Patients with Advanced or Metastasised Non-Small-Cell Lung Cancer with Viscum album L. Therapy in Addition to PD-1/PD-L1 Blockade: A Real-World Data Study.

Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA (Viscum album L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC. We sought to investigate whether the addition of VA to PD-1/PD-L1 inhibitors in patients with advanced or metastasised NSCLC would have an additional survival benefit. In the present real-world data study, we enrolled patients from the accredited national registry, Network Oncology, with advanced or metastasised NSCLC. The reporting of data was performed in accordance with the ESMO-GROW criteria for the optimal reporting of oncological real-world evidence (RWE) studies. Overall survival was compared between patients receiving PD-1/PD-L1 inhibitor therapy (control, CTRL group) versus the combination of anti-PD-1/PD-L1 therapy and VA (combination, COMB group). An adjusted multivariate Cox proportional hazard analysis was performed to investigate variables associated with survival. From 31 July 2015 to 9 May 2023, 415 patients with a median age of 68 years and a male/female ratio of 1.2 were treated with anti-PD-1/PD-L1 therapy with or without add-on VA. Survival analyses included 222 (53.5%) patients within the CRTL group and 193 (46.5%) in the COMB group. Patients in the COMB group revealed a median survival of 13.8 months and patients in the CRTL group a median survival of 6.8 months (adjusted hazard ratio, aHR: 0.60, 95% CI: 0.43-0.85, p = 0.004) after adjustment for age, gender, tumour stage, BMI, ECOG status, oncological treatment, and PD-L1 tumour proportion score. A reduction in the adjusted hazard of death by 56% was seen with the addition of VA (aHR 0.44, 95% CI: 0.26-0.74, p = 0.002) in patients with PD-L1-positive tumours (tumour proportion score > 1%) treated with first-line anti-PD-1/PD-L1 therapy. Our findings suggest that add-on VA correlates with improved survival in patients with advanced or metastasised NSCLC who were treated with PD-1/PD-L1 inhibitors irrespective of age, gender, tumour stage, or oncological treatment. The underlying mechanisms may include the synergistic modulation of the immune response. A limitation of this study is the observational non-randomised study design, which only allows limited conclusions to be drawn and prospective randomised trials are warranted.

Patient-reported outcomes in advanced NSCLC before and during the COVID-19 pandemic: Real-world data from the German prospective CRISP Registry (AIO-TRK-0315).

Patients with lung cancer under treatment have been associated with a high risk of COVID-19 infection and potentially worse outcome, but real-world data on patient-reported outcomes (PROs) are rare. We assess patients' characteristics and PROs before and during the COVID-19 pandemic in an advanced non-small cell lung cancer (NSCLC) cohort in Germany. Patients with locally advanced or metastatic NSCLC from the prospective, multicentre, observational CRISP Registry (NCT02622581) were categorised as pre-pandemic (March 2019 to Feb 2020, n = 1621) and pandemic (March 2020 to Feb 2021, n = 1317). From baseline to month 15, patients' health-related quality of life (HRQoL) was assessed by FACT-L, anxiety and depression by PHQ-4. Association of pandemic status with time to deterioration (TTD) in QoL scales adjusted for potential covariates was estimated using Cox modelling. PROs were documented for 1166 patients (72%) in the pre-pandemic, 979 (74%) in the pandemic group. Almost 60% of patients were male, median age was 66 years, comorbidities occurred in 85%. Regarding HRQoL, mean-change-from-baseline plots hardly differed between both samples. Approximately 15%-21% of patients reported anxiety, about 19%-27% signs of depression. For the pandemic group, TTD was slightly, but statistically significantly, worse for the physical well-being-FACT-G subscale (HR 1.15 [95%CI 1.02-1.30]) and the anxiety-GAD-2 subscale (HR 1.14 [95%CI 1.01-1.29]). These prospectively collected real-world data provide valuable insights into PROs before and during the COVID-19 pandemic in advanced NSCLC. For the patients, the pandemic seemed to be less of a burden than the disease itself, as there was a considerable proportion of patients with anxiety and depression in both groups.

Assessment of efficacy and safety of endoscopic lung volume reduction with one-way valves in patients with a very low FEV1.

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 (FEV1) (≤20% predicted). We aim to compare clinical outcomes of ELVR, in relation to the FEV1 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: FEV1 ≤20% pred and FEV1 21-45% pred. Pulmonary function tests (FEV1, 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 FEV1 ≤20% pred and 265 patients with FEV1 21-45% pred were analysed. After ELVR, an increase in FEV1 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 FEV1 21-45% pred group, and by trend in the FEV1 ≤20% pred group. Pneumothorax was the most frequent complication within the first 90 days in both groups (FEV1 ≤20% pred: 7.7% versus FEV1 21-45% pred: 22.1%; p=0.624). No deaths occurred in the FEV1 ≤20% pred group up to 6 months. Conclusion: Our study highlights the potential efficacy of one-way valves, even in patients with very low FEV1, as these patients experienced significant improvements in FEV1, 6MWD and quality of life. No death was reported, suggesting a good safety profile, even in these high-risk patients.

Genetic and geographic influence on phenotypic variation in European sarcoidosis patients.

Introduction: Sarcoidosis is a highly variable disease in terms of organ involvement, type of onset and course. Associations of genetic polymorphisms with sarcoidosis phenotypes have been observed and suggest genetic signatures. Methods: After obtaining a positive vote of the competent ethics committee we genotyped 1909 patients of the deeply phenotyped Genetic-Phenotype Relationship in Sarcoidosis (GenPhenReSa) cohort of 31 European centers in 12 countries with 116 potentially disease-relevant single-nucleotide polymorphisms (SNPs). Using a meta-analysis, we investigated the association of relevant phenotypes (acute vs. sub-acute onset, phenotypes of organ involvement, specific organ involvements, and specific symptoms) with genetic markers. Subgroups were built on the basis of geographical, clinical and hospital provision considerations. Results: In the meta-analysis of the full cohort, there was no significant genetic association with any considered phenotype after correcting for multiple testing. In the largest sub-cohort (Serbia), we confirmed the known association of acute onset with TNF and reported a new association of acute onset an HLA polymorphism. Multi-locus models with sets of three SNPs in different genes showed strong associations with the acute onset phenotype in Serbia and Lublin (Poland) demonstrating potential region-specific genetic links with clinical features, including recently described phenotypes of organ involvement. Discussion: The observed associations between genetic variants and sarcoidosis phenotypes in subgroups suggest that gene-environment-interactions may influence the clinical phenotype. In addition, we show that two different sets of genetic variants are permissive for the same phenotype of acute disease only in two geographic subcohorts pointing to interactions of genetic signatures with different local environmental factors. Our results represent an important step towards understanding the genetic architecture of sarcoidosis.

Cell-Free Methylated PTGER4 and SHOX2 Plasma DNA as a Biomarker for Therapy Monitoring and Prognosis in Advanced Stage NSCLC Patients.

Notwithstanding some improvement in the earlier detection of patients with lung cancer, most of them still present with a late-stage disease at the time of diagnosis. Next to the most frequently utilized factors affecting the prognosis of lung cancer patients (stage, performance, and age), the recent application of biomarkers obtained by liquid profiling has gained more acceptance. In our study, we aimed to answer these questions: (i) Is the quantification of free-circulating methylated PTGER4 and SHOX2 plasma DNA a useful method for therapy monitoring, and is this also possible for patients treated with different therapy regimens? (ii) Is this approach possible when blood-drawing tubes, which allow for a delayed processing of blood samples, are utilized? Baseline values for mPTGER4 and mSHOX2 do not allow for clear discrimination between different response groups. In contrast, the combination of the methylation values for both genes shows a clear difference between responders vs. non-responders at the time of re-staging. Furthermore, blood drawing into tubes stabilizing the sample allows researchers more flexibility.

Impact of Coronavirus Disease 2019 on Hospital Admissions, Health Status, and Behavioral Changes of Patients with COPD.

Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of acquiring severe coronavirus disease 2019 (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation, accompanied by limited access to health care systems, might influence the outcome of patients with severe COPD negatively. Methods: Data from COPD and pneumonia patients at Charité-Universitätsmedizin Berlin and the volume of endoscopic lung volume reduction (ELVR) surgeries from the German Lung Emphysema Registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to the pandemic period (2020 and 2021). In addition, 52 patients with COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stage 4 status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021. Results: Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction in ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during the pandemic. Increasing proportions of COPD patients with GOLD stage 3 and GOLD stage 4 status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time period. Summary: This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during the pandemic, but a slight increase in mortality among patients hospitalized with COPD, irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status, probably caused by their very strict compliance with lockdown measures.

Evaluation of quality of life in lung cancer patients receiving radiation and Viscum album L.: a real-world data study.

BACKGROUND: Lung cancer (LC) is associated with high mortality and poor quality of life (QoL). The disease as well as oncological treatments such as radiation and chemotherapy with adverse effects can impair the QoL of patients. Add-on treatment with extracts of Viscum album L. (white-berry European mistletoe, VA) has been shown to be feasible and safe and to improve the QoL of cancer patients. The aim of this study was to analyze the changes in QoL of LC patients being treated with radiation according to oncological guidelines and add-on VA treatment in a real-world setting. METHODS: A real-world data study was conducted using registry data. Self-reported QoL was assessed by the evaluation of the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30). Adjusted multivariate linear regression analyses were performed to analyze factors associated with changes in QoL at 12 months. RESULTS: A total of 112 primary LC patients (all stages, 92% non-small-cell lung cancer, median age 70 (ICR: 63-75)), answered the questionnaires at first diagnosis and 12 months later. Assessment of 12 months changes in QoL revealed significant improvement of 27 points for pain (p = 0.006) and 17 points for nausea/vomiting (p = 0.005) in patients who received combined radiation and VA. In addition, significant improvements of 15 to 21 points for role (p = 0.03), physical (p = 0.02), cognitive (p = 0.04), and social functioning (p = 0.04) were observed in guideline treated patients receiving no radiation but add-on VA. CONCLUSIONS: Add-on VA therapy reveals supportive effects for the QoL of LC patients. Particularly in combination with radiation a significant reduction in pain and nausea/ vomiting has been observed. Trial registration The study received ethics approval and was retrospectively registered (DRKS00013335 on 27/11/2017).

Correction: Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis.

[This corrects the article DOI: 10.1371/journal.pone.0203058.].

Endoscopic Lung Volume Reduction with One-Way Valves in Patients with Severe Chronic Obstructive Pulmonary Disease with Hypercapnia.

BACKGROUND: Robust clinical evidence on the efficacy and safety of endoscopic lung volume reduction (ELVR) with one-way valves in patients with severe lung emphysema with chronic hypercapnic respiratory failure is lacking. OBJECTIVE: The aim of this study was to compare patient characteristics, clinical outcome measures, and incidences of adverse events between patients with severe COPD undergoing ELVR with one-way valves and with either a partial pressure of carbon dioxide (pCO2) of ≤45 mm Hg or with pCO2 >45 mm Hg. METHODS: This was a multicentre prospective study of patients with severe lung disease who were evaluated based on lung function, exercise capacity (6-min walk test [6-MWT]), and quality-of-life tests. RESULTS: Patients with pCO2 ≤45 mm Hg (n = 157) and pCO2 >45 mm Hg (n = 40) showed similar baseline characteristics. Patients with pCO2 ≤45 mm Hg demonstrated a significant increase in forced expiratory volume in 1 s (p < 0.001), a significant decrease in residual volume (RV) (p < 0.001), and significant improvements in the quality of life and 6-MWT at the 3-month follow-up. Patients with pCO2 >45 mm Hg had significant improvements in RV only (p < 0.05). There was a significant decrease in pCO2 between baseline and follow-up in hypercapnic patients, relative to the decrease in patients with pCO2 ≤45 mm Hg (p = 0.008). Patients who were more hypercapnic at baseline showed a greater reduction in pCO2 after valve placement (r = -0.38, p < 0.001). Pneumothorax was the most common adverse event in both groups. CONCLUSIONS: ELVR with one-way valves seems clinically beneficial with a remarkably good safety profile for patients with chronic hypercapnic respiratory failure.

ACCEPT®: A Complementary Anthroposophical Program for the Palliative Treatment of Lung Cancer - Rationale and a Randomized Feasibility Study.

BACKGROUND: Lung cancer is the oncological disease with the highest mortality worldwide. Health-related quality of life is severely compromised in the majority of patients. While the efficacy of early palliative psychosocial therapy has been demonstrated in several recent studies, appropriate therapy modules could so far not be integrated into daily practice of care. Therefore, an additive multimodal treatment concept for oncological centers was drafted: the Additive anthroposophic integrative medicine Cancer Concept of Early supportive or Palliative lung cancer Treatment (ACCEPT®). PATIENTS AND METHODS: The first module consisted of a 3-month health education program, the second module was a concept of psychosocial interventions, and the third module was a supervised home training program. Between 2017 and 2018, 20 lung cancer patients (UICC IIIB/IV) were included and randomly assigned to treatment (n = 10) or a waiting control group (n = 10). The treatment group started ACCEPT® for 3 months immediately after diagnosis and received also standard oncological care (SOC) while the waiting control group received SOC only for 3 months, followed by ACCEPT® after this period. Health-related quality of life, disease management, disease-specific symptoms, and feasibility of the ACCEPT® were monitored at 4 time points. RESULTS: 7 out of 10 patients in the treatment group (3 dropped out) and 6 out of 10 in the waiting control group (4 died during the intervention) completed treatment. DISCUSSION/CONCLUSION: Lung cancer patients with high symptom load may benefit from ACCEPT®. The feasibility of this adjunctive therapy was demonstrated. The combination of SOC and ACCEPT® is feasible and applicable to a heterogeneous patient group and should be further evaluated with respect to efficacy and dosing.

Is Adjuvant Radiochemotherapy Always Mandatory in Patients with Resected N2 Non-Small Cell Lung Cancer?

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), the pathologic union for international cancer control (UICC) stage IIIA is a heterogeneous entity, with different forms of N2-lymph node involvement representing different prognoses. Although a multimodality treatment approach, including surgery, systemic therapy, and/or radiotherapy, is almost always recommended, in this retrospective observational study, we sought to determine whether long-term survival might be possible in selected patients who are treated with complete surgical resection alone. METHODS: Between 2013 and 2018, we retrospectively identified 24 patients with NSCLC (16 men and 8 women), who were found to have pathologic N2-lymph node involvement, and were treated with complete surgical lung resection and systematic mediastinal and hilar lymph node dissection but no neoadjuvant or adjuvant treatment. RESULTS: The most frequent reason (n = 14) for forgoing adjuvant treatment was patient refusal. The mean overall survival (OS) was 34.5 months (interquartile range [IQR]: 15.5-53.5 months). The mean disease-free survival (DFS) was 18 months (IQR: 4.75-46.75 months). We identified five patients who survived at least 5 years without recurrence (21%). In each of these cases, the nodal metastases were restricted to a single level and no extracapsular lymph node involvement were detected. Additionally, worse DFS was associated with pT3/4 (vs. a lower T-stage), as well as microscopic lymphovascular invasion. CONCLUSION: Although the small sample size precludes any definitive conclusions, it was possible to demonstrate that long-term survival without neoadjuvant and adjuvant treatment is possible in some patients if complete tumor and nodal resection is performed.

Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema.

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.

KRASG12C/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma.

BACKGROUND: Pembrolizumab is a standard of care as first line palliative therapy in PD-L1 overexpressing (≥50%) non-small cell lung cancer (NSCLC). This study aimed at the identification of KRAS and TP53-defined mutational subgroups in the PD-L1 high population to distinguish long-term responders from those with limited benefit. METHODS: In this retrospective, observational study, patients from 4 certified lung cancer centers in Berlin, Germany, having received pembrolizumab monotherapy as first line palliative treatment for lung adenocarcinoma (LuAD) from 2017 to 2018, with PD-L1 expression status and targeted NGS data available, were evaluated. RESULTS: A total of 119 patients were included. Rates for KRAS, TP53 and combined mutations were 52.1%, 47.1% and 21.9%, respectively, with no association given between KRAS and TP53 mutations (P=0.24). By trend, PD-L1 expression was higher in KRAS-positive patients (75% vs. 65%, P=0.13). Objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the KRASG12C group (n=32, 51.6%) were 63.3%, 19.8 months (mo.) and not estimable (NE), respectively. Results in KRASother and wild type patients were similar and by far lower (42.7%, P=0.06; 6.2 mo., P<0.001; 23.4 mo., P=0.08). TP53 mutations alone had no impact on response and survival. However, KRASG12C/TP53 co-mutations (n=12) defined a subset of long-term responders (ORR 100.0%, PFS 33.3 mo., OS NE). In contrast, patients with KRASother/TP53 mutations showed a dismal prognosis (ORR 27.3%, P=0.002; PFS 3.9 mo., P=0.001, OS 9.7 mo., P=0.02). CONCLUSIONS: A comprehensive assessment of KRAS subtypes and TP53 mutations allows a highly relevant prognostic differentiation of patients with metastatic, PD-L1 high LuAD treated upfront with pembrolizumab.

Pembrolizumab as First-Line Palliative Therapy in PD-L1 Overexpressing (≥ 50%) NSCLC: Real-world Results with Special Focus on PS ≥ 2, Brain Metastases, and Steroids.

INTRODUCTION: Pembrolizumab is a highly effective standard of care in PD-L1 overexpressing (≥ 50%) non-small-cell lung cancer. However, a substantial share of patients from everyday clinical practice is treated without clear evidence from clinical trials. PATIENTS AND METHODS: We performed a retrospective multicentric study including all consecutive patients from 6 certified lung cancer centers in Berlin, Germany, having received pembrolizumab as first-line palliative therapy from January 1 until December 31, 2017. Aims were to validate published clinical trials with a special focus on efficacy and outcome in patients with reduced performance status (PS), brain metastases, and steroids. RESULTS: A total of 153 patients were included (median age 69 years, 58% men, 69% adenocarcinoma). Rates for PS ≥ 2, brain metastases, and steroids were 24.8%, 20.9%, and 24.2%, respectively. Median objective response rate, progression-free and overall survival were 48.5%, 8.2 and 22.0 months for all patients and 52.4%, 8.8 and 29.2 months in patients fulfilling the inclusion criteria for the KEYNOTE-024 trial. Patients with a comorbidity-defined PS ≥ 2, symptomatic brain metastases requiring upfront radiotherapy, or baseline steroids had significantly reduced survival. In contrast, durable responses occurred with a tumor-related PS ≥ 2 or asymptomatic brain metastases. Grade 3/4 and 5 immune-related adverse events affected 13.7% and 2.0% of patients. CONCLUSION: Real-world and clinical trial efficacy with upfront pembrolizumab correspond well. Pembrolizumab may sufficiently control asymptomatic brain metastases and may improve a cancer-related reduced PS. However, the frail share of patients with a comorbidity-defined PS ≥ 2, symptomatic brain metastases, or baseline steroids derives no relevant benefit.

Endoscopic lung volume reduction with endobronchial valves in very low D LCO patients: results from the German Registry - Lungenemphysemregister e.V.

BACKGROUND: Endoscopic lung volume reduction (ELVR) with valves has been suggested to be the key strategy for patients with severe emphysema and concomitant low diffusing capacity of the lung for carbon monoxide (D LCO). However, robust evidence is still missing. We therefore aim to compare clinical outcomes in relation to D LCO for patients treated with ELVR. METHODS: We assessed D LCO at baseline and 3 months follow-up and compared pre- and postprocedural pulmonary function test, quality of life, exercise capacity and adverse events. This is a retrospective subanalysis of prospectively collected data from the German Lung Emphysema Registry. RESULTS: In total, 121 patients treated with ELVR were analysed. Thirty-four patients with a D LCO ≤20% and 87 patients with a D LCO >20% showed similar baseline characteristics. After ELVR, there was a decrease of residual volume (both p<0.001 to baseline) in both groups, and both demonstrated better quality of life (p<0.01 to baseline). Forced expiratory volume in 1 s (FEV1) improved significantly only in patients with a D LCO >20% (p<0.001 to baseline). Exercise capacity remained almost unchanged in both groups (p=0.3). The most frequent complication for both groups was a pneumothorax (D LCO ≤20%: 17.6% versus D LCO >20%: 16.1%; p=0.728). However, there were no significant differences in other adverse events between both groups. CONCLUSIONS: ELVR improves lung function as well as quality of life in patients with D LCO >20% and D LCO ≤20%. Adverse events did not differ between groups. Therefore, ELVR should be considered as a treatment option, even in patients with a very low D LCO.

Joint Statement of the German Respiratory Society and German Society of Thoracic Surgery in Cooperation with the German Radiological Society: Structural Prerequisites of Centres for Interventional Treatment of Emphysema.

Interventional treatment of emphysema offers a wide range of surgical and endoscopic options for patients with advanced disease. Multidisciplinary collaboration of pulmonology, thoracic surgery, and imaging disciplines in patient selection, therapy, and follow-up ensures treatment quality. The present joint statement describes the required structural and quality prerequisites of treatment centres. This is a translation of the German article "Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Thoraxchirurgie in Kooperation mit der Deutschen Röntgengesellschaft: Strukturvoraussetzungen von Zentren für die interventionelle Emphysemtherapie" Pneumologie. 2020;74:17-23.

Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315).

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.

Overall Survival of Nonmetastasized NSCLC Patients Treated With Add-On Viscum album L: A Multicenter Real-World Study.

BACKGROUND: Recent data suggest a beneficial effect of add-on treatment with Viscum album L (VA) on the survival in cancer patients. The objective of this study was to compare the impact of standard oncological therapy plus add-on VA treatment (S+VA) versus standard oncological therapy alone (S) on the overall survival (OS) of patients with nonmetastasized non-small cell lung carcinoma (NSCLC). METHODS: The multicenter real-world data study was conducted using data from the Network Oncology Clinical Registry. The primary end point was OS. OS and impact on hazard in both treatment groups were compared. RESULTS: A total of 275 patients with stages I to IIIA NSCLC were enrolled (mean age = 67.6 years, 57.2% male patients). No significant difference of OS was observed between both groups. Even though not significant, for a subgroup of unresected patients with stage I NSCLC, adenocarcinoma or squamous cell carcinoma, a medium effect size OS improvement was observed for S+VA compared to S. CONCLUSIONS: Our findings support the importance of surgery as the most effective intervention in nonmetastasized NSCLC patients. Add-on VA therapy shows here no additional effect in resected patients. However, a small subgroup analysis suggests a possible role of add-on VA for nonresected subgroups. Our results complement existing knowledge on the clinical impact of add-on VA therapy in NSCLC patients and may serve as hypothesis-generating data for further examinations in this cohort. Further research could be directed towards the role of combined therapy for nonresected early-stage NSCLC.