Theses and Dissertations (Medical Oncology)

Permanent URI for this collectionhttp://hdl.handle.net/2263/32535

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Towards the development of a new technique for mastectomy‐scar electron beam treatment using a variable collimator and computer‐automated treatment table control
(University of Pretoria, 2023) Van Rensburg, Ado J.; MlamboRoy.M@gmail.com; Mlambo, Musikavanhu Roy
Breast cancer in women is the most prevalent cancer in both developed and less developed countries, with an incidence of about 2.3 million new cases diagnosed in 2020, which is about 25% of all cancers in women. Several treatment options and techniques are available for the treatment of breast cancer, including surgery, chemotherapy, hormone therapy and radiotherapy, with treatment sometimes involving a combination of these techniques. Nonrandomized studies comparing breast conservation therapy with either electron beam therapy or interstitial implants, showed that there was no statistical difference between the treatment techniques in terms of disease-free survival, cosmesis, local tumour control or morbidity. The use of orthovoltage x-ray beam treatment has also been considered. It has some advantages, such as less shielding requirements and lower equipment costs. However, it has some drawbacks, such as the limitation on the beam penetration, leading to the maximum dose being deposited on the patient's skin, and also requiring longer treatment times because of the lower dose rates. From a South African context, orthovoltage therapy has become obsolete, as the handful of machines are not in operation with a decline worldwide in favour of using linacs. With linacs becoming more widely used and accessible, electron beam therapy remains a mainstay in treating breast cancer compared to other available treatment modalities. Patients showing locally advanced breast cancer have a risk of both distant and local-regional recurrence. Postmastectomy radiation therapy after surgery reduces the risk of recurrence and improves disease-free and overall survival. A patient undergoing postmastectomy radiotherapy may receive a mastectomy scar electron boost to reduce the risk of local recurrence. Compared with other treatment modalities such as orthovoltage, brachytherapy or photon therapy, electron beam treatment reduces the dose to underlining tissue beyond the target volume and offers a more uniform dose distribution (Khan, 2003). The energy of the electron beam to be used for treatment is determined by the thickness of the breast tissue from the chest wall to the skin (Griem and Hardin, 1998). The physical properties of electron beams make them suitable for chest wall treatment in breast treatment; the crucial motivation for the use of electron beam irradiation is the shape of the depth dose curve. The electron beam, however, needs to be collimated right down to the patient's surface using applicators and cutouts, which are positioned on the applicator as close as possible to the patient to provide a more customized field shape. Due to the disadvantages of traditional electron beam shaping using cutouts, this study proposes an alternative technique which retains the applicator but replaces the end of the applicator with a variable field shaping device allowing the collimator to deliver the dose over the entire region that would have commonly been treated using a cutout. To achieve the required dose distribution, the new technique makes use of the sliding window technique and incorporates the automated movement of the treatment table. This study aimed to develop a new treatment technique for treating the mastectomy scar using a collimated electron beam and a computer-controlled automated treatment table. The research set out to achieve the following objectives: develop a functional variable field shaping device that will allow treating the mastectomy scar; conduct measurements for the new technique; automate the couch movement for automated patient treatment of breast scar and have a working treatment technique. The proof of concept was carried out in developing a technique for treating mastectomy scars that used a variable collimator and automated treatment table. The treatment technique is an alternative to conventional treatment techniques that use lead and Wood’s-alloy electron cut-outs.
Molecular profiling of long non-coding RNAs in prostate cancer cell lines
(University of Pretoria, 2023) Marima, Rahaba; Dlamini, Zodwa; Kgoebane-Maseko, Mmamoletla; mandisambeje@gmail.com; Mbeje, Mandisa Pearl
Prostate cancer (PCa) incidence rates continue to rise with an estimation of 375 000 deaths and 1.4 million new cases in the year 2020. It has become the second most commonly occurring cancer and the fifth most frequent cause of cancer-related deaths in men. Prostate cancer is also the leading cancer to occur in men in the sub-Saharan region. In PCa, the aberrant expression of certain RNA molecules has been linked to PCa progression. Non-coding RNAs (ncRNAs) are RNA transcripts that are known for their involvement in numerous cellular processes. They are important in tumorigenesis and their presence may indicate cancer progression stages. Long non-coding ribonucleic acids (lncRNAs) are transcripts with 200 or more nucleotides. The focus on these lncRNAs can be attributed to their involvement in each of the cancer “hallmarks”. There have been multiple studies that have successfully identified lncRNAs in PCa. However, the landscape of the enriched molecular pathways targeted by these lncRNAs remains to be elucidated. Thus, this study aimed to profile aberrantly expressed lncRNAs and map the biological pathways associated with PCa progression. The differential expression patterns of 86 lncRNAs were compared between PC-3 and LNCaP PCa cell lines, which are highly metastatic and low metastatic (high grade and low grade), respectively. This was achieved by comparing the expression of lncRNAs between PC-3 and LNCaP cells using a 384-well plate of PCa lncRNA gene panel. LncRNA differential gene expression patterns were determined using the CFX Maestro software. The lncRNAs with a ±2 up or downregulation were considered to be differentially expressed. Annotation and enrichment analysis of lncRNA differential gene expression was performed using a human lncRNA sets database, LncSEA and DIANA-miRPath. Based on the PrimePCR array results and bioinformatics analysis, TERC lncRNA was selected for validation. The results of the array were validated with RT-qPCR using TERC primers. Thirty-six (36) of 86 lncRNAs were shown to be upregulated, while 12/86 of the lncRNA panel were downregulated. Bioinformatics analysis revealed that the upregulated lncRNAs are involved in various hallmarks of cancer. Interestingly, HOTAIR and TUG1 were demonstrated to be exosomal lncRNAs. In addition, the hypermethylation of HOTAIR and TERC was shown to sponge various miRNAs, promoting tumour progression. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and the Gene Ontology (GO) analysis revealed several cancer-related pathways, namely the signalling pathways regulating pluripotency of stem cells and the TGF-beta signalling pathway. Cytoscape ceRNA network analysis further illustrated the lncRNA/miRNA/mRNA axis in PCa progression. LncRNAs may be prognostic biomarkers as they have been reported to be stable in liquid and solid biopsies.
Possible effects of HIV infection on overall survival of patients diagnosed with acute myeloid leukaemia
(University of Pretoria, 2019) Dreosti, Lydia M.; gbdyer36@gmail.com; Dyer, Greg Bryan
Background The effects of Human Immunodeficiency Virus (HIV) on the Overall Survival (OS) in patients diagnosed with Acute Myeloid Leukaemia (AML) are not well documented. All studies to date have been with small sample sizes and based on collections of case studies from different facilities with different treatment protocols, as a result it has been difficult to draw definitive conclusions. Method This retrospective record review of a cohort of AML patients (n=304) treated at a single site between 2000 and 2017 was conducted. Age (16-93 years), gender (Male: n=157 ; Female: n=138), ECOG PS (Eastern Co-Operative Oncology Group Performance Status), FAB (French-American-British) staging, blast count, CD4 count, HIV viral load, financial status, response to treatment as measured on bone marrow biopsy and OS were measured. The OS was compared for HIV status. Further comparisons were conducted in a sub-group where age, ECOG PS and FAB staging were controlled. Results 210 (69.07%) were HIV negative, 31 (10.1%) were HIV positive, 63 (20.7%) had an unknown HIV status. A statistically significant difference was found between HIV negative and HIV positive groups’ OS (563 vs. 121 days ; P<0.01)(HR 2.02 ; 95% CI 1.36 - 2.99) in the main analysis. This difference was also noted when patients who were not treated for AML were excluded from the comparison (OS, 740 vs 194 days, P<0.01)(HR, 2.10 ; 95% CI 1.26-3.50). In the main analysis mean ECOG PS was better in the HIV negative population compared to the positive population (1.80 vs. 2.06). In the controlled group sub-study, where Age, ECOG PS and FAB staging were controlled, the OS between HIV positive and HIV negative patients was not statistically significant (141 days vs. 121 days) (P=0.17; 95% CI). CD4 counts ranged from 29 – 1416, with a mean CD4 of 432 on presentation. No statistically significant difference could be found between CD4 and OS (HR, 1.0 ; 95% CI 0.99-1.00), possibly due to very few patients presenting with a low CD4 count. HIV Viral Loads ranged from <100 – 106640. Similarly, no statistically significant difference was found between HIV Viral Load and OS (HR 0.99 ; 95% CI 0.99-1.00). Conclusion HIV has a negative impact upon the OS of patients with AML. HIV appears to impact on OS as a chronic comorbidity by affecting ECOG PS on presentation, reducing their chance of being treated as well as possibly reducing a patients’ functional reserve. This impact does not appear to be as a result of a direct interaction between the HIV and AML disease processes, as when controlling for other factors that may influence OS there is no statistically significant difference in OS between HIV positive and negative patients.
The development and validation of a quality assurance program for intensity modulated radiation therapy
(University of Pretoria, 2012-10-01) Van Rensburg, Ado J.; yousif_kerban@yahoo.com; Yousif, Yousif Abdallah Mohammed
No abstract available.
Design and evaluation of a dosimetry system to verify the radiotherapy procedure from treatment planning to treatment delivery
(University of Pretoria, 2005-09-26) upetd@ais.up.ac.za; Kanduza, Mulape M.; Prof A Janse van Rensburg
In the advent of more radiotherapy centers being set up across the African continent and the introduction of linear accelerators in addition to some of the already existing cobalt radiotherapy machines, it is apparent that verification of treatment delivery is necessary. Also, most audits in radiotherapy concentrated on radiation bean outputs and few exist that check the radiotherapy chain. A dosimetry system has been developed to address need to verify the radiotherapy chain. The aim of this study is to demonstrate dosimetric verification and the feasibility as well as cost effectiveness of manufacture of the dosimetry phantom using material locally available in the radiotherapy department. The phantom is designed and fabricated in the shape of a female pelvis bearing in mind the high incidence of cervical cancer more especially in Africa. It is designed with purpose of accommodating two dosimetric tools: thermoluminescence dosimeters (TLDs) and radiographic film. The delivery of external beam radiation therapy is evaluated for three different modalities by comparison of predicted and measured dose values. Point dose values measured with TLDs were compared with predicted dose values and resulted in differences of ± 5 % were observed for uniform dose regions. Higher discrepancies (up to ± 28%) were observed for points in the penumbra (high dose gradient) of the radiation field. Isodose distribution were determined by radiographic film and compared with those predicted by the treatment planning system. Distance to agreement between predicted and measured isodoses was within ± 5mm. The dosimetric verification methods were quantitative, qualitative and clinically practical. The fabrication of the phantom, dosimetric measurements and analysis demonstrate the feasibility and accuracy of the system for achieving treatment verification. Thus the system provides a means to verify the full radiotherapy chain from the point prior to and after treatment planning and through to treatment delivery.
Comparing target volumes used in radiotherapy planning based on CT and PET/CT lung scans with and without respiratory gating applied
(University of Pretoria, 2012) Janse van Rensburg, A.; tamarisk.duplessis@gmail.com; Du Plessis, Tamarisk
A study was done at Steve Biko Academic hospital to determine the influence that respiratory gating will have on target volumes used in radiotherapy treatment planning. The primary objective was to compare target volumes of respiratory gated scans to ungated scans and to determine whether it will be meaningful to permanently implement a 4D respiratory gating system on CT scanners in the South African public health sector and to use these images for target volume delineation in radiotherapy planning. The study consisted of three sections. In the first section, 4D respiratory gated CT images were obtained and delineated with 4D software. The full-inspiration and full-expiration phases of the gated scans were then fused to obtain ungated images which were also delineated. The gross tumor volumes (GTVs) of the gated phases were compared to the ungated GTVs, and found that on average the volumes decreased by 14.63% with a standard deviation of 7.96% when gating was applied. Yet another aim was to determine the influence that 4D imaging will have on radiotherapy treatment planning. One of the 4D study sets was imported to the XIO treatment planning system where IMRT treatment plans were created on both the gated and ungated scans. The plans conformed to the treatment aims and restrictions when clinical parameters such as DVHs were used to evaluate it. The planned target volume coverage differed by less than 1% between the gated and the ungated plans, but significant dose reductions to the OARs of up to 32.65% to the contralateral lung were recorded on the gated plan. In the second section of this study, respiratory gated CT scans were simulated by applying the breath-hold technique to lung cancer patients. The technique was applied during full-inspiration which fundamentally represents the maximum peak of the sinusoidal respiratory waveform. An ungated scan was also acquired during normal respiration. The clinical target volumes (CTVs) were identified on both scans by three oncologists and the average CTVs were compared. It was found that the CTVs decreased significantly by an average of 14.33%. Palliative patients receive parallel opposing field therapy which is planned from 2D films. It is very unlikely that these opposing field sizes will differ when gating is applied. It was therefore concluded that only radical lung patients, which was estimated to be a mere 0.03% of the total radiation therapy patient population, will benefit by implementing respiratory gating or any motion-reduction technique. For the third section of the study, respiratory gated PET scans were acquired on a PET/CT scanner to evaluate external, non-technical parameters that will influence respiratory gating. The results indicated that time and patient participation were not limiting factors. The biggest concerns however were the effectiveness of the gating system, software limitations and the gated results. These problems might be minimized with thorough training on the system. All three sections as well as the financial implications were considered to conclude that it will not be meaningful to implement 4D respiratory gating techniques in the South African public health sector Copyright
Quality of life in patients with metastatic breast cancer : A South African perspective
(University of Pretoria, 2010-10-06) Falkson, Annette; upetd@up.ac.za; Mertz, Magaretha Susara
Please read the abstract in the section 00front of this document
A comparison of radiotherapy techniques for the irradiation of the whole scalp
(University of Pretoria, 2010) Janse van Rensburg, A.; emmaviviers@hotmail.com; Viviers, Emma Victoria
No abstract available.
The effect of metal based complexes on the survival of aerobic and hypoxic chinese hamster ovary cells, in vitro.
(University of Pretoria, 2007-03-03) Medlen, Connie E.; upetd@up.ac.za; Falzone, Nadia
It is well established that many solid tumours are heterogeneous with respect to oxygenation, and contain regions of hypoxic cells, which due to their inherent resistance to ionizing radiation, limit the success of radiotherapy. Numerous chemicals and drugs have been investigated over the past few decades as potential radiosensitizers. The most notable of these being the organometallic compound, cis-diammine dichloroplatinum(II). The clinical success of this drug led to the synthesis of other types of organic cytotoxic metal-containing drugs. Prof. J.C. Swart from the University of the Orange Free State supplied seventeen novel iridium, ferrecenium and rhodium complexes, which I screened for cytotoxic activity against the CHO cell line. The two most cytotoxic complexes namely, [Rh(fctca)(cod)] and [Rh(fctfa)(cod)], were tested for radiosensitizing potential against aerobic and hypoxic CHO cells in the presence of an 8 MV photon beam by the MTT assay adapted to our laboratory conditions. The ferrocene betadiketones co-ordinated to them, Hfctca and Hfctfa and the Ir compliment of [Rh(fctfa)(cod)] namely, [Ir(fctfa)(cod)] were also assessed by the MTT assay. Interestingly, neither the ferrocene nor the iridium complexes showed noteworthy sensitization, which suggests that the rhodium is responsible for the efficacy observed. The radiosensitizing potential of the most active complex, [Rh(fctfa)(cod)] and cisplatin were also confirmed by the use of the more traditional clonogenic assay. Not only did the MTT assay deliver results comparable to the clonogenic technique, but one of the complexes [Rh(fctfa)(cod)] showed radiosensitizing potential against hypoxic CHO cells, equal to that of cisplatin. The rhodium complex, [Rh(fctfa)(cod)] was also tested for radiosensitization properties against the CHO cell line in the presence of a p(66)/Be neutron beam. Results indicated that [Rh(fctfa)(cod)] sensitizes cells to radiation possibly by inhibition of cell inactivation mechanisms that are normally associated with repairable damage. Consequent work done on the flow cytometer where direct DNA damage after irradiation (8 MV photon beam) and drug treatment, was assessed on aerobic CHO cells by a technique adapted to our laboratory showed no significant increase in the forward angle scattered light (FSC) parameter which is an indication of radiation induced strand breaks. Furthermore, [Rh(fctfa)(cod)] showed a significantly greater increase in the side angle scattered light (SSC) parameter, which is an indication of the binding ability of the complex, compared to cisplatin, after treatment with different concentrations of the drugs. Results obtained from enumerating micronuclei frequencies after drug treatment and radiation confirmed that both cisplatin and [Rh(fctfa)(cod)] are more active under hypoxic conditions, with [Rh(fctfa)(cod)] responsible for more micronuclei per binucleated cell. In conclusion, I have established that [Rh(fctfa)(cod)] has a cytotoxic activity comparable to that of cisplatin and that it sensitizes preferentially hypoxic CHO cells to radiation in the clinically relevant dose range. I have also identified the probable action by which [Rh(fctfa)(cod)] sensitizes CHO cells to radiation as being inhibition of repair capacity. Furthermore, results suggest that this complex binds covalently to DNA base pairs. The complex [Rh (fctfa) (cod)] , has so far proven to possess interesting radiosensitizing potential which must be exploited for eventual therapeutic benefit.

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