Feasibility of implementation of the early tumor shrinkage as a potential predictive marker to daily clinical practice in patients with RAS wild type metastatic colorectal cancer, treated with cetuximab - a non-interventional observational study.

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.

Extrahepatic bile duct malignancies.

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.

Side Effects and Efficacy of Immunotherapy.

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.

[A Development and Overview of the Use of Chemotherapy and the Role of Radiotherapy and Surgery in Patients with Newly Diagnosed Pancreatic Tumor and Cancer in the Current 5-year Center Practice]. / Vývoj a prehled vyuzití chemoterapie a role radioterapie a chirurgie u pacientu s nove diagnostikovaným tumorem a karcinomem pankreatu v bezné 5leté praxi centra.

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.

[Immunotherapy in the Treatment of Lung Cancer]. / Imunoterapie v lécbe karcinomu plic.

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.

[Evaluation of Anti-cancer Therapies with Reimbursement Limited to Comprehensive Cancer Centres Using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale]. / Hodnocení klinického benefitu protinádorových léku limitovaných na komplexní onkologická centra podle metodiky ESMO-MCBS.

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.

[Breast Cancer in Young Women - Correlation of Clinical Histomorphological, and Molecular-genetic Features of Breast Carcinoma in Women Younger than 35 Years of Age]. / Karcinom prsu u mladých zen - korelace klinických, histomorfologických a molekulárne-genetických nálezu karcinomu prsu u zen mladsích 35 let.

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.

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.

[Everolimus in Daily Clinical Practice Focusing to Oral Mucosa Damage Issues - Single Oncology Centre Experience within the Course of the Year 2016]. / Everolimus v denní klinické praxi se zamerením na problematiku postizení sliznice dutiny ústní - zkusenost onkologického centra v prubehu roku 2016.

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.

[Epithelial-mesenchymal Transition in Tumor Tissue and Its Role for Metastatic Spread of Cancer]. / Epitelo-mezenchymální tranzice v nádorové tkáni a její role pri metastatickém sírení karcinomu.

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.

[Radiotherapy Indications in Patients with Hematological Malignancies During the Five Years Course of Modernized Center of Oncology and Radiotherapy Clinic in Pilsen]. / Indikace radioterapie u pacientu s hematologickými malignitami v prubehu peti let provozu modernizovaného centra Onkologické a radioterapeutické kliniky v Plzni.

Submitted: 27. 2. 2016.

[Carcinoid of the Appendix Goblet Cells Metastasize to the Orbit - a Clinical Case Report and Review of the Literature]. / Karcinoid z pohárkových bunek apendixu metastazovaný do orbity -  klinická kazuistika a prehled literatury.

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.

Serum albumin is a strong predictor of survival in patients with advanced-stage non-small cell lung cancer treated with erlotinib.

Molecular targeted therapy based on tyrosine kinase inhibitors (TKI), directed at epidermal growth factor receptor (EGFR) is one of the novel effective agents in management of advanced-stage of Non Small Cell Lung cancer (NSCLC). However several candidate predictors have been extensively studied, apart from activating EGFR gene mutations, no reliable biochemical or molecular predictors of response to erlotinib have been validated. The aim of our retrospective study was to evaluate the association of baseline serum albumin with outcomes in a large cohort of patients with advanced-stage NSCLC treated with erlotinib. Clinical data of 457 patients with locally-advanced (III B) or metastatic stage (IV) NSCLC treated with erlotinib were analysed. Serum samples were collected and the measurement was performed one day before the initiation of erlotinib treatment. Before the treatment initiation, low albumin was (<35 g/l) measured in 37 (8.1%) patients and normal albumin (≥ 35 g/l) was measured in 420 (91.9%). The median PFS and OS for patients with low serum albumin was 0.9 and 1.9 months compared to 1.9 and 11.4 months for patients with normal serum albumin (p=0.001 and p<0.001). The multivariate Cox proportional hazards model revealed that EGFR mutation status (HR=2.50; CI: 1.59-3.92; p<0.001) and pretreatment serum albumin (HR=1.73; CI: 1.21-2.47; p=0.003) were significant independent predictive factors for PFS, whereas EGFR mutation status (HR=3.14; CI: 1.70-5.81; p<0.001), stage (HR=1.48; CI: 1.09-2.02; p=0.013), ECOG PS (HR=1.77; CI: 1.37-2.29; p<0.001) and pretreatment serum albumin (HR=4.60; CI: 2.98-7.10; p<0.001) were significant independent predictive factors for OS. In conclusion, the results of present retrospective study indicate that pretreatment hypoalbuminemia is associated with poor outcome of NSCLC patients treated with erlotinib. Based on these results, measuement of serum albumin is an objective laboratory method feasible for estimation of prognosis of patients with advanced-stage NSCLC.

Cost of skeletal complications from bone metastases in six European countries.

Objective Patients with bone metastases or lesions secondary to solid tumors or multiple myeloma often experience bone complications (skeletal-related events [SREs]-radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression); however, recent data that can be used to assess the value of treatments to prevent SREs across European countries are limited. This study aimed to provide estimates of health resource utilization (HRU) and cost associated with all SRE types in Europe. HRU data were reported previously; cost data are reported herein. Methods Eligible patients from 49 centers across Austria (n = 57), the Czech Republic (n = 59), Finland (n = 60), Greece (n = 59), Portugal (n = 59), and Sweden (n = 62) had bone metastases or lesions secondary to breast, lung, or prostate cancer, or multiple myeloma, and ≥1 index SRE (a SRE preceded by a SRE-free period of ≥ 6.5 months). SRE-related costs were estimated from a payer perspective using health resource utilization data from patient charts (before and after the index SRE diagnosis). Country-specific unit costs were from 2010 and local currencies were converted to 2010 euros. Results The mean costs across countries were €7043, €5242, €11,101, and €11,509 per radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression event, respectively. Purchasing power parity (PPP)-adjusted mean cost ratios were similar in most countries, with the exception of radiation to bone. Limitations The overall burden of SREs may have been under-estimated owing to home visits and evaluations outside the hospital setting not being reported here. Conclusions All SREs were associated with substantial costs. Variation in SRE-associated costs between countries was most likely driven by differences in treatment practices and unit costs.

[Cost-effectiveness Analysis of Panitumumab Plus mFOLFOX6 Compared to Bevacizumab Plus mFOLFOX6 for First-line Treatment of Patients with Wild-type RAS Metastatic Colorectal Cancer--Czech Republic Model Adaptation]. / Analýza nákladové efektivity porovnávající panitumumab plus mFOLFOX6 a bevacizumab plus mFOLFOX6 v první linii metastatického kolorektálního karcinomu s expresí nemutovaného typu onkogenu RAS--adaptace modelu na podmínky Ceské republiky.

BACKGROUND: Pharmacoeconomic assessments are a part of the decision process not only during reimbursement setting, but in clinical practice as well. The presented cost-effectiveness analysis assesses panitumumab+mFOLFOX6 vs. bevacizumab+mFOLFOX6 in 1st line treatment of patients with wildtype RAS metastatic colorectal cancer (mCRC) in the Czech environment. MATERIAL AND METHODS: The adaptation of a Markov model considers the healthcare perspective; clinical data (efficacy, healthcare utilization and adverse events) are derived from a head-to-head comparison (PEAK study). Health states included in the model: progression free on treatment, progression (with/ without active treatment), resection of metastases, disease-free after successful resection and death. Actual reimbursement levels were used to estimate costs, published literature to estimate duration of 2nd line treatment. The analysis assumes a lifetime horizon; uncertainty was limited by performing one-way and probabilistic sensitivity analyses. Analysis outcomes are life-years gained (LYG) and quality-adjusted life-years (QALYs). RESULTS: Panitumumab+mFOLFOX6 is more effective and more costly in 1st line patients with wildtype RAS mCRC. Incremental costs per QALY are 837,270 CZK, per LYG 615,022 CZK; however, below the willingness-to-pay threshold applied in the Czech Republic. CONCLUSIONS: Panitumumab+mFOLFOX6 is cost-effective in 1st line treatment of patients with wildtype RAS mCRC compared to bevacizumab+mFOLFOX6 in the Czech setting.

[The importance of early tumor shrinkage and deepness of response in assessing the efficacy of systemic anticancer treatment with metastatic colorectal cancer]. / Význam casné nádorové regrese a hloubky lécebné odpovedi pri hodnocení úcinnosti systémové lécby metastazujícího kolorektálního karcinomu.

BACKGROUND: The efficacy of anticancer therapy is regularly evaluated using the following indicators -  objective response rate, progression free survival and overall survival. The change in the tumor burden extent is assessed by the cumulative change in the size of target tumor lesions using imaging methods where WHO and RECIST criteria are most frequently used. The main problem of these criteria is that they use different definitions of response rate evaluation. Generally, existing results of these evaluations do not confirm a direct correlation between the objective response rate and survival (progression free survival or overall survival). Another problem of these methods is that the results of the assessment do not correlate with the bio-logical activity of tumor growth, since it is a static evaluation of clinical status. AIM: This review article provides an overview of results related to new possibilities for evaluating the efficacy of anticancer therapy using the concept of depth of response and the concept of early tumor shrinkage in patients with metastatic colorectal cancer. CONCLUSION: The results of numerous posthoc and exploratory analyses of clinical studies consistently suggest that early tumor shrinkage and depth of response are important variables in assessing the efficacy of systemic anticancer treatment.

Cancer incidence and mortality in the Czech Republic.

BACKGROUND: The Czech Republic ranks among the countries with the highest cancer burden in Europe as well as worldwide. The purpose of this study is to summarize longterm trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates after 2011. DATA AND METHODS: The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information collected over a 34-year period of standardized registration covering 100% of cancer diagnoses within the entire Czech population. The CNCR analysis is supported by demographic data and by the Death Records Database. An overview of the epidemiology of malignant tumors in the Czech population is available online at www.svod.cz. RESULTS: All neoplasms, including nonmelanoma skin cancer, reached a crude incidence rate of almost 802 cases per 100,000 men and 681 cases per 100,000 women in 2011. The annual mortality rate exceeded 258 deaths per 100,000 individuals; in other words, more than 27,000 individuals die of cancer each year. The overall incidence of malignancies has increased with a growth index of +27.6% during the last decade (2001- 2011), while the mortality rate has been stabilized over the time span (growth index in 2001- 2011: - 5.0%). Consequently, the prevalence has significantly increased in the observed period and exceeded 475,000 cases in 2011. In addition to demographic aging of the Czech population, the cancer burden has also increased due to the growing incidence of multiple primary tumors (recently more than 15% of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer, and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e. g. the proportion of stage I or II was 75.3% for female breast cancer and 84.2% for skin melanoma), the numbers of early diagnosed cases are generally insufficient, even in the case of highly prevalent cancers such as colorectal carcinoma (only 46.1% of incident cases are diagnosed at stage I or II, according to recent data). CONCLUSION: Population-based data on malignant tumors are available in the Czech Republic. The data survey can help us define national cancer management priorities. The current priority is to achieve a sustained reduction of cases diagnosed at an advanced stage and reduction of the significant regional differences in diagnostic efficiency.

[Colorectal liver metastases surgery - the present and the perspectives]. / Resekce jater pro metastázy kolorektálního karcinomu - soucasnost a perspektivy.

The incidence of colorectal liver metastases (CLM) in the fourth stage of colorectal carcinoma is 80%, liver parenchyma only being impaired in 40% of patients. Liver resection is the "gold standard" of treatment with long-term overall survival. However, only 20-25% of CLM are primarily resectable. Many staged procedures exist for increasing secondary CLM resectability - modern oncologic therapy, portal vein embolization, stem cells application, ALPPS (associating liver partition and portal vein ligation for staged hepatectomy), sequential liver procedures, combined resections with thermoablation procedures. Perioperative oncological therapy in primary resectable CLM is currently recommended. The patients prognosis depends on the biological CLM activity, which is evaluated according to several serum or histopathological markers. Resectable extrahepatic metastases are no more a contraindication for liver resection. One-stage resection of primary tumour and CLM is recommended in cases where one procedure is simple and short. Liver first procedure can be used in patients with the risk of non-resectability of advanced CLM after the treatment of primary colorectal cancer. Up to 55-60% of patients will develop recurrent CLM which are resectable in many cases, or thermoablation methods can be used.

[On the importance of standardization in the assessment of population-based cancer patient survival in the Czech Republic -  methodology and results from the Czech National Cancer Registry]. / Význam standardizace v hodnocení populacního prezití onkologických pacientu v CR -  metodický koncept a výsledky analýzy dat Národního onkologického registru.

BACKGROUND: Calculating 5-year overall and relative survival is the standard method for population-based analyses in oncology. Survival rates based on population data do not, however, guarantee standardized benchmarks for comparison of different patient populations, which is especially true when compared populations differ considerably in age structure and representation of clinical stages. In this paper, we present and compare statistical methods for standardization of cancer survival rates. PATIENTS AND METHODS: Using data of the Czech National Cancer Registry, we estimated 5-year overall and relative survival estimates for periods 2001- 2005 and 2006- 2010. To demonstrate the effect of standardization, we calculated crude and age -standardized survival rates as well as survival rates standardized for both age and clinical stage. RESULTS: Our results show that the particular standardization method influences resulting 5-year overall and relative survival rates regarding both within and between time periods comparisons. In addition, our results document a recent improvement in 5-year relative survival between periods 2001- 2005 and 2006- 2010 for 19 of 20 evaluated diagnoses. All most prevalent cancers including prostate, lung, colorectal, breast, kidney, and uterine cancer and melanoma were observed among the diagnoses with statistically significantly improved patient survival. CONCLUSION: Unless the use of standardization to the age and stage of tumor is limited due to a small number of patients in individual age-  and stage- specific subgroups, this method can be considered as a proper statistical methodology for the population assessment of Czech cancer patient survival rates.

[MRI based 3D brachytherapy planning of the cervical cancer -  our experiences with the use of the uterovaginal Vienna Ring MR CT applicator]. / Na MRI zalozené 3D plánování brachyradioterapie karcinomu delozního hrdla -  nase zkusenosti s pouzitím uterovaginálního aplikátoru Vienna Ring MR CT.

BACKGROUND: Uterovaginal brachytherapy planning is conventionally based on the use of two orthogonal Xray projections. Currently, there is a large development of 3D brachytherapy planning based on the fusion of CT and MRI, which takes into account the extent of the tumor and the location of organs at risk. In this work, we evaluated the dosimetric data and first clinical results in patients with inoperable cervical cancer using MRI/ CT compatible applicator enabling 3D planning. PATIENTS AND METHODS: Between June 2012 and March 2013, we performed 52 uterovaginal applications in 13 patients with inoperable cervical cancer using Vienna Ring MR CT applicator. Planning was carried out by the fusion of MRI and CT. Target volumes and organs at risk delineation were carried out on the basis of GEC ESTRO and ABS recommendations as well as doses report-ing. RESULTS: Overall radiotherapy duration was 37- 52 days with median of 45 days. The median total dose delivered to the HR CTV was 88 Gy (70.7- 97.9) EQD2. The median single dose in brachytherapeutic applications was D90 = 6.45 Gy (3.2- 9.82). The median total doses delivered to the rectum, sigmoid colon and bladder were D2ccrectum = 64.2 Gy (54.3- 74.1), D2ccsigmoid = 68.6 Gy (57- 74.7) a D2ccbladder = 73.9 Gy (58.3- 92.6). In 11 patients (84.6%), complete locoregional remission was achieved, in the remaining two patients (15.4%), partial locoregional remission was achieved. Twelve patients (92.3%) had complete regression of the tumor in the cervix, one patient (7.7%) developed metastatic spread to the liver. Yet we did not observe manifestations of a higher degree of toxicity than the first grade, both GI and GU. Late GI toxicity was manifested in two patients (15.4%) and late GU toxicity was manifested in five patients (38.5%). CONCLUSION: 3D brachytherapy planning of inoperable cervical cancer using the fusion of MRI and CT conclusively raises the possibility of the dose escalation to the tumor and significantly spares the surrounding organs at risk. Subsequently, this way of planning leads to better local control of the disease and to lower radiation morbidity.