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Analysis of prognostic features in patients with breast cancer and colorectal cancer.
Vočka, Michal ; Petruželka, Luboš (advisor) ; Fínek, Jindřich (referee) ; Prausová, Jana (referee)
Cancers represent second the most common cause of death in the Czech Republic. The most common are breast and colorectal cancers. Identification of prognostic factors improving decision-making approaches for treatment optimization belongs to the key aims of clinical research in oncology. Carriers of mutation in cancer-susceptibility genes represent a small but clinically important group of high-risk patients. The implementation of NGS have accelerated predisposing genes analyses. The large extent of data about the presence of variants in predisposing genes is in striking contrast to only a very limited information available about clinico-pathological characteristics of mutation carriers. Determination of the risk of tumor development in carriers of rare mutations or variants of unclear significance in genes with incomplete penetrance represent substantial drawbacks of current NGS analyses. To address these issues, we have attempted i) to introduce a unified approach to NGS analysis in breast cancer patients, ii) to characterize importance of prognostic factors in BRCA1/BRCA2 mutation carriers, and iii) to identify the cancer risks in carriers of germline mutations in the CHEK2 gene. Colorectal cancer represents seemingly histologically homogeneous disease. However, at the molecular level it can be...
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The Utilization of the Molecular-Biology Method One-Step Nucleic Acid Amplification (OSNA) for Examination of Sentinel Lymph Nodes in Endometrial Cancer Patients
Kosťun, Jan ; Presl, Jiří (advisor) ; Fínek, Jindřich (referee) ; Roztočil, Aleš (referee)
Hypothesis The One-Step Nucleic Acid Amplification method could represent an effective intraoperative tool for detection of metastatic involvement of lymphatic nodes on the level of ultrastaging in endometrial cancer patients. Objective Utilization of the One-Step Nucleic Acid Amplification (OSNA) molecular biology method for the detection of the micrometastatic and macrometastatic involvement of sentinel lymph nodes in endometrial cancer patients. The objective is a comparison with the conclusion of the histopathological ultrastaging of sentinel lymph nodes and a description of the clinical consequences of this method. Methods Patients indicated for the surgical treatment of endometrial cancer underwent the detection of sentinel lymph nodes that was executed using the intracervical application of a tracer. Nodes larger than 5 mm were cut into sections 2 mm thick parallel to the short axis of the node. Odd sections were examined using the OSNA method, while even ones were examined by hematoxylin and eosin (H&E) and immunohistochemical examination to detect cytokeratin 19 antibody (IHC CK19) based on an ultrastaging-relevant protocol. Nodes of the size of 5 mm and smaller were divided into halves along the longitudinal axis with one half being examined using the OSNA method and the other half by...
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Cutaneous Side Effects of Targeted Oncological Treatment
Říčař, Jan ; Cetkovská, Petra (advisor) ; Fínek, Jindřich (referee) ; Salavec, Miloslav (referee)
1 Abstract Introduction In recent years, new oncological treatments with targeted effects on cellular level have been introduced into the clinical practice. Some of these agents can cause specific changes affecting skin, skin appendages and mucosa. Currently, the most significant cutaneous side effects in the clinical practice are observed during treatment with inhibitors of the epidermal growth factor receptor (EGFR). Papulopustular exanthema is the most frequent adverse effect of EGFR inhibitors. Skin changes have a crucial impact on the quality of life can cause an interruption or even termination of the oncological treatment, thus worsening the patient prognosis. Objectives The objective of this study was to evaluate the incidence, severity and time of onset of papulopustular exanthema in patients with non-small cell lung cancer (NSCLC) treated with erlotinib. The study also aimed to assess the correlation between papulopustular exanthema and patient prognosis and the incidence of EGFR gene mutations. Another objective was to create informational materials for patients with EGFR inhibitors skin toxicity, its prevention, treatment and recommended regime measures. Methods This was a prospective, open-label, uncontrolled study in which patients with non- small cell lung cancer stage III B and IV treated...
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Circulating tumor cells in breast cancer patients
Bielčiková, Zuzana ; Zemanová, Milada (advisor) ; Gürlich, Robert (referee) ; Fínek, Jindřich (referee)
Circulating tumor cells (CTCs) represent a systemic phase of the localised cancer disease. They can be distinguished and enriched from the peripheral blood and so from the surrounding leukocytes by either physical properties (e.g., density and size) or biological properties (e.g., expression of epithelial proteins such as EpCAM or cytokeratins) and are usually further characterized by immunostaining or RT-PCR assays. Selecting patients with the risk of disease relaps at the time of diagnosis is crucial for clinicians in deciding who should, and who should not, receive adjuvant chemotherapy. We know that CTCs are strong prognostic factor in patients with metastatic as well as localized breast cancer (BC). It is also known that the prognostic power of circulating tumor cells in women with BC is independent from the standard prognostic indicators. Testing of CTCs known recently as "liquid biopsy" could be informative not only as predictor of the disease relapse, but also as the predictor of therapy effectiveness. The clinical use of CTCs must be strictly encouraged by clinical trials results. Monitoring of CTCs in time could zoom in the mechanism of therapy resistance and/or may provide the identification of new druggable targets. The purpose of my work was therefore to assess the CTCs positivity rate...
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Utilisation of New Biomarkers for the Optimalization of Diagnostics and Therapy of Tumors of the Gastrointestinal Tract
Šafanda, Martin ; Kučera, Radek (advisor) ; Fínek, Jindřich (referee) ; Svobodová, Šárka (referee)
Utilisation of New Biomarkers for the Optimalization of Diagnostics and Therapy of Tumors of the Gastrointestinal Tract Introduction: Tumor markers are standard diagnostic tools. They are mainly used to monitor the course of the disease and to check the efficacy of the treatment. It is important to observe dynamics. Changing the level of the biomarker can prevent clinical manifestation and lead to early diagnosis of relapse, which in turn means improving the quality of life, including prolonging survival. Recently, we have encountered a number of diagnostic algorithms that suggest algorithms for estimating the risk of tumor presence or the risk of progression of cancer, using statistical methods. Objectives: The aim of this work is to verify new biomarkers for the diagnosis of gastric cancer and to develop an optimal algorithm for their use. Further, to evaluate the importance of cytokeratin markers - Tissue Polypeptide Antigen (TPA) and Tissue Polypeptide Specific Antigen (TPS) for the diagnosis of metastatic colorectal carcinoma in the liver. To carry out a pilot study of FGF23 levels in people with colorectal carcinoma and other gastrointestinal tumors. Methods and patients: Patient samples were analyzed using immunoradiometric, chemiluminescence and fluorescence assays. For each solved problem,...
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Breast cancer in young women: correlation of molecular-genetic, clinical and morphological features
Metelková, Alena ; Fínek, Jindřich (advisor) ; Tesařová, Petra (referee) ; Ryška, Aleš (referee)
In the first part of the dissertation the author summarizes the current knowledge of breast cancer, which is the most frequent malignancy in female population. The author deals with etiology, classification, diagnostics, biological behaviour, therapeutical forms ranging from surgical treatment and radiotherapy, to systemic therapy. In the following part of the manuscript the author describes specifics of breast cancer diagnosed in premenopausal women. She describes how the risk factors, treatment and prognosis differ from the disease in postmenopausal women. Next section of the dissertation includes a retrospective case series evaluating group of patients with breast cancer ≤ 35 years. There were 16 294 cases of breast cancer proven histologically in Biopticka lab Pilsen, ltd. and Sikl's Department of Pathology, Faculty Hospital Pilsen, during 2006-2015. The cohort of patients in our retrospective study includes 356 young women (2,2%) with breast cancer, under 35 years of age by the time of setting the diagnosis. We sorted out a group of 93 patients from the basic cohort, that were or have been treated in the Department of Oncology and Radiotherapy, Faculty Hospital in Pilsen. A control group consists of 100 postmenopausal women ≥ 65 years of age, chosen randomly from all patients treated in the...
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ATM and TGFB1 polymorphism in prediction of late complications of chemoreadiotherapy in patients with locally advanced cervical cancer
Paulíková, Simona ; Petera, Jiří (advisor) ; Kubecová, Martina (referee) ; Fínek, Jindřich (referee)
Cervical cancer is due to high incidence the third most commonly diagnosed gynecological cancer in the Czech republic. More than 50% of these tumors are diagnosed in advanced stage (st. IIB and higher) and therapy is more difficult than in lower stage tumors. The standard treatement method for locally advanced cervical cancers is combined oncological therapy including external beam radiotherapy, brachytherapy and concomitant chemotherapy. This treatement provides good tumor control, but there is also a risk of late complications in irradiated area. Severe late complications affect 10-15% of patients. It is still not possible to predict late complications and therefore detection of valid predictive factors for high tissue radiosensitivity could help to identify patients with increased risk before therapy. Knowledge of such predictive factors would also help to individualize the treatement. New molecular biological methods brought new findings about cancerogenesis, cell cycle regulation and cellular reaction to the radiation damage. It was hypothized, that mutation of genes involved in DNA damage reparation or cell proliferation are one of causes of high tissue radiosensitivity. The aim of our study was to evaluate relations between ATM and TGFß1 polymorphisms and late tissue toxicity in patients treated for...
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Thyroid Dysfunction after Radiotherapy of Head and Neck Cancer
Bernát, Ladislav ; Hrušák, Daniel (advisor) ; Fínek, Jindřich (referee) ; Jenča, Andrej (referee)
Objectictives: Radiation therapy is often applied to patients with head and neck cancer because of a high sensitivity to these cancers. It improves treatment outcomes and permits the preservation of functions and physical form. However, it has been shown that various complications can result from radiation therapy. Hypothyroidism can be one of them as the thyroid gland is frequently included in radiation fields. In spite of that, thyroid hypofunction is not commonly considered a complication of radiotherapy for head and neck cancer. The purpose of this retrospective study was to determine the frequency of thyroid dysfunction in patients after radiotherapy, to compare thyroid hormone levels in irradiated patients with control group and to predict development of thyroid hypofunction in time. Material and method: Thyroid function was measured by means of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodthyronine (FT3) in 43 patiens who had nonthyroid head-neck carcinomas treated by radiotherapy or radiotherapy in combination with other treatment modalities. These data were compared with hormone levels of 40 control group patients treated solely by surgery. Results: In median follow-up period 34 months after radiation, hypothyroidism was found in 35% of irradiated patients. In...
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Prognostic and Predictive Factors in Breast Cancer
Šefrhansová, Lucie ; Fínek, Jindřich (advisor) ; Pešek, Miloš (referee) ; Tesařová, Petra (referee) ; Nekulová, Miroslava (referee)
of dissertation thesis Prognostic and Predictive Factors in Breast Cancer The mRNA Expression of Selected Genes in Normal and Tumor Breast Tissue Samples and Theirs Clinical Value in Breast Cancer L.Šefrhansová Background: The aim of this work was to describe and to evaluate possibilities of prognosis and prediction in breast cancer. Within the framework of this study-work we carry out a prospective clinical study. The aim of this prospective study was to detect mRNA MMP-7, p53 and TIMP-1 expression in normal and tumor breast tissue samples and to determine the clinical and prognostic significance of our results. Prognosis and prediction: The tumor size, lymph node status, presence of distant metastasis, differentiation of the tumor, perivascular invasion, mitotic activity, expression of ER, PR and HER2 receptors are the basic prognostic factors in breast cancer. Age under/above 35 years was included among independent prognostic breast cancer factors in 2005. It is approved to use uPA/PAI to assess prognosis in node negative breast cancer patients. The hormone receptor status and HER-2 receptor status are the only two predictive markers associated with the target therapy. OncotypeDX analysis could be use to predict the disease recurrence interval of patients with estrogen positive and node negative...
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Does the assesment of tumor markers in the context of the last negative conclusions still have any impact in ovarian cancer?
Svoboda, Tomáš ; Fínek, Jindřich (advisor) ; Skalický, Tomáš (referee) ; Hes, Ondřej (referee) ; Vyzula, Rostislav (referee)
Does the assessment of tumor markers in the context of the last negative conclusions still have any impact in ovarian cancer? Svoboda T.: Dept. Of Oncology and Radiotherapy, Univ.Hospital, Plzen, Czech Republic Summary: The incidence of ovarian cancer is very high in Europe and there is still a lot of encertainaity about the best screening method today. The regular use of ultrasound investigation and CA125 testing is not established as a screening, so the greatest number of patients diagnosed with this tumor has a locally advanced disease. Their prognosis is unfavourable even with the treatment by chemotherapy. We describe the role of main factors associated with the primary tumor (staging, grading, histological type) and it's treatment (surgery type and the influence of residual tumor, type and regimen of chemotherapy and inclusion of radiation therapy in the primary treatment) for disease-free and overall survival. We also confirmed that tumor markers (CA125 incl.) used in screening, during treatment measuring response to chemotherapy and for folow-up as an early predictor of disease recurrence have low specificity and sensitivity to be used today. They have role of a prognostic factor - at least some of them - unfortunately with no impact on survival even when palliative chemotherapy can start...
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