The efficacy and safety of bevacizumab in addition to platinum-based chemotherapy for the first-line treatment of patients with advanced nonsquamous non-small-cell lung cancer: Final results of AVALANCHE, an observational cohort study.

The previous results of former clinical studies confirmed that first-line bevacizumab (BEV) in combination with chemotherapy improves clinical outcomes in patients with advanced non-squamous non-small cell lung cancer. The AVALANCHE study (ClinicalTrials.gov Identifier NCT03170284) was undertaken to assess the clinical outcomes of first-line BEV combined with standard platinum-based regimens in the Hungarian clinical practice. This observational study was conducted in 28 Hungarian sites, with patients enrolled between July 2008 and April 2011. Patients with untreated locally advanced, metastatic or recurrent lung adenocarcinoma received BEV (7.5 mg/kg, q3w) with any platinum-doublet for up to 6 cycles, and then non-progressors proceeded to receive BEV until disease progression or unacceptable toxicity. The primary endpoint was time-to-progression, and secondary endpoints included overall survival (OS), tumour control rate and safety. Patients were also analysed as two cohorts (non-progressors vs. progressors) based on whether or not they received BEV maintenance therapy following completion of first-line chemotherapy plus BEV. The study enrolled 283 patients (median age: 58.2 (18-78) years; males: 50.5%; stage: III/B: 18.4%, IV: 79.9%; adenocarcinoma/other: 95.8/4.2%; ECOG PS 0/1/2/≥3: 30.8/59.7/2.6/1.4%). Centrally located tumours were reported in 21.6%. Cisplatin/carboplatin-based regimens: 53.8/46.2%. A total of 43% of patients received BEV maintenance therapy. The median number of BEV cycles was 6. Median progression-free survival (PFS) was 7.2 months and OS was 15.2 months for the entire cohort. Longer PFS and OS were observed in patients who received BEV maintenance therapy [median OS, 26.2 vs. 10.2 months (P<0.001); median PFS, 9.2 vs. 5.8 months (P<0.001)]. Contrary to the results of previous OCS no significant difference was recorded in the different age groups or gender. Best tumour response: Complete remission/partial remission/stable disease/progressive disease/not reported were: 1.5/29.9/26.9/9.1/32.6% of all patients. In conclusion, clinical outcomes obtained in this real-life population were consistent with pivotal studies. BEV maintenance treatment was associated with a significantly longer PFS and OS.

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE).

OBJECTIVES: Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients. MATERIALS AND METHODS: MOTIVATE is an open-label, multicenter, observational trial with Tarceva(®) (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR). RESULTS AND CONCLUSION: In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD. Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%. Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.

Early diagnosis of chemotherapy-induced cardiomyopathy: a prospective tissue Doppler imaging study.

The aim of our study was to compare the applicability of the conventional echocardiography and a novel method, tissue Doppler imaging (TDI) in detection of late or subclinical cardiotoxicity following anthracycline chemotherapy in long-term follow up. Forty women (31 to 65 years) were enrolled, who had not received anthracyclines previously and had normal cardiac function. The control group consisted of 20 healthy persons of similar age range. In addition to standard echocardiographic measurements, each patient underwent specific measurements (E-septum separation, pulmonary venous flow) as well. Furthermore, the myocardial velocity of numerous segments of the mitral anulus obtained with pulsed wave TDI was also detected over a two-year-long period. Systolic left ventricular function did not change significantly either in the study or in the control group. After one year, diastolic left ventricular function was impaired in 39 patients (97.5%), and 29 (72.5%) of these showed clear changes by means of the traditional E/A ratio and TDI. However, in ten patients (25%) the diastolic dysfunction could only be detected with TDI. At the end of the study diastolic dysfunction was detected in each patient, but in 13 patients (32.5%) the relaxation disorder could be revealed only with TDI. Detectable myocardial damage occurred in the study group as a result of anthracycline therapy. Our results confirmed our assumptions that TDI is a more precise and useful examination method than the traditional ones (E/A ratio or deceleration time) to demonstrate isolated diastolic dysfunction. TDI may become a regularly and more widely used noninvasive method to detect subclinical cardiotoxicity emerging after chemotherapy.

[Tuberculosis due to multidrug resistant Mycobacterium tuberculosis Beijing genotype identified by DNA fingerprinting: the first case identified in Hungary]. / DNS ujjlenyomat-vizsgálattal azonosított Beijing genotípusú Mycobacterium tuberculosis okozta multidrog rezisztens tuberculosis: az elso Magyarországon igazolt eset.

In a 28 years old Mongolian woman in whom pulmonary tuberculosis was diagnosed a poly- and multidrug (isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin) resistant Mycobacterium tuberculosis was isolated from sputum in 2002. Since the patient was from a country with high tuberculosis incidence it was conceivable that she had been infected by a strain with primary resistance in Mongolia. In order to confirm the origin of the strain an IS6110-based DNA fingerprint test was performed on the isolate. The assay revealed that the isolated M. tuberculosis strain belonged to the so-called Beijing family which was never detected in Hungary before.

[Cardiotoxicity induced by chemotherapy: possibilities of diagnosis]. / Kemoterápia okozta szívizom-károsodás: a diagnosztika lehetoségei.

The authors give a brief summary about the process and significance of cardiotoxicity produced by chemotherapy and irradiation used for malignancy. After the introduction, those invasive and noninvasive processes are put into focus and explained in detail, which are applied in the research of the effects of cardiotoxic chemotherapy. The clinical importance of this research is the life prolongation effect of the treatment, which allows the late-appearing toxic cardiomyopathy, resulting in congestive heart failure and increasing mortality. Summarizing the last decade's progress in research, it is evident that even in the planning of chemotherapy, the cardiovascular risks have to be taken into account, because they can greatly influence the cardiac side effect of the treatment.

Co-expression of VEGF, c-Met and HGF/SF in secondary pleural tumors.

Tumor angiogenesis is influenced by a large number of angiogenic factors among which vascular endothelial growth factor (VEGF) is one of the most important cytokines. Together with hepatocyte growth factor/scatter factor (HGF/SF), c-Met receptor forms a paracrine signaling system. The aim was to study the characterization of the proteins, VEGF, c-Met and HGF/SF with expression pattern and possible co-expression in secondary pleural tumors. Biopsy specimens of the pleural region from 70 patients were chosen and analyzed using immunohistochemistry and in situ hybridization. In the investigated tumors, a marked intracytoplasmic expression, sometimes over-expression of VEGF, c-Met and HGF/SF was detected. This expression was not connected to certain tumor types or a certain histogenetic origin of the tumor. These results indicate a role of these factors in angiogenesis. The synthesis of VEGF and c-Met within the tumor cells was established by in situ hybridization. There was a significant co-expression of VEGF and c-Met/HGF. Thus, autocrine stimulation of these angio-genetically effective systems may be present here. Importantly, the autocrine mechanism between over-expressed c-Met and HGF/SF in malignant tumors, already preferred by other authors, with demonstration of the proteins in the same tumor cells, has to be assumed in the process of pleural metastatic spread. Simultaneous synthesis of these three different proteins is also possible via the plasminogen-urokinase system. VEGF is reported to increase vascular permeability, which in turn causes pleural effusions. The results presented here may be the basis for possible future palliative therapeutical strategies in malignant pleural effusions.

[Allergic airway diseases: epidemiology, diagnostic and therapeutic guidelines]. / Allergiás légúti megbetegedések: epidemiológia, diagnosztika és terápiás ajánlások.

Allergic rhinitis and bronchial asthma are characterized by an Ig-E-mediated allergic reaction of the upper and lower airways. The Hungarian and international epidemiological data show significant increase of prevalence of these diseases with a relevant increase of the cost producing a relevant socioeconomic problem. Authors present the frequent inhalative allergens, summarize diagnostical algorithms and therapy based on international therapeutic guidelines.

Impact of c-Met expression on angiogenesis in soft tissue sarcomas: correlation to microvessel-density.

PURPOSE AND METHODS: The c-Met protein is significant for oncogenesis and angiogenesis within the c-Met/HGF/SF-mediator system. The aim of this study was the analysis of c-Met immunoexpression/-synthesis and microvessel density as parameters for angiogenesis and prognosis in 115 soft tissue sarcomas. RESULTS: C-Met could be detected by immunohistochemistry in 87% of sarcomas. In all, 60.9% of cases exhibited absent or faint expression of c-Met protein, and 39.1% high expression of c-Met protein with a correlation between tumor grading and c-Met immunoexpression. Using in situ hybridization with detection of c-met-mRNA-transcripts, c-Met protein synthesis within tumor cells could be demonstrated. A statistically significant correlation between c-Met immunoexpression and tumor microvessel density was found. No prognostic value of c-Met expression and microvessel density could be detected in 56 patients with clinical follow-up ( P=0.8506 and P=0.9329 for disease-free survival). CONCLUSIONS: The results underline a role of c-Met as an oncoprotein in soft tissue sarcomas with correlation between immunoexpression and grading. The statistically significant correlation between c-Met expression and microvessel density (as a parameter of tumor angiogenesis) suggests an angiogenic function of the c-Met/HGF/SF mediator system in malignant mesenchymal tumors.

[Treatment of bronchial asthma in pregnancy]. / Az asthma bronchiale kezelése terhességben.

The prevalence of bronchial asthma, similarly to the normal population, is also increasing among pregnant women. Asthma a chronic inflammatory disease of the airways, is one of the most common medical problems that can complicate pregnancy. The cornerstone of asthma management in pregnancy is to implement such treatment strategies that can maintain normal maternal pulmonary function and prevent fetal complications. The aim of the present article is to summarize the recent publications and guidelines on the safety and efficacy issues of asthma treatment during pregnancy.