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Background/Aim: This study aimed at contributing to a better diagnosis of lung cancer by analyzing the patient’s symptoms and their linkage to other characteristics. Patients and Methods: We analyzed the data of 3,322 patients from LUCAS (LUngCAncerfocuS) National Registry of the Czech Republic. Overall survival was assessed using the Kaplan–Meier method. Results: The most common symptoms were cough (47.5%), dyspnea (45.6%), pain (27.3%), and weight loss (25.7%). Among all patients, 16% were asymptomatic. We demonstrated the negative prognostic significance of increasing number of lung cancer symptoms, that was significant after adjustment for age, TNM stages, and performance status, and morphological types of the cancer. Conclusion: Monitoring the severity and type of symptoms in patients with lung cancer can help in the diagnostics of the disease and the estimation of prognosis.

Background/aim LUCAS is a clinical lung cancer registry (ClinicalTrials.gov identifier is NCT04228237), prospectively collecting data from newly diagnosed lung cancer patients in seven pneumooncology centers in the Czech Republic, since June 1, 2018. The aim of the study was to assess the stage of the disease at the time of diagnosis, percentage of morphological types, survival, percentage of driving mutations, eligibility for radical surgery, and percentage of patients who undergo radical surgery, in the non-smoking population in comparison with smokers and former smokers. Patients and methods The total number of patients in the registry at the time of the analysis was 2,743. Only 2,439 patients with complete records (smoking status, stage, and type of tumor) were included in this study. Results The analysis indicated that non-smokers are diagnosed at a later stage of the disease but they have a better survival rate than smokers. Fewer smokers with stage III disease who are eligible for radical surgery will undergo surgery compared to non-smokers with the same clinical stage. Driving mutations are more common in non-smokers, even after adjustment for the more frequent occurrence of adenocarcinoma in the group of non-smokers. Conclusion The data from LUCAS registry are consistent with already known facts, suggesting that the LUCAS registry is a useful clinical tool.

Background/aim Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond poorly to tyrosine kinase inhibitors (TKIs). This study analyzed real-world data to examine the prognostic and predictive value of these mutations. Patients and methods We conducted a retrospective cohort study using Czech TULUNG Registry data, with data on multiple mutation types, collected in 2011-2020. Results We analyzed 554 (95.85%) patients with EGFR exon-19 deletions or exon-21 L858R substitutions and 24 (4.15%) patients with exon-20 insertions who received first-line high-value therapies. We summarized clinical characteristics and outcomes in all patients and by cohort. The risk of progression was statistically significantly higher (86%) in the exon-20 insertion cohort compared to the cohort with other mutations. Although not statistically significant, the risk of death was 44% higher in patients with exon-20 insertions. Conclusion Advanced NSCLC patients with rare EGFR exon-20 insertions have a high risk of progression.

Background/aim Platinum-based chemotherapy with pemetrexed or paclitaxel/bevacizumab are regimens used in combination with checkpoint inhibitors in non-squamous non-small cell lung cancer (NSCLC) treatment. We conducted a real-world study to compare the outcomes of these chemotherapeutic regimens. Patients and methods We investigated 1,534 patients with advanced non-squamous NSCLC treated with platin/pemetrexed (n=1212) or platin/paclitaxel/bevacizumab (n=322) in 9 cancer centres in the Czech Republic. Results The regimen containing platin/paclitaxel/bevacizumab showed significantly better overall response rate (ORR) compared to the platin/pemetrexed [40.8% vs. 32.7% (p=0.008)] in the overall population and [55.0% vs. 38.8% (p=0.002)] in the Eastern Cooperative Oncology Group performance status 0 group. There was no significant improvement in progression-free survival (PFS) and overall survival (OS) in either of these two groups of patients. Conclusion In our real-world data analysis, patients treated with platin/paclitaxel/bevacizumab had better overall response rate (ORR), but not PFS or OS. Thus, both treatment regimens are similarly effective. Their selection should therefore be based on the potential side effects.

Background/Aim: We investigated efficacy differences for afatinib versus gefitinib in non-small-cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) mutations. Patients and Methods: We retrospectively analysed data for 343 patients with NSCLC with performance status 1 having EGFR mutations treated with gefitinib or afatinib. Overall response rate (ORR) was tested by Fisher & rsquo;s exact test. Overall (OS) and progression free (PFS) survival were estimated by Kaplan & ndash;Meier method. Results: ORR did not differ in any group or subgroup. Among all patients, we observed significantly longer PFS for those treated with afatinib vs. gefitinib (median 13.4 vs. 9.5 months, p=0.026), but only a nonsignificant trend was observed for OS. We showed nonsignificant trends of better PFS and OS using afatinib for exon 19 deletion and L858R subgroups. We observed no significant PFS differences for other EGFR mutations but a nonsignificant trend towards better OS for those treated with afatinib. Conclusion: Afatinib led to longer PFS for patients with common EGFR mutations but not for those with rare mutations.

Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.

Background Data regarding real‐life effectiveness of any treatment may improve clinical decision‐making. The aim of this study was to evaluate real‐life effectiveness of tyrosin‐kinase inhibitors, bevacizumab and pemetrexed as first‐line treatments in patients with advanced/metastatic non‐small cell lung cancer (NSCLC). Methods We analyzed data of 2157 patients of the Czech TULUNG Registry of patients with advanced/metastatic NSCLC who received modern‐era treatments between 2011 and 2018. Patients treated with gefitinib, erlotinib, afatinib, bevacizumab (+ maintenance), pemetrexed (+ maintenance) as first‐line therapy were included in the study. A systematic literature search separately identified clinical trials suitable for calculation of comparator pooled OS and PFS for each regimen. For each subgroup, basic characteristics and survival data (Kaplan‐Meier estimates) are shown. We propose the “index of real‐life effectiveness” (IRE), a ratio of real‐life OS/PFS and comparator pooled OS/PFS. Univariate and multivariate logistic regression identified factors were associated with longer OS (ie, IRE>1.1). Results Survival analysis showed median OS of 23 months for erlotinib, 29.3 months for afatinib, 19.6 months for gefitinib, 12.2 months for pemetrexed, 17.5 months for pemetrexed maintenance, 15.8 months for bevacizumab and 15.8 months for bevacizumab maintenance. Calculated IREs for OS for the regimens were: erlotinib 1.013, afatinib 1.184, gefitinib 0.736, pemetrexed 1.188, pemetrexed maintenance 1.294, bevacizumab 1.178, and bevacizumab maintenance 1.189. Multivariate regression analysis showed that these factors were associated with longer OS: lower PS for afatinib; lower PS, absence of adverse events and female sex for bevacizumab; and lower PS and female sex for pemetrexed. Conclusions This study clearly demonstrated that real‐life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems, and comparison between TULUNG data and pooled survival data from trials showed higher real‐life effectiveness for most of the studied first‐line regimens. Lower ECOG PS, younger age, female sex and adverse events were associated with longer survival in most regimens. Key points Significant findings of the study Comparison between TULUNG data and pooled survival data from trials showed higher real‐life effectiveness for most of the studied first‐line regimens; for most regimens, lower ECOG PS, younger age, female sex and adverse events were associated with longer survival. What this study adds Real‐life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems., Comparison between our TULUNG data and pooled survival data from clinical trials showed higher real‐life effectiveness for most of the studied first‐line regimens. We found that lower ECOG PS, younger age, female sex and adverse events were associated with longer survival. We demonstrated that real‐life effectiveness of certain treatments may strongly differ in various populations and health care systems.

To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Patients and Methods: A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. Results: Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. Conclusion: The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment. © 2020 International Institute of Anticancer Research. All rights reserved.

Background: Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum–etoposide) in treatment-naive patients with ES-SCLC. Methods: This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum–etoposide; durvalumab plus tremelimumab plus platinum–etoposide; or platinum–etoposide alone. All drugs were administered intravenously. Platinum–etoposide consisted of etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL per min or cisplatin 75–80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum–etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum–etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum–etoposide group versus the platinum–etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. Findings: Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum–etoposide group and 269 to the platinum–etoposide group. Durvalumab plus platinum–etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59–0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5–14·8) in the durvalumab plus platinum–etoposide group versus 10·3 months (9·3–11·2) in the platinum–etoposide group, with 34% (26·9–41·0) versus 25% (18·4–31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum–etoposide group and 166 (62%) of 266 in the platinum–etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. Interpretation: First-line durvalumab plus platinum–etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. Funding: AstraZeneca.

We investigated efficacy differences for afatinib versus gefitinib in non-small-cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) mutations.We retrospectively analysed data for 343 patients with NSCLC with performance status 1 having EGFR mutations treated with gefitinib or afatinib. Overall response rate (ORR) was tested by Fisher's exact test. Overall (OS) and progression-free (PFS) survival were estimated by Kaplan-Meier method.ORR did not differ in any group or subgroup. Among all patients, we observed significantly longer PFS for those treated with afatinib vs. gefitinib (median 13.4 vs. 9.5 months, p=0.026), but only a nonsignificant trend was observed for OS. We showed nonsignificant trends of better PFS and OS using afatinib for exon 19 deletion and L858R subgroups. We observed no significant PFS differences for other EGFR mutations but a nonsignificant trend towards better OS for those treated with afatinib.Afatinib led to longer PFS for patients with common EGFR mutations but not for those with rare mutations.

Aim: To compare survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with modern-era drugs (antifolates, antiangiogenics, tyrosine kinase and anaplastic lymphoma kinase inhibitors, immunotherapy) with treatment initiation in 2011-12 and 2015-16, respectively. Patients and Methods: Prospective data from Czech TULUNG Registry (960 patients from 2011-12 and 512 patients from 2015-16) were analyzed. Kaplan-Meier analysis was used to estimate overall survival (OS) and progression free survival (PFS); Cox proportional hazards model to assess factors associated with 2-year survival. Results: Survival at 2 years was more frequent in cohort 2015-16 compared to cohort 201112 (43.2% vs. 24% for adenocarcinoma; p

Aim To investigate potential associations between clinical and standard peripheral blood biomarkers and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Patients and methods A total of 120 patients with advanced NSCLC treated at seven comprehensive cancer care centers were analyzed in this national retrospective study. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. Results Among clinical parameters, histology was significantly associated with progression-free survival. Univariate Cox-proportional hazards model indicated prognostic and predictive role of a panel of laboratory parameters reflecting chronic inflammatory pattern (elevated neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein and decrease in hemoglobin and albumin). Higher serum calcium concentration was also associated with nivolumab treatment effect. Conclusion Tumor histology was the only clinical parameter predicting the outcome of nivolumab treatment. Among the laboratory parameters, our analysis identified a laboratory panel reflecting chronic inflammation as a potential predictive marker of nivolumab treatment.

Purpose To investigate the efficacy and safety of an active cellular immunotherapy (DCVAC/LuCa) and chemotherapy in patients with stage IV non-small cell lung cancer (NSCLC). Patients and Methods SLU01 was a multicenter, open-label, parallel-group, randomized, phase I/II trial. NSCLC patients were randomized in a ratio of 1:1:1 to receive: DCVAC/LuCa and chemotherapy (carboplatin and paclitaxel; Group A); DCVAC/LuCa, chemotherapy, pegylated interferon-α2b, and hydroxychloroquine (Group B); or chemotherapy alone (Group C). DCVAC/LuCa was administered subcutaneously every 3–6 weeks (up to 15 doses). The primary endpoint was overall survival (OS). During the study, enrollment into Group B was discontinued for strategic reasons. Results Forty-five patients were randomized to Group A, 29 patients to Group B, and 38 patients to Group C. The median OS in the modified intention-to-treat (mITT) population was 3.7 months longer in Group A than in Group C (15.5 vs. 11.8 months; p = 0.0179; hazard ratio = 0.54; 95% confidence interval: 0.32–0.91). This OS effect was consistent across subgroups of the mITT population (females, males, current smokers, former smokers, and patients with non-squamous and squamous cell histology). The most common treatment-emergent adverse events of any grade reported in Groups A, B, and C, respectively, were neutropenia (50.0%, 29.6%, and 20.6%), fatigue (40.0%, 18.5%, and 20.6%), anemia (35.0%, 44.4%, and 32.4%), paresthesia (27.5%, 25.9%, and 17.6%), and alopecia (25.0%, 29.6%, and 41.2%). Conclusion DCVAC/LuCa in combination with carboplatin and paclitaxel extended OS and was well tolerated.

Background. The concurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is generally identified as an overlap syndrome. Only limited evidence is available on the prevalence of OSA in patients with stable COPD, and essentially no data on the prevalence of OSA in patients hospitalized for COPD exacerbation. The aims of the study were to determine the ratio of concurrence of OSA in patients hospitalized for COPD exacerbation and to identify the confounders of OSA detected in COPD subjects. Methods. 101 patients were hospitalized for COPD exacerbation at the Department of Respiratory Diseases in the course of four months. Seventy-nine consecutive patients were enrolled in the study and in 35 of these subjects polygraphy was performed. Descriptive statistics, Mann-Whitney test, Kruskal-Wallis test, Spearman correlation and Fisher's test were used to summarize and evaluate results. Results. In 18 (51.4%) subjects with polygraphy examination, the apnea–hypopnea index (AHI) ≥ 5 indicated the presence of OSA. The AHI value, and thus the severity of the sleep disorder, correlated with the class of the Mallampati score, presence of snoring, apnea, coronary heart disease, diabetes mellitus in patient's history, height, body mass index, neck, waist and hip circumferences, and the value of the Epworth sleepiness scale. Conclusion. Polygraphy performed in patients hospitalized for exacerbation of COPD indicated an increased prevalence of OSA compared to the general population and stable COPD patients.

Pemetrexed is an antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of locally advanced or metastatic stage non-small cell lung cancer. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of thyroid transcription factor 1 expression with outcome of a large cohort of patients with non-squamous non-small cell lung cancer treated with pemetrexed. We retrospectively analysed clinical data of 463 patients with advanced-stage non-small cell lung cancer (IIIB or IV) treated with pemetrexed-based chemotherapy. Thyroid transcription factor 1 expression was assessed using indirect immunohistochemical detection in formalin-fixed paraffin-embedded tumour tissue at the time of diagnosis. Thyroid transcription factor 1 expression was detected in the tumour tissue from 76.0% of patients, and tumours from 24.0% of patients were thyroid transcription factor 1 negative. The median progression-free survival and overall survival for patients with thyroid transcription factor 1 positive tumours were 4.8 and 11.8 months compared to 2.8 and 8.3 months for those with thyroid transcription factor 1 negative tumours (p = 0.001 and p

OBJECTIVES: Lung cancer with the ALK rearrangement constitutes only a small fraction of patients with non-small cell lung cancer (NSCLC). However, in the era of molecular-targeted therapy, efficient patient selection is crucial for successful treatment. In this context, an effective method for EML4-ALK detection is necessary. We developed a new highly sensitive variant specific TaqMan based real time PCR assay applicable to RNA from formalin-fixed paraffin-embedded tissue (FFPE). MATERIALS AND METHODS: This assay was used to analyze the EML4-ALK gene in 96 non-selected NSCLC specimens and compared with two other methods (end-point PCR and break-apart FISH). RESULTS: EML4-ALK was detected in 33/96 (34%) specimens using variant specific real time PCR, whereas in only 23/96 (24%) using end-point PCR. All real time PCR positive samples were confirmed with direct sequencing. A total of 46 specimens were subsequently analyzed by all three detection methods. Using variant specific real time PCR we identified EML4-ALK transcript in 17/46 (37%) specimens, using end-point PCR in 13/46 (28%) specimens and positive ALK rearrangement by FISH was detected in 8/46 (17.4%) specimens. Moreover, using variant specific real time PCR, 5 specimens showed more than one EML4-ALK variant simultaneously (in 2 cases the variants 1+3a+3b, in 2 specimens the variants 1+3a and in 1 specimen the variant 1+3b). In one case of 96 EML4-ALK fusion gene and EGFR mutation were detected. All simultaneous genetic variants were confirmed using end-point PCR and direct sequencing. CONCLUSION: Our variant specific real time PCR assay is highly sensitive, fast, financially acceptable, applicable to FFPE and seems to be a valuable tool for the rapid prescreening of NSCLC patients in clinical practice, so, that most patients able to benefit from targeted therapy could be identified.

Nitrogen dioxide (NO2) is a toxic gas, a product of combustion in malfunctioning ice-resurfacing machines. NO2poisoning is rare but potentially lethal. The authors report a case of mass NO2poisoning involving 15 amateur ice hockey players in the Czech Republic. All players were treated in the Department of Respiratory Diseases at Brno University Hospital in November 2010 – three as inpatients because they developed pneumonitis. All patients were followed-up until November 2011. Complete recovery in all but one patient was achieved by December 2010. None of the 15 patients developed asthma-like disease or chronic cough. Corticosteroids appeared to be useful in treatment. Electric-powered ice-resurfacing machines are preferable in indoor ice skating arenas.

The effectiveness of continuation maintenance therapy with pemetrexed versus the watch-and-wait approach was proved by a large randomised phase III trial. We focused on continuance maintenance therapy with pemetrexed in routine clinical practice in the Czech Republic.

Background Ventilatory efficiency ( V ˙ e/ V ˙ co 2 slope [minute ventilation to carbon dioxide output slope]) has been shown to predict morbidity and mortality in lung resection candidates. Patients with increased V ˙ e/ V ˙ co 2 during exercise also exhibit an increased V ˙ e/ V ˙ co 2 ratio and a decreased end-tidal CO 2 at rest. This study hypothesized that ventilatory values at rest predict respiratory complications and death in patients undergoing thoracic surgical procedures. Methods Inclusion criteria for this retrospective, multicenter study were thoracotomy and cardiopulmonary exercise testing as part of routine preoperative assessment. Respiratory complications were assessed from the medical records (from the hospital stay or from the first 30 postoperative days). For comparisons, Student's t test or the Mann-Whitney U test was used. Logistic regression and receiver operating characteristic analyses were performed for evaluation of measurements associated with respiratory complications. Data are summarized as mean ± SD; p Results Seventy-six subjects were studied. Postoperatively, respiratory complications developed in 56 (74%) patients. Patients with postoperative respiratory complications had significantly lower resting tidal volume (0.8 ± 0.3 vs 0.9 ± 0.3L; p = 0.03), lower rest end-tidal CO 2 (28.1 ± 4.3vs 31.5 ± 4.2 mm Hg; p V ˙ e/ V ˙ co 2 ratio (45.1 ± 7.1 vs 41.0 ± 6.4; p = 0.02), and higher V ˙ e/ V ˙ co 2 slope (34.9 ± 6.4 vs 31.2 ± 4.3; p = 0.01). Logistic regression (age and sex adjusted) showed resting end-tidal CO 2 to be the best predictor of respiratory complications (odds ratio: 1.21; 95% confidence interval: 1.06 to 1.39; area under the curve: 0.77; p = 0.01). Conclusions Resting end-tidal CO 2 may identify patients at increased risk for postoperative respiratory complications of thoracic surgical procedures.

Summary Background We evaluated the performance of a galactomannan (GM) assay in bronchoalveolar lavage (BAL) fluid compared to serum samples for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological diseases. Methods Two hundred and fifty-five bronchoscopies were performed on 230 patients. Bronchial and alveolar samples from BAL fluid as well as serum samples were analyzed in the GM assay. Results Twenty-eight cases of IPA (11%) were diagnosed. The sensitivity, specificity, positive predictive value, and negative predictive value of the GM assay using a cut-off of 0.5 were 57.1%, 99.3%, 94.1%, and 92.5%, respectively, for the alveolar sample; 44.0%, 99.3%, 91.7%, and 91.4%, respectively, for the bronchial sample; and 60.7%, 100%, 100%, and 92.9%, respectively, for serum. The highest sensitivity (78.6%) with good specificity (98.6%) was obtained with a ‘triple detection' of GM in bronchial, alveolar, and serum samples. Neutropenia and antifungal therapy for only 24h increased the sensitivity, while antifungal treatment for ≥2 days decreased assay performance. Moreover, a trend towards a higher volume of aspirated fluid in GM-negative BAL ( p =0.092) was observed. Conclusions In contrast to recently published data, we found only moderate sensitivity, but high specificity and high positive predictive value of the detection of GM in BAL fluid. In addition, neutropenia, antifungal therapy, and BAL standardization affected GM assay performance.

Introduction: Gastroesophageal reflux disease (GERD) can lead to esophageal and extraesophageal symptomatology. Extraesophageal reflux (EER) is a condition where refluxate penetrate above the upper esophageal sphincter into the oral cavity, pharynx, upper and lower respiratory tract. Prolonged or repeated exposure to gastric contents leads to mucosal damage and pathological changes. Experimental studies suggested that the damage caused by reflux is not only due to acidic nature of the refluxate, but is caused also by pepsin and bile acids

Introduction: Gastroesophageal reflux disease (GERD) is a disease caused by backflow of gastric contents into the esophagus due to the failure of physiological antireflux mechanisms and can lead to esophageal and extraesophageal symptomatology. Extraesophageal reflux (EER) is a condition where refluxate penetrate above the upper esophageal sphincter in to the oral cavity, pharynx, upper and lower respiratory tract and leads to pathological changes. Monitoring of various parameters in exhaled breath condensate (EBC) in patients suffering from extraesophageal symptoms of GERD is non-invasive and simple approach to assess the gastroesophageal reflux. The aim was to compare the pH and total ionic profile of EBC with 24-hour multichannel intraluminal impedance and pH monitoring (MII-pH) and Peptest in a group of patients with acid reflux (pH

Present study evaluates results of adjuvant chemotherapy (AC) with combination of orally and intravenously applied vinorelbine together with cisplatin (CBDCA) or carboplatin (CDDP) in a multicenter prospective "SWITCH" trial. Patients (pts) after complete resection with stage IB, II and IIIA NSCLC, PS 0 - 1, age of 18 to 75 years were included. Vinorelbine 25 mg/m 2 was applied on day one intravenously and on day eight 60 mg/m 2 orally. CDDP in dose of 80 mg/m 2 or CBDCA (AUC 5) were chosen individually according to center and patient preference. Differences between results of CBDCA and CDDP in AC were evaluated in terms of tolerability, dose intensity, toxic side effects of treatment and survival. 154 pts were included, 48% pts treated with CBDCA and 52% pts treated with CDDP. In pts treated with CBDCA, there were higher relative dose delivery (94% vs 90%), mean No of cycles/patient (3.83 vs 3.76) and total No of applied cycles (283.5 vs 259.5) than in pts treated with CDDP. Most frequent Grade 3 and 4 toxicities were neutropenia (26%) and leucopenia (16%) in CDDP, trombocytopenia (4.8%) was more frequent in CBDCA treatment. Median of overall survival was 69.26 months, median of disease free interval was 41.68 months. Survival was influenced by chosen therapy, TNM classification and tumour grading. Combination of CDDP and CBDCA with oral vinorelbine in 21 day regimens appears to be a feasible and tolerable adjuvant therapy in completely resected NSCLC.This therapy gives better comfort, provides higher dose intensity and more of accomplished treatments than standard AC. Study was supported by National grant IGA MZ CR NT/13569.

Aims: This study evaluates treatment outcomes in 161 NSCLC patients from Czech Republic according to mutations located in exons 19 (Del19) and 21 (L858R). Methods: Patients were treated with gefitinib in first line between 02/2010 and 12/2014 in 10 institutions. Retrospective analyses were carried out to assess the effectiveness and safety of treatment according to mutations Del 19 and L858R. Results: Out of 161 patients, 105 had Del19, and 56 L858R mutation. Between these two groups there was not statistically significant difference in sex (p=0.727), age (p=0.204), in smoking status (p=0.354) and according to performance status (p=0.547).There was statistically borderline significant difference in adenocarcinoma proportion (p=0.045). In the group with Del19 were 96% patients with adenocarcinoma and 85% in the group with L858R. There was not statistically significant difference according to disease control (p=0.479) and according the response (p=0.052). There was not statistically significant difference in OS (p=0.390); in the group of patients with Del19 was 22.7 months (CI 95%: 17.7; 27.8), in the group with L858ROS was 16.3 months (CI 95%:10.8; 21.8), but 70% patients still alive. Without the statistical significance was the difference in PFS; in the group of patients with Del19 it was 11,0 months (CI 95%:9.1; 12.8) and in the group with L8538R it was 9.4 months (CI 95% 6.6; 12.2). SimiIar numbers of adverse effects were observed in either group (35,2% and 35.7%). Conclusion: The treatment with gefitinib was very safe and PFS and OS were satisfactory without statistically significant differences acoording Del19 and L858R mutations.

Ionic analysis of exhaled breath condensate (EBC) offers a simple, non-invasive way of monitoring nitrosative stress markers and corresponding lung status. The aim was to monitor the total ionic profile of EBC among the patients with respiratory diseases and healthy controls by capillary electrophoresis with contactless conductivity detection (CE-C4D) to reveal statistically significant differences. A miniature, portable sampler for EBC collection of single breath was constructed. The analysis of total ionic profile (anions, cations, organic acids) of EBC was accomplished in less than 5 minutes (including 1 minute sampling) from a volume of EBC sample as low as 10 µL. The EBC samples from patients with COPD (n=13), asthma (n=12), pulmonary fibrosis, PF (n=15), sarcoidosis (n=8), cystic fibrosis, CF (n=10) were compared with healthy controls (n=10). In total, 13 ions were detected in all samples. The median values of nitrite were significantly elevated (p The developed collection system and method provide a highly reproducible and fast way of collecting EBC. A fast and sensitive multianalyte determination of EBC by CE-C4D was shown for the first time in clinical setting and can have a significance for future applicability in point-of-care breath diagnostics.

Malnutrition in cancer patients may be associated with poor tolerance of chemotherapy and lower response rate after oncological treatment.Nutritional Risk Screening 2002 (NRS) adapted for oncological patients was used to assess the risk of undernutrition in a group of 188 patients with lung cancer. The risk was evaluated on a 6-point scale according to common signs of nutritional status (weight loss, body mass index, and dietary intake), tumor, and its treatment risk factors. A score of 3 or more (called "nutritional risk") means significant risk of malnutrition and poor outcome.Acceptable NRS score was found in 50.6%, and in 45.3% a score of 3-5 suggested the risk of malnutrition (nutritional risk). Unexpectedly, the toxicity of anticancer treatment was not significantly different between the subgroups (acceptable score vs nutritional risk). The rate of treatment response evaluated by imaging techniques was significantly higher in patients with an acceptable score compared to nutritional risk. Overall survival rate was significantly higher in cytostatically treated patients with lung cancer with an acceptable score.Nutritional risk screening is a significant predictor of tumor response in patients with lung cancer. Early detection of malnutrition is important to determine the prognosis of cancer patients as well as to plan effective supportive care.

Characteristics of NSCLC Patients Treated in First Line Treatment with Tyrosine Kinase Inhibitors (TKI) - Real Data from the Czech Republic.

We herein present a rare case of an EML4-ALK positive patient. A 61-year-old man was diagnosed with locoregional non-small cell lung cancer (NSCLC). No EGFR mutations were detected, and therefore the ALK rearrangement was evaluated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the reverse transcription PCR (RT-PCR) method for EML4-ALK. All methods showed a positive result and, therefore, the patient was treated with crizotinib with a good therapeutic response. However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib. This case shows great EML4-ALK heterogeneity and also that basic detection methods (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full specification seems to be important for an effective TKI indication, and sequencing ALK variants might contribute to optimized patient selection.

Non-small cell lung cancer (NSCLC) remains a highly lethal disease worldwide and research for more effective treatment strategies is ongoing. Identification of molecular prognostic and predictive markers remains under investigation with results that are often conflicting.Seventy-three patients (n= 73) with stage IB-IIIA completely resected NSCLC who were postoperatively treated with 6 cycles of paclitaxel and carboplatin from July 1998 to September 2002 took part in this study. Most stage IIIA patients subsequently received adjuvant radiotherapy. Cyclooxygenase-2 (COX-2), vascular endorhelial growth factor (VEGF), dihydrodiol dehydrogenase (DDH), receptor-binding cancer antigen expressed on SiSo cells (RCAS-1) and epidermic growth factor receptor (EGFR/HER-1) expression were assessed immunohistochemically; Heregulin family (HER1-4), VEGF and p53 were analysed by RT-PCR.Totally, 61 (84%) men and 12 (16%) women with median age of 63 years and median PS of 0 were included in the study. There were 18 stage IB, 29 stage II and 26 stage IIIA patients. Sixty-seven samples were available for immunohistohemistry. COX-2 expression was detected in 24 patients (36%), VEGF in 14 (21%), RCAS1 in 31 (46%), DDH in 15 (22%). For EGFR, only 58 samples were evaluated, 13 of which were positive (22%). Messenger RNA expression data was only available for 60 patients; VEGF was detected in 32 (53%), p53 in 30 (50%), EGFR in 35 (58%), HER2 in 4 (7%) and HER3 in 19 (32%). HER4 was not detected in any sample. In the Cox analysis for overall survival (OS) and disease-free survival (DFS), none of the factors evaluated by IHC or RT-PCR reached statistical significance.Even though the biomarkers tested are expressed in a significant proportion of lung tumors, none of them was found to be of prognostic significance in patients with NSCLC.

Results of seven years of surgical treatment of non-small cell lung cancer are presented in this paper. As neoadjuvant treatment was also performed in this group of patients, its influence on the overall outcome could be evaluated.

An international group of authors have published interim results concerning the drug safety of erlotinib, an anti-tumor drug used in treatment of patients with advanced non-small cell lung cancer within TRUST, a global open-label study of erlotinib.

Somatic tyrosine kinase (TK) domain mutations of the epidermal growth factor receptor (EGFR) gene are associated with sensitivity of non-small cell lung cancer (NSCLC) to tyrosine kinase inhibitors (TKI's), however their incidence in distinct populations is not clarified. We sequenced exons 18-21 of the EGFR TK domain from 60 Greek and Czech patients, enrolled in an adjuvant chemotherapy trial following total resection for stages I-IIIa disease. Somatic mutations were found in 9/60 patients (15.0%), several being novel. EGFR mutations were more common in Stage I tumors (p = 0.023), they were also more common in women and never smokers; however, no other significant association of clinicopathological features with mutations was found. Median TTP and OS of patients with and without mutations were 13.2 and 40 months compared to 22.9 and 43.2 months, respectively. These differences were not statistically significant. K-ras (5/60, 8%) and EGFR mutations were found to be mutually exclusive. We identified a wide spectrum of somatic EGFR TK mutations reporting a relatively high incidence (15%) in NSCLC patients of Greek and Czech origin. As ethnicity seems to be a factor for the origin of these mutations, further studies in distinct populations are warranted.

Between January 1, 1991 until December 31, 1996, 286 patients with non-small cell lung cancer were diagnosed and treated in the Department of Tuberculosis and Respiratory Diseases and Palliative Care Unit in Babice nad Svitavou, Czech Republic. There were 251 (87.8%) males and 35 (12.2%) females. The mean age of the whole group was 63.8 years. According to TNM staging (regarding the locoregional extension of the disease) as the only criterion 112 patients (39.2%) were eligible for surgical resection of primary lung tumour. However lung surgery was performed in 57 patients (19.9%) with successful radical resection in 49 cases (17.1%) out of 286. Surgical procedure was contraindicated in 55 (49.1%) out of 112 potentially resectable patients mostly because of limited cardiopulmonary function. The strategy of neoadjuvant treatment before the resection of lung tumour was used for 12 (4.2%) patients. Chemotherapy, radiotherapy or the combination of both treatment modalities was used in 121 (42.3%) patients. Symptomatic therapy alone was chosen in 104 (36.4%) cases. The performance of radical resection of lung tumours resulted in a significant influence on the overall survival in the subgroup of all patients with potentially locoregionally operable disease according to the TNM staging. The median survival period reached 17 months if radical resection was done compared to 8.5 months if radical resection was not performed. This difference is statistically significant, p = 0.05.

A variety of parameters acknowledged to be markers of proliferation activity of non-small cell lung cancer were followed up and discussed in this paper.

e18062 Background: Erlotinib is approved for NSCLC treatment in Czech Rep since 2005. This analysis was performed to analyze the profile of pts treated with erlotinib longer than 6 months. Methods: This retrospective analysis evaluates data from Czech Tarceva Registry of pts treated outside clinical trials. Survival (mOS, mPFS) was evaluated by the Kaplan-Meier method, survival comparison was performed by Log Rank test. Results: Up to October 2011, 430 out of 2121 pts with completed data in registry were treated with erlotinib for 6 months and longer. Median age 65 years, 54.4% men; 29.8% smokers, 37.9% former smokers, 32.3 % non-smokers; 77% pts ECOG PS 0-1. 74.7% stage IV pts, 21.4% stage IIIB. 43.5% adenoca, 31.9% squamous ca,11% non-specific NSCLC, 6% bronchioloalveolar ca. Erlobinib administered as 1st line treatment in 13% pts, 2L in 50.9%, 3L in 34.9%. Till October 2011, 322 pts (74.9%) finished the treatment, 108 pts (25.1%) still on erlotinib therapy. Treatment discontinued due to progression in 75% pts, death in 15%, toxicity in 3%. The entire group results (n=430): CR in 2.3%, PR in 17.7%, SD in 65.8%, PD in 2.6%. mPFS and mOS from erlotinib initiation 12.4 and 21.4 months respectively. mOS from diagnosis was 43.5 months. Statistical difference in mOS (from the erlotinib initiation) was observed between groups with PS ECOG 0-1 and PS 2-3, 22.0 vs 16.4 months (p=0.001), although there was no difference in both groups in mPFS (12.9 vs. 10.6 months). mPFS and mOS in pts with adenoca (n=187) from erlotinib initiation 14.4 and 23.7 months respectively. mOS from diagnosis was 45.6 months. mPFS and mOS in pts with squamous ca (n=137) from erlotinib initiation was 11.3 and 17.6 months respectively. mOS from diagnosis was 42.2 months. Conclusions: This analysis documented good activity of erlotinib in both adeno and squamous cell carcinoma. The difference in mOS and mPFS between both groups was statistically significant when measured from erlotinib initiation (mOS: p= 0.017, mPFS: p=0.022), however not statistically significant when measured from the date of diagnosis (p=0.361). Patients with PS 0-1 have statistically significantly greater mOS than patients with worse PS (p=0.001).

The purpose of this trial was to evaluate the activity and feasibility of CBDCA together with NVBO as first line treatment in patients with advanced NSCLC. METHODS: Patients with advanced NSCLC received NVBO 80 mg/m2 on D1 and D8 with CBDCA AUC5 on D1 every three weeks. In stage III, chemotherapy was followed by external radiotherapy. The outcomes include following: response, median overall survival (mOS) and median progression free survival (mPFS). The difference in response relative to baseline characteristics was determined using Pearson Chi-square test. Differences in OS and PFS relative to baseline characteristics were evaluated for significance using Log-rank test. RESULTS: 259 patients were treated: 209 men (80,7%) and 50 women (19,3%), median age 65 years. ECOG performance status at inclusion was PS 0 in 47 (18,2% patients, PS 1 in 185 (71,7%) and PS 2 in 26 (10,1%) patients. Most patients had stage IIIB 97 (37,5%) and stage IV NSCLC 130 (50,2%), only 32 (12,4%) were stage IIIA . Adenocarcinoma was confirmed in 52 patients (20,1%), squamous-cell carcinoma in 152 (58,7%), large-cell carcinoma in 8 (3,1%) and other in 47 (18,4%). Complete response was confirmed in 1 (0,4%) patient, partial response in 121 (46,7%), stable disease in 58 (22,4%), 79 (30,5%) patients progressed. The regimen was well tolerated. Median cycles was 4, the dosage of NVBO was without changes in 159 (61%) patients, the dosage of NVBO was reduced in 12 (4,7%) and escalated in 64 (24,8%). In 23 (8,9%) of patients was the dosage of NVBO reduced after escalation. Major toxicities (Grade 3-4) were neutropenia in 69 (26,9%), leucopenia in 51 (19,8%), anemia in 7 (2,7%), and thrombocytopenia in 6 (2,3%) patients. Febrile neutropenia was observed in 17 (6,6%) patients. Gastrointestinal toxicity grade 3-4 was observed in 47 (18,4%) patients. The estimated mOS was 13,8 moths. and the estimated mPFS was 9,4 months by median follow-up 8,5 months. The differences between groups of pts according to PS (0+1 vs. 2) were statistically significant (p < 0,001) better for patiens with PS 0+1. CONCLUSIONS: In this group of 259 non-selected patients with advanced NSCLC was the treatment with full NVBO and CBDCA in first line more convenient and well tolerated with evidence of high antitumour activity. This combination was active in all groups patients according histology.