03/2021

03/2021 MUDr. Michal Eiď; MUDr. Štěpan Tuček, Ph.D.; MUDr. Lumír Kunovský, Ph.D.
Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing, and mortality remains high. It has already been proven that PDAC is not one uniform disease. It is considered a very heterogeneous malignancy. Despite a growing knowledge, no breakthrough therapy leading to long-term survival has been implemented into the clinical practice during last 30 years. An exception is an intensive triplet chemotherapy regimen with 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRINOX), that leads to median overall survival 54,4 months and median disease free survival 21,6 months in adjuvant setting. It should be noted that in this PRODIGE 24 trial, inclusion criteria were strict and study population was selected. This intensive chemotherapy regimen is not feasible for majority of patients in real clinical practice. However, there is a subpopulation of patients with PDAC who long-term survivors are. Several clinical markers helping to predict patienťs prognosis are already available. Recently, number of molecular prognostic markers were described, and they will probably have an important role in future. In this article we will discuss the clinical, histopathological, and molecular prognostic markers that can be useful for the prognostic stratification.

03/2021 MUDr. Peter Matkulčík; MUDr. Tomáš Rohan; MUDr. Pavlína Slováková; MUDr. Tomáš Andrašina, Ph.D., MBA
Increasing incidence of esophageal malignancies led authors to publish this review article regarding possibilities of cooperation between oncologists and interventional radiologists. In this article we summarize up-to-date information about indications and contraindications of different types of stents and their complications. Article is also supplemented with our experience in department of non-vascular interventions at Department of Radiology and Nuclear Medicine of Faculty Hospital Brno and Faculty of Medicine of Masaryk University.

03/2021 MUDr. Jan Zavadil; MUDr. Tomáš Rohan; MUDr. Matej Straka; MUDr. Lenka Ostřížková; MUDr. Tomáš Andrašina, Ph.D., MBA
Transarterial chemoembolization is an integral part of the treatment of intermediate primary and secondary liver tumors. Over the decades, this method has been constantly improved both in terms of technology and the possibilities of embolizing agents used and improves the prognosis of patients who often cannot undergo other therapies. This review article introduces the readers to the basic cha- racteristics of the performance itself, indications, methods, complications, and side effects. Finally, the success of the performances themselves is presented.

03/2021 MUDr. Lenka Ostřížková; MUDr. Ivana Kosíková 
Tumors of the esophagus, gastroesophageal junction (GEJ) and stomach are the sixth other cause of death. The highest incidence and mortality are in Asia and southern and eastern Africa. However, even in the Czech Republic, the incidence and mortality have an upward trend. In more than half of the patients, the diagnosis is made in the primarily advanced or disseminated stage. Histologically, tumors have squamous cell carcinomas, which mainly affect the proximal two-thirds, and adenocarcinomas, which affect the distal third and the GEJ region. There are more adenocarcinomas in gastric tumors at the same time. Squamous cell carcinomas of the esophagus are predominantly found in the countries of Eastern Europe and Asia. Adenocarcinomas dominate in North America and Western Europe. Anatomical localization, histological type of tumor, evaluation, and extent of the disease (TNM classification) are the cornerstones for determining strategic therapy. Treatment is interdisciplinary and should be conducted through multidisciplinary teams. According to the results of clinical studies, new immunotherapeutic strategies, antibodies against cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and antibodies against programmed cell death protein 1 (PD-1) / programmed cell death-ligand 1 (PD-L1) also have their place in the treatment algorithm of esophageal and gastric tumors. The results of clinical studies have shown that the combination of immunotherapy and chemotherapy improves overall survival and prolongation of time to disease progression compared to chemotherapy alone. Both in the treatment of metastatic disease and in adjuvant administration.

03/2021 MUDr. Zdeněk Linke
Initial failure of epidermal growth factor receptor (EGFR) inhibitor therapy in advanced RAS wild-type (wt) colorectal cancers may not necessarily mean its permanent and definitive ineffectiveness. It is possible to re-apply anti-EGFR treatment after previous disease progression (rechallenge), or after a previous interruption for reasons other than progression (reintroduction), or sequence, resp. rotation between two different EGFR blockers (sequence) or an attempt to overcome the resistance of anti-EGFR treatment by increasing its dose (escalation) or the possibility of continuous EGFR blockade. Clinical data are available to demonstrate that, especially after discontinuation of primary anti-EGFR therapy and subsequent differential therapy, sensitivity to this therapy does return. This is by changing the proportion of EGFR positive RAS wt tumor cells. This occurs during another, intervening therapy, which is based on an effect different from EGFR blockade. However, a prerequisite for the effect of reintroduced anti-EGFR treatment is its effectiveness during its previous, primary application.

03/2021 Prof. MUDr. Samuel Vokurka, Ph.D.
Hepatocellular carcinoma is a prognostically unfavorable malignancy with very limited possibilities to influence its course, especially in advanced stages of the disease. Treatment with atezolizumab and bevacizumab in the IMbrave150 study showed a significant prolongation of median progression and overall survival of 19,2 versus 13,4 months in sorafenib group of patients (HR 0,66; p = 0,0009). This has been the longest survival observed in the first-line phase III study in advanced hepatocellular carcinoma, so far.

03/2021 MUDr. Marián Liberko; doc. MUDr. Renata Soumarová, Ph.D., MBA
Pancreatic cancer represents disease with the worst long-term survival across all malignancies. In clinical practice, due to asymptomatic or non-specific signs and symptoms we diagnose patients mainly with locally advanced and metastatic disease, where median survival is approximately one year. Nevertheless, even in early stages after curative surgery we observe early local recurrence, or distant metastases and long-term survival is an exception even in early stages of disease. Nevertheless, in the last few years there is an improvement in median overall survival also in patients with pancreatic cancer. It is due to advancements in diagnostics, surgery, but mainly due to improvements in cancer treatment (chemotherapy - adjuvant, neoadjuvant, perioperative, induction and palliative, and also radiotherapy). There were published results of many studies across all stages (resectable, borderline resectable, locally advanced, metastatic) which showed improved survival. The aim of this article is to provide overview of current treatment options for pancreatic ductal adenocarcinoma.

03/2021 MUDr. Stanislav Batko
Treatment of metastatic colorectal cancer is based on the combination of chemotherapy and targeted therapy, in which anti-EGFR monoclonal antibodies cetuximab and panitumumab play a very important role in RAS + BRAF wild-type subgroup of patients. They have showed prolonged progression-free survival throughout all lines, with prolongation of overall survival demonstrated in first- and third-line studies. The most significant benefit in overall survival can be observed, when they are used in chemonaive metastatic colorectal cancer. In this setting anti-EGFR (epidermal growth factor receptor) therapies pro- vide deep and durable response. This effect of tumor mass reduction simultaneously allows a significant proportion of patients to achieve conversion and secondary resection of metastases associated with longer survival and potential for curability. In addition to the most commonly used doublets FOLFOX and FOLFIRI, panitumumab can be used in combination with 5-fluorouracil and leucovorin in elderly patients while maintaining its efficacy. At the same time, there is increasing experience with the use of anti-EGFR therapies in combination with the FOLFOXIRI triplet, demonstrating high potential to achieve resectability. The indication criteria have been newly expanded to include BRAF V600E mutated pre- treated metastatic colorectal cancer, where the combination of cetuximab with encorafenib resulted in a significant prolongation of overall survival.

03/2021 Doc. MUDr. David Vrána, Ph.D.
Immunotherapy found its firm role in the treatment of several tumor types. Based on the recently pub- lished clinical trials immunotherapy got into treatment algorithm of esophageal and gastroesophageal cancer in the first line and also in later treatment lines. Predictive markers, which play a role in the treatment selection are programmed cell death-ligand 1 (PD-L1), deficient mismatch repair genes and high microsatellite instability (dMMR/MSI-H) and human epidermal growth factor receptor 2 (HER2) expression. Targeted therapy with trastuzumab, ramucirumab or therapy with trifluridine/tipiracil remains the treatment of choice in the case of gastroesophageal cancer. Unfortunately, the reimbursement by the health care insurance is missing so far for any immunotherapy molecule. Bellow mentioned text aims to summarize current data for immunotherapy, targeted therapy in the treatment of the esophageal and gastroesophageal cancer regardless of the insurance reimbursement.

03/2021 MUDr. Eugen Kubala
Adjuvant therapy is considered the standard approach to the treatment of patients with locally advanced stage IIIA, IIIB and IIIC melanoma. The EORTC 1325-MG/KEYNOTE-045 study, which compared pembrolizumab with placebo, clearly demonstrated its efficacy. Long-term follow-up showed that 3-year relapse free survival (RFS) was achieved in 63.7 patients with pembrolizumab versus 44.1% in placebo patients (HR 0.56; 95% CI, 0.47-0.68; p < 0.001). This treatment has been shown to be highly safe with a low incidence of side effects. At the same time, the incidence of immunotherapy-related adverse events has been shown to be associated with better treatment outcomes than without them, especially in endocrine toxicity (p = 0.03). However, the absence of immunotherapy-related adverse events does not lead to a significant reduction in the efficacy of pembrolizumab over placebo.

03/2021 Prof. MUDr. Ivan Špička, CSc. 
Therapy of multiple myeloma has substantially changed during last two decades due to new generation biological drugs proteasome inhibitors, immunomodulators and monoclonal antibodies. Elotuzumab is first in class monoclonal antibody approved for clinical use by Food and Drug Administration as „breakthrough therapy". Its target antigen is surface receptor SLAMF7 (or CS1) from CD2 group and SLAMF (signaling lymphocytic activation molecule) family. At present elotuzumab is approved for relapsed myeloma patients in combination with dexamethasone and either lenalidomide or pomalidomide.

03/2021 MUDr. Markéta Černovská
Anaplastic lymphoma kinase (ALK) mutations were first described in non-small cell lung cancer (NSCLC) in 2007. ALK inhibitors are anti-cancer drugs that act on tumours with variations of ALK such as an EML4-ALK translocation. ALK inhibitors have shown significant benefits in the management of ALK-positive NSCLC compared to conventional chemotherapy. Crizotinib was the first ALK inhibitor which compared to standard chemotherapy prolonged progression-free survival. However, many patients with ALK-positive experience clinical progression and frequent brain metastases in the first year of treatment with crizotinib during the poor accumulation of the drug in the central nervous system (CNS). Second-generation (alectinib, ceritinib, brigatinib) and the third-generation ALK inhibitors (lorlatinib), have increased potency and higher CNS activity compared to the first-generation crizotinib. A sequencing of ALK inhibitors in ALK-positive NSCLC prolonged an overall survival.

03/2021 MUDr. Věra Benešová 
In this case report, I describe the course of treatment of metastatic colorectal cancer in a 44-year-old woman with type 1 diabetes mellitus with insulin therapy and hypertension. The decision on the treatment sequence respected the current recommendations for the treatment of metastatic colorectal cancer, namely: examination in a multidisciplinary team, determination of the genetic type of the tumor, placement of the tumor and the overall lineage of the patient. Because the tumor was KRAS, NRAS wild-type, multiple liver lesions have been found in both lobes and it was left-sided cancer, systemic chemotherapy FOLFOX6 in combination with an epidermal growth factor receptor inhibitor, panitumumab (Vectibix inj.), has been chosen.

03/2021 MUDr. Michaela Barjaková; MUDr. Robert Novák; MUDr. Jana Katolická, Ph.D.; doc. MUDr. Jiří Vaniček, Ph.D.
Urothelial tumors of the upper urinary tract make up only about 5% of the urothelial tumors. In the treatment of metastatic disease, we use chemotherapeutic regimens based on a platinum derivative, as in urothelial bladder cancer. Following failure of a platinum derivative, vinflunine or taxanes (especially paclitaxel) may be given from chemotherapy in case of good performance status.