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L. Irving

Moderator of

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    O18 - Cancer Control and Epidemiology II (ID 133)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Prevention & Epidemiology
    • Presentations: 8
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      O18.01 - Multi-'omic analysis of an arsenic-associated lung squamous cell carcinoma reveals specific DNA level signatures (ID 283)

      10:30 - 12:00  |  Author(s): V.D. Martinez Zamora, K.L. Thu, E.A. Vucic, R. Hubaux, M.I. Adonis, L. Gil, C.E. Macaulay, S. Lam, W.L. Lam

      • Abstract
      • Presentation
      • Slides

      Background
      Chronic low-level exposure to arsenic is an emerging cancer risk factor in many parts of the world, including North America. The lung is one anatomical site prominently affected by the carcinogenic effects of arsenic, evident by the striking incidence of lung cancer in never smokers with chronic exposure. Histologically, arsenic related lung tumors are indistinguishable from those induced by other lung carcinogens, and molecularly, arsenic specific DNA copy-number, methylation and expression changes have been identified. Arsenic mediated carcinogenesis occurs through a combination of molecular mechanisms; however, high resolution, multi-'omic analyses of arsenic related tumors have been difficult due to the lack of fresh frozen samples required to obtain high quality DNA and RNA. In this study, we sought to characterize global changes in DNA sequence and methylation levels and their impacts on gene expression in a lung tumor from a patient with chronic arsenic exposure (As-LUSC).

      Methods
      Tumor and non-malignant lung tissues were obtained from a never smoker with lung squamous cell carcinoma (LUSC) who had no family history of lung cancer and 50 years of chronic exposure to high levels of arsenic-contaminated drinking water. Whole genome sequencing was performed and the tumor's mutational signature was compared to those observed in 194 previously characterized NSCLC tumors from the cancer genome atlas (TCGA). DNA methylation was measured using high density methylation arrays and gene expression by RNA sequencing.

      Results
      The As-LUSC exhibited alterations typical of LUSC, such as copy number gains at 3q26 (SOX2 locus) and expression of squamous markers including up-regulation of KRT6B, DSG3, MMP12, KRT5, and down-regulation of PDK4, which are consistent with LUSC histology. However, the As-LUSC harbored a low number of point mutations (only 49 non-synonymous mutations affecting coding DNA sequences) and had a remarkably high fraction of T>G/A>C and low fraction of C>A/G>T transversions, which are features uncharacteristic of LUSCs that suggest arsenic is associated with a distinct mutational spectrum. Furthermore, at the gene level, we identified a G>C mutation in TP53 which is rare in lung tumors (<0.2%) but has been observed in other arsenic-related malignancies. Clustering analysis using ~450,000 methylation probes revealed that the As-LUSC methylation profile was completely distinct from never smoker LUSCs from the TCGA. Of interest, the As-LUSC exhibited lower levels of methylation at CpG islands sores that are not associated with genes, although have been described to exhibit cell type specific methylation patterns.

      Conclusion
      By applying whole genome sequencing, methylation and expression profiling of a LUSC from a never-smoker patient chronically exposed to arsenic, we identified a distinct mutational spectrum and methylation pattern in the As-LUSC. Our results support the concept that arsenic induces lung cancers through mechanisms different from tobacco smoke and other carcinogens. Further study of the mutational profiles of additional arsenic-related cancers is warranted and may yield valuable insight into arsenic associated tumourigenesis, leading to the development of novel diagnostic and therapeutic targets for environmental monitoring and treatment.

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      O18.02 - Impacts of environmental tobacco smoke on EGFR mutations and ALK rearrangements in never smokers with non-small cell lung cancer: Analyses on a prospective multinational ETS registry (ID 1255)

      10:30 - 12:00  |  Author(s): A. Kubo, M. Ando, R. Soo, T. Kawaguchi, S.I. Ou, M. Ahn

      • Abstract
      • Presentation
      • Slides

      Background
      EGFR and ALK are important driver mutations in never smokers. While we reported the significant association of increased environmental tobacco smoke (ETS) with EGFR mutations in Japanese cohort (Kawaguchi, Clin Cancer Res, 2011), it has not been fully understood in other ethnicities and also the correlation of ETS with ALK has not been reported yet. In this study, we evaluated the association of ETS with the prevalence of EGFR mutations and ALK translocations in various ethnicities including East-Asia (Japan, Korea, China, and Singapore) and the USA.

      Methods
      ETS exposure on never smokers with non-small cell lung cancer (NSCLC) was evaluated using the standardized questionnaire including exposure period, place, and duration. Cumulative dose of ETS (CETS) was defined as a sum of the number of the exposure years in childhood/ adulthood and at home/ workplace, and was treated as a continuous variable or quintile. EGFR mutations and ALK rearrangements were tested by PCR-based detection and fluorescence in situ hybridization, respectively. Multivariate analyses were done using the generalized linear mixed model (GLIMMIX procedure, SAS v9.3).

      Results
      From March 2008 to December 2012, 498 never smokers with NSCLC were registered with the following patient characteristics: ethnicity (nationality) of Asian/ Caucasian/ others, 425 (Japanese 250, Korean 102, Chinese 46, others 2)/ 48/ 25; male/ female, 114/ 384; age <65/ >=65, 286/ 212; histology of adenocarcinoma/ BAC/ squamous cell carcinoma/ adenosquamous cell carcinoma/ other NSCLC, 459/ 12/ 13/ 5/ 9; frequency (%) of CETS < median CETS (40 years) in Japanese/ Korean/ Chinese/ Caucasian, 32.8/ 44.1/ 71.7/ 83.3. EGFR status was wild type 43.6%, exon 19 deletion 25.3%, L858R 21.5% and other mutations 9.6%. ALK status was wild type 52.0%, rearranged 10.6% and unknown 37.3%. Average CETS (years) of NS with EGFR (+), ALK (+) and wild type tumors were 45.4, 26.9 and 37.7, respectively. In multivariate generalized linear mixed model, incidence of activating EGFR mutations, not ALK rearrangements, was significantly associated with the increment of CETS in female, not in male gender. Odds ratios (OR) for EGFR mutations in female (n=384) were 1.084 (95% CI, 1.003-1.171; p=0.0422) for each increment of 10 years in CETS while OR in male (n=114) were not significant (OR 0.890; 95% CI, 0.725-1.093; p=0.2627). OR for ALK rearrangements in female (n=238) and those in male gender (n=74) were 0.930 (0.791-1.094; p=0.3814) and 0.854 (0.620-1.178; p=0.3319).

      Conclusion
      Increased ETS exposure was closely associated with EGFR mutations in never smokers with female gender and NSCLC in the expanded multinational cohort. However, the association of ETS and ALK rearrangements in never smokers with NSCLC was not significant.

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      O18.03 - The BioCAST / IFCT-1002 study: a comprehensive overview of demographic, risk exposure and somatic mutations of non-small cell lung cancer occurring among French never smokers (ID 3293)

      10:30 - 12:00  |  Author(s): S. Couraud, P. Souquet, C. Paris, R. Gervais, H. Doubre, E. Pichon, A. Dixmier, I. Monnet, B. Etienne-Mastroianni, M. Vincent, J. Tredaniel, M. Perrichon, P. Foucher, B. Coudert, D. Moro-Sibilot, E. Dansin, S. Labonne, P. Missy, G. Zalcman

      • Abstract
      • Presentation
      • Slides

      Background
      Lung cancer occurring in never-smoker (LCINS) is a particular entity. Although the definition is strict (less than 100 cigarette in lifetime) never-smokers are frequently misclassified and no study gives a comprehensive analysis of this group, particularly in a European setting.

      Methods
      All consecutive never-smoker patients diagnosed with a non-small cell lung cancer in one of the 75 participating centers throughout France, between November 2011 and January 2013, were included in this prospective survey. All patients underwent a detailed questionnaire supported by a trained staff during a phone interview. Somatic mutations and cancer clinical and histological data were also recorded from medical charts.

      Results
      Overall, 384 never-smokers were included and 336 interviews were completed. Most of them were women (n=319, 83.1%). The mean age at diagnosis was 69.8 ± 12.02 and 10.9% were under 55 years-old. None reported alternative smoking (pipe, cigar, water-pipe, gum, or cannabis). Most of them originated from Western and Southern Europe (90.5%). Overall, 219 (65.6%) reported a passive smoking exposure in a domestic setting (n=198; 59.3%), and/or at workplace (n=60; 18.0%). Patients had a personal history of pneumonia in 6.2%, tuberculosis in 8.3%, COPD in 13.0%, and a cancer at another site in 16.6%. Eighty patients reported at least two relatives with lung cancer (24.0%). Definite occupational exposure was observed in 12.0% (n=44) for diesel, 7,1% (n=26) for asbestos, 3.3% (n=12) for poly-aromatic hydrocarbons, 2.4% (n=9) for silica, 0.8% (n=3) for chrome, and 0.5% (n=2) for painting. Exposure to cooking oil was noted in 123 patients (36.8%) with a mean of 49.4 ± 356.7 cooking-dish year. Moreover, 79.7% (n=259) patients were ever exposed to solid fuel fumes for cooking or heating (21.2% during more than 50% of their lifetime). Among women, 91.7% already reached menopause (mean age 49.3 ± 5.6 years-old), 115 (41.7%) were ever-exposed to oral contraceptive (mostly oestrogen-containing drugs), and 25.5% to post-menopause hormone replacement therapy (oral or transdermal). Most of lung cancers were adenocarcinoma (n=327, 85.2%) followed by squamous cell carcinoma (n=29, 7.6%) and large cell carcinoma (n=17; 4.4%). Among adenocarcinoma, 71% were invasive, 4% in-situ, 2% minimally-invasive, 2% variant of invasive, and 20.0% were NOS. Cancer stage was I in 9.2%, II in 5.8%, III in 11.8% and IV in 73.2%. At least one biomarker was tested in 359 patients (93.5%). We found 148 patients with EGFR mutations (43.5% out of the EGFR-tested patients), 20 with KRAS mutations (6.8%), 24 with ALK translocation (12.5%), 10 with BRAF mutation (4.5%), 8 with HER2 mutation (4.0%) and 4 with PIK3CA (2.1%). Overall, 27.0% samples remain wild type, 2.1% with multiple mutations, 71.0% with a single mutation, and 20.6% with missing data.

      Conclusion
      We provide here the largest cohort of LCINS in a European setting with reliable data on tobacco intoxication, occupational exposure, and hormonal treatments, since collected by a trained staff through phone interview. In this perfectly clinically characterized cohort, molecular analyses showed that 72% of tumors exhibited oncogenic targetable mutations.

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      O18.04 - Impact of Passive Smoking on molecular pattern in Never Smokers with Non-Small Cell Lung Cancer: Findings from the BioCAST / IFCT-1002 Study (ID 3305)

      10:30 - 12:00  |  Author(s): S. Couraud, P. Dumont, L. Moreau, D. Debieuvre, J. Margery, E. Quoix, B. Duvert, L. Cellerin, N. Baize, B. Taviot, M. Coudurier, J. Cadranel, P. Missy, G. Zalcman, P. Souquet

      • Abstract
      • Presentation
      • Slides

      Background
      EGFR and HER2 mutations are usually associated with never-smokers while KRAS and BRAF mutations are thought to be link with smoking behavior in Non-Small Cell Lung Cancer (NSCLC). Passive smoking exposure is a well-known risk factor for lung cancer. Only EGFR and KRAS mutations were investigated in association with passive smoking and showed conflicting results. We aimed to investigate mutation rate of EGFR, HER2, KRAS, BRAF and ALK in a cohort of never smokers regarding their passive smoke exposure.

      Methods
      The BioCAST / IFCT-1002 study is a prospective cohort of NSCLC patients diagnosed in French never-smokers patients (less than 100 cigarettes in lifetime) between November 2011 and January 2013, Passive smoking exposure was evaluated through standardized questionnaire. We obtained biomarkers mutation results through routine testing. We used Fisher, Chi-square, median test and Mann-Whitney U test for comparisons as appropriate. We used logistic regression to calculate adjusted odds ratio for risk of each mutations.

      Results
      Out of the 384 patients included in the BioCAST database, 334 (87.0%) had available data on passive smoking exposure. Among them, 219 patients (65.6%) were ever exposed to passive smoking in their lifetime. 198 (59.3%) reported a domestic exposure (122 during childhood at least) and 60 (18.0%) a workplace exposure. Result of at least one biomarker mutation was available in 313 patients (93.7%). including 128 EGFR mutations in 297 patients, 8/174 HER2 mutations, 18/256 KRAS mutations, 10/196 BRAF mutations, and 20/171 ALK gene rearrangements. We found no difference in mutation rate according to passive smoke exposure (cf. Table 1). There was no difference when comparing cumulative year of exposure, smoker-year or passive-pack year (as continuous variable) to the mutation rate, for any biomarker. When considered as categorical variable – after division in quartiles – we found also no difference. Results were similar when focusing on domestic (childhood versus adulthood included) and workplace exposure only. Finally, we found no significant increased risk for mutation for any biomarker in logistic regression adjusted for most of other lung cancer risk factors.

      EGFR Mt (n=297) HER2 Mt (n=171) KRAS Mt (n=256) BRAF Mt (n=196) ALK Fusion (n=171)
      % % % % %
      Overall exposure Never 46.5 3.5 6.7 5.9 13.0
      Ever 41.3 5.1 7.2 4.7 11.1
      Domestic exposure Never 45.8 2.9 7.7 6.4 11.1
      Ever 41.3 5.7 6.6 4.2 12.0
      Exposure at workplace Never 43.3 5.5 7.0 5.4 12.2
      Ever 42.3 0 7.0 3.6 8.3
      Total 43.1 4.6 7.0 5.1 11.7
      Exposure in childhood Ever 40.5 3.0 6.5 2.7 14.7
      Only in adulthood 42.6 10.3 6.8 6.7 7.5

      Conclusion
      Although we report the largest and more comprehensive study focusing on this topic, we found no significant difference in the biomarker mutation profile of NSCLC occurring in French never-smokers regarding their exposure to passive smoking as compared with the pattern of mutations described never-smoker patients with any passive smoking.

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      O18.05 - DISCUSSANT (ID 3998)

      10:30 - 12:00  |  Author(s): P.P. Massion

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      O18.06 - Vietnamese non-small cell lung cancer patients in California: molecular profiles and clinical characteristics (ID 1079)

      10:30 - 12:00  |  Author(s): K.H. Nguyen, M. Das, K. Ramchandran, J. Shrager, R.E. Merritt, C. Hoang, B. Burt, A. Tisch, J. Pagtama, J. Zehnder, G. Berry, H.A. Wakelee, A. Nguyen, J.W. Neal

      • Abstract
      • Presentation
      • Slides

      Background
      Lung cancer is the leading cause of cancer-related deaths worldwide with 1.3 million deaths per year. Discoveries of oncogenic mutations in non-small cell lung cancer (NSCLC) over the past decade have led to targeted therapies against epidermal growth factor receptor (EGFR) activating mutations, anaplastic lymphoma kinase (ALK) gene rearrangement, and repressor of silencing 1 (ROS1) gene rearrangement. The frequencies of these mutations and gene rearrangements have been elucidated in the Western and East Asian populations. However, the frequencies of these oncogenic alterations remain unknown in Vietnam, where lung cancer is one of the leading causes of cancer mortalities but molecular testing is not routinely performed due to limited resources. In this project, we aimed to analyze the Vietnamese patients treated at Stanford, California, with a future plan to compare with another cohort inside Vietnam.

      Methods
      We collected molecular and clinical variables of NSCLC patients of Vietnamese origin, based on patients' self-reported ethnicity, language, or country of origin, treated at Stanford from 2009 to 2012. Comparison of the molecular and clinical characteristics of never smokers versus smokers was performed with Pearson's chi-squared test for nominal variables and Student's t test for continuous variables. Survival analyses were done using the Kaplan-Meier method and Cox proportional hazards modeling.

      Results
      Forty-six patients of Vietnamese origin were seen at the Stanford thoracic oncology clinic from 2009 to 2012, including 22 men and 24 women with a mean age of 58 years. Twenty-seven (58.7%) were never-smokers. Forty-two (91.3%) of the tumors were adenocarcinoma. Ten patients (21.7%) presented at stage I, none at stage II, 8 patients (17.4%) at stage III, 28 patients (60.9%) at stage IV. Fifteen patients out of 28 tested for EGFR (53.6%) had an activating mutation; 14 of these 15 patients were never-smokers. Five patients out of 16 tested for ALK (31.3%) had ALK gene rearrangement. No ROS1 gene rearrangement out of 3 patients tested was found. Only one patient, a former smoker, out of 23 tested (4.4%) was found to have a KRAS mutation. Eighteen out of 27 never-smokers (66.7%) and 3 out of 19 smokers (15.8%) had a targetable driver mutation (EGFR, ALK, or ROS1). For all stages, the median overall survival (OS) for never-smokers was 22.3 months (95% confidence interval (CI); 11.9 months, 24.3 months) compared to 12.9 months (95% CI; 5.8 months, 20.0 months) for smokers. For only stage IV, the median OS for never-smokers was 21.2 months (95% CI; 13.0 months, 24.3 months) compared to 11.6 months (95% CI; 1.4 months, 30.9 months) for smokers.

      Conclusion
      Approximately two-thirds of never-smoker patients of Vietnamese origin had NSCLC with a targetable driver mutation. OS differ markedly by smoking status. The high percentage of Vietnamese patients in California with driver mutations warrants further studies to evaluate the frequencies of NSCLC driver mutations inside Vietnam, strongly suggesting that nationwide implementation of routine molecular testing will have a positive impact on clinical management of Vietnamese patients with NSCLC.

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      O18.07 - A Retrospective Cohort Mortality Study in Jingchuan of china - the Largest Nickel Population in World (ID 94)

      10:30 - 12:00  |  Author(s): N. Cheng, L. Ma, T. Zheng, J. He, M. Dai, Y. Zhang, Y. Bai

      • Abstract

      Background
      Nickel is an essential trace metal used in the occupational setting and is naturally found in the general environment, resulting in both occupational and nonoccupational exposures to individuals at varying levels. Exposure to nickel has been associated with several toxicites and the International Agency for Research on Cancer has concluded that there is sufficient evidence in humans associating exposure to nickel or nickel compounds with risk of lung cancer. We evaluated overall and cause-specific mortality among Chinese workers involved in nickel production or utilization in order to examine the long-term health effects of occupational exposure to nickel compounds.

      Methods
      The study design was a retrospective cohort mortality study including 432,526 workers who were involved with nickel mining or smelt between 2001 and 2010. We calculated standardized mortality ratios (SMR) using the death rates of Gansu Province in China, and estimated by the exact probabilities of the Poisson distribution.

      Results
      Overall, the all-cause mortality was decreased in all workers compared to the general population of Gansu province (SMR= 0.53, 95%CI: 0.51-0.55). Analyses examining cause-specific mortality revealed an increase in the mortality from bronchogenic carcinoma and lung cancer (SMR = 2.05, 95% CI = 1.84-2.29), cor pulmonale (SMR =4.08, 95% CI = 3.25-5.01), and silicosis (SMR = 13.59, 95%CI =11.90-15.52) in the workers exposed to nickel.

      Conclusion
      This study confirmed a significant excess of mortality from diseases of the lung including silicosis , lung cancer, and cor pulmonale among workers involved in nickel mining or smelt in China.

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      O18.08 - DISCUSSANT (ID 3999)

      10:30 - 12:00  |  Author(s): C. Amos

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.05-009 - Development of small cell lung cancer primary xenografts using specimens obtained by endobronchial-ultrasound transbronchial needle aspiration: a novel pre-clinical model (ID 1549)

      09:30 - 16:30  |  Author(s): L. Irving

      • Abstract

      Background
      Lung cancer has the highest cancer incidence and mortality worldwide. Small cell lung cancer (SCLC) accounts for 15% of all cases. Platinum-based chemotherapy induces responses in up to 70%. However, treatment-resistant recurrence is near universal, and 5-year survival remains poor at 1-2%. Therefore, there is urgent need for pre-clinical models that accurately recapitulate the parent tumour and allow testing for predictive biomarkers of response and resistance to drugs, and also screening of novel anticancer agents. Furthermore, as the vast majority of SCLC are inoperable, it is crucial that the mode of tumour tissue acquisition be minimally invasive and repeatable in cases of recurrence. Here we describe a novel pre-clinical model using samples obtained by the minimally invasive technique of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to develop primary xenografts of SCLC.

      Methods
      Cell suspensions from samples of SCLC obtained by EBUS-TBNA were implanted directly into the flanks of NSG (Non-Obese Diabetic, Severe Combined Immune Deficient, IL2Rγ knockout) mice to generate primary xenografts. The mice were monitored for tumour growth, and if engraftment was successful, pre-graft and post-graft tumours were compared in terms of morphology, immunohistochemistry and molecular characteristics.

      Results
      Thus far, 14 SCLC specimens have been implanted, with 7 cases completing 6 months of tumour monitoring. Of these, 6 have undergone successful engraftment (86%). Samples typically contained over 1 million tumour cells with minimal stromal contamination. Mean engraftment lag time was 96 days. In all cases of engraftment, histological and molecular fidelity to the original tumour was demonstrated.

      Conclusion
      This is the first report of the generation of a primary xenograft model of lung cancer using a new method of tissue acquisition by EBUS-TBNA. Furthermore, it is the largest reported group of primary xenografts of SCLC. The primary xenograft lines from these specimens may provide the much-needed basis for more accurate pre-clinical modeling of SCLC, and hold great translational promise for novel therapeutic agents.

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    P1.17 - Poster Session 1 - Bronchoscopy, Endoscopy (ID 182)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      P1.17-009 - What is the rate of surgical upstaging following negative EBUS-TBNA of mediastinal lymph nodes for NSCLC? (ID 2621)

      09:30 - 16:30  |  Author(s): L. Irving

      • Abstract

      Background
      Mediastinal lymph node evaluation is a critical determinant of treatment strategy in NSCLC. Many staging modalities, both invasive and non-invasive, have been evaluated over the past few decades with varying degrees of accuracy. Despite the fact that CT imaging is the preliminary investigation for diagnosis of lung cancer, various studies have shown that CT scanning is less accurate (sensitivity of 41% to 63%, a specificity of 43% to 57%, and an accuracy of 39% to 59%) for the detection of mediastinal nodal metastasis. According to a meta analysis looking at nodal disease, the sensitivity for PET is 79% to 84% and its specificity is 89% to 91%.The ability of PET CT to provide morphologic and functional information enhances the diagnostic accuracy of mediastinal nodal staging in NSCLC . Most guidelines would however need tissue confirmation which can be obtained by EBUS- TBNA. This procedure has the advantage that it can be performed under sedation , however , the downside to this is the small samples without accurate anatomical definition. In our institute we perform PET-CT scan followed by EBUS TBNA for pre operative staging of the mediastinal lymph node {in selected cases}. However, in cases where EBUS-TBNA of mediastinal lymph nodes is negative for malignancy, there is still a possibility that metastases to these lymph nodes are found at surgery. This will result in an upstaging of the NSCLC following surgery. We aimed to determine the rate of surgical upstaging following negative EBUS-TBNA of mediastinal lymph nodes for NSCLC.

      Methods
      This is a retrospective study. From January 2009 till May 2013, we identified 304 patients who underwent surgery for NSCLC. All the patients who were planned for surgical resection underwent a staging CT scan thorax or a PET CT scan. Only those patients with suspicious lymph nodes on either of the imaging, were subjected to EBUS TBNA. These lymph nodes were then re-evaluated by histopathology following surgery. Of these 65 patients who had EBUS-TBNA prior to surgery , fifty-three patients had negative EBUS-TBNA and they formed the basis of this report.

      Results
      Out of the 53 patients with a negative EBUS-TBNA, nine of them (17%) demonstrated positive lymph nodes in surgery, giving a negative predictive value of 83% for EBUS-TBNA in this selected group. The negative predictive value of PET CT was around 77% whereas negative predictive value for EBUS TBNA was 83%.

      Conclusion
      Our study confirms a negative predictive value (83%) of EBUS-TBNA in excluding N2/3 disease in patients diagnosed with NSCLC which is higher than PET CT scan (77%). The slightly lower negative predictive value of EBUS TBNA may be attributed to the fact that not all the surgical candidates were staged with a pre operative histological confirmation of the mediastinal lymph nodes. However a combination of PET CT scan and EBUS TBNA is a reasonable pre operative staging for mediastinal lymph nodes with low complication rates.

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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-024 - Preliminary experience in bronchoscopic placement and in-treatment imaging of two different fiducial markers for guidance of lung cancer radiation. (ID 2758)

      09:30 - 16:30  |  Author(s): L. Irving

      • Abstract

      Background
      During conventional radiation therapy, treatment image guidance is largely indirect relying on slow acquisition 3D volumetric imaging or the use of bony surrogates. Fiducial marker placement within/adjacent to lung tumours facilitates image guided radiation therapy by …….. Marker placement has been attempted percutaneously but is associated with pneumothorax in up to 45%, with frequent use of chest drain tubes. Furthermore, in-treatment imaging protocols are not standardized, and the impact of marker characteristics on accuracy of in-treatment imaging has not previously been reported. We describe our preliminary experience in bronchoscopic implantation and in-treatment tracking/imaging of two different types of lung fiducial marker.

      Methods
      Study design: Prospective observational case series of NSCLC patients undergoing radical radiation treatment . Bronchoscopic implantation: performed under conscious sedation using radial probe endobronchial ultrasound and fluoroscopic guidance to achieve tumour localization and placement within/adjacent to peripheral tumours. Post-implantation/ in-treatment imaging: Time-resolved 4D CT (Philips Brilliance+bellows system) for treatment planning and after completion of treatment to investigate marker movement. Throughout treatment delivery MV electronic portal images (EPI) were acquired plus kV planar and Cone Beam CT (CBCT) (Varian Medical System) images.

      Results
      Four patients with T1N0 NSCLC underwent bronchoscopic implantation of fiducial markers (two using Visicoil[TM] linear fiducial 10x0.75mm, two using SuperDimension® superLock™ 2-band 13x0.9mm markers. Confirmation of tumour localization was achieved with EBUS in all four patients. Two markers were placed in adjacent airways in one patient, and the remainder had a single marker placed within/adjacent to their peripheral tumour. No complications related to bronchoscopy or marker implantation were observed. No marker migration was observed over the treatment time for both marker types. Visibility of the markers in EPI was only possibly in selected beam directions though they were easily discernible in kV planar images (Figure 1a). While diagnostic CT scanning was able to demonstrate the markers in great clarity (Figure 1b), they caused significant image artefacts in CBCT. Figure 1 Figure 1: Image-guided radiotherapy images demonstrating: a) 4DCT image showing visicoil fiducial on maximum intensity projection images, tumour+motion contoured in red, & b) kV orthogonal image showing superLock™ 2-band marker.

      Conclusion
      Our preliminary experience indicates bronchoscopic implantation of fiducial markers is safe, and is achievable with a high degree of accuracy on initial imaging, and stability on subsequent in-treatment imaging. There is a fine balance of marker size minimising CBCT artefacts while allowing visualisation in EPI imaging which would be an ideal tool to verify gated radiotherapy delivery.

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    P3.17 - Poster Session 3 - Bronchoscopy, Endoscopy (ID 185)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track:
    • Presentations: 1
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      P3.17-007 - Rapid On-Site Cytologic Evaluation (ROSE) of bronchial brushings during bronchoscopic investigation of peripheral pulmonary lesions: diagnostic accuracy and impact on procedure time (ID 2749)

      09:30 - 16:30  |  Author(s): L. Irving

      • Abstract

      Background
      Rapid on-site evaluation (ROSE) of transbronchial needle aspirates is cost-effective due to its ability to reduce biopsy number and complication rates without compromising diagnostic yield. Use of ROSE during sampling of peripheral pulmonary lesions (PPLs) has not previously been examined. We aimed to determine the ability of ROSE performed on transbronchial brushings of peripheral pulmonary lesions to accurately determine final procedural diagnosis. To determine if use of ROSE impacts on procedural time or procedural complication rates.

      Methods
      Prospective cohort of patients undergoing radial probe endobronchial ultrasound-guided bronchoscopy for investigation of PPLs. ROSE was performed using a Rapid Romanowsky stain. If ROSE demonstrated diagnostic malignant material the procedure was determined to be successful and no further sampling was undertaken. Non-diagnsotic ROSE assessment resulted in further sampling including transbronchial lung biopsy, and possibly sampling from different locations.

      Results
      Specimens obtained from 128 lesions in 118 consecutive patients in whom radial EBUS successfully localized a peripheral pulmonary lesion. Final procedural diagnoses included non-small cell lung cancer (n=76), carcinoid (3), metastatic malignancy (n=3), benign inflammatory/infective infiltrate (n=46). Positive predictive value of ROSE for a malignant bronchoscopic diagnosis was 97% (63/65). Two patients had positive diagnoses made on ROSE but final procedural diagnosis was “reactive bronchial cells” however both of these patients were subsequently confirmed to have NSCLC following alternate biopsy procedures. Procedure times were significantly shorter in those in whom ROSE specimens demonstrated malignancy than in those in whom ROSE was non-diagnostic (19+8 minutes vs. 31+11 minutes, respectively. p<0.0001) In four procedures, initial negative ROSE results prompted redirection of sampling from alternate bronchial segments resulting in positive diagnostic tissue being obtained.

      Conclusion
      ROSE examination of brushings specimen had high positive predictive value for bronchoscopic diagnosis of cancer. ROSE of brushings specimens has the potential to shorten bronchoscopy times, reduce complications and is likely to be cost-effective. It may also improve diagnostic performance via live feedback, allowing proceduralists to redirect subsequent sampling procedures.