BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) are often elderly and have various comorbidities, including cardiovascular diseases. Although these patients have extensive co-exposure to targeted therapy and cardiovascular drugs, the impact of this co-exposure on outcomes for patients with mRCC remains unclear. OBJECTIVE: Our objective was to evaluate the association between the use of cardiovascular medication and survival of patients with mRCC. METHODS: The study included 343 consecutive patients with mRCC treated with sunitinib or pazopanib in the first line. Clinical data obtained from the Renal Cell Carcinoma Information System (RENIS) clinical registry and hospital information systems were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of common medications, including antihypertensives (i.e., β-blockers [BBs], angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and diuretics), acetylsalicylic acid (aspirin), statins, and proton pump inhibitors. RESULTS: The univariate Cox analysis evaluating the impact of the assessed comedications on patient survival revealed that only BBs were significantly associated with PFS (hazard ratio [HR] 0.533, p < 0.001) and OS (HR 0.641, p = 0.006). The median PFS and OS for users of BBs was 18.39 and 37.60 months versus 8.16 and 20.4 months for patients not using BBs (p < 0.001 and p < 0.001, respectively). The Cox multivariate analysis showed that the use of BBs was a significant factor for both PFS (HR 0.428, p = 0.001) and OS (HR 0.518, p = 0.001). CONCLUSIONS: The results of this retrospective study suggest that the use of BBs is associated with favorable outcomes for patients with mRCC treated with sunitinib or pazopanib in the first line.

• MeSH
• indazoly MeSH
• indoly farmakologie   terapeutické užití   MeSH
• karcinom z renálních buněk * farmakoterapie   MeSH
• kardiovaskulární látky * MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   MeSH
• přežití bez známek nemoci MeSH
• pyrimidiny MeSH
• pyrroly MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sulfonamidy MeSH
• sunitinib farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• indazoly MeSH
• indoly MeSH
• kardiovaskulární látky * MeSH
• pazopanib MeSH Prohlížeč
• pyrimidiny MeSH
• pyrroly MeSH
• sulfonamidy MeSH
• sunitinib MeSH

BACKGROUND: The anticancer properties of metformin have been suggested in numerous experimental studies and several retrospective clinical studies show that its use is associated with improved outcome of patients with cancer. However, limited data are available for patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. The aim of this retrospective study was to assess the impact of the metformin use on survival of mRCC patients treated with sunitinib or pazopanib. METHODS: Clinical data from 343 patients with mRCC treated with sunitinib or pazopanib in the first line were analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of metformin. RESULTS: The median PFS and OS for patients using metformin was 31.1 (95% CI 20.6-35.1) and 51.6 (95% CI 44.7-NR) months compared to 9.3 (95% CI 8.0-12.0) and 22.4 (95% CI 19.4-26.8) months for patients not using metformin (p<0.0001 and p=0.0002, respectively). Cox multivariate analysis shows that the use of metformin remains a significant factor for PFS (HR=0.55 [95% CI 0.343-0.883], p=0.013) and also for OS (HR=0.45 [95% CI 0.256-0.794], p=0.006). CONCLUSION: The present study results suggest that the use of metformin was associated with favorable outcome of mRCC patients treated with sunitinib or pazopanib.

• Klíčová slova
• metformin, outcome, pazopanib, renal cell carcinoma, sunitinib, tyrosine kinase inhibitors,
• Publikační typ
• časopisecké články MeSH

The role of cytoreductive nephrectomy (CN) in treatment of locally advanced or metastatic renal cell carcinoma (mRCC) in the era of targeted therapies (TT) is still not clearly defined. The study population consisted of 730 patients with synchronous mRCC. The RenIS (Renal carcinoma Information System) registry was used as the data source. The CN/TT cohort included patients having CN within 3 months from the mRCC diagnosis and subsequently being treated with TT, while the TT cohort included patients receiving TT upfront. Median progression-free survival from the first intervention was 6.7 months in the TT arm and 9.3 months in the CN/TT patients (p < 0.001). Median overall survival was 14.2 and 27.2 months, respectively (p < 0.001). Liver metastasis, high-grade tumor, absence of CN, non-clear cell histology, and MSKCC (Memorial Sloan-Kettering Cancer Center) poor prognosis status were associated with adverse treatment outcomes. According to the results of this retrospective study, patients who underwent CN and subsequently were treated with TT had better outcomes compared to patients treated with upfront TT. The results of the study support the use of CN in the treatment algorithm for mRCC.

• Klíčová slova
• cytoreductive nephrectomy, metastatic renal cell carcinoma, overall survival, targeted therapy,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model has been widely used for the prediction of the outcome of metastatic renal cell carcinoma (mRCC) patients treated with systemic therapies, however, data from large studies are limited. This study aimed at the evaluation of the impact of the MSKCC score on the outcomes in mRCC patients treated with first-line sunitinib, with a focus on the intermediate-risk group. METHODS: Clinical data from 2390 mRCC patients were analysed retrospectively. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were analysed according to the MSKCC risk score. RESULTS: ORR, median PFS, and OS for patients with one risk factor were 26.7%, 10.1, and 28.2 months versus 18.7%, 6.2, and 16.2 months, respectively, for those with two risk factors (ORR: p = 0.001, PFS: p < 0.001, OS: p < 0.001). ORR, median PFS, and OS were 33.0%, 17.0, and 44.7 months versus 24.1%, 9.0, and 24.1 months versus 13.4%, 4.5, and 9.5 months in the favourable-, intermediate-, and poor-risk groups, respectively (ORR: p < 0.001, PFS: p < 0.001, OS: p < 0.001). CONCLUSIONS: The results of the present retrospective study demonstrate the suitability of the MSKCC model in mRCC patients treated with first-line sunitinib and suggest different outcomes between patients with one or two risk factors.

• Klíčová slova
• Memorial Sloan–Kettering Cancer Center risk, first line, outcome, renal cell carcinoma, sunitinib,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: It is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC). METHODS: This is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test. RESULTS: The median overall survival from the start of second-line treatment was 17.0 months (95% confidence interval [CI] 14.5-19.5 months), 17.1 months (95% CI 14.5-19.8), and 15.4 months (95% CI 11.0-19.7) for second-line everolimus, sorafenib, and sunitinib, respectively. Patients receiving second-line everolimus were older at the start of second-line treatment, more likely to have metachronous disease, and less likely to be previously treated with cytokines or to continue to third-line treatment than patients treated with second-line sunitinib or sorafenib. Progression-free survival (PFS) correlated with PFS on first-line treatment only for everolimus. CONCLUSIONS: In this retrospective study, no significant differences in survival were observed between the cohorts treated with different second-line agents including everolimus, sorafenib, and sunitinib.

• Klíčová slova
• Everolimus, Pazopanib, Renal cell carcinoma, Sorafenib, Sunitinib, Therapy,
• MeSH
• cílená molekulární terapie * MeSH
• dospělí MeSH
• karcinom z renálních buněk farmakoterapie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• míra přežití MeSH
• nádory ledvin farmakoterapie   sekundární   MeSH
• následné studie MeSH
• papilární karcinom farmakoterapie   sekundární   MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• registrace statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• záchranná terapie * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Matrix-assisted laser desorption/ionization coupled with Orbitrap mass spectrometry (MALDI-Orbitrap-MS) is used for the clinical study of patients with renal cell carcinoma (RCC), as the most common type of kidney cancer. Significant changes in sulfoglycosphingolipid abundances between tumor and autologous normal kidney tissues are observed. First, sulfoglycosphingolipid species in studied RCC samples are identified using high mass accuracy full scan and tandem mass spectra. Subsequently, optimization, method validation, and statistical evaluation of MALDI-MS data for 158 tissues of 80 patients are discussed. More than 120 sulfoglycosphingolipids containing one to five hexosyl units are identified in human RCC samples based on the systematic study of their fragmentation behavior. Many of them are recorded here for the first time. Multivariate data analysis (MDA) methods, i.e., unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-DA), are used for the visualization of differences between normal and tumor samples to reveal the most up- and downregulated lipids in tumor tissues. Obtained results are closely correlated with MALDI mass spectrometry imaging (MSI) and histologic staining. Important steps of the present MALDI-Orbitrap-MS approach are also discussed, such as the selection of best matrix, correct normalization, validation for semiquantitative study, and problems with possible isobaric interferences on closed masses in full scan mass spectra. Graphical Abstract ᅟ.

• Klíčová slova
• MALDI, Orbitrap mass spectrometry, Renal cell carcinoma, Sulfatide, Sulfoglycosphingolipids,
• MeSH
• analýza hlavních komponent MeSH
• karcinom z renálních buněk chemie   diagnóza   patologie   MeSH
• ledviny chemie   patologie   MeSH
• lidé MeSH
• metoda nejmenších čtverců MeSH
• multivariační analýza MeSH
• nádorové biomarkery analýza   MeSH
• nádory ledvin chemie   diagnóza   patologie   MeSH
• senzitivita a specificita MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   MeSH
• sulfoglykosfingolipidy analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH
• Názvy látek
• nádorové biomarkery MeSH
• sulfoglykosfingolipidy MeSH

With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine. Increased urinary or serum concentrations of neopterin have been associated with poor prognosis across a spectrum of malignant disorders of different primary location. Neopterin concentration in peripheral blood as well as in the tumor microenvironment correlates with phenotypic and functional changes of lymphocytes, indicating immune dysfunction. Increased neopterin concentrations are also accompanied by increased rate of conversion of tryptophan to kynurenine. Increasing neopterin concentrations also accompany side effects of anticancer treatment and could predict subsequent complications. Although almost four decades have elapsed since the discovery of increased neopterin concentrations in cancer patients, the full potential of neopterin as a biomarker in this setting has not been so far realized.

• Klíčová slova
• Kynurenine, neopterin, tryptophan,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The aim of the present study was to examine the changes in intima-media thickness (IMT) and myocardial perfusion in association with other laboratory risk factors for atherosclerosis in patients treated with therapy that targeted vascular endothelial growth factor (VEGF). IMT, myocardial perfusion and laboratory risk factors of atherosclerosis were studied in 58 patients with metastatic colorectal carcinoma or metastatic renal cell carcinoma prior to and at 3-monthly intervals during anti-VEGF treatment. Compared with the pretreatment IMT, the results indicated that the IMT was consistently increased during therapy in the two patient groups. Patient blood pressure and concentration of troponin T increased transiently. An increase in the concentration of high-density lipoprotein cholesterol and decrease in the concentrations of C-reactive protein and homocysteine were also observed. Novel myocardial ischemia was evident in individual patients. In conclusion, anti-VEGF therapy affects the laboratory risk factors of atherosclerosis and results in an acceleration of atherosclerosis, as demonstrated by increased IMT.

• Klíčová slova
• atherosclerosis, biomarkers, intima-media thickness, single-photon emission computed tomography,
• Publikační typ
• časopisecké články MeSH

The aim of this study was to describe the characteristics and outcomes of a large cohort of patients treated with sorafenib in clinical practice and to identify predictive factors associated with prognosis. Patient data were obtained from the national Czech registry (RenIS). Data of virtually all Czech patients receiving targeted therapies are entered into this non-interventional post-registration database. Demographics and clinical data, as well as all treatment sequences and clinical outcomes, are reported in this registry. A total of 836 patients treated with sorafenib before March 2013 were included in the analysis. Median age was 63 years and 70% were men. Most patients had received prior treatment with cytokines, sunitinib or both. Sorafenib was the first-line treatment in 15% of patients. Median overall survival and progression-free survival were 21.7 months and 7.5 months, respectively. Median overall survival and progression-free survival was 26.3 and 8.3 months, respectively, in patients receiving sorafenib as first-line therapy. Cox proportional models identified several parameters associated with poor outcome including time ≤1 year from diagnosis to first-line systemic treatment, performance status ≥2, low hemoglobin, and LDH >1.5 times the upper limit of normal. Our data demonstrate that the outcomes of real-life patients are comparable to those enrolled in clinical trials. Prognostic factors identified in the present study were consistent with previously reported models.

• MeSH
• databáze faktografické MeSH
• dospělí MeSH
• fenylmočovinové sloučeniny terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z renálních buněk diagnóza   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mladý dospělý MeSH
• multivariační analýza MeSH
• nádory ledvin diagnóza   farmakoterapie   MeSH
• niacinamid analogy a deriváty   terapeutické užití   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• protinádorové látky terapeutické užití   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sorafenib 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
• Názvy látek
• fenylmočovinové sloučeniny MeSH
• niacinamid MeSH
• protinádorové látky MeSH
• sorafenib MeSH

Patients with metastatic renal cell carcinoma (mRCC) are often treated sequentially with targeted agents, although the optimal strategy is not known. A retrospective, registry-based study has been carried out to assess correlation between clinical response and progression-free survival in patients with mRCC treated sequentially with tyrosine-kinase inhibitors (TKIs) sunitinib and sorafenib. Data on 218 mRCC patients treated with sunitinib and sorafenib who completed therapy with both TKIs were obtained from a database of mRCC patients. Standard nonparametric methods were used to assess correlation between response, PFS and length of treatment on the two agents. A strong correlation between responses to first- versus second TKI was observed (p < 0.001). No significant association was noted between the duration of therapy with the two TKIs (p = 0.056), although there was a weak statistically significant correlation between progression-free survival times in the subgroup patients who discontinued treatment because of disease progression. In conclusion, the duration of response on first TKI is of limited value in selecting mRCC patients for sequential TKI therapy. There is a strong correlation between the types of tumour response on the first- versus the second TKI.

• MeSH
• dospělí MeSH
• fenylmočovinové sloučeniny aplikace a dávkování   MeSH
• indoly aplikace a dávkování   MeSH
• karcinom z renálních buněk farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin farmakoterapie   mortalita   patologie   MeSH
• niacinamid aplikace a dávkování   analogy a deriváty   MeSH
• přežití bez známek nemoci MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   MeSH
• pyrroly aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sorafenib MeSH
• sunitinib MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenylmočovinové sloučeniny MeSH
• indoly MeSH
• niacinamid MeSH
• pyrroly MeSH
• sorafenib MeSH
• sunitinib MeSH