Background: Despite recent advances in the treatment of locally advanced non-small cell lung cancer (NSCLC), most patients relapse after definitive chemoradiotherapy followed by durvalumab consolidation. Due to limited evidence on post-relapse management, no standard treatment approach has been established for this patient population. Objectives: The objective of this study was to evaluate real-world treatment strategies and clinical outcomes in patients with NSCLC who experienced disease recurrence after durvalumab consolidation. Design: This was a multicenter, retrospective cohort study conducted across 12 German lung cancer centers. Methods: A total of 145 patients with recurrent NSCLC following chemoradiotherapy and durvalumab consolidation were analyzed. Clinical, pathological, and treatment-related data were collected, including smoking status, histology, molecular testing, therapeutic sequences, and survival outcomes. Overall survival (OS) and progression-free survival (PFS) were estimated and compared across subgroups according to relapse characteristics and post-relapse treatment strategies. Multivariate analyses were performed to identify independent prognostic factors. Results: The median OS from initial diagnosis was 27.1 months (95% confidence interval (CI): 22.5–31.8). After relapse, median OS was 12.2 months (95% CI: 9.9–14.4), and median PFS was 7.1 months (95% CI: 5.7–8.4). Approximately 70% of patients received systemic therapy after relapse, including platinum-based chemotherapy (18.6%), single-agent chemotherapy (18.6%), immune checkpoint inhibitors with or without chemotherapy (28.3%), and targeted therapy (4.8%). Patients treated with immune checkpoint inhibitors or targeted therapies showed a numerical improvement in OS compared with chemotherapy alone, although this difference did not reach statistical significance. Multivariate analysis identified first-line post-relapse treatment, Eastern Cooperative Oncology Group performance status, and histologic subtype as independent prognostic factors for OS. Conclusion: Patients with relapsed NSCLC after durvalumab consolidation have a poor prognosis and remain a therapeutically underserved population. Clinical outcomes appear to be influenced by performance status, histology, and the choice of post-relapse therapy. Prospective clinical trials are urgently needed to define optimal treatment strategies for these patients.

Das kleinzellige Lungenkarzinom (SCLC) ist eine aggressive Tumorentität mit schlechter Prognose. Zur Standardbehandlung gehören sowohl die Strahlen- und Chemotherapie als auch die Immuntherapie. Doch das Ansprechen ist oft nur kurzfristig. Neue Ansätze umfassen Antikörper-Wirkstoff-Konjugate (ADCs), zielgerichtete Therapien und personalisierte Behandlungsstrategien auf Basis molekularer Biomarker. Besonders vielversprechend sind Kombinationen aus Immuntherapie und innovativen Wirkstoffen. Fortschritte wie die Liquid Biopsy sowie die Erforschung der Tumormikroumgebung eröffnen neue diagnostische und therapeutische Möglichkeiten.

Background: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: This narrative review is based on a selective literature search conducted via PubMed and ClinicalTrials.gov (last updated June 2025). Results: Emerging treatment strategies include bispecific T-cell engagers (e.g., tarlatamab), antibody-drug conjugates (ADCs) such as sacituzumab govitecan, DS-7300, and ZL-1310, as well as targeted therapies. Among these, tarlatamab has demonstrated improved survival outcomes with an acceptable safety profile and is poised to become the new second-line standard. In contrast, ADCs and targeted agents have shown only modest efficacy and have yet to deliver meaningful survival benefits, often accompanied by increased toxicity. Additionally, the identification of molecular subtypes of SCLC has revealed subtype-specific differences in treatment response. However, clinical translation is challenged by intratumoral heterogeneity, plasticity, and the lack of standardized diagnostic assays. Conclusions: While tarlatamab represents a major therapeutic advancement, other agents remain in early clinical development and require validation in large, randomized trials. The clinical implementation of molecular subtyping remains limited, though it holds promise for future personalized treatment approaches. Despite recent progress, SCLC continues to pose substantial therapeutic challenges, emphasizing the need for improved treatment strategies and validated predictive biomarkers.

BACKGROUND:High-dose chemotherapy with melphalan (HDCT) and autologous stem cell transplantation (ASCT) represents a gold standard treatment for younger multiple myeloma (MM) patients (<70 years). The benefit of upfront HDCT/ASCT in elderly patients (≥70 years) remains undefined. This analysis investigated survival outcomes among both age groups undergoing front-line HDCT/ASCT. METHODS:This retrospective analysis included MM patients treated between February 1998 and November 2023 at 2 German university hospitals. Patients were divided into age groups (<70 vs. ≥70), and further categorized whether they received HDCT/ASCT or not. Treatment outcomes, progression-free survival (PFS), and overall survival (OS) were compared using Kaplan-Meier analysis and Cox regression. RESULTS:Of 517 patients (395 patients <70 years; 122 patients ≥70 years), 343 (66.3%) patients underwent HDCT/ASCT (307 patients <70 years, 89.5% of eligible patients; 36 patients ≥70 years, 10.5% of eligible patients). The remaining 174 (33.7%) patients did not receive HDCT/ASCT (88 patients <70 years; 86 patients ≥70 years). HDCT/ASCT significantly improved both PFS and OS in all patients. Elderly recipients demonstrated longer PFS than younger recipients (10.27 vs. 2.74 years; P = .006), likely due to more frequent use of anti-CD38 antibody-based induction and maintenance therapy. OS was significantly longer in younger recipients (17.31 vs. 4.87 years; P = .003). In the multivariate analysis, HDCT/ASCT remained a strong protective factor for both PFS and OS. CONCLUSION:HDCT/ASCT confers a significant survival benefit in both younger and selected elderly MM patients. Advanced age alone should not exclude HDCT/ASCT; therefore, transplant-eligibility should be determined by comprehensive assessment of functional status and comorbidities.

Cardiovascular complications are a hallmark of Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial dysfunction in immune cells as a key contributor. This study investigated whether CD14++ monocytes from long COVID patients exhibit bioenergetic impairment, mitochondrial DNA (mtDNA) damage, and defective oxidative stress adaptation, which may underlie cardiovascular symptoms in PASC. CD14++ monocytes were isolated from 14 long COVID patients with cardiovascular symptoms (e.g., dyspnea, angina) and 10 age-matched controls with similar cardiovascular risk profiles. Mitochondrial function was assessed using a Seahorse Agilent Analyzer under basal conditions and after oxidative stress induction with buthionine sulfoximine (BSO). Mitochondrial membrane potential was measured via Tetramethylrhodamine Ethyl Ester (TMRE) assay, mtDNA integrity via qPCR, and reactive oxygen species (ROS) dynamics via Fluorescence-Activated Cell Sorting (FACS). Parallel experiments exposed healthy monocytes to SARS-CoV-2 spike protein to evaluate direct viral effects. CD14++ monocytes from long COVID patients with cardiovascular symptoms (n = 14) exhibited profound mitochondrial dysfunction compared to age-matched controls (n = 10). Under oxidative stress induced by buthionine sulfoximine (BSO), long COVID monocytes failed to upregulate basal respiration (9.5 vs. 30.4 pmol/min in controls, p = 0.0043), showed a 65% reduction in maximal respiration (p = 0.4035, ns) and demonstrated a 70% loss of spare respiratory capacity (p = 0.4143, ns) with significantly impaired adaptation to BSO challenge (long COVID + BSO: 9.9 vs. control + BSO: 54 pmol/min, p = 0.0091). Proton leak, a protective mechanism against ROS overproduction, was blunted in long COVID monocytes (3-fold vs. 13-fold elevation in controls, p = 0.0294). Paradoxically, long COVID monocytes showed reduced ROS accumulation after BSO treatment (6% decrease vs. 1.2-fold increase in controls, p = 0.0015) and elevated mitochondrial membrane potential (157 vs. 113.7 TMRE fluorescence, p = 0.0179), which remained stable under oxidative stress. mtDNA analysis revealed severe depletion (80% reduction, p < 0.001) and region-specific damage, with 75% and 70% reductions in amplification efficiency for regions C and D (p < 0.05), respectively. In contrast, exposure of healthy monocytes to SARS-CoV-2 spike protein did not recapitulate these defects, with preserved basal respiration, ATP production, and spare respiratory capacity, though coupling efficiency under oxidative stress was reduced (p < 0.05). These findings suggest that mitochondrial dysfunction in long COVID syndrome arises from maladaptive host responses rather than direct viral toxicity, characterized by bioenergetic failure, impaired stress adaptation, and mitochondrial genomic instability. This study identifies persistent mitochondrial dysfunction in long COVID monocytes as a critical driver of cardiovascular complications in PASC. Key defects—bioenergetic failure, impaired stress adaptation and mtDNA damage—correlate with clinical symptoms like heart failure and exercise intolerance. The stable elevation of mitochondrial membrane potential and resistance to ROS induction suggest maladaptive remodeling of mitochondrial physiology. These findings position mitochondrial resilience as a therapeutic target, with potential strategies including antioxidants, mtDNA repair agents or metabolic modulators. The dissociation between spike protein exposure and mitochondrial dysfunction highlights the need to explore host-directed mechanisms in PASC pathophysiology. This work advances our understanding of long COVID cardiovascular sequelae and provides a foundation for biomarker development and targeted interventions to mitigate long-term morbidity.

Background:Small-cell lung cancer (SCLC) is a highly malignant disease with a propensity for early progression and high mortality. The prognostic value of treatment response and survival has been verified for solely established imaging, clinical, and biochemical markers. There is a lack of evidence for the combination of those parameters with machine learning and integrated models, particularly in the context of molecular imaging. Objectives:The aim of this study was to predict early disease progression and survival using CT-based radiomic features (RF), integrating [18F]FDG-PET-CT and clinical parameters. Design:This retrospective pilot study included 62 patients with non-metastatic and metastatic SCLC who underwent stage-based primary treatment following baseline [18F]FDG-PET-CT. The development of a machine learning approach, incorporating clinical and molecular imaging parameters, enables the creation of a model capable of predicting treatment response and survival. Methods:A radiomics signature was generated based on the first-line treatment response by RECIST 1.1 criteria. The RF was integrated using binary logistic regression analysis with the PET parameter metabolic tumor volume (MTV) of the primary tumor and initial disease stage. The integrated model with the highest AUC for predicting early disease progression was evaluated for predicting progression-free survival (PFS) and overall survival (OS) in both non-metastatic and metastatic patients. Results:A single CT-based RF demonstrated predictive capacity (AUC = 0.81). Integration of the MTV and disease stage enhanced the predictive capacity (AUC = 0.9). A Youden index-based threshold of <0.62 was identified as a significant predictor of prolonged PFS: non-metastatic disease with a median PFS of 25 versus 4 months (HR = 0.072; p = 0.002); metastatic disease with a median PFS of 9 versus 5 months (HR 0.219; p = 0.004). The integrated model also predicted OS in metastatic disease with a median OS of 15 versus 8 months (HR 0.381; p = 0.013). Conclusion:A multiparametric approach based on a Radiomics model may potentially be capable of identifying patients at risk for early disease progression, PFS, and OS in non-metastatic and metastatic SCLC.

Background and Objective:The standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions is targeted therapy using tyrosine kinase inhibitors (TKIs). However, data are still lacking on the use of TKIs as a neoadjuvant or induction approach. Therefore, this narrative review aims to summarize the current knowledge on resectable EGFR-mutant and ALK-fused NSCLC regarding available perioperative treatment regimens and off-label neoadjuvant use of targeted therapy. Methods:The relevant literature was identified by using PubMed and ClinicalTrials.gov (last search phase June 2024) and was restricted to English language. Peer-reviewed manuscripts but also conference abstracts that did not undergo peer-review were included. Key Content and Findings:Patients with EGFR-mutations and ALK-fusions have typically been excluded from available phase III perioperative immunotherapy trials due to lower efficacy and higher toxicity of immunotherapy in those patients. In the adjuvant setting, recent evidence from the phase III ALINA and ADAURA trials demonstrated efficacy and safety of targeted therapy in resected ALK-fused and EGFR-mutant NSCLC. However, to date there is no approval for the use of TKIs as neoadjuvant or induction therapy in those patients. We have therefore identified a number of case series and phase II trials using targeted therapy in resectable EGFR-mutant and ALK-fused NSCLC. Conclusions:Current evidence suggests that targeted therapies might be effective in patients with resectable EGFR-mutant and ALK-positive NSCLC, but ongoing trials will need to provide further evidence on the safety and efficacy of perioperative TKI therapy.

Abstract Immunotherapy has revolutionized the treatment of patients with non‐small cell lung cancer (NSCLC). High expression of tissue PD‐L1 (tPD‐L1) is currently the only approved biomarker for predicting treatment response. However, even tPD‐L1 low (1‐49%) and absent (<1%) patients might benefit from immunotherapy but, to date, there is no reliable biomarker, that can predict response in this particular patient subgroup. This study aimed to test whether tumour‐associated extracellular vesicles (EVs) could fill this gap. Using NSCLC cell lines, we identified a panel of tumour‐related antigens that were enriched on large EVs (lEVs) compared to smaller EVs. The levels of lEVs carrying these antigens were significantly elevated in plasma of NSCLC patients (n = 108) and discriminated them from controls (n = 77). Among the tested antigens, we focused on programmed cell death ligand 1 (PD‐L1), which is a well‐known direct target for immunotherapy. In plasma lEVs, PD‐L1 was mainly found on a population of CD45−/CD62P+ lEVs and thus seemed to be associated with platelet‐derived vesicles. Patients with high baseline levels of PD‐L1+ lEVs in blood showed a significantly better response to immunotherapy and prolonged survival. This was particularly true in the subgroup of NSCLC patients with low or absent tPD‐L1 expression, thus identifying PD‐L1‐positive lEVs in plasma as a novel predictive and prognostic marker for immunotherapy.

Einleitung Der M.C. ist eine chronisch entzündliche granulomatöse Erkrankung, die in der Regel den gastrointestinalen (GI) Trakt betrifft, sich aber in einigen Fällen auch extraintestinal manifestieren kann. Pulmonale Manifestationen sind sowohl im Lungenparenchym, als auch in den Atemwegen beschrieben. Unseres Wissens nach ist dies der erste Fallbericht über den Befall der Trachea mit einer sekundären EBV positiven lymphoproliferativen Erkrankung.

Introduction Endobronchial ultrasound (EBUS) guided trans-bronchial needle aspiration (TBNA) is a commonly used technique to assess mediastinal lymph nodes. However, diagnostic yield of TBNA-gathered cytological aspirates in lymphoma diagnosis is limited. While mediastinoscopy is far more invasive, we retrospectively assessed the role of EBUS-guided cryo-biopsy in this subset.

We aimed to evaluate the predictive and prognostic value of baseline 18F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy–chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into “responder” (n = 33) and “non-responder” (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for “PET-Skewness” and 0.75 predicting overall progression for “PET-Median”. In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06–0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11–0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy.

Einleitung COVID-19 ist eine durch SARS-CoV-2 hervorgerufene Multisystemerkrankung. Insbesondere in der Akutphase von COVID-19 wurde eine schwere mikrovaskuläre und Endothelschädigung nachgewiesen. Über 6 Monate nach Akutphase leiden jedoch bis zu 60% der Patienten unter anhaltenden Symptomen, die ihre Lebensqualität stark beeinträchtigen. Die Pathophysiologie des sog. Post-COVID ist nach wie vor nur unzureichend verstanden. Eine mögliche Ursache könnte gleichsam in einer mikrovaskulären Pathologie liegen. Ziel unserer Studie ist, die mikrovaskulären Veränderungen bei Post-COVID Patienten zu charakterisieren.

Sedation techniques in interventional flexible bronchoscopy and endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) are inconsistent and the evidence for required general anesthesia under full anesthesiologic involvement is scarce. Moreover, we faced the challenge of providing bronchoscopic care with limited personnel. Hence, we retrospectively identified 513 patients that underwent flexible interventional bronchoscopy and/or EBUS-TBNA out of our institution between January 2020 and August 2022 to evaluate our deep analgosedation approach based on pethidine/meperidine bolus plus continuous flow adjusted propofol, the bronchoscopist-directed continuous flow propofol based analgosedation (BDcfP) in a two-personnel setting. Consequently, 502 out of 513 patients received BDcfP for analgosedation. We identified cardiovascular comorbidities, chronic obstructive pulmonary disease, and arterial hypertension as risk factors for periprocedural hypotension. Propofol flow rate did not correlate with hypotension. Theodrenaline and cafedrine might be used to treat periprocedural hypotension. Moreover, midazolam might be used to support the sedative effect. In conclusion, BDcfP is a safe and feasible sedative approach during interventional flexible bronchoscopy and EBUS-TBNA. In general, after the implementation of safety measures, EBUS-TBNA and interventional flexible bronchoscopy via BDcfP might safely be performed even with limited personnel.