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H.M. Marshall

Moderator of

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    O23 - Imaging and Screening (ID 125)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Imaging, Staging & Screening
    • Presentations: 8
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      O23.01 - Volume doubling time measurement of pulmonary nodules: comparison between 2D- and 3D-methods (ID 178)

      D. Morimoto, S. Takashima, B. Jiang, Y. Takahashi, H. Numasaki, Y. Tomita, M. Higashiyama

      • Abstract
      • Presentation
      • Slides

      Background
      Measurement of volume doubling time (VDT) of small pulmonary nodules is clinically useful for discrimination between benign and malignant etiology, because this discrimination capability based only on the initial CT is limited. Recent advancement of CT technology enabled direct 3D measurement of volume of pulmonary nodules using commercially available software and enabled VDT measurement with these data. However, there are only a few reports in which accuracy of the 3D method was assessed with comparing the 3D method with the traditional 2D method. Here, we compared intra- and inter-observer variability (OV) to assess the accuracy of these two methods and compared VDT of pulmonary nodules in 2D-method with those in 3D-method. We also discussed the clinical relevance of our results.

      Methods
      Forty-two pulmonary nodules of 3 cm or smaller (CT type, 11 of ground-glass opacity, 15 of mixed type, and 16 of solid type) of peripheral lung cancer (37 of adenocarcinoma, 4 squamous cell carcinoma, and one small cell carcinoma) in 41 patients (mean age±SD, 67±10 years; 25 men and 16 women) who underwent 16-slice MDCT with 1-mm collimation twice (mean interval, 369 days, range 60-1119 days) before surgical resection during June 2006 and December 2008 were included in this study. Five examiners independently calculated VDT by 2D (nodule diameter measurement) and 3D methods (nodule volume measurement using in-house programmed software) with the use of Schwaltz equation and repeated the measurements one month after. Thus, intra- and inter-OV in VDT for the two methods was compared using 95% confidence intervals (CI) in Blant-Altman plots, and VDT calculated with the two methods was compared in each examiner. In evaluating inter-OV, averaged values of the two measurements in each examiner were used for analysis. A p of less than .05 was considered to be significant.

      Results
      As for inter-OV (n=10), 95% CI (mean±SD in days, 398±123) for 3D method was significantly greater than that (231±87) for 2D method (p=0.005). Regarding intra-OV (n=5), 95% CI (291±199) for 3D method tended to be greater than that (195±36) for 2D method (p=0.388). VDT calculated with 3D method was significantly greater than that calculated with 2D method in all of the 5 examiners (all p of <0.05).

      Conclusion
      Inter-OV in VDT measurement was significantly greater in 3D method than in 2D method and VDT calculated with 3D method was greater than that calculated with 2D method. Therefore, in calculating VDT of pulmonary nodules, the same examiner should evaluate with the same method.

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      O23.02 - Positron emission tomography (PET) in lung cancer screening<br /> - Final results after a 5 year screening programe. (ID 1021)

      H. Ashraf, Z. Saghir, A. Dirksen, J.H. Pedersen, J. Mortensen

      • Abstract
      • Presentation
      • Slides

      Background
      PET is a useful tool in the diagnostic workup of lung cancer. However, its role in lung cancer screening with low dose Computed Tomography (CT), in which small sized nodules are detected, is still to be determined. We present final PET results from the 5 year (2005-2010) randomized Danish Lung Cancer Screening Trial (DLCST).

      Methods
      DLCST participants with indeterminate nodules mostly between 5 and 15 mm were referred for a 3-month rescan. Between the initial scan and the 3-month rescan, participants were also referred for a PET scan. Uptake on PET was categorized as most likely benign or malignant on a scale from I to IV). Receiver operating characteristic (ROC) analyses were used to determine the sensitivity and specificity of PET. Resected nodules and indolent nodules (i.e. stable for at least 2 years) were included, and the latter was categorized as benign. Nodules were only included once in the study, thus repeat PET scans were excluded.

      Results
      A total of 90 nodules were included, 50% men, mean age 67 years (58-79), prevalence of lung cancer was 38% (35/90). Mean follow-up time for benign non-resected nodules was approx. 2.8 years in screening. Clinical follow-up in central digital medical logs was done for all participants in 2013. The sensitivity and specificity of PET was 66% and 91%, respectively, with cut-off points for malignancy at PET>II (i.e. categorized as possibly or probably malignant at PET). The positive predictive value was 82% (23/28) and negative predictive value was 81% (50/62). 12 PET results were false negative, and of these 75% (9/12) were either ground glass nodules or partly solid nodules. Figure 1

      Conclusion
      PET is a valuable tool in lung cancer screening; our results show fair sensitivity and high specificity in a trial with long time follow-up of benign nodules. False negative PET results were found in non-solid nodules. We recommend PET as an integrated part of future lung cancer screening programs.

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      O23.03 - Metabolic Imaging Based Prognostic Model for Predicting Survival of Patients with Stage I Non-Small Cell Lung Cancer (ID 1841)

      S.H. Hyun, J.Y. Choi, J. Kim, Y.M. Shim, K. Lee, B. Kim

      • Abstract
      • Presentation
      • Slides

      Background
      The objective of this study was to develop a pretreatment prognostic model based on metabolic imaging biomarkers that could be used to predict overall survival (OS) in patients with stage I non–small cell lung cancer (NSCLC).

      Methods
      We evaluated 198 patients with pathologic stage I NSCLC who underwent pretreatment FDG PET/CT. Metabolic imaging biomarkers included maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and coefficient of variation (COV) for primary tumors. SUV is a semiquantitative index of metabolic activity. TLG is a volumetric measurement of tumor glycolytic activity. COV is an index of tumor uptake heterogeneity. The prognostic significance of clinical variables and imaging biomarkers (age, sex, histologic cell type, tumor size, SUVmax, TLG, COV) was assessed by Cox proportional hazards regression model. Statistically significant clinical variables and imaging biomarkers in the multivariable analysis were used to construct a prognostic model for predicting survival. The predictive accuracy of the prognostic model was evaluated by Harrell's concordance index (C-index).

      Results
      Median follow-up for surviving patients was 7.5 years with a range of 5.2 to 9.9. At the time of analysis, 52 (26.3%) patients had died. Age (HR = 1.05 for 1-year increase, P = 0.007), histologic cell type (HR = 0.54 for adenocarcinoma, P = 0.027), SUVmax (HR = 1.08 for 1-unit increase, P = 0.002), and TLG (HR = 1.23 for a doubling of TLG, P = 0.021) were significantly associated with OS by univariable analysis, whereas only age (HR = 1.07 for 1-year increase, P = 0.005) and SUVmax (HR = 1.04 for 1-unit increase, P = 0.012) were significantly associated with OS by multivariable analysis. The final prognostic model included age as a clinical variable and SUVmax as a metabolic imaging biomarker to predict OS. The predictive performance of the prognostic model for OS was not improved by addition of TLG or COV. The C-index was 0.694 for the final model with age and SUVmax. Kaplan-Meier survival curves stratified by risk score showed high-risk group of patients (n = 58, SUVmax > 12 and age > 60) and low-risk group of patients (n = 48, SUVmax ≤ 12 and age ≤ 60). Figure 1

      Conclusion
      A new prognostic model based on pretreatment metabolic imaging may have potential clinical utility for risk stratification of stage I NSCLC patients.

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      O23.04 - Improved interobserver agreement with PERCIST 1.0, compared to a qualitative method for early response evaluation using FDG-PET/CT in NSCLC (ID 1195)

      J. Fledelius, A.A. Khalil, J. Frokiaer

      • Abstract
      • Presentation
      • Slides

      Background
      During the past decade many studies have used FDG-PET/CT for response evaluation to therapy, both in NSCLC and several other cancer forms. A preferential method for evaluation has not been established as of yet. Two main approaches tend to single out: A visually based model as described by Mc Manus et al in 2003 and semi-quantitative approaches, like the recently proposed PERCIST 1.0 2009, by R. Wahl et al. Few studies have evaluated the interobserver variability when using sequential PET/CT scans for response evaluation, and comparison of qualitative- and semi quantitative approaches are also scarce. The aim of this study is to determine which method will provide the more robust evaluation of response when using FDG-PET/CT, the qualitative approach or the SUV based semi quantitative approach prior to the introduction of routine early response evaluation in NSCLC.

      Methods
      FDG-PET/CT scans at baseline and after 2 cycles of chemotherapy from 35 patients with locally advanced NSCLC were analysed by 8 different readers using two different methods: PERCIST 1.0 and the qualitative McManus approach. Both methods result in allocating patients into one of four response categories. Observers were given short written presentations outlying the criteria for evaluation by the two methods. The observers represent a wide range in experience with PET evaluation, only half had experience in response evaluation in NSCLC, but most were experienced in similar evaluation in lymphoma patients.

      Results
      When using PERCIST 1.0, the agreement between observers in determining the percentage change in SULpeak was “almost perfect” with ICC=0.959 similar ICC values were found looking at SUL peak at baseline and follow up scans. There was strong agreement amongst readers allocating patients to the different response categories with Fleiss kappa of 0.761 (0.714-0.808). In 22 of the 35 patients there was complete agreement. When using the qualitative method (A.M. McManus), agreement was lower, down to moderate agreement, with Fleiss kappa of 0.596 (0.554-0.639). And complete agreement was observed in only 10 of the 25 patients. Using chi squared the difference is statistically significant (p < 0.005). No difference was found between experienced and non-experienced observers.

      Conclusion
      In spite of a wide range of experience among 8 readers receiving minimal introduction to the two methods they were to use, we found rather high kappa values, for both methods compared to its nearest competitor: Size change in CT images, known to be very observer dependent. The more objective, semi-quantitative method showed substantially higher agreement than the more subjective method. We suspect that a more detailed introduction into the methods would have improved the kappa values even further, but believe that our method is more likely to provide an introduction similar to the one you receive when introduced as a new physician at the department. Perhaps then the agreement reflects the long-term agreement.

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      O23.05 - DISCUSSANT (ID 3980)

      S. Leong

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      O23.06 - Diffusion-weighted magnetic resonance imaging at 3.0-T versus fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for detection of pulmonary malignant tumors (ID 88)

      J. Zhang, L. Cui, X. Tang, Y. Zhang, H. Yang, L. Chen, X. Ren, J. Shi, H. Yin

      • Abstract
      • Presentation
      • Slides

      Background
      Emerging evidences suggests that diffusion-weighted magnetic resonance imaging (DW MRI) at 1.5-T could be useful for tumor detection, together with N and M staging in patients with lung cancer, especially non-small cell lung cancer (NSCLC), with accuracy as good as, or even better than, that of FDG PET/CT most recently. This investigation prospectively examined whether DW MRI at 3.0-T might be as useful as FDG PET/CT for detection of pulmonary malignant tumors.

      Methods
      This study was approved by the institutional review board, and written informed consent was obtained from all patients. DW MRI and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules, including lung cancer, lung metastases, and benign lesions, diagnosed by pathological examination. Apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV~max~), and five-point visual scoring were assessed. Immunohistochemical staining for Ki-67 was performed in 36 patients with lung cancer, and Ki-67 score was evaluated. Receiver operating characteristic (ROC) curve analysis was used to determine feasible threshold values. Diagnostic capabilities for detection of pulmonary malignant tumors were compared with the McNemar test on a per-patient basis, and correlation between malignant degree of lung cancer and ADC or SUV~max~ was analyzed by Spearman rank test.

      Results
      As for diagnostic capability, area under ROC curve (A~z~) for ADC (0.91) were significantly higher than that for SUV~max~ (0.78, P < 0.05), and A~z~ value for DW MRI (0.94) were not significantly different from that for FDG PET/CT (0.92, P > 0.05). For quantitative assessment, specificity and accuracy of ADC (91.7%, 92.9%) proved to be significantly higher than those of SUV~max~ (66.7%, 77.9%, P < 0.05), although sensitivity of ADC (93.5%) was not significantly different from that of SUV~max~ (83.1%, P > 0.05). When feasible threshold values were used to assess qualitatively, sensitivity, specificity, and accuracy of DW MRI (96.1%, 83.3%, 92.0%) were also not significantly different from that of FDG PET/CT (88.3%, 83.3%, 86.7%, P > 0.05). Significant correlation was found between Ki-67 score and ADC (Spearman coefficient r = -0.66, P < 0.05), as well as ADC and SUV~max~ (r = -0.37, P < 0.05). On the contrary, Spearman coefficient was -0.11 between Ki-67 score and SUV~max~ (P > 0.05).

      Conclusion
      In conclusion, quantitative and qualitative assessments for detection of pulmonary malignant tumors obtained with DW MRI at 3.0-T are as useful as, even superior to, those obtained with FDG PET/CT. Furthermore, another significant outcome of this study was that ADC in DW MRI at 3.0-T can also play a role in prediction for malignant degree of lung cancer in particular, but SUV~max~ did not in FDG PET/CT.

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      O23.07 - Comparison of diffusion-weighted magnetic resonance imaging versus<br /> F-18 fluorodeoxyglucose positron emission tomography in the assessment of N2 lymph node metastasis due to non-small cell lung cancer (ID 350)

      E. Yilmaz, A. Akkoclu, A. Gulsen, F. Sever, B. Genc, S. Kalaycioglu, I. Karapolat, A. Onen

      • Abstract
      • Presentation
      • Slides

      Background
      To compare the diagnostic efficacies of diffusion-weighted magnetic resonance imaging (DWI) and F-18 fluorodeoxyglucose positron emission tomography (PET) findings for the preoperative prediction of mediastinal nodal metastasis in stage N2 disease of non–small cell lung cancer (NSCLC).

      Methods
      The study included 68 patients (42 men and 26 women; mean age, 62 years) with a supicious stage N2 due to NSCLC. In all patients, DWI (using a sigle-shot echo-planar sequence with diffusion factor of 0-600 s/mm² at 1.5 Tesla) and PET were performed before surgery. In DWI, a patient was regarded to have stage N2 disease when an ipsilateral mediastinal lymph node showed apparent diffusion coefficent (ADC) value of ≤0.98 s/mm², regardless of nodal size. A node was considered as positive for malignancy, if it showed standardized uptake value (SUV) of 3 or higher by PET. Both DWI and PET images were prospectively evaluated for malignancy on a per-node basis by two observers. Histopathologic results served as the reference standard. N2 disease was decided by using the American Joint Committee on Cancer staging system. The results were compared between the two modalities and statistically significant differences in nodal metastasis between DWI and PET were determined with p<.05 obtained by using the McNemar test or with a generalized estimating equation.

      Results
      Nodes were positive for malignancy in 36 (32%) of 114 nodal stations and 22 (32%) of 68 patients. The N2 staging was correctly diagnosed in 56 (82%) and 52 (76%) patients by DWI and PET (p=.09), respectively. For the depiction of malignant nodes, DWI and PET showed sensitivities of 78% (31 of 40 nodal groups) and 78% (28 of 36), specificities of 93% (69 of 74) and 90% (70 of 78), positive predictive values of 86% (31 of 36) and 78% (28 of 36), negative predictive values of 88% (69 of 78) and 90% (70 of 78) and accuracies of 88% (100 of 104) and 86% (91 of 104), respectively (p=.23, p<.05, p<.01, p=.08, and p=.12). There were nine false-positive interpretations by DWI, compared with eight by PET. Eight false-negative assessments were present on PET images, but only five false-negative results were found in DWI. .Figure 1

      Conclusion
      DWI has a higher specificity for N2 staging of NSCLC compared with PET and has the potential to be a reliable alternative imaging method with an advantage of radiation-free imaging for the preoperative staging of mediastinal lymph nodes in patients with NSCLC.

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      O23.08 - DISCUSSANT (ID 3981)

      M.J. Fulham

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

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    CF - A Focus on Lung Cancer - An Interactive Consumer Forum (ID 219)

    • Event: WCLC 2013
    • Type: Other Sessions
    • Track:
    • Presentations: 1
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      CF.3 - Lung Cancer Screening – where are we at? (ID 5650)

      H.M. Marshall

      • Abstract
      • Slides

      Abstract not provided

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    O05 - Cancer Control (ID 130)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      O05.08 - DISCUSSANT (ID 3992)

      H.M. Marshall

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.23 - Poster Session 1 - Tobacco Control, Prevention and Chemoprevention (ID 162)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P1.23-002 - A randomized controlled trial of brief counselling intervention and audio materials for smoking cessation in a low-dose CT screening study (ID 2959)

      H.M. Marshall

      • Abstract

      Background
      Smoking cessation is a highly cost-effective health intervention. Embedding a smoking cessation program within a lung cancer screening program may significantly enhance the cost-effectiveness of screening. Smokers enrolling in Low-dose CT screening studies are motivated to quit but the best strategy to aid smoking cessation is not yet defined.

      Methods
      Population: smokers enrolled in a LDCT screening study, age 60-74years, with >=30 pack-year smoking history. Smokers could enrol at any time during the LDCT study. Intervention: single face-to-face counselling session on the day of attendance for LDCT screening plus audio cessation advice (on mp3 player) plus written quit materials. The individualised counselling session was given by a thoracic physician using motivational interview techniques. Control: written quit materials only. Outcome: point prevalence self-reported smoking cessation at 1 year, confirmed with exhaled CO measurement (ECO) where available; ≥10ppm level indicating non-abstinence.

      Results
      Fifty-four participants were randomized (control group n=26, intervention group n=28). There were no statistically significant differences between groups in age, sex, pack-years smoking, baseline CT scan findings, nicotine dependence score, self-belief in ability to quit (on a scale of 1-5, higher score indicating stronger belief) or education level although the intervention group reported a higher number of cigarettes smoked per day (table 1). Baseline LDCT scans were reported as positive if one or more non-calcified nodules >=4mm diameter were detected. The mean duration of interview was 26 minutes. Overall, ten participants (18.6%) reported smoking cessation (five had ECO confirmation and five did not have ECO testing); two patients (3.7%, one from each group) had missing data and were assumed to be continuing smokers; the remainder reported continued smoking. There was no difference in self-reported cessation between the intervention and control groups (17.8% vs 19.2% respectively).

      Table 1
      Control Intervention p value
      Women 10 10 ns
      Men 16 18 ns
      Education Up to High School 13 13 ns
      Teriary 13 15 ns
      Age, years, mean 64 64 ns
      Age started smoking, years 16 17 ns
      Cigarette consumption per day, n 23 30 0.03
      Pack years smoking, mean 61 64 ns
      FEV1 % predicted, mean 92 90 ns
      Fagerstrom nicotine dependence score, mean 4.9 5.2 ns
      Baseline CT Scan report Negative 12 10 ns
      Positive 14 18 ns
      Self-belief in ability to quit 3.7 3.4 ns

      Conclusion
      The 18% quit rate in this study is higher than reported background rates however the brief intervention provided did not increase quit rates above that of the control group. Smokers in this study reported moderate to high levels of nicotine dependence with extensive smoking histories, and, although motivated to quit, may require more intensive assistance to support smoking cessation.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track:
    • Presentations: 1
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      P3.17-008 - Electromagnetic Navigation Bronchoscopy increases diagnostic yield after non-diagnostic Endobronchial Ultrasound Guide Sheath for peripheral pulmonary lesions (ID 3226)

      H.M. Marshall

      • Abstract

      Background
      Peripheral pulmonary lesions (PPLs) are diagnostic challenges. Computed tomography guided transthoracic needle aspiration (CT TTNA) has high diagnostic sensitivity but also high complication rates[1]. Endobronchial ultrasound guide sheath (EBUS GS) allows confirmation of target localisation but cannot provide guidance to the target. Electromagnetic navigation bronchoscopy (ENB) allows the bronchoscopist to navigate to target without direct vision. We assessed whether ENB could diagnose PPLs that had undergone a non-diagnostic EBUS GS.

      Methods
      We performed 50 ENB procedures for diagnosis of PPLs between 3/2011-6/2013, 15 after non-diagnostic EBUS GS. ENB data was prospectively collected. ENB (superDimension, Minneapolis, US) was performed through a standard 5.9mm bronchoscope under general anaesthesia through a laryngeal mask airway after pathway planning using iLogic software. Once the locatable guide was close to and correctly aligned with the target, it was removed and replaced by EBUS radial probe (EBUS RP) to confirm target localisation. Samples were then taken with forceps biopsy, cytology brush, and mini bronchoalveolar lavage. If ENB was non-diagnostic patients underwent further investigation. Benign diagnoses were followed up for a minimum of 6 months to ensure a consistent clinical course. Primary outcome was diagnostic yield, procedure time, and complications. Characteristics distinguishing diagnostic from non-diagnostic ENB were assessed using the chi-squared test.

      Results
      15 patients (mean age 66.67, 9 females, 12 current or ex smokers, mean BMI 25.16kg/m2) with 15 PPLs who underwent non-diagnostic EBUS GS proceeded onto ENB. Lesion location and characteristics were as follows: left (7), upper lobe/lower lobe=11/4, bronchus sign positive (14), soft tissue density/ground glass=14/1. Mean maximal lesion dimension was 25.64mm+/- 12.38mm and mean closest distance from pleura was 12.04mm +/- 12.18mm. Average total procedure time was 56.83 mins +/- 13.71mins with a mean of 4.53 biopsies taken per patient. All except one procedure was performed under general anaesthesia with a laryngeal mask airway. The target was reached in 12 patients. Median closest distance to target was 12.69mm +/- 7.83mm. Target localisation was confirmed on EBUS RP without any manipulation in 10 patients; a further 2 lesions could be localised with minor manipulation. ENB provided a diagnosis in 5 of 15 patients (33.33%): adenocarcinoma (2), squamous cell carcinoma (1), fungal infection (1), organising pneumonia (1). Non-diagnostic ENB underwent the following additional procedures: CT TTNA (7), repeat EBUS GS (1), and surgical biopsy (2). The following conditions were diagnosed: mycobacterial infection (1), adenocarcinoma (4), fibrosis (1), hamartoma (1), non-small cell carcinoma (1), nodular lymphoid hyperplasia (1). There were no complications. Procedural success was independent of lesion size (p=0.378), location (p=0.714), or morphology (p=0.464), but was related to confirmation on EBUS RP without manipulation (p=0.053), and the ability to view the lesion on Maximal Intensity Projection (MIP) view in 360 degrees (p=0.053).

      Conclusion
      ENB can successfully diagnose PPLs that have been non-diagnostic on EBUS GS. Lesions that can be confirmed on EBUS GS after being navigated to by ENB, as well as those that can be visualised in 360 degrees on MIP view, have a higher chance of success.