Selected articles
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Prostate cancer – cardiac complications of treatment
02/2021 Doc. MUDr. Tomáš Büchler, Ph.D.
Cardiovascular diseases are a very important cause of morbidity and mortality in patients with prostate cancer. Androgen deprivation and androgen receptor signaling therapy (ARTA) increase the risk of cardiovascular complications. Data from randomized trials and clinical practice indicate that when ARTA is used after docetaxel chemotherapy, the cardiovascular risk is even higher than when these drugs are used in the pre-treatment indication. There is an association between prostate cancer and sinus fibrillation, which is an independent predictor of mortality in these patients. In particular, the induced hypoandrogenic state and hypokalemia associated with hormonal treatment contribute to the prolongation of the QT interval in patients with prostate cancer.
ENTIRE ARTICLE
Cardiovascular diseases are a very important cause of morbidity and mortality in patients with prostate cancer. Androgen deprivation and androgen receptor signaling therapy (ARTA) increase the risk of cardiovascular complications. Data from randomized trials and clinical practice indicate that when ARTA is used after docetaxel chemotherapy, the cardiovascular risk is even higher than when these drugs are used in the pre-treatment indication. There is an association between prostate cancer and sinus fibrillation, which is an independent predictor of mortality in these patients. In particular, the induced hypoandrogenic state and hypokalemia associated with hormonal treatment contribute to the prolongation of the QT interval in patients with prostate cancer.
Positron emission tomography in testicular cancer
02/2021 Doc. MUDr. Tomáš Büchler, Ph.D.; MUDr. Aneta Rozsypalová; MUDr. Ludmila Boublíková, Ph.D.
Positron emission tomography using 18-fluorodeoxyglucose (FDG-PET) enables imaging based on the metabolic activity of the imaged tissue by evaluating the activity of glucose metabolism. There are numerous applications for the method in testicular germ cell neoplasms, especially for evaluation of residual tumor or for assessing treatment toxicity such as bleomycin-induced pneumonitis. The importance of FDG-PET is growing especially in advanced tumors and high-risk patients. Here we review indications and limitations of the method in testicular cancer.
ENTIRE ARTICLE
Positron emission tomography using 18-fluorodeoxyglucose (FDG-PET) enables imaging based on the metabolic activity of the imaged tissue by evaluating the activity of glucose metabolism. There are numerous applications for the method in testicular germ cell neoplasms, especially for evaluation of residual tumor or for assessing treatment toxicity such as bleomycin-induced pneumonitis. The importance of FDG-PET is growing especially in advanced tumors and high-risk patients. Here we review indications and limitations of the method in testicular cancer.
Prognostic significance of primary cilia in relation to selected parameters of the tumor microenvironment of clear cell renal cell carcinoma
04/2020 MUDr. Aneta Rozsypalová; MUDr. Blanka Rosová; Mgr. Alžběta Filipová, Ph.D.; MUDr. Dimitar Hadži Nikolov, Ph.D.; Mgr. Renata Chloupková; MUDr. Igor Richter, Ph.D.; MUDr. Jan Prokš; prof. MUDr. Radoslav Matěj, Ph.D.; prof. MUDr. Roman Zachoval, Ph.D.; prof. MUDr. Bohuslav Melichar, Ph.D.; doc. MUDr. Tomáš Büchler, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.
The presence of primary cilia, programmed cell death protein-1 receptor (PD-1) expression and intraepithelial CD8+ TIL (tumor infiltrating lymphocytes) expression were retrospectively evaluated in tumor tissue blocks of the resected specimens of the kidney in 104 patients with clear cell renal cell carcinoma. Median overall survival (OS) was significantly longer in patients with lower frequency of primary cilia (<0.002) than in patients with higher frequency of primary cilia (>0.002) (p<0.001). Median OS was significantly longer in patients with lower (<25%) CD8+ TIL expression than in patients with higher (>25%) CD8+ TIL expression (p=0.006). Median OS was significantly longer in patients with lower (<25%) PD-1 expression than in patients with higher (>25%) PD-1 expression (p=0.006). The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, CD8+ TIL expression and PD-1 expression in patients with clear cell renal cell carcinoma.
ENTIRE ARTICLE
The presence of primary cilia, programmed cell death protein-1 receptor (PD-1) expression and intraepithelial CD8+ TIL (tumor infiltrating lymphocytes) expression were retrospectively evaluated in tumor tissue blocks of the resected specimens of the kidney in 104 patients with clear cell renal cell carcinoma. Median overall survival (OS) was significantly longer in patients with lower frequency of primary cilia (<0.002) than in patients with higher frequency of primary cilia (>0.002) (p<0.001). Median OS was significantly longer in patients with lower (<25%) CD8+ TIL expression than in patients with higher (>25%) CD8+ TIL expression (p=0.006). Median OS was significantly longer in patients with lower (<25%) PD-1 expression than in patients with higher (>25%) PD-1 expression (p=0.006). The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, CD8+ TIL expression and PD-1 expression in patients with clear cell renal cell carcinoma.
Combination avelumab‑axitinib in metastatic renal cell carcinoma treatment
02/2020 Doc. MUDr. Tomáš Büchler, Ph.D.
Several recent clinical studies have shown the benefit of combining checkpoint inhibitors with vascular endothelial growth factor (VEGF) directed agents. JAVELIN Renal 101 was a randomised study comparing the combination of avelumab + axitinib versus sunitinib in the first line therapy for metastatic renal cell carcinoma. A total of 886 patients were enrolled. In patients with programmed cell death ligand 1 (PD-L1) expression, the median progression-free survival was 13.6 months versus 7.2 months favoring avelumab-axitinib. Based on these results, the combination of avelumab and axitinib is a new standard first-line treatment for metastatic renal cell carcinoma.
ENTIRE ARTICLE
Several recent clinical studies have shown the benefit of combining checkpoint inhibitors with vascular endothelial growth factor (VEGF) directed agents. JAVELIN Renal 101 was a randomised study comparing the combination of avelumab + axitinib versus sunitinib in the first line therapy for metastatic renal cell carcinoma. A total of 886 patients were enrolled. In patients with programmed cell death ligand 1 (PD-L1) expression, the median progression-free survival was 13.6 months versus 7.2 months favoring avelumab-axitinib. Based on these results, the combination of avelumab and axitinib is a new standard first-line treatment for metastatic renal cell carcinoma.
Does non‑specific immunotherapy have a place in modern oncology treatment?
Supplementum 01/2019 Imunoterapie
Doc. MUDr. Tomáš Büchler, Ph.D.
The aim of non-specific anti-tumour immunotherapy is to activate innate immunity and enhance adaptive immune responses without targeting specific antigens or a specific receptor. Cytokines were the major class of agents used as non-specific immunotherapy in the treatment of malignancies. Currently, non-specific immunotherapy is used as an adjunct to other types of immune therapies in oncology.
ENTIRE ARTICLE
Doc. MUDr. Tomáš Büchler, Ph.D.
The aim of non-specific anti-tumour immunotherapy is to activate innate immunity and enhance adaptive immune responses without targeting specific antigens or a specific receptor. Cytokines were the major class of agents used as non-specific immunotherapy in the treatment of malignancies. Currently, non-specific immunotherapy is used as an adjunct to other types of immune therapies in oncology.
Axitinib in the treatment of metastatic renal cell carcinoma
03/2018 Doc. MUDr. Tomáš Büchler, Ph.D.
Axitinib is an oral, selective inhibitor of vascular endothelial cell growth factor receptor (VEGFR)-1, -2, -3. It is currently registered for the treatment of metastatic renal cell carcinoma progressing on sunitinib or cytokine therapy. The AXIS phase III registration trial was the first study to directly compare two different targeted agents for metastatic renal cell carcinoma. The study also validated hypertension as a clinical biomarker of axitinib efficacy. The main benefits of axitinib include a relatively favorable toxicity profile, with relatively uncommon, predictable and usually manageable side effects.
ENTIRE ARTICLE
Axitinib is an oral, selective inhibitor of vascular endothelial cell growth factor receptor (VEGFR)-1, -2, -3. It is currently registered for the treatment of metastatic renal cell carcinoma progressing on sunitinib or cytokine therapy. The AXIS phase III registration trial was the first study to directly compare two different targeted agents for metastatic renal cell carcinoma. The study also validated hypertension as a clinical biomarker of axitinib efficacy. The main benefits of axitinib include a relatively favorable toxicity profile, with relatively uncommon, predictable and usually manageable side effects.
Combined immunotherapy in the treatment of metastatic renal cell carcinoma
05/2017 Doc. MUDr. Tomáš Büchler, Ph.D.
New findings in the pathogenesis of metastatic renal cell carcinoma (mRCC) led to the development of VEGF and mTOR pathway inhibitors over the last 20 years. Despite the prolongation of survival achieved with targeted treatment, almost all patients eventually develop resistance. Only new therapeutic strategies can result in a further substantial improvement in survival, or even achieve cure in patients with mRCC. Nivolumab, an inhibitor of the PD-1 immune checkpoint, was the first of the novel immunological agents to be successfully tested in a randomised trial. Regimens in which PD-1 or PD-L1 inhibitors are combined with other immunological drugs or tyrosine kinase inhibitors of angiogenesis are currrently being tested in preclinical and clinical studies seeking to build on the success of nivolumab.
ENTIRE ARTICLE
New findings in the pathogenesis of metastatic renal cell carcinoma (mRCC) led to the development of VEGF and mTOR pathway inhibitors over the last 20 years. Despite the prolongation of survival achieved with targeted treatment, almost all patients eventually develop resistance. Only new therapeutic strategies can result in a further substantial improvement in survival, or even achieve cure in patients with mRCC. Nivolumab, an inhibitor of the PD-1 immune checkpoint, was the first of the novel immunological agents to be successfully tested in a randomised trial. Regimens in which PD-1 or PD-L1 inhibitors are combined with other immunological drugs or tyrosine kinase inhibitors of angiogenesis are currrently being tested in preclinical and clinical studies seeking to build on the success of nivolumab.