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Background: Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous stage due to its subgroups (IIIA-IIIC) comprising both resectable and unresectable tumors. Accurate determination of the extent of the disease is essential for excluding stage IV and choosing the optimal treatment regimen. Whole body positron emission tomography and computed tomography scan (PET/CT) is recommended as an initial staging imaging in locally advanced NSCLC. Despite international guidelines for NSCLC diagnosis and treatment, they are not always adhered to due to various reasons. Even in such a groundbreaking study, the phase 3 trial PACIFIC investigating the efficacy of durvalumab as consolidation therapy in patients with stage III NSCLC PET/CT was not mandatory. With the premise that whole body PET/CT of the trunk is essential for diagnosing stage III NSCLC, we performed a retrospective study evaluating the relationship of the use of PET/CT versus conventional staging with CT of the chest and abdomen, in terms of survival. Methods: This retrospective study of stage III NSCLC patients used the Czech lung cancer registry LUCAS, which was established in June 2018. As of the data export (up to February 9, 2022), a total of 703 patients were eligible for the analysis. Overall survival (OS) was compared using Kaplan-Meier analysis and a Cox regression model. Continuous variables were tested using the Mann-Whitney test, and categorical variables using the Pearson's Chi-square or Fisher's exact test. Results: A total of 703 patients were included in the cohort with an average age of 69 years. PET/CT was performed on 354 patients, and conventional staging using chest and abdominal CT on 349 patients. The median OS among patients with PET/CT was 20.9 months [95% confidence interval (CI): 18.1-23.7], and it was statistically significantly higher (P<0.001) than among patients without PET/CT, where the median OS was 9.0 months (95% CI: 7.3-10.6). The observed effect of PET/CT was also statistically significant when comparing individual stages (IIIA, IIIB, IIIC). The multivariate Cox model confirmed the use of PET/CT as an independent prognostic factor. The most common reason for omission of PET/CT was the local or time unavailability of the examination. Conclusions: Omission of PET/CT can mean a significant decrement in survival for the patients in stage III NSCLC, likely due to poor staging and suboptimal treatment. Routine use of PET/CT is strictly recommended for the optimal management of stage III NSCLC patients even outside the high-income countries.
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BACKGROUND/AIM: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC. PATIENTS AND METHODS: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups. RESULTS: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates. CONCLUSION: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.
Subject(s)
Antibodies, Monoclonal, Humanized , B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Antibodies, Monoclonal, Humanized/therapeutic use , Male , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Aged , Middle Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Retrospective Studies , Neoplasm Staging , Prognosis , Adult , Biomarkers, Tumor/metabolism , Treatment OutcomeABSTRACT
BACKGROUND: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a poor prognosis. The standard palliative treatment for four decades has been chemotherapy as a combination of etoposide with carboplatin or cisplatin, and in recent years, immunotherapy in addition. AIMS: To determine whether there is a difference in the efficacy of palliative chemotherapy as cisplatin or carboplatin in combination with etoposide in patients with ES-SCLC in real-world practice in the Czech Republic. METHODS: This was a retrospective analysis of a cohort of 348 patients from the LUCAS project with ES-SCLC. 79 were treated with etoposide plus cisplatin and 265 were treated with etoposide plus carboplatin. Kaplan-Meier curves and the Cox regression model were used for analysis. RESULTS: No statistically significant difference in median overall survival (mOS) or median progression free survival (mPFS) was found between groups or between patients grouped according to age and performance status (PS) in mOS. The Cox regression result was similar. CONCLUSION: This study shows that cisplatin and carboplatin do not differ in efficacy in a given indication, thus when choosing a treatment, the physician should consider the expected toxicity in a particular patient, assessing the patient's general condition and comorbidities.
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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 Ë50% 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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Pemetrexed/therapeutic use , Bevacizumab/therapeutic use , Protein Kinase Inhibitors/therapeutic use , ErbB ReceptorsABSTRACT
BACKGROUND/AIM: The aim of this study was to investigate possible association between adverse events of nivolumab therapy and the effectiveness of treatment in patients with non-small cell lung cancer (NSCLC). Focusing on serious adverse events (i.e., those of grade ≥3), we evaluated overall survival (OS), progression-free survival (PFS), as well as objective response rate (ORR) to treatment. PATIENTS AND METHODS: We retrospectively analyzed a set of patients from the TULUNG database of NSCLC treated with nivolumab in eight oncology centers. We evaluated OS data based upon this set. To reduce possible bias, we further evaluated a subgroup of patients treated at the University Hospital in Pilsen, where the occurrence of adverse events, PFS, and ORR were independently examined by two experienced physicians. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: We observed significantly greater OS, PFS, and ORR in the group of patients experiencing adverse events upon nivolumab treatment versus in those patients without such events. Although the univariable model analyzing the data set of all patients demonstrated higher OS in patients with serious adverse events, only a nonsignificant trend was observed in the Cox multivariable model. In a subgroup of patients with PFS and ORR evaluation, we did observe significant, favorable effects for patients having had serious adverse effects. CONCLUSION: Patients experiencing severe adverse events show a tendency toward better OS, PFS, and ORR compared to patients without or having only mild adverse events with nivolumab treatment.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/epidemiology , Nivolumab/adverse effects , Lung Neoplasms/drug therapy , Lung Neoplasms/epidemiology , Retrospective Studies , Progression-Free SurvivalABSTRACT
Background: Programmed death-ligand 1 (PD-L1) expression is a standard predictor in the selection of immunotherapy for locally advanced/advanced non-small cell lung cancer (NSCLC). However, comedication with corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) may influence the effectiveness of this treatment as documented in several previous studies. Due to certain molecular linkages between PD-L1 and corticosteroids or NSAIDs, we therefore addressed the question of whether there is a relationship between PD-L1 expression in NSCLC and the use of this comedication. Methods: This is a retrospective study using the Czech tumor registry LUng CAncer focuS (LUCAS), from which patient data were drawn. Independence of two categorical parameters was tested by Pearson's chi-square test. Results: In our group of 1,148 patients, we observed no significant relationship between PD-L1 expression and the use of corticosteroids or NSAIDs. Conclusions: According to our data, treatment with corticosteroids or NSAIDs during biopsy does not affect the expression of PD-L1 and it is therefore not necessary to take this treatment into account in this regard.
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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.
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AIM: This study compared the results of nivolumab treatment in patients with pulmonary adenocarcinomas based upon previous chemotherapeutic regimens. PATIENTS AND METHODS: The data source for this retrospective study was the Czech VILP registry of patients with nivolumab-treated adenocarcinomas in second and higher lines of treatment. In relation to objective response rate, progression-free interval, and overall survival, three comparisons of patient were made: A: Those treated in first line with cisplatin and pemetrexed versus carboplatin with paclitaxel or vinorelbine; B: treatment with cisplatin and pemetrexed versus carboplatin with paclitaxel/vinorelbine and bevacizumab; and C: treatment in previous lines with pemetrexed (first-line cisplatin and pemetrexed plus those treated in second line with pemetrexed) versus treatment with taxane (first-line carboplatin and paclitaxel only plus those treated with second-line docetaxel). RESULTS: We observed no differences in objective response rate or progression-free survival between patients treated with the stated chemotherapeutic regimens. We observed a trend towards better overall survival for patients treated with carboplatin plus taxanes or vinorelbine with/without bevacizumab. CONCLUSION: From our overall survival data, a chemotherapeutic regimen of carboplatin plus taxanes or vinorelbine with/without bevacizumab might be a better partner for immunotherapy than a cisplatin and pemetrexed-based one.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/pathology , Nivolumab/therapeutic use , Retrospective StudiesABSTRACT
BACKGROUND/AIM: Due to some interconnectedness at the molecular level, this study assessed the possible influence of laboratory parameters associated with systemic inflammatory environment on programmed death-ligand 1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: We assessed effects of c-reactive protein (CRP), albumin, haemoglobin, neutrophil, and lymphocyte levels on PD-L1 expression in NSCLC. Patient data were obtained retrospectively from LUCAS, the Czech registry of patients with lung carcinomas. Correlations of two continuous parameters (PD-L1 expression and laboratory parameters) were analysed by correlation coefficient. Differences in continuous parameters between two or more groups were tested by Mann-Whitney or Kruskal-Wallis tests. Independence of two categorical parameters was tested by chi-square test. RESULTS: We demonstrated no influence of the investigated laboratory parameters on PD-L1 expression in NSCLC, either in continuous or categorical division of variables. CONCLUSION: Inflammatory laboratory parameters at time of NSCLC diagnosis are unlikely to affect the determination of PD-L1 expression.
Subject(s)
B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/immunology , Aged , C-Reactive Protein/analysis , Carcinoma, Non-Small-Cell Lung/pathology , Female , Hemoglobins/analysis , Humans , Lung Neoplasms/pathology , Lymphocytes/immunology , Male , Middle Aged , Neoplasm Staging , Neutrophils/immunology , Registries , Retrospective Studies , Serum Albumin, Human/analysisABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung/epidemiology , Lung Neoplasms/epidemiology , Non-Smokers , Small Cell Lung Carcinoma/epidemiology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/surgery , Czech Republic/epidemiology , Ex-Smokers , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Male , Middle Aged , Mutation , Neoplasm Staging , Pneumonectomy , Prospective Studies , Registries , Small Cell Lung Carcinoma/diagnosis , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/therapy , Smokers , Time Factors , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutagenesis, Insertional , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Czech Republic , Disease Progression , Drug Resistance, Neoplasm , ErbB Receptors/genetics , Exons , Female , Genetic Predisposition to Disease , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Phenotype , Protein Kinase Inhibitors/therapeutic use , Registries , Retrospective Studies , Time Factors , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/administration & dosage , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Middle Aged , Neoplasm Metastasis , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Pemetrexed/administration & dosage , Pemetrexed/adverse effects , Progression-Free SurvivalABSTRACT
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's exact test. Overall (OS) and progression-free (PFS) survival were estimated by Kaplan-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.
Subject(s)
Afatinib/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Gefitinib/therapeutic use , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Czech Republic/epidemiology , Disease Progression , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Czech Republic , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Registries , Survival AnalysisABSTRACT
AIM: 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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Outcome Assessment, Health Care/methods , Adrenal Cortex Hormones/administration & dosage , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Kaplan-Meier Estimate , Male , Metformin/administration & dosage , Middle Aged , Nivolumab/administration & dosage , Outcome Assessment, Health Care/statistics & numerical data , Probiotics/administration & dosage , Proportional Hazards Models , Proton Pump Inhibitors/administration & dosage , Retrospective StudiesABSTRACT
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 2011-12 (43.2% vs. 24% for adenocarcinoma; p<0.001 and 28.7% vs. 11.8% for squamous-cell lung carcinoma; p=0.002). Assignment to cohort 2015-16 and treatment multilinearity (two or more lines in sequence) were associated with higher probability of 2-year survival (hazard ratio=0.666 and hazard ratio=0.597; p<0.001). Comparison of 2-year survivors from both cohorts showed no differences. CONCLUSION: Survival at 2 years probability in stage IIIB-IV NSCLC doubled between 2011-12 and 2015-16; advanced-stage NSCLC may be considered a chronic disease in a large proportion of patients.
Subject(s)
Adenocarcinoma of Lung/mortality , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Squamous Cell/mortality , Lung Neoplasms/mortality , Registries/statistics & numerical data , Adenocarcinoma of Lung/epidemiology , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Chronic Disease , Cohort Studies , Combined Modality Therapy , Czech Republic/epidemiology , Female , Follow-Up Studies , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Prognosis , Survival RateABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Inflammation/diagnosis , Lung Neoplasms/drug therapy , Nivolumab/therapeutic use , Adult , Aged , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , Chronic Disease , Female , Humans , Inflammation/complications , Inflammation/mortality , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival AnalysisABSTRACT
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 < 0.001). The multivariable Cox proportional hazards model revealed that thyroid transcription factor 1 expression was significantly associated with progression-free survival (hazard ratio = 1.57, p < 0.001) and also with overall survival (hazard ratio = 1.73, p < 0.001). In conclusion, the results of the conducted retrospective study suggest that the thyroid transcription factor 1 expression was independently associated with progression-free survival and overall survival in patients with advanced-stage non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , DNA-Binding Proteins/biosynthesis , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/biosynthesis , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immunohistochemistry , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Pemetrexed/administration & dosage , Prognosis , Proportional Hazards Models , Retrospective Studies , Transcription Factors , Young AdultABSTRACT
Lung cancer is the leading cause of cancer-related mortality in the world. Chemotherapy has been the mainstay of treatment for advanced non-small cell lung cancer (NSCLC) and platinum-based derivatives have been shown to improve overall survival. The aim of the present study was to investigate the DNA damage [single strand breaks (SSBs) and DNA crosslinks] and DNA repair in peripheral blood lymphocytes in patients with NSCLC treated with platinum derivatives using modified comet assay. Twenty patients in the final (4th) stage of NSCLC and 10 age-corresponding healthy controls participated in the study. Alkaline comet assay was performed according to the appropriate protocol. The DNA base excision repair (BER) activity of the controls was significantly higher compared to that of cancer patients, and the activity of DNA nucleotide excision repair (NER) was almost at the same level both in controls and patients. We observed changes in the amount of SSBs and DNA crosslinks during the course of chemotherapy. We found a significantly higher level of SSBs immediately after administration of chemotherapy. Similarly, we found the highest incidence of DNA crosslinks immediately or 1 day after chemotherapy (compared to measurement before chemotherapy). Moreover, we compared the levels of DNA repair in patients who survived chemotherapy with those in patients who died in the course of chemotherapy: the activity of BER was higher in the case of surviving patients, while the levels of NER were essentially the same. The data arising from the present study confirm the findings of other studies dealing with DNA damage and repair in cancer patients treated with chemotherapy. Moreover, our results indicated that despite the fact that cisplatin-DNA adducts are removed by the NER pathway, BER may also play a role in the clinical status of patients and their survival.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/therapeutic use , DNA Adducts/genetics , DNA Repair , Lung Neoplasms/drug therapy , Aged , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Comet Assay , DNA Breaks, Single-Stranded , Female , HeLa Cells , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Lymphocytes/metabolism , Male , Middle AgedABSTRACT
Spiritual life of the elderly patients is very important, but in practice the medical staff hardly thinks about the spiritual needs. According to foreign studies, a lively faith has a positive curative effect. The aim of our work was the evaluation of the influence of faith to the survival of illness in the elderly and the description of spiritual assessments. FICA assessment is an easy screening test which can be used for obtaining spiritual anamnesis in health care institutions.