Deterioration in voice quality following radiation therapy for the treatment of laryngeal cancers (LC) is well documented in literature. The majority of studies show that these voice problems are long term and in some cases permanent. Deterioration in voice quality, especially over a period of time could lead to significant communication difficulties in daily life or in some cases could even result in loss of profession. Despite the negative effects of radiation therapy on voice quality being well documented, few studies have focused on the efficacy of voice therapy in the irradiated LC population. The purpose of this study was to investigate the efficacy of a well researched, evidence based voice therapy approach, known as Vocal Function Exercises (VFEs) in improving vocal function in patients who have been irradiated for LCs. The present study conducted in three systematic stages with distinct and related study aims. The first involved characterizing the head and neck cancer treatment seeking population at the University of Kentucky (UK). Stage 2 involved characterizing vocal function following irradiation for LC using a multidimensional assessment approach. Stage 3 was a phase 2 clinical trial aimed at treating these deficits in vocal function identified through stage 2 using a systematic evidence based voice therapy approach, Vocal Function Exercises. For the phase 2 clinical trial, the comparison group received vocal hygiene (VH) counseling. Observations from stage 1 showed that majority of patients from the treatment seeking population at UK between a 3 year time period from 2008 to 2010 were diagnosed with laryngeal cancers and were treated with chemoradiation therapy. Stage 2 demonstrated a multidimensional deterioration in vocal function following radiation therapy for laryngeal cancers. Stage 3 demonstrated a significant improvement in vocal function across the primary outcome measure (Voice Handicap Index) as a result of VFE+VH. Improvements were also seen in select parameters across the five domains of voice assessment in the VFE group. No significant improvements were observed in the vocal hygiene group in any parameters in each domain of voice assessment. Our study demonstrated adults irradiated for laryngeal cancers demonstrated a multi-dimensional deterioration of vocal function. These changes were long term since study participants were 2- 7 years post radiation therapy. Implementation of VFE+VH demonstrated a significant improvement in voice related quality of life and select parameters across the five domains of voice assessment. The present study demonstrated promising preliminary evidence for the use of VFE+VH to improve vocal function in patients irradiated for laryngeal cancers.

<p>The developments of highly conformal and precise radiation therapy techniques promote the necessity of more accurate treatment target localization and tracking. On-board imaging techniques, especially the x-ray based techniques, have found a great popularity nowadays for on-board target localization and tracking. With an objective to improve the accuracy of on-board imaging for lung cancer patients, the dissertation work focuses on the investigations of using limited-angle on-board x-ray projections for image guidance. The limited-angle acquisition enables scan time and imaging dose reduction and improves the mechanical clearance of imaging.</p><p>First of all, the dissertation developed a phase-matched digital tomosynthesis (DTS) technique using limited-angle (<=30 deg) projections for lung tumor localization. This technique acquires the same traditional motion-blurred on-board DTS image as the 3D-DTS technique, but uses the planning 4D computed tomography (CT) to synthesize a phase-matched reference DTS to register with the on-board DTS for tumor localization. Of the 324 different scenarios simulated using the extended cardiac torso (XCAT) digital phantom, the phase-matched DTS technique localizes the 3D target position with an localization error of 1.07 mm (± 0.57 mm) (average ± standard deviation (S.D.)). Similarly, for the total 60 scenarios evaluated using the computerized imaging reference system (CIRS) 008A physical phantom, the phase-matched DTS technique localizes the 3D target position with an average localization error of 1.24 mm (± 0.87 mm). In addition to the phantom studies, preliminary clinical cases were also studied using imaging data from three lung cancer patients. Using the localization results of 4D cone beam computed tomography (CBCT) as `gold-standard', the phase-matched DTS techniques localized the tumor to an average localization error of 1.5 mm (± 0.5 mm). </p><p>The phantom and patient study results show that the phase-matched DTS technique substantially improved the accuracy of moving lung target localization, as compared to the 3D-DTS technique. The phase-matched DTS technique can provide accurate lung target localizations like 4D-DTS, but with much reduced imaging dose and scan time. The phase-matched DTS technique is also found more robust, being minimally affected by variations of respiratory cycle lengths, fractions of respiration cycle contained within the DTS scan and the scan directions, which potentially enables quasi-instantaneous (within a sub-breathing cycle) moving target verification during radiation therapy, preferably arc therapy.</p><p>Though the phase-matched DTS technique can provide accurate target localization under normal scenarios, its accuracy is limited when the patient on-board breathing experiences large variations in motion amplitudes. In addition, the limited-angle based acquisition leads to severe structural distortions in DTS images reconstructed by the current clinical gold-standard Feldkamp-Davis-Kress (FDK) reconstruction algorithm, which prohibit accurate target deformation tracking, delineation and dose calculation. </p><p>To solve the above issues, the dissertation further developed a prior knowledge based image estimation technique to fundamentally change the landscape of limited-angle based imaging. The developed motion modeling and free-form deformation (MM-FD) method estimates high quality on-board 4D-CBCT images through applying deformation field maps to existing prior planning 4D-CT images. The deformation field maps are solved using two steps: first, a principal component analysis based motion model is built using the planning 4D-CT (motion modeling). The deformation field map is constructed as an optimized linear combination of the extracted motion modes. Second, with the coarse deformation field maps obtained from motion modeling, a further fine-tuning process called free-form deformation is applied to further correct the residual errors from motion modeling. Using the XCAT phantom, a lung patient with a 30 mm diameter tumor was simulated to have various anatomical and respirational variations from the planning 4D-CT to on-board 4D-CBCTs, including respiration amplitude variations, tumor size variations, tumor average position variations, and phase shift between tumor and body respiratory cycles. The tumors were contoured in both the estimated and the `ground-truth' on-board 4D-CBCTs for comparison. 3D volume percentage error (VPE) and center-of-mass error (COME) were calculated to evaluate the estimation accuracy of the MM-FD technique. For all simulated patient scenarios, the average (± S.D.) VPE / COME of the tumor in the prior image without image estimation was 136.11% (± 42.76%) / 15.5 mm (± 3.9 mm). Using orthogonal-view 30 deg scan angle, the average VPE/COME of the tumors in the MM-FD estimated on-board images was substantially reduced to 5.22% (± 2.12%) / 0.5 mm (± 0.4 mm). </p><p>In addition to XCAT simulation, CIRS phantom measurements and actual patient studies were also performed. For these clinical studies, we used the normalized cross-correlation (NCC) as a new similarity metric and developed an updated MMFD-NCC method, to improve the robustness of the image estimation technique to the intensity mismatches between CT and CBCT imaging systems. Using 4D-CBCT reconstructed from fully-sampled on-board projections as `gold-standard', for the CIRS phantom study, the average (± S.D.) VPE / COME of the tumor in the prior image and the tumors in the MMFD-NCC estimated images was 257.1% (± 60.2%) / 10.1 mm (± 4.5 mm) and 7.7% (± 1.2%) / 1.2 mm (± 0.2mm), respectively. For three patient cases, the average (± S.D.) VPE / COME of tumors in the prior images and tumors in the MMFD-NCC estimated images was 55.6% (± 45.9%) / 3.8 mm (± 1.9 mm) and 9.6% (± 6.1%) / 1.1 mm (± 0.5 mm), respectively. With the combined benefits of motion modeling and free-form deformation, the MMFD-NCC method has achieved highly accurate image estimation under different scenarios. </p><p>Another potential benefit of on-board 4D-CBCT imaging is the on-board dose calculation and verification. Since the MMFD-NCC estimates the on-board 4D-CBCT through deforming prior 4D-CT images, the 4D-CBCT inherently has the same image quality and Hounsfield unit (HU) accuracy as 4D-CT and therefore can potentially improve the accuracy of on-board dose verification. Both XCAT and CIRS phantom studies were performed for the dosimetric study. Various inter-fractional variations featuring patient motion pattern change, tumor size change and tumor average position change were simulated from planning CT to on-board images. The doses calculated on the on-board CBCTs estimated by MMFD-NCC (MMFD-NCC doses) were compared to the doses calculated on the `gold-standard' on-board images (gold-standard doses). The absolute deviations of minimum dose (DDmin), maximum dose (DDmax), mean dose (DDmean) and prescription dose coverage (DV100%) of the planning target volume (PTV) were evaluated. In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MMFD-NCC in the CIRS phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. </p><p>The MMFD-NCC doses matched very well with the gold-standard doses. For the XCAT phantom study, the average (± S.D.) DDmin, DDmax, DDmean and DV100% (values normalized by the prescription dose or the total PTV volume) between the MMFD-NCC PTV doses and the gold-standard PTV doses were 0.3% (± 0.2%), 0.9% (± 0.6%), 0.6% (± 0.4%) and 1.0% (± 0.8%), respectively. Similarly, for the CIRS phantom study, the corresponding values between the MMFD-NCC PTV doses and the gold-standard PTV doses were 0.4% (± 0.8%), 0.8% (± 1.0%), 0.5% (± 0.4%) and 0.8% (± 0.8%), respectively. For the 4D dose accumulation study, the average (± S.D.) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.0% (± 2.4%). The average gamma index (3%/3mm) between the accumulated doses and the radiochromic film measured doses was 96.1%. The MMFD-NCC estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy under different scenarios. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.</p><p>However, a major limitation of the estimated 4D-CBCTs above is that they can only capture inter-fractional patient variations as they were acquired prior to each treatment. The intra-treatment patient variations cannot be captured, which can also affect the treatment accuracy. In light of this issue, an aggregated kilo-voltage (kV) and mega-voltage (MV) imaging scheme was developed to enable intra-treatment imaging. Through using the simultaneously acquired kV and MV projections during the treatment, the MMFD-NCC method enabled 4D-CBCT estimation using combined kV and MV projections. </p><p>For all XCAT-simulated patient scenarios, the average (± S.D.) VPE / COME of the tumor in the prior image and tumors in the MMFD-NCC estimated images (using kV + open field MV) was 136.11% (± 42.76%) / 15.5 mm (± 3.9 mm) and 4.5% (± 1.9%) / 0.3 mm (± 0.4 mm), respectively. In contrast, the MMFD-NCC estimation using kV + beam's eye view (BEV) MV projections yielded results of 4.3% (± 1.5%) / 0.3 mm (± 0.3 mm). The kV + BEV MV aggregation can estimate the target as accurately as the kV + open field MV aggregation. The impact of this study is threefold: 1. the kV and MV projections can be acquired at the same time. The imaging time will be cut to half as compared to the cases which use kV projections only. 2. The kV and MV aggregation enables intra-treatment imaging and target tracking, since the MV projections can be the side products of the treatment beams (BEV MV). 3. As the BEV MV projections originate from the treatment beams, there will be no extra MV imaging dose to the patient.</p><p>The above introduced 4D-CBCT estimation techniques were all based on limited-angle acquisition. Though limited-angle acquisition enables substantial scan time and dose reduction as compared to the full-angle scan, it is still not real-time and cannot provide `cine' imaging, which refers to the instantaneous imaging with negligible scan time and imaging dose. Cine imaging is important in image guided radiation therapy practice, considering the respirational variations may occur quickly and frequently during the treatment. For instance, the patient may experience a breathing baseline shift after every respiratory cycle. The limited-angle 4D-CBCT approach still requires a scan time of multiple respiratory cycles, which will not be able to capture the baseline shift in a timely manner. </p><p>In light of this issue, based on the previously developed MMFD-NCC method, an AI-FD-NCC method was further developed to enable quasi-cine CBCT imaging using extremely limited-angle (<=6 deg) projections. Using pre-treatment 4D-CBCTs acquired just before the treatment as prior information, AI-FD-NCC enforces an additional prior adaptive constraint to estimate high quality `quasi-cine' CBCT images. Two on-board patient scenarios: tumor baseline shift and continuous motion amplitude change were simulated through the XCAT phantom. Using orthogonal-view 6 deg projections, for the baseline shift scenario, the average (± S.D.) VPE / COME of the tumors in the AI-FD-NCC estimated images was 1.3% (± 0.5%) / 0.4 mm (± 0.1 mm). For the amplitude variation scenario, the average (± S.D.) VPE / COME of the tumors in the AI-FD-NCC estimated images was 1.9% (± 1.1%) / 0.5 mm (± 0.2 mm). The impact of this study is three-fold: first, the quasi-cine CBCT technique enables actual real-time volumetric tracking of tumor and normal tissues. Second, the method enables real-time tumor and normal tissues dose calculation and accumulation. Third, the high-quality volumetric images obtained can potentially be used for real-time adaptive radiation therapy.</p><p>In summary, the dissertation work uses limited-angle on-board x-ray projections to reconstruct/estimate volumetric images for lung tumor localization, delineation and dose calculation. Limited-angle acquisition reduces imaging dose, scan time and improves imaging mechanical clearance. Using limited-angle projections enables continuous, sub respiratory-cycle tumor localization, as validated in the phase-matched DTS study. The combination of prior information, motion modeling, free-form deformation and limited-angle on-board projections enables high-quality on-board 4D-CBCT estimation, as validated by the MM-FD / MMFD-NCC techniques. The high-quality 4D-CBCT not only can be applied for accurate target localization and delineation, but also can be used for accurate treatment dose verification, as validated in the dosimetric study. Through aggregating the kV and MV projections for image estimation, intra-treatment 4D-CBCT imaging was also proposed and validated for its feasibility. At last, the introduction of more accurate prior information and additional adaptive prior knowledge constraints also enables quasi-cine CBCT imaging using extremely-limited angle projections. The dissertation work contributes to lung on-board imaging in many aspects with various approaches, which can be beneficial to the future lung image guided radiation therapy practice.</p> / Dissertation

Bakgrund Extern strålbehandling är en viktig del av processen för behandling av cervikal cancer. Målet med denna typ av behandling är att bestråla tumörområdet med så hög dos som möjligt och omkringliggande frisk vävnad med så lite dos som möjligt. Ett problem som upptäckts är att rörelser i tumörområdet under behandling kan påverka precisionen av strålfältet. Syfte Syftet med litteraturstudien var att beskriva omfattning av rörelse och volymförändring i tumörområdet under strålbehandling av cervikal cancer. Metod                  Nio artiklar med kvantitativ design kvalitetsgranskades och resultaten sammanställdes med inspiration av Fribergs modell. Resultat Omfattning av rörelser och volymförändringar upptäcktes variera och är något som skiljer sig mellan individer. Valet av bildtagnings- och mätmetod har stor betydelse gällande patientsäkerhet och stråldos.   Slutsats Hur mycket tumörområdet rör sig/förändras i volym var något som varierade mellan patienterna i studierna och det är därför viktigt att anpassa behandlingen efter dessa variationer. Olika metoder för bildtagning och mätning kan användas både för att upptäcka rörelser och volymförändringar i tumörområdet under extern strålbehandling. De olika metodernas fördelar bör noggrant vägas mot nackdelar innan användning för att hitta en optimal metod som främjar patientsäkerhet. / Background External radiation therapy is an important part when treating cervical cancer. The goal of this type of therapy is to irradiate the tumor area with the highest possible dose and minimize the dose given to the surrounding healthy tissue. One problem showed is that movement in the tumor area during treatment can cause problems regarding keeping the precision as high as possible. Aim The aim of this literature study was to describe the extent of movement and volume change in the tumor area during external radiotherapy treatment of cervical cancer. Method Nine articles with quantitative design were quality-reviewed and the results were compiled with inspiration from Friberg's model. Results The extent of movements and volume changes was discovered varying and is something that differs between individuals. The choice of imaging and measurement method is of great importance in terms of patient safety and radiation dose. Conclusions The extent of movement and change in volume varied between patients in the studies and it is therefore important to adjust the treatment according to these variations. Different methods of imaging and measurement can be used both to detect movements and volume changes in the tumor area during external radiation therapy. The benefits of the different methods should be carefully weighed against disadvantages before use to find an optimal method that promotes patient safety.

La radiothérapie par microfaisceaux (MRT) synchrotron est une méthode de radiothérapie alternative pour les tumeurs cérébrales, qui présente l'avantage unique de pouvoir déposer de très hautes doses d'irradiation (plusieurs 100aines de Gy) au niveau de la masse tumorale. En effet, le fractionnement spatial des rayons X en microfaisceaux parallèles de quelques dizaines de micromètres s'est montré efficace dans le traitement des tumeurs cérébrales du rongeur tout en préservant le tissu cérébral péritumoral. Pour autant, son mode d'action sur le plan biologique n'est qu'en partie connu. Si l'effet différentiel de cette irradiation sur les vaisseaux sains et tumoraux a pu être démontré ces dernières années, il ne peut expliquer à lui seul l'efficacité de la MRT. Dans ce travail, nous avons établi une description de la réponse transcriptomique précoce des tissus sains et tumoraux (gliosarcome 9L) à la MRT et les fonctions biologiques et voies de signalisation associées. Ces résultats constituent une base de données interrogeable à partir d'hypothèses précises. Cette base a ainsi permis d'identifier des transcrits impliqués dans la réponse de la tumeur à la MRT et dont l'inhibition n'interfèrerait pas avec la réparation des tissus sains : nous avons proposé 3 cibles potentielles qui permettraient d'augmenter l'index thérapeutique de la MRT. (i) L'inhibition radio-induite d'un groupe de 13 gènes (Plk1, Cdc20, Ccnb1, Pttg1, Bub1, Dlgap5, Cenpf, Kif20a, Traf4af1, Depdc1b, Mxd3, Cenpe et Cenpf), participerait au contrôle tumoral précoce après MRT par la perturbation de la division cellulaire et pourrait être amplifié pour prolonger l'inhibition de la croissance tumorale. (ii) La mise à profit de l'activation du promoteur de Clecsf6 au sein des tumeurs irradiées permettrait la surexpression locale, via les monocytes modifiés et infiltrés, de protéine d'intérêt thérapeutique. (iii) Areg (codant pour l'Amphiréguline) est surexprimé au sein du tissu tumoral après MRT et son implication connue dans la chimio/radiorésistance nous conduit à considérer que son inhibition pourrait être une stratégie de renforcement des effets de la MRT. Par ailleurs, nous avons montré que la MRT engendrait de meilleurs résultats sur le contrôle tumoral et la survie animale qu'une irradiation synchrotron en champ plein (avec une dose équivalente à la vallée MRT). Cependant, aucune différence transcriptomique ne pouvant soutenir cet effet n'a pu être mis en évidence. / Synchrotron Microbeam Radiation Therapy (MRT) is a novel form of radiosurgery of brain tumors which allows high dose deposition (few hundreds of Gy) in pathologic tissues. The spatial fractionation of the incident beam into arrays of near-parallel microbeams has shown efficiency on brain tumors implanted in rodents while sparing normal tissues. The preferential effects observed on tumor vessels could not entirely explain the efficiency of MRT and other biological mechanisms might be involved in tumor control. In this work, we described the early whole transcriptomic responses of normal and tumoral (9L gliosarcoma) tissues to MRT and the associated biofunctions and pathways. This provides a questionable data base which can be used by the whole MRT community. This base allows to identify transcripts involved in tumor response to MRT and which inhibition would have no consequence in healthy tissue repair. We identified 3 relevant targets which might increase the therapeutic index of MRT. (i) The radio-induced inhibition of a cluster of 13 genes (Plk1, Cdc20, Ccnb1, Pttg1, Bub1, Dlgap5, Cenpf, Kif20a, Traf4af1, Depdc1b, Mxd3, Cenpe and Cenpf) may be involved in tumor control after MRT through the deregulation of cell division and could be amplified to continue the tumor growth inhibition. (ii) We might benefit from the activation of the Clecsf6 promoter in irradiated tumors by delivering, via modified and injected monocytes, some therapeutic proteins. (iii) Finally, Areg (encoding for Amphiregulin) is overexpressed in tumors after MRT and its involvement described in chimio/radioresistance enable to consider that its inhibition might help in tumor control after irradiation. We also showed that MRT induces a greater tumor control and survival rates compared with similar broad beam irradiations but no differences in transcriptomic responses have been highlighted.

Le carcinome hépatocellulaire est l'un des cancers les plus fréquents et des plus sévères à travers le monde. Le diagnostic est souvent tardif et les traitements curatifs ne peuvent être proposés qu'à un nombre limité de patients. Les technologies modernes ont permis le développement de nouvelles méthodes de radiothérapie qui montrent aujourd'hui de bons résultats. Par ailleurs, bien que des déficiences dans les voies de réparation de l'ADN soient associées à une instabilité génomique et une susceptibilité au cancer, une inhibition de ces voies sensibilise les cellules cancéreuses à la chimiothérapie et à la radiothérapie. Dans ce contexte, les inhibiteurs de poly(ADP-ribose) polymérases (PARP) ont déjà montré des résultats prometteurs dans des études pré-cliniques et sont en cours d'évaluation clinique pour de nombreux cancers. Ce travail de thèse a consisté en l'évaluation du potentiel des inhibiteurs de PARP en combinaison avec la radiothérapie comme nouvelle option thérapeutique pour le carcinome hépatocellulaire. La première étape de ce travail a été de caractériser les profils d'expression et d'activité de plusieurs membres de la famille PARP dans des cellules cancéreuses du foie et des hépatocytes primaires humains ainsi que dans des tissus hépatiques. En second lieu, nous avons étudié le potentiel de l'inhibiteur de PARP ABT-888 seul et en combinaison à des radiations ionisantes in vitro. Le traitement par l'inhibiteur de PARP ABT-888 en agent seul a montré une sensibilité variable des différentes lignées cellulaires étudiées à cette drogue. Afin de comprendre la sensibilité variable des cellules cancéreuses hépatiques à l'ABT-888, nous avons analysé leur capacité de réparation des dommages à l'ADN et avons observé des capacités différentes entre les lignées cellulaires. Finalement, nous avons pu montrer que l'ABT-888 sensibilise les cellules cancéreuses hépatiques aux radiations ionisantes. Ce travail de recherche a permis de montrer que les inhibiteurs de PARP ont un fort potentiel pour améliorer les méthodes de radiothérapie utilisées dans la prise en charge du carcinome hépatocellulaire / Hepatocellular carcinoma is the third cause of cancer related death. Due its often late diagnosis and advanced stage, a limited number of patients can benefit from curative treatments. There is thus a constant need for new treatment strategies for patients with hepatocellular carcinoma. Targeting DNA repair pathways to sensitize tumor cells to chemoor radiotherapeutic treatments is now a common strategy under investigation for cancer treatment with inhibitors of poly(ADP-ribose) polymerases (PARP) showing great potential. The aim of this work was to evaluate the potential of PARP inhibitors alone and in combination with radiation therapy as a new strategy for the treatment of hepatocellular carcinoma. We first analyzed the expression and activity of different PARP genes in a panel of liver cancer cell lines and primary human hepatocytes as well as their DNA repair capacity and assess the impact of PARP inhibitors alone and in combination with ionizing radiation in these models on cell survival. A large range in expression of PARP family members, PARP activity and sensitivity to ABT-888 in the panel of liver cells was observed as well as differential excision/synthesis repair capacity. Finally, we showed that ABT-888 sensitizes liver cancer cells to the cell killing effects of ionizing radiation. PARP inhibitors show great potential for improving radiation therapy strategies used in the management of hepatocellular carcinoma

Ces dernières années, les techniques de traitement des cancers par radiothérapie externe se sont complexifiéesafin de cibler la tumeur tout en protégeant les organes à risque. Les systèmes de planification de traitement (TPS)réalisent un calcul prévisionnel de la distribution de la dose absorbée dans le patient (via des images CT).Afin d’obtenir un résultat de dose précis dans un temps raisonnable, le calcul est effectué par des algorithmessimplifiés. En présence de dispositifs médicaux métalliques de masses volumiques élevées (prothèses de hancheou prothèses dentaires), les algorithmes atteignent leurs limites. De plus, ces dispositifs perturbent lareconstruction tomodensitométrique en créant des artéfacts sur les images rendant difficile la délinéation desorganes. L’objectif de ce travail a été d’évaluer les algorithmes implémentés dans les TPS en présenced’hétérogénéités de forte densité avec des mesures expérimentales et le code de calcul Monte-Carlo BEAMnrcdans un fantôme anthropomorphique tout d’abord avec des échantillons naturels, puis avec des échantillonscalibrés. Ensuite, une évaluation rétrospective des algorithmes cliniques par rapport à Monte-Carlo a été réaliséeavec des patients traités en RC3D et en RCMI.Les mesures ont mis en évidence une atténuation pouvant aller jusqu’à 17 % pour l’amalgame dentaire parrapport à l’algorithme clinique sur les images CT avec artéfacts, créant une zone de sous-dosage dans le volumecible. L’ensemble des résultats a donné lieu à des recommandations pour la clinique (corriger les images CT si levolume cible est à moins de 3 cm d’une prothèse, privilégier l’algorithme AAA plutôt que Pencil Beam…). / The last few years, cancer treatment techniques in radiation therapy have become more complex to better targetthe tumor while protecting the organs at risk. The treatment planning systems (TPS) achieve a predictivecalculation of the distribution of the dose absorbed by the patient (via CT images).In order to obtain an accurate dose result within a reasonable time, the calculation is performed with simplifiedalgorithms. In the presence of medical devices made of high density metal (hip prosthesis or dental prosthesis),the algorithms reach their limits. Moreover, these devices disrupt computed tomography reconstruction, creatingartifacts on the images and thus making difficult the delineation of organs. The aim of this work is to evaluatethe algorithms of the TPS in the presence of high density heterogeneity using experimental measurements andthe Monte Carlo BEAMnrc code in an anthropomorphic phantom: on one hand with natural samples, and on theother hand, with calibrated samples. Then, a retrospective evaluation of clinical algorithms compared to MonteCarlo is achieved using treated patients in Conformal Radiotherapy and in Intensity Modulated RadiationTherapy (IMRT). The measurements show an attenuation of up to 17 % for dental amalgam compared with theclinical algorithm on CT images with artifacts, creating an under-dosage area in the target volume. All theseresults lead to recommendations for the clinical treatments (corrected CT images if the target volume is closerthan 3 cm to prosthesis, favor the AAA algorithm rather than Pencil Beam …).

The goal of this study was to improve dosimetry for pelvic, lung, head and neck, and other cancers sites with aspherical planning target volumes (PTV) using a new algorithm for collimator optimization for intensity modulated radiation therapy (IMRT) that minimizes the x-jaw gap (CAX) and the area of the jaws (CAA) for each treatment field. A retroactive study on the effects of collimator optimization of 20 patients was performed by comparing metric results for new collimator optimization techniques in Eclipse version 11.0. Keeping all other parameters equal, multiple plans are created using four collimator techniques: CA0, all fields have collimators set to 0°, CAE, using the Eclipse collimator optimization, CAA, minimizing the area of the jaws around the PTV, and CAX, minimizing the x-jaw gap. The minimum area and the minimum x-jaw angles are found by evaluating each field beam’s eye view of the PTV with ImageJ and finding the desired parameters with a custom script. The evaluation of the plans included the monitor units (MU), the maximum dose of the plan, the maximum dose to organs at risk (OAR), the conformity index (CI) and the number of fields that are calculated to split. Compared to the CA0 plans, the monitor units decreased on average by 6% for the CAX method with a p-value of 0.01 from an ANOVA test. The average maximum dose remained within 1.1% difference between all four methods with the lowest given by CAX. The maximum dose to the most at risk organ was best spared by the CAA method, which decreased by 0.62% compared to the CA0. Minimizing the x-jaws significantly reduced the number of split fields from 61 to 37. In every metric tested the CAX optimization produced comparable or superior results compared to the other three techniques. For aspherical PTVs, CAX on average reduced the number of split fields, lowered the maximum dose, minimized the dose to the surrounding OAR, and decreased the monitor units. This is achieved while maintaining the same control of the PTV. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

Evaluation of dose optimization using the Pencil Beam (PB) and Monte Carlo (MC) algorithms may allow physicists to apply dosimetric offsets to account for inaccuracies of the PB algorithm for lung cancer treatment with Stereotactic Body Radiotherapy (SBRT). 20 cases of Non-Small Cell Lung Cancer (NSCLC) were selected. Treatment plans were created with Brainlab iPlanDose® 4.1.2. The D97 of the Planning Target Volume (PTV) was normalized to 50 Gy on the Average Intensity Projection (AIP) using the fast PB and compared with MC. This exact plan with the same beam Monitor Units (MUs) was recalculated over each respiratory phase. The results show that the PB algorithm has a 2.3-2.4% less overestimation at the maximum exhalation phase than the maximum inhalation phase when compared to MC. Significantly smaller dose difference between PB and MC is also shown in plans for peripheral lesions (7.7 ± 0.7%) versus central lesions (12.7±0.8%)(p< 0.01). / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

The purpose of this research is to accurately match the calculation environment, i.e. the treatment planning system (TPS) with the measurement environment (using a 2-D diode array) for lung Stereotactic Body Radiation Therapy (SBRT) patient-specific quality assurance (QA). Furthermore, a new phantom was studied in which the 2-D array and heterogeneities were incorporated into the patient-specific QA process for lung SBRT. Dual source dual energy computerized tomography (DSCT) and single energy computerized tomography (SECT) were used to model phantoms incorporating a 2-D diode array into the TPS. A water-equivalent and a heterogeneous phantom (simulating the thoracic region of a patient) were studied. Monte Carlo and pencil beam dose distributions were compared to the measured distributions. Composite and individual fields were analyzed for normally incident and planned gantry angle deliveries. The distributions were compared using γ-analysis for criteria 3% 3mm, 2% 2mm, and 1% 1mm. The Monte Carlo calculations for the DSCT modeled phantoms (incorporating the array) showed an increase in the passing percentage magnitude for 46.4 % of the fields at 3% 3mm, 85.7% at 2% 2mm, and 92.9% at 1% 1mm. The Monte Carlo calculations gave no agreement for the same γ-analysis criteria using the SECT. Pencil beam calculations resulted in lower passing percentages when the diode array was incorporated in the TPS. The DSCT modeled phantoms (incorporating the array) exhibited decrease in the passing percentage magnitude for 85.7% of the fields at 3% 3mm, 82.1% at 2% 2mm, and 71.4% at 1% 1mm. In SECT modeled phantoms (incorporating the array), a decrease in passing percentage magnitude were found for 92.9% of the fields at 3% 3mm, 89.3% at 2% 2mm, and 82.1% at 1% 1mm. In conclusion, this study demonstrates that including the diode array in the TPS results in increased passing percentages when using a DSCT system with a Monte Carlo algorithm for patient-specific lung SBRT QA. Furthermore, as recommended by task groups (e.g. TG 65, TG 101, TG 244) of the American Association of Physicists in Medicine (AAPM), pencil beam algorithms should be avoided in the presence of heterogeneous materials, including a diode array. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

Empirical methods of beam angle optimization (BAO) are tested against the BAO that is currently employed in Eclipse treatment planning software. Creating an improved BAO can decrease the amount of time a dosimetrist spends on making a treatment plan, improve the treatment quality and enhance the tools an inexperienced dosimetrist can use to develop planning techniques. Using empirical data created by experienced dosimetrists from 69 patients treated for lung cancer, the most frequently used gantry angles were applied to four different regions in each lung to gather an optimal set of fields that could be used to treat future lung cancer patients. This method, given the moniker FAU BAO, is compared in 7 plans created with the Eclipse BAO choosing 5 fields and 9 fields. The results show that the conformality index improved by 30% or 3% when using the 5 and 9 fields. The conformation number was better by 12% from the 5 fields and 9% from the 9 fields. The organs at risk (OAR) were overall more protected to produce fewer nonstochastic effects from the radiation treatment with the FAU BAO. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection