BACKGROUND:The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer.METHODS:A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken.The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans.RESULTS:At a median follow-up of 22months (4-53months), no patient developed retropharyngeal nodal recurrences.CONCLUSION:Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes.

Bei dieser Arbeit handelt es sich um eine retrospektive Studie bezüglich Inzidenz und Therapie von Mundhöhlen- und Oropharynxkarzinomen, welche in dem Zeitraum von 1993 bis 2009 in der HNO-Klinik der Universität Leipzig als „High Volume Center“ behandelt wurden, mit besonderem Augenmerk auf die Stadien III-IV nach UICC/AJCC. In unserer Studie konnten wir eine Zunahme der an der Universität in Leipzig registrierten Patienten mit Mundhöhlen- und Oropharynxkarzinomen über die Jahre 1993 bis 2009 verzeichnen. Männer waren mehr als fünfmal so häufig betroffen wie Frauen. Diese Verteilung hielt sich über den Beobachtungszeitraum konstant. Bei den weiblichen Patientinnen wurden im Durchschnitt niedrigere Tumorstadien bei Erstdiagnose festgestellt. Frauen hatten insgesamt eine höhere 5-Jahresüberlebensrate. Die Stadienverteilung nach UICC/AJCC bei Erstdiagnose eines Mundhöhlen- und Oropharynxkarzinoms blieb über die Jahre hinweg annähernd gleich. Es wurden meist hohe Stadien festgestellt (62,7% Stadium IV). Das mittlere Erkrankungsalter von Mundhöhlen- und Oropharynxkarzinomen sank über den Beobachtungszeitraum. Das Alter bei Rezidivmanifestation blieb allerdings über die Jahre gleich und lag unter dem durchschnittlichen Alter bei Erstdiagnosestellung. In diesem Zeitraum wird in der Literatur eine zunehmende Infektionsrate mit HPV beschrieben, welche gemäß der Literaturdaten mit einem jüngeren Erkrankungsalter einhergeht. Über die Jahre fanden wir in dem von uns untersuchten Patientenkollektiv der Universitätsklinik Leipzig eine stetige Verbesserung der mittleren Überlebensraten. In zeitlicher Assoziation zu dieser Entwicklung fand eine Änderung der Therapiemodalitäten insbesondere mit Einführung der systemischen Chemotherapie ab ca. 2004 in Richtung einer zunehmenden multimodalen Therapie statt. Es konnte ein Vorteil im Gesamtüberleben nach einer kombiniert-operativen Therapie mit adjuvanter Radiochemotherapie gegenüber allen anderen Therapieformen gezeigt werden. Insbesondere im Stadium IV nach UICC/AJCC zeigte sich ebenfalls ein Vorteil der kombinierten Radiochemotherapie gegenüber einer alleinigen Radiotherapie.

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published_or_final_version / abstract / toc / Surgery / Doctoral / Doctor of Philosophy

The goal of this thesis was to evaluate the cost-effectiveness of implantable Doppler technology (IDT) used to monitor free tissue transfer (FTT) procedures in the treatment of cancer of the upper aerodigestive tract (UADT). First, a systematic review of the literature on the effectiveness of traditional and IDT monitoring techniques was performed. Second, a utility survey using a time trade-off technique was created and administered. The results from this survey were used to establish utility values for health states common in patients undergoing FTT procedures. Third, a cost study using the microcosting data available through the Ottawa Hospital was performed. Finally, a decision analytic model was created and an economic evaluation from the payer perspective was completed. A probabilistic sensitivity analysis (PSA) and a value of information analysis (VOI) were performed. The thesis found that the currently available evidence supports IDT as a cost-effective intervention. Further research should be directed towards determining the effectiveness of both traditional and IDT monitoring.

Background In the treatment of head and neck cancers (HNCs), radiotherapy (RT) has the advantage of organ preservation compared to surgery. However, treatment toxicities associated with RT can affect important functions for everyday life, both in the acute and late stage. RT to macroscopic tumour in HNC is commonly combined with elective RT to cervical lymph nodes at risk of microscopic involvement. The resulting risk reduction of the elective treatment based on dose-volume parameters is sparsely evaluated. So is the relationship between the elective treatment and treatment toxicity. The present thesis addresses these aspects. A strategy aimed at improving the outcome of RT is accelerated fractionation (AF). AF strives to shorten total treatment time to minimise proliferation of the tumour tissue during the RT period. We have investigated the impact of AF on both disease control and toxicity. Methods In the ARTSCAN study, 750 patients with localised HNC were randomised between AF (68 Gy in 4.5 weeks) and conventional fractionation (CF) (68 Gy in 7 weeks). The elective treatment volume was prescribed 46 Gy with CF in both treatment arms. The thesis is based on four individual papers, investigating the issues above in the whole study population or in sub-populations. Results No difference in disease control or late toxicity between CF and AF was observed at five years. However, there was an increased acute toxicity with AF. Weight loss was associated with treatment volume, independent of tumour stage. The elective treatment volume was found to be an independent risk factor for late aspiration, as well as mean dose to the pharyngeal constrictor muscles, neck dissection, and age at randomisation. There was a significant risk reduction for node relapses in volumes treated to an elective dose. Only a relapse in volumes treated to >60 Gy affected the survival. Conclusion The present thesis questions the benefit of AF in definitive RT as well as extensive elective treatment of the cervical nodes.

Head and neck cancer is the sixth leading type of cancer with 90 percent of head and neck cancer arising from squamous cell lining on the epithelium of the oral and nasal cavity, pharynx, and salivary gland. Even with tremendous achievements on chemotherapeutic drugs and therapies, the long-term prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) has shown little improvement over the last three decades. Cisplatin is one of widely used chemotherapeutic drugs for multiple cancers, including head and neck cancer, but the prolonged use of this drug is limited by its toxicity and by the development of resistance. To overcome these major roadblocks to improved prognosis requires mechanism-based therapeutic strategies to maximize the antitumor effect of drugs while limiting their toxicities. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of BCL-2 family-dependent mitochondrial apoptosis. DNA damage activates a tumor suppressor p53 to induce apoptosis. One of its functions is to induce the expression of several pro-apoptotic proteins such as Noxa, which binds to an anti-apoptotic BCL-2 family protein, MCL-1 (myeloid leukemia cell-1) to inactivate its pro-survival function and induce apoptosis. We examined Noxa expression and apoptosis induced by cisplatin in p53-wild-type HN30 and HN31, p53-truncated and inactive HN4 and HN12, and p53-deleted HN22 and HN8 HNSCC cell lines. We found that Noxa was induced in HN30 and HN31 cells and down-regulation of Noxa by shRNA (short-hairpin RNA) decreased apoptosis, indicating Noxa contribution to cisplatin-induced apoptosis. Interestingly, cisplatin treatment induced Noxa and apoptosis even in p53-deleted HN22 and HN8 cells, suggesting the existence of the p53-independent pathways for the induction of Noxa. Based on these observations, we hypothesized that modulation of Noxa/MCL-1 axis could mimic cisplatin-induced cell death. We found that Noxa overexpression induced cell death in all cell lines tested regardless of p53 status. This finding could be applicable as a potential therapeutic strategy to treat head and neck cancer.

Made available in DSpace on 2014-06-11T19:30:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-05-10Bitstream added on 2014-06-13T19:01:05Z : No. of bitstreams: 1 semenzati_go_dr_botfm.pdf: 1378533 bytes, checksum: e7073520a6a74d0502cf0985ad69a22a (MD5) / Universidade Estadual Paulista (UNESP) / O câncer de cabeça e pescoço corresponde a 5% de todas as neoplasias malignas do organismo, sendo os sítios mais prevalentes a cavidade oral, faringe e laringe. O principal fator de risco é o tabagismo e o carcinoma espinocelular é o tipo histológico mais frequente. Marcadores de células tumorais como o p53 e Ki-67 têm sido estudados em tumores de cabeça e pescoço pela sua imunoexpressão positiva para as células neoplásicas e em proliferação. Estudos experimentais possibilitam avaliar os efeitos nocivos do tabaco sobre as vias aéreas, sendo este o objetivo deste estudo. OBJETIVOS: Estudar, em ratos, os efeitos da exposição aguda à fumaça de cigarro sobre as mucosas da língua, faringe e laringe, por meio de análise histológica, morfométrica e imunohistoquímica da expressão das proteínas p53 e Ki-67. MATERIAL E MÉTODO: Ratos Wistar foram subdivididos em dois grupos de 20 animais cada: grupo controle (GC), ração e água ad libitum e grupo tabaco (GT) expostos à inalação de fumaça de 40 cigarro/dia por 60 dias. Os animais foram eutanaziados e realizado biópsias da língua, faringe e laringe para os estudos histopatológico, histomorfométrico e imunohistoquímico das proteínas p53 e do ki-67. RESULTADO: As análises de microscopia de luz da língua dos animais do grupo tabaco (GT) revelaram algumas alterações mais marcantes nesse grupo em cada sítio, sendo que na língua, ganharam destaque a hiperplasia epitelial (GT-90%), hiperplasia de células da camada basal (GT-95%) e displasia epitelial de grau leve a moderado (GT- 85%); na faringe, destacaram-se a hiperplasia de células da camada basal... / INTRODUCTION: The head and neck cancer represents 5% of all malignant neoplasm of the body, with the sites most prevalent oral cavity, pharynx and larynx. The main risk factor is smoking and squamous cell carcinoma is the most frequent histological type. Tumor cell markers such as p53 and ki-67 have been studied in head and neck tumors by their positive immunostaing for proliferating and neoplastic cells. Experimental studies to assess the possible harmful effects of smoking on the airways which are the objective of this study. OBJECTIVES: To study the effects of acute exposure to cigarette smoke on the mucosa of the tongue, pharynx and larynx in rats; using histological, morphometric and immunohistochemical expression of p53 and ki- 67. MATERIALS AND METHODS: Wistar rats were divided into two groups of 20 animals each control group (CG), food and water ad libitum and tobacco group (GT) exposed to inhalation of smoke from 40 cigarettes/day for 60 days. The animals were euthanized and biopsies of the tongue; pharynx and larynx were performed for histological studies, histomorphometric and immunohistochemical study of p53 and ki- 67. RESULTS: The light of the tongue microscopy analysis showed in GT group: epithelial hyperplasia (GT-90%), hyperplasia of the basal cell layer (GT-95%) and dysplasia of mild to moderate (GT-85%); in pharynx, highlighted the hyperplasia of the basal cell layer (GT-85%), dysplasia (GT-25%) and vascular congestion (GT-95%); predominated in the larynx cell hyperplasia of the basal layer (GT-70%), epithelial hyperplasia (GT-55%), congestion (GT-100%) and inflammatory infiltration of polymorphonuclear neutrophils (GT-25%).The morphometric study identified high measures of the keratin layer in group... (Complete abstract click electronic access below)

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science, 2017 / Aim: The aim of this study was to quantify random and systematic setup errors in a population of head and neck cancer patients for the purposes of evaluating departmental positioning and immobilization techniques, verification and treatment protocols, as well as validating the treatment margins used. Methods and Materials: All patients had more than one phase of radiation, each consisting of different megavoltage photon field arrangements. Some phases were also treated with electron fields in addition to the photon fields. Random and systematic setup errors in all three principal directions were calculated for two groups of patients, using record and verify system couch position data. For one group (20 patients) the positioning and immobilization device system was mechanically localized to the treatment couch, and for the other group (38 patients), it was visually centered on the treatment couch. Within both groups of patients, the patient position was either verified online with portal imaging or verified offline on a conventional radiotherapy simulator. Results: For the patient group treated with the base plate visually centered on the treatment table the population random and systematic setup errors calculated for the photon fields were only indicative of setup uncertainties in the anterior-posterior direction. For the patient group treated with the base plate localized to the treatment couch, the population random and systematic setup errors were found to be within the 5 mm clinical to planning target volume expansion margin used at Livingstone Hospital. Due to treatment couch position differences from fraction to fraction, setup errors made during this study could not reliably be determined for electron field treatments Conclusions: Results indicate that the base plate should be localized to the treatment couch when calculating random and systematic setup errors for photon fields using the couch position as a surrogate for patient position. For this method to be used to calculate setup errors for electron fields, shielding should always be fastened to the same position at the endface of the applicator. Offline and online verification did not significantly influence systematic setup errors. / XL2018

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