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J. Eckmayr
Moderator of
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MA05 - Innovative Techniques in Pulmonology and the Impact on Lung Cancer (ID 378)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Pulmonology
- Presentations: 12
- Moderators:J. Eckmayr, P.R. Mohapatra
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 1
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MA05.01 - Virtual Bronchoscopic Navigation-Guided Ultrathin Bronchoscopy for Diagnosing Peripheral Pulmonary Lesions (ID 4875)
16:00 - 16:06 | Author(s): M. Diez-Ferrer, A. Morales, N. Cubero, R. Lopez-Lisbona, N. Koufos, J. Dorca, A. Rosell
- Abstract
- Presentation
Background:
Diagnosis of peripheral pulmonary lesions with ultrathin bronchoscopy (UTH) has fewer complications than transthoracic needle aspiration (TTNA). However, diagnostic yield with UTH is lower. Virtual bronchoscopic navigation (VBN) might increase diagnostic performance of UTH. The main objective was to compare diagnostic yield of UTH with and without VBN.
Methods:
Prospective case-control study paired 1:2 for lesion size and localization, bronchus sign, sex and final diagnosis. LungPoint (Broncus, USA) was used to plan and navigate based upon online image analysis, putting endoscopic and virtual images in correspondence. Fluoroscopy was used in all. Sampling included bronchial washing and brushing (if no direct vision) or biopsy (if lesion directly visualized). Statistical analyses R-3.2.3.
Results:
Total of 63 patients (VBN and non-VBN, 21:42). Clinical characteristics in table 1. Diagnostic yield was 75% vs 43.9% (p=0.029). Factors associated to positive diagnosis in table 2. Further diagnostic techniques were needed in 14% vs 52% (p=0.001). No differences seen in procedure duration or complications. Figure 1 Figure 2
Conclusion:
VBN significantly improves the diagnostic yield of ultrathin bronchoscopy for diagnosing peripheral pulmonary lesions, especially those located in the utmost periphery and fluoroscopically not visible. Therefore, use of VBN reduces the need for further diagnostic procedures. Funded by La MaratóTV3-20133510, FIS-ETES PI09/90917, FUCAP and SEPAR.
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MA05.02 - Electromagnetic Navigation Bronchoscopy: A Prospective, Global, Multicenter Analysis of 1000 Subjects with Lung Lesions (ID 4643)
16:06 - 16:12 | Author(s): E. Folch, J. Flandes, S.J. Khandhar
- Abstract
- Presentation
Background:
Electromagnetic navigation bronchoscopy (ENB) may aid in accessing smaller, more peripheral lesions and hence facilitate earlier diagnosis. ENB may also provide a safer alternative to transthoracic biopsy, and allow adequate tissue capture for molecular testing, diagnosis, staging, and localization for surgery in a single anesthetic event. However, usage patterns, safety, and performance remain largely unexplored in a prospective, multicenter study.
Methods:
NAVIGATE is a global, prospective, multicenter study of ENB using the superDimension™ navigation system (Medtronic, Minneapolis). A pre-specified 1-month interim analysis was conducted on the first 1,000 primary cohort subjects enrolled at 29 centers in the United States and Europe. Enrollment and 2-year follow-up are ongoing.
Results:
One-month follow-up was completed in 933/1,000 subjects. Of 1,000 procedures, ENB was intended for lung biopsy in 96.4%, to place fiducial markers in 21.0%, and for dye marking in 1.7% (multiple indications in 34.9%). Lymph node biopsies were attempted in 33.4% of procedures (322/334 using linear endobronchial ultrasound [EBUS]). General anesthesia was used in 79.7% and radial EBUS in 54.3%. Among 1,129 lung lesions, fluoroscopy was used in 90.1% and rapid on-site pathology evaluation in 683/1035 (66.0%). Median lesion size was 20.0 mm (interquartile range 16.0 mm). Most lesions were in the peripheral (62.6%) or middle (30.1%) lung thirds. A bronchus sign was present in 48.4% and 6.3% were ground glass. Navigation was subjectively considered successful in 1,036 lesions (91.8%). Site-reported pathology results were read as malignant in 452 lesions (43.6%), including 38.1% with primary lung cancer. Of 247 lesions with adenocarcinoma or unspecified non-small-cell lung cancer, 70 (28.3%) were sent for molecular testing with adequate tissue in 56/70 (80.0%). Primary lung cancer clinical stage was 52.9% I; 10.7% II, 18.9% III, and 17.3% IV. Preliminary non-malignant results were obtained in 444 lesions (42.9%). An additional 140 lesions (13.5%) were read as inconclusive. Longer follow-up is required to calculate the true negative rate and diagnostic yield. ENB-related pneumothorax was 4.9% (49/1,000) overall and 3.2% Grade ≥2 based on the Common Terminology Criteria for Adverse Events scale. The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failures rates were 1.0% and 0.6%.
Conclusion:
Interim 1-month results suggest a low adverse event rate in the largest prospective, multicenter ENB study conducted to date. Continued enrollment and 2-year follow-up will elucidate the real-world utilization patterns, diagnostic yield, factors contributing to successful diagnosis, and the impact of ENB on lung cancer management.
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MA05.03 - A Single EBUS-TBNA Pass Yields Sufficient DNA for Targeted Molecular Testing in Lung Cancer (ID 4682)
16:12 - 16:18 | Author(s): T.L. Leong, M. Asselin-Labat, M. Christie, G. Hammerschlag, L. Irving, D.P. Steinfort
- Abstract
- Presentation
Background:
Development of drugs that target molecular pathways in lung cancer has made it increasingly important for diagnostic sampling to yield sufficient material for genotyping. At the same time, minimally invasive sampling techniques such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) result in smaller volume cytological specimens. It has been shown that at least 3 EBUS-TBNA passes per lesion are sufficient for cytological subtyping. However, the number of passes needed for mutational subtyping is unclear. We sought to determine the adequacy of a single EBUS-TBNA for genotyping clinically actionable mutations.
Methods:
Patients undergoing EBUS-TBNA for diagnosis of lung cancer were prospectively recruited. Paired samples from the same target lesion were obtained. The “reference” sample was the routine diagnostic specimen consisting of ≥3 passes, whereas the “study” sample comprised a single pass. DNA was extracted from both samples and subjected to quantitative and qualitative assessment. Sequencing for EGFR, KRAS, BRAF mutations was performed in adenocarcinoma/non-small cell lung cancer not otherwise specified (NSCLC-NOS) cases.
Results:
Samples were obtain in 41 patients. Cytological diagnosis was adenocarcinoma/NSCLC-NOS in 25 (61.0%), squamous cell carcinoma in 10 (24.4%), small cell lung cancer in 5 (12.2%), and carcinoid in 1 (2.4%) case. DNA extraction yielded a mean of 4.03μg, well above the minimum required quantity for targeted sequencing of 10ng (Table 1). DNA quality measured by DNA Integrity Number could be calculated in 35 (85%) cases with a mean of 8.9, where >7 is acceptable for sequencing (Table 1). Sequencing results of adenocarcinoma/NSCLC-NOS cases show mutations in EGFR in 6, KRAS in 8, BRAF in 1 case. Wild type was demonstrated in 6 cases. Molecular analysis of the corresponding study samples is proceeding.Table 1. DNA quantity and quality
Histological subtype Cases, n (%) Mean DNA quantity (μg) Mean DNA Integrity Number (DIN) Adenocarcinoma/NSCLC-NOS 25 (61.0) 3.83 8.8 Squamous cell carcinoma 10 (24.4) 2.65 9.0 Small cell lung carcinoma 5 (12.2) 5.28 9.0 Carcinoid 1 (2.4) 16.24 9.1 Overall 41 4.03 8.9
Conclusion:
A single EBUS-TBNA yields DNA of quantity and quality sufficient for molecular analysis, and is expected to be adequate for lung cancer genotyping.
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MA05.04 - Discussant for MA05.01, MA05.02, MA05.03 (ID 7109)
16:18 - 16:30 | Author(s): V. Kolek
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk of lung cancer (LC) independent of the effect of cigarette smoking. The prognosis of IPF-associated LC (IPF-LC) is known to be worse than the lone IPF or LC mainly due to the complications accompanying LC treatment with no established or standardized consensus. However, despite recent progress in the understanding of pathogenesis and the treatment of LC in general population based on the advances in molecular genomics, the pathogenesis or molecular profiles of IPF-LC has been largely unknown to date.
Methods:
We assessed genomic profiles of IPF-LC using targeted exome-sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling were performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted using CNVkit with focal events determined by GISTIC 2.0, and pathway analysis (KEGG) using DAVID.
Results:
Germline mutations in TERT (rs2736100,n=33) and CDKN1A (rs2395655,n=27) linked with IPF risk were detected in most samples. A total of 410 somatic mutations were identified with an average of 11.7 per tumor including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop, 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C→T transitions despite extensive smoking histories across most study subjects, suggesting more associations with APOBEC3B-related mutagenesis in the process of IPF-LC development, rather than smoking. TP53 (22/35,62.9%) and BRAF (6/35,17.1%) genes were found significantly mutated in IPF-LC. Recurrent focal amplifications in 3 chromosomal loci (3q26.33, 7q31.2, and 12q14.3), and 9p21.3 deletion were identified, and genes associated with JAK-STAT signaling pathway were significantly amplified in IPF-LC (P=0.012).
Conclusion:
IPF-LC is genetically characterized by the presence of somatic mutations reflecting viral and immune-related mutagenic processes in the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations.
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MA05.06 - Diagnosis of Chronic Obstructive Pulmonary Disease in Lung Cancer - A Population Based Study (ID 5974)
16:36 - 16:42 | Author(s): J.R. Goffin, G. Tang, G.R. Pond, S. Corriveau
- Abstract
- Presentation
Background:
Chronic obstructive pulmonary disease (COPD) and lung cancer are associated through tobacco. COPD is underdiagnosed in the general population. Patients with lung cancer suffer from dyspnea and hospitalization for respiratory complications, and underdiagnosis of COPD could confer worse symptoms and morbidity. Using Institute for Clinical Evaluative Sciences (ICES) data, we assessed the diagnosis of COPD in the lung cancer population in Ontario, Canada.
Methods:
Cancer registry, hospital ICD-10 codes, physician billing data, and vital statistics were abstracted in an anonymized manner from ICES. COPD was defined using the validated ICES-derived COPD cohort and spirometry use was assessed through billing codes. Cancer stage was available from cancer registry data. Analysis was conducted using ICES’s confidential, analytic virtual environment using SAS v9.3 in the population age >39 years. The local ethics board approved the study.
Results:
From 2004-2014, 90,783 individuals were diagnosed with lung cancer and 608,347 individuals diagnosed with COPD. Of individuals with lung cancer, 52.7% were male, median age at diagnosis was 65-69 years, and 82.8% have died. Of individuals with COPD, 51% were male, median age at diagnosis was 60-64 years, and 24.7% have died. The diagnosis of COPD was made at a rate of 8.7 persons per 1000 person-years. Among individuals having COPD, 48.4% underwent spirometry. 30.2% of individuals with lung cancer were also diagnosed with COPD and 60.8% underwent spirometry at any time. Among those with a diagnosis of both lung cancer and COPD, 73.6% underwent spirometry. For individuals with registry recorded stage data, 12,110 persons had stage I-II lung cancer, of whom 90.7% had spirometry and 55.9% had a diagnosis of COPD. Conversely, among 31,392 persons with stage III-IV lung cancer, 54.6% had spirometry and 46% were diagnosed with COPD (p<0.001 vs early stage for both).
Conclusion:
The diagnosis of COPD is not based on spirometry in half of cases. More patients with early stage lung cancer underwent spirometry and a higher rate of spirometry was associated with more diagnosis of COPD. Increased use of spirometry may improve the accuracy of a COPD diagnosis and may increase the diagnosis of COPD in advanced stage lung cancer, allowing improved dyspnea management in this population.
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MA05.07 - Identifying Comorbid Disease on Chest CT Scans in a Lung Cancer Screening-Eligible Cohort (ID 5764)
16:42 - 16:48 | Author(s): E.A. Regan, B. Make, G. Kinney, M.J. Budoff, D. Dyer, J. Curtis, R.P. Bowler, M. Han, T.H. Beaty, J. Hokanson, E. Kern, D. Lynch, E. Van Beek, E. Silverman, J.D. Crapo, J.H. Finigan
- Abstract
- Presentation
Background:
Lung cancer screening (LCS) with chest CT scans in high-risk smokers has been demonstrated to save lives. Medicare and private insurers now cover these scans for beneficiaries under specific criteria. However, most smokers will die of comorbid smoking-related diseases rather than lung cancer itself. Important information about comorbid conditions is available on screening chest CT scans, but the prevalence of these comorbidities has not been comprehensively assessed.
Methods:
COPDGene subjects from the Phase 1 visit who met USPSTF criteria for LCS (age > 55, >30 pack years smoking, current or former smokers within 15 years of smoking cessation or current smokers) were assessed for coronary calcification, emphysema, gas trapping, airway wall thickening and vertebral bone density on standard dose CT scans. A new diagnosis of emphysema, osteoporosis, or cardiovascular disease was assumed when there was no self-report of diagnosis or medication use.
Results:
In 76% of CT scans from LCS-eligible COPDGene subjects, we found abnormal emphysema (>5% low attenuation area @-950 Hounsfield units), airway wall thickening or gas trapping (>20% low attenuation area @-856 Hounsfield units). Osteoporosis was identified in 54% of all CT scans, and abnormal coronary artery calcium was present in 51%. In non-COPD smokers a new diagnosis of emphysema, osteoporosis or coronary calcification was found in 741 (48%) subjects. Overall, 75% of LCS eligible CT scans showed one or more non-cancer diagnoses.
Conclusion:
Enhanced readings of the lung cancer screening scans could identify individuals with previously undiagnosed osteoporosis, atherosclerotic heart disease, emphysema and COPD. Identification and treatment for these conditions may reduce morbidity and mortality, improve quality of life and enhance smoking cessation.
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MA05.08 - Discussant for MA05.05, MA05.06, MA05.07 (ID 7047)
16:48 - 17:00 | Author(s): K. Zarogoulidis
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
Radiation pneumonitis is a major toxicity after the thoracic radiotherapy, with no method available to accurately predict the individual risk. This was a prospective study to evaluate the exhaled nitric oxide as a predictive biomarker for radiation pneumonitis in the patients received the thoracic radiotherapy
Methods:
A total of 68 patients with lung cancer or esophageal cancer, who received the thoracic radiotherapy, were enrolled in the present study. Each patients underwent the exhaled nitric oxide measurement before the radiotherapy and at the end of radiotherapy. Pneumonitis toxicity was scored using the Common Terminology Criter
Results:
Of the 68 patients, 65 were evaluable. The pneumonitis toxicity grade were grade 3 for 6, grade 2 for 11 and grade0-1 for48. The exhaled NO measured before radiotherapy and at the end of radiotherapy were 23.05±9.59 (range 10-53) and 22.89±8.60(range 11-60) ppbs.For the exhaled NO ratio, the AUC is 0.879 (95%CI0.774-0.984). The accuracy of predicting the symptomatic patients was identified “good” according to the predictive ability criteria and the optimal cutoff value was tested as 1.305. For the exhaled at the end of RT, the AUC is 0.774 (95%CI 0.656-0.892). The accuracy of predictive the symptomatic patients was evaluated “fair” ,The optimal cutoff value was identified 19.5 ppbs.
Conclusion:
The exhaled nitric oxide ratio>1.305 or the exhaled nitric oxide at the end of radiotherapy>19.5ppbs was found to have a closely relation with radiation pneumonitis.
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- Abstract
- Presentation
Background:
Detection of EGFR mutations using cell-free DNA in plasma has recently emerged as a novel diagnostic approach to lung carcinoma. This “liquid biopsy” (LB) may also be useful for monitoring disease activity in EGFR-mutated tumors as well as in the management of EGFR-tyrosine kinase inhibitor (TKI) therapy. We present data collected in one year of use and report on applicability and diagnostic value in daily clinical practice.
Methods:
EGFR Mutations were analyzed using the semi-quantitative Roche cobas® EGFR Mutation Test v2, comprising 42 mutations. Cell free DNA was extracted from EDTA-Blood with the Qiagen QIAsymphony circulating DNA Kit. LB was initially used for follow-up of known EGFR-mutated tumors and/or in patients under TKI-therapy. Subsequently, we introduced routine LB testing in the primary diagnostic workup of lung cancer patients.
Results:
From July 2015 to June 2016 we performed a total of 92 liquid biopsies in 77 patients (60% male, mean age 65y) in whom EGFR mutations could be detected in 10 cases (13%). EGFR status from histological samples was available in 40 patients, in 14 (18%) of them mutations were reported. Compared to histological EGFR status, LB reached a sensitivity and specificity of 0.57 and 0.96, respectively. A total of 9 patients had multiple LB testing during follow-up. Three of them initially had detectable mutations by LB, which turned undetectable upon tumor-specific treatment. Two patients remained EGFR-positive during follow-up despite of therapy, whereas four patients remained negative throughout follow-up and therapy. Resistance mutations under TKI-therapy were not observed. Primary LB (before initiation of any tumor-specific therapy) was obtained from 47 patients (72% male, mean age 66y). EGFR mutations by LB were detected in 2 patients (4%; 1 Ins. Exon-20, 1 L858R), while histology revealed EGFR mutations in 2 out of 22 patients (9%; both L858R). Comparison yielded a sensitivity of 0.5 and a specificity of 0.95 for LB.
Conclusion:
Testing for EGFR mutations using cell-free DNA has been established as a new powerful tool in the field of pulmonary oncology. Apart from sole detection of EGFR mutations, especially the application of LB in following patients over time will provide valuable new opportunities in clinical routine and decision making
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- Abstract
- Presentation
Background:
Photodynanic therapy (PDT), is a treatment modality for many cancers, and uses a tumor-specific photosensitizer and laser irradiation. PDT is recommended as a treatment option for centrally located early lung cancer. The detection of peripheral lung cancers is increasing, and stereotactic body radiotherapy (SBRT) and percutaneous thermal ablation are emerging as alternatives to surgical resection, but PDT has not been a modality. 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 1.0 mm in diameter composite-type optical fiberscope (COF), and we evaluated the feasibility of PDT using COF for peripheral lung cancer.
Methods:
This phase I study enrolled patients with peripheral lung cancers (primary tumor< 20 mm, stage IA), which were definitively diagnosed by bronchoscopic modalities using radial-probe endobronchial ultrasound (EBUS) and guide sheaths. We conducted irradiation using a diode laser (664 nm) and optical fiberscope (COF), four hours after the administration of NPe6 40 mg/m2. Before performing PDT, we evaluated the tumor lesions using EBUS through the guide sheaths for peripheral small lesions. Then, we introduced the COF into the peripheral lung cancer, observed the lesions and irradiated of red light 664 nm (120 mW, 50 J/cm2).
Results:
Three patients met our criteria, and 2cases were adenocarcinoma and 1 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, there was no morbidity including pneumothorax, pneumonia, skin photosensitivity.
Conclusion:
The 1.0 mm COF was a very useful device of NPe6-PDT for peripheral lung cancers, and PDT using the COF was a feasible and non-invasive treatment. Now, we have started phase II study of PDT using the COF for peripheral lung cancers. In the future, for non-invasive adenocarcinoma such as AIS, NPe6-PDT using COF will play an important role.
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MA05.12 - Discussant for MA05.09, MA05.10, MA05.11 (ID 6990)
17:18 - 17:30 | Author(s): J. Moldvay
- Abstract
- Presentation
Abstract not provided
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