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S. Sasada
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MA 20 - Recent Advances in Pulmonology/Endoscopy (ID 685)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Pulmonology/Endoscopy
- Presentations: 15
- Moderators:C. Lee, S. Sasada
- Coordinates: 10/18/2017, 14:30 - 16:15, F205 + F206 (Annex Hall)
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MA 20.01 - Fiducial Marker Placement Using Electromagnetic Navigation Bronchoscopy in the Prospective, Multicenter NAVIGATE Study (ID 7890)
14:30 - 16:15 | Presenting Author(s): Mark R Bowling | Author(s): E.E. Folch, S.J. Khandhar, J. Kazakov, W.S. Krimsky, G. Lemense, P.A. Linden, B.A. Murillo, M.A. Nead, C. Teba, Christopher W Towe, C.J. Anciano
- Abstract
- Presentation
Background:
Fiducial markers guide stereotactic body radiotherapy (SBRT) and can be used to localize lesions for surgical resection in the management of lung cancer. We report the safety, accuracy and common practice patterns of fiducial placement guided by electromagnetic navigation bronchoscopy (ENB).
Method:
NAVIGATE (www.clinicaltrials.gov, NCT02410837) is a prospective, multicenter, global, single-arm, observational cohort study of ENB using the superDimension™ navigation system (Medtronic, Minneapolis). This abstract presents the patient demographics, procedural characteristics, and 1-month outcomes in the subset of NAVIGATE subjects from the United States cohort who had fiducial markers placed. Continued enrollment in Europe and 2-year follow-up are ongoing. Study sponsored and funded by Medtronic.
Result:
258 subjects from 21 United States centers (29 operators) received fiducial markers during their ENB procedure. Most subjects received between 1 and 5 fiducial markers (mean 2.2±1.7). General anesthesia was used in 69.4%. Real-time confirmation by radial endobronchial ultrasound (r-EBUS) was used in 34.5% of ENB procedures. The median ENB procedure time (first locatable guide [LG] / extended working channel [EWC] entry to last LG/EWC exit) was 31.0 minutes. Among the 258 subjects undergoing ENB-guided fiducial marker placement, 213 subjects also had lung lesion biopsy. Based on subjective operator assessment, 99.2% of fiducial markers were accurately placed. Follow-up imaging an average of 4.7 days post-procedure showed that 94.3% (232/246) of markers were still in place. The ENB-related pneumothorax rate was 5.0% (13/258) overall and 3.1% were Grade ≥2 based on the Common Terminology Criteria for Adverse Events scale (i.e., requiring chest tube placement or hospitalization). The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failures rates were 0.0% and 1.6%, respectively. Among the 39 subjects undergoing fiducial placement alone with no biopsy, there was 1 respiratory failure and no pneumothoraces or bronchopulmonary hemorrhages.
Conclusion:
We report the largest series to date of fiducial marker placement by ENB guidance. Our data suggest that ENB-guided fiducial marker placement is versatile and accurate, with low complication rates. Practice variations in number and type of fiducial placed between operators were noted in our data. We did not identify the type of radiotherapy system used at each institution or how many fiducial markers were useful during the therapy. In addition, not all SBRT systems require fiducial marker placement, and some fiducial markers were placed for surgical localization. Further investigation should explore these practice patterns to further hone the usefulness and accuracy of placement of fiducial markers for SBRT and surgical localization.
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MA 20.02 - Pleural Dye Marking of Lung Nodules by Electromagnetic Navigation Bronchoscopy in the Prospective, Multicenter NAVIGATE Study (ID 8664)
14:30 - 16:15 | Presenting Author(s): Mark R Bowling | Author(s): C.J. Anciano, E.E. Folch, S.J. Khandhar, D. Arenberg, O. Awais, D. Minnich, M. Pritchett, O.B. Rickman, E. Sztejman
- Abstract
- Presentation
Background:
Pleural dye marking guided by electromagnetic navigation bronchoscopy (ENB) has been useful in identifying small peripheral lesions for sublobar resection in the management of non-small cell lung cancer and indeterminate lung nodules. We report the use of this procedure among the participants of the NAVIGATE study.
Method:
NAVIGATE (www.clinicaltrials.gov, NCT02410837) is a prospective, multicenter, global, single-arm, observational cohort study of ENB using the superDimension™ navigation system (Medtronic, Minneapolis). Enrollment of up to 1,500 subjects is planned at 37 sites in the United States and Europe. European enrollment and 2-year follow-up are in progress. This abstract presents a prespecified 1-month interim analysis of NAVIGATE subjects from the United States cohort who underwent ENB-guided pleural dye marking. Study sponsored and funded by Medtronic.
Result:
From April 2015 to August 2016 at 29 clinical sites, 1218 subjects were enrolled in the NAVIGATE United States cohort. In 7 clinical centers (7/29), 23 subjects (24 lesions) underwent pleural dye marking in preparation for surgical resection. Ten subjects underwent dye marking alone while 13 had dye marking concurrent with lung lesion biopsy and/or fiducial placement. The median nodule size was 10 mm (range 4-22) and 83.3% (20/24) were less than 20 mm in diameter. Most lesions (95.5%; 21/22) were located in the peripheral third of the lung. The median distance of the target lesion from the visceral pleura was 3.0 mm. The median total bronchoscopic procedure time was 22.0 minutes and the median ENB procedure time (first locatable guide [LG] / extended working channel [EWC] entry to last LG/EWC exit) was 11.5 minutes (range 4-38). Dye marking was considered accurate for surgical resection in 91.3% of the cases and the median time of dye marking to surgical resection was 0.5 hours (range 0.3-24). Seventy five percent of the lesions were malignant (18/24) and 50% were adenocarcinoma.
Conclusion:
Our data demonstrates that pleural dye marking with ENB guidance is useful for locating small peripheral lesions for surgical resection without adding significant additional time to the procedure. An interesting finding in our report is the underutilization of this procedure in the NAVIGATE cohort (23/1218). Given that sublobar and lung parenchymal sparing resections for non-small cell lung cancer are becoming more common, it is unclear why surgeons are not more frequently utilizing pleural dye marking. Further investigation concerning physician behavior and practice patterns in the use of lung sparing surgery needs to be explored.
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MA 20.03 - Safety of Electromagnetic Navigation Bronchoscopy in Patients with COPD: Results from the NAVIGATE Study (ID 8648)
14:30 - 16:15 | Presenting Author(s): Christopher W Towe | Author(s): M.A. Nead, O.B. Rickman, E.E. Folch, S.J. Khandhar, Y. Perry, P.A. Linden
- Abstract
- Presentation
Background:
Electromagnetic navigation bronchoscopy (ENB) is used to access lung lesions or lymph nodes for biopsy and/or to guide fiducial or dye marking for stereotactic radiation or surgical localization. CT-guided lung biopsy can be complicated by pneumothorax, particularly in patients with emphysema. We examined the safety of ENB in patients with COPD and/or poor lung function.
Method:
NAVIGATE (www.clinicaltrials.gov, NCT02410837) is a prospective, multicenter, global, single-arm, observational study of ENB using the superDimension™ system (Medtronic, Minneapolis). This NAVIGATE substudy analyzes the 1-month follow-up of the first 1,000 subjects enrolled in the United States and Europe. Subjects were determined to have COPD by medical history. Pulmonary function test results (PFTs) were collected if available. Procedure-related pneumothorax, bronchopulmonary hemorrhage, respiratory failure, and composite complications were prospectively captured. Study sponsored and funded by Medtronic.
Result:
1,000 subjects were enrolled at 29 clinical sites, including 448 with COPD and 541 without COPD (COPD data missing in 11). One-month follow-up was completed in 933 subjects (93.3%). Subjects with COPD tended to be older, male, and have history of tobacco exposure, asthma, and recent pneumonia. Nodule size, location, and procedure time were similar between groups. There was no statistically significant difference in the procedure-related composite complication rate between groups (7.4% with COPD, 7.8% without COPD, 9.1% in subjects missing COPD data, P=0.81). CTCAE Grade ≥2 pneumothorax was not different between groups (2.7%, 3.7%, 0.0%, respectively, P=0.63). Severity of FEV1 or DLCO impairment was not associated with increased composite procedure-related complications (ppFEV1 P=0.66, ppDLCO P=0.37). Figure 1
Conclusion:
Patients with a clinical diagnosis of COPD or with poor PFTs can undergo ENB without an increase in complication rates. Because the risk of pneumothorax is not elevated, in patients undergoing ENB in this analysis, ENB may be the preferred method to biopsy peripheral lung lesions in patients with COPD and/or poor PFTs.
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MA 20.04 - Inteligent Biopsy Device for SPN Diagnosis (ID 9771)
14:30 - 16:15 | Presenting Author(s): Jiri Votruba | Author(s): T. Bruha, P. Michálek
- Abstract
- Presentation
Background:
Solitary pulmonary nodules are increasingly encountered in current medicine. There are interesting new technologies available for this difficult diagnostics category of pulmonary pathologies like endobronchial navigation techniques and transparietal CT guided biopsy. In order to increase diagnostic yield of those techniques precise biopsy instruments are needed.
Method:
We utilise new instrument based on near infrared diagnostics. This simple needle sheath can be used during routine bronchoscopy examination and enables simultaneous spectral measurement and obtaining of histology tissue samples in situ at the same time. This intelligent sheath with standard needle can be used both during fluoroscopy navigation and EBUS guided navigation to confirm correct biopsy instrument position during the sampling itself. According to our results diagnostic yield of navigation method is significantly increased using such device. Instrument itself consists of elastic tubing while along the length of tube on opposite sides of cross section perimeter there are two segments fixed with 6 optic microfibers covered with insulation as NIR spectroscopic probe. Core consists of the channel for of standard biopsy needle introduction. Instrument itself is introduced to the area of interest through the working channel of the bronchoscope.
Result:
We performed 40 consecutive examinations of SPN (diameter 1-3cm) using intelligent needle during navigational bronchoscopic procedure executing fluoroscopy and radial EBUS. Correct placement of biopsy instrument confirmed by NIR spectroscopy was possible in 32 cases. In all these cases positive cytology specimen containing diagnostic material was obtained.
Conclusion:
Intelligent NIR based biopsy needle appears to be good adjunct in the diagnosis of SPNs. More extensive studies are needed to prove diagnostic potency of this device.
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MA 20.05 - Discussant - MA 20.01, MA 20.02, MA 20.03, MA 20.04 (ID 10832)
14:30 - 16:15 | Presenting Author(s): Yoon Soo Chang
- Abstract
- Presentation
Abstract not provided
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MA 20.06 - Discerning Lung Cancer Cell Patterns with Confocal Endomicroscopy (ID 8640)
14:30 - 16:15 | Presenting Author(s): Antoni Rosell | Author(s): M. Diez-Ferrer, B. Torrejon, N. Baixeras, E. Minchole, R.M. Ortiz, N. Cubero, R. Lopez-Lisbona, J. Dorca
- Abstract
- Presentation
Background:
Probe-based confocal endomicroscopy (pCLE) allows confocal microscopy of lung tissue in vivo but limited evidence is available. The objective was to discriminate pCLE patterns of lung cancer in vivo.
Method:
Fluorescence properties of methylene blue (MB) were examined ex vivo in confocal microscope. Next, 15 regions of the central airways were studied in vivo with pCLE and a representative image chosen for analysis with ImageJ software. Biopsy was performed for final diagnosis.
Result:
Ex vivo study showed no differences between 1% and 2% MB concentrations and rapid extinction of fluorescence after 10 minutes of MB application (figure). In vivo study included samples of bronchial mucosa (n = 6), inflammation (n = 3) and tumor (n = 6). pCLE image evaluation (table) showed inflammation and tumor nuclei were bigger (except SCLC) and occupied a greater area. Fluorescence of tumor nuclei was more intense. Non fluorescent area was inferior for both inflammation and tumor samples. Number of nuclei could not discriminate between normal and tumor.Figure 1 Table. Imaging features evaluated in pCLE framesArea occupied by nuclei (µm[2]) Intensity of nuclei (UA) Mean size of nuclei (µm[2]) Non-fluorescent area (µm[2]) Number of nuclei (µm[2]) Bronchial epithelium (mean(SD)) 97,769(9,451) 126(9) 107(10) 67,100(12,567) 937(84) Inflammation (mean(SD)) 117,381(22,166) 122(27) 127(15) 35,124(32,630) 933(225) B cell lymphoma 138,354 145 185 49,269 746 Adenocarcinoma 155,033 198 177 5,225 875 Squamous cell carcinoma 102,805 145 155 54,301 663 Small cell lung cancer 107,201 157 63 11,257 1,687 Non-small cell lung cancer 113,173 187 122 32,359 926 Hamartoma 120,188 145 114 25,438 1,058
Conclusion:
1. MB fluorescence is unaffected by stain concentration 2. There is exponential extinction of MB over time 3. Lung cancer cell pattern distinction in vivo is feasible Funded by Fundació MaratóTV3, SEPAR and FUCAP
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MA 20.07 - Endobronchial Ultrasound Elastography: Mediastinal Staging in Non-Small Cell Lung Cancer and Technical Factors (ID 9387)
14:30 - 16:15 | Presenting Author(s): Lokesh Yagnik | Author(s): A. McWilliams, M. Salamonsen
- Abstract
- Presentation
Background:
Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) is the standard of care for diagnosis and mediastinal staging of non-small cell lung cancer (NSCLC). Studies suggest that elastography, an ultrasonic measure of tissue elasticity, may identify malignant lymph nodes (LNs) with sufficient accuracy to guide which LNs need sampling at EBUS and reduce the time and complexity of staging procedures. This study aims to confirm these findings while also describing technical factors that affect elastographic measurements.
Method:
All patients undergoing EBUS TBNA to investigate possible NSCLC were prospectively recruited. Elastographic analysis was performed prior to TBNA of LNs and later correlated with pathology from EBUS TBNA and/or surgical specimens. All LNs were classified qualitatively according to elastographic colour pattern: predominantly blue, predominantly green and mixed. Strain ratios (SR) were calculated to give quantitative measures of elasticity. Measures were compared to PET and sub-group analyses according to LN FDG avidity were performed. Finally the influence of various technical factors (probe pressure, Region of interest selection, and frame average function) were assessed.
Result:
There were 82 LNs from 50 patients who underwent EBUS elastography with the final diagnosis being malignant in 29(35%) and non-malignant in 57(69%). PET was available for 58 LNs. Diagnostic indices relating to elastographic features and effects of various technical factors are shown in Table 1.Table 1 Diagnostic indices for elastographic identification of malignant LNs (A) and Effects of technical factors (B)
A. Variable Sensitivity Specificity PPV NPV Elastography All 88% 47% 42% 90% Elastography PET Positive 90% 64% 66% 90% Elastography PET negative 63% 88% 70% 85% Strain Ratio All Pending Pending Pending Pending Strain Ratio PET positive Pending Pending Pending Pending Strain Ratio PET negative Pending Pending Pending Pending Sonographic features 81% 60% 54% 84% PET All 82% 51% 52% 81% B. Variation in technique Difference p value Probe Pressure - colour map Pending Pending Probe pressure - strain ratio Pending Pending ROI pressure Pending Pending ROI Placement Pending Pending Frame average - colour map Pending Pending
Conclusion:
EBUS elastography can identify malignant LNs with equivalent power to sonography and FDG PET and may have a role in selecting which PET-negative nodes require sampling in staging procedures. It is highly dependent on technique which must be standardised to ensure accuracy of results. Please note: Data acquisition is still underway and planned to continue for a further 2 months. Analysis shall be complete by the time of the conference.
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MA 20.08 - Classification of Confocal Endomicroscopy Patterns for Diagnosis of Lung Cancer (ID 9874)
14:30 - 16:15 | Presenting Author(s): Antoni Rosell | Author(s): R.M. Ortiz Comino, D. Gil, E. Minchole, M. Diez-Ferrer, N. Cubero, R. Lopez-Lisbona, C. Sanchez, O. Ramos, A. Esteban, J. Dorca
- Abstract
- Presentation
Background:
Solitary pulmonary nodules diagnosis and management is so challenging that nNew endoscopic techniques are being introduced to reduce uncertainty in peripheral pulmonary lesions (PPL) diagnosis and management. increase its diagnostic yield. Probe-based confocal laser endomicroscopy (pCLE) is a technique that can microscopically image the lung tissue in vivo during flexible bronchoscopy, though it can be difficult for pulmonologists to distinguish cellular patterns in a monochrome vision under respiratory and cardiac movements. . The goal of this work is to explore explore if Computed-Aided Diagnoses (CAD) tools can obtain a reliable diagnoses with pCLE in lung cancer.
Method:
A pilot study using 2 different methods for pCLE pattern analysis was performed:, one based on visual analysis by 3 experts and the other one based on computeron computerized analysis of visual patterns called Graphcom. Twelve 12 pCLE videos ( obtainedobtained using mMethylene blue dye (1%) and Alveloflex-Cellvizio 660nm miniprobe) were selected from patients with endobronchial lesionsperipheral SPNs (6 with lung adenocarcinoma cancer and 6 with inflammatory disease) during rigid bronchoscopy under general anesthesia. Afterwards, Vvideo sequences from pCLE were visually explored by one of the authors to select between 10 and 15 framesimages that presented a clear cellular pattern, without artifacts. . These images were shown to 3 observers who were familiar with confocal images but ignored the final histopathological diagnosis for a blind visual labellinglabeling. Images were also computationally analyzed using methods from social networks community analysis in a graph representation of pCLE images based on visual features to potentially overlapping groups of images that share common visual properties.
Result:
Our preliminary results indicate that on average visual analysis with 3 independent experts can only achieve a 60.2% of accuracy and has large variability amongst observers, while the accuracy of the proposed unsupervised image pattern classification rai(GraphCom) sesrises to 83,4.4%.
Conclusion:
Visual inspection of CLE images from lung tissue fails to provide accurate diagnosis. CLE images contain enough visual information for in vivo detection of neoplastic cell patterns that could be discriminated using cComputation methods and graph structural analysis applied to deep-learning feature spaces can increase diagnostic accuracy of pCLE images against visual analysis (83.4% vs 60.2%). Future studies are needed to apply this method in a real time scenario during bronchoscopy for PPL diagnoses.
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MA 20.09 - Accuracy & Utility of Systematic Mediastinal LN Staging via EBUS-TBNA in cN0/N1 NSCLC: Systematic Review & Meta-Analysis (ID 9154)
14:30 - 16:15 | Presenting Author(s): Daniel P Steinfort | Author(s): T.L. Leong, P. Loveland, L.B. Irving
- Abstract
- Presentation
Background:
Accurate mediastinal staging is crucial in potentially operable lung cancer to avoid non-therapeutic resection. Performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging of the radiologically normal mediastinum has been reported with inconsistent findings. We assessed the value of pre-operative systematic staging using EBUS-TBNA in cN0/N1 lung cancer.
Method:
For this systematic review and meta-analysis, we searched MEDLINE, PubMed, EMBASE, Cochrane databases from inception to October 2016. We included studies evaluating EBUS-TBNA for systematic mediastinal staging in cN0/N1 lung cancer. For each study, we extracted data on participant age and sex, radiological stage, EBUS-TBNA protocol, number and size of lymph nodes sampled, EBUS-TBNA stage, reference standard stage, and 2x2 tables. We evaluated the diagnostic accuracy of EBUS-TBNA for detection of occult mediastinal metastases. PROSPERO registration number CRD42017057020
Result:
We identified 1,173 articles, of which nine (1,146 patients) were included in meta-analysis. Mean prevalence of N2/N3 disease was 15% (6-24%). EBUS-TBNA had a pooled sensitivity 49% (95%CI 41-57%) (see figure 1), pooled specificity 100% (95%CI 99-100%), and mean negative predictive value 91% (82-100%) for detection of unsuspected N2/N3 disease. Number Needed to Test to detect occult N2/N3 disease was 14 (95%CI 10.8-16.3), NNT was reduced to 7 for studies which added endoscopic ultrasound to EBUS-TBNA. Moderate inter-study heterogeneitywas observed (I[2] 40.6%). Figure 1
Conclusion:
Pre-operative systematic staging by EBUS-TBNA of early lung cancer can reduce rates of non-therapeutic resection and decrease incidence of post-operative upstaging. Sensitivity for detection of radiologically occult mediastinal metastases appears lower than for targeted sampling of pathologic lymph nodes. Verification of negative results by mediastinoscopy in selected cases remains of value.
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MA 20.10 - Discussant - MA 20.06, MA 20.07, MA 20.08, MA 20.09 (ID 10833)
14:30 - 16:15 | Presenting Author(s): Jitsuo Usuda
- Abstract
- Presentation
Abstract not provided
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MA 20.11 - Chronic Obstructive Pulmonary Disease Prevalence in a Lung Cancer Screening Population (ID 9588)
14:30 - 16:15 | Presenting Author(s): John R Goffin | Author(s): G. Pond, A. Tremblay, M. Johnston, Glenwood Goss, G. Nicholas, S. Martel, R. Bhatia, G. Liu, H. Roberts, M. Tammemägi, S. Atkar-Khattra, Ming Sound Tsao, Stephen Lam, S. Puksa
- Abstract
- Presentation
Background:
Chronic obstructive pulmonary disease (COPD) and lung cancer are associated through tobacco use. COPD is underdiagnosed in both the primary care and lung cancer populations. Diagnosis of COPD should lead to improved care and quality of life. Screening programs could provide an opportunity to capture undiagnosed COPD. We analyzed the Pan-Canadian Early Detection of Lung Cancer Study (PanCan Study) to evaluate the prevalence of COPD in a screening population.
Method:
The PanCan Study was a single arm lung cancer screening trial which recruited individuals to low dose CT scan, autofluorescence bronchoscopy, and biomarker screening. Eligible individuals were 50-75 years of age, had smoked within 15 years, and had a minimum six-year risk of lung cancer ≥ 2% based on a risk prediction model derived from PLCO study data, which included COPD as a risk factor. Consenting subjects completed a questionnaire including background medical conditions, high-risk work exposures, and smoking history. Baseline spirometry was performed, and COPD was defined by GOLD criteria. For individuals not receiving post-bronchodilator spirometry, COPD was defined as ‘probable’ if GOLD criteria were met pre-bronchodilator and there was no prior diagnosis of asthma. Individuals with definite or probable COPD were defined as having COPD.
Result:
Of 2537 individuals recruited, 2514 had available spirometry data. Mean age was 62.3 years, 55.3% were male, median pack-years smoked was 50, 62.3% were active smokers, 45.1% had symptoms of dyspnea, 52.4% cough, and 37.5% wheeze. 35.2% had worked in a high-risk occupation. Overall, 1136 (45.2%) met spirometry criteria for COPD. Of 1987 individuals without a prior history of COPD, 41.9% met spirometry criteria for COPD, of which 53.7% had moderate to severe disease. Of 527 individuals (21%) reporting a diagnosis of COPD at baseline, 57.5% met spirometry criteria for COPD, 32.2% did not, and 10.3% had a prior diagnosis of asthma. In a multivariate model for risk of COPD, age (odds ratio (OR)~per year~ 1.06), dyspnea (OR 1.42), being a current smoker (OR 1.43), and pack-years (log transformed OR 1.42) were significant (all p < 0.001) as were high-risk occupation (OR 1.24, p=0.013) and wheeze (OR 1.24, p = 0.024).
Conclusion:
A diagnosis of COPD by spirometry is common in a lung cancer screening trial population. Individuals with a pre-existing self-reported diagnosis of COPD often fail to meet spirometry criteria for their diagnosis. Testing a lung cancer screening population for COPD could significantly improve COPD diagnosis and treatment.
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MA 20.12 - Longitudinal Evaluation of Pulmonary Function in Patients with Advanced NSCLC Treated with Concurrent Chemo-Radiotherapy (ID 10197)
14:30 - 16:15 | Presenting Author(s): Marisol Arroyo Hernandez | Author(s): L. Torre Bouscoulet, L. Bacon, F. Lozano-Ruiz, L. Gochicoa-Rangel, C. García-Sancho, E. Vergara, D. Martínez Briseño, A. Guzmán-Barragán, R. Fernández Plata, M. Blake Cerda, F. Maldonado, Oscar Arrieta
- Abstract
- Presentation
Background:
Patients with locally advanced Non-small cell lung cancer (aNSCLC) receive standard treatment with concurrent chemo-radiotherapy (CCRT). Different studies have tried to identify the changes in lung function after radiation exposition due to the high risk of pulmonary toxicity. The aim of this work is to evaluate lung function with a broad spectrum of respiratory tests as an objective way of assessing lung injury in patients with locally aNSCLC treated with CCRT.
Method:
A prospective study was conducted from June 2013 to July 2015. Fifty-two patients with locally advanced and oligometastatic NSCLC were included. The candidates received treatment with CCRT at the Instituto Nacional de Cancerología (Mexico). Participants were evaluated at baseline, end of RT, week 6, 12, 24 and 48 post-RT through forced spirometry with bronchodilator, body plethysmography, carbon monoxide diffusing capacity (DLCO), arterial blood gases, impulse oscillometry, 6-minute walk test and exhaled fraction of NO (FeNO). The study was registered in clinicaltrials.gov (NCT01580579).
Result:
Before treatment, 34.7% patients presented airflow obstruction (post-BD FEV~1~/FVC < 70%) which remained constant after RT (33.3%). For baseline results, the median of the % of the predictive value in FEV~1 ~post-BD was 97% (79-108), FVC 105% (90-116), TLC 101% (91-111) and DLCO 77% (55-103). At the end of CCRT, FEV~1 ~and FVC showed a significant reduction of 10% within week 12-48 (p=0.0004, p= 0.0005). TLC declined after week 6 post-RT, with a maximum drop of 15% at week 48 (p=0.0015). DLCO changes occurred from RT start to week 48, decreasing up to 20% at week 12 (p=0.0001). FeNO increased, exceeding 20% of its initial/baseline value with a peak at week 6 post-RT. Eighteen patients (34.7%) were hypoxemic (SO2 <90%) at the beginning of the trial, oxygen saturation had a statistically significant reduction at week 6 and week 48 (p<0.03, p<0.01). No significant differences were found in impulse oscillometry and 6-minute walk test. The results of the respiratory tests that decreased with the CCRT did not return to baseline at the end of follow-up.
Conclusion:
Regardless of pre-existing lung damage, the reduction in FEV~1~, FVC, DLCO, TLC and SO2 may represent increased inflammation, tissue remodeling and modification in gas exchange, however further studies are required. The nadir of the lung function occurred at 12 weeks from CCRT initiation. Increased FeNO values may represent a non-invasive marker of airway inflammation that correlates with RT lung injury mechanisms.
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MA 20.13 - etDNA: Tumor-Derived DNA from Pleural Effusion Supernatant as a Promising Source for NGS-Based Mutation Profiling in Lung Cancer (ID 10091)
14:30 - 16:15 | Presenting Author(s): Lin Tong | Author(s): N. Ding, J. Li, X. Wang, Y. Zhang, X. Xu, M. Ye, C. Li, H. Zhang, X. Zhu, Z. Zhu, J. Zhou, J. She, J. Zhou, Y.W. Shao, X. Zhang, H. Bao, S. Xu, X. Zhang, Q. Hong, C. Bai, Jie Hu
- Abstract
- Presentation
Background:
Mutation profiling of circulating tumor DNA (ctDNA) and pleural effusion sediment containing tumor cells (ETCs) were commonly applied in clinical practice. Several studies suggested that tumor-derived DNA from pleural effusion supernatant (etDNA) might be a better candidate for detecting gene alterations in lung cancer. However, little is known regarding the abundance and diversity of tumor DNA acquired among different types of liquid biopsy.
Method:
We performed targeted next generation sequencing (NGS)-based genetic profiling on tumor tissue, pleural effusion (etDNA & ETCs) and contemporaneous ctDNA from 63 lung cancer patients (58 adenocarcinoma, 2 adenosquamous carcinoma, 2 SCLC, 1 neuroendocrine carcinoma), among which 28 patients had paired tumor tissue samples. Genomic DNA from whole blood of each patient was used for germline control. Driver mutation and rearrangement profiling was validated using ARMS-PCR, FISH, or Ventana IHC assay in tumor tissue as golden standard.
Result:
We identified tumor-specific mutations in 98%, 89%, 86%, and 100% of patients in their etDNAs, ETCs, ctDNAs and tumor tissues, respectively (p<0.01). etDNAs showed a significantly higher tumor-specific mutation number per patient (Median: 5) compared to ETCs and plasma ctDNAs (Median of 3 for both), while the median number in tumor tissues is 4 per patient. The detection sensitivity for EGFR mutations in etDNAs is 95%, higher than that in ETCs and ctDNAs (89% and 63%, respectively). Two patients detected ALK fusion in tumor tissue were also positive in etDNA, only one patient was positive in ETCs and ctDNA, respectively. A total of 298 genetic alterations, including point mutations, indels, copy number variations (CNVs) and gene fusions, were identified in etDNAs from all the patients. However, only 74% and 57% of these alterations were detected in contemporaneous ETCs and ctDNA samples, with CNVs having the lowest detection sensitivity as 49% and 11%, especially in lung cancer patients without extrathoracic metastasis, as none of the CNVs detected in etDNAs were captured in plasma ctDNAs of these patients. Furthermore, driver mutations and rearrangements in etDNA showed a strong correlation to targeted therapy efficacy.
Conclusion:
This study demonstrated that etDNA had significantly higher tumor-specific mutation detection rate and sensitivity compared to ETCs and ctDNA. etDNA from supernatant of pleural effusion is a promising source for genetic testing to guide treatment-decision making in lung cancer. This study is funded by Shanghai Science and Technology Program (15ZR1406400).
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MA 20.14 - Genotyping of Lung Cancer Using Cell-Free DNA (cfDNA) from Cytologic Supernatant (CSN) (ID 9057)
14:30 - 16:15 | Presenting Author(s): Nicolas Marie Guibert | Author(s): Hisashi Tsukada, D.H. Hwang, T. Bale, E. Chambers, B. Ulrich, C.P. Paweletz, L.M. Sholl, Geoffrey R. Oxnard
- Abstract
- Presentation
Background:
Tumor genotyping is transforming lung cancer care but increasingly requires more tumor tissue. Advances in minimally invasive bronchoscopic techniques increase access to small lesions, but often result in smaller samples. With the advent of new cfDNA (“liquid biopsy”) genotyping technologies, we hypothesized that CSN might increase the yield from small FNAs, facilitating cancer genotyping.
Method:
We studied patients with known or suspected lung cancer undergoing FNAs. CSN, which is usually discarded, was collected under IRB approval. cfDNA was extracted after a hard spin (1600 Gs) and tested by both ddPCR (EGFR, KRAS mutations) and targeted next-generation sequencing (NGS).
Result:
14 patients with suspected or known lung cancer were studied at time of analysis (final diagnosis: 2 non-malignant, 9 adenocarcinomas, 1 small-cell carcinoma, 2 squamous cell carcinomas), including 12 EBUS-TBNAs and 2 CT-guided FNAs. Among 6 known KRAS and EGFR mutations, all could be detected with ddPCR of CSN, with allelic fraction (AF) ranging from 1%-46% (median 8.5%). No ddPCR false positives were seen across 9 cases. NGS analysis was piloted on 7 specimens; 5 failed due to insufficient residual DNA. In one specimen, an EGFR exon 19 deletion was detected at 6% AF (2% AF ddPCR). In the other, a BRAF V600E, PIK3CA E784D and TP53 V274F mutations were detected at 48% (46% AF ddPCR), 18% and 86% AF, respectively.
Conclusion:
Cytology supernatant, usually discarded, may be a rich source of fresh tumor DNA, increasing the yield from FNAs. This widely available biospecimen has potential for aiding resistance genotyping, reducing turnaround time of cancer genotyping, and possibly a future role in clarifying the malignant potential of non-diagnostic biopsies. Enrollment continues in order to optimize this biospecimen for NGS. Figure 1
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MA 20.15 - Discussant - MA 20.11, MA 20.12, MA 20.13, MA 20.14 (ID 10834)
14:30 - 16:15 | Presenting Author(s): Virginie Westeel
- Abstract
- Presentation
Abstract not provided
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