Selected articles

01/2020 MUDr. Juraj Ďuraš; MUDr. Michal Kaščák; prof. MUDr. Roman Hájek, CSc.
Recent demographic trends with increasing proportion of elderly people are associated with the higher incidence of hematological malignancies including non-Hodgkin's lymphomas. Higher age is associated with a significantly worse prognosis because of physiological decline of organ functions and increasing incidence of comorbidities that both limit treatment options.
Staging procedures in elderly patients do not differ significantly from younger patients. The standard imaging method is computed tomography (CT), positron emission tomography (PET) / CT is recommended in patients with aggressive lymphoma treated with curative intent. In follicular lymphoma, PET/CT is recommended especially before local radiotherapy to confirm localized disease.
A Geriatric 8 (G8) questionnaire is recommended as a screening tool for geriatric assessment. In the case of score ≤14, a comprehensive geriatric assessment including assessment of performance status, activities of daily life, mental status, possible sensory impairment and comorbidities is recommended.
Treatment of elderly patients with lymphoma requires personalized approach. In fit patients who are able to tolerate standard treatment, the outcomes are similar to outcomes in young patients. In vulnerable patients treatment should be conducted with the aim of prolonging life with respect to its quality while avoiding intensive treatment procedures with risk of toxicity. In terminal patients who won't profit from oncological therapy, only symptomatic supportive treatment is recommended. Treatment options for most common lymphoma subtypes are discussed in second part of the article.

01/2020 MUDr. Viktor Maňásek
Chemotherapy-induced neutropenia, and in particular febrile neutropenia, is a serious complication of antitumor systemic therapy. It is possible to indicate the growth factors of myelopoiesis in prophylaxis of neutropenia in specific situations. In addition to filgrastim and pegfilgrastim, a number of biosimillar products have recently been developed with a similar therapeutic and safety profile as compared to the original products. Biosimillar drugs are subject to the same approval processes and the same standards of pharmaceutical quality, safety and efficacy that apply to all biological drugs approved in the European Union. Reducing the cost of biosimilar preparations could optimize the use of growth factors with better availability for indicated patients.

01/2020 MUDr. Tomáš Blažek
Therapy of prostate cancer has improved significantly over the past 10 years. In the treatment of localized stages, the emphasis is on the quality of life of patients after radical treatment and the effort to minimize late adverse effects of treatment. Patients achieve very good treatment results and their overall and cancer-specific survival is significantly better compared to other malignancies. A similar trend is seen in patients with metastatic disease. Advances in palliative systemic therapy noticeably changed and improved overall and cancer-specific survival. The new generation of antiandrogens offers patients with metastatic prostate cancer new perspectives not only in terms of survival but especially in the quality of life during treatment. The aim of this article is to provide an overview of current treatment options for metastatic, hormone-sensitive prostate cancer.

01/2020 Doc. MUDr. Jan Novotný, Ph.D.
Better therapeutic results that are observed in many different tumor types in the last years are primarily caused by the better understanding of principles of tumor growth and tumor progression. When we focus on breast cancer, the knowledge of these crucial events has led to the development new classes of antineoplastic drugs that attack different signaling pathways including mTOR, PI3K, HER2/Neu as well as G1 checkpoint. Until now there are registered three drugs in the letter mentioned group also called CDK4/6 inhibitors - abemaciclib, palbociclib and ribociclib. In this article, we focus on abemaciclib in the context of other two drugs.

01/2020 MUDr. Gyula Nyárs; doc. MUDr. David Vrána, Ph.D.
Atezolizumab is a modified humanized IgG1 monoclonal antibody that inhibits programmed death-ligand 1 (PD-L1). It is the one of few check-point inhibitors which can be used to treat patients with non-small cell lung cancer. Although it is currently registered in the Czech Republic only for the second and higher lines of palliative treatment after progression on chemotherapy or targeted therapy, unfortunately health insurance still does not reimburse it. The goal of this article is to summarize outcomes of the most important studies which proved the efficacy and safety of atezolizumab in the first and second line of palliative treatment.

01/2020 MUDr. Jaromír Roubec, Ph.D.
In this overview are presented data and results of the combination check-point inhibitor atezolizumab and chemotherapy from the clinical trial IMpower133 in the extensive-stage small cell lung cancer. This data new support introducing of this therapeutic modality into clinical praxis based on the prolonged progression free survival and overall survival. Discussed is the problem of the therapy of the small cell lung cancer and next possibilities with using of the immunotherapy in the combination in this time used therapies and next perspectives in this area.

01/2020 MUDr. Jaromír Richter
Prostate cancer represents a most frequent tumor among men. Despite high success rate of iocoregionai 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.

06/2019 MUDr. Daniel Krejčí; MUDr. Jana Krejčí; MUDr. Petr Opálka, CSc.; doc. MUDr. Norbert Pauk, Ph.D.
Malignant mesothelioma belongs to a group of rare tumors and is feared due to the short survival period and limited therapeutic options. Presented case report summarizes the diagnosis and treatment of a patient with extensive malignant mesothelioma, documenting significant late response to the first line standard therapy, and particularly the considerable effect of pembrolizumab in the second line treatment after progression.

06/2019 MUDr. Zuzana Donátová
Breast cancer in metastatic stage is considered as incurable disease. About 20% of all patients have distant metastases. The offer of new cytotoxic and biological agents caused prolongation of the overall survival in patients with metastatic disease. Eribulin is considered as the new effective cytotoxic agent for pre-treated patients with locally recurrent and metastatic breast cancer. Vinorelbin is effective well tolerated treatment, which is important in sequence palliative treatment of metastatic breast cancer.

06/2019 MUDr. Martina Spisarová
Angiogenesis is a crucial part of process in which benign tumors become into more aggressive malignant form and also their subsequent growth and dissemination. The correlation between inhibition of VEGF receptor and its curative effect has been observed in tumors with high microvascular density for a long time. The inhibition of VEGF receptor has a huge therapeutic potential in clear cell renal carcinoma and suchlike tumors.

06/2019 PharmDr. Šárka Kozáková, MBA; Mgr. Vojtěch Ondra; MUDr. Jana Halámková, Ph.D.
Around 30% of patients use food supplements and phytopharmaceuticals in potentially dangerous combinations during systemic cancer treatment. Natural substances may interfere with metabolic enzymes and transport proteins, thereby disrupting drug metabolism. In this review, we will focus on the most commonly used phytopharmaceuticals and medicinal plants, their impact on cancer treatment and the possible serious consequences that they may cause to patients.

06/2019 Prof. MUDr. Josef Vymazal, DrSc.; MUDr. Aaron Michael Rulseh, Ph.D.
Tumor treating fields (Optune™) is an approved method to treat both de novo and recurrent glioblastoma. The method is based on the fact that an alternating electric current of given characteristics inhibits cell division. This principle can also be applied in other tumors. A pilot study of this method was performed in the Czech Republic and fifteen years later 20% of the patients are alive. Based on further international studies, this method was included in NCNN Category 1 criteria for glioblastoma treatment. The treatment is non-invasive, and the main side effect is local skin irritation. This technique is suitable for patients that have finished standard therapy and are in good clinical condition without significant tumor progression at the time of treatment initiation. In some countries the treatment is reimbursed by health insurance providers. Currently, there are intensive negotiations with health insurance companies about its reimbursement in the Czech Republic.

06/2019 MUDr. Eugen Kubala
Treatment of patients with advanced and metastatic melanoma with BRAF V600 mutation has been enriched with new combination therapy with BRAF and MEK inhibitors encorafenib and binimetinib. Pharmacological inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway has brought significant progress in the treatment of metastatic melanoma. A key role is played by the product of the mutated BRAF V600E kinase¹ gene, which is part of the MAPK signaling pathway. Encorafenib is an ATP competitive inhibitor of BRAF kinase that is able to block several mutated forms of BRAF kinase (e.g. V600E, V600D and V600K) in tumor melanoma cells with much greater efficacy - up to ten times higher half-life, i.e. more than 30 hours longer effect of either dabrafenib (2 hours) or vemurafenib (0,5 hours). The COLUMBUS study has achieved its primary goal of increasing the median progression free survival (PFS) of combination therapy with encorafenib and binimetinib for 14,9 months comparing to vemurafenib treatment with 7,3 months PFS. Significant is the comparison of the two BRAF inhibitors encorafenib and vemurafenib, which indicated a higher efficacy of encorafenib over vemurafenib - PFS median 9,6 versus 7,3 months (HR 0,68; 95% CI 0,52-0,88; p = 0,0038 The combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib significantly shifted the PFS median to 16,4 months and the median overall survival to 33,6 months without increasing toxicity against the established combinations of BRAF and MEK inhibitors that we use in the treatment of BRAF V600 mutated melanoma.

06/2019 Prof. MUDr. Vlastimil Válek, CSc., MBA
The prevalence of hepatocellular carcinoma (HCC) is increasing and the Czech Republic is no exception. Therefore, effective care for these patients is becoming increasingly important. Radiology plays a crucial role in the diagnosis and treatment of these patients. The diagnosis of HCC can be made even without histological verification only on the basis of finding by imaging methods. A number of invasive radiological procedures, with thermoablation and chemoembolization, can be used to treat these patients. The data of the Institute of Health Information and Statistics of the Czech Republic show that in centers in the Czech Republic, where a comprehensive diagnostic, and above all therapeutic approach to HCC treatment is offered, the average survival of these patients is statistically significantly longer.

06/2019 Doc. MUDr. Igor Kiss, Ph.D.; MUDr. Martin Ondrák; prof. MUDr. Zdeněk Kala, CSc.; MUDr. Vladimír Procházka, Ph.D.; prof. MUDr. Vlastimil Válek, CSc.; MUDr. Tomáš Andrašina, Ph.D.
The case report describes a case of a patient in excellent general condition, highly motivated for surgical resection of liver, in whom no metastases were recorded before, during or after liver resection. Patients with „hepatic impairment only“ generally have a better prognosis. The patient tolerated the treatment very well and could undergo several cycles of systemic treatment with minimal hematological and neurological toxicity of systemic treatment. Even in the case of relapse, a rapid and significant effect of systemic treatment has been reported.

06/2019 Doc. MUDr. Igor Kiss, Ph.D.; prof. MUDr. Zdeněk Kala, CSc.
Colorectal cancer is the most common tumor of the digestive tract. Still a relatively large proportion of patients are diagnosed in the fourth clinical stage, i.e. the stage of metastatic disease. In the individualization of the treatment strategy, we consider a number of factors, such as the extent and dynamics of the disease, the general condition of the patient, the realistic treatment goals, and especially the patient's wishes. Although the effectiveness of systemic treatment is greatest in the early treatment lines, we can significantly prolong life of good quality in other treatment lines with current medical options.

06/2019 MUDr. Daniel Langer; prof. MUDr. Miroslav Ryska, CSc.
Colorectal cancer significantly contributes to the overall oncological burden of the Czech population. Surgical treatment is crucial in multimodal therapeutic approach. Robot-assisted surgery, primarily used for benign conditions, has quickly become an important method of treatment for malignancies. In the treatment of rectal carcinoma, as well as other conditions, the Da Vinci system brings indisputable advantages to the surgeon given the preparation in narrow pelvic space, which significantly contributes to increased safety of the procedure. The Da Vinci system is routinely used in surgical treatment of rectal cancer at many foreign and domestic workplaces. A feared surgical complication with possible fatal consequences for the patient is anastomotic insufficiency. Assessment of tissue perfusion during surgery by fluorescence angiography using indocyanine green in the near-infrared spectrum represents a potential possibility of reducing the frequency of anastomotic leaks.

06/2019 MUDr. Nagyija Brogyuk; MUDr. Tomáš Grega; prof. MUDr. Miroslav Zavoral, Ph.D.; doc. MUDr. Štěpán Suchánek, Ph.D.
Endoscopic resection techniques such as endoscopic mucosal resection or endoscopic submucosal dissection are effective tools for the treatment of superficial gastrointestinal neoplasia. Endoscopic full-thickness resection (EFTR) is a new endoscopic method with resection of the entire wall of colon. This method combines the application of an over-the-scope clip followed by endoscopic resection using a transparent cap and diathermic loop to produce a targeted perforation that is closed prior to resection. In this case report, we present a case of a 70-year-old female patient with laterally spreading tumor of sigmoideum, non-granular type with negative lifting sign, which was removed endoscopically by EFTR technique. Histologically was confirmed complete resection of intramucosal carcinoma. After the procedure there were no signs of complications and after five days was patient released home from the hospital. This case study documents that EFTR is a safe and effective therapeutic method of early colorectal cancer.

06/2019 MUDr. Michal Volka; MUDr. Tomáš Grega; MUDr. Gabriela Vojtěchová; Mgr. Ondřej Ngo; RNDr. Ondřej Májek, Ph.D.; Mgr. Barbora Bůčková; doc. MUDr. Ilja Tachecí, Ph.D.; MUDr. Marek Beneš; prof. MUDr. Jan Bureš, CSc.; prof. MUDr. Julius Špičák, CSc.; prof. MUDr. Miroslav Zavoral, Ph.D.; doc. MUDr. Štěpán Suchánek, Ph.D.
Background: Fecal immunochemical tests (FIT) have been used as an initial test in CRC screening programs. However, majority of patients don't have advanced neoplasia on colonoscopy. Colon capsule endoscopy (CCE) has the potential to reduce the need for optical colonoscopy (OC).
Main aim of the study was negative predictive value (NPV) of the second generation of colon capsule endoscopy (CCE2) for large polyps (≥ 10 mm). The secondary aims were accuracy of detection of all polyps (polyps ≥ 6 mm and ≥ 10 mm) and cancers, number of complications and target population acceptance of both methods (CCE2 and OC).
Material and methods: In this multicenter (three gastroenterology units) feasibility study, second generation of colon capsule endoscopy (CCE2) has been prospectively compared with OC in persons with positive semi-quantitative FIT with cut-off level 75 ng/ml. Colonoscopy was performed within 10 hours after capsule ingestion. CCE2 videos were viewed independently by a nurse and a physician, both blinded to the results of OC. Complications were assessed as serious (bleeding, perforation) or mild to moderate. The methods of acceptance were evaluated based on the questionnaire completed after both procedures (CCE2 and OC) were finished. The interim analysis of results is presented.
Results: From April 2016, 248 individuals have been enrolled; data from 178 persons has been analyzed. During optical colonoscopy, polyps were diagnosed in 144 persons (81%), polyps ≥ 6 mm and ≥ 10 mm in 90 (51%) and 47 (26%) persons, respectively. The sensitivity of CCE2 for polyps ≥ 6 mm and ≥ 10 mm was 82% (95% confidence interval [CI]: 73-89%) and 79% (95% CI: 64-89%), respectively. The specificity for polyps ≥ 6 mm and ≥ 10 mm reached 85% (95% CI: 76-92%) and 92% (95% CI: 86-96%), respectively. The negative predictive value of CCE2 for polyps ≥ 10 mm was 92% (95% CI: 86-96%). Nurses identified 73 polyps ≥ 6 mm of 90 (83%) and 37 polyps ≥ 10 mm of 47 (79%) found on OC. A total of 119 patients (66%) preferred CCE2 as the primary screening method. Conclusion: Second generation of colon capsule has appeared to have a high negative predictive value for the detection of clinically relevant colorectal neoplasia in screening population. This method might be considered as an adequate tool for colorectal cancer screening.

06/2019 MUDr. Miriama Šmajerová; MUDr. Jakub Foukal, Ph.D.; prof. MUDr. Vlastimil Válek, CSc., MBA
Imaging methods are an important part of the diagnosis and monitoring of patients with colorectal cancer. In addition to the still used ultrasonography and simple chest X-ray, magnetic resonance (MR) of the pelvis is one of the basic methods of staging today. In cases where the finding is unclear or borderline, we use computed tomography (CT) of the chest, abdomen and pelvis or a method combining positron emission tomography (PET) with CT (PET/CT) or PET/MR. Especially in preoperative rectal tumor staging, PET/MR has great potential as a first choice method. In patients with disseminated disease, CT is the standard method for monitoring. In some cases, however, we can take advantage of PET examination.