BACKGROUND: With the aim to show the feasibility of early tumor shrinkage (ETS) concept implementation into daily clinical practice in the Czech Republic, a non-interventional, multicentric, single arm, prospective study in real world set-up was performed. MATERIAL AND METHODS: The study objectives were to explore the time interval from the treatment starting date to the date of the first radiographic control (TFRC) and evaluate the proportion of patients who achieved ≥ 20% tumor regression within the first 8 weeks of first-line therapy, in the real-world settings. RESULTS: The medians of TFRC in all individual participating centers were > 12 weeks (range 14.0-36.4 weeks). TFRC ≤ 8 weeks was reported for only 3% of patients in the cohort with first-line therapy, and there were only 3 patients (1%) who achieved tumor regression of ≥ 20% by day 60 (8.6 weeks). CONCLUSION: These findings indicate that the basic time parameter of ETS could not realistically be employed in routine oncology care of patients with metastatic colorectal cancer (mCRC) in the Czech Republic, unless there would be a strict request to perform TRFC by week 8 since the initiation of the therapy. In addition, the frequency of objective tumor response to first-line therapy with cetuximab + chemotherapy was evaluated. Based on the relative regression in the sum of diameters of measurable metastatic lesions, unconfirmed partial responses were achieved in 42.4 % and unconfirmed complete response in 8.6% of patients, altogether corresponding to the overall response rate of 51% with first-line therapy. The frequency of responses was higher among patients with left than right sided primary tumors. It seems that the regimen of cetuximab/FOLFOX might be more active in frontline therapy of right sided RAS wild type mCRC than cetuximab/FOLFIRI.

• Klíčová slova
• Chemotherapy, chemother­apy, colorectal cancer,
• MeSH
• cetuximab * terapeutické užití   MeSH
• kolorektální nádory * farmakoterapie   patologie   genetika   MeSH
• leukovorin terapeutické užití   MeSH
• lidé MeSH
• prospektivní studie MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• studie proveditelnosti * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cetuximab * MeSH
• leukovorin MeSH
• protinádorové látky imunologicky aktivní MeSH

INTRODUCTION: Biliary tract malignancies belong to very aggressive malignancies of the gastrointestinal tract. The only radical treatment is surgical resection which is possible only in a limited number of cases due to late diagnosis. The aim of this report was to present the experience of our own department with the diagnosis and treatment of these tumours. METHODS: In the years 2005-2021 radical (R0) resection was performed in 27 (28.4%) patients, the same number were managed only symptomatically and in 41 (43.2%) patients we used biliary stenting and external-internal drainage as the definitive procedure. Adjuvant oncological treatment was indicated in 16 (59.3%) of the radically operated and 49 (72.1%) of the non-operated patients. RESULTS: Median overall survival and median progression-free survival in the operated patients were 19.9 months and 15.7 months, respectively. Overall survival in the operated patients was significantly better (p.

• Klíčová slova
• diagnosis, extrahepatic bile duct malignancies, outcomes, results, treatment, type 2 diabetes,
• MeSH
• drenáž MeSH
• lidé MeSH
• nádory žlučových cest * chirurgie   MeSH
• stenty MeSH
• žlučové cesty extrahepatické * chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Modern immunotherapy based on immune checkpoint inhibitors is an innovative treatment, which is already used in the treatment of a number of malignancies, and many other checkpoint inhibitors have been investigated in clinical trials. Monoclonal antibodies against CTLA-4 (cytotoxic T-lymphocyte antigen-4) and PD-1 (programmed cell death-1) or PD-L1 (programmed cell death-1 ligand) are the most commonly used agents. The side effects of these treatments are similar in nature to those of autoimmune diseases. Recently, increasing evidence has indicated that some adverse effects of immunotherapy are associated with the beneficial effect of this treatment. PURPOSE: The aim of this review was to summarize current knowledge of the association between the adverse effects of checkpoint inhibitors and the outcomes of patients treated with this therapy. CONCLUSION: The association between the effect of immunotherapy and the occurrence of adverse reactions has been identified in a number of studies. It has been best documented in patients with malignant melanoma, non-small cell lung cancer, and renal cell carcinoma. Many studies published so far are limited by the relatively low number of patients and their retrospective design, leaving many questions still unanswered. This work was supported by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic and by the Charles University Research Fund (Progres Q39) and by the European Regional Development Fund-Project „Application of Modern Technologies in Medicine and Industry” (No. CZ.02.1.01/0.0/0.0/17_048/0007280). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 3. 11. 2019 Accepted: 8. 12. 2019.

• Klíčová slova
• checkpoint inhibitors, efficacy, immunotherapy, side effects,
• MeSH
• imunoterapie škodlivé účinky   MeSH
• karcinom z renálních buněk farmakoterapie   MeSH
• lidé MeSH
• melanom farmakoterapie   MeSH
• nádory ledvin farmakoterapie   MeSH
• nádory plic farmakoterapie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   MeSH
• protinádorové látky imunologicky aktivní škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky imunologicky aktivní MeSH

BACKGROUND: Chemotherapy (CHT), surgery and radiotherapy (RT) are essential modalities in the treatment of pancreatic malignancies. Their use in practice may be influenced by a number of factors. PATIENTS AND METHODS: Retrospective analysis of CHT, surgery and RT indications and CHT results in patients reported with pancreatic tumor in Pilsen in 2012-2016. RESULTS: A total of 348 patients with median age 68 (19-89) years with newly diagnosed pancreatic tumor, resp., with histology/cytology verified carcinoma in 74.5% cases, with v. s. carcinoma without verification in 21% and with other malignancy not further analyzed here in 4.5% (mostly neuroendocrine tumor). In patients with generalized malignancy (n = 195), exploratory laparotomy was performed in 23% to get tissue samples or verify staging - palliative anastomoses were done in 25% of operated patients, CHT was performed in 29% of the generalized tumors, palliative RT of tumor was performed in 1 patient, and RT of metastases in 3 patients. In patients with local or regional nodal affection (n = 137) laparotomy was done in 59%, R0 resection in 34 (42%) of 81 operated, R1 in 6%, palliative anastomoses were done in 17% and irreversible electroporation in one patients, CHT or radiochemotherapy after R0 and R1 resections was provided in 61% operated patients. The most commonly used CHT was monotherapy with gemcitabine or FOLFIRINOX. The indication of CHT in cytology/histology verified generalized cancers and with excluding patients refusing CHT was proposed in 2012 to 16%, in 2014 to 49% and in 2016 to 84% of patients. In the case of a local or regional nodal involvement the CHT was proposed to 40, 55 and 86% of patients. Median overall survival in generalized tumor patients receiving CHT (n = 137) vs. not-receiving CHT (n = 56) was 2 vs. 8 months (p = 0.0001), and in the local or regional nodal involvement patients receiving CHT (n = 74) vs. not-receiving CHT (n = 62) was 5 vs. 16 months (p = 0.0001). CONCLUSION: CHT and surgery are the dominant treatment modalities. There has been a marked increase in the CHT and histology/cytology verifications indications, with a major factor being a clinician evaluation of a patient to be fit for CHT and its benefit or to complete pancreatic tumor verification. With still very limited results in pancreatic cancer treatment, a careful assessment of each patients indication, respecting patients desire, is always required, knowing that even in the case of advanced disease, CHT can bring benefit, albeit limited.Key words: pancreas - carcinoma - chemotherapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. This study was supported by the grant of Ministry of Health of the Czech Republic - Conceptual Development of Research Organization (Faculty Hospital in Pilsen - FNPl, 00669806).Submitted: 13. 3. 2018Accepted: 18. 4. 2018.

• MeSH
• deoxycytidin analogy a deriváty   terapeutické užití   MeSH
• dospělí MeSH
• fluoruracil terapeutické užití   MeSH
• gemcitabin MeSH
• irinotekan terapeutické užití   MeSH
• kombinovaná terapie MeSH
• leukovorin terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory slinivky břišní * diagnóza   farmakoterapie   radioterapie   chirurgie   MeSH
• oxaliplatin terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• deoxycytidin MeSH
• fluoruracil MeSH
• folfirinox MeSH Prohlížeč
• gemcitabin MeSH
• irinotekan MeSH
• leukovorin MeSH
• oxaliplatin MeSH

BACKGROUND: Metastasis, recurrence, and resistance to chemotherapy are leading causes of the majority of cancer-related mortality worldwide. The process of metastasis can be artificially divided into a series of sequential, highly organized, and organ-specific steps. The underlying mechanisms are still poorly understood, but are believed to be mediated by epithelial-mesenchymal transition (EMT). First described in embryogenesis, EMT is a cellular reprogramming process in which epithelial cells acquire a mesenchymal phenotype. During this transformation, epithelial cells lose their shape, epithelial markers, and ability to grow in colonies. They acquire a spindle-shaped morphology and exhibit more motile and invasive behavior. These phenotypic changes are associated with modifications in different interconnected protein and gene families, such as transcription factors, cadherins, catenins, matrix metalloproteases, and growth receptors. EMT has been observed in many cancers, such as breast, ovarian, colon, and esophageal cancers, and is associated with poor prognosis and metastasis. Also, resistance to cytotoxic treatments is associated with reactivation of embryonic programs. Understanding this process is necessary to provide a better understanding of cancer progression and could lead to the development of new therapeutic or prognostic strategies for the treatment of cancer. CONCLUSION: This article summarizes the known molecular pathways involved in EMT in cancer.Key words: epithelial-mesenchymal transition - carcinoma - metastasisThe authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 24. 6. 2016Accepted: 14. 11. 2016.

• MeSH
• chemorezistence MeSH
• epitelo-mezenchymální tranzice * MeSH
• epitelové buňky patologie   fyziologie   MeSH
• kadheriny metabolismus   MeSH
• lidé MeSH
• metastázy nádorů patofyziologie   MeSH
• mikro RNA metabolismus   MeSH
• nádory patologie   patofyziologie   MeSH
• proteiny hedgehog metabolismus   MeSH
• receptory Notch metabolismus   MeSH
• signální dráha Wnt MeSH
• transformující růstový faktor beta metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kadheriny MeSH
• mikro RNA MeSH
• proteiny hedgehog MeSH
• receptory Notch MeSH
• transformující růstový faktor beta MeSH

BACKGROUND: Worldwide, breast cancer is the leading type of malignancy in women. For premenopausal women, the disease brings much higher risk as it is usually more aggressive with worse prognosis. PATIENTS AND METHODS: In this retrospective study, 92 women treated at the Department of Oncology and Radiotherapy in Pilsen were selected from a basic cohort of 356 women under 35 years of age with breast cancer who were diagnosed between 2006 and 2015. The control group comprised 100 postmenopausal women over 65 years of age who were treated for invasive breast cancer. RESULTS: Overexpression of HER2/neu protein and a triple-negative immunoprofile and basal-like phenotype of cancer were more frequently seen in the women under 35 years of age. In addition, malignant cells were poorly differentiated and more aggressive, and prognostically favourable types were not often seen, in these women. In terms of the course of disease, the outcome was worse for the younger patients, and complete remission was reached less frequently and more cases of advanced disease and death due to the malignancy were detected. CONCLUSION: The incidence of invasive breast cancer in young women is low, representing around 2% of all cases of the disease, but this group of patients is prognostically very important. The cancers at such a young age are usually more aggressive (higher mitotic activity and higher grade), and prognostically worse types, such as triple-negative or basal-like, are seen significantly more often in younger patients. This retrospective study confirmed this premise. Moreover, breast cancer in young women is more often associated with genetic predisposition (e.g., hereditary mutations in BRCA1 and BRCA2 genes) than in older women.Key words: breast cancer - young women - triple negative breast cancer - BRCA mutation - basal-like - tumor-suppressor genes This work was partially supported by the Charles University research fund (project number SVV-2016-260 282). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 10. 1. 2017Accepted: 15. 3. 2017.

• MeSH
• dospělí MeSH
• geny BRCA1 MeSH
• geny BRCA2 MeSH
• incidence MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery analýza   biosyntéza   MeSH
• nádory prsu epidemiologie   genetika   patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery MeSH

BACKGROUND: Lung cancer occupies the leading position of cancer incidence and mortality worldwide, including in the Czech Republic. Despite significant advances in systemic oncology treatments, lung cancer still has the worst prognosis, which is driving the need for innovative therapies and methods to treat this disease. Immunotherapy is a developing area of systemic oncology treatment, which has recently begun to be significantly applied to patients with lung carcinoma. The most useful type of immunotherapy currently employs checkpoint inhibitors, including CTLA-4 inhibitors (ipilimumab and tremelimumab) and PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, durvalumab, and avelumab). Except for monotherapy, different combinations of these inhibitors or combinations between one more of these inhibitors and chemotherapy or targeted treatment are being actively studied. Despite intensive investigations, anti-tumor vaccines and cytokines have not had an important impact on the treatment of lung cancer. Checkpoint inhibitors have yielded favorable results, especially for the treatment of advanced (i.e., stage IIIB and IV) non-small cell lung cancer (NSCLC) and are being extensively investigated for the treatment of SCLC. AIM: The aim of this review was to summarize the most important achievements, possibilities, and perspectives of modern immunotherapy for the treatment of patients with lung cancer. CONCLUSION: Immunotherapy is an important tool in todays arsenal of oncology treatments, and for patients with lung cancer it offers the hope of prolonging life and img iprovints quality.Key words: immunotherapy - lung cancer - NSCLC - SCLC - checkpoint inhibitors This work was supported by National Sustainability Programme I No. LO1503 provided by Ministry of education, youth and sports and program No. 17-30748A devided by The Ministry of Health of the Czech Republic. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 31. 8. 2017Accepted: 7. 9. 2017.

• MeSH
• antigen CTLA-4 MeSH
• antigeny CD274 antagonisté a inhibitory   MeSH
• antigeny CD279 antagonisté a inhibitory   MeSH
• imunoterapie MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nádory plic terapie   MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• CD274 protein, human MeSH Prohlížeč
• CTLA4 protein, human MeSH Prohlížeč
• monoklonální protilátky MeSH
• PDCD1 protein, human MeSH Prohlížeč
• protinádorové látky imunologicky aktivní MeSH

BACKGROUND: Oral mucositis, mTOR associated stomatitis, is a major complication in everolimus (EVE) treatment with an incidence of 44-64%. The management of it in the daily practice has not been described enough, so far. PATIENTS AND METHODS: Retrospective analysis of patients treated with EVE in 2016 at our center, n = 42 patients (69% female), median age 66 (37-81) years, breast cancer in 20 (48%) and renal cell carcinoma in 22 (52%), starting EVE dose of 10mg/day in 34 (81%) and 5mg/day in 8 (19%) patients. RESULTS: Discomfort and/or dysgeusia without mucosa defects (grade 1 NCI-CTC) was in 4/34 (12%) patients, mucosal defects without oral intake limitation (grade 2) in 6/34 (17.5%), mucosal defects limiting oral intake (grade 3) in 7/34 (20.5%) patients. ACTIONS TAKEN: in grade 1 EVE dose reduced to 5mg/day in 1/4 affected patients, in grade 2 locally administered dexamethasone solution recommended in 2/6, reduction of EVE to 5mg/day in 4/6 (in two cases the reduced dose left because of complications recurrences), in grade 3 locally administered dexamehasone solution recommended in 5/7, transient reduction of EVE to 5mg/day in 1/7, permanent reduction of EVE in 5/7 (recurrent aphthous lesions), EVE terminated in 1/7. In patients with EVE starting dose of 5mg/day there was one case (1/8, 12.5%) of grade 2 complication requiring no intervention. The complications developed within 2-20 weeks after EVE initiation (median of 8 weeks). CONCLUSION: The incidence of stomatitis and its severity in this cohort is comparable with published trials data, it confirms the significant incidence of damage affecting the quality of life, oral intake and anti-cancer treatment in daily practice. The interventions used in groups of similarly affected patients appears slightly heterogeneous, influenced by individual physician approach. There is tendency not to interrupt the EVE treatment and keep it either in a dosage of 10 or 5mg/day if the oral damage is tolerable. Local treatment with dexamethasone is not yet fully exploited.Key words: everolimus - stomatitis - mucositis - oral cavity Supported by the grant of Ministry of Health of the Czech Republic - Conceptual Development of Research Organization (Faculty Hospital in Pilsen - FNPl, 00669806) and National Sustainability Program I (NPU I) No. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 27. 2. 2017Accepted: 26. 3. 2017.

• MeSH
• dospělí MeSH
• everolimus škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protinádorové látky škodlivé účinky   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stomatitida chemicky indukované   MeSH
• ústní sliznice účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• everolimus MeSH
• protinádorové látky MeSH

BACKGROUND: The costs of oncology treatments are increasing, due to the rising prevalence of malignant diseases and the introduction of expensive novel anti-cancer agents. The new European Society for Clinical Oncology (ESMO) has recently developed a new parametric system to evaluate the clinical benefit of drugs. The Magnitude of Clinical Benefit Scale (ESMO-MCBS) compares the contribution of a novel drug based on overall and progression-free survival and quality of life with those of current treatment options. MATERIAL AND METHODS: An expert group of the Czech Oncological Society conducted an assessment based on published data and an ESMO-MCBS methodology for antineoplastic agents used for the treatment of solid tumors with limited reimbursement to Comprehensive Cancer Centers. We evaluated drugs categorized as "S" that were eligible for public health insurance as of January 1, 2017. RESULTS AND CONCLUSION: The ESMO-MCBS score is a promising new parameter for the evaluation of new anticancer drugs. The ESMO-MCBS method for assessing the clinical benefit of drugs is simple, robust, and reproducible. The advantage of the assessment is that it is not based on a single index but rather combines several dimensions of drug performance. This parameter will be gradually added to Czech cancer guidelines. Scores obtained in the majority of cases correspond to the observed benefit of a drug in routine clinical practice.Key words: tumors - farmacotherapy - assesment study as a subject - survival - protocols of anti-cancer therapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 3. 5. 2017Accepted: 20. 6. 2017.

• MeSH
• analýza nákladů a výnosů metody   MeSH
• lékařská onkologie ekonomika   MeSH
• lidé MeSH
• nádory farmakoterapie   ekonomika   MeSH
• protinádorové látky ekonomika   terapeutické užití   MeSH
• společnosti lékařské MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Turecko MeSH
• Názvy látek
• protinádorové látky MeSH

Goblet cell carcinoid (GCC) of the appendix is extremely rare, representing approximately 5% of all primary appendiceal neoplasms. Histologically there are three groups of GCC: group A (typical GCC), adenocarcinoma ex GCC signet ring cell type (group B), and adenocarcinoma ex GCC poorly differentiated carcinoma type (group C), which is the most aggressive. GCC metastasizes in 15-60% of cases, mainly to the ovaries, pelvis, abdominal cavity, ribs, vertebrae, and lymph nodes. Hematogenous metastasis to the liver or other parenchymal organs can occur, but this is very rare. The different organs metastases havent been described yet. The primary mode of treatment is radical surgical resection or debulking, followed by chemotherapy; however, patients with unresectable or recurrent GCC are candidates for systemic therapy. Here, we report a case of very aggressive GCC of the appendix, which had metastazed to the liver at the time of diagnosis and subsequently metastasized to the orbit.

• MeSH
• karcinoid sekundární   MeSH
• lidé MeSH
• nádory apendixu patologie   MeSH
• nádory orbity sekundární   MeSH
• pohárkové buňky patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH