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Important mechanisms of tumorigenesis and their role in chemoresistance of head and neck cancers
Zlámalová, Viktorie ; Šírová, Milada (advisor) ; Zíková, Martina (referee)
Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignancy worldwide. Despite improvements in therapeutic outcomes due to advances in surgery, radiotherapy, chemotherapy, and imaging techniques, HNSCC still has high mortality rate. For patients who are not cured with surgery and radiotherapy, there are few effective treatment options. Although HNSCC is heterogeneous in nature, current molecular classification distinguishes only human papilloma virus positive and negative tumors. HNSCC in general are characterized by considerable resistance and high rate of locoregional recurrence. Loss of p53 control pathway and numerous alterations in components of intracellular signaling pathways are consistently observed throughout the majority of HNSCC cases, supporting uncontrolled proliferation. It was proven that common mutations in the HNSCC genome play major role in tumorigenesis as well as in resistance to chemotherapy. The aim of the thesis is to describe the important mechanisms in HNSCC, which are associated with mutations in epidermal growth factor receptor and p53, and those including PI3K/Akt/mTOR and Notch signaling pathways. Association of these pathways with chemoresistance to commonly used drugs and even to advanced targeted therapeutic agents was evidenced by many...
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The results of radiotherapy of head and neck tumors. Comparison of conformal radiotherapy and IMRT
HLAVÁČOVÁ, Veronika
Malignant tumors of the head and neck are globally around 5 % of all malignant tumors. To the group of tumors of the head and neck falls oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands. The main treatment modalities are included surgical treatment, radiotherapy, chemotherapy and biotherapy. The first aim of this thesis was to compare the results of radiotherapy of tumors of the head and neck in a hospital in Ceske Budejovice with specialised literature.The second objective was to compare conformal and IMRT techniques within the meaning of recurrences.Data collection was conducted in patients diagnosed with tumor of the oral cavity and pharynx during years 2004 to 2010. When comparing treatment results with data from the first scientific literature with the results monitored group agree on decreasing tendency on five-year survival with increasing degree of the stadium. When comparing five-year survival rate for tumors of the oral cavity with the reference group of patients with data from the other specialised literature, correspondence does not exist.In this case, the hypothesis can not be confirmed. In the second set hypothesis it was assumed that the lower incidence of relapses occur after irradiation by the technique IMRT. Although the hypothesis was confirmed,although the gap between the technology 3D-CRT and IMRT for recurrences is tiny, only tenths.A crucial factor influencing survival is the time of diagnosis. Improving this fact could be achieved by appropriate preventive programs, which are targeted primarily at risk group of people.
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The Toxicity of Radiotherapy for Head and Neck Tumours
NESEJTOVÁ, Šárka
Abstract The fundamental theoretical findings Head and neck tumours make up approximately 2-3% of all malignancies in our country. There is 4 times higher occurance at men population than women one. It is just smoking which belongs to important susceptible risk factors. The main therapeutic methods are operation, radiotherapy, chemotherapy, biotherapy and their combinations which carry, however, the risk of higher toxicity. The radiotherapy aim is to add the required dosage of ionizing radiation to target volume while maximally protecting treated organs. In order to decrease side effects the bearable radiation procedures are being developed which are trying to improve dosage distribution in target volume and decrease a dosage on surrounding good tissues. The level of treatment toxicity is one of the indicators for treatment effect evaluation. Basically we distinguish acute and chronic toxicity. The most often acute side effects of radiation of head and neck tumours are radiodermatitis, mucositis, xerostomia and dysphagia. Late toxicity is typically resulting in skin and mucous membrane atrophy, pharynx fibrosis and chronic decrease of salivation. Aim The aim of my thesis is to find out whether radiotherapy toxicity with my monitered sample is comparable with expert sources and whether its occurance is influenced by smoking. I have also done research if there is a difference between operated and non-operated patients with the level of side effects of radiation because the multimodal treatment is connected with a higher risk of toxicity. Research procedures My thesis is a theoretical research nature. In order to verify my hypothesis I have used the method of quantitative research with retrospective data collection from medical file archive of the Oncological department in the hospital České Budějovice a.s. In my selective sample I filed the patients who were being treated during 2009 - 2011 at the radiotherapeutical department of Hospital České Budějovice a.s. regardless age, sex, smokers or nonsmokers with an early degree of disease according to TNM classification. I have chosen the patients having neoplasm of larynx, oropharynx, tongue, hypopharynx or oral cavity as they are found at head and neck areas most often. The sample included both patients who had undergone only radiotherapy treatment and also those who had undergone adjuvant cancer therapy after a surgery. The common feature was a degree of side effect radiation and its dependance on smoking. The toxicity degree was evaluated by RTOG scoring for acute toxicity. Results In total I have evaluated 48 patients who met the criteria mentioned above. The Hample was made up of 88% men and 12% women . The average age of patients at the beginning of radiotherapy was 63,5. The most significant part were the ill with larynx tumours who made up 69% of all irradiated, the least occurance count hypopharynx /only 2%/. Smokers represent 29%, nonsmokers 11%, other patients were ex-smokers. 48% of patients were irradiated conventionally, 52% via an IMRT method. 31% of patients underwent adjuvant radiotherapy after surgery, the others only radiation. The most often side effect radiation occurred on skin, mucous membrane, pharynx, less occurance on salivary glands. Conclusion Ionizing radiation damage both malignant and good cells so we have to always consider damaging a good tissue while doing radiation. The sample of acute toxicity occurance seems to lower compared to an expert Study. A higher rate of acute side effects at smokers was not proved, however, the monitored sample shows a significant minority of nonsmokers so comparison does not have to be quite relevant. The nonoperated sample showed fewer side effects at early stage compared to the operated. It was not possible to statistically evaluate late toxicity.
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