Virtual Library

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    ES03 - How to Manage Pleural Plaques and Pleural Effusion with Negative Pleural Biopsy (ID 771)

    • Event: WCLC 2018
    • Type: Educational Session
    • Track: Mesothelioma
    • Presentations: 5
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 206 AC
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    ES08 - The Pathologist - An Essential Member of the Patient Care Team (ID 776)

    • Event: WCLC 2018
    • Type: Educational Session
    • Track: Pathology
    • Presentations: 4
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 206 AC
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      ES08.01 - Targeted Therapy (ID 11383)

      13:30 - 13:50  |  Presenting Author(s): Yasushi Yatabe

      • Abstract

      Abstract not provided

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      ES08.02 - Immunotherapy (ID 11384)

      13:50 - 14:10  |  Presenting Author(s): Sylvie Lantuejoul

      • Abstract

      Abstract not provided

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      ES08.03 - Mesothelioma, Thymic Epithelial Tumors and Others (ID 11385)

      14:10 - 14:30  |  Presenting Author(s): Andrew G Nicholson

      • Abstract

      Abstract not provided

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      ES08.04 - Neoadjuvant Therapy (ID 12811)

      14:30 - 14:50  |  Presenting Author(s): Ignacio I. Wistuba

      • Abstract

      Abstract not provided

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    MA03 - Lung Cancer Screening - Next Step (ID 896)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Screening and Early Detection
    • Presentations: 11
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 206 AC
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      MA03.01 - Manchester Lung Cancer Screening: Results of the First Incidence Screening Round (ID 12568)

      10:30 - 10:35  |  Presenting Author(s): Haval Balata  |  Author(s): Phillip Crosbie, Matthew Evison, Richard Booton

      • Abstract
      • Presentation
      • Slides

      Background

      The European position on lung cancer (LC) screening has recommended planning for implementation to commence throughout Europe (1). The Manchester lung cancer screening pilot is one of the first real world implementation projects to take place in Europe and to publish baseline results (2). In this abstract we share, for the first time, the results from the first incidence screening round of the Manchester pilot.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The methodology and results of the baseline round of the Manchester screening pilot have been published previously (2). In brief, ever smokers, aged 55-74, from deprived areas of Manchester were invited to a free ‘Lung Health Check’ (LHC) in mobile units located at their local shopping centres. The PLCOm2012 LC risk stratification model was incorporated into the LHC and those at high risk of LC (PLCOm2012 ≥1.51%) were offered immediate LDCT in a co-located mobile scanner. At baseline, 75% of attendees were ranked in the lowest deprivation quintile; 56% were at high risk and 1384 screened with LDCT. 3% had LC diagnosed of which 80% were early stage (I+II) and 90% offered curative treatment.

      In this round of screening, all high risk individuals screened at baseline with no subsequent diagnosis of LC (screening or non-screening) were invited back for an annual LDCT scan at the same community locations. Exclusion criteria included death, other malignancies under follow-up and CT thorax within 3-months of due screening date. National and GP specific registries were checked for interval LC diagnosis.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 1,194 LDCT scans were performed as part of the first incidence round of screening. Overall 28 (2.3%) individuals received a positive scan result and were referred to the MDT. Of these, 18 (1.5%) individuals were diagnosed with LC of which 78% (n=14/18) were lower stage (I-II) and 89% (n=16/18) offered curative treatment. The false positive rate was 0.8% of the screened population as a whole and 36% of those with a positive scan result. There were no interval LCs diagnosed at one year.

      The cumulative LC detection rate over the first 12 months of the programme was 4.3% (n=60/1384) of which 80% (n=51/64) were stage I-II.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Annual LDCT screening of high risk individuals in this real world lung cancer screening implementation project continues to identify a significant number of early stage lung cancers amenable to curative treatment. No interval lung cancers were diagnosed at one year suggesting the baseline selection criteria for screening was appropriate.

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      MA03.02 - Prospective Evaluation of the Clinical Utility of the International Lung Screen Trial Lung Nodule Management Protocol (ID 14043)

      10:35 - 10:40  |  Presenting Author(s): Stephen Lam  |  Author(s): Renelle L Myers, Sukhinder Atkar-Khattra, Ren Yuan, John Yee, John English, Kyle Grant, Alex Lee, Anna McGuire, Annette Maree McWilliams, Fraser Brims, Emily Stone, Venessa Chin, Lorraine Chantrill, Mark Connellan, Marhsall Plitt, Henry Marshall, Ian Yang, Rayleen Bowman, Kwun M Fong, John Mayo

      • Abstract
      • Presentation
      • Slides

      Background

      Several protocols are available to guide management of lung nodules identified by low-dose screening CT. It is important to objectively assess their clinical utility in order to weigh the potential harm versus potential beneficial impacts of the following: early recall imaging studies/biopsy and health care resource utilization. We aimed to prospectively evaluate clinical utility of the PanCan lung nodule management protocol in the International Lung Screen Trial (ILST).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Ever smokers age 55 to 80 years were enrolled into ILST if they has a ≥30 pack-years smoking history and smoked within 15 years or if their PLCO m2012 6 year lung cancer risk was ≥1.51%. Figure 1 shows the ILST lung nodule management protocol based on the PanCan nodule malignancy risk calculator (NEJM 2013;369:908 & BMJ 2014;348:g2253).

      4c3880bb027f159e801041b1021e88e8 Result

      Since July 2016, 757 ever smokers (mean age 65 years, 44% female, 15% non-Caucasian) had been enrolled. The distribution of malignancy risk categories (CAT) were: CAT1 70%, CAT2 15%, CAT3 11%, CAT4 3.5%, CAT5 0.4%. CT biopsy or bronchoscopic biopsy for diagnosis/staging was done in 16/26 CAT 4 (62%) and 7/84 CAT 3 (8%) participants. Lung cancer was confirmed in 15/757 (2%). Thus far, surgery was performed in 9 CAT 4 and 2 CAT 3 participants, with one benign resection (9%) for a growing FDG avid nodule. Of the 3 CAT5 participants, one was found to have granulomatous changes in an enlarged paratracheal lymph node and two had segmental atelectasis due to mucoid impaction.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The ILST protocol triaged 70% of the screening cohort with low malignancy risk to biennial screening instead of annual repeat screening. Participants with high malignancy risk (CAT 4+5) were triaged to a diagnostic pathway (4%). Our preliminary results suggest the ILST protocol may decrease resource utilization and potentially minimize risk of screening for participants.

      figure1 ilst lung nodule management protocol.jpg

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      MA03.03 - Prolonged Low-Dose Computed Tomography (LDCT) Screening Beyond 5 Years Reduces Overall and Lung Cancer Specific Mortality (ID 13227)

      10:40 - 10:45  |  Presenting Author(s): Ugo Pastorino  |  Author(s): Federica Sabia, Stefano Sestini, Mario Silva, Mattia Boeri, Anna Cantarutti, Nicola Sverzellati, Gabriella Sozzi, Giovanni Corrao, Alfonso Marchianò

      • Abstract
      • Presentation
      • Slides

      Background

      The National Lung Screening Trial (NLST) showed that lung cancer screening (LCS) by low-dose computed tomography (LDCT) improves the overall survival. The NLST and most of the LCS trials were limited to a 5-year period, therefore there is no prospective evidence about the optimal duration of LCS. The aim of this study was to assess the potential benefit of long term LC screening beyond 5 years, notably its effect in 10-year overall and LC specific mortality.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The Multicenter Italian Lung Detection (MILD) trial prospectively enrolled 4,099 participants, randomized to either LDCT arm (n=2,376) or control arm (n=1,723); 38,561 person-years of follow-up were accumulated between 2005 and March 2017. The primary outcomes were 10-year overall and LC specific mortality. Moreover, a Landmark Analysis was used to test the long-term effect of LCS, beyond 5 years (notably by selective exclusion of events that occurred < 5 years). Cumulative mortality were evaluated using Kaplan-Meier estimator and differences among groups were tested using Log-rank test, adjusted for sex, age and pack-years. The prognostic value of assigned arm in predicting mortality was investigated by Cox’s proportional-hazard’s regression adjusted for the above variables.

      4c3880bb027f159e801041b1021e88e8 Result

      In the whole 10-year LCS, LDCT arm showed a protective non-statistically significant trend for reduction of overall mortality (HR: 0.82, 95% CI 0.63 to 1.07) and a significant 41% reduced risk of LC mortality (HR 0.59, 95% CI 0.38 to 0.92), compared to the control arm.

      Beyond the 5th year of screening, LDCT arm showed a significant 29% reduction of overall mortality (HR: 0.71, 95% CI 0.50 to 0.99), and a significant 62% reduced risk of LC mortality (HR 0.38, 95% CI 0.20 to 0.74) (Figure 1).

      figure1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Prolonged LDCT screening beyond 5 years reduces overall mortality, and it is most beneficial in further reduction of LC specific mortality.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.04 - Discussant - MA 03.01, MA 03.02, MA 03.03 (ID 14578)

      10:45 - 11:00  |  Presenting Author(s): Denise Aberle

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA03.05 - New Subsolid Pulmonary Nodules in Lung Cancer Screening: The NELSON Trial (ID 11998)

      11:00 - 11:05  |  Presenting Author(s): Marjolein A Heuvelmans  |  Author(s): Joan E Walter, Uraujh Yousaf-Khan, Monique Dorrius, Erik Thunnissen, Anna Schermann, Harry J.M. Groen, Carlijn M. Van Der Aalst, Kristiaan Nackaerts, Rozemarijn Vliegenthart, Harry J De Koning, Matthijs Oudkerk

      • Abstract
      • Presentation
      • Slides

      Background

      A central challenge in low-dose computed tomography (LDCT) lung cancer screening is the identification of clinically relevant lung cancer, while preventing overdiagnosis and overtreatment. Subsolid nodules are particularly challenging as they carry a relatively high malignancy rate but possess a slow growth rate. Current guidelines propose a watchful waiting approach with CT surveillance. While new solid nodules after baseline screening have a high lung cancer probability at small size and require lower size cutoff values than baseline nodules, there only is limited evidence on management of new subsolid nodules. Aim of this study was to assess the occurrence and lung cancer frequency of new subsolid nodules and to determine whether a more aggressive follow-up approach is necessary for new subsolid nodules.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Within the Dutch-Belgian randomized controlled LDCT lung cancer screening trial (NELSON), 7557 participants underwent baseline screening between April 2004 and December 2006. Three incidence screening rounds took place 1 year, 3 years, and 5.5 years after baseline screening. Participants with new subsolid nodules detected after the baseline screening round were included. A nodule was classified as (pre-)malignancy when it was diagnosed as lung cancer during diagnostic workup including histologic assessment.

      4c3880bb027f159e801041b1021e88e8 Result

      In the three incidence screening rounds 60 new subsolid nodules not visible in retrospect (43 [72%] part-solid, 17 [28%] nonsolid) were detected in 51 participants (0.7% [51/7295] of participants with at least one incidence screening). Eventually, 6% (3/51) of participants with a new subsolid nodule was diagnosed with a (pre-)malignancy in such a nodule. The (pre-)malignancies were adenocarcinoma (in situ) and diagnostic work-up (referral 950, 364, and 366 days after first detection respectively) showed favorable staging (stage I). Overall, 65% (33/49) of subsolid nodules with follow-up screening were resolving.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Less than 1% of participants in LDCT lung cancer screening presents with a new subsolid nodule after baseline. Contrary to new solid nodules, new subsolid nodules do not require a more aggressive follow-up approach than baseline nodules.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.06 - Descriptive Epidemiology of Significant Incidental Findings in a Large Clinical Lung Cancer Screening Program (ID 12313)

      11:05 - 11:10  |  Presenting Author(s): Shawn M Regis  |  Author(s): Andrea Katalin Borondy Kitts, Andrea B McKee, Carla R Lamb, Kimberly R Christ, Jacob M Sands, Brady J McKee

      • Abstract
      • Presentation
      • Slides

      Background

      The identification and reporting of significant incidental (non-lung cancer) findings in CT lung screening (CTLS) has not been standardized, though there is an available modifier in the LungRADS structured reporting system to identify a scan as including a significant incidental finding. In this study, we describe the significant incidental findings and follow-up in a large, established clinical CTLS program.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed all of the clinically significant or potentially significant non-lung cancer findings, which we will refer to as significant incidental findings, for patients undergoing clinical CTLS in our program from January 2012 through December 2016 with follow-up through December 2017. Significant incidental findings were defined as any unexpected new and/or unknown non-lung cancer finding requiring clinical or imaging evaluation prior to the next CTLS exam. Given the high prevalence of coronary artery calcifications and emphysema in the CTLS population, these findings were not classified as signifi­cant incidentals. We describe the site of the incidental finding, the follow-up intervention, and the outcome. We also calculate the cancer detection rate for non-lung cancers.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 6482 scans performed during the study window, 286 (4.4%) reported a significant incidental finding. These findings were reported in 276 (9.4%) of the 2927 patients screened during that time. Nine patients had more than one CTLS exam with a significant incidental finding. The majority of incidental findings were found in the kidneys (18%), liver (14%), and thyroid (11%). There were 15 non-lung cancers diagnosed for a cancer detection rate of 5.4%. The most common intervention, 43%, involved additional imaging, while 26% had a follow-up phone call or consult with a physician. Biopsy was performed in 9.1% and 6.7% had surgery. Surveillance was recommended for 43.4% of the findings, medical intervention was required for 12.3% of non-cancer findings and 12.9% of findings required no additional follow-up. There were 25 (8.7%) significant incidental findings with unknown follow up and outcomes and 31 (10.8%) that resulted in not finding anything on follow-up to explain the finding seen on the CTLS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Only 4.4% of all scans in our CTLS program reported a significant incidental finding. Almost 70% of the 286 significant incidental findings identified conditions requiring medical treatment, surgical intervention, or surveillance. There was one non-lung cancer diagnosis for every 7.5 lung cancers diagnosed in our screening program.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.07 - Development and Validation of Deep Learning Model for Recognition of Histologic Subtype of Lung Adenocarcinoma from CT Images (ID 14412)

      11:10 - 11:15  |  Presenting Author(s): Yunlang She  |  Author(s): Jiajun Deng, Dong Xie, Chang Chen

      • Abstract
      • Presentation
      • Slides

      Background

      The clinical decision to either follow-up or resection from radiologic features for lung adenocarcinoma (atypical adenomatous hyperplasia [AAH], adenocarcinoma in situ [AIS], minimally invasive adenocarcinoma [MIA] and invasive adenocarcinoma [IA]) appearing as Sub-solid nodules (SSNs) is still challenge, and currently more relies on measures of diameter, solid component ratio. With the successful application of deep learning neuro-network (DLNN) for the classification of skin or common treatable blinding retinal diseases, we hypothesized that DLNN might help the histologic subtype classification of SSNs from CT images. The purpose of this study is to develop and validate a deep neuro-network model to classify AAH, AIS, MIA and IA or define a feasible classification for follow-up or treatment decision.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 869 patients with 1344 pathologic confirmed nodules (AAH: 75, AIS: 340, MIA:321, IA: 608) were enrolled into this study. Two 3D mixed-scale dense-connected convolutional neuro network models (3D MS-DenseNet) were developed for 2 classification tasks: 4-class (AAH, AIS, MIA, IA), 3-class (AAH, AIS/MIA, IA). Eighty percent of whole datasets were randomly selected for training set, while other 20% were used for testing set. The nodules were firstly selected using a bounding box in 3D Slicer, and then cropped into 128 x 128 x 128 matrix size as the input to MS-DenseNet, and the output layer from the network was a 4-node or 3-node softmax classifier. Confusion matrix were used for the performance evaluation of both models and the classification accuracy for each class were reported.

      4c3880bb027f159e801041b1021e88e8 Result

      The classification accuracy of AAH, AIS, MIA, IA in testing set were 0.75, 0.45, 0.52, 0.85 respectively by 4-class, suggesting that the differentiation between AIS and MIA from CT images by neuro-network is challenge. While in the 3-class classification task with purpose of decision supporting for treatment, the classification accuracy of AAH, AIS/MIA, IA were 0.70, 0.73, 0.88 in the same testing set.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The DLNN showed potential capability in differentiating AAH, IA from other adenocarcinoma subtypes, while failed to differentiate AIS and MIA. When combing AIS and MIA for reclassify adenocarcinoma subtypes from the perspective of treatment, the DLNN achieved reasonable performance, suggesting that DLNN might be useful in supporting clinical treatment decision whether to follow-up or take different resection for SSNs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.08 - Discussant - MA 03.05, MA 03.06, MA 03.07 (ID 14579)

      11:15 - 11:30  |  Presenting Author(s): Richard Booton

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA03.10 - Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer  (ID 11268)

      11:30 - 11:35  |  Presenting Author(s): Shamus R Carr  |  Author(s): Lisa A Cannon-Albright, Wallace Akerley

      • Abstract
      • Presentation
      • Slides

      Background

      Published risk estimates for diagnosis of lung cancer based on family history are typically focused on close relatives, rather than a more diverse or complete family history. This study provides relative risks (RR) for lung cancer based on comprehensive family history data obtained from a statewide Cancer Registry linked to a high quality genealogy data resource. Risk estimates presented avoid common recall, recruitment, ascertainment biases, and are based on an individual’s (proband’s) lung cancer family history constellation (pattern of lung cancer affected relatives).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A population-based genealogical resource linked to a statewide electronic SEER cancer registry estimated relative risk (RR) for lung cancer for an individual based upon their lung cancer family history. Family history data available for a proband included degree of relationship (first to third-degree), paternal or maternal family lung cancer history, number of lung cancer affected relatives and age at diagnosis of affected relatives. Over 1.3M probands probands with specific constellations of lung cancer were analyzed. To estimate RRs, the observed number of lung cancer cases among probands with a specific family history constellation was compared to the expected number using internal cohort-specific rates.

      4c3880bb027f159e801041b1021e88e8 Result

      5,048 lung cancer cases were identified. Significantly elevated RR was observed for any number of lung-cancer-affected relatives among first-, second-, or third-degree relatives. RRs for lung cancer were significantly elevated for each additional lung cancer first-degree relative (FDR) ranging from RR=2.57 (2.39, 2.76) for >= 1 FDR to RR=4.24 (1.56, 9.23) for ≥3 FDRs affected. In an absence of FDR family history, increased risk for lung cancer was significant for increasing numbers of affected second-degree relatives (SDR) ranging from 1.41 (1.30, 1.52) for ≥ 1 SDR to 4.76(1.55, 11.11) for ≥ 4 SDRs. This was also seen in the absense of FDRs and SDRs for affected third-degree relatives (TDR) ranging from 1.18 (1.11, 1.24) for ≥1 affected TDR to 1.55 (1.03, 2.24) for ≥ 4 affected TDRs. RRs were significantly increased with earlier age at diagnosis of a first degree relative, and equivalent risks for maternal compared to paternal history were observed.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study provides unbiased, population-based estimates of lung cancer risk based on a proband’s complete family history that can be 2-5+ times increased. Estimates of RR for lung cancer based on family history are arguably very relevant clinically. The constellation RR estimates presented could serve in individual decision making to direct resource utilization, and could be pivotal in decision making for screening, treatment, and post treatment surveillance.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.11 - Trained Dogs Can Identify Malignant Pulmonary Nodules in Exhaled Gas (ID 13056)

      11:35 - 11:40  |  Presenting Author(s): Angela Guirao  |  Author(s): Laureano Molins, Ingrid Ramon, Gemma Sunyer, Nuria Vinolas, Ramon Marrades, David Sanchez, Juan J. Fibla, Jorge Hernandez, Marc Boada, Rudith Guzman, Alejandra Libreros, Alvaro Agusti

      • Abstract
      • Presentation
      • Slides

      Background

      After our recent report that trained dogs can identify the presence of lung cancer (LC) in exhaled air samples of patients with and without large LC(1), we designed a prospective controlled study to investigate if such trained dog can also discriminate between the exhaled gas samples of individuals with and without malignant pulmonary nodules.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We collected samples of exhaled air from 30 patients with indeterminate pulmonary nodules before the diagnostic and therapeutic surgery, and from 77 individuals without LC and without pulmonary nodules. Exclusion criteria were other neoplasm, and chemotherapy treatment. Participants refrained to eat, drink and smoke 30 minutes before they exhaled inside a crystal tube filled with hidrophilic and hidrophovic wool and closed with silicon taps, as we used in our previous report. Likewise, the training method of the dog was also based on a progressive prize-dependent learning method. Tubes containing the samples were introduced in wood boxes with an open side to enable the smelling of the sample. The dog was confronted to samples with and without pulmonary nodules in a proportion of 1/4 in order to discriminate malignant ones.

      4c3880bb027f159e801041b1021e88e8 Result

      The dog was confronted with 90 samples with indeterminate pulmonary nodules (3 per patient) and 372 samples without pulmonary nodules and without LC. The dog was confronted 10 times to each sample of pulmonary nodules with different combinations of “no LC” exhaled gas samples, which represents a total of 900 attempts. The dog must mark the samples he identifies as malignant ones. He achieved successful results with a sensitivity of 0,97, a specificity of 0,99, a PPV of 0,97 and a PNV of 0,99. Out of 30 patients with indeterminate pulmonary nodules the dog recognized 27 of them as positive for LC and 3 as negative for LC. Those results matched with the anatomical pathology surgery report.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Trained dogs can discriminate the presence of malignant pulmonary nodules from exhaled gas samples with an extraordinarily high degree of reliability.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.12 - Discussant - MA 03.10, MA 03.11 (ID 14580)

      11:40 - 11:55  |  Presenting Author(s): Luis M Montuenga

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA06 - PDL1, TMB and DNA Repair (ID 903)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 12
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 206 AC
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      MA06.01 - The Intrinsic PD-L1 Promotes Cellular Invasiveness Via their PD-1 Receptor in Lung Adenocarcinoma Cells (ID 13356)

      13:30 - 13:35  |  Presenting Author(s): Wen-Pin Su  |  Author(s): Hung-Chang Wu, Shuen-Ru Yang, Jheng-Cheng Huang, Jing-Jou Yan, Wan-Chen Kao, Li-Chan Chang, Wu-Chou Su

      • Abstract
      • Presentation
      • Slides

      Background

      Lung cancer is the most frequent cause of cancer death. Programmed death 1 (PD-1) in T cells and its ligand PD-L1 in tumor cells play a key role in immune checkpoint therapy and had applied to advanced stage lung cancer. Migration and invasion of tumor cells is a prerequisite for tumor cell metastasis. Since intrinsic PD-1 receptor functions promote tumor growth was reported, we will investigate the interaction between PD-1 and PD-L1 in lung adenocarcinoma cell lines, the impact on chemosensitivity, and clinical outcome.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In vitro experiments, lung adenocarcinoma CL1-5 cells, derived from CL1-0 cells. We prepared PD-L1-overexpression human lung adenocarcinoma cell line, derived from CL1-0 cells (CL1-0-PD1). Migration and invasion ability were assessed by transwell assay; EMT marker and regulator were evaluated by Western blotting. We also observed the morphology of cells. To explore interaction between PD1 and PD-L1, we added anti-PD-1 antibody into CL1-0, CL1-5, and CL1-0-PDL1 cells, and then test migration, invasion and cellular morphology. We also suppressed PD-1 by siRNA to test whether PD-1/PDL-1 interaction contributed to the EMT change. Further, we evaluated cellular proliferation and chemosensitivity by MTT assay and colony formation assay. We will correlate PD-L1 expression in lung cancer cells with clinical outcome by IHC stain clinically.

      4c3880bb027f159e801041b1021e88e8 Result

      In CL1-5 cells, derived from CL1-0 cells, with high PD-L1 expression possessed higher cellular migration ability than the parental CL1-0 cells with less PD-L1 expression. CL1-0 cells with PD-L1 overexpression had more expression of EMT (epithelial mesenchymal transition) regulator and mesenchymal marker. We also observed that CL1-5 and CL1-0-PDL1, which had more PD-L1 expression, are shaped like spindles; while CL1-0 cells are more rounded. Therefore, PD-L1 up-regulated cell migration and invasiveness in human lung adenocarcinoma cells and promotes EMT.

      After adding anti-PD1 antibody in CL1-5, CL1-0, and CL1-0-PDL1 cells, migration and invasion ability decreased. These result indicated anti-PD-1 antibody block the link between PD-1 and PD-L1 in cancer cells. The phenomenon was confirmed by PD-1 siRNA. Therefore, PD-1/PD-L1 axis regulated cancer cells migration and invasiveness. PD-L1 expression also decreased cellular proliferation and had little influence on chemsensitivity. Finally, we found that higher PD-L1 expression was correlated with lymph node metastasis in clinical specimen.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lung adenocarcinoma cells with higher PD-L1 expression promote cell migration, invasiveness, EMT, and little chemoresistance. PD-L1 expression lowers proliferation rate. PD-1 and PD-L1 interaction on lung adenocarcinoma cells contribute cellular migration and invasiveness.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Information from this presentation has been removed upon request of the author.

      Information from this presentation has been removed upon request of the author.

      • Abstract
      • Presentation
      • Slides

      Background

      Our previous work has demonstrated that higher level of genomic complexity is associated with more heterogeneous neoantigen repertoire, suppressed T cell repertoire and postsurgical relapse in localized non-small cell lung cancers (NSCLC) highlighting the complex interaction of tumor molecular and immune landscape and their impact on cancer biology and patient survival. We launched the ICON Project (Immune Genomic Profiling of NSCLC) to prospectively delineate the molecular and immune landscape of early stage NSCLC and their impact on patient survival through a multidisciplinary approach. Here we report the updated genomic and immune analyses.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Surgical specimens from stage I-III NSCLC were subjected to whole-exome and RNA sequencing for mutational analysis, in silico neoantigen prediction and gene expression analysis as well as T cell receptor sequencing, cytometry by time-of-flight and multiplex immunofluorescence staining.

      4c3880bb027f159e801041b1021e88e8 Result

      From 2016-2018, 127 patients were accrued and 50 surgical samples have undergone WES, RNAseq, TCR sequencing and immune phenotyping. Median age is 66 yrs (range: 39-86), 52% (26/50) were female and 76% (38/50) former smokers. 76% (38/50) are non-squamous carcinomas and 24% (12/50) squamous cell carcinomas. 34% have stage I disease (17/50), 30% stage II (15/50), 34% stage III (17/50) and 2% stage IV (1/50). The majority of patients had upfront surgery (45/50; 90%). With median follow-up of 19 months, 15 patients have relapsed. Median tumor mutational burden is 7.8mut/Mb and predicted neoantigen burden was 10/sample (range: 0-250). Predicted neoantigen burden is significantly correlated with tumor mutational burden (r=0.41, p=0.002). The most commonly mutated genes are TP53, KRAS, CDKN2A, PIK3CA, EGFR, BRAF, GRIN2A and ATM. C->A transversions and C->T transitions were the most common mutational subtypes. PD-1 expression and regulatory T-cell (CD4+/FoxP3+) infiltration are significantly increased in tumor tissue compared to normal tissue (p=0.003 and p=0.02 respectively), while CD3, CD8, granzyme B and CD45RO are decreased in tumor tissue compared to normal lung.

      8eea62084ca7e541d918e823422bd82e Conclusion

      NSCLC tumors have an immunosuppressive microenvironment compared to tumor adjacent normal lung tissues. Clinical data will be adequate to conduct genomic and immune profiling comparisons across different clinical subgroups. Mutational and neoantigen profiling are consistent with previously reported studies and correlations between molecular and immune landscapes and its impact on patient survival are ongoing.

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      MA06.03 - PD-1 and Id-1 Combined Blockade Impacts Tumor Growth and Survival Through PD-L1 Expression and Tumor Infiltration by Immune-Related Cells  (ID 14033)

      13:40 - 13:45  |  Presenting Author(s): Ignacio Gil-Bazo  |  Author(s): Iosune Baraibar, Marta Roman Moreno, Ines Lopez, Jesus Corral, Juan Jose Lasarte, Alfonso Calvo, Silve Vicent, Daniel Ajona

      • Abstract
      • Presentation
      • Slides

      Background

      PD-1/PDL-1 inhibitors are approved in advanced non-small cell lung cancer (NSCLC). Long-term survival rates associated to PD-1/PDL-1 blockade have changed treatment paradigm. However, many patients do not benefit from PD-1/PDL-1 blockade. New therapeutic combinations are under investigation. Id1 is involved in proliferation, angiogenesis and immunosuppression. We described Id1 as an independent prognostic factor in NSCLC (Ponz-Sarvise, Clin Cancer Res 2011) and more recently showed Id1’s role in lung cancer metastasis (Castanon, Cancer Letters 2017). Here we test a combined therapeutic strategy targeting PD-1 and Id1 in a murine lung cancer model.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Three in vivo studies evaluated the impact of Id1 inhibition in tumor cells, tumor microenvironment and in both, on tumor volumes and mice survival. A syngeneic tumor model using C57BL/6 and Id1-/- Id3+/- mice was created by subcutaneous injection of Lewis Lung Carcinoma (3LL) cells and Id1 silenced 3LL (Id1Sh) cells. After injection, mice were treated with an anti-PD-1 (RMP-1-14) monoclonal antibody or PBS. Tumor volumes according to mice strain, Id1 status in tumor cells and treatment were quantified. Mice's survival was calculated in those groups. Tumor CD8+ and CD3+ TILs and CD68+ cells were quantified by specific immunostainings.

      4c3880bb027f159e801041b1021e88e8 Result

      Id1 inhibition in the tumor environment and the injected tumor cells, combined with anti-PD-1 treatment, induced a significant tumor growth impairment (p < 0.0001) and increased survival (p = 0.0051). CD3+ and CD8+ TILs and tumor CD68 + cells were significantly higher in tumors from mice with the combined Id1-PD-1 blockade treated with the anti-PD-1 inhibitor compared to control animals suggesting that tumor increased immune-related cells infiltration exerts the effector phase of the antitumor immune response. Additionally, PD-L1 expression seemed to be higher when Id1 expression was absent in the immune microenvironment (p = 0.04). Additional data based on multiplexed immunohistochemistry results will be presented at the meeting.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Id1 and PD-1 combined blockade in our syngeneic murine lung cancer model significantly impaired tumor growth and increased survival. Increased tumor PD-L1 expression and CD3+ and CD8+ TILs and CD68+ cells may explain these findings.

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      MA06.04 - Discussant - MA 06.01, MA 06.02, MA 06.03 (ID 14593)

      13:45 - 14:00  |  Presenting Author(s): Akihiko Yoshida

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA06.05 - The Micro-Environmental Cross Talk Between Mast Cells and Lung Cancer Cells Through Cell-to-Cell Contact (ID 11140)

      14:00 - 14:05  |  Presenting Author(s): Rachel Shemesh  |  Author(s): Yaara Gorzalczany, Smadar Geva, Laila C. Roisman, Ronit Sagi-Eisenberg, Nir Peled

      • Abstract
      • Presentation
      • Slides

      Background

      Mast cells (MCs) are key effectors in allergic reactions, but are also involved in tissue remodeling, wound healing and protection against pathogens. MCs infiltrate tumors and their number within the tumor microenvironment in certain cancer types, such as lung cancer, have been correlated with poor prognosis. The nature of crosstalk between lung cancer and MCs remain poorly resolved. In this study, we investigated the activation patterns within the MCs following cell-to-cell contact with lung cancer cells showing CD73 involvement and implying metabolic changes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Human MCs (HMC-1 and LAD-2) were exposed to Human lung cancer cells (H1299), derived membranes to recapitulate cell contact mediated activation. Lysates of MCs were tested for protein expression and posttranslational modifications (i.e. phosphorylation) by targeted western blotting. We unraveled the intracellular signaling molecules that are necessary for this signaling pathway by a pharmacological approach using several inhibitors. Each condition was repeated at least twice.

      4c3880bb027f159e801041b1021e88e8 Result

      H1299 membrane exposure activated the ERK 1/2 MAP kinases in HMC-1 and in LAD-2 cells. AKT signaling was also activated in LAD-2 cells as a result of this contact. CD73 dephosphorylates AMP to adenosine within the MCs. Interestingly enough, this ERK 1/2 activation was inhibited by CD73 inhibitor and A3 receptor antagonists in HMC-1 cells. ERK 1/2 activation was inhibited by A3 receptor antagonists and PI3K in LAD-2 cells. Furthermore, we discovered that protein kinase C (PKC) inhibitor augments the activation of ERK 1/2 in LAD-2 cells. In contrast, PKC inhibitor inhibits the activation of ERK 1/2 in HMC-1 cells. In addition, we discovered that the AKT activation was inhibited by A3 receptor and PI3K inhibitors but not by CD 73 inhibitors.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggest that H1299 membranes activate ERK 1/2 in HMC-1 cells by a mechanism that involves autocrine formation of adenosine and is mediated by CD 73 and A3 receptor. In addition, we discovered that there is an important difference between the ERK 1/2 MAP kinase signal transduction in HMC-1 and LAD-2 cells, PKC is an inhibitor of the H1299 activation of ERK 1/2 in LAD-2 cells. In contrast, the H1299 membrane activation of ERK 1/2 kinase in HMC-1 cells is mediated by PKC. Furthermore, we can conclude that H1299 membranes activate AKT in an A3 receptor dependent mechanism that is mediated by PI3K.

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      MA06.06 - An Ex-Vivo Patient-Derived, Immunocompetent (PDI) Culture System to Evaluate Immunotherapeutic Agents’ Anti-Tumor Efficacy (ID 14299)

      14:05 - 14:10  |  Presenting Author(s): Zachary E. Tano  |  Author(s): Stefan Kiesgen, Navin Chintala, Jordan Dozier, John Messinger, Kay See Tan, Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Background

      Anti-tumor efficacy of human immunotherapeutic agents, such as antibodies, chimeric antigen receptor (CAR) and T-cell receptor transduced T cells, are currently being investigated in immunodeficient mice prior to clinical translation. We developed and optimized an ex-vivo culture system utilizing malignant pleural effusions (MPEs) to compliment these investigations in a human, immunocompetent, tumor-like environment. We hypothesized that CAR T cells’ cytotoxicity will vary by the different immune compositions in each MPE, which are conditions unavailable in current efficacy assays.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Mesothelin-targeted CAR T cells from multiple donors were exposed to MPEs derived from non-small cell lung cancer patients (n=15) and RPMI culture medium. Influence of the MPEs on CAR T-cell efficacy was evaluated by viability and phenotype (flow cytometry), cytotoxicity (chromium release assay), and gene expression (NanoString). Group-based trajectory modeling was used to stratify the inhibitory effect of MPEs. MPE composition (ELISA and Luminex assays) was evaluated to interpret its influence on CAR T cells.

      4c3880bb027f159e801041b1021e88e8 Result

      With the incorporation of our optimized protocols, T cells retain their viability, phenotype (CD4/CD8), and percentage of CAR expression when cultured in MPEs. MPE soluble factor levels remained stable over multiple freeze/thaw cycles. CAR T cells co-cultured in MPE exhibited variable antigen-specific cytotoxicity (Fig. A). MPE-induced T-cell inhibition was stratified into groups of strong, mild, or no inhibition. (Fig. B). Compared to MPEs with either mild or no inhibition, MPEs with strong inhibition had significantly higher levels of TGFβ-2 (average TGFβ-2 level in strong vs. mild inhibition: 402 vs. 50 pg/mL, p<0.05) (Fig. C), IL-6, RANTES, and IL-5.

      pdi culture system.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      We present the first human immunocompetent culture system that can be used to evaluate immunotherapeutic agents’ efficacy prior to their clinical translation. Furthermore, analyses of the culture system’s soluble factors sheds light on their relative influence on T-cell efficacy.

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      MA06.07 - Genetic and Epigenetic Alterations are Associated with Tumor Mutation Burden in Non-Small Cell Lung Cancer (ID 12822)

      14:10 - 14:15  |  Presenting Author(s): Liang-Liang Cai  |  Author(s): Hua Bai, Zhi-Jie Wang, Shuhang Wang, Jian-Chun Duan, Shu-Geng Gao, Jie He, Jie Wang

      • Abstract
      • Presentation
      • Slides

      Background

      Although several studies have indicated that tumor mutation burden (TMB) is associated with non-small cell lung cancer (NSCLC) development and clinical efficacy of immune checkpoint inhibitors (CPIs), identification of factors associated with TMB is still a major biological issue. It is well-known that DNA transcription can be regulated through methylation and demethylation, gene silencing caused by DNA hypermethylation is associated with cancer development. However, the relationship between DNA methylation and TMB in NSCLCs remains unclear.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The landscape of DNA sequence in Chinese NSCLCs population were surveyed by using whole-exome sequencing (WES) by profiling 178 lung tissues (89 without any systemic anti-cancer therapy tumors and matched normal lung tissues). According to the 104 median-level of TMB in our cohort, high TMB (n=16, 252-465 range mutations per tumor) and low TMB (n=13, 57-79 range mutations per tumor) groups were divded. The NSCLC methylome between high and low TMB was characterized on a genome-wide scale using Illumina Infinium MethylationEPIC arrays combined with the WES data.

      4c3880bb027f159e801041b1021e88e8 Result

      The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures in high TMB lung cancer. Combining with clinical data, cigarette smoking associated with high TMB were observed in our cohort. Cancer-specific epigenetic alterations were observed in 294,141 CpG sites, comprising both tumor hyper- (769,38) and hypo- (217,203) methylation in high TMB lung cancer while none in low. These different methylations sites cover 1232 genes including 25 HOX genes.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Global DNA hypomethylation and TP53 mutation, associated with increased chromosomal instability, were associated with TMB in NSCLCs.The high TMB NSCLCs are characterized by numerous copy number alterations and aberrantly methylated sites and display distinct mutational signatures. 25 hypermethylated HOX genes can be potentially useful as DNA methylation markers for prediction of TMB level. The results provide insights into the epigenetic impact of TMB, which may contribute to improve precison management of NSCLCs.

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      MA06.08 - Discussant - MA 06.05, MA 06.06, MA 06.07 (ID 14594)

      14:15 - 14:30  |  Presenting Author(s): Jyoti Patel

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA06.09 - XRCC6BP1: A DNA Repair Gene in Cisplatin Resistant Lung Cancer Stem Cells That May Predict Survival Outcomes in Patients (ID 14024)

      14:30 - 14:35  |  Presenting Author(s): Martin P Barr  |  Author(s): Robert Farrell, Saravjeet Singh, Emma Foley, Yuexi He, Lauren Brady, Vincent Young, Ronan Ryan, Siobhan Nicholson, Niamh Leonard, Sinead Cuffe, Stephen Finn

      • Abstract
      • Presentation
      • Slides

      Background

      Alterations in the DNA repair capacity of damaged cells is now recognised as an important factor in mediating resistance to chemotherapeutic agents.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      DNA Repair Pathway RT2 Profiler Arrays were used to elucidate key DNA repair genes implicated in chemoresistant NSCLC cells using cisplatin resistant (CisR) and corresponding parental (PT) H460 cells. DNA repair genes significantly altered in CisR cells were validated at the mRNA and protein level. The translational relevance of differentially expressed genes was examined in a cohort of chemo-naïve matched normal and tumour lung tissues from NSCLC patients. Loss of function studies were carried out using siRNA technology. The effect of XRCC6BP1 gene knockdown on apoptosis was assessed by FACS. Cellular expression and localisation of XRCC6BP1 protein and γH2AX foci in response to cisplatin were examined by immunofluorescence (Cytell™). To investigate a role for XRCC6BP1 in lung cancer stem cells, Side Population (SP) studies were used to characterise stem-like subpopulations within chemoresistant cells. XRCC6BP1 mRNA analysis was also examined in ALDH1+ and ALDH1- subpopulations. Immunohistochemistry analysis was carried out in resected lung tumour tissues and XRCC6BP1 expression was correlated with survival in addition to a number of clinicopathological parameters such as tumour stage & grade, gender, smoking status and chemotherapy.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified a number of critical DNA repair genes that are differentially regulated between PT and CisR NSCLC cells. XRCC6BP1 mRNA and protein expression was significantly increased H460 CisR cells relative to their PT counterparts. Relative to matched normal lung tissues, XRCC6BP1 mRNA was significantly increased in lung adenocarcinoma patients. Gene silencing of XRCC6BP1 induced significant apoptosis of chemoresistant cells and reduced their DNA repair capacity. Immunofluorescence studies showed an increase in XRCC6BP1 protein expression and gH2AX foci in CisR cells. SP analysis revealed a significantly higher stem cell population in resistant cells, while XRCC6BP1 mRNA expression was considerably increased in SKMES-1, H460 and H1299 CisR cells positive for ALDH1 activity (ALDH1+) compared to ALDH1- cells. IHC scoring of XRCC6BP1 demonstrated poor survival outcomes for NSCLC patients with high expression of this DNA repair gene.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data highlight the potential of targeting components of the DNA repair pathway, in particular XRCC6BP1, in chemoresistant lung cancer. Furthermore, XRCC6BP1 may play an important role in subsets of lung cancer stem cells which, at least in part, may be responsible for driving and maintaining the cisplatin resistant phenotype in NSCLC.

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      MA06.10 - Germline Mutation in ATM Affect Lung Cancer Risk with High Effect (ID 12792)

      14:35 - 14:40  |  Presenting Author(s): Xuemei Ji  |  Author(s): Dakai Zhu, Claudio Pikielny, Olga Gorlova, Maria Teresa Landi, John Kirkpatrick Field, Paul Brennan, Mattias Johansson, Rayjean J. Hung, James D McKay, Christopher Ian Amos

      • Abstract
      • Presentation
      • Slides

      Background

      Genome wide association studies have identified several lung cancer susceptibility regions and common variants influencing lung cancer risk. However, few previous studies investigated the association between germline mutations and lung cancer risk.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We analyzed data from a case-control study with 19053 lung cancer cases and 15446 healthy controls of European ancestry in a discovery phase and performed a validation analysis using a case-control study comprising 4261 lung cancer cases and 4152 healthy controls of European ancestry for replication. Logistic regression was used to identify germline mutations with high effect within exome regions associated with lung cancer risk.

      4c3880bb027f159e801041b1021e88e8 Result

      We found rs56009889 in ATM was statistically associated with lung cancer risk in the discovery set (OR = 3.05, P = 3.68 × 10−8) and was nonsignificantly associated with lung cancer risk in the validation set (OR = 1.83, P = 0.16). Stratified analyses by gender with adjustment for age and smoking status showed that females carrying at least one mutated allele of rs56009889 (T/C + T/T) had an increased risk of lung cancer with ORs being 7.77 (95% CI 3.45 - 17.47) in discovery and 6.73 (95% CI 1.46–30.98) in replication, compared to C/C homozygotes among females. Individuals carrying at least one T allele showed a significant 6.9-fold increased risk for lung adenocarcinoma in discovery (adjusted OR = 6.85; 95% CI 4.37 – 10.75) and approximately a 4.9-fold increased risk in replication (adjusted OR = 4.89; 95% CI 2.01 – 11.91). Never smokers with combined genotypes (T/C + T/T) had a greater than 8-fold increased risk of lung cancer in discovery (adjusted OR = 8.03, 95% CI 4.00 – 16.13), while smokers only showed a 2.13-fold increased risk (adjusted OR = 2.13, 95% CI 1.25 – 3.65). In replication, however, the risks from this variant were comparable between smokers and nonsmokers, although the sample size is small for nonsmokers (adjusted OR = 2.16; 95% CI 0.48 – 9.79 for never-smokers and adjusted OR = 2.07; 95% CI 0.66 – 6.52 for smokers). All the T/T homozygotes of rs56009889 developed lung adenocarcinoma in discovery (P = 0.036). The association exhibited a dose-response relationship between the number of T allele of rs56009889 and lung cancer risk in discovery (Ptrend = 1.07 x 10 -9).

      8eea62084ca7e541d918e823422bd82e Conclusion

      rs56009889 highly affected the risk of lung cancer, mainly of lung adenocarcinoma, primarily in women and never smokers. These germline mutations provide important insights for the prevention of lung cancer.

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      MA06.11 - Distinct Origins of Lymphatic and Brain Metastasis in Lung Cancer (ID 13333)

      14:40 - 14:45  |  Presenting Author(s): Tao Jiang  |  Author(s): Yan Yan, Caicun Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      Generally, distant metastases are seeded by lymph node metastases in most solid tumors. This concept provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. However, a recent study found that lymphatic and distant metastases could arise from independent subclones in the primary colorectal cancer. The current study aimed to investigate the origins of lymphatic and brain metastasis in lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      39 samples from twelve patients with primary lung cancer and brain metastases were identified. Three of them had the matched lymph node metastases. All tissues and matched peripheral blood samples were collected before any systemic treatment. Whole-exome (>150×) sequencing were conducted on these samples.

      4c3880bb027f159e801041b1021e88e8 Result

      Compared to the primary lesions, both brain and lymph node metastases had the significantly different patterns of somatic genome alterations. The mutational landscape of brain metastases was also distinctly different from matched lymph node metastases. Primary lesions, matched brain and lymph node metastases showed the similar mutation pattern in terms of transition and transversion, and all of samples displayed a higher percentage of C>T transition. Brain metastases had numerically higher tumor mutational burden (TMB) than primary lesions but it did not reach the statistical significance. Notably, we observed the totally distinct origins of lymphatic and brain metastasis in all three matched cases.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The current evidence suggested that brain metastases and matched lymph node metastases had different mutational landscape in patients with lung cancer. Brain metastases had higher TMB than their primary lesions. Lymphatic and brain metastasis had distinct origins in lung cancer. These results had profound clinical implications for application of immunotherapy and improvement of prognosis in patients with lung cancer and brain metastases.

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      MA06.12 - Discussant - MA 06.09, MA 06.10, MA 06.11 (ID 14595)

      14:45 - 15:00  |  Presenting Author(s): Rebecca Heist

      • Abstract
      • Presentation
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      Abstract not provided

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    MA13 - Interventional Pulmonology (ID 914)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 12
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 206 AC
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      MA13.01 - CT-Guided Transthoracic Needle Biopsy for Evaluation of PD-L1 Expression: Comparison of 22C3 and SP263 Assays (ID 11312)

      10:30 - 10:35  |  Presenting Author(s): Kyongmin Sarah Beck  |  Author(s): Kyo Young Lee, Su Jin Hong

      • Abstract
      • Presentation
      • Slides

      Background

      Although there are a few studies about concordance of different assays testing PD-L1 expression using surgical specimens, there hasn’t been any such concordance study using real-world biopsy specimens. However, many of the patients requiring immunotherapy and thus PD-L1 testing have unresectable lung cancer and have to rely on small biopsy results. Although phase 2 of Blueprint phase 2 does include core biopsy specimens, they are mixed with bronchial biopsy specimens and the absolute number is very small (n=20). We sought to evaluate the concordance of 22C3 and SP263 assays in a larger number CT-guided transthoracic needle biopsy (TNB) specimens.

      The purpose of this study was to assess the concordance of two commercially available diagnostic assays (22C3 and SP263) in evaluating programmed cell death ligand-1 (PD-L1) expression using specimens from CT-guided TNB in a routine clinical setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This retrospective analysis reviewed 202 non-small cell lung cancer (NSCLC) patients who underwent CT-guided TNB at our institution from April 2017 to February 2018. Among these, biopsy specimens tested with both 22C3 and SP263 assays were included for review. Concordance of PD-L1 expression levels determined by the two assays was assessed using intraclass correlation coefficient, and the agreement of dichotomized values at various cut-offs (1%, 25%, and 50%) were assessed using Cohen’s κ coefficient of agreement. Clinical characteristics and biopsy-related factors were also assessed for the association of concordance of PD-L1 expression detected by different assays

      4c3880bb027f159e801041b1021e88e8 Result

      In total, 80 patients (M:F =47:33, mean age: 68.0 years) were included in the study. Concordance of PD-L1 expression levels was high (intraclass coefficient: 0.892) between 22C3 and SP263 assays. Agreements at cut-off levels of 1%, 25%, and 50% were also good, with κ values of 0.878, 0.698, and 0.790 respectively. Positive percent agreement was 93.2%, 100.0%, and 95.2% for agreements at 1%, 25%, and 50%. At multivariate analysis, the presence of emphysema was significantly related to discordant PD-L1 results (odds ratio: 0.059, p= 0.005).

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is a high concordance of PD-L1 expression evaluated with 22C3 and SP263 assays using CT-guided TNB specimens.

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      MA13.02 - PD-L1 Expression in EBUS-Guided Cytology Specimens of Non-Small Cell Lung Cancer is Not Affected by Type of Fixation: A Study of Matched Pairs (ID 11867)

      10:35 - 10:40  |  Presenting Author(s): Alexander Haragan  |  Author(s): John Roy Gosney, Claire Chadwick, Tom Giles, Seamus Grundy, Victoria Tippett, Krishna Gumparthy, Andrew Wight, Hock Tan

      • Abstract
      • Presentation
      • Slides

      Background

      No previous trials of immune modulators (IMs) to treat non-small cell lung cancer (NSCLC) have included ‘cytology’ specimens, dispersed cells aspirated from a tumour deposit or body cavity, for immunochemical assessment of PD-L1, a useful complementary or compulsory companion diagnostic test. This has led to the widely-held view that, in the absence of such ‘validation’, cytology specimens cannot be used to assess it. In many centres, endobronchial ultrasound (EBUS)-guided aspiration of the tumour or intra-thoracic lymph nodes is the preferred means of diagnosis and staging of NSCLC and such specimens account for the majority received for analysis. Failure to asses them has serious implications for appropriate management and might deny patients effective therapy. Much of this reluctance centres on the alleged effect of fixation in alcohol-based fixatives, the preferred method of cytopathologists, rather than formalin, the standard fixation medium for tissue specimens, on the expression of PD-L1 on the cell surface.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We compared expression of PD-L1 in 50 paired specimens of NSCLC, one fixed in an alcohol-based fixative and one in neutral-buffered formalin, taken from the same tumour deposit or lymph node during the same procedure. All were spun down and formed into a cell block before assessment for PD-L1 expression, which was by two appropriately-trained pathologists with extensive experience in its interpretation.

      4c3880bb027f159e801041b1021e88e8 Result

      In none of the 50 pairs studied was there any significant difference, qualitative or quantitative, in the pattern or extent of PD-L1 expression and, in the great majority, it was identical irrespective of fixation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is no evidence from this study that the use of alcohol-based fixatives has any effect on the expression of PD-L1 or its interpretation. Notwithstanding the general challenges in accurately assessing such expression, which are common to specimens of tissue as well as dispersed cells, pathologists should feel able to interpret cytology specimens with confidence and clinicians able to rely on the results.

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      MA13.03 - Heterogeneity Analysis of EBUS-TBNA-Derived Specimens for Evaluation of PD-L1 Expression and Copy Number Alterations in Patients with NSCLC (ID 12664)

      10:40 - 10:45  |  Presenting Author(s): Katsuhiro Yoshimura  |  Author(s): Yusuke Inoue, Kazuo Tsuchiya, Masato Karayama, Yuji Iwashita, Tomoaki Kahyo, Akikazu Kawase, Masayuki Tanahashi, Hiroshi Ogawa, Koshi Yokomura, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Hiroshi Niwa, Takafumi Suda, Haruhiko Sugimura

      • Abstract
      • Presentation
      • Slides

      Background

      Most patients with non-small cell lung cancer (NSCLC) are diagnosed at advanced stages and only small biopsy specimens are available for diagnosis in the majority of the patients. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful diagnostic modality and is becoming more relevant and essential procedure in the real-world clinical setting. However, it is poorly elucidated whether EBUS-TBNA-derived small specimens are suitable for evaluation of biomarkers such as PD-L1 alterations, because heterogeneity of PD-L1 expression limits the power as a guide to select patients who are likely to benefit from the PD-1/PD-L1 blockade therapy. In addition, PD-L1 copy number alterations (CNAs) have been proposed to potentially complement the predictive performance of PD-L1 expression. We here evaluated the utility of EBUS-TBNA-derived specimens in the assessment of PD-L1 protein and CNAs focusing on the heterogeneity with other biopsy/resected samples.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PD-L1 protein expression and CNAs in 71 EBUS-TBNA specimens of NSCLC were assessed. Corresponding 68 transbronchial biopsy (TBB) specimens, 13 resected primary tumors, and 6 resected metastases were comparatively analyzed. PD-L1 expression on tumor cells was assessed by immunohistochemistry (E1L3N). Positivity of ≥1% was used as the cut-off. PD-L1 CNAs were assessed with fluorescent in situ hybridization, and were classified into three categories: amplification, polysomy, and disomy. Concordance between EBUS-TBNA and other specimens were calculated.

      4c3880bb027f159e801041b1021e88e8 Result

      The median age was 68 years (38-90 years). The cohort comprised 48 men (67.6%), 15 never-smokers (21.1%), and 39 adenocarcinomas (54.9%). The concordance of PD-L1 positivity between EBUS and the other specimens was moderate; κ=0.63 for EBUS vs TBB, κ=0.68 for EBUS vs the resected primary tumors, and κ=1.00 for EBUS vs the resected metastases. The concordance of PD-L1 CNA statuses was comparable with that of PD-L1 expression: κ=0.60 for EBUS vs TBB, and κ=0.74 for EBUS vs the resected primary tumors. When the PD-L1 copy number was assessed as a continuous variable, the correlation was also good/moderate: ρ=0.60 for EBUS vs TBB specimens, ρ=0.56 for EBUS vs the resected primary tumors, and ρ=0.80 for EBUS vs the resected metastases. Intratumorally, PD-L1 expression was significantly heterogeneous in whole sections of resected tumors, but PD-L1 CNAs was less heterogeneous than protein expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      EBUS-TBNA-derived specimens can be used for the assessment of PD-L1 alterations including CNAs. The concordance of PD-L1 CNAs between EBUS-TBNA and TBB/resected specimens were comparable with that of PD-L1 expression. However, spatial heterogeneity should be taken into account to interpret both PD-L1 protein expression and CNAs.

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      MA13.04 - Discussant - MA 13.01, MA 13.02, MA 13.03 (ID 14629)

      10:45 - 11:00  |  Presenting Author(s): John Roy Gosney

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA13.05 - The Canada Lymph Node Sonographic Score: National Validation of a Sonographic Score to Determine Mediastinal Lymph Node Malignancy (ID 12084)

      11:00 - 11:05  |  Presenting Author(s): Danielle Alexandria Hylton  |  Author(s): Julie Huang, Simon Turner, Daniel French, Chuck Wen, James Masters, Biniam Kidane, Jonathan David Spicer, Jenelle Taylor, Christian Finley, Yaron Shargall, Christine Fahim, Forough Farrokhyar, Kazuhiro Yasufuku, John Agzarian, Waël C. Hanna

      • Abstract
      • Presentation
      • Slides

      Background

      At the time of endobronchial ultrasound (EBUS) staging for Non-Small Cell Lung Cancer (NSCLC), 6 ultrasonic criteria (Fig. 1) are used to assign a Lymph Node Sonographic Score (LNSS) that is predictive of malignancy. The LNSS has not gained widespread use due to lack of research demonstrating its validity and reliability among endoscopists. We hypothesized that LNSS correlates well with the probability of malignancy, potentially guiding decisions for lymph node (LN) biopsy.

      iaslc abstract lnss - figure 1_jpg.jpg

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a prospective study to assess the validity and reliability of the LNSS. The validation cohort comprised LN that were video-recorded from patients with NSCLC, and assigned a LNSS by an experienced endoscopist. Videos were then circulated to thoracic surgeons and interventional respirologists across Canada, who were asked to assign a score to each LN. All raters had demonstrated proficiency using our online education module, were blinded to staging information, and to each other. Each LN was scored by at least 3 independent raters. Pathological specimens were used as the gold standard for determination of malignancy. Regression, receiver operator curve (ROC), and Gwet’s AC1 analyses were used to test LNSS score performance, discriminatory capacity, and inter-rater reliability.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 300 LNs (18% malignant) from 140 patients were analyzed by 11 endoscopists across 7 Canadian centres. LNSS=0 was strongly predictive of benign LN (NPV= 95.69%, OR=49.2, p=0.001). LNSS ≤2.5 (OR=44, p=0.001) was determined as the cutoff for malignancy based on ROC analysis (c= 0.7757, 95%CI: 0.70281-0.84853). Inter-rater reliability for LNSS=0 was 0.8553 (95%CI:0.8158-0.8947, p=0.0001) and 0.46 for LNSS ≤2.5 (95%CI=0.3521-0.5012, p=0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The Canada LNSS shows excellent performance in identifying benign LN at the time of EBUS. A cutoff ≤2.5 has the potential to inform decision-making regarding biopsy or repeat biopsy/mediastinoscopy if the initial results are inconclusive. Further teaching and education are required to improve inter-rater reliability.

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      MA13.06 - Endosonography with Lymph Nodes Sampling for Restaging the Mediastinum in Lung Cancer: A Systematic Review and Pooled-Data Analysis (ID 11918)

      11:05 - 11:10  |  Presenting Author(s): Long Jiang  |  Author(s): Jun Liu, Wenlong Shao, Kassem Harris, Lonny Yarmus, Weizhe Huang, Jianxing He

      • Abstract
      • Presentation
      • Slides

      Background

      Mediastinal restaging after induction treatment is still a difficult and controversial issue. We aimed to investigate the diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for restaging the mediastinum after induction treatment in patients with lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Embase and PubMed databases were searched from conception to July 2017. Data from relevant studies were analyzed to assess sensitivity and specificity of EBUS-TBNA and EUS-FNA, and to fit the Hierarchical Summary Receiver-Operating Characteristic curves.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of nine studies consisting of 542 patients fulfilled the inclusion criteria. All patients were restaged by EBUS-TBNA, EUS-FNA or both. Negative results were confirmed by subsequent surgical approaches. There were no complications reported during any endosonography approaches reviewed. The pooled sensitivities of EBUS-TBNA and EUS-FNA were 66%(95% CI, 60%-72%) and 73%(95% CI, 52%-87%), respectively; and specificities were 100%(95% CI, 98%-100%) and 99%(95% CI, 90%-100%), respectively. The area under the HSROC curves(AUC) were 0.84(95% CI, 0.81-0.87) for EBUS-TBNA and 0.99(95% CI, 0.98-1) for EUS-FNA. Moreover, for patients who received chemotherapy alone, the pooled sensitivity of endosonography with lymph node sampling for restaging was 69% (95% CI, 63%-75%), and specificity was 100% (95% CI, 97%-100%); and for patients who received chemoradiotherapy, the results seemed similar with sensitivity of 65% (95% CI, 50%-78%) and specificity of 100% (95% CI, 96%-100%).

      Variables

      No. of patients

      Pooled sensitivity (95% CI)

      Pooled specificity (95% CI)

      Negative Likelihood Ratio

      AUC

      In all mediastinal stations

      Overall

      543

      0.70 (0.65-0.75)

      1.00 (0.98-1.00)

      0.30 (0.21-0.43)

      0.93 (0.91-0.95)

      EBUS-TBNA

      424

      0.66 (0.60-0.72)

      1.00 (0.98-1.00)

      0.38 (0.26-0.54)

      0.84 (0.81-0.87)

      EUS-FNA

      226

      0.73 (0.52-0.87)

      0.99 (0.90-1.00)

      0.27 (0.14-0.53)

      0.99 (0.90-1.00)

      Combine

      106

      0.67 (0.53–0.79)

      0.96 (0.86–0.99)

      N/A

      0.81 (0.73–0.87)

      Subgroup analysis

      Chemo alone

      365

      0.69 (0.63-0.75)

      1.00 (0.97-1.00)

      0.35 (0.26-0.48)

      0.90 (0.88-0.94)

      Chemo radiotherapy

      130

      0.65 (0.50-0.78)

      1.00 (0.96-1.00)

      0.25 (0.06-1.02)

      0.97 (0.95-0.98)

      If negative Likelihood Ratio(LR-) is smaller: essentially a definite diagnosis when negative result.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Endosonography with lymph node sampling is an accurate and safe technique for mediastinal restaging of lung cancer. For nondiagnostic results, a further more invasive approach should be thoroughly considered.

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      MA13.07 - Diagnostic Yield of N3 Hilar Staging by Endobronchial Ultrasonography (EBUS) in Lung Cancer (ID 12565)

      11:10 - 11:15  |  Presenting Author(s): Antoni Rosell  |  Author(s): Jaume Bordas Martinez, Jose Luis Vercher Conejero, Guillermo Rodriguez Gonzalez, Cristina Martin Cabeza, Noelia Cubero De Frutos, Rosa-Maria Lopez Lisbona, Marta Diez Ferrer, Paula Notta, Roger Llatjos Sanuy, Jordi Dorca Sargatal

      • Abstract
      • Presentation
      • Slides

      Background

      Systematic lung cancer staging with EBUS has proven to be equivalent to cervical mediastinoscopy. Nevertheless, in the daily practice it is common to explore and sample negative PET-CT hilar N3 lymph nodes (LN). This study aims to explore if there is enough evidence to support this clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective study from our database including 1,013 explorations over the last 5 years. Including criteria were patients with lung cancer staged by PET-CT and EBUS-TBNA. Mediastinal and hilar N3 LN with a short axis ≥ 5 mm were sampled with a 21G needle and assessed by rapid on site evaluation (ROSE). A single nuclear medicine expert reviewed blindly all PET-CT scans and determined the SUVmax of every LN. Those that were ≥ 5 SUVmax by PET-CT and/or ≥ 10mm in short axis by EBUS were considered abnormal.

      4c3880bb027f159e801041b1021e88e8 Result

      87 patients were included, of which 87% were male with a mean age of 66 years (SD 12.6). The final histopathology diagnoses were adenocarcinoma (46%), squamous cell carcinoma (39%) and other histology (14%). EBUS-TBNA was performed 30 days (SD 16.9) after PET-CT. None of the 61 normal hilar and normal mediastinum N3 LN, and none of the 7 normal N3 hilar LN with abnormal mediastinal LN (3 by PET-CT, 3 by EBUS and 1 for both) resulted positive for lung cancer. Of the 19 patients with abnormal N3 hilar LN (6 by PET-CT, 8 by EBUS and 6 for both) malignancy was found in 16.7% , 25% and 60% for both techniques, respectively.ryywawmo--450186-1-any.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      In absence of abnormal N3 hilar LN (PET: SUVmax<5; EBUS<10mm in short axis) it seems there is not enough evidence to sample them, regardless of N3 mediastinal status.

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      MA13.08 - Discussant - MA 13.05, MA 13.06, MA 13.07 (ID 14631)

      11:15 - 11:30  |  Presenting Author(s): Nicole Bouchard

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA13.09 - Electromagnetic Navigation Bronchoscopy as an Integrated Approach to Aid in Diagnosis and Treatment of Pulmonary Lesions (ID 12623)

      11:30 - 11:35  |  Presenting Author(s): Sandeep Khandhar  |  Author(s): Septimiu Murgu, Kyle Hogarth, William Krimsky, Javier Flandes, Otis Rickman, Momen Wahidi, Eric Sztejman, Philip Linden, Sadia Benzaquen, Sandeep Bansal, Erik Folch

      • Abstract
      • Presentation
      • Slides

      Background

      Electromagnetic navigation bronchoscopy (ENB) is an image-guided localization approach to guide endoscopic tools to lung targets. In a single procedure, ENB aids in localizing lung lesions for biopsy or molecular profiling, fiducial placement for stereotactic body radiation therapy (SBRT), or dye marking for surgical resection. The multidisciplinary utility of ENB in a large, prospective, multicenter study is unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      NAVIGATE (clinicaltrials.gov, NCT02410837) is a prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system. From April 2015 to August 2016, 1,215 consecutive subjects were enrolled at 29 United States sites. Two-year follow-up is ongoing. A prespecified 1-year interim analysis is presented.

      4c3880bb027f159e801041b1021e88e8 Result

      ENB was used to aid in lung lesion biopsy (n=1157 subjects), fiducial placement (n=258), pleural dye marking (n=23), and/or lymph node biopsy (n=30). EBUS-guided lymph node staging was conducted in the same procedure in 448 subjects. The median lesion-to-pleura distance was 9mm. The median lesion size was 20mm; most were in the middle (30%) and peripheral (67%) thirds of the lung. Pathology results were malignant in 44.3% (484/1092) (54.1% Stage I, 11.1% Stage II, 17.0% Stage III, 17.7% Stage IV). Molecular testing was attempted in 30.7% (80/261) of adenocarcinoma or NSCLC-not-otherwise-specified cases overall and 57.9% (33/57) of Stage IIIB/IV cases. Tissue was adequate in 87.5% (70/80) of cases. EGFR mutations (14.7%) and ALK translocations (4%) were the most frequently observed genetic alterations. The ENB procedure was well-tolerated; 2.9% of subjects had procedure-related pneumothorax requiring hospitalization or intervention, lower than published rates for CT-guided core biopsy (25%) and CT-guided fine needle aspiration (19%). Subject-reported impact of ENB on daily activities was 0.9 out of 10 (0 = no impact).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In the largest prospective, multicenter study to date, ENB aided in lesion biopsy in the middle and periphery of the lung and tissue collection for molecular testing, with a very low morbidity. ENB facilitates a multidimensional approach to lung biopsy and mediastinal/hilar staging, offering the opportunity for multiple sites/tissues to be safely sampled in one anesthetic event.

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      MA13.10 - Comparison of Pulmonary Nodule Location Between Preprocedural CT and Intra-Procedural Cone-Beam CT During Guided Bronchoscopy (ID 14216)

      11:35 - 11:40  |  Presenting Author(s): Michael A. Pritchett

      • Abstract
      • Presentation
      • Slides

      Background

      Electromagnetic navigation bronchoscopy relies on pre-procedural CT scans to create a virtual airway reconstruction that is used as a roadmap during bronchoscopy. These systems assume similarity between the position of the nodule during bronchoscopy and the pre-procedure CT scan. However, there are multiple factors that suggest that such assumption maybe inaccurate. These include differences in positioning, breathing motion, and the presence of atelectasis. In this study, we evaluated the lung nodule position between pre-procedural CT to interprocedural cone-beam CT (CBCT). In addition, we assessed the ability of a novel augmented endobronchial fluoroscopic guidance system (LungVision, Body Vision Medical Ltd, Israel) to overcome those differences in real-time.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This was a prospective study of 21 patients with 23 peripheral pulmonary nodules. CT scans were imported into the planning software and the physician identified the nodule and navigation pathway. CBCT (Philips Allura Xper FD20) was used to scan the patient during the procedure. LungVision was used for real-time navigation and guidance during biopsy. The divergence in nodule location between the pre-procedural CT and the interprocedural CBCT was measured.

      4c3880bb027f159e801041b1021e88e8 Result

      The average patient age was 69 ± 8.6, median nodule size was 18mm with 74% of the nodules in the upper lobes. The average divergence of the nodule was 14.11 ± 9.9mm. Successful navigation was verified by CBCT in 91% of cases. Malignancy was diagnosed in 20 of 23 nodules for a diagnostic yield of 87%. No adverse events were reported.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study demonstrates a significant divergence in lesion location between pre-procedural CT and intra-procedural CBCT during guided bronchoscopy. This finding indicates that the change in nodule position between the CT and bronchoscopy could have a great impact on the diagnostic success of the procedure. This movement, sometimes greater than the size of the nodule itself, can lead to an inaccurate localization when relying solely on virtual bronchoscopic or electromagnetic navigation.

      CT to patient divergence does not appear to influence the accuracy of this novel navigation platform. The system is capable of tracking the nodules dynamically and can compensate for changes in patient positioning and respiratory motion during both navigation and biopsy which leads to a high diagnostic yield.

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      MA13.11 - Photodynamic Therapy for Peripheral-Type Lung Cancer in a Multi-Center Clinical Trial (ID 13691)

      11:40 - 11:45  |  Presenting Author(s): Jitsuo Usuda

      • Abstract
      • Presentation
      • Slides

      Background

      Photodynanic therapy (PDT), is a treatment modality for many cancers, and uses a tumor-specific photosensitizer and laser irradiation. Recently, we have developed a new minimally invasive laser device using a 1.0 mm in diameter composite-type optical fiberscope (COF), which could transmit laser energy and images for observation in parallel.In this study, we aimed to develop a new endobronchial treatment for peripheral cancer using PDT and a COF, and we evaluated the feasibility of PDT using COF for peripheral lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This phase I study enrolled 3 patients with peripheral lung cancers (primary tumor< 20 mm, stage IA), which were definitively diagnosed by bronchoscopic modalities such as EBUS-GS and brocnhoscopic navigation system. We conducted irradiation using a diode laser (664 nm) and a COF 4 hours after the administration of NPe6 40 mg/m2. We evaluated the tumor lesions using EBUS, and then we introduced the COF into the peripheral lung cancer, and irradiated of red light 664 nm (120 mW, 50 J/cm2 or 100J/cm2). 

      4c3880bb027f159e801041b1021e88e8 Result

      We performed PDT for 3 patients with c-stage IA peripheral lung cancer, using a laser dose (120mW, 50J/cm2), and confirmed the feasibility of the dose. We escalated the laser dose and performed 4 patients using a laser dose (120mW, 100J/cm2).

      Seven patients met our criteria, and 5 cases were adenocarcinoma and 2 case squamous cell carcinoma. We were able to observe the cancer lesions at the peripheral lung by the COF, and feasibly irradiated. Two weeks and 3 months after NPe6-PDT, complications such as pneumonia and pneumothorax were not found, but one mildly found light skin-photosensitivity. Six months later, we found CR in 3 cases and SD in 4 cases.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The 1.0 mm COF was a very useful device of NPe6-PDT for peripheral lung cancers, and PDT was a feasible and non-invasive treatment for a peripheral type early lung cancer. In the future, for non-invasive adenocarcinoma such as AIS, NPe6-PDT will become a treatment modality.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.12 - Discussant - MA 13.09, MA 13.10, MA 13.11 (ID 14632)

      11:45 - 12:00  |  Presenting Author(s): Antoni Rosell

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    MS11 - Stigma and Lung Cancer: Unintended Translational Consequences of Effective Tobacco Control (ID 790)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Prevention and Tobacco Control
    • Presentations: 4
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 206 AC
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      MS11.01 - Identifying Consequences of Stigma on Lung Cancer Care Delivery and Patient Outcomes (ID 11445)

      15:15 - 15:35  |  Presenting Author(s): Heidi Hamann

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      MS11.02 - Stigma of Tobacco and Lung Cancer: A South American Perspective (ID 11446)

      15:35 - 15:55  |  Presenting Author(s): Clarissa Baldotto

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      MS11.03 - Prevalence of Perceived Lung Cancer Stigma Among Medical and Nursing Students (ID 11447)

      15:55 - 16:15  |  Presenting Author(s): Jamie L Studts

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      MS11.04 - Taking a Smoking History in the Context of Lung Cancer Treatment: Missed Opportunities for Stigma-Reducing Empathic Encounters with Throacic Oncologists (ID 11448)

      16:15 - 16:35  |  Presenting Author(s): Peter G Harper

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    MS17 - Life After Lung Cancer: Survivorship (ID 796)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 4
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 206 AC
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      MS17.01 - Unmet needs and QOL of Lung Cancer Survivors (ID 11473)

      13:30 - 13:45  |  Presenting Author(s): Meredith Giuliani

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      MS17.02 - Financial Toxicity and Out of Pocket Costs (ID 11474)

      13:45 - 14:00  |  Presenting Author(s): Bishal Gyawali

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      MS17.03 - Surveillance & Second Primary Malignancies in Lung Cancer Survivors (ID 11475)

      14:00 - 14:15  |  Presenting Author(s): Virginie Westeel

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      MS17.04 - How Important Is Tobacco Cessation as Part of Lung Cancer Treatment? (ID 11476)

      14:15 - 14:30  |  Presenting Author(s): Clarissa Baldotto

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    MS25 - Genetic and Prognostic Markers in Mesothelioma; Going Beyond the Histology Subtypes (ID 803)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Mesothelioma
    • Presentations: 5
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 206 AC
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      MS25.01 - Impact of Tumor Volume on Outcome: What Are the Limitations? (ID 11506)

      10:30 - 10:45  |  Presenting Author(s): Anna K. Nowak

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      Abstract

      A key goal of cancer staging is to stratify patient survival using anatomical tumour characteristics identified on imaging at presentation. The relationship between burden of cancer and patient outcomes is an established tenet of oncology, and most staging and prognostic systems incorporate surrogates or estimates of total tumour burden. Nevertheless, malignant pleural mesothelioma has long posed challenges in quantifying tumour burden for staging and prognostication. Many cancers grow outward from a nidus to form a mass of tumour cells which can be measured in three dimensions and volume of tumour quantified. However, the unique morphology of mesothelioma, growing as a sheet of tumour around the pleural cavity, adds complexity to the routine quantification of tumour burden. Furthermore, CT imaging, at least using human interpretation, may have difficulty distinguishing between pleural tumour and atelectasis, pleural fluid, and pleural scarring or plaques, confounding the accurate measurement of tumour volume.

      The relationship between tumour burden and outcomes in mesothelioma was first reported in 1997, noting that tumour size as measured using 3-D reconstructions of chest CT was prognostic in patients undergoing surgical resection, with a tumour volume <100cc predicting better survival1. These findings have been reproduced in a number of studies, both using CT imaging in the context of extrapleural pneumonectomy2 and using FDG-PET to estimate pleural tumour volume in non-surgically treated patients3. However, the technical challenges of accurately and reproducibly measuring tumour volume have remained barriers to routinely incorporating this metric into clinical practice prognostication, staging systems, and clinical trial stratification.

      In practical terms, what do we need to be able to apply an estimate of tumour volume in everyday clinical practice? Centres of excellence and radiology research laboratories may be able to use computerised estimates of volume as measured by CT scan or FDG-PET scan, however a sound prognostic indicator which can be applied to the population as a whole must also be applicable in a less resource-rich environment. Currently, there are numerous commercial and research tools for measuring tumour volume, however each requires a different level of clinician or radiographer input, and those which require manual oversight or contouring are also prone to inter-observer variability. Furthermore, it is not clear whether there is consistency between platforms.

      The most recent iteration of the IASLC staging database collected information on unidimensional measurements of pleural tumour thickness from 472 patients as a surrogate measure of tumour bulk, attempting to approach the semi-quantification of tumour bulk using a technique which could be rapidly applied in any setting, including community practice or low resource settings. In brief, measurements of pleural tumour were taken perpendicular to the chest wall or mediastinum at the point of maximum tumour thickness, one each in the upper, middle and lower thirds of the thorax4 (Figure 1a and b). As published in the recent update of the AJCC/IUCC staging system for mesothelioma, these measurements could be analysed in a number of ways, but were consistently identified as prognostic indicators and may even provide better discrimination between patient outcomes than existing T stages, which classify by the extent of anatomical organ involvement or invasion, rather than tumour bulk. Whether these measurements were summated, or dichotomised by maximal thickness, or ranked by quartile, these findings were consistent and predicted for overall survival.

      Another recent publication supports the relationship between unidimensional tumour measurements of thickness, and both tumour volume and survival5. Taking three structured measurements from the mediastinum, chest wall, and diaphragm, nine measurements were determined, which correlated significantly (p<0.0001) with total tumour volume as estimated by gross tumour volume from a radiation boost volume calculation. Diaphragmatic tumour thickness was more strongly associated with time to recurrence (p<0.0001) and survival (p=0.001) than mediastinal or chest wall tumour thickness.

      In conclusion, whilst tumour volume is clearly a prognostic indicator in mesothelioma, the question of how to best incorporate this metric into routine staging and clinical practice remains open. The IASLC Mesothelioma Staging Database will shortly open to further data collection, and will again incorporate unidimensional measurements of tumour thickness, in an effort to further define a simple and readily applied surrogate of volume. Automated measurement of volume continues to be refined by multiple investigators, and concordance between platforms will be needed to move the field forward.

      1. Pass HI, Temeck BK, Kranda K, Steinberg SM, Feuerstein IR. Preoperative tumor volume is associated with outcome in malignant pleural mesothelioma. J Thorac Cardiovasc Surg 1998;115:310-7; discussion 7-8.

      2. Gill RR, Richards WG, Yeap BY, et al. Epithelial malignant pleural mesothelioma after extrapleural pneumonectomy: stratification of survival with CT-derived tumor volume. AJR Am J Roentgenol 2012;198:359-63.

      3. Nowak AK, Francis RJ, Phillips MJ, et al. A Novel Prognostic Model for Malignant Mesothelioma Incorporating Quantitative FDG-PET Imaging with Clinical Parameters. Clin Cancer Res 2010;16:2409-17.

      4. Nowak AK, Chansky K, Rice DC, et al. The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma. J Thorac Oncol 2016;11:2089-99.

      5. de Perrot M, Dong Z, Bradbury P, et al. Impact of tumour thickness on survival after radical radiation and surgery in malignant pleural mesothelioma. The European respiratory journal 2017;49.

      Figure 1: In the IASLC T staging database, tumour bulk was estimated by measuring the thickest tumour at the upper, middle and lower hemithorax bounded by structures shown above and below lines in (a), (b). Tumour is measured perpendicular to the chest wall or mediastinum (c).


      wclc extended abstract figure 1.jpg

      e353dbe42c8654f33588d4da0b517469

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      MS25.02 - How Should P16, BAP1, and NF2 Mutations Be Integrated in Therapeutic Algorithms? (ID 11507)

      10:45 - 11:00  |  Presenting Author(s): Francoise Galateau-Salle

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      MS25.03 - Impact of Innate and Adaptive Tumor Infiltrating Cells on Prognosis (ID 11508)

      11:00 - 11:15  |  Presenting Author(s): Thomas John

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      Abstract not provided

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      MS25.04 - Biomarkers in Clinical Practice: Is It Prime Time? (ID 11509)

      11:15 - 11:30  |  Presenting Author(s): Harvey Pass

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      Abstract not provided

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      MS25.05 - Targeting the Micro-RNA: A New Therapeutic Venture (ID 11510)

      11:30 - 11:45  |  Presenting Author(s): Nick Pavlakis

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    MTE09 - Management of Advanced Wild-Type Lung Cancer in Special Situations (Ticketed Session) (ID 819)

    • Event: WCLC 2018
    • Type: Meet the Expert Session
    • Track: Advanced NSCLC
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 07:00 - 08:00, Room 206 AC
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      MTE09.01 - Evidence Based Management of the Patient over 80 (ID 11561)

      07:00 - 07:30  |  Presenting Author(s): Elisabeth Quoix

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      Abstract not provided

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      MTE09.02 - Management of the PS 2 Patient (ID 11562)

      07:30 - 08:00  |  Presenting Author(s): Joan Schiller

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      Abstract not provided

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    MTE12 - IO in the Real World - High Risk Populations And Patient Support (Ticketed Session) (ID 822)

    • Event: WCLC 2018
    • Type: Meet the Expert Session
    • Track: Immunooncology
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 07:00 - 08:00, Room 206 AC
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      MTE12.01 - Is IO an Option for Patients with Contraindications (Auto-immune Disease, Pulmonary Fibrosis, HIV, Hepatitis, Transplant etc) (ID 11566)

      07:00 - 07:40  |  Presenting Author(s): Andrew G Robinson

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      MTE12.02 - How can we Minimize Toxicity for our High Risk Patients? (ID 11567)

      07:40 - 08:00  |  Presenting Author(s): Massey Nematollahi

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      Abstract not provided

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