located, stereotactic ablative body radiotherapy (SABR) should be considered and discussed with the patient. The recent paper of Yankelevitz et al. (9) focused on the frequency, treatment and prognosis of nonsolid nodules encountered the large I-ELCAP screening cohort. Nonsolid nodules were rare, being identified in 2392 (4.2%) of 57,496 baseline screenings, with new nonsolid nodules identified in 485 (0.7%) of 64,677 repeat screenings. All 84 lung cancers identified were stage I adenocarcinomas and survival was 100% a median of 78 months (IQR, 45–122). after diagnosis. The authors concluded that nonsolid nodules of any size could be safely followed at 12-month intervals and that transition to part-solid should prompt a pathologic diagnosis. The authors suggested the nonsolid nodules should be renamed ‘indolent lesions of epithelial origin,’ in part to counter the fear that the word cancer evokes; in part because they behave much like benign lesions. In the COSMOS study, nonsolid lesions constituted 17% of all cancers detected, probably more than in I-ELCAP (although an updated breakdown is not available). This may be because COSMOS investigators removed these nodules if they increased in size or were PET-CT positive. As regards the question of lymph node dissection for early lung cancers, 193 consecutive patients with non-screening detected clinically N0 lung cancers, were studied (10). It emerged that 42/43 cases had negative PET-CT (usually SUVmax <2.0) or nodule ≤10 mm were pN0, suggesting that, for cancers with these characteristics, node dissection can be avoided because the risk of nodal involvement is minimal. To conclude, the results of the National Lung Screening Trial (1) shifted the debate from whether to how screening should be performed. Various diagnostic algorithms have been proposed, most with good results in terms of safety and number of resections for benign disease, however there is still room for improvement. The role of molecular markers, alone or in combination with VDT and PET positivity (FDG uptake), is under evaluation. Nonsolid nodules can be safely monitored at yearly intervals until the appearance of a solid component. Large scale implementation of screening in Europe is now a priority: although many investigators still have reservations, LDCT screening, with an appropriate diagnostic and surgical management protocol, is now good enough to save many lives with limited risks. References 1. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395-409. doi: 10.1056/NEJMoa1102873. 2. Henschke CI, Yankelevitz DF, Libby DM, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355: 1763–1771. 3. Field JK, Smith RA, Aberle DR, et al. IASLC CT Screening Workshop 2011 Participants. International Association for the Study of Lung Cancer. Computed Tomography Screening Workshop 2011 report. J Thorac Oncol. 2012;7(1):10-9. doi: 10.1097/JTO.0b013e31823c58ab. 4. Veronesi G, Maisonneuve P, Spaggiari L, et al. Diagnostic performance of low-dose computed tomography screening for lung cancer over five years. J Thorac Oncol. 2014;9(7):935-9. doi: 10.1097/JTO.0000000000000200. 5. Veronesi G, Travaini LL, Maisonneuve P, et al. Positron emission tomography in the diagnostic work-up of screening-detected lung nodules. Eur Respir J. 2015;45(2):501-10. doi: 10.1183/09031936.00066514. 6. Ashraf H, Dirksen A, Loft A, et al. Combined use of positron emission tomography and volume doubling time in lung cancer screening with low-dose CT scanning. Thorax. 2011;66(4):315-9. doi: 10.1136/thx.2010.136747. 7. Horeweg N, van der Aalst CM, Vliegenthart R, et al. Volumetric computer tomography screening for lung cancer: three rounds of the NELSON trial. Eur Respir J 2013; 42: 1659–1667. 8. Veronesi G, Maisonneuve P, Bellomi M, et al. Estimating overdiagnosis in low-dose computed tomography screening for lung cancer: a cohort study. Ann Intern Med 2012; 157: 776–784 9. Yankelevitz DF, Yip R, Smith JP, et al. As the Writing Committee for The International Early Lung Cancer Action Program Investigators Group. CT Screening for lung cancer: nonsolid nodules in baseline and annual repeat rounds. Radiology. 2015:142554. 10. Veronesi G, Maisonneuve P, Pelosi G, et al. Screening-detected lung cancers: is systematic nodal dissection always essential? J Thorac Oncol. 2011;6(3):525-30. doi: 10.1097/JTO.0b013e318206dbcc.

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    ORAL 24 - CT Detected Nodules - Predicting Biological Outcome (ID 122)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Screening and Early Detection
    • Presentations: 1
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      ORAL24.04 - Discussant for ORAL24.01, ORAL24.02, ORAL24.03 (ID 3358)

      10:45 - 12:15  |  Author(s): G. Veronesi

      • Abstract
      • Presentation

      Abstract not provided

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