Selected articles

01/2021 MUDr. Lucie Reifová
Bone metastases are the major cause of morbidity and sometime mortality of patients with malignant tumours. The cancer with metastases is an incurable disease, however bone metastases are well influenced by modern systemic treatment targeted to bone - bisphosphonates and denosumab - bone modifying agents (BMA). This treatment significantly improves the quality of life of patients with bone metastases and often prolongs their life. However, it is necessary to be able to handle these substances. It is very important to start treatment early, long-term treatment, cooperation with patient and prevention and management of side effects. Bisphosphonates and denosumab are also indicated in the treatment of osteoporosis, but at a much lower dose than in the treatment of bone metastases. BMA therapy related osteonecrosis of the jaw is very difficult to treat and often leads to interruption or termination of this therapy. It is extremely important to prevent this undesirable situation.

01/2021 Doc. MUDr. Jan Novotný, Ph.D.
The advances in molecular biology of gastrointestinal stromal tumors (GIST) in recent years has allowed to distinguish various tumor subtypes that respond differently to anticancer therapy. This fact together with the development of new active drugs has led to the changes in standards of care in both adjuvant and palliative settings.

01/2021 MUDr. David Belada, Ph.D.
Diffuse large B-cell lymphoma represents heterogenous group of diseases. Standard therapy of first line is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) leading to 60% probability of long-term remission. Approximately 40% of patients relapse or the disease is primary refractory. Prognosis of this patient is unfavourable. Standard treatment approach in younger relapsed DLBCL patients is salvage chemotherapy with autologous stem cell transplantation. Only few options are available in group of elderly patients with relapsed DLBCL, mostly combination of bendamustine and rituximab or gemcitabine-based regimens. There are several new treatment options, especially therapy with genetically modified T-lymphocytes (CAR-T), polatuzumab vedotin in combination with bendamustine and rituximab or bispecific antibodies. This targeted therapy to DLBCL subtypes will surely be a large part of how to successfully treat the relapsed DLBCL patients in future.

01/2021 MUDr. Lucie Reifová
Metastatic breast cancer is still an uncurable disease. The prognosis of patients with HER2-positive metastatic breast cancer before the implementation of trastuzumab was poor. This targeted treatment to receptors dramatically improved the fate of patients regarding overall survival and a decrease in difficulties. A number of effective drugs has been invented since trastuzumab was implemented as the standard treatment in the last century - pertuzumab, trastuzumab emtansin (T-DM1) and lapatinib. Despite this almost all patients will suffer progression of disease and it is necessary to develop new drugs and methods. This type of cancer metastasizes to the brain very often and new drugs seem to be effective in that situation.

01/2021 MUDr. Jaromír Richter
Prostate cancer represents a most frequent tumor among men. Despite high success rate of locoregional treatment some patients will finally relapse and develop castration resistant disease even without metastases. Apalutamid represents a new treatment modality in the treatment of this stage of prostate cancer. Apalutamid has shown statistically significant prolongation of the median of the metastasis-free survival as well as time to symptomatic progression. Apalutamid represents new possibility in the treatment of castration resistant prostate cancer without distant metastases.

01/2021 MUDr. Adam Wendrinski
Adjuvant treatment of malignant melanoma developed significantly in recent 20 years. Twenty years ago, just interferon-based therapy was available in adjuvant treatment of malignant melanoma. Recently, due to beginning of anti-programmed death-1(anti-PD-1) therapy era is this therapy significant benefit for patient suffering malignant melanoma. In 2015 CHECKMATE 238 trial was published proving efficacy of anti-PD-1 therapy in adjuvant setting. Later, another trial - KEYNOTE 054 trial was published, confirming efficacy of pembrolizumab in adjuvant setting. Recently, we can use anti-PD-1 therapy in adjuvant treatment of malignant melanoma routinely. The most significant advantage of anti-PD-1 therapy is efficacy and safety with small rate of serious adverse effects. But we should mind, even the rate of serious adverse event is low, the risk of serious complications is still present. In this reason should be used in patients which would have benefit from this treatment.

01/2021 Doc. MUDr. David Vrána, Ph.D.
Non-melanoma skin cancer represents the most frequent cancer overall. Radiotherapy and surgery are the main treatment modalities; however, the best choice depends on tumor location, patient age, comorbidities and also patienťs preference. A small portion of these patients unfortunately progress into locally advanced or metastatic form when surgery and radiotherapy are not possible. Cemiplimab represents another check-point inhibitor molecule (belongs among programmed cell death protein 1 receptor inhibitors [PD-1]) which has proven effectivity and safety in clinical trials for the treatment of locally advancedor metastatic squamous cell and basal cell carcinoma where surgery and radiotherapy are not feasible. Cemiplimab is another reasonable treatment choice for this group of patients since effectivity of conventional chemotherapy is limited.

01/2021 MUDr. Jaromír Roubec, Ph.D.; MUDr. Jaromír Richter
In the overview the authors discuss the actual approaches in the concomitant chemoradiotherapy based on the previous results and meta-analysis and discuss the new possibilities in the combined chemoradiotherapy and immunotherapy of the locoregional advanced non-small cell lung cancer.

01/2021 MUDr. Ondřej Bílek
In about a quarter of cases, non-small cell lung cancer (NSCLC) is diagnosed at the stage of locally advanced disease. The standard treatment for these patients is concomitant chemotherapy and radiotherapy. Currently, immunotherapy is an integral part of the treatment of the NSCLC treatment algorithm, especially anti-PD-1 and anti-PD-L1 check-point inhibitors. Data from the PACIFIC study demonstrated a significant benefit of consolidating immunotherapy with the anti-PD-L1 monoclonal antibody durvalumab after cessation of radiotherapy, including prolongation of overall survival. Durvalumab is currently the reference molecule in this indication. Tolerance and safety profile are favorable, early diagnosis and treatment of immune-related adverse events is necessary.

01/2021 Doc. MUDr. David Vrána, Ph.D.
Metastatic non-small cell lung cancer represents a disease with poor prognosis. Introducing tyrosine kinase inhibitors of specific mutations into daily practice improved the prognosis of a group of patients, however for majority of the patients before the era of immunotherapy the chemotherapy was the only option. Several molecules working as immunotherapeutic agents have proven their effectivity and safety in the first and second line of palliative treatment of the lung cancer. Recently the combination of nivolumab with ipilimumab was introduced into the clinical practice based on the CheckMate 227 and CheckMate 9LA trials. Combined immunotherapy with nivolumab and ipilimumab represents a new treatment option for patients with non-small cell lung cancer without specific mutations regardless of programmed cell death-ligand 1 (PD-L1) expression. Registration in the Czech Republic as well as health care reimbursement is unfortunately missing at this moment for this new combination.

01/2021 MUDr. Lenka Jakubíková, Ph.D.
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with a binding site for a family of extracellular protein epidermal growth factor ligands. The epidermal growth factor receptor is a member of the ErbB (erythroblastic leukemia viral oncogene) receptor family, which consists of a total of four members of closely related receptor tyrosine kinases: EGFR (ErbBI or HER1), ErbB2/neu (HER2), ErbB3 (HER3) and ErbB4 (HER4). Epidermal growth factor and its receptor were discovered by Stanley Cohen. In 1986, Cohen shared the Nobel Prize in Medicine with Rita Levi-Montalcini for his discovery of growth factors. The signal from EGFR can be transmitted by a number of intracellular transporters RAS-RAF-MAPK (leading to cell proliferation), or the singular pathways JAK-STAT3 or PI3K-AKT (affecting cell survival) are activated. Examination of the mutational status of this receptor plays a crucial role in deciding on the treatment of non-small cell lung cancer and is the goal of so-called biological treatment.

01/2021 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Jiří Bartoš, MBA
The systemic treatment of malignant tumors has undergone significant changes in recent years. In addition to the hormonal treatment and chemotherapy, we have new therapeutic approaches as immunotherapy or targeted treatment. Many new drugs are added in the treatment of malignant tumor every year. The treatment guidelines have been updated and changed. The aim of this review is to provide summary of new drugs in treatment of solid tumors. This article presents an overview of the two groups of agents as tyrosine kinase inhibitors and monoclonal antibodies, due to extensive issues.

06/2020 Prof. MUDr. Samuel Vokurka, Ph.D.
Denosumab, 120 mg inj. s.c., significantly contributes to delaying the development of skeletal related events (pathological fracture, spinal cord compression, a condition requiring radiotherapy or surgery to bone) and worsening pain in patients with skeletal metastatic disease. Initial dental care with prophylactic stomatology interventions and proper supplementation of calcium and vitamin D are an integral part and condition for successful treatment with denosumab.

06/2020 MUDr. Eugen Kubala
Treatment of advanced and metastatic melanoma with the BRAF V600 mutation by combination therapy with BRAF and MEK inhibitors encorafenib and binimetinib was demonstrated in the COLUMBUS study, the results of which were updated in June 2020. Encorafenib is an ATP-competitive BRAF inhibitor capable of blocking several mutated forms of BRAF kinase for 30 hours (e.g. V600E, V600D and V600K) in tumor melanoma cells against other BRAF inhibitors dabrafenib (2 hours) or vemurafenib (0.5 hours). It allows almost permanent inhibition of the mutated form of BRAF protein kinase. According to the updated results of the COLUMBUS study, the median PFS results for the combination of encorafenib + binimetinib at 14.9 months versus vemurafenib were confirmed at 7.3 months. Significant is the comparison of the two BRAF inhibitors encorafenib and vemurafenib, which indicated a higher efficacy of encorafenib versus vemurafenib median PFS 9.6 vs 7.3 months HR 0.68 (95% CI 0.52-0.88; p = 0.0038) Combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib significantly shifted the median PFS of 16.4 months and the median overall survival (OS) of 33.6 months without increasing toxicity over the established and used combinations of BRAF and MEK inhibitors used in the treatment of BRAF V600 mutant melanoma. In long-term follow-up of COMBO 450 (the combination encorafenib 450 mg and binimetinib 45 mg) vs vemurafenib (vemurafenib 960 mg) patients, 26% vs 12% of patients achieved 48-month PFS. Another primary endpoint of the COLUMBUS study was an updated outcome of OS.4-year survival was achieved in 39% of patients treated with COMBO450 combination therapy, 37% of patients treated with encorafenib 300 mg (ENCO300) monotherapy, and 26% of patients treated with vemurafenib (VEM). The updated results of the COLUMBUS study presented at ASCO (American Society of Clinical Oncology Congress) 2020 confirmed that the combination of encorafenib and binimetinib is a highly effective treatment for BRAF V600 mutant melanoma.

06/2020 MUDr. Kateřina Benková; MUDr. Zdeněk Kořístek, Ph.D.; MUDr. Petra Richterová; MUDr. Jana Mihályová; Mgr. Dagmar Zámoravcová; Ing. Karel Lach, CSc.; prof. MUDr. Roman Hájek, CSc.
Arsenic trioxide (ATO) is a drug of choice in the treatment of relapsed acute promyelocytic leukemia (APL). Guidelines for the treatment of hemodialysis dependent patients with APL do not exist. Here we describe the treatment of relapsed APL in a hemodialysis dependent patient by ATO at the dose of 10 mg three times a week after hemodialysis with frequent monitoring of laboratory values and QT interval. Molecular remission was achieved without serious adverse events. The authors further discuss the use of ATO in hemodialysis dependent patients and conclude, that ATO can be safely and effectively used in such patients under the condition of close monitoring of toxicity and adverse events; assessment of the arsenic concentration in blood is not useful for treatment management.

06/2020 MUDr. Petra Bělohlávková, Ph.D.
MDS 5q minus syndrome belongs to the category of low-risk MDS with a good prognosis. Lenalidomide treatment can effectively lead to transfusion independence and cytogenetic remission with improved the overall survival. We present a case of a patient in whom long-term remission of the disease lasts 5,5 years after discontinuation of treatment by lenalidomide.

06/2020 MUDr. Zdeněk Chovanec, Ph.D.; MUDr. Alena Berková, Ph.D.; MUDr. Vladimír Červeňák; MUDr. Tomáš Hanslík; MUDr. Adam Peštál, Ph.D.; MUDr. Vadym Prudius, Ph.D.; prof. MUDr. Ivan Čapov, CSc.
The case report presents the case of the 23-year-old, an asthmatic man, being investigated for sudden shortness of breath, non-traumatic pain in the left shoulder and back after abuse alcohol. On the X-ray there was dilated mediastinum to the left side and in CT of chest was 4 * 5 * 5 cm size infiltration of anterior mediastinum. A pulmonary examination and fine needle biopsy were performed during the first hospitalization. In differential diagnosis was from low grade myofibroblastic sarcoma to mediastinal teratoma. It was indicated surgery revision. Procedure start uncomplicated diagnostic videothoracoscopy with frozen section and continuing to sternotomy extended to anterior left thoracotomy with extirpation on the mediastinal infiltration. Definitive histology confirms mature teratoma of the thymus.

06/2020 MUDr. Jana Katolická, Ph.D.
There were limited options for patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel failure or resistance, but now the approved treatment choices for these patients have expanded to include abiraterone acetate, cabazitaxel, enzalutamide and radium-223 dichloride. Although each of these agents has been shown to convey significant survival benefit as a monotherapy, findings suggest that sequence such innovative strategies with traditional treatments may achieve additive or synergistic effects, further augmenting patient benefit.

06/2020 MUDr. Alena Berková, Ph.D.; MUDr. Petr Vlček, Ph.D.; MUDr. Ilona Krejčová; MUDr. Tamara Vystrčilová; MUDr. Vladimír Červeňák; MUDr. Zdeněk Chovanec, Ph.D.; MUDr. Sabina Svobodová
Patient, 59year-old, with ulcerative colitis was examined with intermittent abdominal pain. An abdominal ultrasound examination was performed, mucocele of the appendix was suspected, and subsequently confirmed by magnetic resonance imaging. Mucocele is a cystic dilatation of the appendix caused by luminal obstruction leading to intraluminal mucous accumulation. Mucocele is very often asymptomatic. However, due to the potential malignancy and the risk of rupture with development of pseudomyxoma of the peritoneum, mucocele should be surgically removed. Laparoscopic appendectomy was indicated. Histological examination revealed low-grade mucinous neoplasia of appendix, evaluated as pTis according to WHO 2019 and 8^th edition of the TNM classification. Surgical margins were without pathological involvement. According to the histological findings, appendectomy was a sufficient treatment mode, and the patient was further followed up in the oncology and gastroenterology outpatient department.

06/2020 MUDr. Andrea Jurečková
A case report of a patient with neuroendocrine carcinoma of the liver with hormonal symptomatology is presented. Despite the massive initial involvement of the liver and non-effective 1^st line platinum-based treatment, the patient was eventually treated with three subsequent lines of palliative chemotherapy and survived more than 2,5 years.