Pella, Silvia

Glioblastoma multiforme (GBM) is an aggressive and highly resistant brain tumour, necessitating advanced treatment approaches to improve patient outcomes. This thesis provides a comprehensive review of recent advancements in GBM treatment, including innovations in treatment planning, radiation therapy, and their impacts on patient survival. The study also involves a detailed analysis of five GBM patients, examining critical dosimetric and radiobiological parameters, including Dose Volume Histogram, CT and MRI Images, T1, T2, T3 and T4 images. These parameters are analyzed using key radiobiological models, such as the linear-quadratic model, and factors like α/β, dose per fraction, and survival fractions. Through this data analysis, the study aims to evaluate the effectiveness of the treatment protocols and their impact on tumour control probability (TCP) and normal tissue complication probability (NTCP). The results will contribute to the understanding of GBM radiotherapy outcomes and provide insights for optimizing future treatment strategies.

Dose uniformity in the Planning Target Volume (PTV) can induce a higher-than-expected dose distribution in the nearby critical organs. The goal of this study is to evaluate the influence of the Planning Target volume dose uniformity on the surrounding critical organs (OAR).
Ten cases of anonymized patients’ data were selected for our study including: Breast cancer, Brain cancer, Head and Neck cancer, Lung and Prostate calculations of Conformity indices, Biological Effective Doses (BED), Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) were used to calculate the dose distribution in PTV as well as the dose delivered to the surrounding critical organs of each PTV. We assume that the tumors PTVs have homogeneous density as well as the surrounding normal tissue.
Conformity indices (CI) for Breast (PTV) are between 1.8 – 1.9, for Brain (PTV) are between 1.6 – 2.0, for Lungs are 1.5 – 1.6, for Prostate are between 0.4 – 0.5, for Head and Neck are 0.3 – 0.4. Dose uniformity in all the PTVs is 1.089 which is a good indication of the quality of treatment delivered to the tumor. TCP is averaging of value of 87.94 and NTCP is 3.4445.

Hepatocellular carcinoma is currently one of the most fatal cancers in the world. The routine treatment for this type of cancer consists of surgery, chemotherapy, and finally radiation therapy. Recent advancements in technology have enabled us to deliver highly conformed dose to planning target volume. Two of these methods are Intensity modulated Radiation Therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT). The difference between these two methods is that in the SBRT high radiation dose per fraction is delivered, but smaller number of fractions which renders better tumor control probability. However, better tumor control comes at the price of complications and radiation induced liver damage.
In this work, we compare the outcome of radiation with regards to the probability of radiation damage to the liver after IMRT and SBRT. For this purpose, we analyzed 10 anonymized patients’ data with liver cancer, and we made two similar treatment plans for them. The difference in two plans is dose per fraction and total dose. After optimizing the treatments and calculating the dose volume histogram, we found the effective volume of the liver being irradiated. Finally, this effective volume and the corresponding dose were used to show that SBRT has the advantage of better tumor control probability at the cost of higher probability of complications.

An algorithm to determine IMRT optimization parameters within the Elekta Monaco® treatment planning system that increases dose homogeneity and dose conformity in the planning target volume was developed. This algorithm determines IMRT optimization parameters by calculating the difference between two pairs of dose points along the target volume’s dose volume histogram: Dmax – Dmin, and D2 – D98. The algorithm was tested on the Elekta Monaco® Treatment Planning System at GenesisCare of Coconut Creek, Florida using CT data from 10 anonymized patients with non-small cell lung cancer of various tumor sizes and locations. Nine iterations of parameters were tested on each patient. Once the ideal parameters were found, the results were evaluated using the ICRU report 83 homogeneity index as well as the Paddick conformity index. As an outcome of this research, it is recommended that at least three iterations of IMRT optimization parameters should be calculated to find the ideal parameters.

Due to the difficulty of a complex commissioning technique for a multi energetic, multi-modality linear accelerator, I perform all the commissioning and acceptance testing for a TrueBeam linear accelerator with 4 megavoltage (MV) energies of which 2 are flattening filter-free (FFF) and 6 electron energies varying from 6 MeV to 20 MeV.
A 2 dimensional (2D) water tank was used for scanning all the required field sizes for all the energies. The one dimensional (1D) water tank was used to collect all the output factors for all the photon fields sizes small to medium electron field sizes. For the large electron fields sizes, we had to use the 2D water tank. All the collected data was converted into a file type accepted by the planning system (Eclipse) and subsequently imported there. Treatment plans were generated using multiple forms of planning to verify the viability and quality of the beam data commissioned.

The Computer Tomography (CT) scanned images are very important for the Treatment Planning System (TPS) to provide the electron density of the different types of tissues that the radiation penetrates in the path to the tumor to be treated. This electron density is converted to an attenuation coefficient, which varies with tissue for each structure and even varies by the tissue volume. The purpose of this research is to evaluate the CT numbers, and convert them into relative electron densities. Twenty-five patients’ data and CT numbers were evaluated in the CT scanner and in Eclipse and were converted into relative electron density and compared with each other. The differences between the relative electron density in the Eclipse was found to be from 0 up to 6% between tissue equivalent materials, the final result for all equivalent tissue materials was about 2%. For the patients’ data, the percentage difference of CT number versus electron density was found to be high for high relative electron density organs, namely the final average result for the spine was 8%, less for pelvis, and less for rib while for the other organs it was even less. The very lowest was 0.3% compared with 1% which is acceptable for clinical standards.

Accelerated Partial Breast Irradiation (APBI) is a common treatment of breast cancer with many modalities including 3D Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT), and High Dose Rate Brachytherapy (HDR). In this research, a retrospective analysis of patient’s data was performed to analyze the NTCP/TCP (Normal Tissue Complication Probability/Tumor Control Probability) and Dose Volume Histogram (DVH) parameters for HDR with SAVI, 3D, and IMRT and compare them focusing on critical organs such as the heart, ipsilateral lung, chest wall, ribs, and skin. TCP was 90.275%, 55.948%, and 53.369% for HDR, 3D, and IMRT respectively. The ribs were the most sensitive critical organ for all 3 modalities with a mean NTCP of 8%, 15%, and 8% for HDR, 3D, and IMRT respectively. DVH analysis showed HDR spares critical organs more than EBRT except for 2 patients receiving high doses to the ribs and chest wall.

Stereotactic Body Radiation Therapy (SBRT) is a modern precision radiation therapy to deliver the dose in 1 to 5 fractions with high target dose conformity, and steep dose gradient towards healthy tissues. The dose delivered is influenced by the leaf width of the MLC, especially in case of SBRT. Treatment plans with high definition (HD) MLC having leaf-width 2.5 mm and normal MLC having leaf-width 5 mm, were compared to quantify dosimetric and radiobiological parameters. Dosimetric parameters conformity indices (CI), gradient indices (GI) and heterogeneity indices (HI) were compared. The radiobiological parameters were evaluated by normal tissue complication probability (NTCP) and tumor control probability (TCP) based on the equivalent uniform dose (EUD). The results show that there is dosimetric and radiobiological merit of the HD MLC over the normal MLC. However, the improvement is not consistent with all the plans and thus further research is required prior to conclusion.

Intracavitary high-dose-rate brachytherapy (HDRBT) is a treatment option for
endometrial cancer, depending on the cancer stage. Because of the steep high dose gradient
of HDRBT, very small differences in the treatment plans, surrounding organ’s anatomy, or
procedures during the treatment could potentially cause significant dose variation to the
tumor, as well as organs at risks (OAR) nearby the treatment area, which could result in
unwanted radiobiological side effects. In this retrospective study, the radiobiological plan
evaluation parameters Equivalent Uniform Dose (EUD), Normal Tissue Complication
Probability (NTCP) are used as assessment tools to evaluate HDRBT plans. Furthermore,
gynecological applicator position in the coordinate system, and possible dose variations to
the tumor and critical organs from the initial fraction in comparison with subsequent
fractions over the entire multi fractionated treatment are studied. The evaluations were
performed for 118 HDR treatment plans for 30 patients by registration of the subsequent treatment plans into the initial CT-image guided plan. Dose fractionation regimens varied
from 4Gy to 7Gy per fraction, 1 or 2 fractions per week, depending on the cancer stage.
Our results demonstrate no significant radiobiological impacts on organs at risks (OAR).
In addition, the results of the applicator positions’ study indicate that improvement of
immobilization and localization devices are recommended.

The purpose of this study is to verify and validate the dose at various points of
interest in accelerated partial breast irradiation (APBI) treated with the Strut Adjusted
Volume Implant (SAVI) applicator using Thermoluminescent Dosimeters (TLDs). A set
of CT images were selected from a patient’s data who had received APBI using the SAVI
applicator. The images were used to make 3D models. TLDs were calibrated for
Brachytherapy. Various points of interest were marked out and slots were carved in the 3D
models to fit the TLDs. CT scans were taken of the 3D models with expanded SAVI
applicator inserted. A plan was made following B-39 protocol. The TLDs were read and
the absorbed doses were calculated and compared to the delivered doses. The results of this
study show that the overall average reading of the TLDs is within expected value. The TPS
shows overestimated dose calculations for brachytherapy.