Clinically node-positive bladder cancer: oncological results of induction chemotherapy and consolidative surgery.

Patients with clinically node-positive bladder cancer have a poor prognosis, with many receiving only palliative chemo- therapy. We evaluated oncological results in bladder cancer patients with clinically regional and supraregional lymph- adenopathy treated with induction chemotherapy (IC) and consolidative cystectomy. Twenty-five patients with clinically node-positive bladder cancer (including pelvic and retroperitoneal nodes) were treated with 2-4 cycles of IC followed by consolidative cystectomy between 2010 and 2016. Pathologic complete response (pCR) was defined as no residual tumor in the final specimen (ypT0N0).The 3-year cancer-specific (CSS) and recurrence-free survival (RFS) for the whole cohort were 52% and 39%, respectively. The 3-year RFS differed according to volume of nodal metastases, the rates were 56% for minimal nodal disease (cN1) versus 33% for cN2-3 and 0% for cM1 disease (p<0.001). pCR was seen in 7 (28%) patients; 50% in cN1 versus 13% in cN3-M1. pCR associated with 3-year CSS of 80% versus 45% in patients with persistent disease after IC. In conclusion, a multimodal approach to patients with clinically node-positive bladder cancer, consisting of IC followed by consolidative surgery, may achieve long-term survival in selected patients. Better results may be expected in patients with initially minimal nodal burden and complete pathologic response to chemotherapy. Further studies are warranted to improve patient selection for consolidative surgery, especially with supra-regional metastases.

[Pilot Study on MicroRNAs as Biomarkers of Response to Sunitinib Treatment in Patients with Metastatic Renall Cell Carcinoma]. / MikroRNA jako biomarkery odpovedi na lécbu sunitinibem u pacientu s metastatickým karcinomem ledvin - pilotní studie.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2-3% of all malignant tumours. Metastatic RCC (mRCC) is commonly treated with tyrosine kinase inhibitors (TKI). Effective TKIs administration can be achieved only by accurate prediction of therapeutical response. Therefore, the aim of this study was to analyse papers concerning predictive potential of microRNA (miRNA). MATERIAL AND METHODS: We chose seven candidate miRNAs and analysed their expression on 44 patients divided into cohort with poor and good response to sunitinib treatment. Patients were divided into two groups according to progression-free survival. RNA from tissue samples was isolated and expression of selected miRNAs was measured using quantitative PCR with miRNA-specific TaqMan probes. RESULTS: We successfully validated two miRNAs to be differentially expressed in responding and non-responding patients to sunitinib treatment. Other analysed miRNAs have not shown predictive potential. CONCLUSION: From miRNAs studied so far, two miRNAs had predictive value according to present study.Key words: microRNA - renal cell carcinoma - sunitib 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. Supported by Ministry of Health of the Czech Republic, grant No. 15-34678A. All rights reserved.Submitted: 19. 3. 2018Accepted: 20. 3. 2018.

Prognostic role of serum C-reactive protein in patients with advanced-stage NSCLC treated with pemetrexed.

Pemetrexed is an intravenously administered antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). It has been previously demonstrated that the superiority of pemetrexed is limited to patients with non-squamous histology. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in a large cohort of patients with non-squamous NSCLC treated with pemetrexed. Clinical data of 325 patients were analysed. Serum samples were collected within one week before the initiation of treatment. The median progression-free (PFS) and overall survival (OS) for patients with high CRP was 2.1 and 9.5 compared to 4.2 and 20.5 months for those with normal CRP (p=0.002 and p<0.001, respectively). The multivariable Cox proportional hazards model revealed that serum CRP (HR=1.46, p=0.002) was significantly associated with PFS and also with OS (HR=1.95, p<0.001). In conclusion, the study results suggest that pretreatment serum CRP is associated with poor outcome of non-squamous NSCLC patients treated with pemetrexed.

[Immunotherapy of Renal Cell Carcinoma]. / Imunoterapie zhoubného nádoru ledviny.

Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab. The therapeutic efficacies of combinations such as targeted therapy with immune checkpoint inhibitors and anti-CTLA-4 with anti PD-1 (-L1) have been reported in many studies. Preliminary results are encouraging but the high toxicities and elevated cost are limiting. Treatments with combinations of bevacizumab and atezolizumab, axitinib and pembrolizumab or avelumab, lenvatinib and pembrolizumab, and nivolumab and ipilimumab (results from study phase I, II, and sometimes III) are reported to be highly effective and to result in long-lasting responses with response-rates of 70-100%. So far, valid predictors for these therapies have not been forthcoming, but considerable work is being exerted in this area. Heng and Memorial Sloan Kettering Cancer Center (MSKCC) models are still being used to select patients for immunotherapy. Immunotherapy will definitely continue to play an important role in the treatment of patients with renal cell carcinoma; however, many questions remain.Key words: renal cell carcinoma - immunotherapy - checkpoint inhibitors - target therapy Supported by MH CZ - DRO (MMCI, 00209805) This work was supported by program of the Czech Ministry of Health No. P03-15-34 678A. 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: 16. 8. 2017Accepted: 7. 9. 2017.

[Controversy in the Postoperative Treatment of Low-grade Gliomas]. / Kontroverze v pooperacní lécbe low-grade gliomu.

BACKGROUND: The optimal treatment for low-grade gliomas remains controversial. Neurosurgery, radiotherapy, and chemotherapy are the main treatment options. Despite advances in oncology, there are still a lot of uncertainties, and the optimal sequences, combinations, and timings of these procedures have not yet been optimized. It is still unclear whether temozolomide can replace effective, but toxic PCV chemotherapy (procarbazine, lomustine, vincristine) and whether temozolomide can be used upfront alone instead of radiotherapy alone. Mature results from phase III trials (CODEL, EORTC 22033-26033) will provide answers to these questions. Correlative analyses of survival data and molecular marker findings (1p/19q codeletion, IDH1/2 mutation, and MGMT promoter methylation status) are essential. Due to slow progressive nature of the disease, all clinical trials with low-grade gliomas are complicated by the need for long-term follow-up to obtain valid mature data, which makes any new treatment procedures or developments in basic research developed during the course of closed clinical trials difficult to apply in daily clinical practice. An example is the recently published RTOG 9802 study evaluating the role of adjuvant PCV in combination with radiotherapy for the treatment of high-risk low-grade glioma patients where the recruitment of patients was initiated almost two decades ago. Health-related quality of life after treatment of patients with expected long-term survival is also very important and its maintenance is currently the focus of considerable interest. AIM: The main objective of the present review is to summarize the results of key clinical trials and highlight controversial issues that could have an impact on future daily practice. Another aim is to discuss these issues in the light of newly established molecular markers from the new 2016 WHO Classification of Tumors of the Central Nervous System.Key words: glioma - astrocytoma - radiotherapy - temozolomide - PCV - cognition This work was supported by MH CZ - RVO (MMCI, 00209805) and by project of the Ministry of Education, Youths and Sports of the Czech Republic CEITEC 2020 (LQ1601). 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: 21. 2. 2017Accepted: 20. 3. 2017.

[The Role of Chemotherapy in the Treatment of Low-grade Gliomas]. / Postavení chemoterapie v pooperacní lécbe low-grade gliomu.

BACKGROUND: The standard postsurgical options for low-grade gliomas include watchful waiting or radiotherapy depending on the risk factors for recurrence. The use of chemotherapy for the treatment of this disease is generally controversial, although the recently published results of the first of two large randomized phase III clinical trials (RTOG 9802 a EORTC 22033-26033), focusing on the evaluation of chemotherapy for the upfront treatment of newly diagnosed low-grade gliomas, are reassuring in this respect. The long-term results of a RTOG 9802 comparing radiotherapy alone with radiotherapy and six cycles of adjuvant PCV chemotherapy (procarbazine, lomustine, vincristine) in patients with high-risk low-grade gliomas will probably have an impact on daily clinical practice. The increase in median overall survival from 7.8 years to 13.3 years, mainly for patients with oligodendrogliomas, is unprecedented, but the toxicity of PCV is too high and molecular marker analysis remains inadequate. It is still unclear whether less toxic temozolomide can replace PCV and whether temozolomide can be used upfront alone instead of with radiotherapy. This question is addressed by the ongoing EORTC 22033-26033 study. The preliminary results show no significant difference in progression-free survival between patients receiving radiotherapy and those receiving temozolomide alone. Treatment with temozolomide was not associated with an improvement in cognitive function compared with treatment with radiotherapy. Despite limited follow-up, the study clearly confirmed the importance of molecular characterization of low-grade gliomas, as currently defined in the new 2016 WHO Classification of Tumors of the Central Nervous System. AIM: The aim of the review is to summarize available information from listed key clinical trials of chemotherapy for low-grade gliomas and draw attention to unresolved issues concerning the use of chemotherapy for the treatment of this disease.Key words: glioma - astrocytoma - chemotherapy - PCV - temozolomide - RTOG 9802 This work was supported by MH CZ - RVO (MMCI, 00209805) and by project of the Ministry of Education, Youths and Sports of the Czech Republic CEITEC 2020 (LQ1601). 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: 21. 2. 2017Accepted: 20. 3. 2017.

[Non-Small Cell Lung Cancer - from Immunobiology to Immunotherapy]. / Nemalobunecný karcinom plic - od imunobiologie k imunoterapii.

BACKGROUND: The treatment of early or locally advanced stages of non-small cell lung cancer (NSCLC) is based on surgical resection or radiotherapy. Metastatic disease is always incurable, treatment is palliative, systemic based on chemotherapy or target therapy. NSCLC is the most common cause of cancer-related death worldwide, and new therapeutic approaches are needed. Based on the emerging data on the role of immune system in shaping of tumor outbreak and outcome, immunotherapy is currently in the center of interest of cancer research and therapy of solid cancers including NSCLC. Various anti-cancer vaccination approaches and antigen-independent immunomodulatory drugs are being developed and trialed. The most advanced in terms of approaching clinical practice are the so-called checkpoint inhibitors blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed cell death of the protein and its ligand (PD-1, PD-L1). Beside innovative drug development, the field of cancer immunotherapy focuses on the identification and clinical application of effective biomarkers of clinical efficacy and on the evaluation of combinations of immunotherapeutic drugs or with classical anti-cancer approaches, such as chemotherapy, radiotherapy or with targeted therapy. AIM: In this review, we summarize basic principles of immnobiology of NSCLC in the context of innovative immunotherapeutics, strategy and phase III results of anti-cancer vaccines in NSCLC, results of NSCLC treatment with checkpoint inhibitors, and current challenges in immunotherapy of lung cancers.Key words: non-small cell lung cancer - immunotherapy - cancer vaccines - drug response biomarkersThis work was supported by MEYS - NPS I - LO1413.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. 6. 2016Accepted: 16. 6. 2016.

[Side effects of Modern Immunotherapy and How to Solve Them in the Clinics]. / Nezádoucí úcinky moderní imunoterapie a jejich resení v klinické praxi.

BACKGROUND: The standard treatment of advanced melanoma has been changing in recent years. Palliative chemotherapy is being replaced by more efficient targeted therapies and modern immunotherapies based on antibodies against checkpoints of the immune response (so  called checkpoint inhibitors). Todays standard ipilimumab (ant-iCTLA 4 antibody) could significantly prolong overall survival and achieved longterm disease control in about 20% of patients. There are other perspective immune modulating agents, such as anti-PD 1 antibodies (nivolumab, pembrolizumab, pidilizumab) and anti-PD L1 antibodies. Unique mechanism of action is accompanied by new types of immunerelated adverse events. AIM: The aim of the article is to summarize current knowledge about the toxicity of these antibodies and propose solutions in routine clinical practice.

[A Case of Delayed Dia-gnosis of Acral Lentiginous Melanoma]. / Prípad pozdne dia-gnostikovaného akrolentiginózního melanomu.

BACKGROUND: Melanoma is a malignant skin disease. The tumor development is caused by an uncontrollable proliferation of melanocytes. The most common occurrence is on the skin, but melanoma may also develop on the mucous membrane, meninges, and eyes. Some melanomas develop from melanocytic nevus. Acral lentiginous melanoma occurs on palms, feet, fingers and under nails, and is the most common type of melanoma for phototype VI. The most important factor for successful treatment of malignant melanoma is an early detection, excision of the primary tumor and histological staging. Surgical treatment of an early-stage melanoma is a key to successful therapy; however, many patients (mostly men) do not seek medical attention before it istoo late. CASE REPORT: This case study presents a 59-year-old patient, who suffers from white coat syndrome and whose finger was amputated for alleged gangrene. Subsequently, brownish black nodules appeared across his arm. Histological examination proved metastases of malignant melanoma. It was only at this phase, when the patient admitted a nevus at the tip of his amputated finger, from which ulceration and gangrene gradually emerged. CONCLUSION: This case demonstrates a combination of multiple unfavorable factors, which led to delayed diagnosis and therapy.

[Epidemiological and clinico-pathological characteristics of patients with renal carcinoma: a single institution analysis of 544 cases]. / Epidemiologická a klinicko-patologická charakteristika pacientu s renálním karcinomem: analýza 544 prípadu z jednoho centra.

BACKGROUND: The incidence of renal cell carcinoma in the Czech Republic is one of the highest in the world. Curative treatment is still possible only surgically, while in the palliative treatment, partial success was reached using targeted therapies. While prognostic factors and models are commonly used in clinical practice, unfortunately, predictive biomarkers have not been found. The aim of our study was to verify the validity of selected prognostic factors on a consecutive patient cohort from the Czech population. PATIENTS AND METHODS: The patient cohort consisted of 544 patients with RCC diagnosed and/or treated at our institute from 2003 to 2010. Individual clinical and histological prognostic factors and Heng prognostic model were validated. RESULTS: Median time of follow-up for our cohort was 42 months (range 0.3-326 months), median age at diagnosis was 62 years, and almost 64% of patients were men. Distribution of clinical stages was as follows: 46.5% of I, II. 10.7%, III. 13.1%, IV. 20%. 26.4% of patients in stage I-III relapsed. We diagnosed mainly clear cell (84.6%) and papillary carcinoma (9.2%). Initially, 95.8% of patients underwent surgical treatment, systemic adjuvant and palliative treatment was applied in 3.7 and 37.7% of patients, respectively. Palliative targeted therapy was received by a total of 163 patients (30%). In first-line targeted therapy, the following median TTP was reached (in months): 10.8 for sunitinib, 6.3 for sorafenib and 5.2 months for immunotherapy. The most significant prognostic factors (p < 0.00001) were: stage of disease (HR = 9.61), size of the primary tumor (HR = 5.83), lymph nodes (HR = 8.26), presence of sarcomatoid tumor sections in the tumor (HR = 7.29), and tumor grade (HR = 4.0). Besides these, we also confirmed the prognostic importance of presence of eosinophilic granulations in the tumor (HR = 1.91, p = 0.02). When applying the Heng prognostic model, we achieved similar results for patients treated with targeted therapies. CONCLUSION: The obtained epidemiological and clinico-pathological data are consistent with previously published data. These prognostic factors can be used for a differentiated approach to patients with RCC, both for establishing follow-up plan for patients after surgery as well as indication for targeted therapies.

Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study.

BACKGROUND: A retrospective, registry-based analysis to assess the outcomes of metastatic renal cell cancer (mRCC) patients treated with sunitinib and sorafenib who developed dermatologic adverse events was performed. PATIENTS AND METHODS: Data on mRCC patients treated with sunitinib or sorafenib were obtained from the Czech Clinical Registry of Renal Cell Cancer Patients. Outcomes of patients who developed hand-foot syndrome (HFS) of any grade and/or grade 3/4 rash during the treatment were compared with patients without HFS and no, mild, or moderate rash. RESULTS: The cohort included 705 patients treated with sunitinib and 365 patients treated with sorafenib. For sunitinib, the median overall survival (OS) was 43.0 months versus 31.0 months (P = 0.027) and median progression-free survival (PFS) 20.8 months versus 11.1 months (P = 0.007) for patients with versus without dermatologic toxicity, respectively. For sorafenib, the median OS and PFS were 27.9 and 24.6 months (P = 0.244), and 12.2 and 8.8 months (P = 0.050), respectively. In multivariable Cox regression, the skin toxicity was significantly associated with longer OS in the sunitinib cohort. CONCLUSION: The presence of skin toxicity is associated with improved OS and PFS in patients with mRCC treated with sunitinib.

[Triple-negative breast cancer: analysis of patients diagnosed and/or treated at the Masaryk Memorial Cancer Institute between 2004 and 2009]. / Triple-negativní karcinom prsu: analýza souboru pacientek diagnostikovaných a/nebo lécených v Masarykove onkologickém ústavu v letech 2004 az 2009.

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogeneous group of breast cancers that do not express ER-α, PgR and Her-2 receptors. Generally, these tumors are aggressive and more common in younger women, in which an association of TNBC with mutations in the BRCA1 gene was documented. The aim of our study was to create a representative group of patients with TNBC, which could be analyzed and the data gathered to build basic epidemiological, molecular and clinical characteristics of Czech patients with TNBC. PATIENTS AND METHODS: We performed basic clinical-pathologic correlations in a group of 335 patients diagnosed and/or treated for TNBC at the Masaryk Memorial Cancer Institute between 2004 and 2009. We also performed immunohistochemical examination of expression of cytokeratin 5/6, cytokeratin 14 and EGFR to identify the basal-like subset of TNBC. RESULTS: The median age of patients with TNBC was 56 years, range 25-88 years. A total of 9.25% of TNBC cases were diagnosed in patients under the age of 34, and another 15.22% of cases were in the age group of 35 to 44 years. 'Basal-like' carcinomas accounted for 75% of TNBC. We confirmed the aggressive nature of this disease: in the follow-up period we observed a relapse in 25% of patients: 55% of deaths due to disease progression occured within 2 years after diagnosis of the disease. Treatment strategies include chemotherapy, in most cases (88.4%). Chemotherapy was mostly based on regimens with anthracyclines or in combination with taxanes. The most important negative prognostic factors in relation to OS (disease specific OS) were: higher clinical stage (p < 0.0001), pN - positive status (p < 0.0001), high proliferative activity (as measured by Ki-67, cut-off 50%, HR = 0.4740, p = 0.0411) and positive expression of CK5/6 (HR = 0.4274, p = 0.0338). In relation to DFS, the negative prognostic significance was found for these factors: higher clinical stage (p < 0.0001), pN positive status (p < 0.0001), high proliferative activity (Ki-67, cut-off 50%, HR = 0.04993, p = 0.0240). DFS was longer in patients with a higher number of applied cycles of anthracycline-based chemotherapy (> 4 cycles, HR = 1.7273, p = 0.0467). CONCLUSION: TNBC is an aggressive form of breast cancer, which may occur in patients of all ages, but more frequently in younger patients. Only early detection of disease and intensive treatment gives a high chance of cure. Unfortunately, no reliable predictive factors have been identified so far. Better therapeutic results can be expected from targeted therapy.

Meigs syndrome.

BACKGROUND: Meigs syndrome is defined by the presence of a benign ovarian tumor, ascites, and pleural effusion (predominantly on the right side). A characteristic sign of Meigs syndrome is the complete disappearance of exudate after surgical resection of the ovarian tumor. CASE REPORT: We present a case report of a 58-year-old patient admitted for an advanced ovarian tumor with pleural effusion, ascites, and tumor marker elevation typical for ovarian cancer. Cytological examination of ascites and pleural effusion was repeatedly negative for malignancy. Histopathological examination of the bio-psied tissue was concluded as low-grade mesenchymal neoplasia. The second opinion of histopathological examination was concluded as low grade fibroblastic pelvic tumor without the possibility of exact specification. Dia-gnoses of desmoid fibromatosis and low-grade fibromyxiod sarcoma (less likely) were considered. Surgical resection was indicated, and a large tumor with numerous adhesions to the uterus, bladder, and thin loops with a noticeably thickened peritoneum were perioperatively described. Histologically, left ovarian fibroma with productive peritonitis and sanguine-induced ascites was dia-gnosed. Due to the clinical findings and the result of the histopathological examination, the case was classified as Meigs syndrome. Two months after the surgery, the ascites and pleural effusion disappeared, and the tumor marker levels normalized. CONCLUSION: The present case report documents that it is always necessary to consider diseases other than those most likely at the outset, as the treatment algorithm and prognosis of these rare diseases may differ significantly.

[Metastatic renal cell carcinoma treated with everolimus--data from the RENIS Clinical Registry]. / Výsledky terapie metastatického renálního karcinomu lékem everolimus--analýza udaju z klinického registru RENIS.

Everolimus is an oral mTOR kinase inhibitor approved for the treatment of patients with metastatic renal cell carcinoma (mRCC) progressing during or after treatment with vascular endothelial growth factor (VEGF)-targeted agents. Using the national RENIS clinical registry, we have retrospectively analysed outcomes of patients treated for mRCC with everolimus. A total of 78 patients were evaluable. Median progression-free survival from the start of everolimus therapy was 7 months (95% confidence interval 2-12 months). Partial response or stable disease was achieved in 69% of patients. Treatment toxicity was predictable and serious adverse events occurred in only 6% of patients the most common being respiratory toxicity. Everolimus therapy provides significant clinical benefit for heavily pretreated mRCC patients after failure of VEGF-targeted therapy.

[Multimodal treatment of glioblastoma multiforme: results of 86 consecutive patients diagnosed in period 2003-2009]. / Výsledky multimodální lécby glioblastoma multiforme: Konsekutivní série 86 pacientu diagnostikovaných v letech 2003-2009.

BACKGROUNDS: Glioblastoma multiforme is the most common malignant primary tumor of the brain in adults. Standard therapy consists in maximal surgical resection and adjuvant concurrent chemoradiotherapy and adjuvant therapy with temozolomid. This approach improves survival in comparison with postsurgical radiotherapy alone. PATIENTS AND METHODS: Consecutive patients with histologically confirmed glioblastoma multiforme in the period from January 2003 to December 2009 underwent postoperative radiotherapy (1.8-2.0 Gy/d, total of 60 Gy) plus concurrent daily chemotherapy (temozolomide 75 mg/m2/d), followed by 6 cycles of temozolomide (150 to 200 mg/m2 for 5 days, every 28 days) and were analyzed retrospectively. The primary end point was to describe the correlation between known clinical factors, treatment and progression free survival (PFS) and overall survival (OS). We assessed the toxicity and safety of the chemoradiotherapy. RESULTS: Eighty-six patients (median age, 56 years; 60% male) were included. Most of them (> 80%) were of performance status (PS) 0-1 at the beginning of chemoradiotherapy. Total macroscopic resection was performed in 20% of the patients, subtotal in 65%, partial in 9%, and just biopsy in 6%. Median PFS was 7.0 months (2.0-35.5), median OS was 13.0 months (2.5-70). Postoperative performance status (PS), the extent of resection, and administration of planned treatment without reduction had statistically significant influences on PFS and OS. Median PFS and OS were 22.0, 7.0 and 6.0 months for PFS (p = 0.0018) in patients with PS O, 1 and 2 respectively and 32.0, 13.0 and 9.0 months for OS (p = 0.0023). Patients with total removal of tumor had longer PFS (14.0 vs 6.0 months, HR = 0.5688; p = 0.0301) and OS (23.0 vs 12.0 months, HR 0.4977; p = 0.0093), as did patients without dose reduction of radiotherapy and/or chemotherapy. Patients with radiotherapy dose of over 54 Gy had PFS 8.0 vs 3.0 months (HR = 0.3313; p = 0.0001) and OS 15.0 vs 5.0 months (HR = 0.1730; p < 0.0001). Similarly, treatment with concurrent chemotherapy for more than 40 days was also important: PFS 8.0 vs 5.0 months (HR = 0.5300; p = 0.0023) and OS 17.0 vs 9.5 months (HR = 0.5943; p = 0.0175). Age, gender and position of tumor had no significant influence. Treatment-related hematology toxicity grades 3 and 4 occurred relatively often: thrombocytopenia (9%), leukopenia (6%), neutropenia (6%) and lymphopenia (25%). Thrombo-embolic events were dominant in non-hematology toxicity. Serious toxicity occurred mainly in the subgroup of patients with PS 2. Treatment of progression was useful in selected patients. Second surgery was of the most benefit (OS 24.0 vs 12.5 months, HR = 0.5325; p = 0.0111). CONCLUSION: Postoperative performance status, extent of resection, successful administration of the majority of planned concurrent chemoradiotherapy and possibility of surgical treatment at the time of recurrence correlate with better prognosis for our patients with glioblastoma. Our experience indicates that performance status should be the main factor in decisions about treatment intensity. Treatment of malignant glioma requires a multidisciplinary team.

Cabozantinib in the treatment of metastatic renal cell carcinoma - final data analysis from four oncology centers in the Czech Republic.

BACKGROUND: Current standard treatments for patients with metastatic renal cell carcinoma (mRCC) involve tyrosine kinase inhibitors (TKI) that inhibit angiogenesis. Cabozantinib is a multi TKI used for the treatment of mRCC in the first- and second-line setting. PURPOSE: The aim of this study was the final analysis of treatment outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib after previous targeted therapy. PATIENTS AND METHODS: A total of 54 patients with mRCC from four oncology centers in the Czech Republic were evaluated retrospectively; the median follow-up was 18.5 months. Cabozantinib was administered in a dose of 60mg/day, a subset of patients received an initial dose of 40mg/day. The treatment was administered until the progression. The Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by regression analysis. All statistics were evaluated at the significance level α = 0.05. RESULTS: The median PFS in all patients was 9.3 months (95% CI 7.2 - 11.4). The median OS in all patients was 21.9 months (95% CI 15.5 - 28.4). The median PFS in patients with bone metastases was not statistically significantly different compared with patients without bone metastases (9.3 vs 8.7 months, P = 0.53). The median OS in patients with bone metastases was statistically significantly shorter compared with patients without bone metastases (17.7 vs 26.8 months, P = 0.021). A treatment response was observed in 40.7 % of cases, including one complete remission. The regression analysis demonstrated a significant effect on OS in patients with the presence of subsequent treatment (P = 0.001), patients with treatment duration of first line therapy 6 months (P = 0.019) and 12 months (P = 0.003) and in patients without bone metastases (P = 0.021). CONCLUSION: Our final analysis of patients with mRCC treated with cabozantinib after previous targeted therapy confirmed its effectiveness.

Management of Immune-Related Endocrinopathies in Anticancer Treatment with Checkpoint Inhibitors.

Modern immunotherapy with checkpoint inhibitors has become the backbone treatment for many cancers. However, it is often accompanied by immune-related side effects, which may differ depending on the nature of the treatment. The frequency of adverse reactions increases with the number of patients receiving immunotherapy. The situation has become even more difficult with the advent of combination immunotherapy. Although the kinetics of the onset and duration of toxicity have been well described, caution should be exercised. In clinical practice, cases with atypical courses often occur. Ignorance of the problem can lead to underestimation of symptoms and damage to the patient. Immune-related side effects are variable and any organ can be affected. In addition to skin, intestinal and liver toxicity, immune-related endocrinopathy is another relatively frequent toxicity. Thyroid, pituitary and adrenal glands are most commonly affected. Symptoms of endocrinopathy are often nonspecific, which may complicate a differential diagnosis. Fortunately, most toxicities are grade 1 and 2; however, in routine clinical practice, care must be exercised to detect the onset of life-threatening toxicity such as an adrenal crisis or type 1 diabetes mellitus with ketoacidosis. It is unclear whether high doses of corticosteroids are effective in preserving endocrine gland function. Long-term hormone replacement therapy is essential because immune-related endocrinopathy is often irreversible, unlike other immune-related toxicities. Close cooperation with an endocrinologist is therefore very important. This work was supported by MH CZ - DRO (MMCI, 00209805). 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.

[Profiles of low-molecular proteome spectrum obtained through SELDI-TOF mass spectrometry in the sera of patients with metastatic malignant melanoma: pilot study]. / Profily nízkomolekulárniho proteomového spektra získané pomocí hmotnostní spektrometrie SELDI-TOF v sérech pacientus diseminovaným maligním melanomem: pilotní studie.

BACKGROUNDS: Recently, research at genetic and molecular levels has extensively accelerated due to advances in new technologies. Since the mid-90s, a relatively new discipline--clinical proteomics, has evolved, which focuses on studying gene products--proteins. The evaluation of protein profiles may contribute to the more accurate stratification of patients in the future, in terms of both prediction of treatment results and prognosis. In pursuing this objective, proteomic approaches are currently used for the identification of new biomarkers. This is also the case with malignant melanoma, a disease without typical serum marker possessing high sensitivity and high specificity. METHODS: We analyzed human blood serum samples from 25 patients with metastatic malignant melanoma treated with palliative chemotherapy at the Masaryk Memorial Cancer Institute, Brno, in 2004-2006. The analysis was performed by Surface Enhanced Laser Desorption/lonisation Time of Flight Mass Spectrometry (SELDI-TOF-MS). Our patients were divided into two subgroups: a group relatively resistant to chemotherapy--14 patients--and a group with certain clinical benefit from the treatment (complete and partial remission, stabilized disease)--11 patients. We were searching for a new biomarker or typical protein profile in the selected two subgroups. Then, we recategorized our patients into three groups according to the similarity of their protein profiles regardless of sensitivity to chemotherapy. Finally, we evaluated differences in laboratory and clinical parameters, between both the groups of chemo-resistant and chemo-sensitive patients, and newly defined subgroups with similar protein profiles. CONCLUSION: We did not identify any significant differences in protein profiles or laboratory parameters in the predefined chemo-sensitive or chemo-resistant groups of patients. However, with regard to the new groups with similar protein profiles, we identified a subgroup of patients with different laboratory and clinical parameters. The results are very interesting and merit further research.

[Adjuvant treatment for stage I of testicular germ cell tumours]. / Adjuvantní lecba u i. stádia germinálních nádoru varlat.

BACKGROUND: Testicular germ cell tumors (TGCT) are the most frequent malignancy seen in young men. More than 95% of patients diagnosed with early stage TGCT are cured. In management of stage I seminoma there are several treatment options, including adjuvant radiotherapy, adjuvant chemotherapy with one cycle of carboplatin or surveillance. Patients with stage I nonseminoma are treated with adjuvant chemotherapy, with nerve sparing retroperitoneal lymph node dissection or surveillance being considered another treatment alternatives for stage I disease. METHODS AND RESULTS: Fifty five patients with stage I TGCT were diagnosed and treated in Masaryk Memorial Cancer Institute between January 2000 to December 2004. In a retrospective analysis, we reviewed treatment outcome and treatment strategy used in these patients. Patients characteristics also included histological subtype, risk status, age at the time of diagnosis, relapse rate, delayed toxicity, etc. Despite the small number of patients included in the analysis (55), there was observed a clear preference toward adjuvant radiotherapy in seminoma patients (95%) and adjuvant chemotherapy in nonseminoma patients (97%). During median follow up (5,6 years in seminoma group, 5,7 years in nonseminoma group) only two patients experienced relapse of disease in the seminoma group and none in the nonseminoma group. One patient died of metastatic colorectal cancer. Acute toxicity was acceptable, with no treatment related death. The long- term side effects were not significant (no grade 3 or 4 toxicity). CONCLUSION: The achieved cure rates were high, with acceptable toxicity. The role of adjuvant chemotherapy with carboplatin in stage I seminoma remains controversial. Further management of TGCT should be guided by complete and correct assessment of known risk factors to ensure the potential for cure.

Oligometastatic Prostate Cancer.

BACKGROUND: With advancements in diagnostic techniques, oligometastatic prostate cancer is diagnosed in patients who were, in the past, considered to have localized disease. Moreover, evidence of the effectiveness of treatment intensification for this disease is increasing, focusing on primary tumors as well as metastatic lesions. Thus, we can delay the start of systemic palliative treatment and improve overall survival. Many questions remain unclear, such as the definition of oligometastasis disease, or which patients should be offered aggressive treatment. Data are limited and come from small retrospective studies but show conclusively the benefits of survival in targeted primary prostate and metastatic prostate cancer therapy with surgery or radiotherapy. Often, stereotactic radiotherapy is used in this indication, with minimal side effects. In retrospective studies, 3-5 metastatic lesions were generally accepted for definition of oligometastatic disease, but patient subgroups were heterogeneous. A recent study attempts to better define oligometastatic disease and find out the right degree of intensification of treatment. When and in which patient to use metastasis-targeted therapy and when the standard systemic treatment is already meaningful. It is already clear that selected patients benefit from targeted personalized treatment. PURPOSE: The purpose of this review is to offer an update of the problem of oligometastatic prostate cancer. The article presents an overview of data from contemporary literature, modern possibilities of diagnostic imaging methods and treatment options of oligometastatic prostate cancer including surgery and radiotherapy.  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: 8. 2. 2019 Accepted: 5. 3. 2019.