BACKGROUND: Improved prediction of prognosis among lung cancer patients could facilitate better clinical management. We aimed to study the prognostic significance of circulating proteins at the time of lung cancer diagnosis, among patients with and without smoking history. METHODS: We measured 91 proteins using the Olink Immune-Oncology panel in plasma samples that were collected at diagnosis from 244 never smoking and 742 ever smoking patients with stage I-IIIA non-small cell lung cancer (NSCLC). Patients were recruited from nine centres in Russian Federation, Poland, Serbia, Czechia, and Romania, between 2007-2016 and were prospectively followed through 2020. We used multivariable Survey-weighted Cox models to assess the relationship between overall survival and levels of proteins by adjusting for smoking, age at diagnosis, sex, education, alcohol intake, histology, and stage. RESULTS: The 5-year survival rate was higher among never than ever smoking patients (63.1% vs. 46.6%, P<0.001). In age- and sex-adjusted survival analysis, 23 proteins were nominally associated with overall survival, but after adjustment for potential confounders and correcting for multiple testing, none of the proteins showed a significant association with overall survival. In stratified analysis by smoking status, IL8 [hazard ratio (HR) per standard deviation (SD): 1.40, 95% confidence interval (CI): 1.18-1.65, P=1×10-4] and hepatocyte growth factor (HGF) (HR: 1.45, 95% CI: 1.18-1.79, P=5×10-4) were associated with survival among never smokers, but no protein was found associated with survival among ever smokers. Integrating proteins into the models with clinical risk factors did not improve the predictive performance of NSCLC prognosis [C-index of 0.63 (clinical) vs. 0.64 (clinical + proteins) for ever smokers, P=0.20; C-index of 0.68 (clinical) vs. 0.72 (clinical + proteins) for never smokers, P=0.28]. CONCLUSIONS: We found limited evidence of a potential for circulating immune- and cancer-related protein markers in lung cancer prognosis. Whereas some specific proteins appear to be uniquely associated with lung cancer survival in never smokers.
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Physical activity is reduced in patients with interstitial lung disease (ILD) and physical inactivity is related to poor health outcomes. We investigated the effect of a telecoaching intervention to improve physical activity in patients with ILD. METHODS: Eighty patients with ILD were randomized into the intervention or control group. Patients in the intervention group received a 12-week telecoaching program including a step counter, a patient-tailored smartphone application, and coaching calls. Patients in the control group received usual care. Physical activity (primary outcome), physical fitness and quality of life were measured at baseline and 12 weeks later with an accelerometer, 6-min walking test and quadriceps muscle force and the King's Brief Interstitial Lung Disease questionnaire (K-BILD). RESULTS: Participation in telecoaching did not improve physical activity: between-group differences for step count: 386 ± 590 steps/day, p = .52; sedentary time: 4 ± 18 min/day, p = .81; movement intensity: 0.04 ± 0.05 m/s2, p = .45). Between-group differences for the 6-min walking test, quadriceps muscle force and K-BILD were 14 ± 10 m, p = .16; 2 ± 3% predicted, p = .61; 0.8 ± 1.7 points, p = .62 respectively. CONCLUSIONS: Twelve weeks of telecoaching did not improve physical activity, physical fitness or quality of life in patients with ILD. Future physical or behavioural interventions are needed for these patients to improve physical activity.
- MeSH
- cvičení MeSH
- intersticiální plicní nemoci * terapie MeSH
- kvalita života MeSH
- lidé MeSH
- mentoring * MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie 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.
Dlaždicobuněčné karcinomy dutiny ústní představují nejpočetnější skupinu malignit v této oblasti. V současné době existuje mnoho prognostických histopatologických faktorů, podle kterých je maxilofaciální chirurg ve spolupráci s onkologem schopen určit prognózu a následně také nastavit vhodnou terapii. V současné době se jako velmi důležitý prognostický faktor jeví vzor invaze dlaždicobuněčného karcinomu v oblasti „invazivní fronty nádoru”. Vzor invaze souvisí s metastatickým potenciálem (a s přítomností subklinických mikroskopických metastáz) a může být odpovědí na otázku, proč ani nádory v časném stadiu nereagují na standardní léčbu. To znamená, že na základě různého invazivního vzoru se dlaždicobuněčné karcinomy dutiny ústní se stejným TNM projevují různým klinickým chováním a růstovými tendencemi a různým metastatickým potenciálem.
Squamous cell carcinomas of the oral cavity represent the largest group of malignancies in this area. Currently, there are many prognostic histopathological factors, according to which the maxillofacial surgeon in collaboration with the oncologist is able to determine the prognosis and subsequently also set an appropriate therapy. Nowadays, the squamous cell carcinoma invasion pattern in the area of the “invasive tumor front” seems to be a very important prognostic factor. The invasion pattern is connected to metastatic potential (and to the presence of subclinical microscopic metastases) and may well be the answer to why even early-stage tumors do not respond to standard therapy. That is to say, based on varying invasion pattern, oral cavity squamous cell carcinomas with identical TNM manifest varying clinical behavior and growth tendencies and a varying metastatic potential.
INTRODUCTION: Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published an update on the Global Strategy for Prevention, Diagnosis and Management of COPD, introducing a new classification of chronic obstructive pulmonary disease (COPD). Our aim was to assess the prognostic value of the new GOLD classification system in comparison with the previous GOLD classification systems (GOLD stages I-IV and GOLD groups A-D) and the BODE index. METHODS: We used the data of 784 patients with COPD from the Czech Multicenter Research Database of COPD. Patient survival was analyzed with the use of Kaplan-Meier estimate and Cox model of proportional risks. ROC analysis and area under curve (AUC) were used for comparison of GOLD classifications and BODE index. The analyses were performed with the use of software R (version 4.2.0). RESULTS: We analyzed data of 782 patients with complete data on GOLD classifications. The study population comprised 72.9% of men, 89.1% current or former smokers, with a mean age of 66.6 years, a mean BMI of 27.4 and a mean FEV1 44.9% of predicted. Probability of 5-year survival differed by GOLD classification. Application of the 2023 GOLD classification showed increased risk of death in group B (HR 1.82, 95% CI 1.14-2.92; p = 0.013) and in group E (HR 2.48, 95% CI 1.54-3.99; p˂0.001). The ROC analysis showed that the overall prognostic value of the 2023 GOLD classification was similarly weak to previous A-D GOLD classification schemes (AUCs 0.557-0.576) and was lower compared to the GOLD 1-4 system (AUC 0.614) and even lower when compared to the BODE index (AUC 0.715). CONCLUSION: We concluded that the new GOLD classification system has poor prognostic properties and that specific prediction tools (eg, the BODE index) should be used for mortality risk assessment.
- MeSH
- chronická obstrukční plicní nemoc * diagnóza terapie MeSH
- hodnocení rizik MeSH
- lidé MeSH
- prognóza MeSH
- progrese nemoci MeSH
- proporcionální rizikové modely MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Although early diagnosis and surgical resection of the tumor have been shown to be the most important predictors of lung cancer survival, long-term survival for surgically-resected early-stage lung cancer remains poor. AIMS: In this prospective study we aimed to investigate the survival and prognostic factors of surgically-resected early-stage non-small cell lung cancer (NSCLC) in Central and Eastern Europe. METHODS: We recruited 2052 patients with stage I-IIIA NSCLC from 9 centers in Russia, Poland, Serbia, Czech Republic, and Romania, between 2007-2016 and followed them annually through 2020. RESULTS: During follow-up, there were 1121 deaths (including 730 cancer-specific deaths). Median survival time was 4.9 years, and the 5-year overall survival was 49.5%. In the multivariable model, mortality was increased among older individuals (HR for each 10-year increase: 1.31 [95% CI: 1.21-1.42]), males (HR:1.24 [1.04-1.49]), participants with significant weight loss (HR:1.25 [1.03-1.52]), current smokers (HR:1.30 [1.04-1.62]), alcohol drinkers (HR:1.22 [1.03-1.44]), and those with higher stage tumors (HR stage IIIA vs. I: 5.54 [4.10 - 7.48]). However, education, chronic obstructive pulmonary diseases (COPD), and tumor histology were not associated with risk of death. All baseline indicators of smoking and alcohol drinking showed a dose-dependent association with the risk of cancer-specific mortality. This included pack-years of cigarettes smoked (p-trend = 0.04), quantity of smoking (p-trend = 0.008), years of smoking (p-trend = 0.010), gram-days of alcohol drank (p-trend = 0.002), frequency of drinking (p-trend = 0.006), and years of drinking (p-trend = 0.016). CONCLUSION: This study shows that the 5-year survival rate of surgically-resected stage I-IIIA NSCLC is still around 50% in Central and Eastern Europe. In addition to non-modifiable prognostic factors, lifetime patterns of smoking and alcohol drinking affected the risk of death and disease progression in a dose-dependent manner in this population.
- MeSH
- lidé MeSH
- malobuněčný karcinom plic * patologie MeSH
- nádory plic * epidemiologie chirurgie MeSH
- nemalobuněčný karcinom plic * epidemiologie chirurgie MeSH
- prognóza MeSH
- prospektivní studie MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Polsko 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
BACKGROUND: Germline genetic variation contributes to lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated susceptibility loci involved in smoking behaviors and DNA repair genes, but further work is required to identify susceptibility variants. METHODS: To identify LC susceptibility loci, a family history-based genome-wide association by proxy (GWAx) of LC (48 843 European proxy LC patients, 195 387 controls) was combined with a previous LC GWAS (29 266 patients, 56 450 controls) by meta-analysis. Colocalization was used to explore candidate genes and overlap with existing traits at discovered susceptibility loci. Polygenic risk scores (PRS) were tested within an independent validation cohort (1 666 LC patients vs 6 664 controls) using variants selected from the LC susceptibility loci and a novel selection approach using published GWAS summary statistics. Finally, the effects of the LC PRS on somatic mutational burden were explored in patients whose tumor resections have been profiled by exome (n = 685) and genome sequencing (n = 61). Statistical tests were 2-sided. RESULTS: The GWAx-GWAS meta-analysis identified 8 novel LC loci. Colocalization implicated DNA repair genes (CHEK1), metabolic genes (CYP1A1), and smoking propensity genes (CHRNA4 and CHRNB2). PRS analysis demonstrated that these variants, as well as subgenome-wide significant variants related to expression quantitative trait loci and/or smoking propensity, assisted in LC genetic risk prediction (odds ratio = 1.37, 95% confidence interval = 1.29 to 1.45; P < .001). Patients with higher genetic PRS loads of smoking-related variants tended to have higher mutation burdens in their lung tumors. CONCLUSIONS: This study has expanded the number of LC susceptibility loci and provided insights into the molecular mechanisms by which these susceptibility variants contribute to LC development.
- MeSH
- celogenomová asociační studie * MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- mutace MeSH
- nádory plic * epidemiologie genetika patologie MeSH
- zárodečné buňky patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Introduction: The concept of phenotyping emerged, reflecting specific clinical, pulmonary and extrapulmonary features of each particular chronic obstructive pulmonary disease (COPD) case. Our aim was to analyze prognostic utility of: "Czech" COPD phenotypes and their most frequent combinations, "Spanish" phenotypes and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages + groups in relation to long-term mortality risk. Methods: Data were extracted from the Czech Multicenter Research Database (CMRD) of COPD. Kaplan-Meier (KM) estimates (at 60 months from inclusion) were used for mortality assessment. Survival rates were calculated for the six elementary "Czech" phenotypes and their most frequent and relevant combinations, "Spanish" phenotypes, GOLD grades and groups. Statistically significant differences were tested by Log Rank test. An analysis of factors underlying mortality risk (the role of confounders) has been assessed with the use of classification and regression tree (CART) analysis. Basic factors showing significant differences between deceased and living patients were entered into the CART model. This showed six different risk groups, the differences in risk were tested by a Log Rank test. Results: The cohort (n=720) was 73.1% men, with a mean age of 66.6 years and mean FEV1 44.4% pred. KM estimates showed bronchiectases/COPD overlap (HR 1.425, p=0.045), frequent exacerbator (HR 1.58, p<0.001), cachexia (HR 2.262, p<0.001) and emphysematous (HR 1.786, p=0.015) phenotypes associated with higher mortality risk. Co-presence of multiple phenotypes in a single patient had additive effect on risk; combination of emphysema, cachexia and frequent exacerbations translated into poorest prognosis (HR 3.075; p<0.001). Of the "Spanish" phenotypes, AE CB and AE non-CB were associated with greater risk of mortality (HR 1.787 and 2.001; both p=0.001). FEV1% pred., cachexia and chronic heart failure in patient history were the major underlying factors determining mortality risk in our cohort. Conclusion: Certain phenotypes ("Czech" or "Spanish") of COPD are associated with higher risk of death. Co-presence of multiple phenotypes (emphysematous plus cachectic plus frequent exacerbator) in a single individual was associated with amplified risk of mortality.
- MeSH
- chronická bronchitida * MeSH
- chronická obstrukční plicní nemoc * diagnóza MeSH
- fenotyp MeSH
- lidé MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Španělsko 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
