Selected articles

01/2019 Mgr. Zuzana Šporiková; MUDr. Vladimíra Koudeláková; MUDr. Marián Hajdúch, Ph.D.
Current oncology is mainly focused towards the search of novel prognostic and predictive biomarkers, new therapeutics and therapeutic strategies leading to the development of personalized medicine. Current diagnostics of breast cancer uses the estrogen, progesterone and HER2 expression for prediction of endocrine and anti-HER2 therapy response and prognosis determining. Recently, BRCA1 and BRCA2 mutation testing for prediction of response to PARP inhibitors was introduced into clinical practice. In last decade, a number of biomarkers have been identified, however, they must be clinically validated by independent prospective study. The properly validated biomarkers have huge significance in current personalized oncology.

01/2019 MUDr. Radmila Lemstrová, Ph.D.; MUDr. Martina Spisarová
Immunotherapy and targeted therapy have radically changed prognosis of patients with advanced malignant melanoma. Nowadays up to 40 % of patients reach long term remission of disease. Around 50 % of malignant melanomas harbor BRAF V600 mutation. Combination of BRAF and MEK inhibitors in the treatment of BRAF V600 mutated melanomas has led to increased efficacy with acceptable toxicity of the treatment. Unfortunately, the secondary resistance develops to combination therapy too. New strategies to overcome the secondary resistance are subject of many clinical trials as well as appropriate sequence of treatment of BRAF V600 mutated melanoma. The results of ongoing clinical trials will hopefully lead to further optimizing of the treatment. This review summarizes the combination of vemurafenib and cobimetinib in the treatment of advanced BRAF V600 mutated malignant melanoma.

01/2019 MUDr. Jana Katolická, Ph.D.; MUDr. Jiří Vaníček, Ph.D.
Cabozantinib is a novel multitargeted tyrosine kinase inhibitor that improved progression-free survival and overall survival in patients with advanced renal cell carcinoma after one or more prior vascular endothelial growth factor receptor targeted therapies. The safety profile of cabozantinib is acceptable.

01/2019 MUDr. Jana Katolická, Ph.D.
Metastatic urothelial carcinoma is a chemotherapy sensitive disease and platinum-based chemotherapy is the standard primary treatment. Vinflunine is a third-generation antimicrotubuline agent of the vinca alkaloid class. In a randomized study a prolongation of overall survival was shown in eligible patients. The data from European studies represents the excellent experience with vinflunine in patients in daily clinical practice.

01/2019 MUDr. Jana Krejčí; MUDr. Daniel Krejčí; MUDr. Petr Opálka, CSc., MBA
Lung cancer is one of the most common and most serious diseases. At present, we have different treatment approaches for non-small cell lung cancer not only according to histology but also on the basis of molecular genetic properties. Different treatment strategies exist according to molecularly defined markers in non-small-cell lung cancer. Molecular testing for at least epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) should be performed in all patients before therapy. Crizotinib is a tyrosine kinase inhibitor targeting ALK translocation. Based on Profile 1007 and Profile 1014 trial, it has become the basis of treatment for patients with ALK translocation. Our case report is a demonstration of the good performance of crizotinib in the second line of treatment of patients with lung adenocarcinoma.

01/2019 MUDr. Stanislav Hloušek; doc. MUDr. Milada Zemanová, Ph.D.; prof. MUDr. David Feltl, Ph.D., MBA
Case presents a patient with non-small cell lung cancer at clinical stage IA3, who refused surgical removal of the tumor. Instead of surgery, the patient was offered a variant with stereotactic radiotherapy that the patient agreed to and underwent without complications. Partial remission was observed in subsequent CT scans. One year after the therapy the patient is without signs of progression or generalization. The case therefore presents an alternative to standard surgical treatment for patients for whom, for various reasons, this modality is not indicated or preferred.

01/2019 MUDr. Petra Zemanová
The author presents a case of a 70-year-old man, a current smoker on the treatment for COPD and internal comorbidities, who underwent the diagnostic procedures for a tumor located in the apex of the right upper pulmonary lobe. After the complete pulmonary function tests the right upper lobectomy was indicated and subsequently performed. Due to the clinical stage IIB the adjuvant chemotherapy was administered. The discussion engages in the pulmonary function tests before the lung resection.

01/2019 Doc. MUDr. Milada Zemanová, Ph.D.
In the treatment of pulmonary cancer, radiotherapy is a basic method that has demonstrated therapeutic benefit in both radical and palliative indications in up to 76% of all patients. In the Czech Republic, the proportion of patients with bronchogenic carcinoma treated with radiotherapy does not exceed 25%. In the case of clinically inoperable non-small cell lung cancer (NSCLC) in stage I, stereotactical radiotherapy is the method of choice which allows local control of the disease up to 90% of the patients after three years while it's efficiency is comparable to the surgery with better tolerance. Postoperative radiotherapy is appropriate for the affected mediastinal lymph nodes. In locally advanced inoperable NSCLC, the standard of concomitant chemoradiotherapy is co-administered with chemotherapy based on the two platinum-containing cytostatics. No flat-rate escalation over 60 Gy/6 weeks for increased toxicity with higher risk of death has been demonstrated. Flat-rate escalation over 60 Gy/6 weeks has not been proven useful as it increases the toxicity and the risk of death. Technical innovations, such as beam-modulated radiotherapy, image-based radiotherapy, or breathing movement monitoring over time, improve treatment outcomes. Technical innovations, such as beam-modulated radiotherapy, image-based radiotherapy, or breathing movement monitoring over time, improve treatment outcomes. In small-cell carcinoma, at the stage of limited disease, the most effective is concomitant chemoradiotherapy, starting at the latest from the third cycle of chemotherapy, at a dose of 66 Gy/33 fractions or twice daily for 3 weeks to a dose of 45 Gy. Radiotherapy is also recommended at the extensive disease stage as a consolidation treatment after chemotherapy with a very good response. In the treatment of small cell carcinomas, preventive brain irradiation is recommended as standard, although recent studies, as an alternative, include careful and frequent magnetic resonance imaging (MR) and early treatment in an asymptomatic stage. In NSCLC, preventive irradiation reduces the proportion of patients with brain metastasis from 30% to 8%, but survival prolongation has not been demonstrated.

01/2019 Prof. MUDr. Vítězslav Kolek, DrSc.
Adjuvant chemotherapy (AC) after radical resection is a standard treating method of non-small cell lung cancer (NSCLC) in stage IB (in tumors of 4 cm in diameter), II and IIIA. The recommendation is based on the results of extensive meta-analyzes, which confirmed the reduction in the relative risk of death and an absolute improvement in the 5-year survival rate from 4% to 5%. Due to relatively low profits and side effects, AC use is limited in practice. Combination of vinorelbine with cisplatin is preferred, but carboplatin is used as well, particularly in patients with older age, worse performance status and co-morbidities. Current efforts aim to improve efficacy and patient selection. Prognostic and predictive biomarkers are sought to allow the personalization of adjuvant chemotherapy. In patients with NSCLC after radical surgery, other systemic treatment options are verified. Biologically targeted treatment has not yet been unambiguously put into common practice although two studies have shown improved survival with long-term TK inhibitors in the epidermal growth factor receptor (EGFR) mutation tumors. There are several extensive Phase 3 studies with immunotherapy in patients with different PDL-1 expressions. Their results are expected with great hope.

01/2019 MUDr. Jiří Votruba, Ph.D.
Modern pulmonary diagnostic and therapeutic bronchology is a dynamically developing discipline, which has long been focused not only on endobronchial problems but also on diagnosis and treatment of parenchymal pathologies of mediastinum and pleural cavity. We remain in the standard division of the endoscopic method as determined, even though it is increasingly perceived as being overwhelmed by the potential of hybrid and combined procedures.

01/2019 Prof. MUDr. Robert Lischke, Ph.D.
The gold standard is lobectomy and systematic mediastinal lymphadenectomy. In high-risk patients, sublobar resections may be considered in very selected cases. VATS (video-assisted minithoracothomy, minithoracotomy) resection becomes the method of choice for faster recovery of patients, lower morbidity and comparable oncological effectiveness compared to open chest surgery. Centralization to high-volume specialized pneumo-oncosurgical centers is key for good results.

06/2018 MUDr. Daniel Krejčí; MUDr. Jana Krejčí; doc. MUDr. Norbert Pauk, Ph.D.
It has been shown that patients with non-small cell lung cancer with confirmed mutation of epidermal growth factor receptors significantly benefit from treatment by tyrosine kinase inhibitors. However, resistant mutations develop within approximately 10 months, of which 60 % are formed by T790M mutations. Multiple clinical trials showed that osimertinib is an efficient molecule in both patients with common epidermal growth factor receptor mutations as well as in those with T790M positivity. AURA III met its primary endpoint showing that the PFS was significantly prolonged in T790M positive patients being treated with osimertinib compared to standard chemotherapy in the second line. Clinical study FLAURA also showed significant prolongation PFS in comparison to standard first line treatment in epidermal growth factor receptor mutated patients. Osimertinib has favorable safety profile and good efficacy even in CNS. In the Czech Republic osimertinib is registered for the first line treatment of patients with activating epidermal growth factor receptor mutations and for patients with confirmed T790M mutations. At the time that this article was written, full reimbursement of osimertinib is not available in the Czech Republic.

06/2018 MUDr. Marek Hakl, Ph.D.
Pain is one of the most common manifestations of oncological illness. Its basic treatment strategy is based on the World Health Organization's three-step ranking. Non-opioid analgetics, weak opioids and strong opioid medication are available for treatment. For the treatment of breakthrough pain, transmucosal fentanyls are now also available. In the treatment of oncological pain, non-invasive administration of analgesics is preferable to invasive, preferring retarded drugs or transdermal opioids, supplemented by fast-release forms for the treatment of acute pain worsening. Analgesic medication can be supplemented with additional comedications, especially from the group of anticonvulsants and antidepressants.

06/2018 Doc. MUDr. David Pavlišta, Ph.D.; MUDr. Lukáš Dostálek; MUDr. Petra Šašková
Rewiev about history, present and future of axillary staging in breast cancer.

06/2018 MUDr. Markéta Pospíšková
Tumors of the head and neck are among the world's most incidences of cancer. In the last decade there has been an increase in tumors associated with HPV infection and a decrease in the incidence of tumors associated with smoking and alcohol abuse. Despite the awareness, there are still 60% of patients in locoregional advanced stages and 12 % of patients have distant metastasis at the time of diagnosis. The basis of treatment is a multidisciplinary approach. Thanks to new knowledge about tumor biology, which has brought new therapeutic options (antibodies, immunotherapy), generalized and relapsing cancers have improved survival.

06/2018 MUDr. Markéta Černovská
Neuroendocrine tumors are neoplasm that arise from cell of the endocrine and nervous systems. Pulmonary neuroendocrine tumors include a spectrum of tumors from the low-grade typical carcinoid and intermediate-grade atypical carcinoid to the high-grade large-cell neuroendocrine carcinoma and small-cell carcinoma. The most common neuroendocrine lung tumor is SCLC, which accounts for 15-20% of invasive lung malignancies. Immunotherapy has proved to be a promising therapeutic modality in lung cancer well. Treatment with the blockade of immune checkpoints involves monoclonal antibodies blocking CTLA-4 (cytotoxic T-lymphocyte antigen) and antibodies blocking the PD-1 receptor (programmed cell death membrane protein) and its ligand PD-L1.

06/2018 MUDr. Igor Richter, Ph.D., doc. MUDr. Josef Dvořák, Ph.D., MUDr. Jiří Bartoš, MBA
Metastatic colorectal cancer is one of the day-to-day diagnoses of oncology centers. In addition to chemotherapy, we also have the opportunity to receive targeted treatment. Bevacizumab is a monoclonal antibody against vascular endothelial factor and we have more than ten years of experience with it. The review article evaluates the current status of bevacizumab in the treatment of metastatic colorectal cancer, where its position in the treatment algorithm of the disease has recently been clarified without a clear predictive factor. Finally, there is a case report of the patient who responds well to chemotherapy in combination with bevacizumab in the first line, despite left-hand localization and the non-mutated RAS gene.

06/2018 MUDr. Viera Bajčiová, CSc.
Merkel cell carcinoma (MCC) is a rare aggressive skin neuroendocrine cancer, metastatic disease is associated with poor prognosis and overal survival. The efficacy of avelumab in the JAVELIN Merkel 200 registration study in metastatic MCC refractory to chemotherapy patients and also in untreated chemotherapy naive patients with MCC resulted in its approval by the Food and Drug Administration (FDA) in the US in March 2017 and subsequently in Europe in September 2017. The administration of avelumab in advanced MCCs on both first and subsequent treatment lines has shown prolongation of the interval in both progression and overall survival and good safety profile with manageable side effects.

06/2018 Prof. MUDr. Miroslav Ryska, CSc.
Pancreatic carcinoma is the second most common cancer of the gastrointestinal tract in the Czech Republic after the colorectal cancer and the sixth most common cancer. The 5-year survival rate of all stages of the pancreatic carcinoma is below 5 %. It is expected that in 10-15 years, mortality of pancreatic carcinoma will take the first place among other malignancies. Over the last period, survival has not changed significantly despite the improvement of imaging methods and surgical performance becoming more precise. The pancreatic carcinoma develops relatively slowly, approximately over a decade, and we cure it until its terminal phase. Diseases should be understood as systemic, not local and regional. Improving the quality of guidelines and their compliance is the way to improve the care of these patients at present and in the near future. This is not only a health-organizational problem but also a social and economic problem.

06/2018 MUDr. Peter Grell, Ph.D.; MUDr. Radka Obermannová, Ph.D.
Gastric and gastro-oesophageal junction cancers are aggressive diseases, and only 25 % of patients with early stage disease achieve a long-term survival. The modern multimodal approach to treatment nearly doubled survival in these patients. The primary requirement for successful treatment is performing adequately radical resection in centers specialized in these challenging surgeries. In gastric cancer, the use of perioperative chemotherapy is recommended as a standard of care. The most effective regime in this approach is FLOT chemotherapy. In gastro-oesophageal junction carcinomas, in addition to perioperative therapy, neoadjuvant chemoradiotherapy appears to be appropriate strategy, mostly in cases with locally advanced carcinomas where tumor regression is required in order to perform an R0 resection.