No description available.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13032号 / 論医博第2114号 / 新制||医||1016(附属図書館) / 32990 / 横浜市立大学大学院医科学専攻 / (主査)教授 増永 慎一郎, 教授 坂井 義治, 教授 小川 修 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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.

Objectifs : Etablir des corrélations dose-volume effet entre les paramètres dosimétriques proposés par le GEC-ESTRO et la probabilité de survenue d’événements tels que le contrôle tumoral ou une toxicité radio-induite.Matériel et méthodes : Les données cliniques et dosimétriques de cohortes de patientes traitées à Gustave Roussy et dans différents centres ont été confrontées. Dans un premier temps les paramètres dosimétriques de la curiethérapie 3D ont été comparés à ceux de la curiethérapie classique. Dans un second temps, la topographie des zones les plus exposées des organes à risque, ainsi que l’impact des mouvements de la vessie, du rectum, et du colon sigmoïde sur l’évaluation de la dose délivrée, ont été étudiés. Enfin, des analyses dose-volume effets ont été réalisées.Résultats : Les valeurs des paramètres dosimétriques volumétriques (D2cm3) de la vessie et du rectum se sont révélées faiblement corrélées et significativement supérieures aux doses évaluées aux points de l’ICRU ou à un point vésical alternatif. Les zones les plus exposées de la vessie et du rectum sont apparues situées au-dessus des points de l’ICRU. Les mouvements des organes autour de l’implant pendant la délivrance du traitement sont apparus marginaux pour la vessie et sigmoïde, en dehors de variations individuelles. En revanche, la dose délivrée au rectum étaient en moyenne plus élevée que le dose planifiée. Les analyses dose-volume effets ont montré des corrélations significatives entre D0.1cm3 et D2cm3 et la probabilité de survenue d’une morbidité tardive urinaire ou rectale. De la même manière, des corrélations significatives ont été établies entre la D90 des CTV à haut risque et à risque intermédiaire et la probabilité d’obtention du contrôle local. Divers caractéristiques tumorales (largeur au diagnostic, volume du CTV-HR, stade FIGO), impactent ces relations, de même que l’étalement total du traitement.Conclusion : Des corrélations dose-volume effets ont été établies entre les paramètres dosimétriques modernes et la probabilité d’obtenir le contrôle local ou d’entraîner une morbidité tardive. En ce qui concerne le contrôle tumoral, les objectifs de prescription doivent être personnalisés en fonction de critères carcinologiques. Pour les organes à risque, de contraintes de dose basées sur l’expérience de la curiethérapie 3D peuvent être établies, mais doivent être affinées dans de futures études en fonction de cofacteurs tels que les comorbidités. Les points gardent un intérêt en recherche clinique, pour l’étude de la morbidité vésicale ou vaginale.Ce travail a l'objet de 6 publications dans des revues internationales à comité de lecture. La septième est présentée sous forme de manuscrit. / Objectives: To establish dose-volume effects correlations between volumetric dosimetric parameters proposed by the GEC-ESTRO and the probability of occurrence of events such as tumor control or radiation-induced toxicity.Methods: Clinical and dosimetric data of patients treated at Gustave Roussy and in different centers have been reviewed. At first step, dosimetric parameters of image-guided brachytherapy were compared with those of conventional brachytherapy. Secondly, the topography of the most exposed areas of the organs at risk, and the impact of the movements of the bladder, rectum, and sigmoid colon on the assessment of the delivered dose, were studied. Finally, analyzes dose-volume effects were performed.Results: The values of volumetric dosimetric parameters (D2cm3) of the bladder and rectum appeared weakly correlated and significantly higher than the doses evaluated at ICRU points of bladder and rectum , an even in an alternative bladder point. The most exposed areas of the bladder and rectum appeared located above the points of the ICRU. The movements of the organs around the implant during the delivery of the treatment appeared marginal for the bladder and sigmoid, apart from individual variations. However, the mean delivered dose to the rectum was higher than the planned dose. Dose-volume effects correlations showed significant correlations between D0.1cm3 and D2cm3 and the probability of occurrence of urinary or rectal late morbidity. Similarly, significant correlations have been established between the D90 of the high risk, intermediate risk-CTV and the probability of achieving local control. Various tumor characteristics (width, HR-CTV volume, FIGO stage) impact these relationships, as well as the treatment time.Conclusion: Dose-volume effects correlations have been established between modern dosimetric parameters and the probability of achieving local control or cause late morbidity. Regarding tumor control, prescription aims must be customized according to oncologic criteria. For organs at risk, new dose constraints based on 3D brachytherapy experience can be established but should be refined in future studies based on cofactors such as comorbidities. The points retain an interest in clinical research for the study of bladder or vaginal morbidity.

Construction of radiotherapy treatments for cancer is a laborious and time consuming task. At the same time, when presented with a treatment plan, an oncologist can quickly judge whether or not it is suitable. This means that the problem of constructing these treatment plans is well suited for automation. This thesis investigates a novel way of automatic treatment planning. The treatment planning system this pipeline is constructed for provides dose mimicking functionality with probability density functions of dose–volume histograms (DVHs) and spatial dose as inputs. Therefore this will be the output of the pipeline. The input is historically treated patient scans, segmentations and spatial doses. The approach involves three modules which are individually replaceable with little to no impact on the remaining two modules. The modules are: an autoencoder as a feature extractor to concretise important features of a patient segmentation, a distance optimisation step to learn a distance in the previously constructed feature space and, finally, a probabilistic spatial dose estimation module using sparse pseudo-input Gaussian processes trained on voxel features. Although performance evaluation in terms of clinical plan quality was beyond the scope of this thesis, numerical results show that the proposed pipeline is successful in capturing salient features of patient geometry as well as predicting reasonable probability distributions for DVH and spatial dose. Its loosely connected nature also gives hope that some parts of the pipeline can be utilised in future work. / Skapandet av strålbehandlingsplaner för cancer är en tidskrävande uppgift. Samtidigt kan en onkolog snabbt fatta beslut om en given plan är acceptabel eller ej. Detta innebär att uppgiften att skapa strålplaner är väl lämpad för automatisering. Denna uppsats undersöker en ny metod för att automatiskt generera strålbehandlingsplaner. Planeringssystemet denna metod utvecklats för innehåller funktionalitet för dosrekonstruktion som accepterar sannolikhetsfördelningar för dos–volymhistogram (DVH) och dos som input. Därför kommer detta att vara utdatan för den konstruerade metoden. Metoden är uppbyggd av tre beståndsdelar som är individuellt utbytbara med liten eller ingen påverkan på de övriga delarna. Delarna är: ett sätt att konstruera en vektor av kännetecken av en patients segmentering, en distansoptimering för att skapa en distans i den tidigare konstruerade känneteckensrymden, och slutligen en skattning av sannolikhetsfördelningar med Gaussiska processer tränade på voxelkännetecken. Trots att utvärdering av prestandan i termer av klinisk plankvalitet var bortom räckvidden för detta projekt uppnåddes positiva resultat. De estimerade sannolikhetsfördelningarna uppvisar goda karaktärer för både DVHer och doser. Den löst sammankopplade strukturen av metoden gör det dessutom möjligt att delar av projektet kan användas i framtida arbeten.