Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial.

BACKGROUND: Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. PATIENTS AND METHODS: Patients with relapsed/refractory disease following ≥1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m(2)/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes. RESULTS: Two hundred and two patients with progressive disease following clinical benefit from afatinib were randomized to afatinib plus paclitaxel (n = 134) or single-agent chemotherapy (n = 68). PFS (median 5.6 versus 2.8 months, hazard ratio 0.60, P = 0.003) and ORR (32.1% versus 13.2%, P = 0.005) significantly improved with afatinib plus paclitaxel. There was no difference in OS. Global health status/quality of life was maintained with afatinib plus paclitaxel over the entire treatment period. The median treatment duration was 133 and 51 days with afatinib plus paclitaxel and single-agent chemotherapy, respectively; 48.5% of patients receiving afatinib plus paclitaxel and 30.0% of patients receiving single-agent chemotherapy experienced drug-related grade 3/4 adverse events. Treatment-related adverse events were consistent with those previously reported with each agent. CONCLUSION: Afatinib plus paclitaxel improved PFS and ORR compared with single-agent chemotherapy in patients who acquired resistance to erlotinib/gefitinib and progressed on afatinib after initial benefit. LUX-Lung 5 is the first prospective trial to demonstrate the benefit of continued ErbB targeting post-progression, versus switching to single-agent chemotherapy. TRIAL REGISTRATION NUMBER: NCT01085136 (clinicaltrials.gov).

Bronchial capillary hemangioma in adults.

Two cases with capillary hemangioma of the trachea and the left upper lobe bronchus are presented. The adult patients were referred to the hospital because of hemoptysis and cough. The chest radiographs were normal in both cases. The bronchoscopic examination revealed circumscribed lesions with a capillarized surface protruding into the lumen of the trachea and the left upper lobe bronchus, respectively. The lesions were excised in toto with flexible bronchoscopic forceps. The specimens contained typical capillary hemangiomas without any signs of malignancy. Capillary hemangioma in the bronchial tree is an extremely rare benign lesion in adults. Nevertheless, it should be considered as a possible cause of hemoptysis and cough.

P53 expression in stage I squamous cell lung cancer.

P53 expression was studied using immunohistochemistry in patients (n=94) with pathologic stage I squamous cell lung cancer treated surgically between 1991-1992. The overall p53 positivity ratio was 48/94. 83 of the cases proved to be suitable for follow-up analysis carried out in November, 1995. 46/83 were p53 positive, and 25/46 patients were alive at the time of analysis. The patients who died (21/46) had a mean survival time of 17.5 months. In p53 negative cases (37/83), however, 29/37 patients were still alive at the time of follow-up, and 8/37 had died with a mean survival time of 23.1 months. A significant correlation could be found between p53 immunopositivity and reduced survival time (p=0.0125). Interestingly, out of 83 cases analyzed histologic evidence of tuberculous scar tissue was present in 9 tumors with a p53 positivity ratio of only 1/9. When flow cytometry was used to examine tumor samples from all subgroups mentioned above (n=32), no correlation was found between the p53 immunopositivity or the prognosis and the DNA content of tumor tissues. Our results suggest that in the early stage of squamous cell lung cancer the p53 positivity may be an indicator of a more aggressive tumor behavior and a shortened survival time.

[Bronchoalveolar lavage: clinical routine examination or research method?]. / Bronchoalveolaris lavage: klinikai rutinvizsgálat, vagy kutatási módszer?

Bronchoalveolar lavage is a relative simple bronchological method just slightly loading the patient. The data about recovered cellular fraction--except the detection of tumour cells and certain pathogens--rarely forms a basis for diagnosis. The determination of the activity of inflammatory processes on the basis of cellular data or immunocytological characteristics can not be considered reliable parameter to be used in the clinical practice. Bronchoalveolar lavage proved to be an optimal experimental method to study the pathomechanism of different lung diseases. Due to the high costs, examinations are worth performing only in well equipped centres.

[Postintubation stenosis of the trachea treated by silicone stent implantation]. / Postintubatiós tracheastenosis kezelése stentbeültetéssel.

22 patients with postintubation trachea stenosis were treated by silicone stent insertion. The stenosis were discovered 107 days after an average 14 days of mechanical ventilation. Mechanical and/or laser photocoagulation were followed by silicone stent implantation. In 13/22 case this combined therapy resulted a significant improvement in the ventilation. After unsuccessful intervention in 2 cases surgical resection, in 5 cases Montgomery T-tube implantation were performed. A tracheotomy was performed in one case, an other patient died due to the unresolved main airway stenosis. These results suggest that in the treatment of postintubation stenosis the silicone stent implantation is indicated as a first line therapy. 12 months after the insertion could attempt to remove the prosthesis. In the case of restenosis surgical resection or Montgomery T-tube implantation are the choice of therapy.

[Surgical excision of tracheal and bronchial tumors after endobronchial Nd-YAG laser photocoagulation]. / Trachea és hörgödaganatok sebészi eltávolítása endobronchialis Nd-YAG laser photocoagulatio után.

Sixteen patients with tracheal and bronchial (13 malignant and 3 benign) tumours were operated 4-6 weeks after Nd-YAG laser photocoagulation. The indication of the laser photocoagulation was predicted to maintain the airway patency, to aspirate the accumulated secretion due to tumour obstruction and to examine the bronchial system beyond the tumour. The endobronchial laser photocoagulation is applied in most of the cases as a palliative treatment, since its application may contribute to decrease the perioperative complications of bronchial tumours.

[Bronchoscopic evaluation of pulmonary complications following kidney transplantation]. / Vesetranszplantáción átesett betegek késöi tüdöszövödményeinek bronchoscopos vizsgálata.

The authors evaluated the efficiency of bronchoscopy in kidney transplanted patients with late pulmonary complications (mean 370 days after transplantation). The bronchoscopy was made meanly 9.5 days after recognizing pulmonary diseases, in that time 7 patients were mechanically ventilated. In 15 cases therapy guided by the cytological, histological and microbiological results has been hoped to improve outcome. This study suggest that bronchoscopy might be important in the diagnosis of the late pulmonary complications of kidney transplanted patients.

[Changes in interleukin-2 receptor levels in active and inactive pulmonary sarcoidosis]. / Serum interleukin-2 receptor szint változása aktív és inaktív tüdö sarcoidosisban.

Current concepts of the immunopathology of sarcoidosis claim a central role for activated pulmonary T-lymphocytes in the maintenance of inflammatory processes. We hypothesized that the pulmonary sarcoidosis disease activity could be monitored by the measurement of serum levels of sIL-2R. We evaluated the sIL-2R in 28 sarcoidosis patients at multiple time points before, during and after therapy and compared the results with the clinical activity of the disease. Before therapy out of 24 episodes with active disease 20 exhibited elevated levels of sIL-2R. Six out of 21 episodes with inactive disease after tappering off corticoid therapy had sIL-2R levels above the upper limit of the normal range. Disease activity under therapy as well segregated with the sIL-2R serum level. Our results demonstrate that the activity of pulmonary sarcoidosis is reflected accurately by the serum level of sIL-2R suggesting that phenomenons of T-cell activation determining the course of the disease are monitored by this approach.

[Rare association of rare diseases: Langerhans-cell histiocytosis and lymphangioleiomyomatosis in the lung]. / Ritka betegségek ritka társulása: Langerhans-sejtes histiocytosis és lymphangioleiomyomatosis együttes elöfordulása a tüdöben.

This is a case history of a 24-year-old female patient in whom two rare pulmonary diseases occurred: Langerhans cell histiocytosis and four years later lymphangioleiomyomatosis were diagnosed. Both diseases were verified by the examination of the lung tissue removed by the surgery for pneumothorax. The patient's symptoms were characterised by coughing, dyspnoe, repeated pneumothorax. The authors summarised the characteristics and treatment of these diseases. This case history is worth of reporting for its unique rareness.

[Virtual bronchoscopy: a new non-invasive diagnostic method in pulmonology]. / Virtuális bronchoszkópia: új noninvazív vizsgálati lehetóség a pulmonológiában.

Virtual reality (3 dimensional modelling of the human body) has developed as a convergence of advancing digital imaging modalities and computer graphics technologies. With this method endoscopic simulations of cavitary organs are feasible. Virtual bronchoscopy was initially described in 1993. The authors selected patient with previously detected stenosis of the trachea or the main bronchi with bronchofiberscope. They performed targeted, thin-slice helical computer tomography of the lesions. These data were transferred to a workstation and the virtual endoscopic models of the airways were generated using dedicated software. Based on cases the authors describe their preliminary experience with the method. The findings were compared with those of bronchofiberscopy. Analyzing these results and the literature the potential clinical applications of virtual bronchoscopy are discussed.

[Combination of high dose after-loading radiation therapy and percutaneous irradiation in the management of tumors of the major airways]. / Endobronchialis magas dózisú afterloading sugárkezelés és percutan besugárzás kombinációja nagylégúti daganatok kezelésében.

17 patients with malignant main airway tumours were treated with combined high dose rate afterloading and external beam irradiation. The improvement of the general conditions of the patients and that of the leading symptoms (dyspnoe, cough) were observed in all cases. First experiences corresponding with those of others suggest that this method should be integrated routinely in the management of main airway malignancies with endoluminal exophytic involvement.

[The importance of CT-guided needle biopsy in the diagnosis of thoracic diseases]. / A CT-vezérelt tübiopsziák jelentösége a mellkasi elváltozások diagnosztikájában.

In the report on 35 CT-guided fine needle transthoracic biopsies the authors show the relevance of invasive radiological methods in tumor diagnostics. The results are compared with those published in the literature. CT-guided transthoracic biopsy is of crucial importance in final diagnosis of certain thoracic diseases.

[Fiberoptic bronchoscopy in intensive care units]. / Bronchofiberoscopia az intenzív osztályokon.

The authors have retrospectively analysed 161 bedside fiberoptic bronchoscopies performed at intensive care units and demonstrate its' main indications, results and influences on the patients' condition. In 35.4% of cases immediate improvement was observed, in 31.6% the examination contributed to choose the proper treatment. Due to the safe method only one serious complication occurred because of bronchoscopy. The results justify-according to the literature-that fiberoptic bronchoscopy is an indispensable method to check airways and for diagnostical and therapeutic interventions of critically ill patients.

[Expression of macrophage markers in childhood and adult Langerhans histiocytosis (LCH)]. / Lymphoid és macrophag markerek expressziója gyermekkori és felnöttkori Langerhans-sejtes histiocytosisban (LCH).

In the diagnosis of the Langerhans cell histiocytosis several monocyte and macrophag markers have been tested in the recent years. We compared the expression of macrophage and lymphoid markers in childhood and adult type Langerhans cell histiocytosis. Ten childhood and 11 adult cases were tested using paraffin sections of biopsy samples. We have examined 6 markers: the S-100, Lysozyme, CD68 macrophag and the CD1a, CD4, HLA-DR lymphoid markers. We have found that the CD68 marker was more frequently positive than the other examined macrophag markers, and proved to be almost as reliable as the recently discovered CD1a. The most interesting result was that the expression of the markers was different in the childhood and adult type of the disease. On the basis of our experience the possibility arise that the phenotype of the childhood and adult type of the Langerhans cell histiocytosis is different.

[The role of Nd-YAG in the management of tracheobronchial stenosis]. / Neodymium-YAG laser szerepe a tracheobronchialis szükületek kezelésében.

122 patients with the main airway stenosis were treated with Nd-YAG laser phototherapy. The endobronchial laser treatment was performed either with flexible bronchoscope (64%), or with rigid instrument (36%). This method can result a final recovery of the patients with benign tumors, or inflammatory processes, at the patients with malignant tumors can be achieved an effective palliation. Taking account the generally accepted indications and contraindications of the endobronchial laser phototherapy the number of the complications can be reduced.

[The use of endoprostheses (stents) in airway stenosis]. / Endoprothesisek (stentek) alkalmazása nagylégúti szükületek esetén.

Six patients with obstruction of the trachea were treated with silicone rubber endothracheal stents implanted with flexible bronchoscope. In every case the stent caused significant clinical improvement of the ventilation. At the postintubation stenosis the stent can result a final recovery, at the malignant processes the implantation seems to be a new palliative method.

[Experience with transbronchial lung biopsy]. / Transbronchialis tüdöbiopsiával szerzett tapasztalataink.

The histological results of transbronchial lung biopsies have been analysed in 109 patients with diffuse or localised lung diseases. This diagnostic procedure is relatively safe, well tolerable and can be carried out in outpatients. In diffuse lung diseases its use can replace the open lung biopsy. The efficacy of this method depends on the availability of biplanar fluoroscopy, the quality of the excisors, the quantity and size of the biopsy material and the technique of the histological handling.