Selected articles

06/2017 MUDr. Marek Sochor, MUDr. Jiří Bartoš
Patients with advanced cancer, with limited prognosis, are the most demanding group of oncological patients. In that patients anticancer therapy isn't applied with curative intent, it is oriented to prolong life and to make better quality of life. Patients suffer from many physical symptoms, are suspended to psychic distress and have almost complicated social situation. These all factors worsen quality of life, complicate anticancer treatment and shorten life. In the last ten years grows knowledge about significance of early application of multimodality palliative care initiated in time of diagnosis of cancer and realized parallel to anticancer treatment. This concept was confirmed in many randomized trials. In a next future of scientific investigation and real clinical practice we have to figure out who will provide palliative care, which modalities are the most effective and which models of care between palliative care specialists and oncologist are the most suitable for patients. Review article documents our current knowledge about early palliative care in oncology.

06/2017 MUDr. Viktor Maňásek
Tumor diseases are posed a significant risk of developing malnutrition. Nutritional therapy is an essential part of a comprehensive treatment strategy for malignancies. We have enough valid data supporting the meaningfulness of nutritional support to improve the clinical condition of patients and compliance with the treatment plan. The presence of active tumor causes the development of varied metabolic and humoral changes, interfering with the intake and processing of the individual nutrition components. This article summarizes the current view of nutritional intervention options in the conditions of the Czech Republic, including an overview of enteral and parenteral nutrition focusing on indication in various clinical situations.

06/2017 MUDr. Jiří Tomášek, Ph.D.
Approximately 40 % of patients with colorectal cancer will develop metastatic disease. Survival of patients with metastatic colorectal cancer has improved with the introduction of targeted therapies. Survival has also improved with utilization of molecular parameters (oncogens RAS, BRAF) and other factors such as sidedness of the primary tumor. The basics of intensive chemotherapy are regimens based on oxaliplatin and irinotecan. Targeted treatment increases the effectiveness of chemotherapy. A multidisciplinary approach to treatment is needed. In brief, we describe the basic strategy of systemic treatment in metastatic colorectal cancer

06/2017 Prof. MUDr. Miroslav Ryska, CSc., MUDr. Daniel Langer, MUDr. Jaroslav Kalvach
The authors deal with some current aspects of surgical treatment of colorectal carcinoma. Right-side tumours including coecum, ascending colon, hepatic flexure, transversum and spleen flexure are clinically, biologically and genetically distinct from tumours in the left-handed localization, which includes a descending colon, sigma and rectum. Right-hand localization is a negative prognostic marker, especially for stage III and IV carcinomas. Regardless of right-handed treatment, compared to the left-hand side, it significantly increases the risk of death. There are currently no clear recommendations for indication for the protective ileostomy. Despite some proven benefits, the protective stoma probably only reduces the frequency of clinically manifest anastomotic leakage. The benefit of ileostomy should be carefully considered in the knowledge of possible risks and complications. The rate of anastomotic leakage in colorectal surgery is literally in the range of 1-19 % depending on the type of resection, respectively on anatomical localization of anastomosis. In the case of anastomotic leakage, a crucial role is played by early diagnosis with an active treatment approach which can minimize the consequences of anastomotic leakage. The surgical treatment of the most serious cases of anastomotic leakage plays a key role in surgical treatment, which needs to be repeated in many cases.

06/2017 MUDr. Petr Vítek, Ph.D., MBA; MUDr. Ivana Mikoviny Kajzrlíková, Ph.D.
Endoscopic resection techniques include endoscopic polypectomy, endoscopic mucosal resection, endoscopic submucosal dissection and full-thickness resection. These resection methods are curative in cases of superficial invasive colorectal cancer provided that favourable prognostic criteria are met. Endoscopic placement of self-expandable metallic stent is preferred treatment for palliation of malignant colonic obstruction except in patients treated with antiangiogenic drugs. Endoscopic dilation is an effective treatment of colorectal anastomotic stenosis. Endosponge placement is beneficial for patients with colorectal anastomotic dehiscence and presacral cavity.

06/2017 MUDr. Šárka Bohatá, Ph.D.; prof. MUDr. Vlastimil Válek, CSc., MBA
The golden standard for primary diagnosis of colorectal cancer is colonoscopy together with biopsy. Exact staging and the preoperative assessment are crucial for optimal management of colorectal carcinoma, influencing decision making in case of neoadjuvant treatment and also determining the prognosis. EUS depicts the anatomic layers of the rectal wall with a high degree of accuracy and thus enables precise determination of the tumor extent in relation to the different wall layers (T staging). EUS accuracy is about 85% for T staging and 70-75% for nodal staging. Compared with the other commonly used techniques, CT scan is more largely accessible, faster, inexpensive and less operator-dependent, however CT is not the first choice method for local staging, because the definition of the bowel wall layers is not possible, but is one of the preferred tools to evaluate mainly distant spread, because of its high reproducibility and availability. High-resolution MRI in hands of experienced radiologist plays a pivotal role and has become almost mandatory in the pretreatment assessment of primary rectal cancer. MRI is currently the only imaging modality that is highly accurate (with specificity 92%) in predicting whether or not it is likely that a tumor-free margin can be achieved and in determination of the local invasion depth. Especially in distal tumors MRI provides important information for surgeon's decision whether sphincter-sparing surgery is possible. In patients with advanced rectal cancer extramural vascular invasion of the tumor can be depicted, used as an independent negative prognostic factor for local and distant recurrence rate and shorter overall survival rate. MRI can determine which patients can be treated with surgery alone and which will require radiation therapy to promote tumor regression. MRI can differentiate patients with good therapy response from non-responders. Tumor regression grade assessment is an independent predictor of overall survival and overall symptom-free survival rates and also plays substantial role in patients with the local recurrence. In patients with rectal cancer who have received concurrent chemotherapy and radiation therapy before surgery, all methods have lower accuracy in prediction of the pathologic stage owing to overstaging or understaging. The factors related to this problem include fibrosis, desmoplastic reaction, oedema, inflammation, and viable tumor nets at a fibrotic scar from a previous tumor.

06/2017 MUDr. Petr Kocna, CSc.
Colorectal cancer screening has a long tradition in the Czech Republic. High specificity of screening tests is a prerequisite for use in mass screening. Unlike individual diagnostics, there is a higher risk of false positivity than negativity in population screening because it leads to increased costs, unnecessary investigation, complications, and a negative impact on the quality of life of healthy people. Quantitative haemoglobin detection in stool is currently the most accurate method of determining occult bleeding suitable for colorectal cancer screening. Optimization of screening is addressed in all countries where faecal immunochemical test (FIT) has replaced guaiac tests and involves cut-off criteria for positivity, number of tests performed, combination of FIT with other biomarkers, and distribution and sample analysis. Standardization and harmonization of FIT is a prerequisite for population screening of colorectal cancer and the accuracy and reliability of quantitative detection of haemoglobin in the stool should be ensured by external quality control.

05/2017 MUDr. Igor Sirák
Locally advanced breast carcinoma is generally treated with systemic therapy prior to locoregional surgery and/or radiotherapy. Antracycline and taxane based chemotherapy is the method of choice in the neoadjuvant treatment, with considerable toxicity that make the treatment impossible in elderly and frail patients. On the other hand, peroral vinorelbine is generally well tolerated in older women with metastatic breast carcinoma, on the basis of prospective trials and long-term clinical practice. This is a case report describing excellent effect and tolerance to long-term vinorelbine chemotherapy in very old and frail woman with chemonaive locally advanced breast carcinoma. Long-term treatment with lasting and re-inducible response and good quality of life can be achieved by this accessible and inexpensive approach.

05/2017 MUDr. Lenka Jakubíková, Ph.D., MUDr. Jana Špeldová, MUDr. Marcela Tomíšková, prof. MUDr. Jana Skřičková, CSc.
The authors of the first part of the article summarize the current therapeutic results of nivolumab in both squamous and non-squamous lung cancer, as well as the safety profile of this type of immunotherapy, including recommendations for prevention and measures for the occurrence of side effects. In particular, adverse events, particularly weakness and exhaustion, were reported in two selected patients who experienced a severe fatigue with the need for permanent discontinuation of treatment immediately after initiation of treatment with nivolumab, but two months after the last dose of immunotherapy, partial healing response that lasted for one year in both patients was observed.

05/2017 MUDr. Beatrix Bencsiková, Ph.D.
Trifluridin/tipiracil (Lonsurf, TAS-102) represents a new option for the treatment of patients with metastatic colorectal cancer (mCRC) on the 3^rd and upper line. It reduces the risk of death by 31% compared to placebo (overall survival, OS 71 vs. 5.3 months, hazard ratio [HR], 95% CI 0.68 [0.58-0.81], p < 0.001), and a risk of disease progression by 52% compared to placebo (progression free survival [PFS] 2.0 vs. 1.7 months, p < 0.001), confirmed by the phase III clinical trial RECOURSE [1]. The benefit was observed in all subgroups of patients regardless of the KRAS mutation, refractoriness to 5-fluorouracil in previous lines. The following case study confirms the benefit of the combination of trifluridine/tipiracil in a pre-treated patient with mCRC.

05/2017 MUDr. Viera Bajčiová, CSc.
Currently the most children with cancer can be cured with standard therapy (surgery, chemotherapy, radiotherapy). The only limiting factor is its severe acute toxicity and late adverse events. In pediatric oncology immunotherapy has some delay, but the initial clinical trials of immunotherapy show a good tolerance and promising results, specially in the setting of refractory or recurrent high-risk tumors. In this article we will discuss a current situation in pediatric oncology, what immunotherapies are being tested in the clinical practice, from monoclonal antibodies, check-point inhibitors to tumor vaccines, chimeric antigene receptors, cytokines and innate immunity.

05/2017 RNDr. Ing. Bc. Libor Staněk, prof. MUDr. Robert Gürlich, CSc., doc. MUDr. Petra Tesařová, CSc.
Colorectal cancer is a serious global disease with high incidence and mortality. With the development of diagnostics in molecular oncology, we try to find predictive and prognostic factors in the search for the most effective therapy. At present, it is a molecular testing of tumors prior to considering anti-EGFR therapy. The latest available studies, however, show that the carcinoma located in the right part of the intestine has a lower sensitivity and response to this treatment than the carcinoma on its left. The essence of this phenomenon remains a question. If these changes can be identified, they can be used to optimize therapy.

05/2017 Prof. MUDr. Jindřich Fínek, Ph.D., MHA
Bevacizumab is a universal anti-VEGF drug effective in numerous solid tumors in combination with chemotherapy.

05/2017 MUDr. Zdeněk Linke
Gastrointestinal stromal tumor was one of the first solid tumors, where previous palliative treatment with chemotherapy was completely replaced by biological treatment. Imatinib mesylate was significant turning point for patients, imatinib against previous treatments significantly prolonged survival in metastatic gastrointestinal stromal tumor cases and reduced recurrence rates and prolonged survival in patients following radical resections of risk groups of patients with gastrointestinal stromal tumors. After imatinib failure, preparations such as sunitinib and regorafenib are available. In recent years, new molecules for gastrointestinal stromal tumors treatment are under research and the dependence of therapy effect on c-Kit receptor mutation status and the serum concentration of imatinib is being investigated.

05/2017 MUDr. Andrea Jurečková
Malignant tumours of the thyroid gland are relatively rare, their incidence is, however, permanently escalating. The most frequent among them is the differentiated thyroid cancer: papillary, follicular and Hurthle cell carcinomas. In the initial stages the prognosis of these tumours is excellent. Nevertheless, only few therapeutic modalities are available for advanced or metastatic disease. In the last decade, a better understanding of the molecular events involved in the thyroid cancer has led to introduction of new targeted agents for the management of advanced radioiodine-refractory disease. Multikinase inhibitors are able to block pathways involved in the proliferation, invasion, and neoangiogenesis of thyroid cancer. Their effectiveness was proved in several clinical placebo-controlled clinical trials. The purpose of this paper is a special focus on lenvatinib, a multikinase inhibitor.

05/2017 MUDr. František Folber, Ph.D.
Relapsed/refractory adult acute lymphoblastic leukemia is a serious clinical issue poorly manageable by the standard of care chemotherapy. Too many of these patients do not achieve a remission and survive only several months. Blinatumomab is a new promising immunotherapy drug targeting CD19 antigen present on a vast majority of B lineage adult acute lymphoblastic leukemia cells. Clinical trials have proven it to induce a remission more frequently compared to the standard treatment and thus such patients can proceed to an allogeneic transplant and take their chance towards a permanent cure. Adverse events are usually moderate and easily manageable. The major limiting factor for its use in a broader spectrum of patients is a very high market price, making blinatumomab the most expensive cancer drug on the market.

05/2017 MUDr. Leona Koubková
The epidermal growth factor receptor (EGFR) plays an important role in the development and progression of human epithelial carcinomas, including non-small cell lung cancer (NSCLC). Activation of the EGFR pathway promotes tumor growth and progression, stimulates tumor cell proliferation, angiogenic factors, invasion and metastasis, and suppresses apoptosis. Several studies have confirmed the predictive role of activation mutations in EGFR exons 19 and 21 for NSCLC. Their presence is clearly associated with higher efficacy of EGFR tyrosine kinase inhibitors (EGFR TKI). We have reversible EGFR TKI of the 1^st generation erlotinib and gefitinib, the irreversible EGFR TKI 2^nd generation afatinib, and also the already irreversible EGFR TKI 3^rd generation osimertinib, the indication of which is above all the proven T790M mutation.

05/2017 MUDr. Jana Katolická, Ph.D., MUDr. Sabina Svobodová, MUDr. Jiří Vaniček, Ph.D., Mgr. Pavlína Prosecká
Targeted treatment is currently a standard therapeutic method for metastatic clear cell renal carcinoma. Cabozantinib is an oral tyrosine kinase inhibitor including MET, VEGFR, and AXL. In a randomized phase III METEOR study, prolongation of survival in patients following prior VEGFR treatment with tyrosine kinase inhibitors has been demonstrated.

05/2017 MUDr. Alexandr Poprach, Ph.D., MUDr. Radek Lakomý, Ph.D.
Disseminated renal cell carcinoma is incurable. In the second line of palliative treatment, we can now usually use everolimus or axitinib. The breakthrough in treatment in the second line is the results of Phase 3 studies (METEOR - Cabozantinib study and CHECKMATE 025 - Nivolumab study). Nivolumab prolonged overall survival when compared to everolimus, the time to progression was the same, but cabozantinib prolonged both progression and overall survival when compared to everolimus. Cabozantinib is an oral inhibitor of many receptor tyrosine kinases. Unlike other commonly used multi-enzyme inhibitors that are used in renal cell carcinoma, it also inhibits MET and AXL protein kinases. These are more pronounced in patients after sunitinib treatment and also in patients in a poor prognostic group. In this review we will look at cabozantinib - the mechanism of its effect, the characteristics of the drug and the recent results of the studies.

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.