Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF) cells and TIM3+PD1+, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells. Conversely, CD8+ T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1+ PD1+ T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8+ T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that - at odds with NSCLC - HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1+PD1+ CD8+ T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.

• MeSH
• CD8-pozitivní T-lymfocyty MeSH
• ektopické lymfoidní struktury * MeSH
• fenotyp MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory plic * MeSH
• nádory vaječníků * patologie   MeSH
• nemalobuněčný karcinom plic * MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios predict prognosis and the need for oxygen therapy in patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aims of the present study were to evaluate the changes of these biomarkers early in the course of infection, the association with the prior coronavirus disease (COVID-19) vaccination and therapeutic administration of Anti-SARS-CoV-2 monoclonal antibodies, investigation of other potential biomarkers including neuropilin, 8-hydroxy-2-deoxyguanosine and 8-hydroxyguanosine in patients hospitalized with SARS-CoV-2 infection and an assessment of these biomarkers and vitamins A, E and D in patients with post-COVID syndrome. METHODS: Urine and blood samples were obtained on the 1st to the 4th day and 4th to 7th day from 108 patients hospitalized with COVID-19. Chromatography tandem mass spectrometry methods were used to analyse neopterin, kynurenine, tryptophan, liposoluble vitamins, and DNA damage biomarkers. RESULTS: A statistically significant decrease of neopterin, kynurenine and kynurenine/tryptophan ratios was observed on after 4th to 7th day of hospitalization, and concentrations of these biomarkers were increased in patients with poor prognosis and subsequent post-COVID syndrome. The concentrations of remaining biomarker and vitamins were not associated with outcomes, although markedly decreased concentrations of vitamin A, E and D were noted. CONCLUSIONS: The concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios decrease during the course of infection SARS-CoV-2 and are associated with the post-COVID syndrome. No other prognostic biomarkers were identified.

• MeSH
• biologické markery * krev   MeSH
• COVID-19 * krev   MeSH
• dospělí MeSH
• hospitalizace MeSH
• kynurenin * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neopterin * krev   moč   MeSH
• postakutní syndrom COVID-19 MeSH
• SARS-CoV-2 * izolace a purifikace   MeSH
• senioři MeSH
• tryptofan * krev   MeSH
• vitamin A krev   MeSH
• vitamin D krev   MeSH
• vitamin E krev   MeSH
• vitaminy krev   MeSH
• zánět krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: The aim of our study was to evaluate if therapeutic success in the first-line of anticancer treatments in patients with NSCLC may predict treatment success in the following lines. METHODS: We analyzed the data of patients with NSCLC stage III/IV from the TULUNG registry separately for chemotherapy, TKIs, ALK inhibitors, and immunotherapy in the first line during the years 2011-2019. "Succesful treatment " was defined as PFS ≥ 6 months, a "good responder " was a patient with ˃50% of "successful treatment " lines. Treatment responses were analyzed separately for each drug group. Descriptive statistics, Fisher exact test, Pearson Chi-Squared test, log-rank test, and univariate/multivariate logistic regression models were used. RESULTS: The first-line TKI therapy was successful in 66.2%, while good responders accounted for 50.7% of the cohort and their rates were similar for all types of TKIs. First-line platinum-based chemotherapy was successful in 43.1% and 48.6% for combinations with pemetrexed and bevacizumab, respectively. Good responders accounted for 29.5% and 25.9%, respectively. In the group of ALK inhibitors, we observed treatment success in 52.3% of cases, while alectinib showed the highest effectiveness (up to 70%). Good responders constituted 50% of the group. In the first-line immunotherapy group, survival benefit was observed in 52.3%, and good responders constituted 52.3% of the cohort. CONCLUSION: We concluded that the treatment success in first-line therapies in patients with NSCLC may predict survival benefits in the subsequent lines, particularly in EGFR- or ALK-positive disease and immunotherapy-treated patients.

• MeSH
• bevacizumab terapeutické užití   MeSH
• erbB receptory MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé MeSH
• nádory plic * MeSH
• nemalobuněčný karcinom plic * MeSH
• pemetrexed terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Purpose: Aim was to analyze demographic and tumor characteristics, treatment, and survival of patients with lung cancer younger than 40 years of age (U40) compared to older subgroups (41-70 and >70 years). Methods: We analyzed data of young patients diagnosed and treated in 2011-2019 in five pneumo-oncology centers in Czechia. Standard descriptive statistics, chi-squared test, Fisher exact test, and Kaplan-Meier survival analysis were used. p-Values <0.05 were considered significant. These data were compared with two control subgroups (cohort 1: 41-70 years, cohort 2: >70 years). Results: We identified 66 patients U40, 61 with non-small cell lung cancer (NSCLC)-50.8% men, mean age 34.6 years, 54.1% nonsmokers, daily good performance status, and 82% in stage IV. Adenocarcinomas dominated, endothelial growth factor receptor (EGFR) positivity was less common than in older groups contrary to anaplastic lymphoma kinase (ALK) mutations. Median progression-free survival was 3.7 months (vs. 4.9 and 6.2 months; p = 0.006) and overall survival reached 11.7 months (vs. 22.3 and 27.3 months; p < 0.001). Young patients in stage IV and never-smokers had shorter survival than older patients. Conclusion: Patients with NSCLC U40 had significantly worse prognosis than older patients.

• MeSH
• anaplastická lymfomová kináza MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádory plic * MeSH
• nemalobuněčný karcinom plic * genetika   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• dendritické buňky metabolismus   MeSH
• dospělí MeSH
• imunoterapie metody   MeSH
• karboplatina farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory plic farmakoterapie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   MeSH
• paclitaxel farmakologie   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

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.

• MeSH
• časové faktory MeSH
• chemorezistence MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• exony MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• inzerční mutageneze * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory plic farmakoterapie   genetika   mortalita   patologie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   genetika   mortalita   patologie   MeSH
• progrese nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

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.

• MeSH
• analýza přežití MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic farmakoterapie   mortalita   patologie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   mortalita   patologie   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• registrace MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung syndrome, caused by long-term inhalation of noxious gases and particles, which leads to gradual airflow limitation. All health care professionals who care for COPD patients should have full access to high-quality spirometry testing, as postbronchodilator spirometry constitutes the principal method of COPD diagnosis. One out of four smokers 45 years or older presenting respiratory symptoms in primary care, have non-fully reversible airflow limitation compatible with COPD and are mostly without a known diagnosis. Approximately 50.0%-98.3% of patients are undiagnosed worldwide. The majority of undiagnosed COPD patients are isolated at home, are in nursing or senior-assisted living facilities, or are present in oncology and cardiology clinics as patients with lung cancers and coronary artery disease. At this time, the prevalence and mortality of COPD subjects is increasing, rapidly among women who are more susceptible to risk factors. Since effective management strategies are currently available for all phenotypes of COPD, correctly performed and well-interpreted postbronchodilator spirometry is still an essential component of all approaches used. Simple educational training can substantially improve physicians' knowledge relating to COPD diagnosis. Similarly, a physician inhaler education program can improve attitudes toward inhaler teaching and facilitate its implementation in routine clinical practices. Spirometry combined with inhaled technique education improves the ability of predominantly nonrespiratory physicians to correctly diagnose COPD, to adequately assess its severity, and to increase the percentage of correct COPD treatment used in a real-life setting.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH