Objectives: In 2021, the German Federal Joint Committee (G-BA) introduced minimum volume regulations (MVRs) for the surgical treatment of lung cancer with the aim of improving quality of care through centralization. The present study aimed to evaluate the impact of this regulation on the development of lung cancer surgery in Germany. Methods: We performed a retrospective analysis based on the AOK (medical insurance) minimum volume transparency lists (2024-2026) and certification data from the German Cancer Society (DKG). Primary endpoint was the development of hospital locations according to MVRs. Secondary endpoints included the number of operations, the number of DKG-certified lung cancer centers (LCs), and the percentage of procedures performed in DKG-certified LCs. Results: Nationwide, the number of hospital locations fell by 19.6% between January 2022 and June 2025 following the implementation of the MVRs, while the number of anatomical lung resections increased by 11.3%. The proportion of procedures performed at hospital locations with ≥75 operations per year (≙MVRs) increased from 42.3% to 82.2%. The number of DKG-certified LCs went up by 24.2% (62 to 77), and the percentage of resections performed there went from 56.6% to 69%. Lastly, 17.8% of hospital sites still got a billing permission, even though they did not meet the MVRs. Conclusions: Implementation of the MVRs was associated with substantial structural centralization of lung cancer surgery in Germany, characterized by fewer hospital sites (-19.6%), increased surgical volumes (+11.3%), and a growing proportion of care delivered in DKG-certified LCs (+24.2%).

BACKGROUND:Endoscopic lung volume reduction (ELVR) is increasingly used for treating patients with chronic obstructive pulmonary disease (COPD) and severe hyperinflation. Data on sex differences in ELVR outcomes are lacking, highlighting the need for detailed analysis. METHODS:This retrospective analysis examines sex-specific outcomes of ELVR with bronchoscopic valve placement using data from the German Lung Emphysema Registry (January 2017 to January 2025). RESULTS:The final analysis included 778 patients, 378 (47.2%) women, mean age 65.9±7.6 years. No significant differences in age or body mass index. At baseline, women had slightly better forced expiratory volume in 1 s (FEV1)% (31.4±8.5 vs 28.1±8.1, p<0.001) and vital capacity% (63.6±16.9 vs 59.2±14.8, p<0.001), but similar residual volume (RV)%. Men had higher rates of cardiovascular diseases, including coronary artery disease (20.9% vs 11.7%) and atrial fibrillation (7.3% vs 3.5%), p<0.05. Despite this, women reported a higher symptom burden with higher COPD Assessment Test (CAT) scores (25.9±6.1 vs 24.9±6.1, p<0.001), but similar St. George's Respiratory Questionnaire (SGRQ) scores. Follow-up at 3 months for 574 patients showed no sex differences in ΔFEV1%, ΔRV% or Δdiffusing capacity of the lung for carbon monoxide%. Differences in treatment response were noted for ΔCAT score (-4.3±6.8 vs -1.9±6.1, p<0.001), ΔSGRQ (-13.2±17.3 vs -5.5±12.48, p<0.001), but not for dyspnoea. Multivariable analyses showed female sex (OR 1.89) as an independent predictor for SGRQ response, along with emphysema heterogeneity (OR 1.01) and pulmonary function response (ΔRV, OR 0.73). CONCLUSIONS:Sex may not influence physiological outcomes but may impact symptom severity and quality of life, raising the question of whether sex should be considered when determining minimal clinically important differences in COPD.

INTRODUCTION:Endoscopic lung volume reduction (ELVR) via valves is a proven therapeutic option for patients with advanced chronic obstructive pulmonary disease (COPD) and emphysema without collateral ventilation. Body mass index (BMI), a simple measure of adiposity, has a complex relationship with COPD. A lower BMI is associated with increased mortality in this patient population. However, the influence of BMI on the outcome of ELVR remains unclear. METHODS:This analysis was conducted with data from the Lung Emphysema Registry (www.lungenemphysemregister.de), a national, prospective, multicentric, producer-independent, open-label clinical trial. The aim of this study was to evaluate the impact of baseline BMI on treatment outcomes after ELVR. Patients were grouped according to their BMI as follows: underweight (BMI <20 kg/m2, n = 76), normal weight (20-24.9 kg/m2, n = 282), overweight (BMI = 25-30 kg/m2, n = 146), and obese (BMI >30 kg/m2, n = 45). RESULTS:Baseline parameters were characteristic of patients with advanced lung emphysema. Emphysema scores and heterogeneity indices of the target lobe were greater in patients with lower BMI. Patients with a lower BMI had worse lung function parameters (FEV1, RV, DLCO, pCO2) and a higher CAT score. All groups showed significant improvements after ELVR at the 3-month follow-up in terms of lung function parameters, exercise capacity, and quality of life. Treatment outcomes were comparable across BMI groups, with the notable exception of more pronounced improvement in CAT scores among underweight patients. The complication rates were low and comparable among the groups, although obese patients had a higher rate of ICU admissions. CONCLUSION:This study suggests that ELVR provides meaningful clinical benefits regardless of BMI in patients with advanced lung emphysema, particularly when dyspnea is primarily attributable to pulmonary pathology. The findings suggest that BMI should be considered as a reflection of disease phenotype and clinical state rather than serving as a predictor for treatment response after ELVR.

Endoscopic lung volume reduction (ELVR) using endobronchial valves is an established treatment for advanced COPD and emphysema. To reduce procedure-related complications such as pneumonia or exacerbations, peri-interventional antibiotic prophylaxis is commonly used; however, its clinical benefit remains uncertain. We aimed to evaluate the effect of different peri-interventional antibiotic strategies in a German COPD cohort. Comparative analyses were performed using data from 900 patients enrolled in the multicentre, observational German Lung Emphysema Registry (LE-Registry). Patients were categorized by peri-interventional antibiotic strategy: single-dose prophylaxis, prolonged prophylaxis for 5–7 days, or no prophylaxis. Baseline characteristics, airway colonization, lung function, symptom burden, exercise capacity, and adverse events were assessed up to three months after ELVR. Among 900 patients undergoing ELVR, 104 received single-dose prophylaxis, 344 prolonged 5–7-day prophylaxis, and 309 no antibiotic prophylaxis. Clinical improvements in lung function, symptom burden, and exercise capacity over three months were similar across all groups. Exacerbations occurred in 11.5

BACKGROUND:Superior sulcus tumors (SST) are usually treated with multimodal therapy, mainly trimodal therapy encompassing radiochemotherapy (CRT) followed by surgery. However, high-level evidence from randomized trials remains limited. We conducted a systematic review to assess the evidence of treatment strategies considering adverse events and oncologic outcomes. METHODS:We systematically searched MEDLINE, CINAHL, EMBASE, Web of Science, CENTRAL, grey literature databases, and clinical trial registries. We included prospective and retrospective studies published between 1990 and 2024 with mono-, bi- or trimodal treatment reporting outcomes such as overall survival (OS), progression-free survival (PFS), resection rates, postoperative mortality/morbidity, and adverse events. Studies required histologically confirmed SST and a minimum of 30 patients. RESULTS:Thirty-five studies were included (28 retrospective, 7 prospective), with follow-up ranging from 10 to 107 months. Most studies originated from Europe (n = 16) and North America (n = 14). Sample sizes ranged from 30 to 2910 patients, predominantly male and aged in the late 50s to early 60s. Induction CRT protocols varied widely. R0 resection rates were reported in 33 studies, and trimodal therapy outcomes in 12. Hematotoxicity and esophagitis were the most common adverse events. Five-year OS rates varied between 11.8 % and 77 %, with trimodal therapy associated with better survival and distant metastasis as the dominant recurrence pattern. There were no studies addressing immunotherapy. CONCLUSION:While trimodal therapy remains the guideline-endorsed standard for SST, comparative evidence remains sparse. The role of immunotherapy in induction regimens warrants further investigation.

BackgroundData regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with a very low 6-min walk test (6MWT) are limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutic benefits and increased complication risk.Study designs and methodsThis study utilised data from the Lungenemphysemregister e.V., a large German national multi-centre prospective open-label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6MWT ≤140 m and dyspnoea primarily attributed to hyperinflation.Results54 patients with a baseline 6MWT ≤140 m and 365 patients with a baseline 6MWT between 140 and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6MWT ≤140 m at baseline had a lower forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide and higher symptom burden. In the 3-month follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6MWT ≤140 m at baseline showed significantly more 6MWT improvement compared to patients with baseline 6MWT between 140 and 450 m. Moreover, complication rates were similar in both groups.InterpretationIn summary, the data indicate that ELVR may be an effective and safe treatment for emphysema patients with a very low 6MWT of ≤140 m if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6MWT.

Adoptive cell therapy (ACT) with TCR-engineered T-cells represents a promising alternative to TIL- or CAR-T therapies for patients with advanced solid cancers. Currently, selection of therapeutic TCRs critically depends on knowing the target antigens, a condition excluding most patients from treatment. Direct antigen-agnostic identification of tumor-specific T-cell clonotypes and TCR-T manufacturing using their TCRs can advance ACT for patients with aggressive solid cancers. We present a method to identify tumor-specific clonotypes from surgical specimens by comparing TCRβ-chain repertoires of TILs and adjacent tissue-resident lymphocytes. In six out of seven NSCLC-patients analyzed, our selection of tumor-specific clonotypes based on TIL-abundance and high tumor-to-nontumor frequency ratios was confirmed by gene expression signatures determined by scRNA-Seq. In three patients, we demonstrated that predicted tumor-specific clonotypes reacted against autologous tumors. For one of these patients, we engineered TCR-T cells with four candidate tumor-specific TCRs that showed reactivity against the patient’s tumor and HLA-matched NSCLC cell lines. The TCR-T cells were then used to screen for candidate neoantigens and aberrantly expressed antigens. Three TCRs recognized recurrent driver-mutation KRAS Q61H-peptide ILDTAGHEEY presented by HLA-A*01:01. The TCRs were also dominant in a tumor relapse, one was found in cell free DNA. The finding of homologous TCRs in independent KRAS Q61H-positive cancers suggests a therapeutic opportunity for HLA-matched patients with KRAS Q61H-expressing tumors.

Einleitung Daten zur Sicherheit und Komplikationen einer endoskopischen Lungenvolumenreduktion mit Ventilen (ELVR) in Patient*innen mit fortgeschrittenem Lungenemphysem und hochgradig eingeschränktem 6-Minuten Gehtest (6MWT) in der Ausgangsuntersuchung fehlen. In randomisiert kontrollierten Studien zur Ventiltherapie wurden Patient*innen mit einem 6MWT≤140m, aufgrund der Annahme von erhöhten peri-interventionellen Komplikationen und einem geringeren Therapieerfolg infolge von muskulärer Dekonditionierung unterrepräsentiert. Ziel der Analyse ist, die Komplikationsrate drei Monate nach ELVR zwischen Patient*innen mit einem 6MWT von 140-450m und≤140m zu vergleichen.

Trotz der breiten Anwendung der endobronchialen LVR stellt die chirurgische LVR weiterhin ein weltweit etabliertes Verfahren in der Therapie des schweren Lungenemphysems dar. Technisch erfolgt die operative LVR durch die peripher atypische Resektion von betroffenen Lungenanteilen (shaving) oder eine Lobektomie des durch das Emphysem am meisten veränderten Lappen. Bisher gibt es nur keine Studien die beide Verfahren direkt miteinander Vergleich. Eine erste Auswertung der Daten des Lungenemphysemregisters e.V. soll klären, ob ein Verfahren dem anderen überlegen ist

Streptococcus pneumoniae is the most common causative agent of community-acquired pneumonia worldwide. A key pathogenic mechanism that exacerbates severity of disease is the disruption of the alveolar-capillary barrier. However, the specific virulence mechanisms responsible for this in the human lung are not yet fully understood. In this study, we infected living human lung tissue with Strep. pneumoniae and observed a significant degradation of the central junctional proteins occludin and vascular endothelial cadherin, indicating barrier disruption. Surprisingly, neither pneumolysin, bacterial hydrogen peroxide nor pro-inflammatory activation were sufficient to cause this junctional degradation. Instead, pneumococcal infection led to a significant decrease of pH (similar to 6), resulting in the acidification of the alveolar microenvironment, which was linked to junctional degradation. Stabilising the pH at physiological levels during infection reversed this effect, even in a therapeutic-like approach. Further analysis of bacterial metabolites and RNA sequencing revealed that sugar consumption and subsequent lactate production were the major factors contributing to bacterially induced alveolar acidification, which also hindered the release of critical immune factors. Our findings highlight bacterial metabolite-induced acidification as an independent virulence mechanism for barrier disruption and inflammatory dysregulation in pneumonia. Thus, our data suggest that strictly monitoring and buffering alveolar pH during infections caused by fermentative bacteria could serve as an adjunctive therapeutic strategy for sustaining barrier integrity and immune response.