[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.

Shifting cancer care towards Multidisciplinarity: the cancer center certification program of the German cancer society.

BACKGROUND: Over the last decades numerous initiatives have been set up that aim at translating the best available medical knowledge and treatment into clinical practice. The inherent complexity of the programs and discrepancies in the terminology used make it difficult to appreciate each of them distinctly and compare their specific strengths and weaknesses. To allow comparison and stimulate dialogue between different programs, we in this paper provide an overview of the German Cancer Society certification program for multidisciplinary cancer centers that was established in 2003. MAIN BODY: In the early 2000s the German Cancer Society assessed the available information on quality of cancer care in Germany and concluded that there was a definite need for a comprehensive, transparent and evidence-based system of quality assessment and control. This prompted the development and implementation of a voluntary cancer center certification program that was promoted by scientific societies, health-care providers, and patient advocacy groups and based on guidelines of the highest quality level (S3). The certification system structures the entire process of care from prevention to screening and multidisciplinary treatment of cancer and places multidisciplinary teams at the heart of this program. Within each network of providers, the quality of care is documented using tumor-specific quality indicators. The system started with breast cancer centers in 2003 and colorectal cancer centers in 2006. In 2017, certification systems are established for the majority of cancers. Here we describe the rationale behind the certification program, its history, the development of the certification requirements, the process of data collection, and the certification process as an example for the successful implementation of a voluntary but powerful system to ensure and improve quality of cancer care. CONCLUSION: Since 2003, over 1 million patients had their primary tumors treated in a certified center. There are now over 1200 sites for different tumor entities in four countries that have been certified in accordance with the program and transparently report their results from multidisciplinary treatment for a substantial proportion of cancers. This led to a fundamental change in the structure of cancer care in Germany and neighboring countries within one decade.

Prospective, Noninterventional Study of Nivolumab in Real-world Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer After Prior Chemotherapy (ENLARGE-Lung).

Nivolumab was the first immune checkpoint inhibitor approved for use in advanced non-small cell lung cancer (NSCLC). This noninterventional, prospective cohort study investigates real-world effectiveness of nivolumab in pretreated NSCLC patients in Germany (Enlarge-Lung/CA209-580). Patients with squamous (SQ) or nonsquamous (NSQ) NSCLC previously treated for locally advanced or metastatic (stage IIIB/IV) disease received nivolumab according to the current Summary of Product Characteristics. Overall survival (OS) was the primary endpoint. Of 907 patients enrolled, 660 patients who were followed for at least 12 months across 79 study centers in Germany, were analyzed. Median OS was 11.2 months [95% confidence interval (CI), 9.1-12.9]; outcomes for the 418 patients with NSQ histology [13.1 mo (95% CI, 10.6-15.6)] were more favorable than outcomes for the 242 patients with SQ histology [8.9 mo (95% CI, 6.4-11.3)]. Patients' age, presence of distant or brain metastases, or line of therapy did not affect outcomes; however, patients with poor performance status (ECOG-PS ≥2, n=80) had shorter median OS [4.7 mo (95% CI, 3.1-5.4)]. This study represents one of the largest real-world cohorts providing outcomes of nivolumab in pretreated NSCLC. The results match well with the published evidence from pivotal clinical trials and demonstrate clinical effectiveness of nivolumab in advanced NSCLC.

Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer.

BACKGROUND: Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients. METHODS: Between Oct 1, 1995, and July 1, 2003, patients with stage IIIA-IIIB NSCLC and invasive mediastinal assessment from 26 participating institutions of the German Lung Cancer Cooperative Group (GLCCG) were randomly assigned to one of two treatment groups. The intervention group were scheduled to receive three cycles of cisplatin and etoposide, followed by twice-daily radiation with concurrent carboplatin and vindesine, and then surgical resection (those with positive resection margins or unresectable disease were offered further twice-daily radiotherapy). The control group were scheduled to receive three cycles of cisplatin and etoposide, followed by surgery, and then further radiotherapy. The primary endpoint was median progression-free survival (PFS) in patients eligible for treatment after randomisation. Secondary endpoints in patients eligible for treatment after randomisation were overall survival (OS) and the proportion of patients undergoing surgery. Secondary endpoints in patients with tumour resection were the proportion with negative resection margins, the proportion with complete resection, the proportion with histopathological response, and the proportion with mediastinal downstaging. Additionally, exploratory (not prespecified) post-hoc analyses in terms of PFS and OS were done on patients not amenable to resection and on further subgroups of patients undergoing resection. Analyses were by intention to treat. This trial is registered on the ClinicalTrials.gov website, number NCT 00176137. FINDINGS: 558 patients were randomly assigned. 34 patients did not meet inclusion criteria and were excluded. Of 524 eligible patients, 142 of 264 (54%) in the interventional group and 154 of 260 (59%) in the control group underwent surgery; 98 of 264 (37%) and 84 of 260 (32%) underwent complete resection. In patients with complete resection, the proportion of those with mediastinal downstaging (45 of 98 [46%] and 24 of 84 [29%], p=0.02) and pathological response (59 of 98 [60%] and 17 of 84 [20%], p<0.0001) favoured the interventional group. However, there was no difference in PFS (primary endpoint) between treatment groups-either in eligible patients (median PFS 9.5 months, range 1.0-117.0 [95% CI 8.3-11.2] vs 10.0 months, range 1.0-111.0 [8.9-11.5], 5-year PFS 16% [11-21] vs 14% [10-19], hazard ratio (HR) 0.99 [0.81-1.19], p=0.87), in those undergoing tumour resection, or in patients with complete resection. In both groups, 35% of patients undergoing surgery received a pneumonectomy (50/142 vs 54/154). In patients receiving a pneumonectomy, treatment-related mortality increased in the interventional group compared with the control group (7/50 [14%] vs 3/54 [6%]). INTERPRETATION: In patients with stage III NSCLC amenable to surgery, preoperative chemoradiation in addition to chemotherapy increases pathological response and mediastinal downstaging, but does not improve survival. After induction with chemoradiation, pneumonectomy should be avoided. FUNDING: German Cancer Aid (Bonn, Germany).

18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense?

UNLABELLED: (18)F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. METHODS: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after (18)F-FDG PET (90-150 min after 250 MBq of (18)F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (- - - through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. RESULTS: SUVs in metastatic lymph nodes were higher (mean +/- SD, 7.1 +/- 4.5; range, 1.4-26.9; n = 70) than in tumor-free lymph node stations (2.4 +/- 1.7; range, 0.6-14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 +/- 2.0; range, 0.8-14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 +/- 0.022; SUV, 0.899 +/- 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. CONCLUSION: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on (18)F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.

Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin.

PURPOSE: The combination of paclitaxel with carboplatin is effective in advanced-stage non-small cell lung cancer (NSCLC). This phase III study was designed to compare the efficacy and tolerability of a weekly versus an every-3-week schedule in the first-line treatment of advanced-stage NSCLC. PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive paclitaxel 100 mg/m2 and carboplatin at an area under the curve of 2 once weekly for 6-8 weeks (arm A) or paclitaxel 200 mg/m2 and carboplatin at an area under the curve of 6 on day 1 every 21 days (arm B). RESULTS: A total of 883 patients received >or= 1 chemotherapy cycle and were included in the results. The objective response rates observed (complete response plus partial response) were 38% for arm A and 33% for arm B. Median times to progression and median survival times were 6.1 months and 8.9 months in arm A and 7.2 months and 9.5 months in arm B, respectively. There were no significant differences between treatment arms. The chemotherapy was well tolerated in both schedules. However, grade 3/4 sensory neuropathy occurred more frequently with the every-3-week schedule (9.1% vs. 4.4%), whereas grade 3/4 diarrhea occurred more frequently with the weekly schedule (4.2% vs. 1.1%). CONCLUSION: In terms of response and survival, paclitaxel/carboplatin administered once weekly is comparable with the every-3-week schedule. Toxicity differences should be considered when choosing the appropriate schedule for the individual.

[National Disease Management Guideline for Asthma: recommendations and evidence for "asthma prevention" issues]. / Nationale VersorgungsLeitlinie Asthma: Empfehlungen und Evidenz zum Thema "Asthma-Prävention".

The National Disease Management Program (NDM Program) represents the basic content of structured, cross-sectoral healthcare. In particular, the NDM Program is directed towards coordinating different disciplines and areas of healthcare. The recommendations are developed through interdisciplinary consensus of the scientific medical societies on the basis of the best available evidence. Within this scope the scientific medical societies concerned with the prevention, diagnosis, therapy and rehabilitation of asthma consented upon a National Disease Management Guideline for Asthma in 2005. Among other things, the following cornerstones of asthma prevention were agreed upon: Breastfeeding and non-smoking were suggested as primary prevention measures for (expectant) parents. With respect to secondary prevention, recommendations have been made for allergen avoidance, active/passive smoking and immunotherapy. Regarding tertiary prevention, position statements on vaccination and specific immunotherapy are developed. The present paper presents both the original texts of the recommendations and the evidence underlying them.

2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography in target volume definition for radiotherapy of patients with non-small-cell lung cancer.

PURPOSE: To discuss the potential contribution of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) in radiotherapy planning for non-small-cell lung cancer (NSCLC) considering new concepts on target volume definition. PROCEDURES: Recent investigations on the topic are reviewed with regard to current concepts of target volume definition for NSCLC. RESULTS: As intrathoracic recurrence is the leading cause of death after primary radiotherapy of NSCLC, there is a need for improving local control by escalating treatment intensity to gross disease. The value of elective nodal irradiation (ENI), resembling prophylactic irradiation of macroscopically unaffected parts of the mediastinum, is being considered. CONCLUSION: As FDG-PET has been shown to enhance the diagnostic accuracy of computed tomography (CT), and to have a potentially high impact on the identification of malignant tissue, it should be implicated in prospective clinical trials on dose escalation and three-dimensional conformal radiotherapy, especially in those including a reduction of target volumes.

Value of F-18-fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma.

OBJECTIVES: Induction therapy is an important treatment option in locally advanced non-small cell lung cancer. F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) has an important role in initial staging. The aim of this study was to assess the value of FDG-PET in restaging after induction therapy and in analyzing tumor viability, nodal status, distant metastases, and prognosis. METHODS: Forty-seven patients with locally advanced non-small cell lung cancer accepted for resection after induction therapy underwent FDG-PET. Images were interpreted visually for mediastinal nodal status and metastatic spread. The FDG accumulation in the tumor site was measured by using the maximum standardized uptake value. RESULTS: Unexpected metastases were detected by means of FDG-PET in 9 patients. Surgical intervention was not performed in 8 patients with confirmed metastases. The rate of unexpected findings increased from complete radiologic remission (0%) over partial remission (9%) to no change (67%). The standardized uptake value was higher in tumors with (n = 26) than in those without (n = 11) histologic proof of viability (6.4 +/- 5.3 vs 2.9 +/- 1.6, P = .006). All patients with standardized uptake values of greater than 5.8 had viable tumors. Sensitivity, specificity, and negative predictive value were 81%, 64%, and 58% for tumor viability and 50%, 88%, and 85% for persistent mediastinal disease. Median survival after resection was greater than 56 months for patients with tumor standardized uptake values of less than 4 and 19 months for patients with standardized uptake values of 4 or greater ( P < .001). CONCLUSION: FDG-PET helps in the selection of patients for resection after induction therapy. It can be used to detect unexpected distant metastases, especially after poor response to induction therapy. Its high negative predictive value in mediastinal restaging allows for omission of repeat mediastinoscopy. Tumor standardized uptake value after induction is a prognostic factor.

Mediastinal lymph node staging in suspected lung cancer: comparison of positron emission tomography with F-18-fluorodeoxyglucose and mediastinoscopy.

BACKGROUND: In patients with bronchogenic carcinoma, mediastinal lymph node staging is essential for determining treatment options. In this retrospective analysis we compared the results of positron emission tomography (PET) using F-18 fluorodeoxyglucose with those of mediastinoscopy in nodal staging for suspected bronchogenic carcinoma. METHODS: From March 1997 to June 2001, 102 patients (86 male,16 female, age 62 +/- 9 years) underwent both PET and mediastinoscopy for radiologically suspected mediastinal lymph node disease in bronchogenic carcinoma. Total body emission scans were acquired 90 to 150 minutes after injection of 230 MBq of F-18 fluorodeoxyglucose. Mediastinoscopic evaluation of lymph node stations was performed according to the method of Mountain and Dresler (1R, 1L, 2L, 2R, 4L, 4R,7). Patients were eligible if surgical staging was performed within 6 weeks after the PET scan. RESULTS. Of the 102 patients, benign lesions were diagnosed in 15. In 87 patients malignant disease was proven by histology, and bronchogenic carcinoma was found in 82. Of 469 nodal stations analyzed, malignancy was documented by histology in 84. In PET analysis 79 true-positive and 304 true-negative samples were found. Five lymph node stations were false negative, and 81 samples were false positive. False-positive findings in PET frequently were seen in inflammatory lung disease. The sensitivity of PET was 94.1%, specificity was 79% with a diagnostic accuracy of 81.6%. The positive predictive value of PET was 49.3%, and the negative predictive value was 98.4%. CONCLUSIONS: In patients with positive PET scan results histologic verification appears necessary for exact lymph node staging. In view of the negative predictive value mediastinoscopy can be omitted in patients with bronchogenic carcinoma whose PET scan results were negative.

[Tuberculosis--current news about the "white pestilence" in the year 2004]. / Tuberkulose--Aktuelles zur "weissen Pest" anno 2004.

Among infectious diseases tuberculosis is the second leading cause of death world-wide, killing nearly 2 million people each year. In Africa the incidence of tuberculosis has increased mainly as a result of the burden of HIV infection, and in the former Soviet Union due to socio-economic changes and a decline of the healthcare system. Chemotherapeutic treatment with several drugs for 6 months or more can deliver cure to more than 95% of the patients. Direct observation of treatment (DOT) is regarded as the standard of care.

Bronchial asthma: diagnosis and long-term treatment in adults.

INTRODUCTION: Bronchial asthma is a serious global health problem. 5% to 10% of persons of all ages suffer from this chronic airway disorder. This review article presents important considerations of diagnosis and treatment in view of the current national and international asthma guidelines. METHODS: Selective literature review, with attention to the current national and international guidelines. RESULTS/DISCUSSION: Bronchial asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperreactivity and a variable degree of airway obstruction. It is diagnosed on the basis of the clinical history, physical examination, and pulmonary function tests, including reversibility testing and measurement of bronchial reactivity. The goal of treatment is to control the symptoms of the disease effectively and in lasting fashion. Long-term treatment with inhaled corticosteroids is the basis of asthma treatment, alongside preventive measures and patient education. Bronchodilators such as beta2 sympathomimetics are used for rapid symptomatic relief of acute attacks.

Ciclesonide is more effective than budesonide in the treatment of persistent asthma.

BACKGROUND: Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma. METHODS: A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 microg ex-actuator (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12 weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study. RESULTS: Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416 and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174; p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly improved FVC and PEF from baseline (p<0.0001), and significantly greater increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide, respectively). Analysis of morning PEF revealed an earlier onset of action for ciclesonide versus budesonide; a significant improvement was seen by day 2 (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide (p=0.047 versus baseline). Adverse events occurred with a similar incidence in both treatment groups. Neither treatment caused significant changes in urinary cortisol levels. CONCLUSION: Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.