Purpose: The aim of the study is to compare the positioning accuracy of two immobilization systems commonly used in stereotactic body radiation therapy (SBRT) of non–small cell lung carcinoma (NSCLC) and lung oligometastases, Polyurethane Foam Cradles (PFC) and the BodyFIX System (BFS) with 2D and 3D image guidance. Both the interfraction and intrafractional positional errors were analyzed. Methods and Materials: 189 CBCT scans from 44 patients with NSCLC or lung oligometastases who received SBRT between August 2008 and April 2014 were analyzed retrospectively. Of these, 20 and 24 patients were immobilized with a Polyurethane Foam Cradle (PFC) and the BodyFIX System (BFS) respectively. The results of on board imaging (OBI) and pre-treatment cone-beam computed tomography (CBCT) at initial setup and after correction were registered to planning CT for online matching. The positional errors in anteroposterior (AP), superior-inferior (SI) and medial-lateral (ML) directions were analyzed. Post-treatment CBCT were used to assess intrafraction tumour displacement for 19 patients. The planning target volume margins were calculated using the van Herk’s formula. Other possible factors contributing to setup uncertainty were also analyzed. Result: By using skin mark as a reference, the mean setup errors were 0.09, -0.10 and 0.02 cm for PFC and 0.04, -0.19 and -0.10 cm for BFS in AP, SI and ML directions respectively. The mean setup errors were decreased to 0.04, 0.02 and 0.04 cm for PFC; and -0.04, -0.04 and -0.02 cm for BFS after the application of OBI. The errors were further decreased to below 0.02 cm in all directions after the application of first pre-treatment CBCT in both immobilization methods. Statistically significant difference (p < 0.05 ) was only found in the comparison of AP error between the two devices, when OBI was used as the verification method. For PFC, the 3D vector errors of skin mark, OBI and first pre-treatment CBCT were 6.4 mm, 2.9 mm and 0.5 mm, respectively cases. For BFS, the errors were 7.1 mm, 3.0 mm and 0.4 mm, respectively. Smaller PTV margins in various directions were needed in BFS when using CBCT as the verification method. Positioning errors of skin mark setup in AP and SI directions had major contributions to all the setup errors; gender and tumour location might significantly affect the setup uncertainties. Comparatively large intrafractional errors were found in the post-treatment CBCT results of PFC. Conclusion: When employing the CBCT-based final couch position as the benchmark, the setup errors of skin mark, OBI and first CBCT results were compared relatively. The positioning accuracies of PFC and BFS were similar. Apart from the vertical error (AP direction) found in the OBI verification, there was no significant difference between the positioning accuracy of both immobilization devices. Both imaging guided RT techniques were superior to skin mark. OBI and CBCT online correction improved the positioning accuracy of lung SBRT and substantially reduces required target margins and normal tissue irradiation. / published_or_final_version / Diagnostic Radiology / Master / Master of Medical Sciences

published_or_final_version / Radiation Oncology / Master / Master of Philosophy

No description available.

Monoclonal antibody fragments (Fab') which recognise tumour-associated antigens provide an ingenious means of selectively targeting a therapeutic radionuclide to a tumour for radioimmunotherapy. The radionuclide yttrium-90, a long range β(^-) emitter, was chosen to deliver a sterilising dose of radiation to the tumour. A selection of novel functionalised macrocyclic ligands based on a 1,4,7,10-tetraazacyclododecane skeleton have been synthesised, and the stabilities of their yttrium (III) and gadolinium (III) complexes studied in vitro through association and dissociation measurements, and in vivo through animal biodistribution studies. The radiolabelled complexes do not dissociate in vivo. Maleimides are compounds which are capable of selectively reacting with a thiol of an antibody fragment. Selective functionalisation of one of the yttrium binding macrocyclic ligands with either one or three maleimides has been carried out, and the resulting compounds conjugated to tumour seeking humanised antibody fragments. Subsequent radiolabelling with (^90)Y, gave the desired tumour targeting drug for use in radioimmunotherapy. Acridines are a class of intercalating agents which are capable of reversibly binding to DNA. A maleimide functionalised ligand derivatised with acridine was formed. Conjugation of this compound to antibody fragments capable of entering a tumour cell, may permit drug binding to tumour cell DNA, and thus enhance the targeting efficacy of the radiolabelled conjugate.

A simple method to verify the total treatment time generated by the treatment planning system (TPS) when the CONTURA MLB or the SAVI applicator are used for APBI treatments has been developed. The method compares the time generated by the TPS to a predicted time, calculated by inserting parameters obtained from the TPS in equations generated in this Thesis. The equations were generated by linearly fitting data from clinical cases that had been treated using the Contura MLB or the SAVI applicator at the Lynn Cancer Institute of the Boca Raton Regional Hospital. The parameters used were the PTV coverage, Air Kerma Strength, Balloon Volume (Contura data fit) and Evaluation PTV (SAVI data fit). As an outcome of this research, it is recommended that the plan should be reevaluated when the percent difference between the generated and the predicted times exceeds 5% for the Contura MLB, or 10% for the SAVI. / by Andreas Kyriacou. / Thesis (M.S.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

No description available.

The purpose of the present thesis was to better understand the effect of targeting key biological mechanisms in order to improve radiotherapy response. Two important and distinct pathways were targeted using novel agents: (1) the phosphoinoside-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway; (2) the ataxia telangiectasia-mutated-Rad3-related (ATR)/Chkl pathway. The role of the PI3K1mTOR signalling pathway in tumour radiosensitivity and tumour microerivlronment (TME) was examined using three, recently-developed signalling inhibitors obtained from Novartis Pharma: NVP-BEZ235 (dual PI3K1mTOR inhibitor), NVP-BGT226 (dual PI3K1mTOR inhibitor) and NVP-BKM120 (single PI3K inhibitor). The radiosensitising potential of NVP-BEZ235 and NVP-BGT226 was demonstrated in tumour and endothelial cells. Additionally, a thorough research into the effects ofNVP-BKM120 and NVP-BEZ235 on TME showed that oncogenic signalling inhibitors can improve vascular morphology and increase tumour oxygenation and perfusion in tumour xenograft models, resulting in improved radiation response. Furthermore, a highly potent and selective A TR inhibitor, VE-822, that was obtained from Vertex Pharmaceuticals (Europe) Ltd, was tested in pancreatic ductal adenocarcinoma (PDAC) cells and tumour xenograft models. A TR inhibition by VE-822 resulted in sensitisation of tumour cells but not normal cells to radiation and gemcitabine. Similarly, VE-822 strongly enhanced radiation- and chemoradiation-induced tumour growth delay in tumour xenograft models. Importantly, VE-822 did not potentiate radiation-induced gastrointestinal tract epithelial damage. To summarize, the impact of targeting two distinct pathways in combination with radiation and chemoradiation was explored. Inhibition of the PI3K1mTOR and ATRlChkl signalling pathways increases response of tumours to radiotherapy they and might be promising targeting strategies for cancer treatment. Our findings have considerable translational implications and future clinical trials should aim to validate these observations.

published_or_final_version / Surgery / Master / Master of Philosophy

Thesis (Ph.D.)--University of Western Australia, 2007.

No description available.