[Surgical Therapy for Lung Cancer: Why it Should be Performed in High Volume Centres]. / Chirurgische Therapie des Lungenkarzinoms: Argumente für die Behandlung in großen Zentren.

Data on surgical lung cancer cases were extracted from the German Federal Statistics on Diagnosis-related groups (DRG) and a possible association between hospital volume and surgical mortality was explored. All treatment cases documented between 2005 and 2015 with the main diagnosis of lung cancer (International Classification of Disease code C34) and the German Operations and Procedure Key (OPS) codes 5-323 to 5-328 for anatomical lung resections were analysed. The treatment cases were assigned to hospital groups, defined according to the number of procedures performed per year. The total number of anatomical lung resections for the diagnosis of lung cancer increased by 24 % from 9376 resections in 2005 to 11,614 resections in 2015. In 2015, 57 % of anatomical lung resections in patients with lung cancer were performed in 47 high volume centres (hospitals with ≥ 75 resections/year); the remaining 43 % of the resections were distributed among 271 hospitals performing fewer than 75 resections per year. In hospitals performing fewer than 25 procedures/year, hospital mortality was almost twice as high as in large centres with ≥ 75 resections per year (5.7 vs. 3.0 %, mean value 2005 to 2015). In summary, our data indicate that a small number of high-volume hospitals perform the major part of lung resections of lung cancer in Germany with better survival as compared to low-volume hospitals. Based on current nationwide data a clear association between hospital volume and surgical mortality could be demonstrated.

[Pathological-anatomical diagnosis according to the German lung cancer guideline 2018]. / Pathologisch-anatomische Diagnostik gemäß S3-Leitlinie Lungenkarzinom 2018.

The German S3-guideline on prevention, diagnosis, therapy and follow-up of lung cancer, published in February 2018, expands on the 2010 guideline to include a total of 19 recommendations and statements regarding the "processing of lung resection specimens (tumor resection specimens)", "processing of lymph nodes", "histo-pathological typing and immunophenotype", "extent of tumor growth in resection specimens", "resection margins" or "R-classification", "grade of malignancy (grading)", "regression grading" as well as the "examination of molecular targets". The statements regarding the analysis of molecular targets result from the diagnostic requirements of the current targeted therapy of advanced lung cancer. At the same time, a pathological-anatomical diagnosis according to the current S3-guideline fulfills all corresponding requirements in certified lung cancer centers.

Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase II trial.

BACKGROUND: Large-cell neuroendocrine carcinoma of the lung (LCNEC) is a rare disease with poor prognosis and limited treatment options. Neuroendocrine tumors frequently show overactivation of the mTOR pathway. Based on the good activity of the mTOR inhibitor everolimus in different types of neuroendocrine tumors and the results of a previous phase I trial, we evaluated the efficacy and safety of everolimus in combination with carboplatin and paclitaxel as upfront treatment for patients with advanced LCNEC. PATIENTS AND METHODS: In this prospective, multicenter phase II trial chemotherapy-naive patients with stage IV LCNEC received 5 mg everolimus daily combined with paclitaxel 175 mg/m2 and carboplatin AUC 5 every 3 weeks for a maximum of four cycles followed by maintenance everolimus 5 mg daily until progression. Efficacy parameters were determined based on central radiologic assessment. RESULTS: Forty-nine patients with a mean age of 62 ±9 years and a predominance of male (71%) smokers (98%) were enrolled in 10 German centers. The overall response rate was 45% (95% confidence interval [CI] 31%-60%), the disease control rate 74% (CI 59%-85%), the median progression-free survival 4.4 (CI 3.2-6) months and the median overall survival 9.9 (CI 6.9-11.7) months. The progression-free survival rate at 3 months (primary end point) was 76% (CI 64%-88%) according to Kaplan-Meier. Grade-3/4 toxicities occurred in 51% of patients and mainly consisted of general physical health deterioration (8%), cytopenias (24%), infections (10%) and gastrointestinal problems (8%). Typical everolimus-related adverse events, like stomatitis, rash and ocular problems occurred only in a minority of patients (<15%) and were exclusively of grade 1-2. CONCLUSION: Everolimus in combination with carboplatin and paclitaxel is an effective and well-tolerated first-line treatment for patients with metastatic LCNEC. REGISTERED CLINICAL TRIAL NUMBERS: EudraCT number 2010-022273-34, NCT01317615.

[Management of Lung Abscess]. / Therapie von Lungenabszessen.

A lung abscess is an infectious pulmonary disease characterised by the presence of a pus-filled cavity within the lung parenchyma. The content of an abscess often drains into the airways spontaneously, leading to an air-fluid level visible on chest X-rays and CT scans. Primary lung abscesses occur in patients who are prone to aspiration or in otherwise healthy individuals; secondary lung abscesses typically develop in association with a stenosing lung neoplasm or a systemic disease that compromises immune defences, such as AIDS, or after organ transplantation. The organisms found in abscesses caused by aspiration pneumonia reflect the resident flora of the oropharynx. The most commonly isolated organisms are anaerobic bacteria (Prevotella, Bacteroides, Fusobacterium, Peptostreptococcus) or streptococci; in alcoholics with poor oral hygiene, the spectrum of pathogens includes Staphylococcus aureus, Streptococcus pyogenes and Actinomyces. Chest radiography and computed tomography (CT) are mandatory procedures in the diagnostic algorithm. Standard treatment for a lung abscess consists of systemic antibiotic therapy, which is based on the anticipated or proven bacterial spectrum of the abscess. In most cases, primary abscesses are successfully treated by calculated empiric antibiotic therapy, with an estimated lethality rate of less than 10 %. Secondary abscesses, despite targeted antimicrobial therapy, are associated with a poor prognosis, which depends on the patient's general condition and underlying disease; lethality is as high as 75 %. Negative prognostic factors are old age, severe comorbidities, immunosuppression, bronchial obstruction, and neoplasms. Surgical intervention due to failure of conservative treatment is required in only 10 % of patients, with a success rate of up to 90 % and postoperative mortality rates ranging between 0 and 33 %. Treatment success after endoscopic or percutaneous drainage is achieved in 73 to 100 % of cases, with an acceptable mortality rate (0-9 %).

[Quality of Care in Certified Lung Cancer Centers]. / Versorgungsqualität in zertifizierten Lungenkrebszentren.

BACKGROUND: Since 2008, lung cancer centers can be certified in accordance with the criteria set out by the German Cancer Society (Deutsche Krebsgesellschaft). This paper reports on the certification program for lung cancer centers and presents data on 18 quality indicators collected during certification. METHODS: After checks for plausibility and completeness, data on quality indicators for the 2011 and 2012 patient cohorts as well as data of the treating centers were analyzed descriptively (relative/absolute frequencies, means, site medians). PATIENTS: 23,222 patients with ICD-10 diagnoses C33 und C34 from 35 (2012) and 24 operating sites (2011), respectively. RESULTS: From 2011 to 2012, both the number of certified sites and the number of patients treated increased. Fulfillment of the certification requirements is already high and improved slightly from 2011 to 2012. The implementation of indicators without target values is less advanced. CONCLUSION: Thanks to the medical and professional associations as well as the oncologic medical experts, the lung cancer certification program is evolving continuously. There has been a steady increase both in the number of patients treated and the number of lung cancer centers; certification requirements are also being increasingly fulfilled.

[Interdisciplinary treatment of non-small cell lung cancer]. / Interdisziplinäre Therapie des nicht-kleinzelligen Lungenkarzinoms.

At the time of diagnosis of non-small cell lung cancer, about two thirds of the patients manifest tumor disease limited to the lungs without distant metastases. In this group localized tumor spread (stages I and II) can be distinguished from locally advanced spread including lymph node metastases (stages IIIA and B). In stages I and II with sufficient cardiopulmonary function, surgical resection is considered the standard treatment approach. If lobe resection is not possible due to comorbidities or limited pulmonary function, parenchyma-sparing resection or definitive radiotherapy is advocated. Postoperative adjuvant chemotherapy is recommended for individual cases in stage IB and as the standard treatment in stage II. In stages IIIA and IIIB interdisciplinary consultation involving pneumologists/oncologists, surgeons, and radiation oncologists is necessary to reach decisions on treatment recommendations. Generally multiple treatment modalities are employed in these stages, such as induction chemotherapy followed by surgery and subsequent irradiation or simultaneous chemoradiotherapy. These treatment combinations with curative intent should be differentiated from the numerous treatment methods with palliative intent.

[Drug-induced pulmonary diseases]. / Arzneimittelinduzierte Lungenerkrankungen.

It is well-known that more than 350 drugs can cause unwanted effects in the lungs, bronchi, and neighboring structures of the thorax with a corresponding spectrum of pathological changes. Cardinal symptoms are often new onset of dyspnea on exertion and a cough that is usually dry. Further diagnostic work-up includes comprehensive pulmonary function testing with determination of diffusing capacity, high-resolution computed tomography, and bronchoscopy with bronchoalveolar lavage. There is no specific pathological alteration for a defined drug. In case of doubt the potentially pneumotoxic drug should be discontinued. An attempt should be made to treat severely compromised lung function with systemic corticosteroids.

[Ciclesonide -- a new inhaled corticosteroid]. / Ciclesonid -- ein neues inhalatives Kortikosteroid -- Pharmakologische Eigenschaften und klinische Wirksamkeit in der Asthmatherapie.

Ciclesonide is a novel inhaled corticosteroid delivered as inactive prodrug via a hydrofluoroalkane metered-dose inhaler with a deposition rate of 50 - 60 %. At its target sites, the lungs, ciclesonide is converted to an active metabolite, desisobutyryl-ciclesonide (des-CIC) [so-called on-site activation]. High lipophilicity and formation of local depot prolong pulmonary duration of action, explaining once-daily administration of ciclesonide. High protein binding and rapid clearance reduce systemic interactions. In long-term studies, ciclesonide at doses as high as 1280-1600 microg/d did not suppress biochemical markers of adrenal function. Since ciclesonide is not being activated in the oropharynx, the incidence of local adverse effects is comparable to that of placebo. Compared to other ICS, ciclesonide shows a improved therapeutic index and can, therefore, be regarded as prototype of a new, third generation of inhaled corticosteroids.

Value of FDG PET in the management of NSCLC.

Metabolic imaging with positron emission tomography (PET) using 18F-fluoro-2-deoxy-glucose (FDG) has been accepted as an important imaging modality in lung cancer. FDG PET may have important impacts on the management of lung-cancer patients, for instance by improvement of locoregional (mediastinal) and extrathoracic staging (unexpected metastases). Interesting findings have now been reported in the response assessment to induction therapy providing results of greater prognostic significance than that obtained by conventional imaging methods. In the field of thoracic irradiation, FDG PET may provide advantages in terms of reduced toxicity, treatment intensification, better local tumour control and increased survival.

Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma.

OBJECTIVES: This study evaluated the efficacy and safety of a novel asthma management strategy--budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy)--compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma. METHODS: This was a 12-month, randomised, double-blind, parallel-group study. Symptomatic patients with asthma (n = 1890; mean age 43 years [range 11 years-80 years], mean baseline forced expiratory volume in 1 s [FEV(1)] 70% of predicted, mean inhaled corticosteroid [ICS] dose 746 microg/day) received either budesonide (160 microg, 2 inhalations twice daily) plus terbutaline 0.4 mg as needed or a daily maintenance dose of budesonide/formoterol (160/4.5 microg, 2 inhalations once daily) with additional inhalations of budesonide/formoterol 160/4.5 microg as needed. Time to first severe exacerbation (hospitalisation/emergency room [ER] treatment or systemic steroids due to asthma worsening or a fall in morning peak expiratory flow [PEF] to < or = 70% of baseline on 2 consecutive days) was the primary outcome variable. RESULTS: A total of 1890 patients were randomised, of whom 1563 (83%) had severe asthma. The time to first severe exacerbation was prolonged by budesonide/formoterol single inhaler therapy (p < 0.001) compared with a higher dose of budesonide. The risk of having a severe exacerbation was 39% lower with budesonide/formoterol single inhaler therapy compared with budesonide (p < 0.001). The number needed to treat to prevent one severe exacerbation per year with budesonide/formoterol compared with budesonide was 5. The budesonide/formoterol group had 45% fewer severe exacerbations requiring medical intervention per patient compared with the budesonide group (p < 0.001). Budesonide/formoterol patients had fewer hospitalisations/ER treatments (15 vs 25 events, respectively [descriptive statistics]) and fewer treatment days with systemic steroids (1776 days vs 3177 days, respectively [descriptive statistics]) compared with budesonide patients. Budesonide/formoterol single inhaler therapy patients used less as-needed medication compared with budesonide patients (0.90 vs 1.42 inhalations/day; p < 0.001). The mean daily ICS dose was lower in the budesonide/formoterol group than in the budesonide group (466 microg/day vs 640 microg/day). Over the 12-month study period, the budesonide/formoterol group achieved asthma control sufficient to not require any additional as-needed medication on 60% of days. Overall, budesonide/formoterol single inhaler therapy gave 31 more asthma control days (a night and day with no asthma symptoms and no as-needed medication use) per patient-year and 12 additional undisturbed nights per patient-year compared with a higher dose of budesonide. Both treatments were well tolerated. CONCLUSION: Budesonide/formoterol single inhaler therapy has the potential to provide a complete asthma management approach with one inhaler, demonstrating a high level of efficacy in patients with moderate to severe asthma.

[Pulmonary diseases in the elderly. Problems of pharmacotherapy]. / Pulmonale Erkrankungen im Alter. Probleme der Pharmakotherapie.

In asthma, inhaled corticosteroids (ICS) can be regarded as disease-modifying drugs. They represent the mainstay of pharmacotherapy of asthma. In elderly, ICS are currently underused. In chronic obstructive pulmonary disease (COPD), there is recent evidence to suggest that ICS may reduce the rate and severity of COPD exacerbations and may improve health-related quality of life. Particularly patients with moderate-to-severe COPD appear to benefit from ICS therapy. In both asthma and COPD, fixed combinations of ICS and long-acting beta 2-agonists may provide clinically meaningful benefits to patients and may represent a further therapeutic advantage.

[Optimization of radiotherapy planning for non-small cell lung cancer (NSCLC) using 18FDG-PET]. / Optimierung der Bestrahlungsplanung beim nicht-kleinzelligen Bronchialkarzinom (NSCLC) mit Hilfe von 18FDG-PET.

AIM: In recent years, FDG-PET examinations have become more important for problems in oncology, especially in staging of bronchogenic carcinoma. In the retrospective study presented here, the influence of PET on the planning of radiotherapy for patients with non-small-cell lung cancer (NSCLC) was investigated. METHODS: The study involved 39 patients with NSCLC who had been examined by PET for staging. They received radiotherapy on the basis of the anterior/posterior portals including the primary tumour and the mediastinum planned according to CT- and bronchoscopic findings. The results of the PET examination were not considered in initial radiotherapy planning. The portals were retrospectively redefined on the basis of FDG uptake considering the size and localization of the primary tumour; and FDG activities outside the mediastinal part of the portals. RESULTS: In 15 out of 39 patients, the CT/PET-planned portals differed from the CT-planned ones. In most causes (n = 12) the CT/PET field was smaller than the CT field. The median geometric field size of the portals was 179 cm2, after redefinition using PET 166 cm2. In 20 patients with disturbed ventilation caused by the tumour (atelectasis, dystelectosis), a correction of the portal was suggested significantly more frequently than in the other patients (p = 0.03). CONCLUSIONS: Our results demonstrate the synergism of topographical (CT) and metabolic (FDG-PET) information, which could be helpful in planning radiotherapy of bronchial carcinoma, especially for patients with disturbed ventilation.