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Background: PARP inhibitors can upregulate PD-L1 expression and promote immune-mediated responses, and may improve efficacy of first-line anti‒PD-1‒based therapies in patients with metastatic squamous NSCLC., Methods: In this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received 4 cycles of induction therapy (pembrolizumab 200 mg Q3W plus carboplatin and paclitaxel or nab-paclitaxel). Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg Q3W plus olaparib 300 mg orally twice-daily or placebo. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (IA2; the final PFS analysis); OS was tested at final analysis., Results: 851 patients received induction treatment; 296 were randomized to pembrolizumab plus olaparib and 295 to pembrolizumab plus placebo. At IA2, with median follow-up of 27.1 months, median (95% CI) PFS was 8.3 (6.7‒9.7) in the pembrolizumab plus olaparib group and 5.4 (4.1‒5.6) months in the pembrolizumab plus placebo group (HR, 0.77 [95% CI, 0.63‒0.93]; P=0.0040 [not significant at a 1-sided at superiority boundary of P=0.003). At final analysis, with median follow-up of 33.4 months, median (95% CI) OS was 19.1 (15.9‒22.2) and 18.6 (16.0‒21.6) months, respectively (HR, 1.01 [95% CI, 0.83‒1.24]; P=0.5481). Treatment-related adverse events occurred in 76.5% and 65.1% of patients, respectively., Conclusion: Adding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo, neither PFS nor OS met the prespecified statistical significance boundary. No new safety signals were identified., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Adherence to COPD management strategies is complex, and it is unclear which intervention may enhance it., Objectives: We aim to evaluate the effectiveness of adherence-enhancing interventions, alone or compared to interventions, for patients with COPD., Methods: This review comprises a component network meta-analysis with a structured narrative synthesis. We searched MEDLINE, Embase, CENTRAL, CINAHL and trial registries on 9 September 2023. We included controlled studies that explored adherence in patients with COPD. Two review authors independently performed the study selection, data extraction and the risk of bias assessment. We involved patients with COPD in developing this systematic review through focus group interviews and displayed the findings in pre-designed logic models., Results: We included 33 studies with 5775 participants. We included 13 studies in the component network meta-analysis that explored adherence. It was mainly assessed through questionnaires. As a continuous outcome, there was a tendency mainly for education (standardised mean difference 1.26, 95% CI 1.13-1.38, very low certainty of evidence) and motivation (mean difference 1.85, 95% CI 1.19-2.50, very low certainty of evidence) to improve adherence. As a dichotomous outcome ( e.g. adherent/non-adherent), we found a possible benefit with education (odds ratio 4.77, 95% CI 2.25-10.14, low certainty of evidence) but not with the other components. We included six studies that reported quality of life in the component network meta-analysis. Again, we found a benefit of education (mean difference -9.70, 95% CI -10.82- -8.57, low certainty of evidence) but not with the other components., Conclusions: Education may improve adherence and quality of life in COPD patients. Patient focus group interviews indicated that interventions that strengthen patients' self-efficacy and help them to achieve individual goals are the most helpful., Competing Interests: Conflict of interest: S. Andreas reports grants from Boehringer, and personal fees from Boehringer, AZ, GSK, Chiesi, Novartis and Menerini, outside the submitted work. T. Friede reports personal fees for statistical consultancies, including data monitoring committees, from Actimed, Aslan, Bayer, Biosense Webster, BMS, CSL Behring, Enanta, Fresenius Kabi, Galapagos, IQVIA, Immunic, Janssen, Kyowa Kirin, LivaNova, Minoryx, Norvartis, PPD, Recardio, Relaxera, Roche, Servier, Viatris, VICO Therapeutics and Vifor, all outside the submitted work. The other authors declare no competing interests., (Copyright ©The authors 2024.)

Both tobacco cessation and low-dose CT screening in at-risk individuals reduce lung cancer-specific and all-cause mortality. As part of a national screening program for the early detection of lung cancer, smoking cessation must be a mandatory part of the counseling given to participants. This increases the cost-benefit effectiveness of the screening program. As part of the initial consultation evidence-based measures for smoking cessation must be offered to smoking participants of the screening program in form of a minimal intervention. If participants do not want to participate in a quit smoking measure they must actively refuse (opt-out rule). The costs of quitting smoking, including the costs of withdrawal-inhibiting medication, have to be fully covered by statutory health insurance for participants in the lung cancer screening program., Competing Interests: Alexander Rupp ist Berater der Firma Sanero Medical GmbH Stuttgart, die eine Internetplattform und eine digitale Gesundheitsanwendung (DiGA) zur Tabakentwöhnung betreibt.Christa Rustler ist Leiterin des Büros des Deutschen Netz rauchfreier Krankenhäuser und Gesundheitseinrichtungen (DNRfK), welches zur Implementierung des „rauchfrei tickets“ Zuwendungen der Bundeszentrale für gesundheitliche Aufklärung (BZgA) erhält.Die anderen Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: MET amplification is a common resistance mechanism to EGFR inhibition in EGFR-mutant non-small cell lung cancer (NSCLC). Several trials showed encouraging results with combined EGFR and MET inhibition (EGFRi/METi). However, MET amplification has been inconsistently defined and frequently included both polysomy and true amplification., Methods: This is a multicenter, real-world analysis in patients with disease progression on EGFR inhibition and MET copy number gain (CNG), defined as either true amplification (MET to centromere of chromosome 7 ratio [MET-CEP7] ≥ 2) or polysomy (gene copy number ≥ 5, MET-CEP7 < 2)., Results: A total of 43 patients with MET CNG were included, 42 of whom were detected by FISH. Twenty-three, 7, and 14 received EGFRi/METi, METi, and SoC, respectively. Patients in the EGFRi/METi cohort exhibited a superior real-world clinical benefit rate, defined as stable disease or better, of 82% (95% confidence interval [CI], 60-95) compared to METi (29%, 4-71) and SoC (50%, 23-77). Median real-world progression-free survival was longer with EGFRi/METi with 9.8 vs. 4.3 months with METi (hazard ratio [HR], 0.19, 95% CI, 0.06-0.57) and 3.7 months with SoC (0.41, 0.18-0.91), respectively. Overall survival was numerically improved. Interaction analysis with treatment and type of CNG (amplification vs. polysomy) suggests that differences were exclusively driven by MET-amplified patients receiving EGFRi/METi (HR for OS, 0.09, 0.01-0.54)., Conclusion: In this real-world study, EGFRi/METi showed clinical benefit over METi and SoC. Future studies should focus on the differential impact of the type of MET CNG with a focus on true MET amplification as predictor of response., Competing Interests: Disclosure F. A. received support for attending meetings and speaker's honoraria from AstraZeneca, and consultant fees from IQVIA. P. C. received research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Merck, Novartis, Roche, and Takeda, speaker's honoraria from AstraZeneca, Gilead, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, and Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Daiichi Sankyo, Janssen, Gilead, Novartis, Pfizer, Takeda, and personal fees for participating to advisory boards from AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche, all outside the submitted work. H.-D. H. received personal fees for participating to advisory boards from Amgen, speaker's honoraria from Amgen, Boehringer Ingelheim, and Bristol-Myers Squibb. C. F. W. received personal fees for participating to advisory boards from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Merck, MSD, Novartis, Pfizer, Roche, and Takeda, consultancy fees from Mylan/Viatris, Alvotech, Roche, support for attending meetings from Amgen, Bristol-Myers Squibb, Janssen, Lilly. A. Ri. received speaker's honoraria and consulting fees from Abbvie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Lilly, GSK, MSD, Novartis, Pfizer, Roche/Genentech. H. Z. received support for attending meetings from Janssen, speaker's honoraria from Pierre Fabre, and Roche. A. L. received support for attending meetings from Abbvie. D. K.-G. received consultant fees from AstraZeneca, Boehringer Ingelheim, Roche, MSD, Pfizer, Bristol-Myers Squibb, GSK, Novartis, Takeda, Sanofi, and Janssen, support for attending meetings from Takeda, Boehringer-Ingelheim, Janssen. R. B. received honoraries for lectures and advisory boards for AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Illumina, Janssen, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche, Targos MP Inc. R.B. is a Co-Founder and Co-Owner of Targos Inc / Kassel (previous); Gnothis Inc / Stockholm (current); Timer Therapeutics Inc / Fulda & Freiburg (current). M. D. received personal fees for participating in advisory boards from AstraZeneca, Bayer, Diaceutics, Biocartis, Sophia Genetics, and ThermoFisher. F. C. A. has received research grants from Novartis, support for attending meetings and/or travel from Amgen, and consultant fees from IQVIA. S. H. has received research grants from Novartis and travel support from BeiGene. J. A. S. received personal fees from Boehringer Ingelheim, AstraZeneca, Roche, Bristol-Myers Squibb, Amgen, LEO pharma, Novartis, and Takeda. J. W. received speaker's honoraria and personal fees for participating in advisory boards from Amgen, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, Merck, Mirati, MSD, Novartis, Nuvalent, Pfizer, Roche, Seattle Genetics, Takeda, and Turning Point and received institutional research grants from Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and AstraZeneca. M. S. received research grants from AstraZeneca, consulting fees from AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Lilly, Roche, Boehringer Ingelheim, Amgen, Takeda, Johnson, Merck-Serono, and GSK, and speaker's honoraria from AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Lilly, Roche, Boehringer Ingelheim, Amgen, Takeda, Johnson, CureVac, BioNTech, Merck-Serono, GSK, Daiichi, and Pfizer. S. M. has received research grants from Novartis and Pfizer, personal fees from Eli Lilly, Janssen, and Astra Zeneca as well as support for attending meetings and/or travel from Eli Lilly, and Janssen. A. S. has received speaker's honoraria from Agilent, Aignostics, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Eli Lilly, Illumina, Incyte, Janssen, MSD, Novartis, Pfizer, Qlucore, Roche, Seagen, Servier, Takeda, and Thermo Fisher, and institutional research grants from Bayer, BMS, Chugai, and Incyte. All other authors declared no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Almost all e-cigarettes contain flavorings that make the product more attractive. In the evaluation of e-cigarettes on health, flavors have so far played a subordinate role., Method: Selective literature search in PubMed, supplemented by legal regulations on the use of flavors in e-cigarettes., Results: Flavors make it easier to start using e-cigarettes and have a consumption-promoting effect. Deeper inhalation increases nicotine uptake and the absorption of toxic substances from the e-cigarette liquid. For some flavors, pathological effects have been demonstrated in addition to other toxic components of the e-cigarette. To date, no toxicological analyses are available for the vast majority of flavors contained in e-cigarettes., Conclusions: The proven consumption-promoting effect and the health risks that can be extrapolated from preclinical data are significant for the political discussion of a ban on flavors for e-cigarettes, analogous to the ban on flavors in tobacco products already in force., Competing Interests: Klaas Franzen, Stefan Andreas, Wulf Pankow, Wilfried Kunstmann und Reiner Hanewinkel sind ehrenamtlich für das Aktionsbündnis Nichtrauchen tätig. Natascha Sommer erhielt für Ihre Forschung zu E-Zigaretten finanzielle Unterstützung der Balzan-Preis Forschungsgruppe des Deutschen Zentrums für Lungenforschung (DZL) – Erika von Mutius, Klaus F. Rabe, Werner Seeger und Tobias Welte., (Thieme. All rights reserved.)

A 43-year-old quarry worker, after being exposed to fine quartz dust for 16 years in a German quarry, is on the waiting list for a lung transplant. The inhalation of the fine dust irreversibly damaged his lungs and facilitated the occurrence of fulminant mycobacterial and fungal infections, which have already led to a unilateral pneumonectomy and increasing respiratory failure. Despite regular monitoring by the occupational health and safety board, this dramatic development of silicosis could not be prevented., Competing Interests: C.L. hat Vortragshonorare von den Firmen Gilead, GSK und Insmed erhalten und war Mitglied in einem wissenschaftlichen Beratergremium von Insmed. B.K. hat Vortragshonorare von der Firma Insmed erhalten. D.N. hat Vortragshonorare von den Firmen Bristol MyersSquibb, Berlin Chemie, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, Hexal, Lilly erhalten und Forschungsunterstützung von EU, DFG, BMBF, BMG, DGUV, BGW, Verwaltungs-BG, Bundesarbeitsministerium, Bayerische Ministerien, Industrie (MAN, FMG, Siemens, Audi), Versicherungen, ADAC/ÖAMTC u.a., Kliniken, Erzbischöflichem Ordinariat, Caritas. Die Tätigkeiten liegen außerhalb der Thematik dieser Arbeit. J.E., D.S., S.S. und P.H. geben an, dass keine Interessenkonflikte bestehen., (Thieme. All rights reserved.)

In this study, we investigated the outcomes and factors influencing treatment efficacy in 93 patients with limited disease small cell lung cancer (LD-SCLC), with a median age of 64 years. We focused on the impact of chemotherapy regimens, prophylactic cranial irradiation (PCI), and patient-related variables. The median follow-up for OS was 17.3 months. We observed a statistically significant difference in PFS between LD-SCLC patients treated with cisplatin and etoposide (EP) and those treated with carboplatin and etoposide (CP) (PFS: EP 13.63 months vs. CP 6.54 months, p < 0.01). Patients treated with EP had better overall survival (OS) than CP-treated patients (OS: EP 26.9 months vs. CP 16.16 months, p < 0.01). Concomitant chemotherapy was associated with improved PFS ( p = 0.003) and OS ( p = 0.002). Patients receiving PCI showed superior OS ( p = 0.05) and a trend towards improved PFS ( p = 0.057). Female gender was associated with better OS ( p = 0.025). Most patients had an ECOG performance status of 0 (71%). This real-world study underscores the importance of multidisciplinary LD-SCLC management, emphasizing the roles of chemotherapy, radiotherapy, and PCI. These findings inform personalized treatment strategies and emphasize the need for prospective trials to validate these results and optimize LD-SCLC treatment.

E-cigarettes are primarily used by teenagers and young adults. Flavors in e-cigarettes increase their attractiveness and encourage young people and adults to start using them. This exposes young people in particular to the risk of nicotine addiction and various toxic substances from the aerosol of e-cigarettes. There are indications that various flavors in e-cigarettes are harmful to health, although toxicological studies are still lacking for the majority of flavors. There is a need for independent scientific investigations in this area. The scientific societies involved are calling for a ban on flavors in e-cigarettes, a ban on disposable e-cigarettes, effective regulation of the sale of e-cigarettes and effective control and implementation of the provisions for the protection of minors., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRAS and TP53 mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap., Methods: A total of 696 consecutive patients with programmed death-ligand 1-high (≥50%), nonsquamous NSCLC, having received molecular testing within the German National Network Genomic Medicine Lung Cancer between 2017 and 2020, with Eastern Cooperative Oncology Group performance status less than or equal to 1 and pembrolizumab as first-line palliative treatment, were included into this retrospective cohort analysis. Treatment efficacy and outcome according to KRAS/TP53 status were correlated with TME composition and gene expression analysis of The Cancer Genome Atlas lung adenocarcinoma cohort., Results: Proportion of KRASmut and TP53mut was 53% (G12C 25%, non-G12C 28%) and 51%, respectively. In KRASmut patients, TP53 comutations increased response rates (G12C: 69.7% versus 46.5% [TP53mut versus wild-type (wt)], p = 0.004; non-G12C: 55.4% versus 39.5%, p = 0.03), progression-free survival (G12C: hazard ratio [HR] = 0.59, p = 0.009, non-G12C: HR = 0.7, p = 0.047), and overall survival (G12C: HR = 0.72, p = 0.16, non-G12C: HR = 0.56, p = 0.002), whereas no differences were observed in KRASwt patients. After a median follow-up of 41 months, G12C/TP53mut patients experienced the longest progression-free survival and overall survival (33.7 and 65.3 mo), which correlated with high tumor-infiltrating lymphocyte densities in the TME and up-regulation of interferon gamma target genes. Proinflammatory pathways according to TP53 status (mut versus wt) were less enhanced and not different in non-G12C and KRASwt, respectively., Conclusions: G12C/TP53 comutations identify a subset of patients with a very favorable long-term survival with immune checkpoint inhibitor monotherapy, mediated by highly active interferon gamma signaling in a proinflammatory TME., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials., Methods: Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels., Results: We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival., Conclusion: First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JAS reports personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from Roche, personal fees from BMS, personal fees from Amgen, personal fees from LEO pharma, personal fees from Novartis, personal fees from Takeda, outside of the submitted work. FCA has received a research grant from Novartis, support for attending meetings and/or travel from Amgen, and consultant fees from IQVIA.PD has nothing to disclose. JR has nothing to disclose. AT has nothing to disclose. ANH has nothing to disclose. NF reports personal fees from AbbVie, Amgen, AstraZeneca, BeiGene, Berlinchemie, Boehringer Ingelheim, Bristol Myers&Squibb, Lilly, Merck Sharp&Dohme, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, outside of the submitted work. HY has nothing to disclose. PC has received research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, Roche, and Takeda, speaker’s honoraria from AstraZeneca, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Daiichi Sankyo, Gilead, Novartis, Pfizer, Takeda, and personal fees for participating to advisory boards from Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche, all outside the submitted work. OB has nothing to disclose. CMB has nothing to disclose. ABVD has nothing to disclose. JA has nothing to disclose. SPA as nothing to disclose. MW has nothing to disclose. SK has nothing to disclose. MU has nothing to disclose. GT has nothing to disclose. CFW has nothing to disclose. AR reports grants from AbbVie, grants from AstraZeneca, grants from BMS, grants from Boehringer Ingelheim, grants from Daichi Sankyo, grants from Eli Lilly, grants from GSK, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, outside the submitted work. PH has nothing to disclose. JB has nothing to disclose. HGK has nothing to disclose. CG has nothing to disclose. MSch has nothing to disclose. CSch has nothing to disclose. FG reports personal fees from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, Ariad, Abbvie, Tesaro / GSK, Sanofi, Daiichi-Sankyo, Beigene, outside of the submitted work. MSch has nothing to disclose. MS reports personal fees from Lilly, Astra-Zeneca, Bristol-Myers & Squibb, Merck Sharp & Dohme, Pfizer, Takeda, Roche, AbbVie, Boehringer-Ingelheim, Celgene, Novartis, grants from Astra Zeneca outside the submitted work. NR reports personal fees from Amgen, personal fees from AstraZeneca, personal fees from Bristol-Myers Squibb, personal fees from Boehringer-Ingelheim, personal fees from Daiichi Sankyo, personal fees from GSK, personal fees from Hoffmann-La Roche, personal fees from Janssen, personal fees from MSD, personal fees from Merck, personal fees from Lilly, personal fees from Pfizer, personal fees from Takeda, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tobacco smoking is widespread in Germany. An increase in the number of teenagers and young adults that smoke has recently been a cause for concern. The high prevalence in Germany is contrasted by inadequate preventive measures compared to international standards. Smoking behavior should always be inquired about and documented in the same way as vital signs. All smokers, regardless of the reason for contact and motivation, should receive short, low-threshold advice, e.g. using the ABC approach (ask, brief advice, cessation). In addition to repeated advice and referral to further services, the use of nicotine replacement or drug therapy is essential for the success of quitting. The combination of long- and short-acting nicotine replacement products doubles the success rate. Electronic nicotine delivery systems are not recommended for smoking cessation., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on the early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present key points for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process. CITATION FORMAT: · Vogel-Claussen J, Blum TG, Andreas S et al. Position paper on the implementation of a nationally organized program in Germany for the early detection of lung cancer in high-risk populations using low-dose CT screening including the management of screening findings requiring further workup. Fortschr Röntgenstr 2024; 196: DOI 10.1055/a-2178-2846., Competing Interests: T. G. B. gibt eine Forschungsförderung von EU4Health an.J. V.-C. gibt Forschungsförderungen von BMBF, NIH, AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim an.S. A. gibt eine Mitarbeit im Aktionsbündnis Nichtraucherschutz und in der Task Force Tabakentwöhnung der DGP an.H.-U. K. gibt Forschungsförderungen von Siemens, Philips und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von Siemens, Boehringer Ingelheim, Philips, Sanofi und Median an.Alle weiteren Autorinnen und Autoren haben keine potenziellen COI angegeben., (Thieme. All rights reserved.)

After several years of declining tobacco consumption, the number of smokers in Germany is currently stagnating or rising again. The reasons seem to be manifold, e. g. stress caused by the pandemic with social isolation, rising cost of living and war in Europe.With tobacco use still widespread in the German population, evidence-based tobacco cessation is rarely implemented.According to recent studies, e-cigarettes are involved in the pathogenesis of lung disease, cardiac and vascular damage. In addition, their ingredients also have carcinogenic effects. However, clinical studies on long-term use are not yet available.E-cigarettes as a consumer product are not superior to nicotine replacement products and addiction-reducing medications recommended in guidelines. In the therapeutic setting, they are slightly more effective than nicotine replacement products. However, they are usually consumed continuously and thus perpetuate nicotine dependence. Their use increases the risk of relapse to tobacco smoking.Despite the various new approaches, such as Internet-based offerings, app, etc., talks and pharmacotherapy are the gold standard and more effective than any therapy on its own., Competing Interests: PD Dr. med. K. F. Franzen und Prof. Dr.med.W. Pankow sind im Pfizer Advisory Board zur Tabakentwöhnung tätig. Prof. Dr. med. S. Andreas hat keine Interessenkonflikte im Bezug auf diese Publikation., (Thieme. All rights reserved.)

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process., Competing Interests: T. G. B. gibt eine Forschungsförderung von EU4Health an.J. V.-C. gibt Forschungsförderungen von BMBF, NIH, AstraZeneca, Siemens Healthineers, Glaxo Smith Kline und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim an. S. A. gibt eine Mitarbeit im Aktionsbündnis Nichtraucherschutz und in der Task Force Tabakentwöhnung der DGP an.H.-U. K. gibt Forschungsförderungen von Siemens, Philips und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von Siemens, Boehringer Ingelheim, Philips, Sanofi und Median an.Alle weiteren Autorinnen und Autoren haben keine potenziellen COI angegeben., (Thieme. All rights reserved.)

Purpose: The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses., Methods: Patients received tiragolumab 600 mg/placebo, plus atezolizumab 1,200 mg and CE (four cycles), then maintenance tiragolumab/placebo plus atezolizumab. Primary end points were investigator-assessed PFS and OS in patients without history/presence of brain metastases (primary analysis set [PAS]). Additional end points included PFS and OS in all patients regardless of brain metastases status (full analysis set [FAS]), response, and safety., Results: Four hundred ninety patients were randomly assigned (FAS): 243 to tiragolumab arm and 247 to control arm. At the cutoff date (February 6, 2022; median duration of follow-up, 14.3 months [PAS] and 13.9 months [FAS]), final analysis of PFS in the PAS (n = 397) did not reach statistical significance (stratified hazard ratio [HR], 1.11; P = .3504; median, 5.4 months tiragolumab v 5.6 months control). At the cutoff date (September 6, 2022; median duration of follow-up, 21.2 months [FAS]), median OS in the PAS at final OS analysis was 13.1 months in both arms (stratified HR, 1.14; P = .2859). Median PFS and OS in the FAS were consistent with the PAS. The proportion of patients with immune-mediated adverse events (AEs) in the tiragolumab and control arms was 54.4% and 49.2%, respectively (grade 3/4: 7.9% and 7.7%). AEs leading to treatment withdrawal occurred in 8.4% and 9.3% of tiragolumab- and control-treated patients, respectively., Conclusion: Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals.

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process., Competing Interests: T.G.B. gibt eine Forschungsförderung von EU4Health an.J.V.-C. gibt Forschungsförderungen von BMBF, NIH, AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim an. S.A. gibt eine Mitarbeit im Aktionsbündnis Nichtraucherschutz und in der Task Force Tabakentwöhnung der DGP an.H.-U.K. gibt Forschungsförderungen von Siemens, Philips und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von Siemens, Boehringer Ingelheim, Philips, Sanofi und Median an.Alle weiteren Autorinnen und Autoren haben keine potenziellen Interessenkonflikte angegeben., (Thieme. All rights reserved.)

Evaluating cancer treatments in real-world data (RWD) requires informative endpoints. This study replicated the atezolizumab and docetaxel arms of the OAK trial using RWD and compared progression-free survival (PFS) outcomes derived from abstracted physician's notes in RWD (rwPFS) against PFS outcomes derived from the clinical trial PFS (ctPFS). Atezolizumab and docetaxel arms of the phase III OAK randomized controlled trial (RCT; NCT02008227) were replicated in a US nationwide real-world database using selected OAK inclusion/exclusion criteria and propensity score-based adjustment for baseline prognostic variables. Concordance of outcomes was assessed using Kaplan-Meier medians and hazard ratios (HRs). The RWD cohorts comprised 133 patients on atezolizumab and 479 patients on docetaxel. After adjustment, prognostic variables were balanced between RCT arms and corresponding RWD cohorts. The rwPFS and ctPFS outcomes showed better concordance for docetaxel (2.99 vs. 3.52 months; HR: 0.99, 95% confidence interval (CI): 0.85-1.15) than for atezolizumab (3.71 vs. 2.76 months; HR: 0.8, 95% CI: 0.61-1.02). Excluding events labeled "pseudo-progression" from both RWD and RCT improved concordance for atezolizumab (4.24 vs. 4.14 months; HR: 0.95, 95% CI: 0.70-1.25). These findings were robust across sensitivity analyses. Replicating RCTs using RWD and comparing outcomes can help characterize RWD endpoints. Similarity of results between rwPFS and ctPFS at the cohort level may depend on drug category, highlighting the need for further studies to verify and understand when the corresponding outcomes can be compared, including within the same patient., (© 2023 F. Hoffmann-La Roche Ltd and The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

Background: IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here., Patient and Methods: The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1 : 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition). Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay)., Results: At a median of 45.3 months' follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified hazard ratio (HR) was 0.995 [95% confidence interval (CI) 0.78-1.28]. The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n = 882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 tumour cell (TC) ≥1% (n = 476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n = 229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis [grade 3/4 in 53 (10.7%) and grade 5 in 4 (0.8%) of 495 patients, respectively]., Conclusions: Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Endoscopic lung volume reduction (ELVR) with one-way valves produces beneficial outcomes in patients with severe emphysema. Evidence on the efficacy remains unclear in patients with a very low forced expiratory volume in 1 s (FEV 1 ) (≤20% predicted). We aim to compare clinical outcomes of ELVR, in relation to the FEV 1 restriction., Methods: All data originated from the German Lung Emphysema Registry (Lungenemphysem Register), which is a prospective multicentric observational study for patients with severe emphysema after lung volume reduction. Two groups were formed at baseline: FEV 1 ≤20% pred and FEV 1 21-45% pred. Pulmonary function tests (FEV 1 , residual volume, partial pressure of carbon dioxide), training capacity (6-min walk distance (6MWD)), quality of life (modified Medical Research Council dyspnoea scale (mMRC), COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ)) and adverse events were assessed and compared at baseline and after 3 and 6 months., Results: 33 patients with FEV 1 ≤20% pred and 265 patients with FEV 1 21-45% pred were analysed. After ELVR, an increase in FEV 1 was observed in both groups (both p<0.001). The mMRC and CAT scores, and 6MWD improved in both groups (all p<0.05). The SGRQ score improved significantly in the FEV 1 21-45% pred group, and by trend in the FEV 1 ≤20% pred group. Pneumothorax was the most frequent complication within the first 90 days in both groups (FEV 1 ≤20% pred: 7.7% versus FEV 1 21-45% pred: 22.1%; p=0.624). No deaths occurred in the FEV 1 ≤20% pred group up to 6 months., Conclusion: Our study highlights the potential efficacy of one-way valves, even in patients with very low FEV 1 , as these patients experienced significant improvements in FEV 1 , 6MWD and quality of life. No death was reported, suggesting a good safety profile, even in these high-risk patients., Competing Interests: Conflict of interest: S. Eisenmann reports receiving grants or contracts from DFG, outside the submitted work; consulting fees from Acceleron, AstraZeneca and Sanofi Genzyme, outside the submitted work; payment for expert testimony for Nanovation, outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim and Sanofi Genzyme, outside the submitted work. Conflict of interest: M. Witzenrath reports grants or contracts from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsche Gesellschaft für Pneumologie, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Stiftung, Capnetz Stiftung, Bayer Health Care, Biotest and Pantherna, outside the submitted work; consulting fees from Insmed, Pantherna, Pherecydes, Aptarion, GlaxoSmithKline, Inflarx and Biotest, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Insmed, Chiesi, Novartis, Teva, Actelion, Boehringer Ingelheim, GlaxoSmithKline, Biotest and Bayer Health Care, outside the submitted work; patents issued EPO 12181535.1 (IL-27 for modulation of immune response in acute lung injury), WO/2010/094491 (Means for inhibiting the expression of Ang-2), DE 102020116249.9 (Camostat/Niclosamide cotreatment in SARS-CoV-2 infected human lung cells) and PCT/EP2021/075627 (New medical use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators), outside the submitted work. Conflict of interest: A. Holland reports being a board member of Lungenemphysemregister e.V., outside the submitted work. Conflict of interest: W. Gesierich reports lectures fees from PulmonX GmbH, outside the submitted work. Conflict of interest: R-H. Hübner reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pulmonx, Olympus and AstraZeneca, outside the submitted work; participation on a data safety monitoring board or advisory board for Bento Study (sponsor: IHF GmbH – Institut für Herzinfarktforschung), outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group for Head of Lungenemphysem Register e.V., outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy., Methods: This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786., Findings: Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4-11·9] vs 9·2 months [5·9-11·2]; stratified hazard ratio 0·78 [0·63-0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3-29·4) with atezolizumab compared with 12% (6·7-18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3-4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%])., Interpretation: First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy., Funding: F Hoffmann-La Roche and Genentech Inc, a member of the Roche group., Competing Interests: Declaration of interests SML declares support from Roche for attending meetings and travelling to present the first-line atezolizumab versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS) trial at the European Society of Medical Oncology 2022 meeting, and membership for the UK commission on Human Medicines and the Oncology and Haematology Expert Advisory Group. CS declares provision of study material from Roche; clinical trial support, consulting fees, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, from AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Pfizer, Roche, and Takeda; and support for attending meetings or travel from AstraZeneca, Boehringer Ingelheim, Roche, and Takeda. KP declares institutional funding from Alkem Laboratories and Roche. DK declares membership on an advisory board for Bristol Myers Squibb, MSD, Amgen, Roche, Pfizer, AstraZeneca, Boehringer Ingelheim, Novartis, Takeda, Sanofi-Aventis, and Janssen. AR declares consulting fees from AbbVie, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, and Roche and support for attending meetings or travel from Bristol Myers Squibb, GlaxoSmithKline, and Roche. TT declares payment for advisory board activity relating to atezolizumab in early-stage NSCLC. DV declares consulting fees from Lilly, Roche, AstraZeneca, Pfizer, Novartis, MSD, Bristol Myers Squibb, Takeda, and Gilead; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Roche, MSD, Bristol Myers Squibb, Pfizer, Gilead, Takeda, and Bayer; and support for attending meetings or travel from AstraZeneca and Pfizer. RC declares receiving a grant to run the study; consulting fees from AstraZeneca, Boehringer Ingelheim, Lilly Oncology, Roche, Pfizer, MSD, Bristol Myers Squibb, Takeda, Bayer, Sanofi, Novartis, and Janssen; honoraria from AstraZeneca, Boehringer Ingelheim, Lilly Oncology, Roche, Pfizer, MSD, Bristol Myers Squibb, Takeda, Bayer, Sanofi, Novartis, and Janssen; support for attending meetings or travel from MSD, Takeda, Roche, and Janssen; participation on advisory boards for AstraZeneca, Boehringer Ingelheim, Lilly Oncology, Roche, Pfizer, MSD, Bristol Myers Squibb, Takeda, Bayer, Sanofi, Novartis, and Janssen; and owning stock or stock options for Leaders in Oncology at The Christie Private Care. DC declares payment for speakers bureaus or scientific advisory from MSD, Bristol Myers Squibb, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Amgen, and Sanofi Genzyme. GL declares institutional grants or contracts from the US National Cancer Institute, the Canadian Institutes of Health Research, Canadian Cancer Society Research Institute (Canada), AstraZeneca, Takeda, Boehringer Ingelheim, and Amgen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Pfizer, EMD Serono, Takeda, Jazz, and Novartis; and participation on a data safety monitoring board or advisory board for AstraZeneca, Pfizer, EMD Serono, Merck, AbbVie, Jazz, Takeda, Roche, Bristol Myers Squibb, Novartis, and Lilly. MR declares consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, and support for attending meetings or travel from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, GlaxoSmithKline, Mirati, Merck, MSD, Novartis, Pfizer, Sanofi, and Roche; and participation on a data safety monitoring board or advisory board for Sanofi and Daiichi-Sankyo. RP declares consulting fees from AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Guardant Health and Pfizer; support for attending meetings or travel from MSD; and participation on a data safety monitoring board or advisory board for AstraZeneca. MPM declares honoraria for lectures from Roche and MSD. YH and SM are employed by Roche. EH declares study support from Roche, discounted prices on stocks as a Roche employee, and employment by Roche. MC declares stocks as part of employment at Genentech and employment at Genentech. HKV is employed by Roche and declares holding stock for Roche. SP declares consultation or an advisory role for AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi-Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GlaxoSmithKline, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, Medtoday, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, PharmaMar, Phosplatin Therapeutics, Physicians' Education Resource, Peerview, Pfizer, PRIME, Regeneron, RMEI, Roche and Genentech, Research to Practice, Sanofi, Seattle Genetics, Takeda, and Vaccibody; speaking in a company's organised public event for AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, GlaxoSmithKline, Illumina, Imedex, Ipsen, Medscape, Merck Sharp & Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Prime, Roche and Genentech, RTP, Sanofi, and Takeda; and receipt of grants and research support (institutional financial support for clinical trials) as a principal investigator in trials sponsored by Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, and Roche and Genentech. SML is partially supported by the University College London Hospitals and University College London Biochemical Research Centre. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tobacco smoking is the greatest preventable health risk. The effects are serious, both individually and societal. Nevertheless, the current prevalence of tobacco smokers in Germany is still high at around 35 %. A recent strong increase in actively smoking adolescents (14- to 17-year-olds, current prevalence approx. 16 %) and young adults (18- to 24-year-olds, current prevalence approx. 41 %) is also a cause for concern. About a third of all inpatients continue smoking while being treated. The hospitalization of active smokers in acute and rehabilitation hospitals serves as a "teachable moment" for initiation of cessation offers. An intervention that begins in hospital and continues for at least a month after discharge results in about 40 % additional smokefree patients. It is scientifically well-researched, effective and cost-efficient. After initiation in hospital these measures can be continued via ambulatory cessation programs, rehabilitation facilities, an Internet or telephone service. In Germany, there are structured and quality-assured cessation offers, both for the inpatient and for the outpatient area. The biggest obstacle to broad establishment of such offers is the lack of reimbursement. Two feasible ways to change this would be the remuneration of the existing OPS 9-501 "Multimodal inpatient treatment for smoking cessation" and the establishment of quality contracts according to § 110a SGB V. An expansion of tobacco cessation measures in healthcare facilities would reduce smoking prevalence, associated burden of disease and consecutive costs., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

(1) Background: The main objectives of our study are (i) to determine the prevalence of NTRK ( neurotrophic tyrosine kinase ) fusions in a routine diagnostic setting in NSCLC (non-small cell lung cancer) and (ii) to investigate the feasibility of screening approaches including immunohistochemistry (IHC) as a first-line test accompanied by fluorescence in situ hybridization (FISH) and RNA-(ribonucleic acid-)based next-generation sequencing (RNA-NGS). (2) Methods: A total of 1068 unselected consecutive patients with NSCLC were screened in two scenarios, either with initial IHC followed by RNA-NGS ( n = 973) or direct FISH testing ( n = 95). (3) Results: One hundred and thirty-three patients (14.8%) were IHC positive; consecutive RNA-NGS testing revealed two patients (0.2%) with NTRK fusions ( NTRK1-EPS15 ( epidermal growth factor receptor pathway substrate 15 ) and NTRK1-SQSTM1 ( sequestosome 1 )). Positive RNA-NGS was confirmed by FISH, and NTRK -positive patients benefited from targeted treatment. All patients with direct FISH testing were negative. RNA-NGS- or FISH-positive results were mutually exclusive with alterations in EGFR ( epidermal growth factor receptor ), ALK ( anaplastic lymphoma kinase ), ROS1 ( ROS proto-oncogene 1 ), BRAF ( proto-oncogene B-Raf ), RET ( rearranged during transfection ) or KRAS ( kirsten rat sarcoma viral oncogene ). Excluding patients with one of these alterations raised the prevalence of NTRK -fusion positivity among panTrk-(tropomyosin receptor kinase-) IHC positive samples to 30.5%. (4) Conclusions: NTRK fusion-positive lung cancers are exceedingly rare and account for less than 1% of patients in unselected all-comer populations. Both RNA-NGS and FISH are suitable to determine clinically relevant NTRK fusions in a real-world setting. We suggest including panTrk-IHC in a diagnostic workflow followed by RNA-NGS. Excluding patients with concurrent molecular alterations to EGFR/ALK/ROS1/BRAF/RET or KRAS might narrow the target population.

Tobacco dependence is a common comorbidity in patients with COPD (Chronic Obstructive Pulmonary Disease) that negatively affects the course of the disease. However, clinically relevant improvement in COPD can only be achieved by complete and permanent abstinence. Therefore, abstinence from tobacco use is a central therapeutic concept in smoking patients with COPD and requires specific and targeted treatment.After detailed documentation of smoking behaviour and motivational counseling outlining the risks of smoking, all such patients shall be offered a structured therapy for tobacco cessation. There is high-quality evidence for the effectiveness of a combination therapy of behavioral therapy and medication (to treat the withdrawal syndrome). Due to insufficient data, there is currently no recommendation for the use of e-cigarettes as a primary option for a cessation attempt.Smoking is the most important cause of COPD. Smoking cessation is the most effective and cost-efficient single intervention to reduce the risk of developing and progressing COPD., Competing Interests: SA erhielt Forschungsförderung von Boehringer Ingelheim und Honorar für Referententätigkeit von Boehringer Ingelheim, Novartis, AstraZeneca, GSK, Chiesi, Merini. SA ist Leiter der Task Force Tabakentwöhnung der DGP und Mitglied des ABNR.DK erhielt Forschungsförderung vom Bundesministerium für Gesundheit für die Durchführung der Deutschen Befragung zum Rauchverhalten (DEBRA; DRKS00017157 und DRKS00028054) und für die ABC-II-Studie (RCT zum Training von Hausärzten in der leitliniengerechten Kurzberatung zur Tabakentwöhnung; DRKS00012786).AB erklärt: Förderung durch die Bundeszentrale für gesundheitliche Aufklärung, eigenes Tabakentwöhnungsprogramm (Nichtraucher in sechs Wochen). Mitglied im Vorstand des Wissenschaftlichen Aktionskreises Tabakentwöhnung (WAT) e. V. und der Deutschen Gesellschaft für Suchtforschung und Suchttherapie (DG-Sucht) e. V.AH hielt Vorträge für Orion Pharma.SM erklärt: Pfizer (Vortragshonorar + Beratung); Johnson + Johnson (Honorartätigkeit Workshop + Advisory Board); Leitung Raucherambulanz Chemnitz; Wissenschaftlicher Arbeitskreis Tabakentwöhnung; Mitarbeit S3 LL Alkohol und Tabak.DN erhielt Forschungsunterstützung für Forschungsprojekte des Instituts von EU, DFG, BMBF, BMG, DGUV, BGW, Verwaltungs-BG, Bundesarbeitsministerium, Bayerischen Ministerien, Industrie (MAN, FMG, Siemens, Audi), Versicherungen, ADAC/ÖAMTC, Kliniken, Erzbischöfliches Ordinariat, Caritas. DN erhielt Vortragshonorare von Bristol MyersSquibb, Berlin Chemie, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, Hexal, Lilly. DN ist Mitglied eines Advisory Boards von Pfizer zur Rauchentwöhnung. DN ist Vertreter der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin im Aktionsbündnis Nichtrauchen (ABNR).KS erhielt Forschungsförderung von der Deutschen Rentenversicherung Bayern Süd und Honorare für Referententätigkeit von AstraZeneca, GSK, Chiesi, Sanofi Genzyme und Berlin-Chemie.HW erklärt, während der letzten 3 Jahre keine wirtschaftlichen oder persönlichen Verbindungen im oben genannten Sinne zu haben.SS begleitet im Rahmen ihrer Tätigkeit beim ÄZQ die Erstellung von Leitlinien methodisch und organisatorisch., (Thieme. All rights reserved.)

Purpose: Superior vena cava syndrome (SVCS) often results from external vessel compression due to tumor growth. Urgent symptom-guided radiotherapy (RT) remains a major treatment approach in histologically proven, rapidly progressive disease. Despite several publications, recent data concerning symptom relief and oncological outcome as well as potential confounders in treatment response are still scarce., Methods: We performed a retrospective single-center analysis of patients receiving urgent RT between 2000 and 2021 at the University Medical Center Göttingen. Symptom relief was evaluated by CTCAE score during the RT course. Effects of variables on symptom relief were assessed by logistic regression. The impact of parameters on overall survival (OS) was evaluated using Kaplan-Meier plot along with the log-rank test and by Cox regression analyses. Statistically significant (p-value < 0.05) confounders were tested in multivariable analyses., Results: A total of 79 patients were included. Symptom relief was achieved in 68.4%. Mean OS was 59 days, 7.6% (n = 6) of patients showed long-term survival (> 2 years). Applied RT dose > 39 Gy, clinical target volume (CTV) size < 387 ml, concomitant chemotherapy, and completion of the prescribed RT course were found to be statistically significant for OS; applied RT dose and completion of the prescribed RT course were found to be statistically significant for symptom relief., Conclusion: Symptom relief by urgent RT for SVCS was achieved in the majority of patients. RT dose and completion of the RT course were documented as predictors for OS and symptom relief, CTV < 387 ml and concomitant chemotherapy were predictive for OS., (© 2022. The Author(s).)

Purpose: Smoking cessation in patients with diagnosed lung cancer has positive effects on cancer therapy and overall prognosis. Despite this, knowledge on smoking cessation in lung cancer patients is sparse., Methods: This is an observational single centre, 12-week, prospective, single-arm trial at a tertiary lung cancer centre. Responsive patients were enrolled following confirmed lung cancer diagnosis. Smoking cessation intervention included counselling as well as pharmacotherapy. The primary endpoint was the point prevalence abstinence rate at week 12 based on biochemical verification. Secondary endpoints were the abstinence rate at week 26, quality of life and side effects., Results: 80 patients were enrolled. Mean age was 62.6 ± 7.9 years. Most patients (63%) were treated with chemotherapy or radiochemotherapy. 39 patients used nicotine replacement therapy, 35 varenicline whereas six patients did not use pharmacotherapy. During the study period 13 patients died. Data were available in 72 patients after 12 weeks and 57 patients at week 24. Point prevalence abstinence rates were 37.5% (95% CI 26.4-49.7%) at week 12 and 32.8% (95% CI 21.8-45.4%) at week 26, respectively. Quality of life and side effects were not significantly affected by pharmacotherapy., Conclusion: In conclusion, our results suggest that smoking cessation is feasible in patients with newly diagnosed lung cancer. The observed abstinence rate is comparable to other patient cohorts. Furthermore, pharmacotherapy in addition to cancer therapy was safe and did not show novel side effects in these seriously ill patients. Thus, smoking cessation should be an integral part of lung cancer treatment. Trial registration The study was conducted in accordance with good clinical practice standards (GCP) and approved by the local ethics committee (16/3/14), the European PAS registry (EUPAS8748) and the German BfArM (NIS-Studien-Nr. 5508). All patients provided written informed consent before study enrollment., (© 2022. The Author(s).)

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with changes in the sputum microbiome, including an increased prevalence of pathogenic bacteria. Vaccination against the most frequent bacteria identified in AECOPD might reduce exacerbation frequency. We assessed the efficacy, safety, and immunogenicity of a candidate vaccine containing surface proteins from non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) in patients with COPD., Methods: This multicentre, randomised, observer-blinded, placebo-controlled, proof-of-concept, phase 2b trial recruited patients with stable COPD, moderate-to-very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2, 3, or 4), at 67 clinical sites in Belgium, Canada, France, Germany, Italy, Spain, UK, and USA. Eligible patients were aged 40-80 years and had a history of at least one moderate or severe exacerbation in the previous year. Patients were allocated (1:1) using a minimisation algorithm to receive two intramuscular injections of NTHi-Mcat vaccine or placebo 60 days apart, in addition to standard care. The allocation algorithm considered age category, number of previous exacerbations, COPD severity at study entry, and country as minimisation factors, to guarantee treatment balance within each factor. Vaccine recipients and those responsible for evaluating study endpoints were masked to group allocation. In the analysis of efficacy, the primary outcome was the rate of any moderate or severe AECOPD occurring within a 1-year period, starting 1 month after the second dose in patients who received two vaccine doses (modified total vaccinated cohort). Safety was assessed in the total vaccinated cohort. The trial is registered with ClinicalTrials.gov, number NCT03281876, and is complete., Findings: Between Nov 27, 2017, and Nov 30, 2018, 606 adults were enrolled and included in the total vaccinated cohort (304 in the NTHi-Mcat vaccine group, 302 in the placebo group); 571 received two doses and were included in the primary efficacy analysis (279 in the NTHi-Mcat vaccine group, 292 in the placebo group). 23 participants dropped-out in the NTHi-Mcat vaccine group and 39 in the placebo group; this included 4 patients in the NTHi-Mcat vaccine group and 15 in the placebo group who withdrew from the study because of an adverse event. The primary analysis included 340 exacerbations (in follow-up time 102 123 days) in the NTHi-Mcat vaccine group and 333 (in 104 443 days) in the placebo group, with a yearly rate of moderate or severe AECOPD of 1·22 in the NTHi-Mcat vaccine group and 1·17 in the placebo group, with vaccine efficacy in reducing the yearly rate of moderate or severe AECOPD estimated to be zero (vaccine efficacy point estimate 2·26% [87% CI -18·27 to 11·58]; p=0·82). Solicited local adverse events were more frequent in the NTHi-Mcat vaccine group (216 [72%] of 301 patients) than with placebo (34 [11%] of 299 patients), and the frequency of solicited general adverse events was similar between groups (239 [79%] of 301 vs 235 [79%] of 299 patients). There was one death in the NTHi-Mcat vaccine group (acute respiratory failure, not related to vaccination) and ten in the placebo group (seven due in part to COPD or respiratory failure). There were 158 serious adverse events (89 [29%] of 304 patients) in the NTHi-Mcat vaccine group, not related to vaccination, and 214 (99 [33%] of 302 patients) in the placebo group., Interpretation: NTHi-Mcat vaccine administered to patients with COPD did not show efficacy in reducing the yearly rate of moderate or severe exacerbations. No safety concerns were identified., Funding: GlaxoSmithKline Biologicals SA., Competing Interests: Declaration of interests SA reports grants and personal fees from Boehringer Ingelheim, grants from Pfizer, and personal fees from Novartis, AstraZeneca, the GlaxoSmithKline (GSK) group of companies, Chiesi, and Merini, outside of the submitted work. AKA, DC, GDM, ML, LM, SS, and AT are employees of the GSK group of companies. MT was an employee of the GSK group of companies when this study was conducted and is now an employee of Janssen–Cilag SpA. ML and SS also hold shares in the GSK group of companies. GB reports having received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, the GSK group of companies, Novartis, and Teva, and for advisory boards from Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, the GSK group of companies, Novartis, Sanofi–Regeneron, and Teva, all outside of the submitted work. WJ reports grants from AstraZeneca, Chiesi, Roche, and Boehringer Ingelheim outside of the submitted work. EK has served on advisory boards and received consulting fees and travel reimbursements from Amphastar, AstraZeneca, Boehringer Ingelheim, Chiesi, Connect Biopharmaceuticals, the GSK group of companies, Mylan, Novartis, Sunovion, and Theravance, outside of the submitted work. AP reports receiving fees for board membership, consultancy, payment for lectures, grants for research, travel expense reimbursement from Chiesi, AstraZeneca, the GSK group of companies, Boehringer Ingelheim, and Teva; fees for board membership, consultancy, payment for lectures, travel expense reimbursement from Mundipharma, Novartis, Zambon, and Sanofi–Regeneron; and grants for research, payment for lectures, travel expenses reimbursement from Menarini, fees for board membership, consultancy, travel expenses reimbursement from Roche, grants for research from Fondazione Maugeri, Fondazione Chiesi, and consultancy fees from Edmondpharma, all outside of the submitted work. LP-M reports, outside of the submitted work, financial support for educational activities and advisory from AstraZeneca, financial support for educational activities and a grant for non-committed investigation from the GSK group of companies, investigation grant from Esteve and Menarini, travel bourses from Boerhinger Ingelheim and Teva, travel bourse, and personal fees for educational activities from Novartis, financial support for educational activities from Chiesi, and personal fees for advisory from Merck Sharpe & Dohme and Boston Scientific. DS, BP, and LB declare no financial and non-financial relationships and activities and no conflicts of interest. HW reports a grant to his employer from the GSK group of companies during the conduct of this study, and grants or personal fees from the GSK group of companies, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Menarini, Takeda, and Bayer outside of the submitted work. TMAW received grants from the GSK group of companies during the conduct of this study. TMAW also received grants from AstraZeneca, Synairgen, UK Research and Innovation, and MyMHealth, and fees or non-financial support from Boehringer Ingelheim, Chiesi, and AstraZeneca, outside of the submitted work. TMAW is an inventor on patent applications: 2018 US Patent application 62/479562—immunogenic composition, use and methods of treatment—a novel vaccine to prevent exacerbations of COPD pending to the GSK group of companies; and US patent application 62/479550 (novel COPD vaccine). TMAW is the founder and director of MyMHealth Ltd. FM reports a grant paid to his institution by the GSK group of companies during the conduct of this study, and grants paid to his institution by the GSK group of companies, AstraZeneca, Sanofi; unrestricted grant paid to his institution by Novartis, Boehringer Ingelheim, Grifols; personal fees for participating in speaker bureau from the GSK group of companies, Boehringer Ingelheim, Grifols, Novartis; and financial participation in Oxynov, all outside of the submitted work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: This phase III OAK trial (NCT02008227) subgroup analysis (data cutoff, January 9, 2019) evaluated the predictive value of 2 PD-L1 IHC tests (VENTANA SP142 and Dako 22C3) for benefit from atezolizumab versus docetaxel by programmed death ligand 1 (PD-L1) status in patients with previously treated metastatic non-small cell lung cancer., Methods: PD-L1 expression was assessed prospectively with SP142 on tumor cells (TC) and tumor-infiltrating immune cells (IC) and retrospectively with 22C3 using a tumor proportion score (TPS) based on TC membrane staining. Efficacy was assessed in the 22C3 biomarker-evaluable population (22C3-BEP) (n = 577; 47.1% of SP142-intention-to-treat population) and non-22C3-BEP (n = 648) in PD-L1 subgroups (high, low, and negative) and according to selection by 1 or both assays., Results: In the 22C3-BEP, overall survival benefits with atezolizumab versus docetaxel were observed across PD-L1 subgroups; benefits were greatest in SP142-defined PD-L1-high (TC3 or IC3: hazard ratio [HR], 0.39 [95% confidence interval (CI), 0.25-0.63]) and 22C3-defined PD-L1-high (TPS ≥ 50%: HR, 0.56 [95% CI, 0.38-0.82]) and low (TPS, 1% to < 50%: HR, 0.55 [95% CI, 0.37-0.82]) groups. Progression-free survival improved with increasing PD-L1 expression for both assays. SP142 and 22C3 assays identified overlapping and unique patient populations in PD-L1-high, positive, and negative subgroups. Overall survival and progression-free survival benefits favored atezolizumab over docetaxel in double PD-L1-positive and negative groups; patients with both SP142- and 22C3-positive tumors derived the greatest benefit., Conclusions: Despite different scoring algorithms and differing sensitivity levels, the SP142 and 22C3 assays similarly predicted atezolizumab benefit at validated PD-L1 thresholds in patients with non-small cell lung cancer., Competing Interests: Disclosure Dr. Gadgeel reports personal fees from Genentech/Roche, AstraZeneca, Merck, Bristol Myers Squibb, Novartis, Daichii-Sanyko, Boehringer-Ingelheim, Xcovery, Jazz Pharmaceuticals, Pfizer, and Janssen, outside the submitted work. Dr. Hirsch reports scientific advisory board for Genentech/Roche, Merck, Bristol Myers Squibb, Novartis, AstraZeneca/Daiichi, Regeneron/Sanofi, and Amgen, outside the submitted work. Dr. Kerr reports personal fees from AbbVie, Amgen, AstraZeneca, Archer Diagnostics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Debiopharm, Diaceutics, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, and Roche Diagnostics/Ventana, outside the submitted work. Dr. Barlesi reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda, outside the submitted work. Dr. Park has nothing to disclose. Dr. Rittmeyer reports grants from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Pfizer, Roche, and Novartis, outside the submitted work. Dr. Zou reports employment from Genentech, outside the submitted work. Dr. Bhatia reports employment from Genentech, outside the submitted work. Dr. Koeppen reports employment from Genentech, outside the submitted work. Dr. Paul reports employment from Genentech, outside the submitted work. David Shames reports employment from Genentech and stock ownership from Roche, outside the submitted work. Dr. Yi reports employment and spousal employment from Genentech and stock ownership from Roche, outside the submitted work. Dr. Matheny reports employment from Genentech, during the conduct of the study, and employment from Genentech, outside the submitted work. Dr. Ballinger reports employment from Genentech and stock ownership from Roche, outside the submitted work. Dr. McCleland reports employment from Genentech, outside the submitted work. Dr. Gandara reports personal fees and institutional grants from Genentech, outside the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Tobacco smoking is associated with severe health risks. In 2020, the WHO estimated that 8 million people have died due to smoking. Furthermore, smoking tobacco is a well-known risk factor for various infectious pulmonary diseases. The question raised, whether smoking is facilitating SARS-CoV-2-infections and increases adverse outcomes of COVID-19. To answer these questions a narrative review was conducted, finally including 7 systematic reviews with meta-analyses published in January and February 2021. Tobacco smoking was associated with an increased COVID-19 disease severity (odds ratio range of active vs. never smokers 1.55-2.19 and former vs. never smokers 1.20-2.48) and an increased COVID-19 in-hospital mortality (odds ratio range of active vs. never smokers 1.35-1.51 and former vs. never smokers 1.26-2.58). Beside immediate pulmonary toxic effects through active smoking, the cumulative livelong tobacco exposition and subsequent tobacco-associated diseases seem to predominantly predict adverse outcomes in patients with COVID-19. Data regarding an increased risk of infection among smokers is conflicting. However, a large observational study from England with 2.4 million persons reported an association between tobacco smoking and typical symptoms of COVID-19. For e-cigarettes and vaping less data exist, but experimental and first clinical investigations also suggest an increased risk for adverse outcomes for their use and SARS-CoV-2 infections. Especially during the current SARS-CoV-2 pandemic with limited therapeutic options it is particularly important to advise smokers of their increased risks for unfavourable COVID-19 outcomes. Evidence based support for smoking cessation should be offered. In Germany, the existing and well-established methods to support tobacco cessation need to be reimbursed by statutory health insurances., Competing Interests: R. Bals erhielt Forschungsunterstützung durch das BMBF, Wilhelm Sander Stiftung, Deutsche Krebshilfe, Mukoviszidose e. V., Schwiete Stiftung sowie Zuwendungen für Advisory Boards oder Vorträge von AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, CSL Behring.W. Pankow hatte Einkünfte aus Beratungstätigkeit für Pfizer Deutschland GmbH.C. Rustler: Geschäftsführung im Deutschen Netz Rauchfreier Krankenhäuser & Gesundheitseinrichtungen, Zuwendungen zur Implementierung des „rauchfrei tickets“ zur Vermittlung in die Rauchstoppberatung am Telefon der BZgA, Mitgliedschaft im Wissenschaftlichen Aktionskreis Tabakentwöhnung WAT e. V., Mitautorin der S3-Leitlinie „Rauchen und Tabakabhängigkeit: Screening, Diagnostik und Behandlung“ (2021).Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: As incidence rates for lung cancer are still very high and lung cancer remains the most deadly cancer since the turn of the millennium, efforts have been made to find new approaches in cancer research. This systematic review highlights how therapeutic options were extended and how the development of new drugs has picked up speed during the last 20 years., Methods: A systematic search was performed in PubMed, Cochrane Library and the European Union Trial Register and 443 records were identified. Our inclusion criteria constituted completed phase I, II and III studies investigating drugs approved by the European Medicines Agency (EMA). Overall, 127 articles were analysed., Results: During the 5 year interval from 2015 to 2020, significantly more drugs were approved after phase III, and occasionally after phase II, trials than between 2000 and 2005 (p=0.002). Furthermore, there was a significant time difference (p=0.00001) indicating an increasingly briefer time interval between the publication of phase I and phase III results in the last few years., Discussion: Due to novel therapeutic approaches, numerous new drugs in lung oncology were approved. This has improved symptoms and prognoses in patients with advanced lung cancer. However, faster approval could make it difficult to scrutinise new options regarding safety and efficacy with sufficient diligence., Competing Interests: Conflict of interest: A. Rittmeyer reports grants from EliLilly, BMS, Boehringer Ingelheim, AstraZeneca, MSD, Pfizer, AbbVie, Novartis and Roche, outside the submitted work. Conflict of interest: A. Schiwitza has nothing to disclose. Conflict of interest: L. Sahovic has nothing to disclose. Conflict of interest: B. Eul has nothing to disclose. Conflict of interest: S. Andreas reports grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, AstraZeneca, GSK, Chiesi and Merini, and grants from Pfizer, outside the submitted work., (Copyright ©ERS 2021.)

Background: Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations. However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI., Methods: Retrospective data were collected during routine care from German thoracic oncology centers. Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint., Results: Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis., Conclusions: D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS and will require further investigations., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-197). Albrecht Stenzinger serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. The following authors received honoraria for lectures, presentation, speakers bureaus, manuscript writing or educational events: WMB from AstraZeneca, Boehringer, Novartis, MSD, BMS, Roche and Lilly; MR from Amgen, AstraZeneca, BMS, Boehringer, Lilly, Minde, Merck, MSD, Novartis, Pfizer and Roche; AR from AbbVIe, AstraZeneca, BMS, Boehringer, Lilly, MSD, Novartis, Pfizer and Roche; CW from Boehringer, Lilly, MSD, Roche, AstraZeneca, BMS, Sanofi Aventis and Takeda; GHW from Boehringer, Lilly, MSD, Roche, AstraZeneca, BMS, Sanofi Aventis, Takeda, Glaxo and Berlin Chemie; PC from Roche, Takeda, AstraZeneca and Novartis; AS from Aignostics, Bayer, Thermo Fisher, Illumina, AstraZeneca, Novartis, Pfizer, Roche, Seattle Genetics, MSD, BMS, Takeda and Lilly; AT from GSK, Novartis, Amgen, BMS, MSD, Lilly, Pfizer, Boehringer, Roche, Takeda and Celgene; JHF from AstraZeneca, Boehringer, Novartis, MSD, BMS and Roche. The following authors received support for attending meetings and/or travel: WMB from Boehringer, AstraZeneca and Roche; CW from Boehringer, MSD, Roche, AstraZeneca and BMS; GW from Boehringer, MSD, Roche, AstraZeneca and Berlin Chemie; PC from AstraZeneca, Takeda, Novartis and Lilly; AT from GSK, Novartis, Amgen, MSD, BMS, Lilly, Pfizer, Boehringer, Roche, Takeda and Celgene; JHF from Boehringer and AstraZeneca. The following authors participated on a data safety monitoring board or an advisory board: WMB on AstraZeneca, Boehringer, Novartis, MSD, Lilly, BMS and Roche; JK on Roche, Boehringer, BMS, Merck, Amgen, Takeda and Lilly (all outside the submitted work and all without receiving any personal fees; CW on Boehringer, MSD, Roche, AstraZeneca and MBS; GHW on Boehringer, MSD, Roche, AstraZeneca and BMS; PC on Pfizer, Chugai, Boehringer and Roche; AT on GSK, Novartis, Amgen, MSD, BMS, Lilly, Pfizer, Boehringer, Roche, Takeda, Celgene and AIO Leadership Group; PH on Lilly, MSD, BMS, AstraZeneca, Takeda, Roche, Boehringer and Pfizer; JHF on AstraZenca. The following authors receipt equipment, materials, drugs, medical writing, gifts or other services: WMB from Boehringer (for medical writing); JHF from Novartis (for medical writing); the following authors received consulting fees: AR from AbbVie, AstraZeneca, BMS, Boehringer, Lilly, MSD, Novartis, Pfizer and Roche. The following authors received grants or contracts form any entity: PC from Roche, Takeda, AstraZeneca and Novartis (all research grants to the institution; AT from AstraZeneca (research grant). The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown., Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021., Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n  = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death., Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated., Competing Interests: Conflict of interest statement: Oliver Illini, Received speaker fees and/or honoraria for advisory boards from Boehringer Ingelheim, Eli Lilly, Menarini, Merck Sharp & Dohme, Pfizer, and Roche. Maximilian Johannes Hochmair, Honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, and Roche, and has had consulting or advisory roles with Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, and Roche. Hannah Fabikan, Speaker fee from Roche. Christoph Weinlinger, No conflict of interest. Amanda Tufman, Advisory Boards: Lilly, Pfizer, MSD, BMS, GSK, Celgene, Roche, Takeda, Boehringer Ingelheim, Amgen, AstraZeneca. Projects financed by AstraZeneca und Takeda. Aurélie Swalduz, Roche, Bristol-Myers Squibb, Takeda, Lilly, Pfizer, AstraZeneca, Boehringer-Ingelheim. Kristina Lamberg, Advisory boards: MSD and AstraZeneca. Sayed M.S. Hashemi, Advisory board/research grants: Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, GSK, MSD, Novartis, Roche, Takeda, Xcovery. Florian Huemer, Advisory Boards and Honoraria: MSD, BMS, Roche, Sanofi, Lilly, Takeda, Astra Zeneca, Boehringer Ingelheim. Anders Vikström, Ad-boards: AstraZeneca, Abbvie, BMS, Boehringer-Ingelheim, Pfizer, Roche, Takeda. Lectures: AstraZeneca, BMS, Boehringer-Ingelheim, MSD, Roche, Takeda. Grants: Boehringer-Ingelheim Consultancies: Astra Zeneca, Boehringer-Ingelheim, Roche. Martin Wermke, Received speaker fees and/or honoraria for advisory boards from BMS, Merck, Roche, Novartis, Kite, Boehringer Ingelheim, Astra Zeneca, Heidelberg Pharma. Gudrun Absenger, Honoraria from: AMGEN, AstraZeneca, BMS, Böhringer Ingelheim, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda. Alfredo Addeo, Personal fees from Bristol-Myers Squibb, AstraZeneca, Roche, Pfizer, Merck Sharp and Dohme, and Boehringer-Ingelheim for work performed outside of the current study. Shantanu Banerji, Honoraria for advisory board: AstraZeneca, Bayer, BMS, EMD-Serono, Merck, Novartis, Pfizer, Roche, Takeda Speaker Fees: None Research Funds: AstraZeneca. Antonio Calles, Honoraria/consulting fees from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche/Genentech, Eli Lilly and Company, Takeda, Novartis, Merck Sharp & Dohme, and Bristol-Myers Squibb; Research grants from MSD and PharmaMar. Stephen Clarke, Advisory board and speaking remuneration from AstraZeneca. Massimo Di Maio, Honoraria and had roles as consultant or advisor for AstraZeneca, Pfizer, Novartis, Roche, Takeda, Eisai, Janssen, Astellas; received institutional research grant by Tesaro – GlaxoSmithKline. Alice Durand, No conflict of interest. Michaël Duruisseaux, Membership of an advisory council or committee for Roche, BMS, MSD, AstraZeneca, Abbvie, Takeda, Boehringer Ingelheim, Merus, Amgen and Pfizer; consulting fees from Roche, BMS, MSD, AstraZeneca, Abbvie, Takeda, Boehringer Ingelheim, and Pfizer; research grants from Takeda, NanoString, and Blueprint. Malinda Itchins, AdBoard: Pfizer, Takeda. Consultancy: Roche, Merck. Honoraria: AZ, Pfizer, takeda, Roche, Novartis. Academic travel support: Roche, MSD. Okko-Sakari Kääränien, No conflict of interest associated with this study. Florian Krenn, Advisory Boards: Roche, MSD. Eckart Laack, Honoraria for advisory boards: AstraZeneca, BMS, Boehringer-Ingelheim, Pfizer, Roche, Takeda, MSD, Novartis, Lilly. Speaker fees. AstraZeneca, BMS, Boehringer-Ingelheim, Pfizer, Roche, Takeda, MSD, Novartis, Lilly. Research grants and clinical study: AstraZeneca, BMS, Boehringer-Ingelheim, Pfizer, Roche, Takeda, MSD, Novartis, Lilly. Adrianus Johannes de Langen, Research grants: BMS, MSD, AstraZeneca, Boehringer, Merus Non-financial support: Merck, Roche Advisory boards: Lilly, Bayer, MSD, AstraZeneca. Katja Mohorcic, Honoraria for ad-boards and speaker from MSD, Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, BMS, Abbvie. Georg Pall, Speakers honoraria and advisory board-member: Eli Lilly, Roche. Antonio Passaro, Honoraria for consulting, advisory role or lectures from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer and Roche Genentech. Gerald Prager, Advisory Board Meetings/Symposiums: Merck, Roche, Amgen, Sanofi, Lilly, Servier, Taiho, Bayer, BMS, MSD, Celgene, Pierre Fabre, Terumo. Achim Rittmeyer, Grants as an advisor or speaker: AbbVie, Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer and Roche. Jeffrey Rothenstein, Advisory Boards: Amgen, AZ, BMS, Merck, Pfizer, Roche. Michael Schumacher, Consulting, speakers fee, advisory panel membership, travel grants: AstraZeneca, Pfizer, Boehringer Ingelheim, Takeda, Roche, Amgen, Eli Lilly, MSD, BMS, Novartis. Ewald Wöll, Advisory boards or speaker fees: Amgen, Astra Zeneca, BMS, Celgen, Ebewe, Eli Lilly, Eisai, Janssen Cilag, Merck, MSD, Pierre Fabre, Pfizer, Ratiopharm, Roche, Sanofi Aventis. Arschang Valipour, Personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini, Merck, Novartis, and Roche for lectures and/or advisory boards outside of the submitted study., (© The Author(s), 2021.)

In hospital, effective smoking cessation can be organized through counselling, pharmacological aids and, above all, continuous care in outpatient structures following discharge. Pharmacological treatment has proven to be effective and safe with nicotine replacement therapy as well as varenicline. Counselling plus pharmacotherapy is more effective in combination than either therapy is on its own. To better implement structures medical societies in Germany are seeking adequate funding e. g. in the DRG system for hospitalised patients.There are obvious and relevant benefits in smoking cessation. Not only for the main tobacco-related diseases such as coronary heart disease or chronic obstructive pulmonary disease (COPD), positive effects of quitting on morbidity and mortality have been confirmed by high-quality meta-analyses. Furthermore, quality of life is increasing following cessation. Presently, smoking is found to be a significant risk factor for severe disease and mortality following coronavirus infection.Do e-cigarettes offer an alternative in smoking cessation? No. Animal and human data are suggesting toxic effects especially following longer use. The long-term effectiveness of e-cigarettes in tobacco cessation is still uncertain and epidemiologic data clearly point toward ineffectiveness. Furthermore, dual use with potentiation of the toxic effects is common. Therefore, e-cigarettes cannot be recommended for tobacco cessation., Competing Interests: W. Pankow: Beratungshonorar von Pfizer., (Thieme. All rights reserved.)

Background: Treatment-induced accelerated tumor growth is a progression pattern reported with immune checkpoint inhibitors that has never been evaluated in randomized phase III studies because it requires two pretreatment scans. This study aimed to develop clinically relevant and applicable criteria for fast progression (FP), incorporating tumor growth kinetics and early death from disease progression to analyze data from the randomized phase III OAK study., Methods: The OAK study evaluated the efficacy and safety of atezolizumab versus docetaxel as second-line or third-line treatment for stage IIIb/IV non-small cell lung cancer. FP rates and associated baseline factors were analyzed. FP was defined as either a ≥50% increase in the sum of largest diameters (SLDs) within 6 weeks of treatment initiation or death due to cancer progression within 12 weeks (absent post-baseline scan)., Results: Forty-two of 421 patients (10%) receiving atezolizumab and 37 of 402 (9%) receiving docetaxel had FP. Twenty patients with FP (48%) receiving atezolizumab versus 12 (30%) receiving docetaxel had a ≥50% SLD increase within 6 weeks. FP was significantly associated with an ECOG (Eastern Cooperative Oncology Group) performance status of 1 (vs 0), ≥3 metastatic sites at baseline, and failure of preceding first-line treatment within 6 months, but not with epidermal growth factor receptor mutation, programmed cell death 1 ligand 1 or tumor mutational burden. Overall survival in patients with FP and a ≥50% SLD increase at week 6 was similar with atezolizumab and docetaxel (unstratified HR 0.89 (95% CI 0.41 to 1.92))., Conclusions: FP rates were similar with atezolizumab and docetaxel in the OAK study, suggesting that FP may not be unique to checkpoint inhibitors, although the underlying mechanisms may differ from those of chemotherapy. Applying the FP criteria to other phase III checkpoint inhibitor trials may further elucidate the risk factors for FP., Trial Registration Number: NCT02008227., Competing Interests: Competing interests: Editorial support, funded by the sponsor, was provided by an independent medical writer under the guidance of the authors. DG reports research grants from Amgen, Merck, and Roche/Genentech; personal fees for consulting or advisory roles for Inivata, Lilly, Merck, Roche/Genentech, and Samsung Bioepis; and institutional grants with no personal income for CellMax, Guardant Health, IO Biotech, and Oncocyte. MR reports grants and non-financial support from F. Hoffmann-La Roche during the conduct of the study and personal fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Lilly, Merck, Merck Sharpe and Dohme, Novartis, Pfizer, and Roche outside the submitted work. SP reports personal fees for speaking or attending advisory boards, and has participated in investigation in trials for Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, and Pfizer; and personal fees for speaking or attending advisory boards for AbbVie, Bayer, Biocartis, Bioinvent, Daiichi Sankyo, Debiopharm, Eli Lilly, Foundation Medicine, Janssen, Merrimack, Pharma Mar, Regeneron, Sanofi, Seattle Genetics, and Takeda. DM-S reports grants, personal fees, and non-financial support from Roche/Genentech related to the current work, and from AbbVie, AstraZeneca, Boehringer, Bristol-Myers Squibb, and Pfizer; personal fees and non-financial support from Merck Sharp and Dohme; and personal fees from Novartis and Takeda. JM reports grants, personal fees, and non-financial support from Roche/Genentech related to the current work, and from Bristol-Myers-Squibb; grants or personal fees for participation in advisory boards or speaking for Amgen, AstraZeneca, Lilly/ImClone, Merck Sharp and Dohme, Novartis, and Pierre Fabre; and personal fees and non-financial support for participation in advisory boards or speaking for Pfizer. SMG reports personal fees from Genentech/Roche related to the current work, and from AstraZeneca, Takeda, Boehringer-Ingelheim, Bristol-Myers Squibb, Novocure, Xcovery, and AbbVie. SM is an employee of and has ownership interest in F. Hoffmann-La Roche. AC is an employee of F. Hoffmann-La Roche. DM is an employee of Genentech, Inc. MB is an employee of Genentech, Inc. AR reports personal fees from Roche/Genentech related to this work, and from Lilly, Bristol-Myers Squibb, Boehringer-Ingelheim, AstraZeneca, Merck Sharpe and Dohme, Pfizer, AbbVie, and Novartis., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the "real-world" setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany., Patients and Methods: This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1., Results: In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4-10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9-9.2) with druggable ALK alterations., Conclusion: Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The German Respiratory Society (DGP) turns against the e-cigarette as a means for harm reduction because of potential health risk and dangers to young people. The aerosol of e-cigarettes contains toxic ingredients that have been shown to be damaging to the lungs, the cardiovascular system and the immune system and are potentially carcinogenic. Studies on e-cigarettes as a means of smoking cessation are not very convincing, in order to favor e-cigarettes over nicotine replacement therapy, which have been tried and tested for many years, or other drugs that reduce the desire to smoke., Competing Interests: W. Pankow: Beratungshonorar von Pfizer. A. Rupp: Vortragshonorar von Pfizer.S. Andreas und M. Pfeifer geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Introduction: The phase 2 POPLAR and phase 3 OAK studies of the anti-programmed death-ligand 1 (PD-L1) immunotherapy atezolizumab in patients with previously treated advanced NSCLC revealed significant improvements in survival versus docetaxel (p = 0.04 and 0.0003, respectively). Longer follow-up permits evaluation of continued benefit of atezolizumab. This study reports the final overall survival (OS) and safety findings from both trials., Methods: POPLAR randomized 287 patients (atezolizumab, 144; docetaxel, 143) and OAK randomized 1225 patients (atezolizumab, 613; docetaxel, 612). The patients received atezolizumab (1200 mg fixed dose) or docetaxel (75 mg/m 2 ) every 3 weeks. Efficacy and safety outcomes were evaluated., Results: A longer OS was observed in patients receiving atezolizumab versus docetaxel in POPLAR (median OS = 12.6 mo versus 9.7 mo; hazard ratio = 0.76, 95% confidence interval [CI]: 0.58-1.00) and OAK (median OS = 13.3 versus 9.8 mo; hazard ratio = 0.78, 95% CI: 0.68-0.89). The 4-year OS rates in POPLAR were 14.8% (8.7-20.8) and 8.1% (3.2-13.0) and those in OAK were 15.5% (12.4-18.7) and 8.7% (6.2-11.3) for atezolizumab and docetaxel, respectively. Atezolizumab had improved OS benefit compared with docetaxel across all PD-L1 expression and histology groups. Most 4-year survivors in the docetaxel arms received subsequent immunotherapy (POPLAR, 50%; OAK, 65%). Of the 4-year survivors, most had Eastern Cooperative Oncology Group performance status of 0 and nonsquamous histological classification and approximately half were responders (POPLAR: atezolizumab, seven of 15; docetaxel, three of four; OAK: atezolizumab, 24 of 43; docetaxel, 11 of 26). Treatment-related grade 3/4 adverse events occurred in 27% and 16% of atezolizumab 4-year survivors in POPLAR and OAK, respectively., Conclusions: Long-term follow-up suggests a consistent survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC regardless of PD-L1 expression, histology, or subsequent immunotherapy. Atezolizumab had no new safety signals, and the safety profile was similar to that in previous studies., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer: 20-002., (Thieme. All rights reserved.)

Background: Current treatment options for stage III non-small cell lung cancer (NSCLC) consist of different combinations of chemotherapy, surgery, radiotherapy and immunotherapy. Treatment choices are highly individual decisions, in which adverse events (AEs) are relevant for decision-making. This study aims to analyse reporting of AEs in prospective stage III NSCLC trials, focussing on trials including radiotherapy and/or surgery., Methods: PubMed was searched for prospective studies dealing with stage III NSCLC from January 1987 to April 2019. Meta-analyses were screened as a positive control. Pearson's Chi-squared test and smooth kernel distribution were used to estimate distributions. Data was resampled using bootstrapping., Results: Out of 1193 initially identified studies, 119 met the inclusion criteria. Of these, 31 had a surgical procedure in any study arm. Grade 3 and 4 AEs were reported in 94.12% and 92.44% of the included studies, respectively. Reporting of grade 5 AEs was provided in 87.39% of cases. Grade 1 and 2 AEs were less commonly reported at 53.78% and 63.03%, respectively. One study did not mention any AEs. Of the 31 treatment arms including any form of surgery, AEs were not reported in 10. Overall, 231 different AE items were reported, only 18 of them were included in at least 20% of the analysed studies., Conclusion: Overall, AE reporting in stage III NSCLC was inconsistent and inhomogeneous. Studies including surgical study arms often reported only treatment-related deaths in regards of surgical AEs. Underreporting of AEs prohibits the extraction of patient-relevant information for decision-making and represents a suboptimal use of invested resources., Competing Interests: Conflict of interest: I. Iseli has nothing to disclose. Conflict of interest: T. Berghmans has nothing to disclose. Conflict of interest: M. Glatzer has nothing to disclose. Conflict of interest: A. Rittmeyer reports grants from AbbVie, AstraZeneca, BMS, Eli Lilly, Boehringer Ingelheim, MSD, Pfizer and Roche, outside the submitted work. Conflict of interest: G. Massard has nothing to disclose. Conflict of interest: V. Durieux has nothing to disclose. Conflict of interest: T. Buchsbaum has nothing to disclose. Conflict of interest: P.M. Putora has nothing to disclose., (Copyright ©ERS 2020.)

Introduction: In recent years, the number of patients requiring mechanical ventilation has increased steadily. In some cases, weaning is not successful. These patients depend on home mechanical ventilation and intensive outpatient care. Surprisingly, most of these patients were never treated in a weaning center. Thus, weaning might still be possible in at least some of them. Health insurance companies have recognized this problem., Methods: AOK Hessen, a major health insurance company in the German federal state of Hesse, identified some starting points for improvement after having surveyed their patients in ambulant intensive care. Principal points for future measures are expertise of the treating medical center (weaning experience, weaning center), establishment of new centers for homecare ventilation for long term therapy of these patients and a coordinated follow up., Results: Centers for homecare ventilation are wards with a non-hospital atmosphere affiliated to a weaning center. The main focus here is not weaning itself but daily physical and speech therapy. Patients in home care ventilation centers have time (up to 6 months) to improve their physical and mental strength. Afterwards, depending to their development, they can be transferred to the weaning center again., Discussion: In this paper, we introduce the concept of the home care ventilation centers. Initial data suggests that home care ventilation centers can contribute to successful weaning., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV., Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated., Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred., Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first-line treatment., Competing Interests: Declaration of Conflicting Interest:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.M.B. and J.H.F. have received honoraria for consulting from Astra Zeneca, BMS, Boehringer Ingelheim, Celgene, Lilly, MSD, Pfizer, and Roche Pharma. P.C. reports consulting honoraria from Astra Zeneca, Boehringer Ingelheim, Chugai, Lilly, Novartis, Pfizer, Roche, and Takeda. P.H. has received honoraria for consulting from Boehringer Ingelheim, Pfizer, Takeda, Roche Pharma, Lilly, BMS, MSD, AstraZeneca, and Abbvie. F.R. has received honoraria for consulting from Astra Zeneca, Chugai Pharma, and Roche Pharma. C.W. and G.H.W. have received honoraria for consulting from Astra Zeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Pfizer, and Roche Pharma. The other authors reported no conflict of interest., (© The Author(s) 2020.)

Objective: There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions., Methods: We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy., Results: Among the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity ( D LCO ) were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and D LCO was slow and did not differ significantly between patients with or without antifibrotic therapy., Conclusions: Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and D LCO ., Competing Interests: Conflict of interest: J. Behr reports grants and personal fees from Boehriger Ingelheim, personal fees from Actelion, Roche, Galapagos, Promedior, BMS and MSD, during the conduct of the study. Conflict of interest: A. Prasse reports grants and personal fees from Roche/InterMune and Boehringer Ingelheim, outside the submitted work. Conflict of interest: H. Wirtz reports personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: D. Koschel has nothing to disclose. Conflict of interest: D. Pittrow reports personal fees from Actelion, Bayer, Boehringer Ingelheim, Sanofi, Biogen, Shield and MSD, outside the submitted work. Conflict of interest: M. Held has nothing to disclose. Conflict of interest: J. Klotsche has nothing to disclose. Conflict of interest: S. Andreas reports grants and personal fees from Boehringer Ingelheim, personal fees from Roche, outside the submitted work. Conflict of interest: M. Claussen reports personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: C. Grohé has nothing to disclose. Conflict of interest: H. Wilkens reports personal fees from Boehringer Ingelheim, Roche, Actelion, Biotest, GSK, Pfizer and Bayer, outside the submitted work. Conflict of interest: L. Hagmeyer has nothing to disclose. Conflict of interest: D. Skowasch reports personal fees from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: J.F. Meyer reports personal fees for lectures from Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: J. Kirschner has nothing to disclose. Conflict of interest: S. Gläser reports grants and personal fees from Boehringer Ingelheim and Novartis, personal fees from Roche, Actelion, Berlin Chemie and Astra, outside the submitted work. Conflict of interest: N. Kahn has nothing to disclose. Conflict of interest: T. Welte reports grants and personal fees from Boehringer Ingelheim, grants from Roche, outside the submitted work. Conflict of interest: C. Neurohr reports personal fees from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: M. Schwaiblmair has nothing to disclose. Conflict of interest: T. Bahmer reports grants from German Center of Lung Research (DZL), personal fees from Roche, AstraZeneca, Chiesi, GSK and Novartis, outside the submitted work. Conflict of interest: T. Oqueka has nothing to disclose. Conflict of interest: M. Frankenberger has nothing to disclose. Conflict of interest: M. Kreuter reports grants and personal fees from Roche/InterMune and Boehringer Ingelheim, outside the submitted work., (Copyright ©ERS 2020.)

Background: MET amplifications occur in human tumors, including non-small cell lung cancer (NSCLC). MET inhibitors have demonstrated some clinical activity in MET amplified NSCLC, presumably with a gene dose effect. However, the definition of MET positivity or MET amplification as a potential oncogenic driver is still under debate. In this study, we aimed to establish the molecular subgroup of NSCLC with the highest unequivocal MET amplification level and to describe the prevalence, and histologic and clinical phenotype of this subgroup., Methods: A total of 373 unselected patients with NSCLC were consecutively tested for MET gene copy number (GCN) by FISH. Mean GCN, MET /CEN7 ratio and other FISH parameters were identified and correlated with morphological and molecular pathological characteristics of the tumors as well as with clinical data., Results: Based on the variability of obtained data a top-level category of MET amplification was newly defined (>90th percentile of average GCN; ≥10 MET gene copies per tumor cell). This criterion was fulfilled in 2% of analyzed tumors. These tumors were exclusively poorly differentiated adenocarcinomas with a predominant solid subtype and pleomorphic features. Rarely, co-alterations were detected ( KRAS mutation or MET exon 14 skipping mutation). In this top-level group, there were no EGFR mutations or ALK or ROS1 alterations. The most important clinical feature was a significantly shortened overall survival (HR 3.61; median OS 8.2 vs. 23.6 months). Worse prognosis did not depend on initial stage or treatment., Conclusions: The newly defined top-level category of MET amplification in NSCLC defines a specific subgroup of pulmonary adenocarcinoma with adverse prognosis and characteristic morphological features. Lower levels of MET gene copy number seem to have probably no specific value as a prognostic or predictive biomarker., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-19-339). TRO reports personal fees from AstraZeneca, personal fees from BMS, personal fees from Boehringer-Ingelheim, personal fees from Eli Lilly, personal fees from Medac, personal fees from MSD, personal fees from Novartis, personal fees from Roche/Genentec, personal fees from Sanofi-Aventis, outside the submitted work. KS reports personal fees from MSD Germany, personal fees and non-financial support from Roche Austria, personal fees and non-financial support from Novartis Austria, outside the submitted work. AR reports grants from AbbVie, grants from AstraZeneca, grants from BMS, grants from Boehringer Ingelheim, grants from Eli Lilly, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, outside the submitted work. HUS reports grants and personal fees from Novartis Oncology, personal fees from MSD, personal fees from BMS, personal fees from Pfizer, personal fees from ZytoVision, personal fees from Roche, from Abbvie, personal fees from Zytomed Systems, outside the submitted work. The other authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

High resting heart rate (RHR) is associated with higher mortality in the general population and in cardiovascular disease. Less is known about the association of RHR with outcome in chronic obstructive pulmonary disease (COPD). In particular, the time-updated RHR (most recent value before the event) appears informative. This is the first study to investigate the association of time-updated RHR with mortality in COPD. We compared the baseline and time-updated RHR related to survival in 2218 COPD patients of the German COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network). Patients with a baseline RHR > 72 beats per minute (bmp) had a significantly (p = 0.049) higher all-cause mortality risk (adjusted hazard ratio (HR) of 1.37 (1.00-1.87) compared to baseline RHR ≤ 72 bpm. The time-updated RHR > 72 bpm was markedly superior (HR 1.79, 1.30-2.46, p = 0.001). Both, increased baseline and time-updated RHR, were independently associated with low FEV1, low TLCO, a history of diabetes, and medication with short-acting beta agonists (SABAs). In conclusion, increased time-updated RHR is associated with higher mortality in COPD independent of other predictors and superior to baseline RHR. Increased RHR is linked to lung function, comorbidities and medication. Whether RHR is an effective treatment target in COPD, needs to be proven in controlled trials.

The abscopal effect describes the ability of locally administered radiotherapy to induce systemic antitumor effects. Over the past 40 years, reports on the abscopal effect following conventional radiation have been relatively rare, especially in less immunogenic tumors such as lung cancer. However, with the continued development and use of immunotherapy, reports on the abscopal effect have become increasingly frequent during the last decade. Here, we present three illustrative case reports from our own institution and previous published cases of the abscopal effect in patients with non-small cell lung cancer, treated with immune checkpoint inhibitors and radiotherapy. We also present a concise review of the clinical and experimental literature on the abscopal effect in non-small cell lung cancer.

Background: Atezolizumab (a monoclonal antibody against PD-L1), which restores anticancer immunity, improved overall survival in patients with previously treated non-small-cell lung cancer and also showed clinical benefit when combined with chemotherapy as first-line treatment of non-small-cell lung cancer. IMpower130 aimed to assess the efficacy and safety of atezolizumab plus chemotherapy versus chemotherapy alone as first-line therapy for non-squamous non-small-cell lung cancer., Methods: IMpower130 was a multicentre, randomised, open-label, phase 3 study done in 131 centres across eight countries (the USA, Canada, Belgium, France, Germany, Italy, Spain, and Israel). Eligible patients were aged 18 years or older, and had histologically or cytologically confirmed stage IV non-squamous non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and received no previous chemotherapy for stage IV disease. Patients were randomly assigned (2:1; permuted block [block size of six] with an interactive voice or web response system) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin [area under the curve 6 mg/mL per min every 3 weeks] plus nab-paclitaxel [100 mg/m 2 intravenously every week]) or chemotherapy alone for four or six 21-day cycles followed by maintenance therapy. Stratification factors were sex, baseline liver metastases, and PD-L1 tumour expression. Co-primary endpoints were investigator-assessed progression-free survival and overall survival in the intention-to-treat wild-type (ie, EGFR wt and ALK wt ) population. The safety population included patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02367781., Findings: Between April 16, 2015, and Feb 13, 2017, 724 patients were randomly assigned and 723 were included in the intention-to-treat population (one patient died before randomisation, but was assigned to a treatment group; this patient was excluded from the intention-to-treat population) of the atezolizumab plus chemotherapy group (483 patients in the intention-to-treat population and 451 patients in the intention-to-treat wild-type population) or the chemotherapy group (240 patients in the intention-to-treat population and 228 patients in the intention-to-treat wild-type population). Median follow-up in the intention-to-treat wild-type population was similar between groups (18·5 months [IQR 15·2-23·6] in the atezolizumab plus chemotherapy group and 19·2 months [15·4-23·0] in the chemotherapy group). In the intention-to-treat wild-type population, there were significant improvements in median overall survival (18·6 months [95% CI 16·0-21·2] in the atezolizumab plus chemotherapy group and 13·9 months [12·0-18·7] in the chemotherapy group; stratified hazard ratio [HR] 0·79 [95% CI 0·64-0·98]; p=0·033) and median progression-free survival (7·0 months [95% CI 6·2-7·3] in the atezolizumab plus chemotherapy group and 5·5 months [4·4-5·9] in the chemotherapy group; stratified HR 0·64 [95% CI 0·54-0·77]; p<0·0001]). The most common grade 3 or worse treatment-related adverse events were neutropenia (152 [32%] of 473 in the atezolizumab plus chemotherapy group vs 65 [28%] of 232 in the chemotherapy group), anaemia (138 [29%] vs 47 [20%]), and decreased neutrophil count (57 [12%] vs 19 [8%]). Treatment-related serious adverse events were reported in 112 (24%) of 473 patients in the atezolizumab plus chemotherapy group and 30 (13%) of 232 patients in the chemotherapy group. Treatment-related (any treatment) deaths occurred in eight (2%) of 473 patients in the atezolizumab plus chemotherapy group and one (<1%) of 232 patients in the chemotherapy group., Interpretation: IMpower130 showed a significant and clinically meaningful improvement in overall survival and a significant improvement in progression-free survival with atezolizumab plus chemotherapy versus chemotherapy as first-line treatment of patients with stage IV non-squamous non-small-cell lung cancer and no ALK or EGFR mutations. No new safety signals were identified. This study supports the benefit of atezolizumab, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer., Funding: F. Hoffmann-La Roche., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: Radiological criteria alone do not reflect the entire population benefitting from checkpoint inhibitor therapy (CIT). This study aimed to detect patterns to assess CIT efficacy in non-small-cell lung cancer (NSCLC) patients. Materials & methods: We evaluated clinical, radiological and laboratory parameters in a retrospective cohort of NSCLC patients treated with nivolumab. Results:  A total of 51 patients were included in the analysis. Most single parameters failed to reflect treatment benefit. Three laboratory parameters (lactate dehydrogenase, C-reactive protein and the neutrophil/lymphocyte ratio) combined in a weighted score could predict benefit with a sensitivity of 92.3% and a hazard ratio of 0.31 (95% CI: 0.16-0.59) in an early phase of therapy. Sorting patients by score showed a 1-year survival of 36% in those predicted as not benefitting versus 68% in those predicted to benefit. Conclusion: A weighted score integrating common serum markers could help detect patients benefitting from checkpoint inhibitors during ongoing CIT.

The aim of the present study was to assess the expression of epithelial-mesenchymal transition biomarkers (E-cadherin and vimentin) and their potential significance as prognostic markers in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC) enrolled in the INNOVATIONS trial, receiving treatment with either erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB). The tumor tissues of 104 patients were retrospectively analyzed using immunohistochemistry to assess the expression of E-cadherin and vimentin. The distribution between the treatment arms was 46 patients in the EB-arm and 58 in the PGB-arm. Comparing the treatment arms according to E-cadherin and vimentin expression, the analysis revealed that progression-free survival (PFS) was increased in the PGB treatment group when compared with EB treatment in patients with low expression of E-cadherin [hazard ratio (HR)=0.353; 95% confidence interval (CI) 0.189- 0.658; log-rank P=0.0007] and in those with high expression of vimentin [HR=0.276 (95% CI, 0.115- 0.659), log-rank P=0.0021]. In patients that exhibited high E-cadherin and were negative for vimentin, there was no difference in the PFS between the PGB and EB treatment groups. In conclusion, in non-squamous NSCLC with downregulated E-cadherin and upregulated vimentin, the efficacy of chemotherapy with PGB was superior compared with EB; but the same effect was not observed in patients with high E-cadherin and low vimentin. Although increased PFS was observed in patients with PGB treatment compared with EB treatment in the whole analysis populations, in the subgroup of patients with the mesenchymal phenotype, no prognostic or predictive value of either biomarker could be identified. The potential role of bevacizumab in overcoming chemotherapy resistance in the population with the mesenchymal phenotype has to be further explored.