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.

[Molecular pathological diagnosis in cytopathology of non-small-cell lung cancer. Standardization of specimen processing]. / Molekularpathologische Diagnostik in der Zytopathologie des nichtkleinzelligen Lungenkarzinoms. Standardisierung der Materialprozessierung.

BACKGROUND: Personalized medicine is becoming standard for the treatment of non-small-cell lung cancer. For example, patients with activating EGFR mutations or EML4-ALK translocations largely benefit from targeted therapies with tyrosine kinase inhibitors with better response rates and progression-free survival compared to standard chemotherapy regimens. However, the application of the respective molecular biomarker analyses requires great expertise in the handling of different cell and tissue specimens. A major challenge for reliable analyses is the usually low amount of tumor material. There are currently relatively few standardized and evidence-based guidelines for the processing and analysis of respective specimens as well as for interpretation of the test results. MATERIALS AND METHODS: To establish a basis for standardized predictive cytopathological analyses, different material processing approaches and molecular pathological tests are discussed, and novel concepts and strategies are lined out in order to improve the quality and reliability of the respective diagnostic procedures. RESULTS AND DISCUSSION: Predictive analyses of cytological specimens can be reliably performed using smears, cytospins or cell blocks; there is no need for histological specimens. The diagnostic work-up of cytological probes should be performed as carefully as possible in order to save further tumor material for subsequent predictive analyses. With standardized and reliable procedures at hand cytopathology is an important contribution to the multidisciplinary, complex care, and treatment of lung cancer patients.

[Diagnostic and predictive analyses of cytological specimens of non-small cell lung cancer: strategies and challenges]. / Diagnose und prädiktive Analysen an zytologischen und bioptischen Tumorproben nicht-kleinzelliger Lungenkarzinome: Aktuelle Strategien und Herausforderungen.

Personalised medicine is becoming the standard care for advanced non-small cell lung cancer. Tumour-specific therapies based on biomarker analyses, e. g., EGFR mutations or translocations of the ALK gene locus, result in a superior patient outcome compared to unselected therapy approaches. However, predictive molecular analyses can be challenging and require significant experience with cell- and tissue-based diagnostic methods. The major challenge relates to the sometimes low amount of available tumour material for both diagnostic and predictive analyses. As yet, there are no standardised or evidence-based recommendations concerning biopsies, specimen processing, and analyses. Respective guidelines require combined interdisciplinary actions to consider both clinical and pathological aspects. In order to establish a basis for high quality procedures, different approaches, methods, and protocols were interdisciplinary discussed with an emphasis on cytological specimens. Detailed evaluation of the parameters and consented recommendations might contribute to optimised strategies in the interdisciplinary, more and more complex care of non-small cell lung cancer patients.

[Palliative measures in lung cancer]. / Palliative Massnahmen bei Lungenkrebs.

A patient in the final stages of lung cancer primarily needs effective pain management, treatment of symptoms such as coughing, breathing difficulty, fatigue and if necessary, relief through anti-metastasis therapy when a curative therapy is no longer useful. After all best possible medical measures have been employed, the final tasks of the family physician include speaking and listening to the patient, ideally without time pressure, and providing supportive information for the patient and his family.

[Prevention of lung cancer]. / Prävention des Lungenkarzinoms. Schluss mit der Qualmerei!

Prevention of lung cancer is based primarily on education and the avoidance of exposure. Efforts to quit smoking can be effectively supported by the family doctor with appropriate medication and additional behavioral therapeutic measures. The highest success rates are achieved with combination treatment. The inhalation of carcinogenic dusts can be prevented by taking suitable protective measures. Lung cancer occurring after occupational exposure to a carcinogen, may be recognized as an occupational disease. The possible development of chemoprevention is still in its early stages.

[Chemotherapy in cancer of the lung]. / Chemotherapie des Lungenkarzinoms. Lebensverlängerung und Symptomkontrolle als Ziel.

In the early stages of non-small cell lung cancer, postoperative administration of a combination of vinorelbine and cisplatin is of proven benefit. Chemotherapy is applied pre-operatively in the case of locally advanced stages, and in parallel with radiotherapy in the case of inoperable tumors. For advanced and metastatic stages of non-small cell lung cancer, combination therapy or monotherapy with antibodies may be considered. These are directed against tumor-specific structures (targeted therapy). In the case of early-stage non-small cell lung cancer the classical combinations, but also new substances are employed.

[Patient with left-sided pleural effusion and large structures of soft-tissue-density in the mediastinum]. / Patient mit Pleuraerguss links und grossen weichteildichten Strukturen im Mediastinum. Pankreatitis mit Pleuritis und mediastinaler Beteiligung.

A patient was admitted to the hospital to clarifying a left-sided pleural effusion. Typical cytological findings in pleural effusion did not leave a doubt about being present a pancreatitis in conformity with clearly increased levels of lipase and amylase in the effusion fluid. The CT of the upper abdomen showed signs of a exsudative pancreatitis. In the chest CT as well as in transesophageal ultrasound evaluation large structures of soft-tissue-density together with areas of encapsulated fluid were seen in the dorsal mediastinum reaching down to the diaphragm and abdomen. Just with subsequent diet and strict termination of any alcohol consumption the pathological findings recovered completely. Due to the expansive involvement of the pleural, mediastinal and abdominal compartments this is an extraordinary case of acute pancreatitis.

[Dyspnea, alopecia areata, protrusio bulbi. Which systemic disease is responsible?]. / Luftnot, fleckige Alopezie, Protrusio bulbi. Welche Systemerkrankung steckt dahinter?

Sarcoidosis is a systemic disease of unknown etiology and highly variable clinical presentation that manifests most frequently in the hilus lymph nodes, skin and eyes. The present case is a 63-year-old woman who was admitted for investigation of progressive apnea. Numerous typical, but also rare, organic symptoms were assignable to a chronic form of sarcoidosis: epileptiform attacks and depression, as also cutaneous changes affecting the scalp, and long wrongly diagnosed granulomatous "tumour" in the left orbit. The correct diagnosis was established on the basis of bronchoscopy and a chest CT that revealed inflammatory fibrotic changes in the lungs, and the histological work-up of tissue biopsies obtained from the various cutaneous lesions.