BACKGROUND:Lung cancer screening offers an opportunity to enhance COPD detection among adults exposed to tobacco smoke; however, guidance on CT scan-based referral for spirometry is limited. RESEARCH QUESTION:Which low-dose CT scan emphysema threshold best identifies previously undiagnosed COPD in lung cancer screening patients, and does the addition of quantitative airway biomarkers enhance detection? STUDY DESIGN AND METHODS:In adults undergoing lung cancer screening, we performed spirometry to identify previously undiagnosed COPD, defined by airflow obstruction (FEV1/FVC < 0.70) in patients who currently smoke and patients who formerly smoked with ≥ 10 pack-years. We quantified emphysema extent, airway wall thickness (standardized square root wall area of airways with a theoretical internal perimeter of 10 mm), and airway branch count on low-dose CT scan using artificial intelligence-based software and combined these measures with clinical characteristics, mainly smoking history and dyspnea, to develop an ensemble tree-based machine-learning model (Extreme Gradient Boosting) for COPD detection. A sensitivity analysis using the lower limit of normal definition for FEV1/FVC was additionally performed. RESULTS:Among 5,014 screening patients with available spirometry, 1,115 had previously undiagnosed COPD, corresponding to a prevalence of 22.2%. In patients without known airway disease, emphysema alone at an optimized threshold of 5.1% showed moderate performance for COPD detection (area under the receiver operating characteristic curve [AUC], 0.69; 95% CI, 0.67-0.72; accuracy, 66%; positive predictive value [PPV], 44%), where 41% of patients exceeded this threshold and met criteria for confirmatory spirometry. An integrated model combining emphysema, standardized square root wall area of airways with a theoretical internal perimeter of 10 mm, airway branch count, and clinical characteristics significantly improved detection (AUC, 0.83; 95% CI, 0.80-0.86; accuracy, 78%; PPV, 59%) while reducing the proportion requiring confirmatory spirometry to 34%. In a sensitivity analysis using the lower limit of normal definition of COPD, the best-performing model achieved an AUC of 0.86 (95% CI, 0.83-0.89), accuracy of 84%, and PPV of 53%, while referring 22% for confirmatory spirometry. INTERPRETATION:Our results show that an integrated approach combining CT scan-derived airway biomarkers and clinical characteristics enables more efficient and targeted COPD detection within lung cancer screening programs. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT04913155; URL: www. CLINICALTRIALS:gov.

Abstract Background Standard treatment for unresectable stage III non-small cell lung cancer (NSCLC) involves chemoradiation (CRT) followed by PD-L1 targeting immune checkpoint inhibition (IO). Integrating 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT into radiotherapy planning reduces toxicity, improves CRT outcomes, and potentially enhances immunotherapy response. Hypofractionated, accelerated CRT shortens treatment time, improves compliance, and may increase CRT completion rates, qualifying more patients for consolidative IO. Methods/design PACCELIO is a multinational, multicenter, randomized, phase II trial comparing the safety and efficacy of FDG-PET/CT based, volume-reduced, hypofractionated CRT with consolidation durvalumab to standard-volume, conventionally fractionated CRT with consolidation durvalumab in inoperable stage III NSCLC. One hundred and ten patients will be enrolled in Germany, Austria, and Switzerland, randomized 1:1, stratified by age, NSCLC stage, and site. The primary objective is to increase completion of CRT with successful transition to consolidation immunotherapy. Secondary outcomes include locoregional and distant tumor control rates, overall survival, safety, and health-related quality of life (HR-QoL). Exploratory outcomes involve prognostic immunomarkers and PET parameters. The primary endpoint of treatment completion will be analyzed using Fisher's Exact test, with safety and efficacy outcomes analyzed via Kaplan-Meier. Discussion The PACCELIO trial addresses a clinical need in stage III NSCLC by combining FDG-PET/CT based RT volume reduction with hypofractionated accelerated CRT and durvalumab immunotherapy. This approach aims to improve treatment completion, compliance, tumor control, and reduce toxicity. The trial will provide insights into the efficacy and safety of this combined treatment, potentially influencing future standards in stage III NSCLC treatment. Recruitment began in July 2024, with ongoing enrollment. Trial registration Clinicaltrials.gov identifier: NCT06102057 (Date of initial registration: 26th October 2023), https://clinicaltrials.gov/study/NCT06102057 .

Abstract:The nationwide introduction of lung cancer screening using low-dose computed tomography (LDCT) is imminent in Germany. In contrast to other cancer screening programs, lung cancer screening follows a risk-based approach and specifically targets heavy current and former smokers aged 50 to 75 years. Following several years of pilot phases and regulatory preparation, the Federal Joint Committee (G-BA) decided in June 2025 to include this program as a regular benefit covered by statutory health insurance starting in 2026.Evidence from large international studies demonstrates a significant reduction in lung cancer mortality of approximately 20%. However, there are also risks such as overdiagnosis, unnecessary invasive procedures in false-positive findings, secondary cancers due to radiation exposure, and psychological burden.Key factors for program success include the structured involvement of qualified physicians in the identification, information, and assessment of eligibility of potential participants. Physicians in the fields of general medicine, occupational medicine, and internal medicine have been authorized after specific qualification, the latter of which includes pulmonologists - who, while not explicitly mentioned, will certainly have the closest contact with the high-risk population of smokers. This white paper provides practical information and materials for participating in lung cancer screening. It highlights the importance of dedicated interdisciplinary collaboration to detect as many lung cancer patients as possible at an early and therefore potentially curable stage.

In Deutschland steht die nationale Einführung der Lungenkrebsfrüherkennung mittels Niedrigdosis-Computertomografie (LDCT) kurz bevor. Im Gegensatz zu anderen Krebs-Screening-Programmen verfolgt das Lungenkrebsscreening einen risikobasierten Ansatz und richtet sich speziell an starke (inklusive ehemalige) Raucher im Alter von 50–75 Jahren. Nach mehrjähriger Pilotphase und regulatorischer Vorbereitung hat der Gemeinsame Bundesausschuss (G-BA) im Juni 2025 beschlossen, dieses Programm als kassenärztliche Regelleistung ab 2026 einzuführen.Die Evidenzlage aus großen internationalen Studien zeigt eine signifikante Reduktion der Lungenkrebsmortalität um etwa 20%. Jedoch bestehen auch Risiken wie Überdiagnosen, unnötige invasive Eingriffe bei falsch-positiven Befunden, Folgekarzinome durch Strahlenexposition und psychische Belastung.Ein zentraler Erfolgsfaktor ist die strukturierte Einbindung qualifizierter Ärzte zur Identifikation, Information und ärztlichen Prüfung der Eignung potenzieller Teilnehmer. Hierfür wurden Fachärzte in fortgeschrittener Weiterbildung der Bereiche Allgemeinmedizin, Arbeitsmedizin und Inneren Medizin nach entsprechender Qualifizierung legitimiert. Dies schließt Pneumologen mit ein, die sicherlich die engsten Berührungspunkte mit der Risikogruppe der Rauchenden haben.Dieses Whitepaper bietet praxisnahe Informationen und Materialien zur Mitwirkung an der Lungenkrebsfrüherkennung. Es hebt die Relevanz einer engagierten interdisziplinären Zusammenarbeit hervor, um ab sofort bei möglichst vielen Patienten Lungenkarzinome frühzeitig und damit potenziell heilbar zu entdecken.

BACKGROUND:Low-dose chest CT screening can reduce lung cancer mortality through early diagnosis. Several studies suggest that risk prediction models are more efficient than categorical age and smoking criteria for participant selection, but there are still reservations from policy makers about their implementation. We aimed to compare the effectiveness of a predefined PLCOm2012 model threshold with the categorical NELSON risk criteria. METHODS:In this ongoing prospective cohort study, current or former smokers aged 55-79 years who met either NELSON risk criteria or had a PLCOm2012 6-year risk of at least 1·58% were recruited from three certified German lung cancer centres in Großhansdorf, Hannover, and Lübeck, and received low-dose CT at baseline and 1-year follow-up screening rounds, including all downstream follow-up procedures. The PLCOm2012 cutoff point of at least 1·58% was predefined and estimated to result in an equal group size as with the NELSON inclusion criteria. The primary outcome was the comparison of the positive predictive values for lung cancers detected in PLCOm2012-selected versus NELSON-selected groups. Here, we report the final results of the primary analysis. This study is registered with ClinicalTrials.gov, NCT04913155. FINDINGS:Between July 23, 2021, and Aug 19, 2022 (end of recruitment), 5191 participants (2208 [43·5%] female, 2983 [57·5%] male, and 5076 [97·8%] of European White ethnicity) who met either one or both high-risk criteria were enrolled (4167 PLCOm2012-selected vs 3916 NELSON-selected participants) and underwent the baseline low-dose CT scan. In the observation period between the two low-dose CT screening rounds (mean volume CT dose index 1·15 mGy [SD 0·15]) with a median time interval of 1·05 years (IQR 0·95-1·08), 111 lung cancers were detected. The positive predictive value (lung cancer detection rate) in the PLCOm2012-selected group was 108 of 4167 participants (2·59% [95% CI 2·13-3·12]) compared with 85 of 3916 participants (2·17% [1·74-2·68]) in the NELSON-selected group (p=0·0016), resulting in a lower number needed to screen (38·6 [32·1-46·9] vs 46·1 [37·3-57·5]). INTERPRETATION:Participant selection using the PLCOm2012 risk prediction model with a 6-year risk of at least 1·58% cutoff is more efficient and effective in detecting lung cancer than the NELSON criteria and should therefore be implemented in lung cancer screening programmes. FUNDING:Federal Ministry of Education and Research (German Center for Lung Research) and AstraZeneca.

Background: Incidental pulmonary nodules (IPNs) detected during routine thoracic CT scans offer a promising opportunity to shift lung cancer (LC) diagnoses toward earlier, more curable stages across a broad patient population. Despite their high potential to reduce LC-related mortality, the complexity and heterogeneity of existing guidelines, combined with inefficient follow-up processes, continue to limit the diagnostic and therapeutic benefits of IPN detection. Summary: This article examines the systemic barriers to effective IPN management and outlines strategic solutions, including automation and structured workflows as well as standardized patient communication. With the recent implementation of national lung cancer screening (LCS) programs, new opportunities arise to synergize infrastructures and optimize pulmonary nodule management within a unified framework. Key Message: Therefore, a clearer understanding of how IPNs should be managed - and how they can be integrated into broader early detection strategies - is essential for a truly holistic approach to early LC detection. .

Background Despite the high prevalence and mortality of lung cancer and proven effectiveness of low-dose computed tomography (LDCT) to reduce mortality, Germany still lacks a national screening program. The German Institute for Quality and Efficiency in Health Care (IQWiG) and the Federal Office for Radiation Protection (BfS) both published positive scientific evaluations recommending a quality-controlled national screening program. IQWiG underlined the importance of a clear risk definition, integrated smoking cessation programs, and quality assurance, highlighting the necessity of procedural optimization. Methods and Objectives In the HANSE study, former and current smokers aged 55-79 years are assessed for their lung cancer risk by the NELSON and PLCO (M2012) risk scores. 5000 high-risk participants, defined as PLCO (M2012) 6-year risk >= 1.58 % or fulfilling NELSON risk inclusion criteria, will be screened by LDCT at baseline and after 12 months. Lung nodules are analyzed by a modified Lung-RADS 1.1 score of the HANSE study, and values of emphysema and coronary calcium are determined and randomly reported to the participants. 7100 low-risk participants serve as a control. All patients are followed-up for up to 10 years. The sensitivity and specificity of the two risk assessments and LDCT screening, effects of the randomized LDCT reporting, efficiency of lung nodule management, and several other factors are assessed to analyze the success and quality of the holistic screening program. Conclusion The HANSE study is designed as a holistic lung cancer screening study in northern Germany to answer pressing questions for a successful implementation of an effective German lung cancer screening program. Citation Format Vogel-Claussen J, Lasch F, Bollmann B et al. Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography. Fortschr Rontgenstr 2022; DOI: 10.1055/a-1853-8291

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, and early LC diagnosis can significantly improve outcomes and survival rates in affected patients. Implementation of LC screening programs using low-dose computed tomography CT in high-risk subjects aims to detect LC as early as possible, but so far, adoption of screening programs into routine clinical care has been very slow. In recent years, the use of CT has significantly increased the rate of incidentally detected pulmonary nodules. Although most of those incidental pulmonary nodules (IPNs) are benign, some of them represent early-stage LC. Given the large number of IPNs detected in the range of several millions each year, this represents an additional, maybe even larger, opportunity to drive stage shift in LC diagnosis, next to LC screening programs. Comprehensive evaluation and targeted work-up of IPNs are mandatory to identify the malignant nodules from the crowd, and several guidelines provide radiologists and physicians' guidance on IPN assessment and management. However, IPNs still seem to be inadequately processed due to various reasons including insufficient reporting in the radiological report, missing communication between stakeholders, absence of patient tracking systems, and uncertainty regarding responsibilities for the IPN management. In recent years, several approaches such as lung nodule programs, patient tracking software, artificial intelligence, and communication software were introduced into clinical practice to address those shortcomings. This review evaluates the current situation of IPN management and highlights recent developments in process improvement to achieve first steps toward stage shift in LC diagnosis.

Zielsetzung Am 26. Juli 2021 startete das bisher größte deutsche Programm zur Früherkennung von Lungenkrebs mit über 12.000 Probanden (www.hanse-lungencheck.de). Zielgruppe sind (Ex-)Raucherinnen und Raucher zwischen 55 und 79 Jahren, die ein erhöhtes Risiko für Lungenkrebs aufweisen. Bis zu 5.000 Personen erhalten eine kostenlose Untersuchung mit einer modernen Niedrigdosis-Computertomographie (LD-CT) in zwei jährlichen Screening Runden in einem mobilen Studien-Truck, der zwischen den drei Studienstandorten Hannover, Lübeck und Großhansdorf bei Hamburg wechselt.

Background: Pemetrexed and cisplatin is a first-line standard in non-squamous non-small-cell lung cancer without targetable mutations. It became the backbone of checkpoint-inhibitor–chemotherapy combinations. Single high doses of cisplatin pose toxicity risks and require hyperhydration, potentially prolonging outpatient application. The aim of this study was to compare efficacy, safety and tolerability of split-dose cisplatin with the standard schedule. Methods: Patients with metastatic non-squamous non-small-cell lung cancer were randomly assigned to up to six 21-day cycles of pemetrexed 500 mg/m 2 and cisplatin 75 mg/m 2 on day 1 (arm A), or pemetrexed 500 mg/m 2 (day 1) and cisplatin 40 mg/m 2 (day 1 + 8, arm B), followed by pemetrexed maintenance. Primary endpoint was objective response rate. Secondary objectives were overall survival, progression-free survival, time to progression, treatment compliance, toxicity profile, and quality of life. Results: We enrolled 130 patients (129 evaluable). Median cycle numbers in A and B were six (1–6) and five (1–6). Dose intensities were comparable between arms. More patients in A received pemetrexed maintenance (24.2% versus 11.1%). With 16 (24.2%) in A and 19 (30.2%) patients in B achieving objective responses [odds ratio 0.74 (0.34–1.62), p = 0.55] the primary endpoint was met. Overall survival was not different between arms (median 14.4 versus 14.9 months); [HR = 1.07; (0.68–1.68), p = 0.78]. Median progression-free survival was 7.0 months in A and 6.2 months in B [HR = 1.63; (1.17–2.38); p = 0.01]. Adverse events of CTCAE grade ⩾3, particularly hematological, were more frequent in B. No difference in grade 4 and 5 infections between arms was noted. Treatment-related asthenia and nausea/vomiting of any grade were more frequent in A. Global health status, fatigue and constipation measured on day 1 of cycle 4 demonstrated superior scores in B. Conclusion: Pemetrexed and split-dose cisplatin is safe and effective. Advantages of split-dose cisplatin with regard to specific toxicities allow personalization of this important chemotherapy backbone. Trial Registration: European Clinical Trials Database (EudraCT) number 2011-001963-37.

BACKGROUND: The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. OBJECTIVES: The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. METHODS: Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. RESULTS: In total, 125 patients underwent coil treatment and had evaluable 12-month follow-up results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]+), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVM+ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean +/- SE improvement in FEV1 (15.2 +/- 3.1%), St. George's Respiratory Questionnaire (-12 +/- 2 points), and residual volume (-0.57 +/- 0.13 L). DISCUSSION: This post hoc analysis found that both significant hyperinflation (residual volume >= 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (< 20% low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes.

Background: The PneumRx endobronchial coil system for patients with severe emphysema has been shown to improve quality of life, exercise capacity, and pulmonary function in patients with emphysema. A post hoc analysis of the RENEW trial has identified patient characteristics and lobar selection methods associated with improved outcomes, which have to be confirmed prospectively. Methods: The ELEVATE trial is a prospective, multicenter, open label, randomized (2:1), controlled trial comparing outcomes in patients treated with endobronchial coils (treatment) to a medically managed control group (control). The trial aims to enroll 210 patients (140 in the treatment group and 70 in the control group) with severe emphysema. Control patients will be eligible to crossover to coil treatment after 6 months of follow-up. The co-primary effectiveness endpoints are percent change in forced expiratory volume in 1 s and quality of life measured by change in St. George’s Respiratory Questionnaire from baseline to 6 months. Secondary objectives are determination of responder rates of clinical endpoints and mean change in other functional and physiologic endpoints. All patients will be followed for 24 months after initial treatment. Adverse events will be collected on an ongoing basis throughout the trial. Discussion: The primary objective of the ELEVATE trial is to prospectively confirm the safety and effectiveness profile of the coil system for the treatment of severe emphysema in consideration of the findings of previous randomized controlled trials. Secondary objectives are the determination of responder rates in all clinical endpoints and mean change in physiologic endpoints.

In patients with non-small cell lung cancer (NSCLC), the most frequent oncogene driver mutation in Western countries is Kirsten rat sarcoma viral oncogene homolog (KRAS), and KRAS-mutant NSCLC is associated with smoking. There are various sources of biological heterogeneity of KRAS-mutant NSCLC, including different genotypes that may be associated with specific clinical outcomes, the presence of other co-mutations that exhibit different biological features and drug sensitivity patterns, and mutant allelic content. The efficacy of chemotherapy in patients with KRAS-mutant NSCLC is generally poor and numerous novel therapeutic strategies have been developed. These approaches include targeting KRAS membrane associations, targeting downstream signalling pathways, the use of KRAS synthetic lethality, direct targeting of KRAS, and immunotherapy. Of these, immunotherapy may be one of the most promising treatment approaches for patients with KRAS-mutant NSCLC. Recent data also suggest the potential for distinct efficacy of immunotherapy according to the presence of other co-mutations. In view of the biological heterogeneity of KRAS-mutant NSCLC, treatment will likely need to be individualised and, in future, may require the use of rational combinations of treatment, many of which are currently under investigation.

Abemaciclib, ein selektiver CDK4- und CDK6 Inhibitor, zeigt Antitumor-Aktivität im humanen NSCLC Xenotransplantat Modell und hat eine erhöhte Wirksamkeit gegen Tumore mit KRAS Mutationen (Gelbert et al, 2014; Patnaik et el, 2016). In der Phase 1 erhielten 68 Patienten mit fortgeschrittenem NSCLC und median 4 systemischen Vortherapien Abemaciclib in Monotherapie. In der Gesamtpopulation (n = 68) betrug die Krankheitskontrollrate (DCR) 49% (CR + PR + SD). Ein Patient mit KRAS mutiertem NSCLC und 1 Patient mit plattenepithelialem KRAS Wildtyp NSCLC und CDKN2A-Kopiezahlverlust zeigten PR. Die DCR betrug in der Population mit KRAS Mutation 55%, bei KRAS Wildtyp 39%. Auch erreichten 31% der Patienten mit KRAS Mutation eine Tumorstabilisierung für ≥24 Wochen, bei KRAS Wildtyp Tumor 12%. Das mediane progressionsfreie Überleben (PFS) betrug bei KRAS Mutation 2,8 Monate, bei KRAS Wildtyp 1,9 Monate.

Non-small cell lung cancer (NSCLC) has usually been thought to be a non-immunogenic tumor, because early studies with Bacillus Calmette-Guerin, interleukin-2, or interferon have failed to demonstrate any benefit in NSCLC. Recently, some studies indicated that immune mechanisms play a vital role in the origin and development of lung cancer, and the abnormality of immune checkpoints would be the chief culprit. Immune checkpoint-inhibitors have shown promising activity in several solid tumors, including NSCLC. But interfering with the complex immune system in tumor immunosurveillance can trigger not only long lasting responses, but also severe and sometimes irreversible immunological side effects, as seen with the first approved cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab. This reminds one of a famous German poem written by Johann Wolfgang von Goethe in the year 1797, where an apprentice takes the opportunity to “play a little” with some magic when his master wizard had gone out of the house. But the apprentice summoned some powerful spirits he couldn’t actually control.

Background: Switch maintenance is an effective strategy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Pazopanib is an oral, multi-targeted tyrosine kinase inhibitor (TKI). EORTC 08092 evaluated pazopanib given as maintenance treatment following standard first line platinum-based chemotherapy in patients with advanced NSCLC.Methods: Patients with non-progressive disease after 4-6 cycles of chemotherapy were randomised to receive either pazopanib 800 mg/day or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival and secondary end-points were progression-free survival (PFS) and safety.Results: A total of 600 patients were planned to be randomised. The trial was prematurely stopped following an early interim analysis, after 102 patients were randomised to pazopanib (n = 50) or placebo (n = 52). Median age was 64 years in both arms. Median overall survival was 17.4 months for pazopanib and 12.3 months for placebo (adjusted hazard ratio (HR) 0.72 [95% confidence interval (CI) 0.40-1.28]; p = 0.257). Median PFS was 4.3 months versus 3.2 months (HR 0.67, [95% CI 0.43-1.03], p = 0.068). PFS rates at 4 months were 56% and 45% respectively. The majority of treatment-related adverse events (AEs) were grade 1-2. Grade 3-4 AEs (pazopanib versus placebo) were hypertension (38% versus 8%), neutropenia (8% versus 0%), and elevated SGPT (6% versus 0%). Of the patients randomised to pazopanib, 22% withdrew due to a treatment-related AE.Conclusions: Switch maintenance with pazopanib following platinum-based chemotherapy in advanced NSCLC patients had limited side-effects. This study was stopped due to lack of efficacy by stringent criteria for PFS at a futility interim analysis. (C) 2015 Elsevier Ltd. All rights reserved.