Thesis (MMed)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Radiotherapy in the Management of Carcinoma of the Vulva in Human Immune-Deficiency Virus (HIV) Positive and Negative Patients: An Institutional Experience. Opakas J. Department of Medical Imaging and Clinical Oncology, Division of Radiation and Clinical Oncology, Tygerberg Academic Hospital and the University of Stellenbosch Background: Radiotherapy and chemotherapy are integral parts of the effective and optimal management of patients with vulva cancer, especially when initiated early in the course of this disease. Often, surgical resection alone cannot effect total removal of the tumour or may not be feasible. Human Immune-Deficiency Virus (HIV) infection has been an epidemic in sub-Saharan Africa. Highly Active Antiretroviral Therapy (HAART) is available in public health facilities in the region to arrest and control HIV infection, delaying the progression to AIDS and death. Infection with HIV has now been transformed into a manageable, chronic disease and this has allowed patients to live longer, healthier and more productive lives. Human Immune-Deficiency Virus (HIV) infection may further complicate the management of vulva cancer disease as patients are immunocompromised and may have difficulty in completing treatments prescribed. This study aims to identify and assess the outcomes, tolerances, toxicities and factors influencing treatment completion in both HIV positive and negative patients with vulva cancer treated at Tygerberg Academic Hospital. Study Design and Methods: This is a retrospective, observational, cross-sectional review of the factors influencing the completion of radical radiotherapy in the treatment of locally advanced cancer of the vulva. Patients are classified as either HIV positive or HIV negative. The period of the study was between 1st. January 2007 and 31st December 2012 and it was conducted at the Division of Radiation Oncology, Tygerberg Academic Hospital, Cape Town, South Africa. All the HIV positive patients were already on antiretroviral therapy at the outset. The disease and treatment characteristics are described as well as toxicities of treatment of patients undergoing radiotherapy and chemo-radiation. Treatment completion for the two groups is evaluated. The toxicities that led to treatment interruptions for these groups are also listed. Results: Of the 68 patients screened, 25 met inclusion criteria; of these patients, seven (28%) were HIV positive while the other 18 (72%) were negative. Vulva cancer patients infected with HIV presented at a younger age and with more locally advanced tumours compared to HIV negative patients. There is no statistically significant difference between the two groups in treatment completion rates and tumour failure rates. Conclusion: This retrospective study concludes that HIV positive patients with vulva cancer presented with a more locally advanced disease and at a younger age when compared to HIV negative patients. There was no statistically significant difference in overall therapeutic outcomes although cutaneous toxicities were more pronounced in the HIV positive subset. Chemo-radiotherapy sequentially or concurrently can be regarded as a standard of care in both HIV positive and negative patients provided that the HIV patients are on antiretroviral therapy. / AFRIKAANSE OPSOMMING: Nie beskikbaar

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Nursing Studies / Master / Master of Nursing

A dissertation submitted in partial fulfillment of the requirements for the degree Master of Science, Department of Medical Physics, school of Physics. Johannesburg 2017 / Objective: Intensity Modulated Radiation Therapy (IMRT) treatment techniques have evolved and the current level of interest in IMRT warrants a determination of the accuracy in delivering IMRT, in multiple institutions practicing IMRT. The aim of this study was to (a) perform inphantom end to end testing accuracy of 3D-Conformal Radiation Therapy (CRT) and different IMRT techniques, (b) check the dosimetric impact of dose delivered with deliberate offsets in the physical positioning of the phantoms using Cone-Beam Computed tomography (CBCT) and (c) use CBCT based IGRT to establish the extrinsic setup errors achieved between set-up and delivery of the planned dose on phantoms. Materials and Method: Studies were conducted in 3 institutions. An anthropomorphic phantom and a MatriXXEvolution with MULTICube were CTscanned and the CT slices were transferred to the treatment planning systems (TPSs). The transfered CT-slices were used to create a patient model and plans were created on hypothetical targets situated adjacent to an organ at risk (OAR). A virtual water phantom was also created in the same TPS and the same plans were created for verification purposes. The plans were transferred to a linear accelerator using a record and verify network system. The phantoms were positioned on the treatment couch and the dose delivered according to the treatment planning protocol. Statistical tools were used to analyse the delivered dose to the planed dose. Results and discussion: The end to end testing per institution was found to be less than 5% for dynamic IMRT and 2% for 3D-CRT when comparing planned to the measured dose. Comparison between institutions resulted in less than 7% dose difference for dynamic IMRT and 2% difference for 3D-CRT. Phantom setup errors were found to be less than 6 mm, 4 mm and 3 mm for the pretreatment, post-correction and post-delivery setups respectively. The dose difference delivered with a deliberate 3mm setup error was found to be less than 1%, 3% and 4% for the Catphan®, Pelvis and Head and Neck plans respectively. Conclusion: The overall accuracy of the treatment techniques at each institution was determined successfully. Independent phantom setups are likely to indicate the best possible setup precision as they are much easier to setup reproducibly than a patient with an internal margin for involuntary movement. Pre-treatment imaging was able to detect setup errors of 6 mm in Pelvis cases. Head and neck treatments delivered with advanced techniques are the most sensitive dosimetrically to small setup errors. / XL2018

Nasopharyngeal carcinoma (NPC) is an endemic malignant disease in Southern China. Intensity-modulated radiotherapy (IMRT) has been employed as a standard treatment for NPC because it delivers highly conformal dose distribution to target volumes and spares organs at risk (OARs). The success of radiotherapy depends on the accurate delivery of the planned doses throughout the treatment. This can be achieved with the help of advanced image-guided adaptive radiotherapy (IGART) such as kilovoltage (kV) cone beam computed tomography (CBCT) which can reduce the geometric setup uncertainty, monitor the intra-course anatomic and dosimetric changes and adjust the treatment plan. The aim of this thesis is to study the role of repeat imaging for NPC and the radiation dose from CBCT to patients. The objectives of this thesis are to evaluate the volumetric and dosimetric changes during a course of IMRT for loco-regionally advanced NPC patients with the contribution of repeat computed tomography (CT) and magnetic resonance imaging (MRI) scans; to quantify the absorbed dose, effective dose and the estimation of the additional risk of inducing fatal cancers from CBCT for NPC patients undergoing IMRT; and to compare the image quality of different head protocols. Nineteen loco-regionally advanced NPC patients treated with IMRT were recruited prospectively. Repeat CT and MRI were acquired at 30 and 50 Gy intervals. Recontouring of target volumes and OARs was based on the fused CT-MRI images. Hybrid plans with recontouring were generated. The volumetric and dosimetric changes were assessed by comparing the hybrid plans with the original plan. There was volume reduction of target volumes and parotid glands over the course of IMRT. Relative to the original plan, the hybrid plans demonstrated significantly higher dose to the target volumes with greater dose inhomogeneity, higher maximum doses to the spinal cord and brainstem, and higher medium doses to the parotid glands. The image quality and dosimetry on the Varian CBCT system between software Versions 1.4.13 (“new” protocol) and 1.4.11 (“old” protocol) were studied. A calibrated Farmer-type ionization chamber and a standard cylindrical Perspex CT dosimetry head phantom were used to measure the weighted CBCT dose index (CBCTDIw) of the Varian CBCT system. The absorbed dose of different organs was measured in a female anthropomorphic phantom with thermoluminescent dosimeters (TLD) and the total effective dose was estimated according to ICRP Publication 103. The dosimetry and image quality were studied for head-and-neck region and comparison was made between the new and old protocols. The values of the CBCTDIw, absorbed dose, effective dose of the new head protocol were much lower than the old head protocol in each imaging group. The additional fatal cancer risk from daily CBCT might be up to 1.6%. In conclusion, replanning with repeat imaging at 30 Gy is essential to keep a satisfactory dose to the target volumes and avoid overdosing the OARs for NPC patients. The new Varian CBCT provides volumetric information for image guidance with acceptable image quality and lower radiation dose. This CBCT gives a better standard for NPC patient daily setup verification. / published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

Nasopharyngeal cancer (NPC) is more common in the Southern China region than the rest of the world. Radiation therapy (RT) is the contemporary and standard treatment for nasopharyngeal cancer. Chronic complications arise from RT including hearing loss, xerostomia, trismus and dysphagia. Previous research has shown that dysphagia is prevalent in irradiated NPC patients. Radiation therapy techniques have improved in the last decade with the emergence of Intensity Modulated Radiation Therapy (IMRT), which allows more precise radiation beams directed at the tumor. In turn, it should also allow greater sparing of surrounding structures that are vital for preservation of swallowing function. This study was designed to investigate the difference in the degree of swallowing function preservation in two groups of irradiated NPC patients: the conventional RT and the IMRT group. Thirty patients with NPC who received RT from 1998 to 2006 in Queen Mary Hospital, Hong Kong were randomly recruited during the period from January to December 2011. Participant’s swallowing competence and its effect on the quality of life was assessed by videofluoroscopic swallowing study (VFSS) and by the MD Anderson Dysphagia Inventory, respectively. In comparison of swallowing performance with VFSS between the two groups, only one measure (Duration of Laryngeal Elevation) out of 13 showed significant difference on thin liquid and congee diet. Results from the MDADI did not show significant difference between the two groups. From the results, it was concluded that IMRT only resulted in subtle improvement in preserving the swallowing function as compared to conventional RT. One possibility is the subject self-compensation of their swallowing impairments that led to functionally similar performance despite their differences in the anatomy and physiology. Swallowing is a highly complex body function and no single parameter can be used to accurately quantify and characterize one’s swallowing function. The interaction between the anatomical and physiological impairments resulted from radiation therapy and the compensatory mechanism could not be clearly explained with this study. Future research could adopt a longitudinal approach such that the changes in NPC patients who received radiation therapy can be better understood. / published_or_final_version / Speech and Hearing Sciences / Master / Master of Philosophy

Materials/Methods: Ten patients who underwent thoracic SBRT with primary stage I (T1/2N0) lung cancer or oligometastatic lung lesion, with PTV diameter ≤ 5cm were selected and were immobilized with Easyfoam or Vac-Lock. Planned/treated with inspiratory breath-hold (25 seconds, 70 to 80% of vital capacity) assisted with Active Breathing Control (ABC). Four treatment plans: non-coplanar 3DCRT, coplanar static gantry IMRT, coplanar VMAT (FF) and VMAT (FFF) were generated. Field arrangements, either static fields or partial arcs (duration=20 sec) were used to avoid direct beam entry to contralateral lung. All plans were compared in terms of dosimetric performance included dose to PTV or organs at risk (OAR), high/low dose spillage, integral dose (body and lungs), dose delivery efficiency (MU/Gy) and estimated beam-on time (BOT) with reference to the RTOG 0813 protocol. Results: All plans complied with RTOG 0813 protocol. VMAT (FF/ FFF) techniques improved target coverage and dose conformity, with the highest conformity number (CN > 0.91), compared to IMRT (0.88) and 3DCRT (0.85). The control of high dose spillage (NT>105% and CI) for IMRT (3.04% and 1.08) and VMAT (FF/ FFF) (1.08/ 1.06% and 1.03/ 1.04) techniques were comparable (p > 0.05) and significantly better than 3DCRT (4.22% and 1.11, p < 0.005) technique. In addition, VMAT (FF/ FFF) techniques performed the best in controlling low dose spillage (D2cm and R50%) compared with IMRT (reduction: 4.7%, p=0.036 and >5.9%, p = 0.009) and 3DCRT (reduction: > 16.3%, p < 0.001 and > 10%, p = 0.002). Benefits of rapid and isotropic dose fall-off were shown from superior tissue sparing (reduction ranges from 3.2% up to 67%) of ipsilateral brachial plexus, skin (0-5mm), great vessels and ribs. Also lung V10, V12.5, esophagus and heart tend to receive lower dose with VMAT technique. The relatively lower integral dose to whole body (> 3Gy∙L reduction, p < 0.013) and ipsilateral lung (0.65Gy∙L reduction, p = 0.025) compared with 3DCRT, were associated with lower risk of radiation induced cancers. The MU/Gy and BOT were substantial lower for VMAT (FF) (22.4% and 32.4%) compared with IMRT. Apart from higher (7%) maximum skin dose, dosimetric performance for VMAT (FFF) was comparable with VMAT (FF), with advantages of further reduction of MU/Gy (1.8% lesser), partial arc numbers (from 12-14 arcs down to 8 arcs) and BOT (35% shortened), owing to the increased dose output with flattening filter removal. Conclusions: VMAT (FF and FFF) plans maintained IMRT equivalent plan qualities, simultaneously enhanced the delivery efficiency with shortened BOT. VMAT (FFF) further reduced the required arcs number and BOT, significantly minimized the intra-fraction motions and more tolerable to patient with long SBRT treatment duration. / published_or_final_version / Medicine / Master / Master of Medical Sciences

Stereotactic body radiotherapy (SBRT) is a promising treatment strategy for early–stage lung cancers. Conventional three–dimensional (3D) SBRT based on a static patient geometry is an insufficient model of reality, posing constraints on accurate Monte Carlo (MC) dose calculation and intensity–modulated radiotherapy (IMRT) optimization. Four–dimensional (4D) radiotherapy explicitly considers temporal anatomical changes by characterizing the organ motion and building a 4D patient model, generating a treatment plan that optimizes the doses to moving tissues, i.e., 4D dose (as opposed to the static 3D dose to tissue), and delivering this plan by synchronizing the radiation with the moving tumor. This thesis focuses on 4D robotic tracking lung SBRT. By recalculating the conventional 3D plan on the 4D patient model using MC simulation, it was found that 4D moving dose distributions could detect increase of normal tissue doses and complication probabilities (NTCP), and decrease of tumor dose and control probability. For one patient, the risk of myelopathy was estimated at 8% and 18% from the 3D equivalent path–length corrected (EPL) and the 4D MC doses, respectively. Such increased NTCP suggests that better estimations of different dosimetric quantities using 4D MC dose calculation are crucial to improve the existing dose–response models. Dosimetric error in 4D robotic tracking SBRT was found to be caused predominately by tissue heterogeneities, as assessed by the comparisons of the 4D moving tissue doses calculated using the conventional EPL and MC algorithms. At 3% tolerance level, our results indicated clinically significant dose prediction errors only in tumor but not in other major normal tissues. Furthermore, 4D tracking radiotherapy was found to have greater ability to limit the normal tissue volume receiving high to medium doses than the other advanced SBRT strategy combining volumetric–arc radiotherapy with 4D cone–beam CT verification. Invariant target motion was found to be an unrealistic assumption of 4D radiotherapy from the analysis of probability motion function (pmf) of motion data. Systematic and random variations of motion amplitude, frequency, and baseline were found to reduce the reproducibility of pmfs, on average, to just 30% for the principal motion of 3400 seconds. Experimental evaluations showed that systematic motion change reduced the gamma passing rate of radiochromic film measurements at 3mm distance–to–agreement and 3% dose difference criteria from 91% for 4D dose calculated with MCand EPL algorithms to 47% and 53% in the static object, respectively,. For moving target object, gamma passing rates of the 4D MC doses hardly changed with reproducible and non–reproducible motion (95% vs. 93%), and barely differed between conventional 3D and 4D MC doses (95% vs. 95% with reproducible, and 96% vs. 93% with non–reproducible motions). Distortions due to image artifacts and registration errors were consistently observed in the 4D dose distributions but not the 3D dose distributions. In conclusion, 4D Monte Carlo planning shall be considered for robotic target tracking only if robustness against uncertainties of patient geometry, and accuracy of 4DCT imaging and deformation registration are significantly improved. / published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

Breast cancer is the most common cancer among women worldwide. Millions of new breast cancer cases are diagnosed every year, accounting for one-tenth of all new cancer cases. Because of the proof of equivalent efficacy between breast-conserving therapy (BCT) plus radiotherapy and mastectomy, increasing number of patients received breast irradiation during the past three decades, and radiotherapy plays a more and more important role in managing breast cancer. With the advancement of technology, the radiotherapy treatment techniques changed from conventional wedged technique to intensity modulated radiotherapy (IMRT), resulting in an improvement in the dose homogeneity. Regardless of the treatment techniques, peripheral dose to the contralateral breast is inevitable. The possibility of the peripheral dose causing contralateral breast cancer (CBC) has re-attracted the interest. However, the variation of the peripheral dose with different treatment techniques has not been well identified. Thus this study aims to compare the contralateral breast dose from the primary breast irradiation using various radiotherapy treatment techniques and types of shielding. Six treatment plans by different treatment techniques, including paired physical wedges (PW-P), a lateral physical wedge only(PW-L), paired enhanced dynamic wedges (EDW-P), a lateral enhanced dynamic wedge only(EDW-L), field-in-field tangential opposing (TO-FiF), and inverse-planned intensity modulated radiotherapy (IMRT-IP), were generated using a female Rando phantom. The phantom was treated by all plans, and 15 metal oxide semiconductor field effect transistor(MOSFET)detectors on the surface and inside the contralateral breast were utilized for measuring the contralateral breast dose for each plan. Measurement was repeated with the application of 0.2, 0.3 and 0.5cm lead sheets or 0.5 and 1cm superflab (SF) on the TO-FiF to demonstrate the effect of shielding on the contralateral breast dose. The measured contralateral breast doses were: 2.05Gy for PW-P, 1.44Gyfor PW-L, 1.51Gyfor EDW-P, 1.52Gyfor EDW-L, 1.25Gyfor TO-FiF, and 1.17Gyfor IMRT-IP, corresponding to 2.35% to 4.11% of total dose. PW-P producedthe highest contralateral breast dose while IMRT-IP producedthe lowest. For the addition of shielding, the doses were: 1.25Gy for no shielding, 0.65Gy for 0.2cm lead, 0.61Gy for 0.3cm lead, 0.49Gy for 0.5cm lead, 0.76Gy for 0.5cm SF, and 0.72Gy for 1cm SF. Lead sheet with 0.5cm thickness most effectively reduced the contralateral breast dose by 60%.All techniques showed that the surface dose was much higher than the dose at depth, and the dose dropped exponentially from the surface to the internal. Low energy radiation constitutes a large portion of the contralateral breast dose, so all types of shielding could decrease the surface dose effectively, but not the internal dose. The radiation-induced CBC risks were estimated to be about 0.77% to 1.36%. To conclude, it is important that the contralateral breast dose to patients, especially those under 45, is maintained minimal. Therefore, TO-FiF or IMRT-IP are recommended to be the treatment of choices. The used of shielding, either lead or SF, is also advisable. / published_or_final_version / Diagnostic Radiology / Master / Master of Medical Sciences