Background Accurate delivery of radiotherapy is a paramount component of providing safe oncological care. Margins are applied when planning radiotherapy to account for subclinical tumour spread, physiological movement and set-up error. Set-up error is unique to each radiotherapy institution and should be calculated for each organ site to ensure safe delivery of treatment. Aim and setting The aim of this study is to calculate the random and systematic set-up error for a cohort of patients with intracranial tumours treated with 3D Conformal Radiotherapy at the Department of Radiation Oncology, Groote Schuur Hospital, South Africa. After obtaining above mentioned data the ideal CTV-PTV expansion margin was calculated using published CTV-PTV expansion margin recipes. Patients and methods The Electronic Portal Images (EPID) of 20 patients who met the inclusion criteria were compared to their Digitally Reconstructed Radiograph (DRR). The set-up error for each patient was measured after which the random (s) and systematic (S) set-up error for the study group could be calculated. With both these values known the CTV-PTV expansion margin could be determined. Results The largest error was in the Superior/Inferior (SI) direction, followed by the Medial/Lateral (ML) direction and least in the Anterior/Posterior (AP) direction with 87.7%, 76.2% and 91.6% of the errors in the ML, SI and AP directions respectively being less than 3mm. There was no error larger than 5mm in the ML or AP direction with 6.1% of the SI error larger than 5mm. The random and systematic error in all three directions for this patient cohort were less than 2mm conforming to acceptable standards of delivering safe radiotherapy. Using Stroom's margin recipe (2S + 0.7s) a CTV-PTV expansion margin of 5mm can safely be applied for this patient cohort. Conclusion When treating patients with intracranial tumours at Groote Schuur Hospital the CTV-PTV expansion margin can safely be reduced from 1cm to 5mm.

It is generally accepted that energy is required for repair of radiation-induced damage in living cells. Some of this energy is probably provided by adenosine triphosphate (ATP), which is derived from energy substrates via energy metabolism. This dissertation follows two general avenues. The first explores the effect of radiation on ATP levels after irradiation of cells. The second investigates the effect of inhibitors of certain pathways associated with energy metabolism on radiation response. It was proposed that ATP levels might be raised after irradiation in some systems and that this rise in ATP might be due to compensatory mechanisms related to repair. Experiments were conducted using B16 melanoma cells in vitro and using normal murine liver and CaNT tumours in vivo. ATP concentration was measured in extracts of these cells after irradiation using the luciferase-luciferin method. No major changes from unirradiated controls were found. Several types of substrates exist from which cells can derive energy, including glucose and glutamine which are initially metabolised via glycolysis and glutaminolysis, respectively, before their products are further metabolised in respiration. Since energy is necessary for repair of radiation damage, it has been proposed that the inhibition of energy metabolism might alter the radiation response of cells. An inhibitor of glycolysis, 2-deoxyglucose (2DG), and an inhibitor of glutaminolysis, aminooxyacetic acid (AOA), were administered to CHO cells in vitro to determine the effects of these substances on cellular radiosensitivity and repair. Repair was assessed by means of a split radiation dose experiment. The design of such an experiment required that cells be exposed to inhibitory test media for different times between two fractions of radiation. Any changes in clonogenic survival with time between tween fractions could, therefore be as a result of repair effects or as a result of changes in radiosensitivity. A method of estimating and subtracting the effects of radiosensitivity to make conclusions concerning repair is presented and discussed. Most combinations of 2DG, AOA, glucose omission and glutamine omission in culture media resulted in reductions in repair rate but the extent of repair was found to vary from one medium variation to the next. In addition, the effects of various culture media on glycolysis/PPP (glycolysis/pentose phosphate pathway) and glutaminolysis were investigated by determining the production of CO2 and lactate from radiolabelled-glucose and -glutamine substrates. It was apparent that the presence of either of the inhibitors, 2DG or AOA, could inhibit the activity of glutaminolysis and reduce oxygen consumption. 2DG was shown to inhibit glycolysis/PPP but AOA was shown to stimulate glycolysis/PPP, suggesting a regulatory link between glutaminolysis and glycolysis/PPP. The presence of either inhibitor resulted in a reduction in the rate of radiation damage repair. The medium which had the most significant effect in respect of repair inhibition and increased radiosensitivity was medium lacking both glucose and glutamine and containing both 2DG and AOA. This medium was shown to inhibit oxygen consumption and to result in a depression of both cellular glycolysis/PPP and glutaminolysis. The effect of 2DG on the rate of growth and radiation induced growth delay of three murine tumours in vivo was assessed. 2DG alone inhibited the growth of B16 tumours. However, 2DG alone produced little if any change in the rates of growth of Fib/T tumours and rhabdomyosarcomas but the combination of 2DG and AOA produced an inhibition of growth in the Fib/T tumour. 2DG appeared to enhance the effects of radiation in the Fib/T and B16 tumours but not in the rhabdomyosarcoma, although, in the Fib/T, the combination of AOA, 2DG and radiation was less effective in inhibiting tumour growth than was radiation alone. The effects of radiation and 2DG did not appear to be additive in the Fib/T tumour and the B16 tumours which may imply an influence of 2DG on repair or radiosensitivity. This work suggests that the effects of radiation can be altered by manipulation of metabolic pathways associated with the supply of energy. However, a complex interaction of pathways is probably also involved and it is the detail of this interaction which may partially determine the severity of radiation response.

OBJECTIVES: To retrospectively review the patient demographics, disease profile and treatment outcomes of paediatric patients treated for ependymoma at our institution. STUDY DESIGN AND METHODS: 51 eligible patients were treated between 1980 and 2013. The median age at presentation was 6 years. The majority of patients were male (66,7%), had infratentorial tumours (62,7%) and had low-grade tumours (70,6%). Gross total resection (GTR) was achieved in 22 patients (43,1%). Thirtyeight patients received adjuvant radiotherapy (76,5%) and 10 (19,6%) received adjuvant chemotherapy. RESULTS: The 5-year overall survival (OS) was 63,3 % (median follow up of 46 months). The 5 year progression free survival (PFS) was 50,70%. Seventeen (33,3%) patients experienced treatment failure, of which 13 (76,5%) represented local failure. The median time to first relapse was 20 months. The 5 year PFS for children > 3 was 50,0 % and 27,7% for children ≤ 3 years of age (p = 0.0356). GTR had a superior 5- year OS of 73,9% over subtotal resection with a value of 56,7% (p = 0.0016). Similarly an improved 5-year PFS of 70,3% versus 29,1% was observed with GTR over subtotal resection (p = <0.0001). Patients who received adjuvant radiotherapy (RT) had significantly better outcomes than those in whom RT was not given (p = <0.0001, 5 year OS of 69,7% versus 37,5%). CONCLUSION: This review confirms the finding that GTR is associated with improved outcomes and that adjuvant radiation therapy positively impacts survival. The worse outcomes in the younger age group requires further evaluation and possible change in treatment protocol for this group of patients.

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Includes bibliographical references. / Whilst the benefit of adjuvant radiotherapy in gastric cancer is known, the optimal means of delivery, including two dimensional conventional, three dimensional conformal radiotherapy, intensity modulated radiotherapy and volumetric modulated arc therapy is less certain. The purpose of this study is to assess and compare volumetric modulated arc therapy (VMAT) and three dimensional conformal radiotherapy (3DCRT) plans in adjuvant radiation of gastric cancer.

Background: Predictive factors for long-term outcomes in osteosarcoma patients are still controversial. There is no literature available regarding these factors in a patient population in a developing country. Objectives: To determine the outcome of treatment of osteosarcoma patients treated at Groote Schuur Hospital from 1990-2012 in terms of local control (LRC), disease free survival (DFS) and overall survival (OS) and to determine the value of suggested predictive factors in this population. Patients and methods: Retrospective review of all patients diagnosed and treated with osteosarcoma at Groote Schuur Hospital between 1990 and 2012, considering OS, DFS and LC. This review assesses the significance of suggested predictive factors from other studies, namely, HIV status, age at diagnosis, site of primary disease, type of chemotherapy used, response to chemotherapy and type of surgery in terms of OS, DFS and LC. Results: Forty-three patients with histologically confirmed osteosarcoma were treated at Groote Schuur Hospital between 1990 and 2012. Median 5 year OS was 57.8%. On univariate analysis, the site of disease was the only statistically significant predictive factor for prognosis. Conclusion: On univariate analysis, patients with axial disease have a worse predicted prognosis than those with primary disease in their extremities. The long-term outcome in our local clinical setting correlates favourably with the available international data. Due to the limited number of patients in the review, further research into HIV status, age, type of chemotherapy, type of surgery and their predictive value for prognosis in our patients with osteosarcoma is warranted.

Objective: A retrospective review was conducted to ascertain whether there are differences in outcome or complications between node-negative patients with stage IB cervical cancer who were treated with adjuvant standard field as opposed to small pelvic field radiotherapy (RT). Study design: A retrospective observational study of patients with stage IB cervical cancer treated with radical surgery between 1984 and 2010 at Groote Schuur Hospital, Cape Town, South Africa. Two different pelvic radiation field sizes were used for adjuvant post-operative RT in node-negative patients during this period: standard whole pelvic fields (WPF), or with reduced-size, "small pelvic field" (SPF) RT since 1991. These two methods reflect changes in protocol over the period of this review. Cisplatin given concurrently with radiation has been used since 1999. Cancer control and grade 3 and 4 toxicities were compared between the two groups. The aim of this study was primarily to examine whether adjuvant SPF RT is a safe approach. A literature review was conducted on the subject of post-operative adjuvant RT, especially in node-negative patients; one aim was to discover how widely the SPF approach is used throughout the world. There was no indication in the literature that this approach has been used elsewhere in South Africa. Results: The SPF technique was first advocated by Prof Neville Hacker in Australia in 1991. The first publication by his group on SPF was in 1999, followed by several subsequent retrospective reports from Asian centers. In the current audit study, 31 patients were found in the WPF group, and 56 in the SPF group. The overall 5-year survival rate was 85%. No significant differences in survival rates were found between the WPF and SPF groups (log rank p=0.67) It was found that relapse patterns did not differ between the two groups and the same applied to the crude grade 3-4 treatment morbidity rates, although two patients in the WPF group (6%) died from their complications. Conclusions: The expected benefit of the SPF approach, which targets the central pelvic tumour bed, is a reduction in small bowel morbidity and lymphoedema. It is not possible to conclude from this study whether the SPF technique is unsafe by increasing out-of-field pelvic relapses, or whether it truly reduces complications. The literature review reveals that most studies of SPF involved relatively few patients and events were infrequent, whether recurrences or morbidity. A randomized controlled trial could theoretically settle this issue but it seems unlikely ever to be performed as a large sample size would be required. Intermittent single institution, or multi-institutional pooled comparisons, with historical WPF controls seem to be the best option.

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Objectives: The objective of this study was to compare the outcome of two cohorts of patients with anal squamous carcinoma treated with split course chemoradiation as opposed to continuous chemoradiation at Groote Schuur Hospital. Demographics including age at diagnosis, gender and HIV status were reviewed. The stage at diagnosis, the acute treatment toxicities and all surgical procedures were noted. The outcomes included complete response rate, local control rate, loco-regional failure free survival, colostomy-free survival and overall survival. Design and Methods: The data was obtained from patient records of all patients with histologically confirmed anal squamous cell carcinoma seen and registered at the Department of Radiation Oncology at Groote Schuur Hospital. Patients included were those treated with radical intent that presented between the years of 2008 and 2012. This data was then compared with a similar study performed between 2000-2 004-. Results: A total of 72 patients diagnosed with anal squamous carcinoma were seen at Groote Schuur Hospital in the 5-year period, of which 4-0 patients fitted the criteria for this study. The median age was 53 years, with a slight male preponderance (55%) and 27.5% tested HIV positive. A total of 68% of patients had T3 and T4- disease, with 4-2.5% node positive disease. The complete response rate was 60%, the local control rate was 52.5% and the loco-regional failure free survival at 5 years was 56%. The colostomy-free survival was I-"4-% and the 5-year overall survival was 4-0.67%. Haematological, gastrointestinal and skin toxicities were reviewed and the most common acute side effect experienced was grade 2[32.5%] and grade 3[4-15%] skin toxicity. Conclusion: The patient characteristics and treatment toxicities are in keeping with previous study findings. However, complete response rate and overall survival were less than expected. Although there was no statistically significant difference in overall survival between the two cohorts of patients, there was a definite trend to inferior treatment outcomes of those patients treated with continuous chemoradiation. We propose radiation dose escalation for future treatment of patients presenting with anal carcinoma at Groote Schuur Hospital.

Includes abstract. Includes bibliographical references.