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Airway obstruction; Cryobiopsy; Paediatric bronchoscopy Obstrucción de las vías respiratorias; Criobiopsia; Broncoscopia pediátrica Obstrucció de les vies respiratòries; Criobiòpsia; Broncoscòpia pediàtrica Background and objective Cryotherapy in interventional bronchoscopy is a new treatment modality, which has recently been made available for the paediatric airway. Lack of experience and safety concerns have led to hesitant adaptation. The aim of this study was to assess indications, success rates and complications of airway cryotherapy in children. Methods Bronchoscopists from medical centre performing cryotherapy in patients between 0 and 18 years were invited to participate in a prospective study based on an online questionnaire. Patient and participant data were collected between June 2020 and June 2021. Results A total of 69 cryotherapy procedures were performed in 57 patients a for three main indications: Biopsy (30), restoration of airway patency (23) and foreign body aspiration (16). The overall success rate was 93%, the remaining 7% were performed for foreign body removal and required a switch of technique. Restoration of airway patency was successfully applied in various pathologies, including mucus plugs, bronchial casts and post traumatic stenosis. The diagnostic yield of transbronchial biopsies was 96%. No severe complications were encountered; one pneumothorax following a cryobiopsy required a chest drain for 48 h. No child was admitted to intensive care or died from a procedural complication. Conclusion In this largest paediatric case collection to date, cryotherapy was safe and carried a high success rate. Cryobiopsy compares favourably to the widely used forceps biopsy and could replace it in the future. Paediatric bronchoscopists are encouraged to add cryotherapy to their armamentarium of airway interventions. Open Access funding enabled and organized by Projekt DEAL.

Background. MYC (v-myc avian myelocytomatosis viral oncogene homolog) is one of the most frequently amplified genes in lung tumors. For the analysis of gene copy number variations, dPCR (digital PCR) is an appropriate tool. The aim of our study was the assessment of dPCR for the detection of MYC copy number variations (CNV) in lung tissue considering clinicopathological parameters. Material and Methods. MYC status was analyzed with dPCR as well as qPCR (quantitative PCR) using gDNA (genomic DNA) from tumor and adjacent nontumor tissue samples of lung cancer patients. The performance of MYC was estimated based on the AUC (area under curve). Results. The results of the MYC amplification correlated significantly between dPCR and qPCR (rS=0.81, P<0.0001). The MYC copy number revealed by dPCR showed statistically significant differences between tumor and adjacent nontumor tissues. For discrimination, a sensitivity of 43% and a specificity of 99% were calculated, representing 55 true-positive and one false-positive tests. No statistically significant differences could be observed for age, sex, and smoking status or the clinicopathological parameters (histological subtype, grade, and stage). Conclusion. The results of the study show that dPCR is an accurate and reliable method for the determination of MYC copy numbers. The application is characterized by high specificity and moderate sensitivity. MYC amplification is a common event in lung cancer patients, and it is indicated that the determination of the MYC status might be useful in clinical diagnostics.

Objectives MET c-Cbl binding site mutations constitute about 2 % of MET exon 14 alterations in lung cancer. Preclinical data suggests regarding these mutations as functional analogs of MET exon 14 skipping mutations, but clinical validation is lacking. Results We report the case of a patient with metastastic lung adenocarcinoma harboring a c-Cbl binding site alteration and demonstrate clinical, radiological and metabolic response to crizotinib with a PFS of 10.6 months. As escape mechanism, a typical MET resistance mutation could be identified. Conclusion MET c-Cbl binding site mutations should be regarded as a distinct subtype of MET exon 14 alterations. Patients with lung cancer harboring such mutations should be offered targeted therapy.

Purpose The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by 18F-FDG PET/CT and systematic endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) for precise target volume definition in stage III NSCLC. Methods This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011–06/2018). Inclusion criteria were curative treatment intent, 18F-FDG PET/CT and EBUS-TBNA prior to start of treatment. The lymphatic drainage was classified into echelon-1 (ipsilateral hilum), echelon-2 (ipsilateral LN-stations 4 and 7) and echelon-3 (rest of the mediastinum, contralateral hilum). The pattern of spread was classified according to all permutations of echelon-1, echelon-2, and echelon-3 EBUS-TBNA findings. Results In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (p p p = 0.0021, Breslow-Day test), while PET did not (p = 0.19). Conclusion Frequent patterns of LN-metastatic spread could be defined by EBUS-TBNA and PET and discrepancies in the pattern were seen between both methods. EBUS-TBNA showed more lobe and tumor laterality specific patterns of LN-metastases than PET and skipped lymph node stations were rare. These systematic relations offer the opportunity to further refine multi-parameter risk of LN-involvement models for target volume delineation based on pattern of spread by EBUS-TBNA and PET.

Purpose The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by 18F-FDG PET/CT and systematic endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) for precise target volume definition in stage III NSCLC. Methods This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011–06/2018). Inclusion criteria were curative treatment intent, 18F-FDG PET/CT and EBUS-TBNA prior to start of treatment. The lymphatic drainage was classified into echelon-1 (ipsilateral hilum), echelon-2 (ipsilateral LN-stations 4 and 7) and echelon-3 (rest of the mediastinum, contralateral hilum). The pattern of spread was classified according to all permutations of echelon-1, echelon-2, and echelon-3 EBUS-TBNA findings. Results In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (p

Background Tracheal and laryngotracheal surgery provides both excellent functional results and long-term outcomes in the treatment of tracheal stenosis. Consequently, challenging re-resections are rarely necessary. The purpose of this study was to compare the outcome of (laryngo-)tracheal re-resection and surgery after bronchoscopic interventions with that of primary surgery. Methods Patients undergoing resection for benign tracheal stenosis at our center between 1/2016 and 4/2020 were included. Perioperative characteristics and functional outcomes of patients were used for statistical analysis. Results Sixty-six patients who underwent (laryngo-)tracheal resection were included (previous resection [A = 6], previous stent [B = 6], previous bronchoscopic intervention w/o stenting [C = 19], untreated [D = 35]). Baseline parameters were largely comparable between groups with exception from group B that had significantly worse lung function. Group A necessitated more complex reconstructions (end-to-end: n = 1: 17%| cricotracheal n = 2: 33%| cricotracheal with mucosectomy n = 2: 33%| laryngoplasty: n = 1: 17%) than patients in group D (end-to-end n = 21: 60%| cricotracheal n = 14: 40%). Postoperative outcomes were comparable throughout groups (intensive care unit: 1[1–18] days; hospital stay: 8[5–71] days). Anastomotic complications were higher after previous stenting (A: 0%; B: 33.3%; C: 10.5%; D: 2.9%; B/D p = 0.008| surgical revisions: A: 16.7%; B: 33.3%; C: 0%; D: 5.7%; B/D, p = 0.035). Overall, postoperative lung function was significantly better (forced expiratory volume in 1 second: 63% ± 24 vs. 75% ± 20; p = 0.001 | PeakEF 3.3 ± 1.9 vs. 5.0 ± 2.2L; p = 0.001). No 90-day mortality was observed in any group. Median follow-up was 12(1–47) months. Conclusion In carefully selected patients treated in a specialized center, tracheal or laryngotracheal resection after previous tracheal interventions provides comparable outcome to primary surgery.

ZusammenfassungCOVID-19, ausgelöst durch Coronavirus SARS-CoV-2, ist eine neue, sich pandemisch ausbreitenden Infektionserkrankung, welche aktuell weltweit zu einer erheblichen Belastung der Gesundheitssysteme geführt hat. Krankenhausmitarbeiter stellen in Ländern mit hoher Krankheitsaktivität, wie China oder Italien, einen signifikanten Anteil der an COVID-19 Erkrankten und Verstorbenen dar. Bronchoskopische Untersuchungen führen beim untersuchten Patienten zu Hustenreiz und Aerosolbildung und beinhalten daher ein erhöhtes Infektionsrisiko für das Untersuchungsteam und für andere Patienten. In der aktuellen Pandemie sind daher besondere Maßnahmen bei der Durchführung bronchoskopischer Untersuchungen zu beachten, um das Infektionsrisiko zu senken.

Durch die steigende Anzahl an durchgefuhrten Thorax-Computertomographie(CT)-Untersuchungen in den letzten Jahren nimmt die Rate an zufallig entdeckten peripheren Lungenherden zu. Die fruhe Diagnosestellung geht bei Lungenkarzinomen einher mit einer Verbesserung der Prognose dieser meist todlich verlaufenden Erkrankung. Die diagnostische Sicherheit der Bronchoskopie mit konventionellen bioptischen Moglichkeiten (transbronchiale Zangenbiopsie unter Rontgendurchleuchtung) ist niedrig. Ein operatives Vorgehen sollte angestrebt werden, wenn kein begrundeter Zweifel an der Malignitat besteht und keine relevanten Komorbiditaten vorliegen. Bildgebende Verfahren, wie die 18F-Fluordeoxyglukose-Positronenemissionstomographie/Computertomographie (FDG-PET/CT) konnen die Dignitat eines Herds nicht sicher klaren und sind in dieser Situation wenig hilfreich. Die Verbesserung der diagnostischen Sicherheit durch eine histologische Sicherung, meist durch bronchoskopische Probeentnahme, sollte in dieser Situation gepruft werden. In den letzten Jahren wurden mehrere bronchoskopische Verfahren entwickelt, welche die diagnostische Sicherheit von peripheren Lungenherden deutlich erhohen. Durch die verbesserte Erreichbarkeit der Herde kommt zukunftig die Moglichkeit einer bronchoskopischen Lokaltherapie in Betracht.

Endobronchial ultrasound-guided transbronchial needle aspirations (EBUS-TBNAs) are well established for staging lung cancer. A growing number of publications report on lymphoma diagnosis via EBUS-TBNA-acquired cytology; however current guidelines recommend histologic diagnosis. Research on the value of EBUS-TBNA-acquired cytology versus surgical-acquired histology in the diagnosis of lymphoma is lacking.We conducted a retrospective review of patients with mediastinal lymphoma diagnosed between 2010 and 2016. Mediastinal lymphadenopathy was accessible through both EBUS-TBNAs and surgical procedures. All data were extracted from our clinic's medical database and analyzed.Fifty-one patients newly diagnosed with lymphoma in the mediastinum were identified (median age, 43.5 years; mean age, 48.6 ± 20.6 years). A minimally invasive procedure was performed as a first diagnostic step in 29 patients, whereas surgical biopsy was performed in the remaining 22. The time to final diagnosis was significantly longer if a minimally invasive procedure was performed first compared with a surgical procedure (mean, 44 days [median, 38 days] vs 16 days [median, 8 days]; p0.030). The number of procedures to obtain a final diagnosis ranged from one to five (median, 2 procedures per patient) in the EBUS-TBNA group. This was significantly higher than that in the surgical group (median, 1 procedure per patient; p0.00005).We demonstrate that surgical biopsies are safe and well tolerated for lymphoproliferative disease diagnosis and lead to a final diagnosis in the shortest possible time. Unnecessary procedures were significantly reduced if a surgical biopsy was performed as the first step.

Bronchial Thermoplasty (BT) is indicated in patients suffering from severe and symptomatic bronchial asthma despite maximal medical therapy. However, treatment of the right middle lobe (RML) bronchus is currently not recommended. The aim of this study was to investigate the safety and efficacy of BT if the RML bronchus is included. BT was performed in 17 consecutive patients, quality of life and pulmonary function were characterized before and 90 days after BT completion. Furthermore, we performed a clean-up bronchoscopy following every BT. This study was approved by the IRB of the University of Essen (No. 17-7356 BO) and registered as a retrospective observational study at the German Clinical Trials Registry (No. DRKS 00011550). The median baseline values of FEV1 and Asthma Questionnaire of Life Quality (AQLQ) were 1.33 l (0.91; 1.73) and 3.01 (2.76; 3.61), respectively, and significantly improved 90 days after treatment with FEV 1 at 1.75 l (p-value 0.002) and AQLQ 3.8 (p-value

Background:Large cell neuroendocrine carcinomas of the lung (LCNEC) is a rare entity occurring in less than 4% of all lung cancers. Due to its low differentiation and high glucose transporter 1 (GLUT1) expression LCNEC demonstrates an increased glucose turnover. Thus, PET/CT with 2-[18F]-fluoro-deoxyglucose (FDG) is suitable for LCNEC staging. Surgery with curative intent is the treatment of choice in early stage LCNEC. Prerequisite for this is correct lymph node staging. This study aimed at evaluating the diagnostic performance of FDG PET/CT validated by histopathology following surgical resection or mediastinoscopy. N-staging interrater-reliability was assessed to test for robustness of the FDG PET/CT findings.Methods:Between 03/2014 and 12/2020 46 patients with LCNEC were included in this single center retrospective analysis. All underwent FDG PET/CT for pre-operative staging and subsequently either surgery (n=38) or mediastinoscopy (n=8). Regarding the lymph node involvement, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for FDG PET/CT using the final histopathological N-staging (pN0 to pN3) as reference.Results:Per patient 14 ± 7 (range 4 - 32) lymph nodes were resected and histologically processed. 31/46 patients had no LCNEC spread into the lymph nodes. In 8/46 patients final stage was pN1, in 5/46 pN2 and in 2/46 pN3. FDG PET/CT diagnosed lymph node metastasis of LCNEC with a sensitivity of 93%, a specificity of 87%, an accuracy of 89%, a PPV of 78% and a NPV of 96%. Interrater-reliability was high with a strong level of agreement (κ=0.82).Conclusions:In LCNEC N-staging with FDG PET/CT demonstrates both high sensitivity and specificity, an excellent NPV but a slightly reduced PPV. Accordingly, preoperative invasive mediastinal staging may be omitted in cases with cN0 disease by FDG PET/CT. In FDG PET/CT cN1-cN3 stages histological confirmation is warranted, particularly in case of only moderate FDG uptake.

Background: The need to determine the aetiology of solitary pulmonary nodules (SPN) is high. The ArchimedesTM System combines virtual bronchoscopy navigation (VBN) with fused fluoroscopy (FF) in order to improve the guidance. Objective: To analyze the feasibility of ArchimedesTM interventions for the diagnosis of SPN. Methods: From 01-05/2020 16 patients with SPN were examined. Based on a specific CT scan the access way to the SPN was calculated and adjusted as needed. Interventions were done in general anesthesia with chest tube. Results: 16 Patients (43,8% female, 56,3% male) aged 64 years (±8,3) were included with a malignancy risk for the SPN (calculated with the Brock Model) of 40,6% (±19,3). SPN measured 14,9mm (±7,1). Localization were 43,8% left upper lobe, 25% right lower lobe, 25% right upper lobe, 6,3% middle lobe. The distance from the last reconstructed bronchus to the lesion was 21,5mm (± 12,7), the distance between target and pleura 20,1mm (± 16,8). Time for calculation 21 minutes (± 10,4), time to location of the SPN 14 minutes (±15,5). Bronchoscope with 4,2mm (93,8%) and 3mm (6,3%) outside diameter were used. The lesion could be seen in radial EBUS in 87,5% (50% adjacent, 25% central, 12,5% stop phenomenon). There were no major complications (25% mild bleeding managed by suction, no pneumothoraxes). Sensitivity was calculated 71,4%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 33,3% and accuracy 75%. Conclusion: A high diagnostic yield for small peripheral SPN can be achieved with ArchimedesTM interventions even if the distance from the last reconstructed bronchus to the target is over 20mm.

Introduction: In the era of targeted therapy of lung cancer, availability of adequate specimen samples for molecular analysis is increasingly important. EBUS-TBNA is often used for tissue acquisition, and the choice of the needle might influence the rate of successful molecular analysis. This prospective study evaluated quality and quantity of specimens obtained using different EBUS-TBNA needles. Methods: Consecutive patients with advanced lung cancer referred for EBUS-TBNA were included. A 22G steel needle (N1), a more flexible needle with a nitinol stylus (N2), or a core biopsy needle (N3) were used for EBUS-TBNA. Specimens were placed on a slide and weighed before transfer of tissue into formalin and sending for histopathological analysis, immunohistochemistry and next-generation sequencing (NGS). Tumour cellularity was assessed by an experienced pathologist. Results: 50 patients (28 male;mean 62.9y) with NSCLC (adeno n=38; squamous cell n=5; large cell n=3; other n=4) were included in the analysis. 25, 12 and 13 specimens were obtained with N1,N2 and N3, respectively. Mean specimen weight was 42.6±38.0 mg. Tumour cellularity was 1000 tumour cells in 6, 5, 6, 3, 8, 9 and 12 cases, respectively. Immunohistochemistry could be performed in all but 3 cases (2 with N2, 1 with N3). NGS could be done in 41 cases (82.0%; failure in 2 cases with N1, 6 with N2, 1 with N3). Tumour cellularity, sample weight and rate of successful NGS were significantly lower when EBUS-TBNA was performed with N2. Conclusion: The needle used for EBUS-TBNA had an impact on quantity and quality of tissue obtained for molecular analysis in NSCLC.

Background The optimal treatment for patients with locally advanced non-small-cell lung-cancer (NSCLC) cT4 cN0/1 cM0 is still under debate. The purpose of this study was to examine the long-term survival of cT4 cN0/1 cM0 NSCLC patients undergoing induction chemotherapy and concurrent radiochemotherapy before surgery. Methods All consecutive patients with confirmed NSCLC (cT4 cN0/1 cM0) treated with neoadjuvant chemotherapy, concurrent radiochemotherapy (RT/CTx) (45–46 Gy) and surgical resection between 2000 and 2015 were included. According to the UICC guidelines (8th edition), T4 stage was reanalysed by an expert radiologist. The mediastinal staging was performed by systematic EBUS-TBNA or mediastinoscopy. The primary end-point was overall-survival (OS). The power to detect an increase of early tumour-associated mortality (hazard ratio > 3.5) within the first 5 years after treatment in comparison to late deaths beyond 96 months was >80%. Results Overall, 67 patients were treated with concurrent RT/CTx. T4 criteria were fulfilled by all patients, and multiple T4 criteria by 53 patients. Seventy percent of patients had an initial PET/CT staging. The median follow-up period was 134 months. OS rates at 2, 5, 10 and 15 years were 83.6 ± 4.5%, 65.4 ± 5.9%, 53.3 ± 6.3% and 36.6 ± 6.8%, respectively. A total of 44.8% of patients achieved a pathologic complete response. In multivariable analysis, ypT category was the most predictive factor. OS at 5 years for ypT0 (n = 31) was 80.5%, and ypT1 (n = 11) was 62.5%. Main sites of failure were brain and pulmonary metastases in seven and three patients, respectively. The intercurrent annual death rate was estimated from the survival curve beyond 96 months and was found to be 4.75% (95% CI 2.40–9.27%). No significant increased mortality was observed during the first 5 years (annual death rate: 8.31% [95% CI 5.60–12.24%], hazard-ratio = 1.72 [95% CI 0.81–3.65]). Conclusions The effectiveness of this trimodality schedule is high in patients with cT4 cN0/1 cM0 NSCLC with excellent local control rates. Considering the annual death rate beyond 8 years of survival as an intercurrent death rate due to comorbidity, this treatment schedule reduces annual mortality to background even in the first 5 years after therapy.

These recommendations for physicians who perform bronchoscopy will help to protect those patients (un)-affected by the current COVID-19 pandemic, minimize the risk of transmission, and maintain clinical care for all patients.

Supplemental material, Reviewer_2_v.1 for Predictive value of Chartis measurement for lung function improvements in bronchoscopic lung volume reduction by Johannes Wienker, Rüdiger Karpf-Wissel, Faustina Funke, Christian Taube, Julia Wälscher, Jane Winantea, Sandra Maier, Khaled Mardanzai and Kaid Darwiche in Therapeutic Advances in Respiratory Disease

Supplemental material, Reviewer_1_v.1 for Predictive value of Chartis measurement for lung function improvements in bronchoscopic lung volume reduction by Johannes Wienker, Rüdiger Karpf-Wissel, Faustina Funke, Christian Taube, Julia Wälscher, Jane Winantea, Sandra Maier, Khaled Mardanzai and Kaid Darwiche in Therapeutic Advances in Respiratory Disease

Supplemental material, Author_Response_1 for Predictive value of Chartis measurement for lung function improvements in bronchoscopic lung volume reduction by Johannes Wienker, Rüdiger Karpf-Wissel, Faustina Funke, Christian Taube, Julia Wälscher, Jane Winantea, Sandra Maier, Khaled Mardanzai and Kaid Darwiche in Therapeutic Advances in Respiratory Disease

Supplemental material, Regression_Model_Supplementary for Predictive value of Chartis measurement for lung function improvements in bronchoscopic lung volume reduction by Johannes Wienker, Rüdiger Karpf-Wissel, Faustina Funke, Christian Taube, Julia Wälscher, Jane Winantea, Sandra Maier, Khaled Mardanzai and Kaid Darwiche in Therapeutic Advances in Respiratory Disease

Background: Despite the proof of principle that gene therapy can cure various monogenic diseases, limited clinical progress has been noted for gene therapy of the respiratory system. Certain anatomic features of the lungs, along with the suboptimal gene delivery vehicles utilized up to now, have significantly delayed successful clinical practice. Thus, the need for additional improvements towards safety and efficacy of the procedure is indispensable. Objective: The objective of this work was to review the progress and limitations of gene therapy in the treatment of lung disease with a focus on monogenic disease, chronic obstructive pulmonary disease and asthma and to present studies that provide a proof of principle that it works in different model systems and in patients. Method: A thorough search was performed on the aforementioned topic using Pubmed in order to identify relevant manuscripts. Several gene therapy studies for monogenic disorders affecting other organs or systems were also taken into consideration. Results: A hundred and thirty one papers were included. Inclusion criteria regarded novel gene transfer technologies of the past decade, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for pulmonary diseases. Conclusion: Current gene transfer protocols and vector design require additional amelioration. The rapidly evolving and much promising technology of CRISPR/Cas9 might possibly overcome the hurdles posed to date for effective implementation of gene therapy and become the basis for the onset of new clinical trials.

Background Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. Patients and methods The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. Results A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33–74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995–1.015), P=0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986–1.012), P=0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. Conclusions HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Register No. Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection).

OA embargo Objectives Chromosomal rearrangements involving ROS1 define a rare entity of lung adenocarcinomas with exquisite sensitivity to molecularly targeted therapy. We report clinical outcomes and genomic findings of patients with ROS1-positive lung cancer who were prospectively identified within a multiplex biomarker profiling program at the West German Cancer Center. Methods Standardized immunohistochemical (IHC) analysis, fluorescence in situ hybridization (FISH), and hotspot mutation analyses were performed in 1345 patients with advanced cancer, including 805 patients with metastatic lung adenocarcinoma. Clinical and epidemiological data were retrieved from the institutional database. Results ROS1 positivity by IHC analysis was detected in 25 patients with lung cancer (4.8% of lung adenocarcinomas), including 13 patients (2.5%) with ROS1 FISH positivity with a cutoff of at least 15% of events. Of the ROS1 IHC analysis–positive cases, 36% presented with concomitant oncogenic driver mutations involving EGFR (six cases, five of which were clinically validated by response to EGFR-targeting agents), KRAS (two cases), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), and BRAF. Three cases initially classified as ROS1 FISH–negative passed the threshold of 15% positive events when repeat biopsies were analyzed at progression. The median overall survival of the ROS1-positive patients (104 months) was significantly superior to that of the 261 patients with EGFR/anaplastic lymphoma kinase/ROS1–negative lung adenocarcinoma (24.4 months, p = 0.044). Interestingly, the overall survival of the 13 ROS1-positive patients with lung cancer from initiation of pemetrexed-based chemotherapy was significantly prolonged when compared with that of 169 pemetrexed-treated patients with EGFR/anaplastic lymphoma kinase/ROS1–negative adenocarcinoma (p = 0.01). Conclusions ROS1-positive metastatic lung adenocarcinomas frequently harbor concomitant oncogenic driver mutations. Levels of ROS1 FISH–positive events are variable over time. This heterogeneity provides additional therapeutic options if discovered by multiplex biomarker testing and repeat biopsies. © 2016 International Association for the Study of Lung Cancer

Introduction: Endobronchial ultrasound bronchoscopes (EBUS-scopes) actually represent the gold-standard to investigate mediastinal lymph nodes and centrally located lesions in patients affected by lung cancer. The commonly used EBUS-scope (Olympus BF-UC180F), however, does not allow a complete exploration of the segmental bronchi, just reaching the lobar bronchi or, sometimes, lower lobes segmental bronchi. The new EBUS-scope (Olympus BF-UC190F) has a smaller diameter and greater flexibility, and promises to provide a better access to more peripheral lesions. The aim of this study is to compare the two different generations of EBUS-scopes, to assess if peripheral access is improved by using the new one. Materials and Methods: We subsequently submitted 4 patients to an EBUS procedure with both EBUS-scopes (BF-UC180F and BF-UC190F), intending to introduce them into the segmental bronchi 1-6 on both sides. For a more careful evaluation of the results we created a numeric score, based on which part of the instrument was able to enter each of the bronchi. The statistical analysis was performed with the Student´s T test. Results: Despite the fact that our statistical analysis could be affected by the limited number of patients involved, we highlighted a statistically significative difference between the two generations of EBUS-scopes. Particularly, we were already able to prove that the new EBUS instrument allows a better exploration regarding LB 1+2 (p Conclusions: in our experience, the new EBUS-scope (BF-UC190F) allows a deeper access into segmental bronchi, therefore improving the diagnosis of peripheral lesions.

Introduction: Central Airway Obstruction (CAO) is life threatening condition and caused by various benign and malignant conditions. Airway Stents (AS) are used to alleviate symptoms by providing patency to airway lumen. AS have gone timely modifications over the years and the reasons for their use have varied. We present a retrospective analysis of 40 patients, who underwent AS placement at our center Methods: 40 patients, who underwent stent placement for CAO were included in this retrospective analysis. The stenotic segment was identified, and AS were introduced using rigid bronchoscopy under general anesthesia. Self-expanding Metal-Stents (SEMS) used were Ultraflex (7), Leufen Aerstent (8), Hanaro (4) Nitinol (2), others (2), polymer-stents used were Dumon (12), Vergnon (2) Polyflex (1) and Biodegradable Stents (4). Results: 26 M and 14 F with mean age of 65±13 yrs were included in this study. The underlying pathology was benign in 16 and malignant in 24 patients. Length of CAO was ≤ 4 cm in 29 and >4 cm in 6 patients. 5 cases presented with a fistula. Complications included granulation tissue formation (3), migration (8) and mucostasis (1). The location, type and complications of AS are summarized in Table 1. Discussion: Our analysis gives an overview about the choice and possible complications of AS. Migration occurred mostly in polymer AS (5/8) and those introduced in intermediate Bronchus (3/6). Though the AS are relatively safe, but complications such as migration need to be timely anticipated and sent securing procedure may be considered in such situations.