Miroslav Kašpar, Lucia Kaliská
Petr Macek, Michal Pešl, Annick Mombet, Rafael Sanchez‑Salas, Xavier Cathelineau
Alexandr Poprach, Radek Lakomý
Aneta Rozsypalová, Blanka Rosová, Alžběta Filipová, Dimitar Hadži Nikolov, Renata Chloupková, Igor Richter, Jan Prokš, Radoslav Matěj, Roman Zachoval, Bohuslav Melichar, Tomáš Büchler, Josef Dvořák
Alena Berková, Petr Vlček, Tamara Vystrčilová, Ilona Krejčová, Vladimír Červeňák, Zdeněk Chovanec, Sabina Svobodová, Ivan Čapov
Daniel Krejčí, Jana Krejčí, Petr Opálka, Petr Zůna, Norbert Pauk
Igor Richter, Josef Dvořák
Current treatment algorithms for metastatic renal cell carcinoma are based on the sequential use of drugs. It is therefore advisable to have prognostic and predictive markers available before starting treatment so that the right drug can be chosen for a particular patient with a particular type of kidney tumor. The following article discusses potential biomarkers.
For the correct treatment of renal tumors, the most accurate diagnosis is necessary, histological examination is still the most accurate, but recently the diagnosis has been improved by imaging methods both in determining the histological type and in the detection of small kidney tumors. Of the total number of kidney tumors, 20% are benign tumors, the rest are malignant tumors that require a more aggressive treatment. The most important is to distinguish between benign and malignant lesions, which is achieved by using imaging techniques with relatively high accuracy. The effort continues to distinguish between individual types of malignant tumors, where the results are not yet fully satisfactory, but individual imaging methods are being improved.
Renal tumor incidence is the highest worldwide in Czech Republic. However, the mortality here is slowly declining in recent years. Possible management in non-metastatic renal tumors includes surgical removal (partial or total nephrectomy), thermal ablation methods, surveillance, or palliative embolization. Partial nephrectomy is a preferred method for cT1 renal tumors. For those of cT2 category a minimally invasive nephrectomy is preferred. Thermal ablation is indicated following individual assessment in patients not suitable for surgical removal. In locally advanced (non-metastatic) tumors a radical nephrectomy is a method of choice. Renal mass biopsy is indicated usually in less typical cases, where a knowledge of histology may affect management choice. Tumor surveillance in patients not suitable for active treatment provides favorable disease specific shortand mid-term survival.
Cytoreductive nephrectomy and metastasectomy at the time of modern immunotherapy and targeted treatment
Cytoreductive nephrectomy followed by systemic therapy had been considered the standard of care for metastatic renal cell carcinoma patients during the cytokines era. The publication of two randomized clinical trials (CARMENA and SURTIME) has reinvigorated debate about the utility of cytoreductive nephrectomy as well as the optimal treatment sequence for patients newly diagnosed with metastatic renal cancer. The prospective clinical trials supporting cytoreductive nephrectomy were needed in immunotherapy era.
We have a long-term and good experience with multikinase inhibitors in the treatment of metastatic kidney cancer. However, modern immunotherapy by inhibitors of programmed cell death receptor 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) shows itself to be highly effective and represents next treatment alternative moving from further therapy lines to primary treatment. Both groups of these drugs are highly different, we do not have any appropriate predictors to prefer one of them and also it's toxicity profiles seem to vary but are frequent. Moreover, we do not have enough data of higher immunotherapy effectivity in this indication so we to acknowledge position of tyrosine kinase inhibitor monotherapy remains to be strong, it can be used successfuiiy in primary treatment whiie ieaving immunotherapy for further lines, as far as it is possible to switch sequencing of these groups of drugs.
Combination immunotherapy and tyrosine kinase inhibitors with immunotherapy in patients with metastatic renal cell carcinoma
The treatment of patients with mRCC is still palliative, but recently we have the results of several studies combining modern therapy, where we have seen a significant increase in time to disease progression and overall survival compared to tyrosine kinase inhibitors (TKI), as well as the numbers of overall treatment responses. We must not forget that if there is a therapeutic response to immunotherapy, it is often long-term again compared to TKI, which is particularly underlined for complete remissions. In this review below we will present the current results of three studies combining advanced immunotherapy with TKI or a combination of anti-programmed cell death protein 1 (anti-PD-1) antibody with anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA-4) antibody.
Patient with metastatic renal cell carcinoma, who was treated with tyrosine kinase inhibitor in first and second line of palliative treatment
Disseminated renal cancer is an incurable disease. The fundamental of treatment is targeted therapy with tyrosine kinase inhibitors (TKI). We present a case report of a polymorbid patient with disseminated renal clear cell carcinoma treated with two lines of TKI with a good response to treatment while a good quality of life.
Prognostic significance of primary cilia in relation to selected parameters of the tumor microenvironment of clear cell renal cell carcinoma
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.
Metastatic renal carcinoma belongs to the class of malignancies in which an immunologic response is described, observed and used as a treatment strategy. In 2019, four randomized controlled trials studying four novel immunotherapy-based regimens have been published (nivolumab with ipilimumab, atezolizumab plus bevacizumab, avelumab plus axitinib and pembrolizumab with axitinib). Some of these regimens exert a survival advantage to the appropriately selected patients. All aspects of these studies are discussed in presented paper.
The prognosis and treatment patients with myelodysplastic syndrome (MDS) depend on the conventional determination of IPSS (International Prognostic Scoring System) or its revised form IPSS-R, which divide patients into lower and higher risk groups. The risk of transformation into acute myeloid leukemia is a major problem in high-risk patients, while anemia represents the major issues for low-risk MDS patients. Improving erythropoiesis and eliminating the symptoms of anemia is a major therapeutic goal in this group of patients. Treatment by erythropoiesis-stimulating agents achieves a response rate in 50% of patients, but the median duration of response is between 15 to 18 months. Therapy by lenalidomide is indicated in patients with deletion 5 chromosome (MDS 5qsyndrome). The erythrocyte response is usually achieved in 70-80% of patients and the achievement of transfusion dependence occurs in 60-70% of patients. The newly approved drug this year is luspatercept, which is especially effective in forms of MDS with ring sideroblasts or SF3B1 mutation. Roxadustat and imetelstat are promising drugs for the treatment of anemia in low-risk MDS patients.
Gastric cancer is one of the malignancies in the Czech Republic with a declining incidence over time and is the third most common cause of death from oncological diagnosis worldwide. The most common histological subtype is adenocarcinoma. The treatment of gastric adenocarcinomas is always complex, including surgery, chemotherapy, radiotherapy and targeted therapy. Ramucirumab is a monoclonal antibody against vascular endothelial growth factor receptor 2 (VEGFR-2), which blocks the binding of a specific ligand, thereby preventing signal transduction and triggering a signaling pathway leading to tumor neoangiogenesis. Efficacy has been described in two studies - RAINBOW and REGARD.
Presacral tumors, whether benign or malignant, are rare and often asymptomatic in adults. Due to its rare incidence and specific placement, they can cause considerable difficulties in the diagnosis and the therapeutic process. The diagnosis is based on a carefully taken anamnesis, clinical findings and display methods. Treatment for presacral tumors is determined by the type of tumor, comorbidities, and age of the patient. It is necessary to take into consideration that with increasing age the size of the tumor increases, the probability of its malignancy increases, and last, but not least, the number of associated comorbidities also increase. Specifically, due to the possibility of growth and the risk of malignant reversal, presacral tumors are primarily indicated for surgical treatment, even though they are small or asymptomatic. Knowledge of the etiology, diagnosis and therapeutic procedures is important in the treatment of these tumors. Incorrect diagnosis or improper treatment can lead to adverse tumor development and significant morbidity.
Anti-HER2 therapy has long been an integral part of the treatment of patients with HER2-positive breast cancer, which has significantly improved treatment outcomes and disease prognosis. However, despite effective therapy, some patients still relapse. Therefore, other possibilities are being sought to further improve the already very effective therapy.
Despite a small percentage of these patients, the issue of patients with a positive mutation in the anaplastic lymphoma kinase (ALK) gene is highly debated. Alectinib demonstrated a statistically significant prolongation of progression-free time and an excellent therapeutic and preventive effect in the central nervous system in phase III ALEX, J-ALEX and ALUR studies.1-3 At the time of writing, alectinib is fully reimbursed in first-line treatment even after crizotinib failure.4
Metastatic colorectal cancer is still a challenge for physicians. Various modalities are used in its treatment, including chemotherapy, targeted treatment and local methods of intervention, including surgical resection, radiofrequency ablation, radiotherapy, chemoand radioembolization. There are relatively loose recommendations for systemic treatment, the involvement of other treatment modalities is defined much more freely, as well as applied in practice. A proactive approach combining the maximum use of systemic treatment, together with the agile application of local methods, can lead to a significant benefit in the overall survival of patients through generally available methods.
The Czech Republic is the world leader in the incidence of kidney cancer worldwide. Approximately 70% of renal cancers are clear cell renal, which is associated with von Hippel-Lindau (VHL) gene dysfunction. This disorder is associated with the accumulation of hypoxia-inducible factor (HIF), which results in similar metabolic events as in hypoxia. The result is the induction of vascular endothelial growth factor (VEGF) with subsequent stimulation of angiogenesis. Inhibition of angiogenesis is therefore a rational basis for therapy. According to the current reimbursement decree, sunitinib and pazopanib inhibitors are of the greatest importance in the first-line treatment of metastatic clear cell renal cell carcinoma of the vascular endothelial growth factor receptor (VEGFR). In most patients, however, the disease gradually progresses. The newer VEGFR inhibitor cabozantinib, which also acts on other signaling pathways (MET, AXL), can currently be indicated in the second line. This fact makes it possible to overcome resistance to previous VEGFR inhibitors. This is evidenced by the results of the METEOR study, where cabozantinib showed a significant prolongation of progression-free survival, overall survival and response to previous treatment with VEGFR inhibitors compared to everolimus. We started using cabozantinib in clinical practice at our workplace in 2018. Below we describe the case report of a patient treated with cabozantinib.