La radiochirurgie par Gamma Knife constitue une modalité thérapeutique reconnue de certaines affections cérébrales. Le traitement se base sur l’administration d’un rayonnement focalisé au niveau d’une cible intracrânienne. L’efficacité de ce traitement repose sur la délivrance d’une dose d’irradiation efficace au sein d’un volume-cible associé à la délivrance d’une dose d’irradiation négligeable à l’extérieur de ce même volume-cible. En pratique, la dose d’irradiation administrée à l’intérieur du volume-cible n’est pas distribuée de manière homogène, et la dose d’irradiation reçue par les tissus situés en-dehors du volume-cible n’est pas nécessairement faible. Notre travail est basé sur l’hypothèse que l’imperfection de la distribution de la dose d’irradiation au sein du volume-cible et en-dehors de celui-ci peut être responsable des échecs et des complications rencontrées en radiochirurgie. Dans deux modèles cliniques de traitement radiochirurgical, le schwannome vestibulaire et la névralgie du trijumeau, nous avons montré qu’il existait une relation entre les paramètres de distribution de dose d’irradiation et certains résultats du traitement radiochirurgical par Gamma Knife de ces pathologies. Nous avons développé deux modèles expérimentaux d’irradiation radiochirurgicale de rats, l’un ciblé sur le striatum et l’autre sur le nerf trijumeau, permettant d’analyser les conséquences histologiques des variations de la distribution de dose à l’intérieur du volume-cible ainsi qu’à distance de celui-ci. Nous avons démontré que la réponse radiobiologique des tissus irradiés était fortement dépendante de ce paramètre dosimétrique, et que ce dernier constituait une donnée de la planification chirurgicale aussi importante que la dose de prescription. Nous avons corrélé ces résultats avec certaines observations réalisées dans d’autres indications de traitement radiochirurgical ainsi que dans l’analyse histologique de tumeurs traitées par Gamma Knife. Ces études mettent en évidence le rôle important joué par l’optimalisation de la distribution de la dose d’irradiation dans l’amélioration des résultats cliniques du traitement radiochirurgical. Les valeurs optimales de la distribution de dose dans les différentes indications de traitement radiochirurgical doivent être recherchées, et les différentes méthodes mises à notre disposition lors de la planification dosimétrique pour améliorer la distribution de dose doivent être utilisées avec discernement pour obtenir la dosimétrie radiochirurgicale la plus parfaite possible. / Doctorat en sciences médicales / info:eu-repo/semantics/nonPublished

In this thesis work, a system for proton beam alignment was studied and optimized in many of its functional areas. The resulting system was named Positioning Alignment Control System (PACS). The PACS system is an integrated and efficient system as a result of the work done on it in the course of this thesis work.

Object Rupture of intracranial arteriovenous malformations is a leading cause of stroke in children and young adults. Treatment options include surgery and highly focused radiation (stereotactic radiosurgery). For large and deep seated lesions, the risks of surgery may be prohibitively high, while radiosurgery has a disappointingly low efficacy and long latency. Radiosurgery carries the most promise for significant advances, however the process by which radiosurgery achieves obliteration is incompletely understood. Inflammation and thrombosis are likely to be important in the radiation response and may be amenable to pharmacological manipulation to improve radiosurgical efficacy. Materials and methods Immunohistochemistry and electron microscopy were used to study normal cerebral vessels, cavernous malformations and AVMs, some of which had previously been irradiated. An attempt was made to culture AVM endothelial cells to study the immediate response of AVM endothelium to radiosurgery. The effects of radiosurgery in a rat model of AVM were studied using immunohistochemistry and the results used to determine the choice of a pharmacological strategy to enhance the thrombotic effects of radiosurgery. Results Vascular malformations have a different endothelial inflammatory phenotype than normal cerebral vessels. Radiosurgery may cause long term changes in inflammatory molecule expression and leads to endothelial loss with exposure of pro-thrombotic molecules. Ultrastructural effects of irradiation include widespread cell loss, smooth muscle cell (SMC) proliferation and thrombosis. Endothelial culture from AVMs proved difficult due to SMC predominance in initial cultures. Radiosurgery upregulated several endothelial inflammatory molecules in the animal model and may induce pro-thrombotic cell membrane alterations. The administration of lipopolysaccharide and soluble tissue factor to rats following radiosurgery led to selective thrombosis of irradiated vessels. Conclusions Inflammation and thrombosis are important in the radiosurgical response of AVMs. Lumen obliteration appears to be mediated by proliferation of cells within the vessel wall and thrombosis. Upregulation of inflammatory molecules and perhaps disruption of the normal phospholipid asymmetry of the endothelial and SMC membranes are some of the earliest responses to radiosurgery. The alterations induced by radiation may be harnessed to selectively initiate thrombus formation. Stimulation of thrombosis may improve the efficacy of radiosurgery, increasing treatable lesion size and reducing latency.

No description available.

In external electron beam therapy arbitrarily shaped inserts (cutouts) are used to define the contours of the irradiated field. This thesis describes the implementation and verification of a software system to calculate output factors for cutouts using Monte Carlo simulations. The design goals were: (1) A stand-alone software system running on a single workstation. (2) Task oriented graphical user interface with shape input capability. (3) Implementation on Mac OS XRTM (10A.x Tiger). (4) CPU multicore support by job splitting. (5) EGSnrc (Patch level V4-r2-2-5) for particle transport and dose scoring. (6) Validation for clinical use. / The system, called Cutout Manager, can calculate output factors with 1% statistical error in 20 minutes on Mac Pro computer (Intel XeonRTM, 4 cores). When the BEAMnrc linac model correctly reproduces percentage depth doses in the buildup region and around R100, calculated and measured output factors are in good agreement with precision measurements of circular cutouts at 100 cm source-to-surface distance (SSD) and extended SSD. Cutout Manager simulations are consistent with measurements of clinical cutouts within a 2% error margin.

Brain metastases are treated with surgery, radiotherapy, radiosurgery, and chemotherapy. In this review, recently published studies concerning different treatment strategies are presented with respect to solitary lesions, multiple metastases, and recurrent tumor growth. Selection criteria for the appropriate therapy are: control of the primary tumor, extent of extracerebral metastases, time interval between diagnosis of the primary tumor and the development of cerebral lesions, number of cerebral metastases, Karnofsky performance scale score, and age. Treatment approaches were evaluated with respect to median survival time and quality of life. A singular brain metastasis can be treated with surgery or with radiosurgery. Especially when the primary tumor is under control, there are few extracerebral lesions which are stable, the Karnofsky performance scale score is above 70, the lesion is larger than 3 cm in diameter and surgically accessible surgery is the treatment of choice. Postoperative adjuvant radiotherapy may delay relapse. Median survival time ranges between 10 to 18 months. Radiosurgery can be applied in lesions smaller than 3 cm in diameter and is the treatment of choice in lesions which are surgically not accessible. Multiple metastases are treated either by conventional radiotherapy, radiosurgery or surgery. Commonly, no more than 3 lesions are approached by either surgery or radiosurgery. Median survival time ranges between 6 to 9 months for both treatment concepts, but without therapy only is 4–6 weeks. According to the clinical and neurological condition of the patient, recurrent brain metastases can be treated by operation, reirradiation, or radiosurgery. The efficacy of chemotherapy depends on the chemosensitivity of the primary tumor and the ability to penetrate the blood-brain barrier. Long-term survivors with cancer disease encourage to perform active treatment strategies. / Hirnmetastasen werden durch Operation, Ganzhirnbestrahlung, Radiochirurgie und Chemotherapie behandelt. In dieser Übersichtsarbeit werden kürzlich publizierte Studien bezüglich der Therapiekonzepte für solitäre Läsionen, multiple Metastasen und Tumorrezidive vorgestellt. Auswahlkriterien für eine angemessene Behandlung sind: Kontrolle des Primärtumors, Ausmaß der extrakraniellen Metastasen, Zeitintervall zwischen Diagnose des Primärtumors und dem Auftreten der Hirntumoren, Anzahl der zerebralen Metastasen, Karnofsky-Performance-Scale-Score und Lebensalter. Behandlungskonzepte wurden nach der medianen Überlebenszeit und Lebensqualität ausgewertet. Singuläre Hirnmetastasen können operativ oder radiochirurgisch behandelt werden. Insbesondere wenn der Primärtumor unter Kontrolle ist, wenige extrazerebrale Läsionen bestehen und diese stabil sind, der Karnofsky-Performance-Scale-Score über 70 ist, die Tumoren größer als 3 cm im Durchmesser und chirurgisch erreichbar sind, ist die Operation die Methode der Wahl. Postoperative adjuvante Strahlentherapie kann erneute Progression verzögern. Die mediane Überlebenszeit liegt zwischen 10 und 18 Monaten. Für Läsionen, die kleiner als 3 cm sind und chirurgisch nicht erreicht werden können, ist die Radiochirurgie die Therapie der Wahl. Multiple Metastasen können durch konventionelle Ganzhirnbestrahlung, Radiochirurgie oder Operation behandelt werden. Im allgemeinen werden nicht mehr als 3 Herde operativ oder radiochirurgisch angegangen. Die mediane Überlebenszeit liegt bei beiden Therapieformen zwischen 6 und 9 Monaten, ohne Behandlung hingegen bei nur 4–6 Wochen. Entsprechend dem klinischen und neurologischen Zustand der Patienten können Rezidive von Hirnmetastasen durch chirurgische Entfernung, erneute Bestrahlung oder durch Radiochirurgie therapiert werden. Die Wirkung der Chemotherapie hängt von der Chemosensitivität des Primärtumors und der Durchlässigkeit der Blut-Hirn-Schranke für das Chemotherapeutikum ab. Langzeitüberleber motivieren zu aktiven Behandlungsstrategien. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The thesis presents a comparison of four techniques used for stereotactic radiosurgery, consisting of the static conformal beam, static cone-based, proton therapy, and the Gamma Knife techniques. The comparisons involved six test cases in which phantom target lesions were created in the center of the modified anthropomorphic RandoRTM head. The phantom lesions presented in the study were extreme irregular cases that ranged in shape and volume and were near a critical structure to receive minimal dose during treatment planning. The best treatment plans from each technique for all studies were selected and the extracted data was analyzed using physical and biological parameters. Correlations between integral biological effective dose (normal brain) and normal tissue complication probability were analyzed as a function of dose conformity (PITV), and correlations between tumor control probability and integral biological effective dose (tumor) as a function of dose homogeneity (MDPD) were analyzed, as well. These parameter pairings showed strong links. The static conformal beam and the proton SOBP techniques consistently provided low PITV and MDPD values for all cases, including the most irregular and complicated cases. Higher PITV and MDPD values, typically associated with static cone-based and the Gamma Knife techniques, were due to normal tissue and tumor tissue, respectively, being irradiated at higher dose levels than the prescribed dose. For these cases, as the PITV increased, the NTCP increased, as well, due to high doses created within the normal tissue found within the prescription isodose surface.

Thesis (M.Sc.). / Written for the Medical Physics Unit. Title from title page of PDF (viewed 2009/06/23). Includes bibliographical references.

INTRODUCTION: Cancers of the gastrointestinal tract are the second most prevalent malignancy with 289,610 new cases last year and the second most common cause of cancer-related death with 150,000 deaths last year in the United States. Prognosis for patients with these malignancies is poor and worsens significantly once the cancer has metastasized to the brain. We evaluated the outcome of patients following Stereotactic Radiosurgery (SRS) for brain metastases (BM) in individuals with GI cancers to identify safety and effectivity of treatment and we assessed prognostic factors that affect tumor control and survival. OBJECTIVES: By the conclusion of this session, participants should be able to: 1) Identify an effective treatment for brain metastases from GI cancers in terms of increasing survival; 2) Identify which treatment provides the best local and distant control of CNS disease; 3) Discuss the effects of different prognostic factors on local control and survival. METHODS: This is a retrospective analysis of 58 brain metastases from 18 consecutive patients who underwent SRS treatment at BIDMC between 2006 and 2013. 11/18 patients underwent prior microsurgical resection for their metastases and 3/18 patients had undergone Whole Brain Radiation Therapy (WBRT). Overall Survival (OS), Local Control (LC), Distal control (DC), and prognostic factors such as age, number of brain metastases (BM), Karnofsky Performance Status (KPS), Recursive Partition Analysis (RPA) and Disease Specific Graded Prognostic Assessment (Ds-GPA) class were evaluated. RESULTS: The median overall survival (mOS) for the entire cohort was 14 months after the diagnosis of BM. The mOS for patients receiving only SRS, Surgical Resection + SRS, and WBXRT + SRS were 8 months, 18 months, and 13 months respectively. The difference in overall survival between treatment groups was not found to be statistically significant. Increasing number of BM was a factor shown to negatively influence survival. Local control was achieved in 55% of lesions after SRS, and in 75% of lesions that were surgically resected followed by SRS boost to the resection cavity. The difference in local control between SRS alone vs. Surgery + SRS was found to be statistically significant (p = 0.013). CONCLUSION: With a higher overall survival and significantly better local control rates, Surgery followed by SRS boost to the resection cavity should be considered as the treatment of choice in this specific subgroup of cancer patients as this study shows that they benefit from this more aggressive treatment option.

No description available.