Jiri Polivka

Precizn? onkologie p?edstavuje nov? pojet? onkologick? p??e, kter? umo??uje co mo?n? nejlep?? individualizaci l??by pro konkr?tn?ho pacienta a konkr?tn? tumor. Toho je dosa?eno s vyu?it?m v?sledk? pokro?il?ch molekul?rn?‑genetick?ch dia...

Background/Aim: Non-invasive circulating tumor biomarkers in liquid biopsy, such as microRNAs (miRNA), provide for better personalization of treatment strategies. The aim of our study was to assess the prognosis of patients with melanoma undergoing tumor resection with curative intent based on analysis of selected circulating miRNAs. Patients and Methods: A total of 22 patients with stage I to III melanoma were enrolled into this prospective study. Plasma samples were obtained pre-surgery and early post-surgery from peripheral blood draws. A panel of 23 candidate miRNAs was designed and expression of miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction with exogenous reference control cel-miR-39-3p. Results: Higher preoperative expression levels of miR-99a (p=0.008), miR-320 (p=0.009), miR-1908 (p=0.001), miR-494 (p=0.018) and miR-4487 (p=0.048) were associated with a shorter disease-free interval. Similarly, higher preoperative plasma levels of miR-99a (p=0.017), miR-221 (p=0.026), miR-320 (p=0.016), miR-494 (p=0.009), miR-1260 (p=0.026) and miR-1908 (p=0.024) were associated with worse overall survival. No significant differences between pre- and postoperative plasma miRNA levels were observed. Conclusion: Liquid biopsy is a minimally-invasive approach which can lead to a better understanding of cancer behavior and offers the possibility of precise patient prognosis, allowing selection of the most appropriate treatment. Our study showed that preoperative plasma levels of miR-99a, miR-221, miR-320, miR-494, miR-1908 and miR-4487 were associated with disease-free interval and overall survival of patients with early-stage melanoma. This approach may help in decision-making about the appropriateness of modern adjuvant treatment administration in patients with resectable melanoma.

The model of centralized stroke care in the Czech Republic was created in 2010-2012 by Ministry of Health (MH) in cooperation with professional organization-Cerebrovascular Section of the Czech Neurological Society (CSCNS). It defines priorities of stroke care, stroke centers, triage of suspected stroke patients, stroke care quality indicators, their monitoring, and reporting. Thirteen complex cerebrovascular centers (CCC) provide sophisticated stroke care, including intravenous thrombolysis (IVT), mechanical thrombectomy (MTE), as well as other endovascular (stenting, coiling) and neurosurgical procedures. Thirty-two stroke centers (SC) provide stroke care except endovascular procedures and neurosurgery. The triage is managed by emergency medical service (EMS). The most important quality indicators of stroke care are number of hospitalized stroke patients, number of IVT, number of MTE, stenting and coiling, number of neurosurgical procedures, and percentage of deaths within 30days. Indicators provided into the register of stroke care quality (RES-Q) managed by CSCNS are time from stroke onset to hospital admission, door-to-needle time, door-to-groin time, type of ischemic stroke, and others. Data from RES-Q are shared to all centers. Within the last 5years, the Czech Republic becomes one of the leading countries in acute stroke care. The model of centralized stroke care is highly beneficial and effective. The quality indicators serve as tool of control of stroke centers activities. The sharing of quality indicators is useful tool for mutual competition and feedback control in each center. This comprehensive system ensures high standard of stroke care. This system respects the substantial principles of personalized medicineind-ividualized treatment of acute stroke and other comorbidities at the acute disease stage; optimal prevention, diagnosis and treatment of possible complications; prediction of further treatment and outcome; individualized secondary prevention, exactly according to the stroke etiology. The described model of stroke care optimally meets criteria of predictive, preventive, and personalized medicine (PPPM), and could be used in other countries as well with the aim of improving stroke care quality in general.

IDH1 mutation is associated with lower expression of VEGF but not microvessel formation in glioblastoma multiforme IDH1 mutation is associated with lower expression of VEGF but not microvessel formation in glioblastoma multiforme

Febrile neutropenia (FN) is a common and potentially fatal complication of anticancer treatment, particularly in patients receiving myelosuppressive chemotherapy. It has been shown that prophylaxis with granulocyte colony-stimulating factor (G-CSF), especially its pegylated forms, significantly reduces the incidence of FN, the likelihood of chemotherapy dose intensity reduction and, also, the number of hospitalizations due to FN. This review discusses currently published results from clinical trials dealing with FN prophylaxis in routine clinical practice in patients with solid tumors and myeloproliferative malignancies with a focus on lipegfilgrastim, which is the newest modification of the original molecule filgrastim. The discussed results proved that prophylactic administration of lipegfilgrastim can almost eliminate the risk of FN and significantly reduce the risk of chemotherapy (CHT) dose reduction in routine clinical practice in cases of a clear high-risk chemotherapy regimen or in the presence of risk factors (such as age, comorbidities, performance status, etc.) in patients who received chemotherapy with medium risk of FN.

Monoclonal antibodies binding the epidermal growth factor receptor (EGFR), such as cetuximab or panitumumab, are widely used targeted therapeutics for the treatment of patients with colorectal cancer. The clinical significance of these drugs has so far been associated with combined chemotherapy or radiation. It has been shown that these treatment strategies have their clinical limitations and do not fully exploit the immunomodulatory effect of these drugs. In this review, we discuss the mechanisms of immunomodulation together with the anticancer immune response to the monoclonal antibodies targeted to the EGFR. The combination of anti-EGFR monoclonal antibodies with other immunotherapeutic treatment modalities certainly brings new opportunities for targeted therapy in patients with colorectal cancer.

Neurology is one of the typical disciplines where personalized medicine has been recently becoming an important part of clinical practice. In this article, the brief overview and a number of examples of the use of biomarkers and personalized medicine in neurology are described. The various issues in neurology are described in relation to the personalized medicine and diagnostic, prognostic as well as predictive blood and cerebrospinal fluid biomarkers. Such neurological domains discussed in this work are neuro-oncology and primary brain tumors glioblastoma and oligodendroglioma, cerebrovascular diseases focusing on stroke, neurodegenerative disorders especially Alzheimer’s and Parkinson’s diseases and demyelinating diseases such as multiple sclerosis. Actual state of the art and future perspectives in diagnostics and personalized treatment in diverse domains of neurology are given.

Anaplastic oligodendrogliomas (AO) are rare tumors. Two phase III clinical trials (RTOG 9402 and EORTC 26951) proved favorable effects of radiotherapy (RT) with chemotherapy (procarbazine, lomustine and vincristine; PCV) in patients with AO carrying chromosomal mutation of co-deletion1p/19q even if it was not the primary endpoint of these studies. We assessed 1p/19q co-deletion as a prognostic and predictive biomarker for our patients with AO. 1p/19q co-deletion was assessed by fluorescence in situ hybridization in tumor samples from 23 patients and correlated with progression-free (PFS) and overall (OS) survival for the entire cohort and for the subgroups of patients with different treatment (neurosurgery plus RT alone vs. RT plus PCV). 1p/19q co-deletion was identified in 12 out of 23 tumors (52.2%). Patients with co-deletion had longer OS (587 vs. 132 weeks, p=0.012) and a trend for longer PFS (321 vs. 43 weeks, p=0.075). Patients with co-deletion treated with neurosurgery and RT plus PCV vs. neurosurgery and RT alone also had longer OS (706 vs. 423 weeks, p=0.008). There was no survival difference for patients without 1p/19q co-deletion in relation to treatment. The prognostic value of 1p/19q co-deletion in our patients with AO was verified. The strong positive predictive value of this biomarker for OS was also shown for patients with co-deletion treated with neurosurgery and RT plus PCV vs. neurosurgery and RT alone.

The main goal of personalized medicine is the individualized approach to the patient’s treatment. It could be achieved only by the integration of the complexity of novel findings in diverse “omics” disciplines, new methods of medical imaging, as well as implementation of reliable biomarkers into the medical care. The implementation of personalized medicine into clinical practice is dependent on the adaptation of pre-graduate and post-graduate medical education to these principles. The situation in the education of personalized medicine in the Czech Republic is analyzed together with novel educational tools that are currently established in our country. The EPMA representatives in the Czech Republic in cooperation with the working group of professionals at the Faculty of Medicine in Pilsen, Charles University in Prague have implemented the survey of personalized medicine awareness among students of Faculty of Medicine in Pilsen—the “Personalized Medicine Questionnaire”. The results showed lacking knowledge of personalized medicine principles and students’ will of education in this domain. Therefore, several educational activities addressed particularly to medical students and young physicians were realized at our facility with very positive evaluation. These educational activities (conferences, workshops, seminars, e-learning and special courses in personalized medicine (PM)) will be a part of pre-graduate and post-graduate medical education, will be extended to other medical faculties in our country. The “Summer School of Personalized Medicine in Plzen 2015” will be organized at the Faculty of Medicine and Faculty Hospital in Pilsen as the first event on this topic in the Czech Republic.

Oligodendrogliomas are uncommon tumors in neurooncology that represent about 5% of primary brain malignancies. Their high sensitivity to radiotherapy and chemotherapy was observed a long time ago. Nonetheless, the evidence-based proof of the significantly longer survival in patients with oligodendrogliomas treated with combined chemotherapy and radiotherapy in comparison to radiotherapy-alone did not exist. The long-term follow-up of two landmark phase III clinical trials: RTOG 9402 and EORTC 26951, recently demonstrated favorable effects of combined radiotherapy and chemotherapy (procarbazine, lomustine and vincristine) in patients with anaplastic oligodendrogliomas and anaplastic oligoastrocytomas carrying the chromosomal mutation of co-deletion of 1p/19q. There is also an increasing role of other molecular biomarkers, such as mutations in the metabolic enzyme isocitrate dehydrogenase 1/2, O6-methylguanine DNA methyltransferase gene promoter methylation, or glioma genome cytosine-phosphate-guanine islands methylator phenotype. The analysis of molecular genetics in oligodendrogliomas is now recommended as an important part of the management of these tumors and together with the novel chemotherapeutic regimens means a paradigm shift in current clinical practice in neurooncology.