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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.

This post-hoc analysis of the AIRFLOW-2 trial investigated the changes in airway CT-parameters after targeted lung denervation (TLD) and whether these changes are associated with treatment response. In the treatment group (n = 32), an improvement in air trapping was significantly associated with an improvement in residual volume (RV). Furthermore, improvements in Pi10 and airway lumen were significantly associated with an improvement in both RV and FEV1. Our results could suggest that when improving airway characteristics like decreasing airway wall thickness and increasing the airway lumen, this leads to less air trapping and an improvement in clinical outcomes.

Purpose EGFR tyrosine kinase inhibitor (TKI) therapy in EGFR-mutated lung cancer is limited by acquired resistance. In half of the patients treated with first/second-generation (1st/2nd gen) TKI, resistance is associated with EGFR p.T790M mutation. Sequential treatment with osimertinib is highly active in such patients. Currently, there is no approved targeted second-line option for patients receiving first-line osimertinib, which thus may not be the best choice for all patients. The present study aimed to evaluate the feasibility and efficacy of a sequential TKI treatment with 1st/2nd gen TKI, followed by osimertinib in a real-world setting. Methods Patients with EGFR-mutated lung cancer treated at two major comprehensive cancer centers were retrospectively analyzed by the Kaplan–Meier method and log rank test. Results A cohort of 150 patients, of which 133 received first-line treatment with a first/second gen EGFR TKI, and 17 received first-line osimertinib, was included. Median age was 63.9 years, 55% had ECOG performance score of ≥ 1. First-line osimertinib was associated with prolonged progression-free survival (P = 0.038). Since the approval of osimertinib (February 2016), 91 patients were under treatment with a 1st/2nd gen TKI. Median overall survival (OS) of this cohort was 39.3 months. At data cutoff, 87% had progressed. Of those, 92% underwent new biomarker analyses, revealing EGFR p.T790M in 51%. Overall, 91% of progressing patients received second-line therapy, which was osimertinib in 46%. Median OS with sequenced osimertinib was 50 months. Median OS of patients with p.T790M-negative progression was 23.4 months. Conclusion Real-world survival outcomes of patients with EGFR-mutated lung cancer may be superior with a sequenced TKI strategy. Predictors of p.T790M-associated resistance are needed to personalize first-line treatment decisions.

OA Förderung 2023

Background: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. Objective: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. Method: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score at 6 months. Results: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by −10.6 [−15.9 to −5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. Conclusion: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

Purpose/introduction [18F]FDG-PET/CT is the standard imaging-technique for radiation treatment (RT) planning in locally advanced non-small cell lung cancer (NSCLC). The purpose of this study was to examine the additional value of endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) to standard PET/CT for mediastinal lymph-node (LN) staging and its impact on clinical target volume (CTV). Materials and methods All consecutive patients with primary stage III NSCLC who underwent [18F]FDG-PET/CT and EBUS-TBNA prior to RT were analyzed from 12/2011 to 06/2018. LN-stations were assessed by an expert-radiologist and a nuclear medicine-physician. CTV was evaluated by two independent radiation oncologists. LNs were grouped with increasing distance along the lymphatic chains from primary tumor into echelon-1 (ipsilateral hilum), echelon-2 (LN-station 7 and ipsilateral 4), and echelon-3 (remaining mediastinum and contralateral hilum). Results A total of 675 LN-stations of which 291 were positive for tumor-cells, were sampled by EBUS-TBNA in 180 patients. The rate of EBUS-positive LNs was 43% among all sampled LNs. EBUS-positivity in EBUS-probed LNs decreased from 85.8% in echelon-1 LNs to 42.4%/ 9.6% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher’s exact test). The false discovery rate of PET in comparison with EBUS results rose from 5.3% in echelon-1 to 32.9%/ 69.1% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher’s exact test). Sensitivity and specificity of FDG-PET/CT ranged from 85 to 99% and 67 to 80% for the different echelons. In 22.2% patients, EBUS-TBNA finding triggered changes of the treated CTV, compared with contouring algorithms based on FDG-avidity as the sole criterion for inclusion. CTV was enlarged in 6.7% patients due to EBUS-positivity in PET-negative LN-station and reduced in 15.5% by exclusion of an EBUS-negative but PET-positive LN-station. Conclusion The false discovery rate of [18F]FDG-PET/CT increased markedly with distance from the primary tumor. Inclusion of systematic mediastinal LN mapping by EBUS-TBNA in addition to PET/CT has the potential to increase accuracy of target volume definition, particularly in echelon-3 LNs. EBUS-TBNA is recommended as integral part of staging for radiochemotherapy in stage III NSCLC.

Sarcoidosis is a granulomatous systemic disease of unknown etiology most commonly affecting the lungs and thoracic lymph nodes. The diagnosis is based on typical clinical radiologic appearance and histology with evidence of noncaseating epithelioid cell granulomas without central necrosis. In the acute form, Löfgren's syndrome, histologic confirmation may not be necessary. Approximately half of patients may develop a chronic form, and extrathoracic organ involvement should be investigated during the course. Indications for therapy are based on functional limitations, marked organ-related or systemic symptoms, and life-threatening organ manifestations (cardiac, central nervous system, renal, and ocular sarcoidosis). To date, there is no approved drug therapy for sarcoidosis. Administration of immunosuppressants such as glucocorticosteroids and as add-on or sequential, methotrexate, azathioprine or mycophenolate mofetil is recommended in the currently published international guideline.

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.

Rebiopsies of non-small cell lung cancers (NSCLC) are mainly performed to (i) cover the evolution of potentially amenable resistance mechanisms against a targeted therapy, and (ii) to identify new therapeutic targets which were not detected in the initial diagnostic biopsy. Comprehensive systematic analyses evaluating the value of rebiopsies are missing.Clinical databases from two large comprehensive cancer center networks were queried following prespecified criteria to identify prospectively entered NSCLC cases with at least one rebiopsy at disease progression. Clinicopathological and biomarker findings including multigene sequencing were correlated with clinical outcomes.From a total of 17,477 stage IV NSCLC patients, a cohort of 403 evaluable patients undergoing at least one rebiopsy of a primary tumor or metastasis was retrieved. Changes in biomarker profiles as compared to baseline were observed in 48.9%. In 31.3% of cases, findings of potential therapeutic relevance were revealed, including 18 patients (4.4%) with a targetable marker only detected at rebiopsy. New findings were more frequent (greater than50%) in NSCLC with EGFR/ALK/ROS1 alterations, including mutations of the dominant oncogene, TP53 mutations, and MET or ERBB2 amplifications. Patients undergoing rebiopsy exhibited superior overall survival compared to a control group, irrespective of presence (HR 0.28) or absence (HR 0.20, both p 0.001) of a therapeutically targetable aberration.Rebiopsies at progression of advanced NSCLC are strongly supported by a high rate of clinically relevant findings. Current clinical practice selects a patient population with exceptional outcomes, which merits further characterization.

in press

The pivotal PACIFIC trial defined durvalumab consolidation as the new standard of care in patients with stage III non-small-cell lung cancer treated with definitive radiochemotherapy. The authors characterized the durvalumab effect after induction chemotherapy according to the ESPATUE trial and definitive radiochemotherapy. All consecutive patients with stage III non-small-cell lung cancer receiving definitive radiochemotherapy between January 2017 and February 2020 were included. Primary end points were progression-free survival and overall survival. Altogether, 160 patients (75 PD-L1-positive, 62 PD-L1-negative, 23 unknown) received definitive radiochemotherapy, 146 (91%) of whom received prior induction chemotherapy. Durvalumab consolidation showed high effectiveness overall and in the good-risk group according to the PACIFIC trial (log-rank test: p < 0.005). Hazard ratios for progression-free survival and overall survival were at the lower limits of those in the PACIFIC trial. These results were robust to adjustment for potential confounders by propensity score weighting. Eastern Cooperative Oncology Group (ECOG) performance status was the most important pretreatment prognostic factor. Tweetable abstract High effectiveness according to the PACIFIC and ESPATUE trials: patients were treated with induction chemotherapy, definitive radiochemotherapy and consolidation immunotherapy. A durable and remarkable tumor response was achieved in the real-world clinical routine. Plain language summary The PACIFIC trial is the major landmark trial for stage III non-small-cell lung cancer (NSCLC) patients treated with combined chemoradiation and defined immunotherapy as maintenance treatment and the new standard of care in patients with stage III NSCLC. Here the authors report a retrospective study comparing consecutive stage III NSCLC patients receiving induction chemotherapy and definitive chemoradiation with or without durvalumab consolidation in a high-volume lung cancer center. After induction chemotherapy, chemoradiation and immune checkpoint inhibition, a durable and remarkable tumor response can be achieved in the clinical routine. Consolidation immunotherapy with durvalumab can be confirmed as a strong innovative therapeutic option in NSCLC in almost all subgroups of patients.

Johannes Wienker, Kaid Darwiche, Julia Wälscher, Jane Winantea, Michael Hagemann, Erik Büscher, Abhinav Singla, Christian Taube, Rüdiger Karpf-Wissel Department of Pneumology, University Medicine Essen- Ruhrlandklinik, Essen, Nordrhein-Westfalen, GermanyCorrespondence: Johannes Wienker, Department of Pneumology, University Medicine Essen- Ruhrlandklinik, Tüschener Weg 40, Essen, Nordrhein-Westfalen, 45239, Germany, Tel +49 2014334222, Fax +49 2014331988, Email johannes.wienker@stud.uni-due.deBackground: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) can be a successful treatment for end-stage emphysema patients. The reduction of hyperinflation enhances ventilatory mechanics and diaphragm function. Understanding predictors for treatment success is crucial for further improvements.Purpose: The aim of this study was to assess the effect of the target lobe volume reduction (TLVR) in relation to the ipsilateral lung volume reduction (ILVR), affected by the compensatory expansion of the adjacent lobe, on the outcome after BLVR with valves.Patients and Methods: The volumetric relationship of ILVR% to TLVR%, addressed as Reduction Ratio (R), was recorded in 82 patients and compared to changes in lung function, physical performance and quality of life. A small value for R implies a relatively low volume reduction of the ipsilateral lung (ILVR) compared to the volume reduction of the target lobe (TLVR). Additionally, the minimal clinically important difference (MCID) for R was calculated.Results: Patients with a smaller Reduction Ratio (R < 0.2) showed minor improvements at the 3 months follow-up compared to patients with R ≥ 0.2 (mean changes of 39 mL (5.8%), – 395 mL (– 4.9%) and 96 mL (7.1%) versus 231 mL (33%), – 1235 mL (– 20%) and 425 mL (29%) in the forced expiratory volume in 1s (FEV1), residual volume (RV) and inspiratory vital capacity (IVC), respectively, and – 3 m and 0 points versus 20.4 m and – 3.4 points in the 6-minute-walking-distance (6MWD) and COPD assessment test (CAT) score respectively). With a combined value of 0.185, a MCID for R was calculated with established anchors (FEV1, RV, and 6MWD) for emphysema patients.Conclusion: Extensive compensatory hyperinflation of the adjacent non-treated lobe after BLVR results in decreased ILVR, which is responsible for a lack of meaningful improvements in ventilatory mechanics and clinical outcome, despite technically successful lobe volume reduction.Keywords: emphysema, ipsilateral lung volume, reduction ratio, volume shift

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis. Methods: In this post hoc analysis of a prospective, randomized, controlled, multicentre study, 359 patients with ILD requiring diagnostic bronchoscopic tissue sampling were included. TBLF and TBLC were both used for each patient in a randomized order. Histological assessment was undertaken on each biopsy and determined whether sarcoid was a consideration. Results: A histological diagnosis of sarcoidosis was established in 17 of 272 cases for which histopathology was available. In 6 out of 17 patients, compatible findings were seen with both TBLC and TBLF. In 10 patients, where the diagnosis of sarcoidosis was confirmed by TBLC, TBLF did not provide a diagnosis. In one patient, TBLF but not TBLC confirmed the diagnosis of sarcoidosis. Conclusions: In this post hoc analysis, the histological diagnosis of sarcoidosis was made significantly more often by TBLC than by TBLF. As in other idiopathic interstitial pneumonias (IIPs), the use of TBLC should be considered when sarcoidosis is suspected.

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.

Simple Summary Neoadjuvant immunotherapy is a novel approach for lung cancer patients in stages where curative intent treatment is possible. The rationale is a based on the idea that recognition by the immune system is activated by the entire tumor prior to surgical resection. Promising pathologic response rates have been reported and the impact on survival is currently investigated in ongoing studies. Abstract In early-stage lung cancer, recurrences are observed even after curative resection. Neoadjuvant immunotherapy might be a promising approach to eliminate micrometastasis and to potentially reduce recurrence rates and improve survival. Early trials have shown encouraging rates of pathologic response to neoadjuvant therapy and have demonstrated that surgery can be safely performed after neoadjuvant immunotherapy with various agents and in combination with chemo-(radio)therapy. However, whether these response rates translate into improved disease-free survival rates and overall survival rates remains to be determined by ongoing phase III studies.

Background Large cell neuroendocrine carcinoma 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 ([18F]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 [18F]FDG PET/CT validated by histopathology following surgical resection or mediastinoscopy. N-staging interrater-reliability was assessed to test for robustness of the [18F]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 [18F]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 [18F]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, the final stage was pN1, in 5/46 pN2 and in 2/46 pN3. [18F]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%. In the four false positive cases, the [18F]FDG uptake of the lymph nodes was 33 to 67% less in comparison with that of the respective LCNEC primary. Interrater-reliability was high with a strong level of agreement (κ = 0.82). Conclusions In LCNEC N-staging with [18F]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 [18F]FDG PET/CT. In [18F]FDG PET/CT cN1-cN3 stages histological confirmation is warranted, particularly in case of only moderate [18F]FDG uptake as compared to the LCNEC primary.

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.

Major advances in molecular profiling for available targeted treatments and immunotherapy for lung cancer have significantly increased the complexity of tissue-based diagnostics. Endobronchial ultrasound-guided transbronchial needle aspirations (EBUS-TBNA) are commonly performed for diagnostic biopsies and lymph node staging. EBUS-TBNA has increasingly become one of the main sources of tumor cells for molecular analyses. As a result, there is a growing need for high quality EBUS-TBNA samples with adequate cellularity. This has increased the technical demands of the procedure and has created additional challenges, many of which are not addressed in the current EBUS guidelines. This review provides an overview of current evidence on the technical aspects of EBUS-TBNA in light of comprehensive sample processing for personalized lung cancer management. These include sonographic lymph node characterization, optimal needle choice, suction biopsy technique, and the role of rapid on-site evaluation. Attention to these technical details will be important to maximize the throughput of EBUS-TBNA biopsies for molecular testing.

Objective BRAF mutations have been subtyped in three functional classes with different oncogenic modes of action. The clinical impact of BRAF mutational subtypes in non–small-cell lung cancer (NSCLC) remains to be defined. So far, ambiguous results were reported from analyses of heterogeneous patient cohorts. Methods We studied patients with metastatic or recurrent NSCLC who were sequentially enrolled in precision oncology programs at two large German lung cancer centres from 2009 to 2019. The study period allowed evaluating the specific impact of BRAF V600E-targeting. Results In a cohort of 72 patients, BRAF mutation subtyping revealed p.V600E mutations in 31 cases (43%), whereas 41 cases (57%) harboured 18 different BRAF mutational subtypes of functional classes II/III. Functionally relevant comutations were observed in 6.4% of class I, and 24.4% of class II/III BRAF mutations. Most patients were treated with chemotherapy. Targeted therapy was administered in 11 patients with a response rate of 72.7%. PD-1/PD-L1-immunotherapy was given in 14 patients with a response rate of 28.6%. Overall survival of patients with BRAF-mutated NSCLC was inferior (HR 1.38, p = 0.048) as compared to patients with BRAF wild-type cancers. Median time-to-treatment-failure with BRAF-targeting agents was shorter as compared to approved targeted therapy of other oncogenic drivers (HR 1.97, p = 0.05). Survival outcomes were not impacted by BRAF mutation subtype functional class. Conclusions Patients with BRAF-mutated NSCLC have an inferior prognosis, which is not determined by BRAF mutation functional class. In contrast to NSCLC with other tractable driver mutations, BRAF-mutated NSCLC exhibit high susceptibility to immune checkpoint inhibitors.