Diss. (sammanfattning) Umeå : Umeå universitet, 2008. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Die Behandlung von Patienten mit Tumoren im Kopf-Hals-Bereich gestaltet sich als komplexer und herausfordernder Prozess sowohl für den Patienten als auch für die behandelnden Ärzte und Chirurgen. Zur Gewährleistung der bestmöglichen individuellen Therapie werden vor Beginn der Behandlung zahlreiche diagnostische Verfahren durchgeführt. Hierzu zählen unter anderem medizinische bildgebende Verfahren wie z.B. Computertomographie (CT) oder Magnetresonanztomographie (MRT) sowie die Entnahme von tumorverdächtigem Gewebe während einer Panendoskopie zur exakten Bestimmung der Tumorart (Histologie, Grading, TNM-Klassifikation nach UICC, genaue Lokalisation des Primärtumors, der lokoregionären Metastasen und ggf. Fernmetastasen). Die gewonnenen Informationen bilden anschließend die Grundlage für die Entscheidung über die durchzuführende Therapie und stehen in unterschiedlichen klinischen Informationssystemen sowie auf Papierakten zur Verfügung. Leider werden die Daten im klinischen Alltag häufig nur unstrukturiert und schwer auffindbar präsentiert, da die führenden Informationssysteme nur unzureichend in den klinischen Arbeitsprozess integriert und untereinander schlecht vernetzt sind. Die präzise und erschöpfende Darstellung der jeweiligen individuellen Situation und die darauf aufbauende Therapieentscheidung sind aber entscheidend für die Prognose des Patienten, da der erste, gut geplante \"Schuss\" entscheidend für den weiteren Verlauf ist und nicht mehr korrigiert werden kann. In dieser Arbeit werden neue Konzepte zur Verbesserung des Informationsmanagements im Bereich der Kopf-Hals-Tumorbehandlung entwickelt, als prototypische Software implementiert und im klinischen Alltag in verschiedenen Studien wissenschaftlich evaluiert. Die Erlangung eines tiefgreifenden Verständnisses über die klinischen Abläufe sowie über beteiligte Informationssysteme und Datenflüsse stellte den ersten Teil der Arbeit dar. Aufbauend auf den Erkenntnissen wurde ein klinisches Informationssystem oncoflow entwickelt. Oncoflow importiert vollautomatisch relevante Patientendaten von verschiedenen klinischen Informationssystemen, restrukturiert die Daten und unterstützt Ärzte und Chirurgen im gesamten Therapieprozess. Das System wurde anschließend in unterschiedlichen Studien evaluiert und der klinische Nutzen in Bezug auf effizientere Arbeitsabläufe und eine verbesserte Informationsqualität gezeigt. Im folgenden Teil der Arbeit wurden Machine Learning Methoden genutzt um von Daten in der elektronischen Patientenakte auf den aktuellen Prozessschritt im Therapieprozess zu schließen. Der letzte Teil der Arbeit zeigt Möglichkeiten zur Erweiterung des Systems zur Nutzung in weiteren klinischen Fachdisziplinen auf.

O objetivo deste estudo foi avaliar a efetividade de uma formulação farmacêutica experimental (solução com 1,54% de pilocarpina em spray) sobre o fluxo salivar (FS), experiência de boca seca e qualidade de vida (QV), comparado com placebo, em pacientes tratados com radioterapia (RTx) para câncer de cabeça e pescoço (CCP). Este ensaio clínico randomizado, controlado, duplo-cego e crossover foi realizado em pacientes com xerostomia (n=28). O FS foi medido pela sialometria estimulada (técnica do hálito fresco), a experiência de boca seca pelo Xerostomia Inventory (XI) e a QV pelo Oral Health Impact Profile (OHIP-14). As avaliações foram feitas antes do início da terapêutica - baseline (T0), um (T1), dois (T2) e três (T3) meses após iniciar o uso do spray, além da mensuração do FS uma hora após o baseline (T0+), seguido de período washout de 01 mês e após crossover, os mesmos períodos foram avaliados. O FS apresentou maior após uma hora (p=0,003 - teste de Wilcoxon) e dois meses (p=0,002 - teste de Friedman) de uso do spray com pilocarpina; melhoria na experiência de xerostomia, verificado pela diminuição significante (p<0,05 - teste de Friedman) dos escores em cinco itens do XI; melhoria na QV, verificado pela diminuição significante (p<0,05 - teste de Friedman) dos escores em três itens do OHIP-14, com o passar de alguns dos períodos de avaliação. A aplicação tópica da formulação de pilocarpina em spray melhoraram significantemente o FS, experiência de xerostomia e QV para os pacientes tratados com RTx para CCP. / The aim of this study was to evaluate the effectiveness of an experimental pharmaceutical formulation (1.54% pilocarpine spray solution) on salivary flow (SF), dry mouth experience and quality of life (QoL), compared to placebo, in patients treated with radiotherapy (RTx) for head and neck cancer (HNC). This randomized, controlled, double-blind, crossover clinical trial was performed in patients with xerostomia (n = 28). SF was measured by stimulated sialometry (fresh breath technique), dry mouth experience by Xerostomia Inventory (XI) and QoL by the Oral Health Impact Profile (OHIP-14). The evaluations were done before - baseline (T0), one (T1), two (T2) and three (T3) months after starting the spray, besides the measurement of FS one hour after the baseline (T0+), followed by a washout period of 1 month and after crossover, the same periods were evaluated. The SF presented higher after one hour (p=0.003 - Wilcoxon test) and two months (p=0.002 - Friedman test) of the use of the pilocarpine spray; improvement in the xerostomia experience, verified by the significant decrease (p<0.05 - Friedman test) of the scores in five items of XI; improvement in the QoL, verified by the significant decrease (p<0.05 - Friedman\'s test) of the scores on three items of the OHIP-14, with the passing of the evaluation of some periods. Topical application of the pilocarpine spray formulation significantly improved SF, xerostomia experience and QoL for patients treated with RTx for HNC.

AIM & OBJECTIVES: Human papilloma virus (HPV) has been related to cervical infection, however, its part in Head and Neck Squamous Cell Carcinoma (HNSCC) is still debatable and is easy to refute. Suspicion of HPV causation is heightened when carcinomas arise in patients that are young and have never smoked. The present UK based study undertaken at Northampton NHS Trust endeavoured to determine the extent to which HPV is an entity in HNSCC in the UK. Furthermore, the study investigated whether sexual behaviour (as measured by sexual health clinic (SHC) attendance) is linked the acquisition of HPV associated HNSCC in young age groups. HNSCC incidences and sexual trends in the UK were collected from publicly available databases to identify if there were any changes at a national level in sexual behaviours and their influence on HNSCC in young age groups. MATERIALS & METHODS: PCR was used to evaluate the presence of HPV in biopsy samples from of 99 patients diagnosed with HNSCC at Northampton Hospital from 2006 to 2014. Patient demographics on age, sex, smoking, alcohol use and SHC attendance were also collected. All HPV PCR positive biopsies were further genotyped using an ABI 3130xl genetic analyser. Databases in the UK; including GLOBOCAN, NATSAL and PHE were searched for data on HNSCC prevalence, sexual behaviour trends and vaccine uptake. Multinomial regression explored the relationship between HPV positivity and sex, age, smoking, drinking, race and SHC attendance. RESULTS: PCR showed that 25.2% (25/99) of biopsies tested were positive for HPV and were all obtained from white participants. Most specimens (23, 92%) were high-risk (HR) HPV 16 positive with a mean age of 56 for HPV positivity and 72% of the cases 50-60 years old. Smokers were 11% in total (11/99) with most 88.9% participants (88/99) being non-smokers. HPV positivity was strongly linked with non-smoking history (p < 0.001); no alcohol abuse (p < 0.001); male gender (p < 0.001); young age less than 60 years (p < 0.001) and SHC attendance (p < 0.001). A Kruskal-Wallis post hoc test affirmed the impact of age on HPV positivity (p= < 0.05). GLOBOCAN and Cancer Research demonstrated a rising UK HNSCC pattern of over 200% for both sexes from 1975 to 2011. The three NATSAL surveys undertaken in 1990-1991, 1999-2001 and 2010-2012 demonstrated an overall increase in opposite and same sex partners. The UK average of individuals engaging in oral sex was in the younger age groups of between 16 and 54 with at least 70% of males and 63% females of that age engaging in oral sex. Finally, NASTAL 1, 2 and 3 surveys reported 20 vs 15; 25 vs 55; 55 vs 65 of males and females respectively with more than 10 sexual partners to have attended the SHC. The UK immunization take-up was over 90% countrywide. CONCLUSION: Few research studies have been conducted to date on HPV as a cause of HNSCC in the UK. The present research showed 25.2% of HNSCC to be caused by HPV, with the high risk (HR) genotype 16 (the leading cause of cervical cancer) accounting for 92% (23/25) of the cases. These outcomes affirmed the high prevalence of HR-HPV in HNSCC, with a rate of 25.2% similar to those reported previously. Routine HPV testing in those aged below 60 is therefore warranted. Smoking and drinking showed negative correlation; the young age of below 60 and attendance of the SHC for both sexes showed a positive correlation with HPV positive HNSCC. NATSAL data showed increased sexually risky behaviour coupled with attending the SHC in younger ages for both sexes. Increased sexually risky behaviour as shown in NASTAL surveys may be the reason why young age and SHC attendance is positively correlated with HPV HNSCC. The study highlights a conceivable relationship between HPV positive HNSCC in those under 60 years with no smoking history who attended the SHC. Smoking and drinking are known risks for HNSCC in those past 65 years of age; the negative association with HPV HNSCC in the young in the present research revealed smoking and drinking to have reduced association with HPV HNSCC. The reported HR-HPV positive HNSCC in young age groups inform future vaccination strategies and consequently decrease the quantity of HPV HNSCC's.

Orientador: Paula Rahal / Banca: Ana Elizabete Silva / Banca: Erika Cristina Pavarino Bertelli / Banca: Erico Tosoni Costa / Banca: Raphael Bessa Parmigiani / Resumo: O carcinoma de células escamosas de cabeça e pescoço (HNSCC) é uma doença heterogênea que afeta o epitélio da cavidade oral, laringe e faringe. A maioria dos pacientes é diagnosticada em estágios avançados da doença e ainda não existe nenhum marcador sensível e específico para o comportamento agressivo deste tumor. Portanto, uma detecção precoce e biomarcadores de prognóstico são altamente necessárias para uma administração mais racional da doença. A hipermetilação de ilhas CpGs é um dos mecanismos epigenéticos mais importantes que levam a um silenciamento gênico em tumores e tem sido extensivamente utilizados para a identificação de biomarcadores. Neste estudo foram combinados as análises de Rapid Substractive Hybridization (RaSH) e microarray de uma maneira hierárquica para selecionar genes que, supostamente, são reativados pelo agente desmetilante 5'Aza'2'deoxicitidina (5Aza'dC) em linhagens celulares derivados de carcinoma de cabeça e pescoço (FaDu, UM' SCC'14A, UM'SCC'17A e UM'SCC'38). Esta análise combinada identificou 78 genes dos quais 35 foram reativados em, pelo menos, 2 linhagens celulares e apresentavam ilha CpG nas suas regiões 5'. A reativação de três destes 35 genes (CRABP2, MX1 e SLC15A3) foi confirmada por PCR em tempo real (Fold change ≥ 3). O seqüenciamento de bissulfito de sódio das suas ilhas CpGs revelou que eles estão, de fato, diferencialmente metilados em linhagens celulares derivadas de carcinoma de cabeça e pescoço. Foram detectadas uma maior freqüência de hipermetilação dos genes CRABP2 (58.1% para a região 1) e MX1 (46.3%) em amostras primárias de câncer de cabeça e pescoço quando comparados a linfócitos de indivíduos saudáveis utilizando o PCR de metilação específica (MSP). Finalmente a ausência da proteína CRABP2 foi associada com... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Most patients are diagnosed at late stages of the disease and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined Rapid Subtractive Hybridization (RaSH) and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5'aza'2'deoxycytidine (5Aza'dC) in HNSCC cell lines (FaDu, UM'SCC'14A, UMSCC'17A, UM'SCC'38A). This combined analysis identified 78 genes of which 35 were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of three out of these 35 genes (CRABP2, MX1 and SLC15A3) was confirmed by qRT'PCR (fold change ≥ 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using Methylation Specific PCR (MSP), we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC, when compared to lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease'free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients / Doutor

O câncer de cabeça e pescoço (CCP) abrange cerca de 10% dos tumores malignos, sendo uma doença cujo tratamento é agressivo em suas diferentes abordagens. Tanto a doença quanto os tratamentos podem gerar impactos na qualidade de vida (QV) dos pacientes de forma temporária ou definitiva. O objetivo deste estudo foi verificar mudanças na percepção de QV e nas condições de saúde bucal de um grupo de pacientes de CCP tratados em um hospital de Porto Alegre, em relação ao período pré-tratamento após 30 meses decorridos de seu tratamento oncológico. Outro objetivo foi identificar diferenças entre os participantes sobreviventes e falecidos quanto às medidas registradas na linha de base. Na linha de base, foram entrevistados e examinados 46 pacientes com tumores primários em regiões de cabeça e pescoço e que ainda não haviam iniciado o tratamento oncológico. No acompanhamento, foram constatados 23 óbitos e 04 perdas entre os integrantes do grupo inicial, conseguindo-se entrevistar e examinar 19 sobreviventes. Foram utilizados os questionários de QV geral abreviado da Organização Mundial de Saúde (WHO Quality of Life Bref – WHOQOL Bref) e o de QV relacionado à saúde específico para pacientes de CCP da European Organisation for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire Head &Neck 35 – EORTC H&N 35), e os índices de dentes cariados, perdidos e obturados (CPO-D), e de Uso e Necessidade de Prótese. Ainda, foram registradas informações de autopercepção de saúde bucal, acesso e satisfação dos sobreviventes em relação ao atendimento odontológico. Para a análise estatística, as medidas iniciais e finais foram comparadas utilizando-se os testes qui-quadrado, Exato de Fisher, T de Student e Mann-Whitney. Na linha de base, foram encontradas diferenças significativas entre os pacientes sobreviventes e falecidos em relação ao estadiamento tumoral, tipo de tratamento, disfagia, domínio físico do questionário de QV WHOQOL Bref, escore geral do questionário de qualidade de vida relacionado à saúde EORTC H&N35 e seus itens dor, deglutição e comer em público. De forma geral, após uma média de 32 meses de acompanhamento, os sobreviventes apontaram impactos físicos relacionados ao câncer e seu tratamento, contudo, sua percepção de QV não sofreu alteração significativa no acompanhamento de longo prazo. Em relação às condições de saúde bucal, houve elevação do escore médio do CPO-D e do uso de próteses dentárias. Os pacientes sentiram necessidades de atendimento odontológico em razão de dor e reabilitação protética no período pós-tratamento oncológico e, com exceção de quatro casos, não receberam acompanhamento odontológico sistematicamente organizado com relação ao CCP. Os achados deste estudo acompanham as recomendações da literatura para incluir, rotineiramente, a avaliação de QV pelos serviços oncológicos, como uma ferramenta que potencializa a qualificação deste cuidado posto que permite aprofundar a compreensão dos pacientes e de suas necessidades. / Head and neck cancers, which represent approximately 10% of all malignancies, usually have an aggressive treatment, irrespective of the therapeutic approach. Both the disease and its treatment may impact temporarily or definitively on quality of life. The objective of this study was to verify changes in the perception of quality of life and in the oral health of patients with head and neck cancer in a hospital of the city of Porto Alegre, immediately before and at least 30 months after the cancer treatment. Additional objective was to evaluate the differences between survivors and deaths in respect to baseline measures. Baseline evaluation comprised interviews carried out with 46 patients diagnosed with primary head and neck tumors before the start of the oncologic treatment. The follow up study was carried out with 19 survivors, while 23 participants died during the follow up and the 4 remaining were not located. Quality of life was assessed using WHOQOL Bref and EORTC H&N 35 questionnaires, while oral health examinations included DMFT and dental prostheses assessments following the WHO criteria. Information in respect to self-perceived oral health, access to and satisfaction with oral health services were also collected. Baseline and follow up measures were compared using Chi-square, Fisher’s exact, Student’s t and Mann-Whitney tests. Baseline results revealed significant differences between survivors and deaths in respect to tumor stage, type of treatment, dysphagia, physical domain WHOQOL Bref scores, EORTC H&N 35 full scores and pain, swallowing and eating in public items. Overall, survivors reported physical impacts related to the disease and its treatment. However, the perception of quality of life was not significantly changed during follow up. In respect to oral health, there was an increase in the mean DMFT and in the use of dental prostheses between the baseline and the follow up after 30 months. Participants of the follow up reported the need of dental treatment due to pain and dental prosthetic rehabilitation after the completion of the cancer treatment. With the exception of four participants, cancer patients who took part of the study did not receive systematic oral care. The findings of this study are in accordance with the previous recommendations of the inclusion of quality of life evaluations routinely by oncologic services in order to provide a tool to potentiate the quality of care and to improve the understanding of the cancer patients and their needs.

O câncer representa um importante problema de saúde pública no mundo, devido ao aumento da sua prevalência, além do grande impacto individual, institucional e social. Assim, merece uma abordagem ampliada, integral e interdisciplinar, a fim de minimizar as seqüelas decorrentes da doença ou do seu tratamento, visando à cura com manutenção da qualidade de vida (QV). Dessa forma, este trabalho teve como objetivos descrever o perfil sócio-demográfico e de saúde bucal de pacientes com câncer de cabeça e pescoço assistidos no HNSC, Porto Alegre – RS e, verificar o impacto na QV destes de um protocolo de cuidados odontológicos sistemático, antes, durante e depois da terapia oncológica. O estudo, delineado como um Ensaio Clínico Randomizado, teve a participação de 46 sujeitos com diagnóstico de neoplasia primária de cabeça e pescoço, captados por conveniência, consecutivamente e distribuídos aleatoriamente em dois grupos. No grupo controle, os pacientes foram examinados e orientados sobre os possíveis efeitos do tratamento oncológico e encaminhados aos serviços de atenção básica de referência para atendimento odontológico. No grupo intervenção, os pacientes foram examinados e orientados, sobre os possíveis efeitos do tratamento oncológico. Os sujeitos incluídos neste grupo receberam um protocolo de cuidados odontológicos na instituição, com acompanhamento profissional sistemático antes, durante e depois da terapia oncológica. Também foram fornecidas, aos cuidadores e pacientes, em ambos os grupos, orientações sobre os possíveis efeitos secundários da terapia oncológica e de ações para minimizar estes problemas. Os dados coletados referem-se a condições sócio-demográficas e de saúde bucal e também de avaliação da QV através de dois questionários - EORTC (específico para pacientes com câncer de cabeça e pescoço) e WHOQOL (avaliação geral da QV), aplicados em dois momentos distintos: antes e quinze dias depois da terapia oncológica concluída. Os resultados mostraram uma maior prevalência do câncer de cabeça e pescoço em homens, de baixo nível educacional e sócio-econômico, com pobre condição oral e média de idade de 54,2 anos. O diagnóstico histopatológico mais freqüente foi o carcinoma epidermóide, sendo as localizações preferenciais a língua e orofaringe. Mais de 60% dos diagnósticos foram realizados nas fases avançadas (III e IV – TMN) e os principais tratamentos realizados a cirurgia e a radioterapia. Apesar das características basais serem desfavoráveis, o grupo intervenção apresentou melhora na avaliação geral de QV e manutenção da específica após o tratamento oncológico, enquanto que o grupo controle mostrou piora em ambos, porém não houve diferença significativa entre os grupos. Entretanto, a variação das medidas (delta) no grupo intervenção, quando comparadas as características basais e finais, mostra uma projeção que tendencia uma melhoria significativa ao longo do tempo. Verifica-se também uma redução de candidíase (p<0,05) e mucosite no grupo intervenção. Conclui-se que os pacientes assistidos no Serviço de Oncologia do HNSC apresentaram o perfil típico dos tumores de localização de cabeça e pescoço no país, com maior prevalência de homens, tabagistas, de baixo nível sócio-econômico e educacional e pobre saúde oral. O protocolo de cuidados odontológicos desenvolvido foi capaz de reduzir danos decorrentes da terapia oncológica, além de poder contribuir para uma melhoria da QV ao longo do tempo aos pacientes com câncer de cabeça e pescoço. / Cancer represents a major public health problem all over the world due to the increase in its prevalence, besides its great individual institutional, and social impact. Thus, it deserves a wide, integral, and interdisciplinary approach in order to minimize the sequelae resulting from the disease or its treatment, and aiming to the healing with maintenance of the quality of life (QoL). This way, this study aimed to describe the social-demographic and oral health profile of head and neck cancer patients treated in Hospital Nossa Senhora da Conceição (HNSC), Porto Alegre, Brazil, and to check the impact of a systematic dental care guideline on the QoL before, during, and after the oncological therapy. The study, designed as a Randomized Clinical Trial, had the participation of 46 subjects with diagnosis of head and neck primary neoplasy, captured by convenience, consecutively, and randomly distributed in two groups. In the control group, patients were examined and advised about the possible effects of the oncological treatment and referred to the basic health care services for dental care. In the test group, patients were examined and advised about the possible effects of oncological treatment. The subjects included in this group received a dental care guideline in the institution, with a systematic professional follow-up before, during, and after the oncological therapy. Also, both caretakers and patients from each group received guidance about the possible secondary effects of the oncological therapy and the actions to minimize these problems. Collected data refer to the social-demographic and oral health status, as well as the evaluation of QoL by means of two questionnaires - EORTC (specific for head and neck cancer patients), and WHOQOL (general evaluation of QoL). These were administered in two distinct moments: before the onset and fifteen days after the conclusion of the oncological therapy. Results showed a higher prevalence of head and neck cancer in men, with low educational and social-economic level, with a poor oral condition, and an average age of 54.2 years. The most frequent histopathological diagnosis was epidermoidis carcinoma, being the preferential sites the tongue and the oropharynx. More than 60% of the diagnosis was done in the advanced phases (III e IV – TMN), and the main treatments performed were surgery and radiotherapy. In spite of the unfavorable baseline characteristics, the test group showed an improvement in the general evaluation of QoL, and maintenance of the specific QoL after the oncological treatment. The control group showed a worsening in both of them, although there was no significant difference between the groups. However, the range of the measures (delta) in the test group, when compared to the baseline and final characteristics, shows a projection tending to a significant improvement along time. A decrease in candidiasis (p<0,05) and muccositis was also shown in the test group. It is concluded that the patients treated in the Oncology Service of HNSC have shown a profile that is typical of the head and neck tumors in the country, with higher prevalence in men, smokers, low social-economic and educational level, and poor oral health. The dental care guideline that was developed was able to decrease harm resulting from the oncological therapy, as well as to contribute for an improvement of QoL along the time for the patients with head and neck cancer.

Anatomic changes occur throughout head and neck radiotherapy, and a new treatment plan is often required to mitigate the resulting changes in delivered dose to key structures. This process is known as adaptive radiotherapy (ART), and can be labour-intensive. The aim of this thesis is to optimise ART, addressing some of the technical and clinical challenges facing its routine clinical implementation. Optimising the frequency and timing of adaptive replanning is important, and it has been shown here that intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are equally robust to weight loss during head and neck radiotherapy. Plan adaptation strategies that have previously been developed for IMRT are therefore applicable to VMAT.Contour propagation is an important component of ART, and it is essential to ensure that propagated contours are accurate. A method for assessing the suitability of a metric for measuring automatic segmentation accuracy has been developed and applied to the head and neck. For the parotids and larynx, metrics based on surface agreement were better than the commonly used Dice similarity coefficient. By establishing a consensus on which metrics should be used to assess segmentation accuracy, comparison of different algorithms is more objective and should lead to more accurate automatic segmentation. A novel method of assessing contour propagation accuracy on a patient-specific basis has also been developed. This was demonstrated on a cohort of head and neck patients and shows potential as a tool for identifying propagated contours that are subject to a high degree of uncertainty. This is a novel tool that will increase the efficiency of automatic segmentation and, therefore, ART.Optimum ART requires consideration of different radiotherapy-related toxicities, and image-based data mining is a powerful technique for spatially localising dose-response relationships. Correction for multiple comparisons through permutation testing is essential, but has so far only been applied to categorical data. A novel method has been developed for performing permutation testing and image-based data mining with a continuously variable clinical endpoint. Application to trismus for head and neck radiotherapy identified a region with a dose-response relationship in the ipsilateral masseter. Sparing this structure during radiotherapy should reduce the severity of radiation-induced trismus. ART mitigates the dosimetric effects of anatomic changes, and this thesis has addressed technical and clinical challenges that have so far limited its clinical implementation. Detailed knowledge of dose-response relationships will enable selection of patients for ART based on potential clinical benefit, and accurate contour propagation will make ART more efficient, facilitating its routine implementation.