The chief aim in developing radiation treatment plans is to maximise tumour cell kill while minimising the killing of normal cells. The acceptance by a radiation oncologist of a radiation therapy treatment plan devised by the radiation therapist, at present is largely based on the oncologists' previous clinical experience with reference to established patterns of treatment and their clinical interpretation of the dose volume histogram. Some versions of radiotherapy planning computer software now incorporate a function that permits biologically based predictions about the probability of tumour control (TCP) and/or normal tissue complications (NTCP). The biological models used for these probabilities are founded upon statistical and mathematical principles as well as radiobiology concepts. TCP and NTCP potentially offer the capability of being able to better optimise treatments for an individual patient's tumour and normal anatomy. There have been few attempts in the past to correlate NTCPs to actual treatment complications, and the reported complications have generally not shown any significant correlation. Thus determining whether either or both NTCPs and TCPs could be correlated with the observed clinical outcomes of prostate radiotherapy is the central topic of this thesis. In this research, TCPs and NTCPs were prospectively calculated for prostate cancer patients receiving radiation therapy, and subsequently assessed against the clinical results of the delivered treatments. This research was conducted using two different types of NTCP models, which were correlated against observed treatment-induced complications in the rectum and bladder. The two NTCP models were also compared to determine their relative efficacy in predicting the recorded toxicities. As part of this research the refinement of some of the published bladder parameters required for NTCP calculations was undertaken to provide a better fit between predicted and observed complication rates for the bladder wall which was used in this research. TCPs were also calculated for each patient using the best available estimate of the radiosensitivity of the prostate gland from recent research. The TCP/NTCP data was analysed to determine if any correlations existed between the calculated probabilities and the observed clinical data. The results of the analyses showed that a correlation between the NTCP and a limited number of toxicities did occur. Additionally the NTCP predictions were compared to existing parameters and methods for radiotherapy plan evaluation - most notably DVHs. It is shown that NTCPs can provide superior discriminatory power when utilised for prospective plan evaluation. While the TCP could not be correlated with clinical outcomes due to insufficient follow-up data, it is shown that there was a correlation between the TCP and the treatment technique used.

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La radiothérapie occupe une place majeure dans l’arsenal thérapeutique des cancers.Malgré des progrès technologiques importants depuis près de vingt ans, des tissus sains au voisinage ou à distance de la tumeur cible continuent à être inévitablement irradiés à des niveaux de doses très différents. Ces doses sont à l’origine d’effets secondaires précoces (Œdème, radionécrose, Dysphagie, Cystite) ou tardifs (rectorragies, télangiectasie, effets carcinogènes, les pathologie cérébrovasculaires).Il est donc primordial de quantifier et de prévenir ces effets secondaires afin d'améliorer la qualité de vie des patients pendant et après leur traitement.La modélisation du risque d'événements iatrogènes radio-induits repose sur la connaissance précise de la distribution de doses au tissu sain d'intérêt ainsi que sur un modèle de risque capable d'intégrer un maximum d'informations sur le profil d'irradiation et des autres facteurs de risques non dosimétriques. L'objectif de ce travail de thèse a été de développer des méthodes de modélisation capables de répondre à des questions spécifiques aux deux aspects, dosimétriques et statistiques, intervenant dans la modélisation du risque de survenue d'événements iatrogènes radio-induits.Nous nous sommes intéressé dans un premier temps au développement d'un modèle de calcul permettant de déterminer avec précision la dose à distance due au rayonnements de diffusion et de fuite lors d'un traitement par radiothérapie externe et ce, pour différentes tailles des champs et à différentes distances de l'axe du faisceau. Ensuite, nous avons utilisé des méthodes d'analyse de données fonctionnelles pour développer un modèle de risque de toxicité rectales après irradiation de la loge prostatique. Le modèle proposé a montré des performances supérieures aux modèles de risque existants particulièrement pour décrire le risque de toxicités rectales de grade 3. Dans le contexte d'une régression de Cox flexible sur données réelles, nous avons proposé une application originale des méthodes de statistique fonctionnelle permettant d'améliorer les performances d'une modélisation via fonctions B-splines de la relation dose-effet entre la dose de radiation à la thyroïde.Nous avons également proposé dans le domaine de la radiobiologie une méthodes basée sur l’analyse en composantes principales multiniveau pour quantifier la part de la variabilité expérimentale dans la variabilité des courbes de fluorescence mesurées. / Radiotherapy plays a major role in the therapeutic arsenal against cancer. Despite significant advances in technology for nearly twenty years, healthy tissues near or away from the target tumor remain inevitably irradiated at very different levels of doses. These doses are at the origin of early side effects (edema, radiation necrosis, dysphagia, cystitis) or late (rectal bleeding, telangiectasia, carcinogenic, cerebrovascular diseases). It is therefore essential to quantify and prevent these side effects to improve the patient quality of life after their cancer treatment.The objective of this thesis was to propose modelling methods able to answer specific questions asked in both aspects, dosimetry and statistics, involved in the modeling risk of developing radiation-induced iatrogenic pathologies.Our purpose was firstly to assess the out-of-field dose component related to head scatter radiation in high-energy photon therapy beams and then derive a multisource model for this dose component. For measured doses under out-of-field conditions, the average local difference between the calculated and measured photon dose is 10%, including doses as low as 0.01% of the maximum dose on the beam axis. We secondly described a novel method to explore radiation dose-volume effects. Functional data analysis is used to investigate the information contained in differential dose-volume histograms. The method is applied to the normal tissue complication probability modeling of rectal bleeding for In the flexible Cox model context, we proposed a new dimension reduction technique based on a functional principal component analysis to estimate a dose-response relationship. A two-stage knots selection scheme was performed: a potential set of knots is chosen based on information from the rotated functional principal components and the final knots selection is then based on statistical model selection. Finally, a multilevel functional principal component analysis was applied to radiobiological data in order to quantify the experimental Variability for replicate measurements of fluorescence signals of telomere length.