Bojan Zaric

A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1)

BACKGROUNDnThis trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination.nnnPATIENTS AND METHODSnPatients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS).nnnRESULTSnOf 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191).nnnCONCLUSIONnAdvanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the studys primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.

Pneumothorax after transbronchial needle biopsy

Currently there several diagnostic techniques that re used by radiologists and pulmonary physicians for lung cancer diagnostics. In several cases pneumothorax (PNTX) is induced and immediate action is needed. Both radiologists and pulmonary physicians can insert a chest tube for symptom relief. However; only pulmonary physicians and thoracic surgeons can provide a permanent solution for the patient. The final solution would be for a patient to undergo surgery for a final solution. In our current work we will provide all those diagnostic cases where PNTX is induced and treatment from the point of view of expert radiologists and pulmonary physicians.

Pneumothorax: from definition to diagnosis and treatment.

Pneumothorax is an urgent situation that has to be treated immediately upon diagnosis. Pneumothorax is divided to primary and secondary. A primary pneumothorax is considered the one that occurs without an apparent cause and in the absence of significant lung disease. On the other hand secondary pneumothorax occurs in the presence of existing lung pathology. There is the case where an amount of air in the chest increases markedly and a one-way valve is formed leading to a tension pneumothorax. Unless reversed by effective treatment, this situation can progress and cause death. Pneumothorax can be caused by physical trauma to the chest or as a complication of medical or surgical intervention (biopsy). Symptoms typically include chest pain and shortness of breath. Diagnosis of a pneumothorax requires a chest X-ray or computed tomography (CT) scan. Small spontaneous pneumothoraces typically resolve without treatment and require only monitoring. In our current special issue we will present the definition, diagnosis and treatment of pneumothorax from different experts in the field, different countries and present different methods of treatment.

Tube thoracostomy; chest tube implantation and follow up

Pneumothorax is an urgent medical situation that requires urgent treatment. We can divide this entity based on the etiology to primary and secondary. Chest tube implantation can be performed either in the upper chest wall or lower. Both thoracic surgeons and pulmonary physicians can place a chest tube with minimal invasive techniques. In our current work, we will demonstrate chest tube implantation to locations, methodology and tools.

Acute respiratory distress syndrome and pneumothorax.

Acute respiratory distress syndrome (ARDS) can occur during the treatment of several diseases and in several interventional procedures as a complication. It is a difficult situation to handle and special care should be applied to the patients. Mechanical ventilation is used for these patients and several parameters are changed constantly until compliance is achieved. However, a complication that is observed during the application of positive airway pressure is pneumothorax. In our current work we will present definition and causes of pneumothorax in the setting of intensive care unit (ICU). We will identify differences and similarities of this situation and present treatment options.

Pneumothorax in Cystic Fibrosis

Pneumothorax is recognized as a common and life-threatening complication in cystic fibrosis (CF) patients, especially in those who are infected with P. aeruginosa, B. cepacia or Aspergillus, need enteral feeding, are diagnosed as suffering from allergic bronchopulmonary aspergillosis (ABPA), developed massive hemoptysis, and their respiratory function is seriously compromised. Structural impairment and altered airflow dynamics in the lungs of CF patients are considered as the main predisposing factors, but also inhaled medications and non-invasive positive pressure ventilation (NIPPV) could increase the risk of pneumothorax. Clinical presentation could range from dramatic to very mild. Management of spontaneous pneumothorax occurring to patients with CF is essentially similar to that for non-CF patients. Therapeutic options include intercostal tube drainage, video-assisted thoracoscopic surgery (VATS), and medical or surgical pleurodesis. Pneumothorax increases both short- and long-term morbidity and mortality in CF patients and causes significant deterioration of their quality of life.

Interleukin-6 and procalcitonin as biomarkers in mortality prediction of hospitalized patients with community acquired pneumonia.

INTRODUCTION: Community acquired pneumonia (CAP) may present as life-threatening infection with uncertain progression and outcome of treatment. Primary aim of the trial was determination of the cut-off value of serum interleukin-6 (IL-6) and procalcitonin (PCT) above which, 30-day mortality in hospitalized patients with CAP, could be predicted with high sensitivity and specificity. We investigated correlation between serum levels of IL-6 and PCT at admission and available scoring systems of CAP (pneumonia severity index-PSI, modified early warning score-MEWS and (Confusion, Urea nitrogen, respiratory rate, Blood pressure, ≥65 years of age-CURB65). METHODS: This was prospective, non-randomized trial which included 101 patients with diagnosed CAP. PSI, MEWS and CURB65 were assessed on first day of hospitalization. IL-6 and PCT were also sampled on the first day of hospitalization. RESULTS: Based on ROC curve analysis (AUC ± SE = 0.934 ± 0.035; 95%CI(0.864-1.0); P = 0.000) hospitalized CAP patients with elevated IL-6 level have 93.4% higher risk level for lethal outcome. Cut-off value of 20.2 pg/ml IL-6 shows sensitivity of 84% and specificity of 87% in mortality prediction. ROC curve analysis confirmed significant role of procalcitonin as a mortality predictor in CAP patients (AUC ± SE = 0.667 ± 0.062; 95%CI(0.546-0.789); P = 0.012). Patients with elevated PCT level have 66.7% higher risk level for lethal outcome. As a predictor of mortality at the cut-off value of 2.56 ng/ml PCT shows sensitivity of 76% and specificity of 61.8%. CONCLUSIONS: Both IL-6 and PCI are significant for prediction of 30-day mortality in hospitalized patients with CAP. Serum levels of IL6 correlate with major CAP scoring systems.

Clinical Characteristics, Tumor, Node, Metastasis Status, and Mutation Rate in Domain of Epidermal Growth Factor Receptor Gene in Serbian Patients with Lung Adenocarcinoma

Objective: Mutation rate in domain of EGFR gene varies between populations of lung cancer patients. Primary aim of this study was to analyze clinical and pathological characteristics, and tumor, node, metastasis status and stage of diseases, in relation to mutation status. Methods: After histological confirmation of lung adenocarcinoma tissue obtained during bronchoscopy was consecutively sent for EGFR testing. Genomic DNA extraction was performed with the QIAamp DNA FFPE Tissue kit. Clinical data for multivariate analysis were extracted from hospital based-lung cancer registry. Results: Among 360 tested patients, there was 67.8% males and 32.2% females, aged 61 ± 9.8 years. Majority of patients were smokers (57.0%) with Eastern Cooperative Oncology Group 1 performance status (92.2%). Mutation in EGFR gene was detected in 42 (11.7%) patients. Deletion in exon 19 was detected in 24 (6.7%) patients, mutation in exon 21 in 17 (4.7%), and mutation in exon 18 in one patient (0.3%). Patients were mostly diagnosed in stage IV adenocarcinoma (74.4%). Statistically significant differences were determined in relation to smoking (p < 0.001), T descriptor (size; p = 0.019) and gender (p = 0.002). Conclusions: Mutation rate in domain of EGFR gene in investigated lung cancer population is in range with reported data in Caucasian race. Smoking, T descriptor and gender were found to be related to the EGFR status.

EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA–IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the treatment of lung cancer might offer significant number of advancements. Having in mind the significant duration of response observed in advance disease setting, there could be place for prolongation of response in adjuvant setting potentially, leading to improvement in survival. TKIs could offer less-toxic adjuvant treatment with better efficiency than chemotherapy. However, there is a chronic lack of randomized controlled trials in this field, leading to inability to draw any scientifically sound conclusion with regard to the adjuvant treatment. For now, the use of EGFR-TKIs outside clinical trial setting is not recommended. The purpose of this review is to evaluate current and available data.

Neodymium yttrium-aluminium-garnet laser resection significantly improves quality of life in patients with malignant central airway obstruction due to lung cancer.

Neodymium yttrium-aluminium-garnet (Ndu2009:u2009YAG) laser resection is one of the mostly used interventional pulmonology techniques for urgent desobstruction of malignant central airway obstruction (CAO). The major aim of this trial was to evaluate potential influence of Ndu2009:u2009YAG laser resection on overall quality of life (QoL) in patients with central lung cancer. Patients with malignant CAO scheduled for Ndu2009:u2009YAG laser resection were prospectively recruited in the trial. All patients were given European Organization for Research and Treatment, Quality of Life questionnaire (EORTC QLQ-30 v.3) before the procedure and approximately 2 weeks after the treatment. There were 37 male and 10 female patients, average age 54u2009±u200910 years. Most common tumour type was adenocarcinoma diagnosed in 51% of patients. Majority of patients were diagnosed in stage IIIB (53.2%) and stage IV (25.5%). Most common Eastern Cooperative Oncology Group performance status was 1 (72.3%). Ndu2009:u2009YAG laser resection significantly improved (P<0.0001) QoL and overall health according to EORTC QLQ-30. However, in some of the questions dealing with nausea, vomiting, diarrhoea, constipation, family life, social activities and financial situation, we did not observe statistically significant improvement. Ndu2009:u2009YAG laser resection of malignant CAO significantly improves QoL and overall health in patients with lung cancer.