Saudi Cultural Missions Theses & Dissertations
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Item Restricted Lung Density and Algorithm Choice in Radiotherapy: Implications for Accurate Lung Cancer Treatment Planning(Saudi Digital Library, 2025-06-01) Alhamdan, Hesham; Brad, ObornAccurate dose calculation is crucial for effective lung cancer radiotherapy, particularly in heterogeneous media where density variations can result in significant deviations between planning algorithms. This study systematically compared the fast collapsed cone convolution (CCC) algorithm against a high-accuracy Monte Carlo (MC) dose engine within the RayStation treatment planning system. Two main investigations were conducted: (1) a controlled phantom study consisting of a water block with lung-equivalent inserts of varying densities (1.0, 0.4, 0.3, 0.2 g/cm3 ) irradiated by 6 MV and 10 MV photon beams across four field sizes (2×2, 3×3, 5×5, 10×10 cm2), and (2) a clinical patient study involving three anonymised VMAT plans for small, medium, and large lung tumours. In the phantom study, PDD, lateral profiles, and sagittal dose slices revealed that CCC overestimates superficial (skin) dose and in-lung dose relative to MC. These effects intensified with smaller field sizes, lower lung densities, and higher beam energy due to lateral electronic disequilibrium. Quantitative ROI analyses showed that, although out-of-field differences were notable, they were statistically indistinguishable when accounting for MC noise. CCC’s deviations in lung-insert dose became significant for small fields (≤ 3×3 cm2) in low-density media. In the patient study, CCC overestimated entrance skin dose yet underestimated tumour and organs at risk coverage by up to 5.9 % of the clinical goal. These findings align with prior literature on lateral scatter limitations in CCC. Clinically, our results affirm that CCC plans should be verified by MC, especially for small-field, low-density lung targets, to ensure accurate tumour coverage and normal tissue sparing.13 0Item Restricted INTERVENTIONS USED IN THE TREATMENT OF RADIOTHERAPY INDUCED TRISMUS: A SYSTEMATIC REVIEW(University College London, 2024) Aladwani, Reem; Mercadante, ValeriaAbstract Introduction: Trismus is a chronic debilitating complication of radiotherapy to the head and neck highly prevalent among head and neck cancer survivors. Affected patients may experience a marked restriction of jaw movements causing difficulties with daily activities, such as eating, chewing and swallowing, all of which have a direct impact on the quality of life of patients. Objectives: To assess the effects of available intervention to manage radiotherapy-induced trismus. Methods: We have included controlled trials involving adults with a diagnosis of radiotherapy-induced trismus. Four main databases were included in our search (MEDLINE OVID, EMBASE, OVID, the COCHRANE library, and Web of Science core collection) with a throughout, comprehensive search conducted in all databases. Search was carried out in June 2024 for randomized controlled trials (RCTs) and non-randomized controlled studies incorporating trismus treatments for head and neck cancer. Results: In total 9 studies were included, 7 RCT, and two non-randomized controlled studies, with a total of 530 patients who received radiotherapy alone, or combined chemoradiotherapy. Most of the studies were focusing on the range of motion exercise, one study focused on low-intensity ultrasound, and low-level laser therapy, other study focused on photobiomodulation (FTBM) and conventional speech therapy. However, others focused on Myofascial Release (MFR) technique, Therabite System, Engstrom jaw device and Matrix Rhythm Therapy. Conclusion: The results of this systematic review showed that there is no high-level evidence for the effectiveness of one type of management interventions over another. Further RCTs are required to draw reliable and generalizable conclusions on the treatment of trismus in head and neck cancer survivors.12 0Item Restricted An Anthropomorphic Multimodality (CT/MRI) Head and Neck Phantom for Radiotherapy Applications(University of Leeds, 2024-10) Alzahrani, Meshal; Speight, Richard; Broadbent, David; Teh, Irvin; Alqaisieh, BasharAims: To develop and evaluate an anthropomorphic multimodality phantom for the head and neck (H&N) anatomy that can be used with computed tomography (CT) and magnetic resonance imaging (MRI) for radiotherapy (RT) applications. The research aims to identify suitable materials for creating these phantoms, assess the suitability and effectiveness of a 3D head and neck phantom for MRI-based quality assurance (QA) in RT planning, and to optimise cone beam computed tomography (CBCT) protocols for H&N imaging as part of QA processes. Methods: Through literature research, candidate materials potentially suitable for developing multimodality (MRI/CT) phantoms were identified and produced. Their suitability and stability over time and after exposure to radiation were then evaluated. An anthropomorphic multimodality H&N phantom was used to evaluate the benefits of using such a phantom for conducting QA tests recommended by international bodies in MRI guided RT treatment planning services. Moreover, the scope of the phantom's use has been expanded to include optimising CBCT protocols, further demonstrating its value in enhancing QA processes across multiple imaging modalities. Results: The results of this project indicate that while some materials meet specific requirements for creating anthropomorphic multimodality phantoms, it has been challenging to find materials that simultaneously satisfy the needs of both MRI and CT modalities. However, the results have shown that the T1 and T2 relaxation times and CT numbers of 10% polyvinyl alcohol cryogel closely match those of normal brain grey matter, and remain stable over a year, and after exposure to radiation levels up to 1000 Gy, demonstrating its potential effectiveness in making phantoms. The anthropomorphic multimodality phantom has demonstrated superior performance to non-anthropomorphic phantoms in certain aspects of MRI-based RT planning QA, particularly in end-to-end testing. The phantom can be used in optimising CBCT protocols as part of QA processes, with results showing that it allows for a reduction in radiation doses by more than 50% compared to the default protocol for patients with head and neck tumours without significantly affecting image or registration quality and with the expectation that this would not have a consequential impact on treatment plans. Conclusions: The identification of only one suitable material underscores the need for expanded research into multimodality phantom materials. The phantom proves effective for MRI-based QA. Additionally, it was employed to test and optimise CBCT protocols, leading to reductions in radiation doses without compromising image quality.22 0Item Restricted Electron FLASH beams from a modified Elekta Precise LINAC: characterisation and dosimetry(University College Dublin, 2024-12) Mousli, Majed Hussain; Vintró, Luis LeónRadiotherapy treatment aims to administer a substantial dose of ionising radiation to the tumour volume while limiting exposure to surrounding healthy tissue to reduce potential side effects. Typically, daily fractionated doses of about 2 Gy each, extended over an average of around 20 fractions (typically ranging from 5 to 39 fractions) across diverse tumour sites are employed. This conventional dose fractionation utilises techniques like 3D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic ablative radiotherapy (SABR) to deliver the dose, with average dose rates varying from 6 Gy/min (using conventional flattened beams) to 24 Gy/min (employing flattening filter-free (FFF) beams) to expedite treatment duration and enhance patient comfort. Recently, FLASH radiotherapy, which makes use of ultra-high dose rates (UHDR) of >40 Gy/s to irradiate targets, has been the subject of much research. This approach holds the potential to augment the therapeutic ratio and significantly reduce treatment times, where the therapeutic ratio signifies the balance between tumour control probability (TCP) and normal tissue control probability (NTCP) likelihood. The main aim of this thesis was to investigate the possibility of making use of a suitably modified standard radiotherapy linear accelerator (LINAC) to produce FLASH level electron beams, and to characterise the resulting beams with a range of different detectors, including a novel inorganic scintillator detector. As a first step in this study, a Monte Carlo (MC) model of the Elekta Precise LINAC was developed using the EGSnrc MC code to characterise conventional systems utilising 10, 12, and 15 MeV electrons. The MC model was employed to investigate the effect of making changes to the LINAC towards achieving FLASH-level beams, and to assess detector responses, encompassing dose, dose linearity, and dose rate dependence when subjected to FLASH beam conditions. The model's validation was performed against an advanced Markus ionising chamber (AMIC) and Gafchromic EBT XD film measurements for both conventional and modified LINAC set ups. The results showed very good agreement between simulated and measured data, with depth dose percentages (PDD), as well as the relative distances R90, R50, and Rp giving variations within ±1 mm for both conventional LINAC across the 10, 12, and 15 MeV electron energies and modified LINAC for the 12 MeV electron energy. Bremsstrahlung contamination was found to be 1% and 2% for conventional LINAC and modified LINAC, respectively. The beam profiles showed deviations of ±2% (cross-plane) and (in-plane) for the 12 MeV electron beam under conventional and modified LINAC conditions. In conclusion, the MC model demonstrates robust agreement between measured and calculated data for both conventional and modified LINAC settings, offering potential utility in validating diverse dosimetry detectors for assessing dose, dose rate, and dose per pulse (DPP) dependencies under FLASH irradiation. The second objective was to characterise multiple dosimetric detectors using a modified Elekta Precise linear accelerator (LINAC) to generate an electron FLASH beam for radiotherapy (eFLASH-RT), achieving radiobiological research-level FLASH conditions, and to compare the results with those predicted using Monte Carlo (MC) simulation. The 12 MeV electron beam was adapted into an eFLASH setup by adjusting beam parameters and positioning the carousel at an open port with primary and secondary scattering foils. A microcontroller unit (MCU) circuit was used to control the pulse count. Gafchromic EBT-XD films were used to established PDD, beam profiles and DPP, and these were validated against MC simulations. Both conventional beam radiotherapy (CONV-RT) and eFLASH-RT showed that the simulated and measured data for reference depths R90, R50, and Rp agreed to within ± 1 mm. Gamma analysis, with passing rates >95% (gamma criteria 3%/3mm), showed good PDD and beam profile agreement. DPP changed with SSD (54 to 150 cm) from 0.2 to 0.025 cGy/pulse in CONV-RT to 60 to 8 cGy/pulse in FLASH-RT, with negligible differences (< 2 cGy) between MC and each detector. By taking secondary scattering foils out of the beam path and reducing the SSD, the model predicted that dose rates in excess of 40 Gy/s could be achieved. This was confirmed by using the PTW AMIC detector and EBT XD films. The model was used to analyse parameters like PDD, large-field beam profiles, dose, dose rate, and DPP dependencies. The results of this study demonstrate that the modified LINAC can be used as a tool to assess dosimetry detectors for FLASH radiotherapy, potentially aiding online real-time radiation dose evaluation during therapy and facilitating radiobiological investigations into eFLASH-RT's cellular impact. The final part of the thesis investigated the use of a novel inorganic scintillating detector (ISD) employing Gd2O2S:Tb with a short temporal resolution (2.8 ms), as well as a plastic scintillation material (PSD), for real-time dosimetry in ultra-high dose rate applications. The modified LINAC was used to deliver a 12-MeV electron FLASH beam (eFLASH) at an average dose rate of 85 Gy/s. The response of the scintillation dosimeters (operated using the HYPERSCINT radiation platform) were compared to that of the AMIC detector across various field sizes and electron applicators to assess linearity, repeatability, DPP, and output factors at a 4-cm water-equivalent depth. The plastic (PSD) and inorganic scintillator detector (ISD) measurements were validated against EBT-XD Gafchromic films and Monte Carlo (MC) simulations. Relative IC measurements exhibited linear behaviour, with PSD and ISD responses differing within 1% and 14%, respectively, over a 50 to 7000 cGy range. PSD maintained linearity with increasing pulse repetition frequency (PRF) up to 172 Hz (max value 1.1), while ISD response at 40, 72, and 172 Hz yielded linearity indices of 1.2, 1.35, and 1.24. PSD and ISD showed consistent dose responses under ultrahigh dose rate conditions, agreeing within 4% with EBT-XD film readings. Furthermore, DPP linearity at different SSDs was studied, yielding favourable agreement for 5 cm2 field sizes using EBT-XD film, AMIC, and MC models. The novel PSD and ISD detectors, integrated into the HYPERSCINT platform, demonstrated a robust response to 12 MeV eFLASH beam irradiation, accommodating DPP of up to 0.65 Gy and an ultra-high dose rate of 85 Gy/s. This work will establish a versatile dosimetry platform that will be applicable to various research domains, including in vitro and in vivo radiobiology investigations of ultrahigh dose rate irradiation.13 0Item Restricted Developing a Treatment Plans System (TPS) to Optimize Radiation-Induced Immune Response Through Type 1 Interferon Beta Upregulation in Cancer Patients(Purdue University, 2024-01-01) Almalki, Abdulrahman; Stantz, KiethIntroduction: Radiotherapy is a treatment modality that is prescribed for more than 50% of cancer patients around the globe. Through decades of clinical application, RT has witnessed considerable advancements achieving significant tumor control with minimal damage to healthy tissues. Recently, a paradigm shift has recognized RT's potential to induce anti-tumor immune responses, where patients receiving radiation to the primary tumor also resolved lesions outside the treatment field. This out-of-field response also referred to as an abscopal effect, is believed to promote immunogenic cell death (ICD) initiated by the radiation-induced DNA damage and subsequent activation of the cGAS-STING-IFNβ pathways. However, clinical realization of an abscopal effect remains rare. We hypothesize by selectively irradiating cancer cells with high metastatic potential within a solid tumor (intra-tumor radiotherapy treatment planning) with high metastatic potential, a more efficient anti-tumor response can be achieved while minimizing inflammatory responses from surrounding tumor and normal tissues, obfuscating a potential adaptive immune response, thus help in overcoming the rarity observed in the clinical practice. To achieve this objective, radiotherapy treatment plans targeting hypoxic regions (known to harbor a metastatic phenotype) within a solid tumor and optimally activating IFN will be investigated. Methods: Hypoxic conditions within tumor microenvironments significantly reduce DNA damage, conferring a radioresistant phenotype that leads to RT failure. To address the inherent radioresistance and immunosuppression of hypoxic tumors, high linear energy transfer (LET) modalities are used. Our research aims to enhance the specificity and efficiency of ICD, particularly in highly metastatic (hypoxic) regions within the tumor, by employing heavy charged particle (HCP) beams to optimize DSB induction. Empirical mathematical models have been developed to predict the dose-response of IFNβ based on in vitro data and Monte Carlo methods of DSB-induction. These methods are used in maximizing type I interferon (IFNβ) production and subsequent immune response while minimizing the inflammatory response and damage to surrounding tissue. Immunogenic treatment plans, iTPS, have been developed to integrate charged particle beam models for proton, helium, and carbon ions and the above-empirical models into FLUKA Monte Carlo simulations and subsequently evaluated in clinical case studies of brain and lung cancer. Next, new biophysical models accounting for tumor hypoxia were developed and integrated into the iTPS, and clinical case studies were reevaluated. Results: SA(1): Developed and integrated charged particle beam models into FLUKA MC for both homogeneous and heterogeneous treatment planning. Empirical equations for RBEDSB, pO2, LET, and IFNβ dose-response were incorporated into FLUKA for voxel-based simulations across oxygen levels. SA(2): RBEDSB-weighted optimization yielded uniform IFNβ production. High LET enabled carbon ion beams to require the lowest doses, achieving superior peak-to-entrance ratios of 15.85 compared to 10.78 and 7.60 for helium and proton beams, respectively. Patient simulations demonstrated carbon ions' superiority, with D95% values of 7.68 Gy for the brain and 7.60 Gy for lung tumors, excelling in IFNβ production. SA(3): An optimized treatment plan for uniform IFNβ in hypoxia utilizing empirical equations for RBEDSB across hypoxia levels was created for different charged particles. MCC13 adjustments based on OERDSB from MCDS were confirmed by measured data in U251 cell lines, showing an OER of 1.5 between normoxia and 1% hypoxia, closely matching MCDS predictions within a 7% discrepancy. Carbon ions achieved optimal IFNβ at 11.02 Gy for brain tumors under 0.1% hypoxia in FLUKA simulations. Conclusions: Our results from both homogeneous target and patient cases demonstrate that charged particles have the potential to elicit higher levels of IFNβ at lower doses compared to photon irradiations in different pO2 levels. High LET irradiation not only ensures a highly localized IFNβ response in the target but also effectively spares surrounding normal tissues, thereby minimizing treatment-related toxicity. This finding underscores the superiority of high LET irradiation in achieving targeted immunogenic effects while enhancing the therapeutic window by reducing damage to normal cells.13 0