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B. Stiles

Moderator of

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    MINI 19 - Surgical Topics in Localized NSCLC (ID 138)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 15
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      MINI19.01 - Benefits of Surgical Treatment and Complementary Utility of Metabolic Tumor Volume in Selecting Therapy for Stage III NSCLC (ID 3143)

      16:45 - 18:15  |  Author(s): L. Xiong, K. Wroblewski, Y. Jiang, R. Salgia, H. Macmahon, M. Ferguson, Y. Pu

      • Abstract
      • Presentation
      • Slides

      Background:
      Stage III NSCLC has large variations in primary and nodal metastatic tumor burden and its treatment is controversial.We determined the benefit to overall survival (OS) of these patients from surgery, and potentially complementary role of FDG-PET/CT-based metabolic tumor volume of primary tumor (MTV~T~), nodal metastasis (MTV~N~), and whole-body (MTV~WB~) in selecting patients for surgery.

      Methods:
      With IRB approval, we retrospectively reviewed 239 stage III NSCLC cases with pre-therapy FDG-PET/CT scans treated 2004 – 2013 (141 IIIA and 98 IIIB, 115 men and 124 women, median age 67.2 years), and measured MTV~T~,MTV~N~, and MTV~WB~. Kaplan-Meier curves and log-rank test were used for determining survival differences between surgically and non-surgically treated patients. Multivariate Cox regression analyses were conducted. Logistic regression analysis was used to evaluate whether each covariate was associated with receiving surgery(including surgery alone and surgery in combination with chemo or radiation). Wilcoxon rank-sum tests were performed for determining differences of primary, nodal, and whole-body MTV between the groups.

      Results:
      30% (42/141) of IIIA patients and 10% (10/98) of IIIB patients had surgical treatment (p<0.001, Chi-square test). OS was different between surgically and non-surgically treated patients (p<0.001) at 1 year(86% vs. 54%), 2 years(64% vs. 32%), 3 years(52% vs. 21%), and 5 years(39% vs. 14%), with median survival of 37.3 months vs.13.6 months, respectively. Covariates associated with OS were: surgery (0.43 ≤ HR ≤ 0.46, p≤0.001), log~10~MTV~T~ (HR=1.54, p<0.001), log~10~MTV~N~ (HR=1.63, p<0.001), and log~10~MTV~WB~ (HR=2.06, p<0.001) (Figure 1). Log~10~MTV~T~, Log~10~MTV~N~, and Log~10~MTV~WB ~were inversely associated with receiving surgery, with odds ratio of 0.53(p=0.01), 0.55(p=0.036), and 0.38 (p=0.002), respectively. MTV~T~, MTV~N~, and MTV~WB~ were smaller in surgically treated patients, with median of surgically vs. non-surgically treated patients of 17.8 vs. 55.0, 5.3 vs. 15.1, and 27.8 vs. 92.0 cc, respectively (p≤0.004). Additionally, those with stage IIIB disease were significantly less likely to receive surgery after controlling for age, gender, and MTV. No statistically significant interactions were found between surgery and stage or between surgery and log~10~MTV~T~, log~10~ MTV~N~, or log~10~MTV~WB~.Figure 1



      Conclusion:
      Surgery and smaller MTV are associated with better OS of stage-III NSCLC patients. Smaller MTV and stage IIIA (vs. IIIB) are associated with receiving surgery. FDG PET/CT-based metabolic tumor volume can potentially inform surgical treatment decisions to further improve survival outcome.

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      MINI19.02 - Mediastinal Nodal Involvement in Patients with Clinical Stage I Non-Small-Cell Lung Cancer - Possibility of Rational Lymph Node Dissection - (ID 2320)

      16:45 - 18:15  |  Author(s): T. Haruki, K. Aokage, T. Miyoshi, T. Hishida, G. Ishii, J. Yoshida, M. Tsuboi, H. Nakamura, K. Nagai

      • Abstract
      • Presentation
      • Slides

      Background:
      Recent developments of radiological examinations have been able to bring more accurate information about the biological malignancy of primary tumors in non-small cell lung cancer (NSCLC). The aim of this study is to elucidate the optimal candidate of lobe-specific selective lymph node dissection (LND) that reduces the extent of mediastinal LND according to clinical information including radiological evaluation of primary tumor on thin-section computed tomography (TSCT) and tumor location in clinical(c)-stage I NSCLC patients.

      Methods:
      Eight hundred and seventy-six patients with c-stage I NSCLC (adenocarcinoma and squamous cell carcinoma), who underwent complete surgical resection between January 2003 and December 2009 were included in this study. For all tumors, we obtained the maximum dimension of the tumor (tumor) and solid component (consolidation) using a lung window level setting from the TSCT scan images, and estimated the consolidation-to-tumor ratio (C/T ratio) for each tumor. We elucidated the lymph node metastatic incidence and distribution according to the primary tumor lobe location and extracted the associated clinicopathological factors with mediastinal lymph node involvement.

      Results:
      The patients included 490 men and 386 women, with a median age of 66 years old. The radiological findings were ground glass opacity (GGO)-predominant (C/T ratio ≤ 0.5) in 134 patients and solid-predominant (C/T ratio > 0.5) in 742 patients. There were 744 adenocarcinoma cases and 132 squamous cell carcinoma cases, and the incidences of mediastinal lymph node metastasis were 9.9% in adenocarcinoma cases and 4.5% in squamous cell carcinoma cases, respectively. There were no cases with hilar and mediastinal lymph node metastasis in GGO-predominant tumors. There was no significant association of clinical factors with subcarinal lymph node metastasis in right upper-lobe and left upper-division lung adenocarcinoma. In 257 bilateral lower-lobe lung adenocarcinomas, a total of 32 cases (12.5%) were positive for mediastinal lymph node metastasis, and seven cases (2.7%) were negative for subcarinal lymph node metastasis but positive for upper mediastinal lymph node metastasis (mediastinal skip metastasis). An elevated preoperative serum carcinoembryonic antigen (CEA) level (p < 0.001) showed only a significant association with upper mediastinal lymph node metastasis in the patients with bilateral lower-lobe primary lung adenocarcinoma.

      Conclusion:
      It would be acceptable to perform selective LND in patients with c-stage I NSCLC with GGO-predominant tumor. Elevated serum CEA was associated with upper mediastinal lymph node involvement in lower-lobe primary lung adenocarcinoma with radiologically solid-predominant tumor. We should be careful when applying selective LND to patients with solid-predominant tumor, especially located in the lower lobe.

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      MINI19.03 - Subcarinal Lymph Node Dissection Is Also Necessary in Upper Lobectomies for Lung Cancer (ID 596)

      16:45 - 18:15  |  Author(s): J. Eckardt, E. Jakobsen, P.B. Licht

      • Abstract
      • Presentation

      Background:
      Mediastinal lymph node evaluation in Non Small-Cell Lung Cancers (NSCLC) is of paramount importance for optimum planning of treatment. Recently, it was claimed that subcarinal lymph node dissection could be spared in upper lobe NSCLC resections because of the low incidence of metastatic disease. These data, however, were single institution reports. We used complete national data to investigate patterns of unsuspected mediastinal lymph node involvement in patients operated for NSCLC.

      Methods:
      A national registry was used to identify every single patient operated for NSCLC during an 11-year period (2003-2013). Unsuspected mediastinal lymph node involvement was investigated by comparison of clinical and final pathological nodal stage, and patients with clinical mediastinal lymph node metastases were excluded. For every patient we extracted information about tumor location, histopathology, clinical and pathological TNM-stage. All preoperative imaging and staging investigations were recorded.

      Results:
      An unsuspected mediastinal lymph node metastasis was found in 426 patients (9.8%) of 3953 patients and 167 (4.4%) had unsuspected subcarinal metastases, which were significantly more frequent in patients with lower lobe or middle lobe cancers compared with upper lobe cancers 7 % (101/1440) versus 1.8% (42/2258), (p<0.01). Preoperative invasive mediastinal staging was used in 57% (n=2253) of all patients and significantly more frequent in upper lobe cancers (62% (n=1400), p<0.01), in patients who had unsuspected mediastinal lymph node metastasis (75% (n=320), p< 0.01) and in patients with subcarinal metastases (74% (n=124), p< 0.01).

      Location of the tumor All patients Patients with N2 disease Metastasis in station 7
      RUL 1254 121 28 (2.2 %)
      LUL 1004 116 14 (1.4 %)
      RLL 672 78 52 (7.7 %)
      LLL 585 62 36 (6.2 %)
      Middle lobe 183 16 13 (7.1 %)
      Bilobectomy 255 33 24 (9.4 %)
      Total 3953 426 167


      Conclusion:
      A substantial number of patients undergoing surgery for NSCLC have unsuspected subcarinal mediastinal lymph node involvement despite 74% had preoperative invasive mediastinal staging. Unsuspected subcarinal metastases were most common in lower and middle lobe cancers but were also frequent in upper lobe NSCLC. Subcarinal lymph node dissection should therefore be a routine part of surgery for NSCLC - regardless of tumor location to avoid undiagnosed subcarinal lymph node metastasis.

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      MINI19.04 - Relationship Between Adequacy of Intra-Operative Lymph Node Sampling During Surgical Resection of NSCLC and Survival (ID 1239)

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

      • Abstract
      • Presentation
      • Slides

      Background:
      Intra-operative lymph node sampling during lung cancer resection is a key surgical performance measure. It informs prognosis, treatment selection for adjuvant chemotherapy and surveillance programs following treatment. This study aimed to analyse the relationship between adequacy of intra-operative lymph node sampling and survival at a large thoracic oncology centre in the United Kingdom.

      Methods:
      A retrospective review of pathological reports for all patients undergoing lung cancer resections at the University Hospital South Manchester from 01/01/2011 to 31/12/2013 was undertaken. Intra-operative lymph node sampling was assessed for adequacy against standards set out by the IASLC Staging Manual in Thoracic Oncology. Survival data was obtained through national death registry data and provided a minimum of twelve months follow-up for all patients at the time of analysis in January 2015.

      Results:
      A total of 987 patients underwent surgical resection for NSCLC in the study period. Overall, there was no significant difference in survival between patients with adequate intra-operative lymph nodal sampling and those with inadequate sampling (log rank p=0.66). Median survival times were not estimable for pN0 and pN1 patients as only a small proportion died. However there was a significant difference in the median survival time of pN2 patients according to whether the intra-operative lymph node sampling was adequate or inadequate (Figure 1). Figure 1Figure 2





      Conclusion:
      Few patients have died in the pN0 and pN1 categories limiting interpretation. As the data matures we expect to see a survival difference according to adequacy of intra-operative nodal sampling that is supported by the differential median survival data of pN2 patients according to nodal adequacy. The data supports that the survival difference is due to inaccurate staging, inadequate resection (R1) and inappropriate omission of adjuvant.

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      MINI19.05 - Discussant for MINI19.01, MINI19.02, MINI19.03, MINI19.04 (ID 3548)

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

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MINI19.06 - External Validation of a Chinese Developed Survival Score in a Western Cohort Undergoing Surgery for Non-Small Cell Lung Cancer (ID 2226)

      16:45 - 18:15  |  Author(s): U. Kumbasar, H. Raubenheimer, M. Al Sahaf, N. Asadi, M.E. Cufari, C. Proli, P. Perikleous, L. Azcarate, Z. Niwaz, E. Beddow, V. Anikin, N. McGonigle, S. Jordan, G. Ladas, M. Dusmet, E. Lim

      • Abstract
      • Presentation
      • Slides

      Background:
      Currently adjuvant chemotherapy is not recommended for patients with completely resected stage I lung cancer. The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al recently published a Chinese multi-institutional logistic regression derived model to predict post-operative survival in over 5000 patients undergoing lung cancer surgery for all stages. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I.

      Methods:
      We retrospectively analysed data from a prospectively collected database from our institutions. Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively.

      Results:
      From April 2007 to February 2015 a total of 1442 patients underwent surgery for primary lung cancer at our institution. We excluded 118 patients with carcinoid tumours (not in the original Chinese development set) and 86 patients without complete lymph node assessment leaving 1238 patients for validation. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI 0.58 to 0.67). This was lower than the 0.71 reported by the Chinese group when split into 1,3 and 5 year survival. When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. Figure 1. Survival discrimination within Stage I Figure 1



      Conclusion:
      Our results of external validation suggested lower survival discrimination than reported by the original group, however discrimination between survival remained evident for stage I.

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      MINI19.07 - ICG Fluorescence Localization of Small Sized Pulmonary Nodules for VATS (ID 70)

      16:45 - 18:15  |  Author(s): T. Anayama, K. Hirohashi, R. Miyazaki, H. Okada, M. Kume, N. Kawamoto, T. Sato, K. Orihashi

      • Abstract
      • Presentation
      • Slides

      Background:
      Video-assisted thoracoscopic wedge resection of multiple small, non-visible, and nonpalpable pulmonary nodules is a clinical challenge. We propose an indocyanine green (ICG) injection and intraoperative fluorescence detection with a near-infrared (NIR) fluorescence for localization of small sized pulmonary nodules.

      Methods:
      Fluorescence properties of ICG topically injected into the lung parenchyma were determined using a resected porcine lung and previously reported by the authors. In clinical study, 15 cases of VATS pulmonary resection for small sized pulmonary nodules were enrolled in the study. The ICG mixed with iopamidol was injected into the pulmonary nodules by CT-guided percutaneous injection. ICG fluorescence was visualized by a near-infrared (NIR) thoracoscope, then the target nodule was excised by VATS procedure.

      Results:
      Topically injected ICG / iopamidol mixture spot remained at the injected point of the lung parenchyma for more than 6 hours in each case, and each ICG fluorescence was identified at the pulmonary nodule with the NIR thoracoscope. Each target nodule was successfully removed with negative surgical margin.

      Conclusion:
      CT guided ICG injection and intraoperative NIR thoracoscopic detection is a feasible method to localize small sized pulmonary nodules.

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      MINI19.08 - Validation of a Surgical Predictive Score for 90 Day Mortality in Lung Cancer and Comparison with Thoracoscore (ID 2754)

      16:45 - 18:15  |  Author(s): E.L. O'Dowd, T. McKeever, D.R. Baldwin, H.A. Powell, R.B. Hubbard

      • Abstract
      • Presentation
      • Slides

      Background:
      Current British Thoracic Society (BTS) guidelines advocate the use of a global risk prediction score such as Thoracoscore to estimate the risk of death prior to radical surgical management in those with non-small cell lung cancer (NSCLC). A recent publication by Powell et al(1) used the National Lung Cancer Audit (NLCA) linked to Hospital Episode Statistics (HES) to produce a score to predict 90 day mortality. The aim of this study is to validate this score, henceforth called the NLCA score, and compare its performance with Thoracoscore.

      Methods:
      We identified data on all patients in the NLCA who received curative surgery for NSCLC between 2010 and 2012. We calculated the proportion that died in hospital and within 90 days of surgery. Each person was given a score based on the coefficients and constants in the NLCA score and Thoracoscore. The discriminatory power of both scores was assessed by a receiver operating characteristic (ROC) and an area under the curve (AUC) calculation.

      Results:
      We identified 2858 patients for whom we had complete data to form our validation cohort. The 90 day mortality was 5%. We generated ROC curves to assess the discrimination of the NLCA score in predicting 90 day mortality and to test the ability of Thoracoscore to predict in-hospital mortality. Area under the ROC curve was 0.68 and 0.60 respectively. We performed a post hoc analysis using data from the NLCA on all 15554 patients who underwent curative surgery for NSCLC between 2004 and 2012 to derive summary tables for 90 day mortality, stratified by procedure type, age and performance status (table 1).

      Conclusion:
      These results suggest that although the NLCA score performs slightly better than Thoracoscore neither performs well enough to be advocated for routine use to risk stratify patients prior to lung cancer surgery. It may be that the addition of physiological parameters to demographic and procedural data or use of physiological measurements alone would better predict mortality; however this would form the basis of a further project. In the interim we advocate the use of our summary tables that serve to provide clinicians and patients the real-life range of mortality according to performance status and age for both lobectomy and pneumonectomy. 1. Powell HA, Tata LJ, Baldwin DR, Stanley RA, Khakwani A, Hubbard RB. Early mortality after surgical resection for lung cancer: an analysis of the English National Lung cancer audit. Thorax. 2013;68(9):826-34. Figure 1



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      MINI19.09 - Adjunct Intraop Cone Bean CT (CBCT) with Real Time 3D Overlay Improves Diagnostic Accuracy of Electromagnetic Navigational Bronchoscopy (ENB) (ID 1078)

      16:45 - 18:15  |  Author(s): S. Sachidananda, J.E. Hasson, G. Avignon, C.G. Alvarado

      • Abstract
      • Presentation

      Background:
      ENB is limited by diagnostic accuracy of 60-80%[ [1]]. We hypothesize that using intraoperative CBCT with real time 3D overlay onto fluoroscopic images to confirm placement of biopsy tools in the lesion will increase the diagnostic accuracy of ENB biopsies. [1] Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-Analysis of Guided Bronchoscopy for the Evaluation of the Pulmonary Nodule. Chest. 2012;142(2):385-393. doi:10.1378/chest.11-1764

      Methods:
      Patients with undiagnosed small pulmonary nodules (<20 mm) underwent biopsy where an initial CBCT of the chest under breath hold was performed, followed by a 3D model reconstruction of the lesions while the surgeon started the ENB. At the end of the bronchoscope navigation, the 3D model of the lesion was fused and automatically registered in real time over the 2D fluoroscopy, allowing an evaluation of the biopsy tool positioning in 3-dimensions. Multiple samples were collected after confirmation of the tool position using various oblique views. Figure 1



      Results:
      In our initial experience with 10 cases, CBCT acquisition, reconstruction and 3D-overlay was successful in all cases. This procedure enabled confirmation of biopsy tool position within the target lesion in all cases. In one case, the new information obtained successfully discriminated a diaphragm implant from what previously had been interpreted as a basilar parenchymal nodule. In a second case, CBCT reconstruction enabled biopsy of a 15mm lesion thought to be a solitary metastasis. The biopsy was interpreted as normal, albeit in clinical circumstances which were suspicious for malignancy. The patient elected non-surgical treatment of an esophageal primary, precluding definitive pathologic confirmation. A third case provided a biopsy interpreted as normal in a patient who ultimately proceeded to resection for growth of the nodule. While frozen section suggested a benign entity, final pathology demonstrated scattered elements of malignancy. In the remaining cases, CBCT and 3D overlay assisted in successful and accurate biopsy of nodules <20mm.

      Conclusion:
      Intraoperative CBCT and real time 3D overlay onto fluoroscopic images to confirm appropriate positioning of the biopsy tools in the lesion during ENB is technically feasible. It effectively combines the advantage of real time CT imaging with the advantages of ENB biopsy. This has the potential to increase the diagnostic accuracy of ENB aided tissue diagnosis of small pulmonary nodules. This novel technique will facilitate early accurate diagnosis of lung cancer in small nodules with a minimally invasive approach.

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      MINI19.10 - Discussant for MINI19.06, MINI19.07, MINI19.08, MINI19.09 (ID 3544)

      16:45 - 18:15  |  Author(s): C. Manegold

      • Abstract
      • Presentation

      Abstract not provided

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      MINI19.11 - Use of Electromagnetic Navigational Bronchoscopy to Localize Pulmonary Nodules Prior to Minimally Invasive Sublobar Resection (ID 2303)

      16:45 - 18:15  |  Author(s): S. Sachidananda, J.E. Hasson, G. Avignon, C.G. Alvarado

      • Abstract
      • Presentation

      Background:
      Sublobar resection of small pulmonary nodules by minimally invasive techniques can be a challenge, as this approach reduces the haptic feedback often required to reliably localize small lesions. Use of Electromagnetic Navigational Bronchoscopy (ENB) is a relatively new technique that has potential to assist in real time operative localization of such lesions, as ENB can deliver visual cues for their location in the form of either a dye marking or a radio-opaque clip, or both. There is limited data available on the feasibility of this approach. We want to describe our experience with this technique.

      Methods:
      A retrospective review of cases in which ENB was used to localize small pulmonary nodules was done from August 1, 2013 to February 1, 2015. We start by using ENB to navigate to the target lesion. In our initial experience, methylene blue was injected into the parenchyma around the mass, and dye migration to the pleural edge was used as a visual cue for location. We then amended our protocol to include placement of both methylene blue dye and a radio-opaque clip in the parenchyma immediately adjacent to the target lesion. Fluoroscopy was then used to triangulate the location of the clip, and by extension the mass, via markings on the chest wall with the lung deflated prior to incision. The visual cue of the dye marking as well as the fluoroscopic localization of the clip served to confirm each other. This was followed by minimally invasive resection of the lesion using these cues to assist in port placement. Figure 1



      Results:
      A total of 28 cases were identified. ENB was successful in navigating to the lesion in all cases. ENB dye localization alone was successful in 5 of 6 cases. After the first unsuccessful dye localization, our amended protocol of dye marking and clip placement led to successful localization in 22 consecutive cases.

      Conclusion:
      Use of electromagnetic navigational bronchoscopy to localize small pulmonary nodules is a feasible approach and is technically straightforward. As we see broader implementation of lung cancer screening protocols, thoracic surgeons can expect to encounter many more small pulmonary nodules requiring resection. There is accumulating data that sublobar resection is equivalent to lobar resection for small, peripherally located lung cancer. Use of the algorithm – ‘Navigate, Triangulate and Resect’ will enable thoracic surgeons to more successfully perform sublobar resections of small pulmonary nodules by minimally invasive techniques.

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      MINI19.12 - The Value of Video-Assisted Mediastinoscopic Lymphadenectomy in Clinical Stage I Non-Small Cell Lung Cancers (ID 2921)

      16:45 - 18:15  |  Author(s): A. Turna, H.V. Kara, K. Kaynak

      • Abstract
      • Presentation
      • Slides

      Background:
      The rate of mediastinal lymph node metastasis is controversial for patients with clinical N0 non-small cell lung cancer. The primary advantage of video-assisted mediastinoscopic lymphadenectomy(VAMLA) over conventional mediastinoscopy or videomediastinoscopy is to reduce the false-negative rate. We aimed to analyze to evaluate the value of routine VAMLA for patients with clinical T1a-T2aN0 patients prospectively.

      Methods:
      From March 2010-January 2015, 41 patients with non-small cell lung cancer with clinical stage T1-T2aN0 by postireon emission tomography/computed tomography underwent routine VAMLA before planned resectional surgery.Routinely, stations #2L, 2R, #4R, #4L, 7 were nearly completely resected. In some patients, #10R and #8 lymph nodes were biopsied. The prevalence of mediastinal lymph node metastases at VAMLA and lung resection was recorded.

      Results:
      There were 5 females (12.2%) and 36 (87.8%) males. The mean age was 62.5 . years. A total of 5 patients were had cT1a-bN0, whereas 36 patients had T2aN0. Eleven patients (26.8%) had occult mediastinal lymph node metastasis. A total of 26 patients underwent lung resectional surgery; only one patient (3.8%) were upstaged to pN2, whereas 3 patients (11.5%) were upstaged to pN1.

      Conclusion:
      VAMLA seems to disclose considerable number of mediastinal lymph node metastasis in these patients with T1 and T2 clinically staged N0 by positron emission tomography/computed tomography. Routine use of VAMLA is recommended with limited use of mediastinal lymph node evaluation in patients during resectional surgery.

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      MINI19.13 - Nodal Staging via Robotic-Assisted Thoracic Surgery for Clinical Stage I Non-Small Cell Lung Cancer (ID 1018)

      16:45 - 18:15  |  Author(s): V.M. Dipasquale, R.T. Hughes, S.C. Grant, B.E. Lally, W.J. Petty, A. Proto, L.J. Wudel

      • Abstract
      • Presentation
      • Slides

      Background:
      One measure of the quality of thoracic surgery for non-small cell lung cancer (NSCLC) is the adequacy of nodal evaluation; the rate of pathological nodal upstaging can introduce bias in patient selection for surgical therapy. Robotic-assisted thoracic surgery (RATS) offers the ability to sample nodal stations not easily assessed with conventional open surgical methods. We sought to determine the rate of nodal upstaging as a function of the frequency of various lymph node stations sampled in clinical stage I NSCLC patients undergoing RATS.

      Methods:
      We retrospectively reviewed the charts of patients with right-sided clinical stage I NSCLC who underwent robotic-assisted pulmonary resection with mediastinal lymph node dissection at our institution from 2013 to 2015. CT or PET scan was used to determine clinical stage. The DiPasquale Quality Index (DQI) defines a complete lymph node dissection (LND) as sampling LN 4R, 7, and 9 for right-sided tumors. Our institutional policy for the initial two years of our RATS program was to limit such to right-sided tumors.

      Results:
      Robotic anatomic lung resection was performed in 70 patients with right-sided clinical stage I NSCLC. The majority were of the upper lobe (41; 58.6%). The most frequent lymph node stations sampled robotically were LN 4R, 7, 9, 10, and 11 (60.6%, 90.1%, 66.2%, 49.3%, and 64.8%, respectively). According to the DQI, 31 (44.3%) tumors underwent complete LND. Pathologic nodal upstaging occurred in 5 patients (7.1% [pN1 4, 5.7%; pN2 1, 1.4%]). Hilar (pN1) upstaging occurred in 2.8%, 0%, and 20.0%, respectively, for cT1a, cT1b, and cT2a tumors. Comparatively, historic hilar upstage rates of video-assisted thoracoscopic surgery (VATS) versus thoracotomy versus recent robotic data for cT1a, cT1b, and cT2a were 5.2%, 7.1%, and 5.7%, versus 7.4%, 8.8%, and 11.5%, versus 3.5%, 8.6%, and 10.8%, respectively. The 1-year overall survival was 97% and the disease-free survival was 98% at 1 year.

      Conclusion:
      When patients are appropriately selected and proper lymph node sampling is performed, the rate of upstaging with RATS is comparable to VATS and lower than thoracotomy. The rate of hilar upstaging with robotic resection, however, increases with increasing clinical T stage and appears superior to both VATS and thoracotomy for cT2a tumors. This also has implications for patients who may be considered for therapies like stereotactic radiation therapy. Larger studies comparing matched open, VATS, and robotic approaches are necessary to quantify long term survival and local failure rates.

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      MINI19.14 - Survival After Sub-Lobar Resection for Early Stage Lung Cancer: Methodological Obstacles in Comparing the Efficacy to Lobectomy (ID 1583)

      16:45 - 18:15  |  Author(s): E. Taioli, R. Yip, I. Olkin, A. Wolf, D. Nicastri, C.I. Henschke, H.I. Pass, R. Flores

      • Abstract
      • Presentation
      • Slides

      Background:
      Surgery is the treatment of choice for early stage lung cancer (LC). While lobectomy (L) is the historic standard, whether long term outcomes of sub-lobar resection (SL) are comparable is still under debate. The only randomized trial was conducted 20 years ago; 5 subsequent meta-analyses showed inconclusive or conflicting results. We present a comprehensive review of the literature on 5 year-survival after SL compared to L for early stage LC.

      Methods:
      A priori inclusion criteria were: 1) observational studies, 2) L compared to SL for early stage LC, 3) at least CT staging, 4) 5-year survival reported. A Medline search through January 2015 resulted in 32 studies, representing 24 distinct datasets. The absolute difference in 5-year survival was calculated and plotted for each study.

      Results:
      There were 4,702 cases treated with L, 2,323 treated with SL. Of 20 studies reporting the reason for SL, 11 indicated that SL was performed because of comorbidities, or impaired cardiopulmonary function. Among all 24 studies, 4 showed no difference in 5-year survival, 13 favored L, and 7 favored SL (Figure 1). Of the two studies using propensity scores, one favored L and the other SL. No meta-estimate could be calculated due to high statistical heterogeneity. Of 21 studies reporting recurrence rate (Figure 2), 11 favored L and 10 favored SL. Figure 1



      Conclusion:
      Studies comparing 5-year survival rates of SL to L are heterogeneous, and traditional meta-analytic summary estimates of survival and recurrence could not be calculated. SL survival is often similar to L survival, despite the fact that SL is performed in patients with comorbidities or impaired cardiopulmonary function. New approaches to comparing L to SL survival are needed.

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      MINI19.15 - Discussant for MINI19.11, MINI19.12, MINI19.13, MINI19.14 (ID 3475)

      16:45 - 18:15  |  Author(s): J.H. Pedersen

      • Abstract
      • Presentation

      Abstract not provided

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    GR 01 - Management of Challenging Clinical Scenarios in Localized Lung Cancer (ID 14)

    • Event: WCLC 2015
    • Type: Grand Rounds
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      GR01.02 - Should All Lung Tumors Invading the Chest Wall Be Treated Like Pancoast Tumors? (ID 1829)

      14:15 - 15:45  |  Author(s): B. Stiles

      • Abstract
      • Presentation

      Abstract:
      Chest wall involvement is rare in patients with non-small cell lung cancer (NSCLC), occurring in <8% of patients (1). Invasion of the chest wall accords a T3 designation in both the 7[th] and in the newly proposed 8[th] edition TNM staging systems (2). The overall five-year survival for patients with clinically staged T3N0 NSCLC is approximately 45% (2). With clinically suspected nodal disease, even limited to N1 stations, survival is markedly worse. While cT3N2 NSCLC patients are designated stage IIIA and typically given neoadjuvant therapy, optimal treatment protocols are less clear for cT3N0 or even for cT3N1 patients with chest wall tumors, despite the fact that cT3N1 patients are also classified stage IIIA. An en bloc surgical resection of the involved lung and of the chest wall with or without adjuvant therapy has historically been the treatment algorithm of choice for these patients. Little data exists to determine whether neoadjuvant chemotherapy or chemoradiation might be beneficial in this setting. In contrast, the preferred treatment algorithm for a unique subset of chest wall tumors, Pancoast tumors, has been clearly defined (1). These T3 or T4 superior sulcus tumors arise in the apex of the lung and invade the chest wall at the level of the first rib or above, often with involvement of the brachial plexus, subclavian vessels, or spine. For these patients with clinical T3-4N0-1 disease, two carefully conducted prospective, multi-institutional trials demonstrated that induction chemoradiation therapy was associated with high rates of pathological response, improved resectability, and increased survival over historical controls (3,4). In the Southwest Oncology Group Trial 9416 (Intergroup Trial 0160), following neoadjuvant cisplatin and etoposide with concurrent radiation (45 Gy), 61% of patients had either a pathologic complete response or minimal microscopic residual tumor (3). Among all patients undergoing surgery, 94% were able to undergo an R0 resection. Patients with pathologic complete response had a marked advantage in five year overall survival (median survival not reached for complete responders versus 30 months for those with residual disease). Overall survival of the entire cohort was 44%, but was 54% after complete resection. Similar results were found in a multi-institutional trial from Japan (JCOG 9806), in which 21% of patients experienced a complete pathologic response following neoadjuvant therapy with mitomycin, vindesine, and cisplatin and concurrent radiation of 45 Gy (4). Among surgical patients, 89% underwent an R0 resection. Overall five-year survival for the cohort exceeded 50%, with survival of complete responders again especially favorable. The successful adoption of neoadjuvant therapy followed by surgery for Pancoast tumors raised the question of whether a similar induction strategy should be used in patients with other T3 chest wall tumors outside of the superior sulcus. Previous reports have suggested that prognostic factors for survival in patients with chest wall tumors include lymph node status and depth of chest wall invasion, but also completeness of surgical resection and completion of chemotherapy (5,6). It seems logical that neoadjuvant chemotherapy or chemoradiation may facilitate an R0 resection and that such therapy may be better tolerated preoperatively in patients undergoing potentially morbid chest wall resections. Along those lines, a prospective phase II study of trimodality therapy was performed in Japan (CJLSG 0801) for patients with T3N0 or T3N1 NSCLC involving the chest wall (7). Fifty-one patients were entered into the study, among whom 49 (96%) completed neoadjuvant cisplatin and vinorelbine with concurrent radiation (40 Gy) and among whom 44 (92%) underwent complete resection. Similar to prospective studies in NSCLC patients with superior sulcus tumors, in resected tumors there was a high rate of complete pathological response (25%) and of only minimal residual disease (65%). Treatment was relatively safe. However, one patient did die during neoadjuvant therapy secondary to infection following neutropenia and seven additional patients (16%) experienced grade 4 toxicity. Despite this, 86% of patients completed the induction regimen. Among the 29 patients (66%) who went on to surgery, 5 patients experiencing major complications and there was 1 postoperative mortality. Although median follow up was only 16 months, the 2-year overall and progression-free survival rates were excellent at 85% and 71% respectively. While the results of CJLSG 0801 perhaps make a compelling argument to treat chest wall tumors with neoadjuvant therapy prior to resection, several caveats must be considered. From previous studies, it would seem that nodal disease is the strongest indicator of the need for systemic therapy. However, previously reported rates of nodal disease for chest wall tumors are generally only between 20-40% (5). The rate of nodal disease reported in a recently published review of a Japanese registry of chest wall tumors was only 27% (8). These patients without nodal disease will not clearly benefit from systemic therapy. Furthermore, as opposed to Pancoast tumors, the rate of complete resection of chest wall tumors outside the superior sulcus is high even without neoadjuvant therapy, 88% in the Japanese registry study (8). This ability to obtain an R0 resection calls into question the need to include radiation therapy in the preoperative treatment regimen for most cT3N0 patients, given the potential added morbidity. In conclusion, it would seem most reasonable to utilize neoadjuvant therapy in chest wall tumors with clinical N1 nodal disease. These patients are designated as stage IIIA and need chemotherapy as part of their treatment regimen. Neoadjuvant therapy prior to surgery makes sense, although care should be taken to avoid complications that may prevent surgical resection. For T3N0 patients, the treatment algorithm is less clear. Conceptually, large bulky tumors in which it is expected that difficulty in obtaining negative margins surgically would seem to be good candidates for chemotherapy and radiation preoperatively. Further studies need to explicitly compare neoadjuvant versus adjuvant chemotherapy for T3N0 chest wall tumors and need to better evaluate whether there is any beneficial role of radiation in this challenging group of NSCLC patients. 1. Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in non-small cell lung cancer, diagnosis and management of lung cancer 3[rd] ed: American College of of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143(5):e3696S-e399S. 2. Rami-Porta R, Bolejack V, Crowley J et al. Proposals for the Revisions of the T descriptors in the forthcoming eight edition of the TNM classification for lung cancer. J Thorac Oncol 2015;10:990-1003. 3. Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol 2007;25:313-318. 4. Kunitoh H, Kato H, Tsuboi M, et al. Phase II trial of preoperative chemoradiotherapy followed by surgical resection in patients with superior sulcus non-small-cell lung cancers: report of Japan Clinical Oncology Group Trial 9806. J Clin Oncol 2008;26:644-649. 5. Riquet M, Arame A, Le Pimpec Barthes F. Non-small cell lung cancer invading the chest wall. Thorac Surg Clin 2010;20:519-527. 6. Lee CY, Syun CS, Lee JG, et al. The prognostic factors of resected non-small cell lung cancer with chest wall invasion. World J Surg Onc 2012;10:9. 7. Kawaguchi K, Yokoi K, Niwa H, et al. Trimodality therapy for lung cancer with chest wall invasion: initial results of a phase II study. Ann Thorac Surg 2014;98:1184-91. 8. Kawaguchi K, Miyaoka E, Asamura H, et al. Modern surgical results of lung cancer involving neighboring structures: a retrospective analysis of 531 pT3 cases in a Japanese Lung Cancer Resistry Study. J Thorac Cardiovasc Surg 2012;144:431-7.

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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P1.02-007 - The Histologic Subtype of Lung Adenocarcinoma Should Not Deter Sublobar Resection for Patients with Clinical Stage IA Lung Cancer (ID 2516)

      09:30 - 17:00  |  Author(s): B. Stiles

      • Abstract
      • Slides

      Background:
      The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society pathological classification of lung cancer allows for a more comprehensive understanding of the prognostic factors associated with subtypes of lung adenocarcinoma. Micropapillary and solid (MIP/SOL) subtypes have been associated with higher recurrence rates. Some have therefore suggested that sublobar resection (SLR) should be considered a compromise procedure in patients with MIP or SOL tumors. We conducted this study to examine the effect of the resection type [lobectomy (LO) or SLR] on oncological outcomes of patients with MIP/SOL.

      Methods:
      A retrospective review of a prospective database (2000-2014) was performed to identify patients with clinical stage IA adenocarcinoma, excluding pure ground glass opacities. Propensity score matching (age, gender, FEV1%, and clinical tumor size) was done to obtain balanced cohorts of patients undergoing LO and SLR. The presence of MIP and/or SOL components (≥5%) was assessed by a single pathologist to avoid inter-observer bias. The SLR group of patients had more comorbidities. Therefore, deaths from causes other than lung cancer were censored and freedom from recurrence was used to assess oncological outcomes. Survival analysis was done using the Kaplan Meier method. Multivariable analysis (MVA) was done using Cox regression.

      Results:
      This study included 300 patients (150 LO vs. 150 SLR, including 77 segmentectomy and 73 wedge resection). Patients undergoing SLR had higher Charlson comorbidity index (P=0.002) and lower DLco% (P=0.01). Patients undergoing LO were more likely to have nodal assessment (99% vs. 85%,P<0.001). Otherwise, no differences in the clinicopathological characteristics were found between the two groups. The presence of ≥5% MIP and/or SOL components was found in 135 patients; LO (58), SLR (77). The 3-year probability of freedom from recurrence in the whole cohort was: MIP (77%), synchronous MIP/SOL (76%), and SOL (61%), compared to 86% freedom from recurrence for other pathological subtypes (median follow-up 41 months). The probability of freedom from recurrence in patients with MIP/SOL subtypes showed a trend favoring the LO group (P=0.092). However, when we excluded patients with SLR with resection margin <1 cm (n=64), there was no difference between LO (80%-72%) and SLR (81%-75%) at 3 and 5 years respectively (P=0.812)(Fig.1). Also, the type of resection (LO/SLR) was not associated with higher recurrence rates in the MVA of the whole cohort. Figure 1



      Conclusion:
      SLR can be safely performed in clinical stage-IA lung adenocarcinoma, regardless of the histological subtype, provided that a resection margin >1 cm is obtained.

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    P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P1.03-005 - Bilobectomy for Lung Cancer: Postoperative Results, and Long-Term Outcomes (ID 3124)

      09:30 - 17:00  |  Author(s): B. Stiles

      • Abstract
      • Slides

      Background:
      Bilobectomy for treatment of lung cancer is considered a high-risk procedure as it is associated with increased postoperative complication rate and the negative impact on survival. We analyzed the safety and the oncologic results of this procedure.

      Methods:
      We retrospectively reviewed a prospectively collected database to retrieve patients who underwent bilobectomy for lung cancer between 1991 and 2015. Age, gender, neoadjuvant treatment, bilobectomy type and indication, complications, pathology, stage, and survival were analyzed using Cox regression in univariate and multivariate analysis. Kaplan–Meier survival curves were obtained and compared by log–rank.

      Results:
      From our 4144 resected lung cancer cases, bilobectomy was performed on 106(2.5%) patients (55 men; mean age, 65.5 years). There were 51 upper-middle and 55 middle-lower bilobectomies (adenocarcinoma,67 (63.3%); squamous cell carcinoma,35(33%); carcinoid tumor,4(3.8%)). Indications were tumor invasion of the bronchus intermedius in 58 (54.7%), vascular invasion in 26 (24.5%), and tumor crossing the fissure in 22 (20.8%) patients. Induction therapy was performed in 24 patients (24.5%). Thirty-day mortality was 1.89% (n = 2). Overall major morbidity occurred in 13 patients ( 12.3%) among them 9 patients(69.2%) had pulmonary complications . Overall 3 and 5-year survivals were 64.5% and 56.2% respectively. Disease free 3 and 5-year survivals were 47.4% and 43.8% respectively. Significant decrease in 5 year survival was observed among smoker (p=0.046), higher tumor grades (Grade3 versus 1or2 (p=<0.005)), higher stages (stage I, 66.6%; stage II, 51.5%; stage III, 31.2%; p = 0.012)(see Figure) and the nodal(N) disease s (N0, 58.2%; N1and 2, 38.1%; p = 0.054) adversely influenced survival. Multivariate analysis demonstrated that a higher tumor grade (p = 0.005), a larger tumor (p=0.019), advanced N status (p=0.085) and smoking (p=0.056) adversely affecting prognosis. Figure 1



      Conclusion:
      Bilobectomy is associated with a low mortality and an acceptable morbidity. Survival relates to disease stage and N factor. Optimal prognosis is obtained in patients with early stage, low grade tumors and nonsmoker.

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