Selected articles

04/2017 Mgr. et Mgr. Anna Rubešová, Ph.D., Bc. Michaela Čadková Svejkovská, Mgr. Zita Dubová
Psychosocial care provided to people with cancer improves quality of their lives and reduces treatment costs. A survey, the first of its kind in the Czech Republic, was conducted to identify the needs of these patients and the importance of their needs. In order to explore the needs we have created a questionnaire, which was completed by 253 respondents. Responses showed that patients with cancer have a special need for a good relationship with health care professionals, psychological support and information regarding what state support they are entitled to during and after the disease. In all these areas, care of cancer patients can be improved.

04/2017 MUDr. Libor Havel
The activating epidermal growth factor receptor mutation is present in almost 50% of patients with advanced non-small cell lung cancer, who are of Asian ethnicity¹ compared with only 12% in the Caucasian population.² These molecular alterations predict sensitivity to first and second generation epidermal growth factor receptor tyrosine kinase inhibitors such as erlotinib, gefitinib, afatinib. Response rate and progression-free survival with epidermal growth factor receptor tyrosine kinase inhibitors are superior to standard first-line platinum doublet chemotherapy, making them the standard of care.

04/2017 MUDr. Petr Karásek
Pancreatic cancer is a highly aggressive malignancy with poor treatment results at all stages. At the time of diagnosis, metastatic spread or locally advanced disease is present in most patients. Despite low efficacy, gemcitabine monotherapy has been used in palliative treatment of advanced disease for many years. In recent years therapeutic options have expanded significantly. In palliative treatment of the first line, FOLFIRINOX and nab-paclitaxel/ gemcitabine regimens have been introduced into clinical routine, which increased the overall survival by 4-5 months. Other possibilities prolongation of survival is the second line treatment with nanoliposomal irinotecan in combination with 5-fluorouracil and leucovorin in patients pretreated with gemcitabine regimen. Interesting results brings the studies aimed at influencing the extracellular matrix of tumor cells.

04/2017 MUDr. Beatrix Bencsiková, Ph.D.
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of gastrointestinal tract. Oncogenic activating mutations in the receptor tyrosine kinases KIT (78 %) and PDGFRA (platelet-derived growth factor receptor alpha; 5-8 %) play a crucial role in the molecular pathogenesis of GIST. Better treatment strategies and targeted therapies have improved survival rates for patients with GIST significantly. Imatinib, the receptor tyrosine kinase inhibitor, has revolutionized the therapeutic landscape for GIST patients and remains the mainstay first-line clinical option for both unresectable and advanced GISTs, as well as for adjuvant treatment after resection of high risk GIST. Sunitinib is indicated as second-line therapy. Regorafenib has been approved as third-line treatment of patients who progressed on or are intolerant to prior imatinib and sunitinib. Early identification of patients with suboptimal response to therapy is an important issue of a personalized treatment of patients with GIST.

04/2017 Prof. MUDr. Vítězslav Kolek, DrSc.
An immuno-therapy directed at the inhibition of PD-L1 (programmed death-ligand 1) protein ligand in patients with non-small cell lung cancer in the second or third line of treatment is reported, according to the results of the POPLAR and OAK studies. The atezolizumab treatment product showed an improvement in survival compared to docetaxel in all subgroups of patients with the exception of tumors with epidermal growth factor receptor and anaplastic lymphoma kinase positivity. Efficacy was greatest in tumors with high expression of PD-L1 and large lymphocytic infiltration of the tumor but was found even in low or inconclusive expression. The drug was very well tolerated and is another hope for patients with metastatic and locally advanced non-small cell lung carcinoma.

04/2017 Prof. Ing. Jiří Neužil, CSc.
Breast cancer is highly heterogeneous and its different types are differently susceptible to therapy. Some types are hard to manage and some are practically incurable. It is therefore important to find new target sites that would not be subject to mutations and that would be utilised for targeted therapy of neoplastic diseases with limited toxicity of normal tissues. Therefore, we designed and tested a novel anti-cancer agent derived from tamoxifen, which is targeted to mitochondria. Contrary to tamoxifen, the new agent is efficient against hard-to-treat types of breast cancer. We are currently preparing phase 1 clinical trial of our new agent.

04/2017 MUDr. Tomáš Svoboda, Ph.D.
A new group of targeted drugs is coming to the fore of clinical practice in endocrine dependent metastatic breast cancer. At this point CDK4/6 inhibitors are introduced whereas given in combination with aromatase inhibitors. The most recently published data from MONALLESA-2 study with letrozol and ribociclib show very high efectivity and good toxicity profile of this combination. The median PFS in ribociclib arm was not reached in this study until now. It seems to us that this regimen has a big chance to become a new treatment standard in the first line setting soon as it is proved already in the most important treatment guidelines worldwide.

04/2017 MUDr. Miloš Holánek
Hormonal treatment in patients with disseminated, hormonal dependent breast cancer is a clearly preferred treatment alternative. It should be considered in all patients, regardless of the extent and location of the disease. Only in the case of a rapidly progressive and aggressive disease with signs of a visceral crisis is chemotherapy an option, because the onset of chemotherapy is faster than the onset of the hormone treatment. Currently, the possibilities of hormonal therapy of advanced breast cancer are changing - due to the combination of hormone therapy with cyclin-dependent kinase 4/6 inhibitors (CDK4/6), there has been a marked improvement in the effectiveness of therapy. Improvement in treatment occurred in all subgroups of patients who received CDK4/6 inhibitors. Until now, no predictor has been identified. Palbociclib, ribociclib, and abemaciclib were evaluated in clinical trials. This article summarizes the effectiveness and tolerance of these preparations.

04/2017 MUDr. Dagmar Brančíková, Ph.D., MUDr. Markéta Protivánková
Treatment of locally advanced breast cancer with HER2/neu amplification is systemic and consists of chemotherapy and receptor blockade. The neoadjuvant procedure is designed to rapidly reduce tumor mass and operability, despite the misgivings of several studies, the complete remission remains pathological (pCR) is a reliable substitute Time to progression or overall survival. In this paper we present a summary of some experience with chemotherapy regimens and HER2/neu blockers and their potential combinations. The most promising 3-year data from trial NeoSphere show a promising trend to improve progression free survival for the combination of docetaxel/trastuzumab/pertuzumab that increased pCR from 29% to 46%. In all neoadjuvant studies, the group of patients with a hormone-positive disease had less benefit from anti-HER2 blockade and chemotherapy, but this procedure has yet to be verified as the best.

04/2017 Doc. MUDr. Michal Zikán, Ph.D.
A new drug using a unique mechanism of action - an intervention in DNA repair - is being introduced into the treatment of ovarian cancer. Olaparib is a drug of the so-called PARP inhibitor group. Interference with the mechanism of DNA repair is particularly effective in BRCA1/2 gene mutation carriers, in whom one of reparation ways is primarily faulty by a germ-line or somatic mutation. Olaparib in the treatment of platinum-sensitive recurrent ovarian cancer in BRCA1/2 mutation carries leads to prolonged progression-free survival and increased overall survival.

04/2017 Doc. MUDr. Lenka Foretová, Ph.D.
Hereditary cause, inherited mutation in BRCA1 or BRCA2 genes, is responsible for 3-5% of unselected breast cancer cases and 15-20% of ovarian cancer cases. The carriers of these mutations have many times increased risk of breast, ovarian cancer, but also the risks of other solid tumors. Preventive care should be offered through comprehensive oncology and gynecology centers. Women carriers of mutations should be seen from age of 25 by oncologist every 6 month with ultrasound and MRI of breasts, from 30-65 with mammography and MRI, followed by ultrasound and mammography itself. Prophylactic bilateral mastectomy decreases the risk of breast cancer from 85% of lifetime risk to only 1-5%. Prophylactic oophorectomy is necessary for the reduction of risk of ovarian cancer, since no preventive care is effective for early detection of ovarian cancer. Explaining all these preventive procedures, their importance for cancer risk reduction, is important part of specialized preventive care.

04/2017 RNDr. Ing. Bc. Libor Staněk, doc. MUDr. Petra Tesařová, CSc.
Triple negative breast carcinoma accounts for approximately 15-20 % of all breast carcinoma and is characterized by loss of expression of a-estrogen, progesterone and HER2 receptors, predominantly low differentiation, mostly in the basal form of the subgroup. They are more common in younger women and are associated with the occurrence of hereditary or sporadic forms of breast cancer caused by a pathogenic mutation in the BRCA1 and BRCA2 gene or another genetic disorder leading to HR-deficient tumors.

04/2017 MUDr. Věra Benešová
The breast carcinoma belongs to the most frequently occurred malignant tumours by females. 90 up to 95 % of tumours emerge coincidentally. 5 up to 10% of tumours belong to hereditary tumours. The most common cause of the hereditary tumours is the mutation of the gene BRCA1/2. The following article deals with indication for the genetic test and medical care about those affected female patients.

03/2017 MUDr. Darja Šustrová
Czech Republic has the highest incidence of kidney cancer in the world. Although the incidence of renal cell carcinoma has been increasing, the survival rate has improved substantially. Renal cancer consists of an heterogeneous group of tumors with distinct genetic and metabolic characteristics and histopathologic and clinical features. It has become more evident that a multidisciplinary team approach is necessary to provide optimal care to patients. This team includes medical oncologists, radiologists, urologist pathologists, radiation oncologists and surgeons. In the era of tyrosinkinase inhibitors therapy the role of cytoreductive nephrectomy should be discussed. There is a role of surgeon in the management of oligometastatic disease. Resection of oligometastatic disease can in selected patients prolong survival and delay the need to commence systemic treatment. When determining the prognosis of RCC, MSKCC criteria based on Motzer criteria are still used, although The MSKCC model was developed during the cytokine era, and was subsequently validated in the TKI population era by Heng, who confirmed four of the five MSKCC criteria (excluding elevated LDH) as independent predictors of poor prognosis, and added neutrophilia and thrombocytosis as additional risk factors, with a median survival rate of 43.2, 22.5 and 7.8 months in the favourable, intermediate and poor prognostic groups. Renal cell carcinoma can sometimes follow an indolent course, therefore a period of observation should be considered before starting treatment.

03/2017 MUDr. Eugen Kubala
The treatment of a metastatic melanoma has progressed so much that before we choose it, we have to ask some questions. What first-line treatment strategy should we choose for patients with the BRAF mutation? Which first-line patients are suitable for immunotherapy? Is the presence of BRAF mutation definite predictor for biological treatment? Pharmacological inhibition of mitogen-activated protein kinase signaling pathways (MAPK) has brought significant advances in the treatment of patients with BRAF-mutated metastatic melanoma. Among these successful pharmaceutics belong BRAF inhibitors (vemurafenib, dabrafenib, encorafenib), and MEK inhibitors (trametinib, selumetinib, cobinetinib, binimetinib). Their advantage is a fast induction of the overall response to 70 %, but the major disadvantage is the development of resistance in the majority of patients (100 %). Its overcoming is investigated in the use of other kinase inhibitors of the MAPK signaling pathway including RAS/RAF/MEK/ERK kinase. A certain disadvantage is the ability to induce resistance to immunotherapy anti-PD1 by inducing mesenchymal transformation. Innately resistant tumors exhibit transcriptional signature (IPRES or innate resistance to PD-1), which exhibits an increased expression of genes involved in the regulation of mesenchymal transformation, cell adhesion, extracellular matrix remodeling, angiogenesis, and wound healing. The same genetic signature that induces IPRES, was observed in melanoma tissues after treatment BRAF inhibitors, and thus induces cross-resistance to anti-PD-1 treatment. Immunotherapy is another treatment option for metastatic melanoma. Its use does not require the presence of BRAF mutation, however, it also lacks a clear predictor of treatment effectiveness. The number of responses to treatment is only about 30-40 %, but the resistance occurs in only about 25 %. We can influence the immune system by blocking anti-CTLA4 antibody ipilimumab, or by blockade of a local immune response in the tumor itself using anti PD1 antibodies nivolumab. Both drugs belong to a group checkpoint inhibitors, which block the blinding of the immune system and the tumor escape from immune surveillance. At present, we can use both compounds in the first-line treatment in the monotherapy or in combination. More effective treatment is by nivolumab. If we achieve the treatment response it lasts even long after discontinuation of therapy. Evidence showed the advantages of biological treatment over immunotherapy in the first-line treatment of metastatic melanoma. This could help in the correct orientation in choosing the right method of treatment for an individual patient.

03/2017 Prof. MUDr. Jana Skřičková, CSc.
Bronchogenic carcinoma is one of the most common carcinomas of the world. Roughly 85% of all bronchogenic carcinoma is a non-small-cell lung carcinoma (NSCLC). A new approach to its treatment is immunotherapy. This treatment is not directed to the tumor itself, but on the immune system of the patient. Pembrolizumab is a human monoclonal antibody that binds to a PD-1 receptor of programmed cell death and thus blocks its interaction with ligands of PD-L1 and PD-L2. Blocking PD-1 receptor by pembrolizumab prevents binding of the respective ligands and, thus, enhances the T-cell immune response, which may thus be used in the fight against the tumor itself. The article presents the results of studies that demonstrate the effectiveness pembrolizumab in the first and other lines of treatment. It is necessary to know the state of PD-L1 expression in all NSCLC, regardless of histological type, before pembrolizumab can is indicated for any line of treatment.

03/2017 MUDr. Libor Havel
Lung cancer is one of the most common cancer worldwide. There is approximately 1.8 million of new lung cancer cases, and 1,6 million deaths by lung cancer. There are changes is in frequency of histologic subtypes during past two decades. Predominant histology became non-squamous non-small cell lung cancer, and majority of new therapies are related to this histologic subtype. Is there any fundamental difference in treatment strategy between squamous and non-squamous lung cancer?

03/2017 MUDr. Igor Richter, Ph.D., doc. MUDr. Josef Dvořák, Ph.D., MUDr. Věra Hejzlarová, MUDr. Jiří Bartoš, MBA
Introduction: The aim of this retrospective study is demonstrated efficacy and tolerance of enzalutamide therapy in real clinical practice in 33 patients with metastatic castration-resistant prostate cancer (mCRPC) who had previous chemotherapy.
Patients and methods: Between November 2014 and June 2016 we treated with enzalutamide a total of 33 patients with metastatic castrate resistant prostate cancer. The all patients were previous treated by one or two lines of chemotherapy. The enzalutamide was administered by standard dose 160 mg daily.
Results: One patient had cerebral hemorrhage grade IV. In other patients the non-hematological toxicity evaluation did not achieve the grade III or IV. Anemia grade III-IV was described in 6 patients and thrombocytopenia grade III-IV in 2 patients. The median of progression free survival was 7.0 (95% CI 6.1-7.9) months. The median of overal survival was 8.4 (95 % CI 5.1-11.7) months.
Conclusion: The study demonstrated our first experience with enzalutamid in postchemo-indication in patients with mCRPC with good toleration and efficacy.

03/2017 MUDr. Otakar Čapoun, FEBU
Castration-resistant prostate cancer is a heterogeneous disease, which maintains a dependence of tumor cells to hormonal stimulation. In the case of a failure of the first-line testosterone-lowering therapy one of the next options are new hormonal agents (abiraterone, enzalutamide). Enzalutamide proved to be more effective in the second-line treatment than commonly used bicalutamide. Subanalysis of an abiraterone trial shows that the greatest benefit from the second-line hormonal therapy have patients with low levels of prostate-specific antigen, minimal pain and more differentiated tumors. However, higher Gleason score should not affect the choice of the second-line treatment. Extended follow-up in the trial with enzalutamide before chemotherapy confirmed the efficacy of this drug. The duration of a prior castration therapy has only a minimal impact on the efficacy of abiraterone in the second-line hormonal therapy. Patients receiving corticosteroids concurrently with enzalutamide in the post-docetaxel trial had generally poorer survival outcomes, however enzalutamide always demonstrated superior efficacy in comparison with placebo. Questions about sequence of treatment in the third and additional lines have not yet been resolved. The future of new hormonal agents lies in their using within the first-line hormonal therapy or adjuvantly to a radical treatment.

03/2017 MUDr. Leona Koubková
Targeted therapy on the basis of predictive biomarkers that predict the efficacy, at least some patients allows to individualize the treatment and in recent years led to improved treatment outcomes in patients with unfavorable diagnosis of NSCLC (non-small-cell lung cancer). One of these predictive biomarkers is a gene rearrangement EML-4-ALK and ROS1, where is indicated treatment with ALK and ROS1 inhibitors.