Radiation Oncology

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Audits of oncology units – an effective and pragmatic approach
(Health and Medical Publishing Group, 2017) Abratt, R. P.; Eedes, D.; Bailey, B.; Salmon, C.; Govender, Y.; Oelofse, I.; Burger, H.
Background. Audits of oncology units are part of all quality-assurance programmes. However, they do not always come across as pragmatic and helpful to staff. Objective. To report on the results of an online survey on the usefulness and impact of an audit process for oncology units. Methods. Staff in oncology units who were part of the audit process completed the audit self-assessment form for the unit. This was followed by a visit to each unit by an assessor, and then subsequent personal contact, usually via telephone. The audit self-assessment document listed quality-assurance measures or items in the physical and functional areas of the oncology unit. There were a total of 153 items included in the audit. The online survey took place in October 2016. The invitation to participate was sent to 59 oncology units at which staff members had completed the audit process. Results. The online survey was completed by 54 (41%) of the 132 potential respondents. The online survey found that the audit was very or extremely useful in maintaining personal professional standards in 89% of responses. The audit process and feedback was rated as very or extremely satisfactory in 80% and 81%, respectively. The self-assessment audit document was scored by survey respondents as very or extremely practical in 63% of responses. The feedback on the audit was that it was very or extremely helpful in formulating improvement plans in oncology units in 82% of responses. Major and minor changes that occurred as a result of the audit process were reported as 8% and 88%, respectively. Conclusion. The survey findings show that the audit process and its self- assessment document meet the aims of being helpful and pragmatic.
Automated radiation treatment planning for cervical cancer
(Elsevier, 2020-10) Rhee, Dong Joo; Jhingran, Anuja; Kisling, Kelly; Cardenas, Carlos; Simonds, Hannah; Court, Laurence
The radiation treatment-planning process includes contouring, planning, and reviewing the final plan, and each component requires substantial time and effort from multiple experts. Automation of treatment planning can save time and reduce the cost of radiation treatment, and potentially provides more consistent and better quality plans. With the recent breakthroughs in computer hardware and artificial intelligence technology, automation methods for radiation treatment planning have achieved a clinically acceptable level of performance in general. At the same time, the automation process should be developed and evaluated independently for different disease sites and treatment techniques as they are unique from each other. In this article, we will discuss the current status of automated radiation treatment planning for cervical cancer for simple and complex plans and corresponding automated quality assurance methods. Furthermore, we will introduce Radiation Planning Assistant, a web-based system designed to fully automate treatment planning for cervical cancer and other treatment sites.
Automated treatment planning of postmastectomy radiotherapy
(American Association of Physicists in Medicine, 2019-05-11) Kisling, Kelly; Zhang, Lifei; Shaitelman, Simona F.; Anderson, David; Thebe, Tselane; Yang, Jinzhong; Balter, Peter A.; Howell, Rebecca M.; Jhingran, Anuja; Schmeler, Kathleen; Simonds, Hannah; Du Toit, Monique; Trauernicht, Christoph; Burger, Hester; Botha, Kobus; Joubert, Nanette; Beadle, Beth M.; Court, Laurence
Purpose: Breast cancer is the most common cancer in women globally and radiation therapy is a cornerstone of its treatment. However, there is an enormous shortage of radiotherapy staff, especially in low- and middle-income countries. This shortage could be ameliorated through increased automation in the radiation treatment planning process, which may reduce the workload on radiotherapy staff and improve efficiency in preparing radiotherapy treatments for patients. To this end, we sought to create an automated treatment planning tool for postmastectomy radiotherapy (PMRT). Methods: Algorithms to automate every step of PMRT planning were developed and integrated into a commercial treatment planning system. The only required inputs for automated PMRT planning are a planning computed tomography scan, a plan directive, and selection of the inferior border of the tangential fields. With no other human input, the planning tool automatically creates a treatment plan and presents it for review. The major automated steps are (a) segmentation of relevant structures (targets, normal tissues, and other planning structures), (b) setup of the beams (tangential fields matched with a supraclavicular field), and (c) optimization of the dose distribution by using a mix of high- and low-energy photon beams and field-in-field modulation for the tangential fields. This automated PMRT planning tool was tested with ten computed tomography scans of patients with breast cancer who had received irradiation of the left chest wall. These plans were assessed quantitatively using their dose distributions and were reviewed by two physicians who rated them on a three-tiered scale: use as is, minor changes, or major changes. The accuracy of the automated segmentation of the heart and ipsilateral lung was also assessed. Finally, a plan quality verification tool was tested to alert the user to any possible deviations in the quality of the automatically created treatment plans. Results: The automatically created PMRT plans met the acceptable dose objectives, including target coverage, maximum plan dose, and dose to organs at risk, for all but one patient for whom the heart objectives were exceeded. Physicians accepted 50% of the treatment plans as is and required only minor changes for the remaining 50%, which included the one patient whose plan had a high heart dose. Furthermore, the automatically segmented contours of the heart and ipsilateral lung agreed well with manually edited contours. Finally, the automated plan quality verification tool detected 92% of the changes requested by physicians in this review. Conclusions: We developed a new tool for automatically planning PMRT for breast cancer, including irradiation of the chest wall and ipsilateral lymph nodes (supraclavicular and level III axillary). In this initial testing, we found that the plans created by this tool are clinically viable, and the tool can alert the user to possible deviations in plan quality. The next step is to subject this tool to prospective testing, in which automatically planned treatments will be compared with manually planned treatments.
Breast cancer diagnosed in women with the Human Immune-Deficiency Virus (HIV)
(Stellenbosch : Stellenbosch University, 2014-12) Langenhoven, Lizanne; Barnardt, Pieter; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiation Oncology.
ENGLISH ABSTRACT: Background: HIV is the defining pandemic of our era, with an estimated 5.9 million people infected in South Africa according to World Health Organization (WHO) estimates for 2011. The expression and treatment of non-AIDS defining cancers has become an important consideration in this cohort, as antiretroviral therapy (ART) has prolonged survival in a subgroup previously at risk of early mortality. Study Design: A retrospective cohort study of all women seen at the Combined Breast Cancer Clinic at Tygerberg Hospital between January 2010 and December 2011, stratified into three subgroups based on HIV status. Methods: Of the 816 patients screened, 586 met inclusion criteria; of which 31 (5.3%) patients were HIV positive, 420 (71.7%) HIV negative, and 135 (23%) had an unknown HIV status. The disease phenotype was described in each subgroup, as well as toxicities associated with standard chemotherapy regimens, with an emphasis on completion rates of systemic cytotoxic treatment. The insult of cytotoxic therapy to the CD4 count was described for this cohort. Results: Women with HIV had a statistically significant (p<0.001) younger age at presentation of breast cancer with a median age of 42 years (range 39 – 45 years) in comparison with the HIV-negative cohort with a median age of 54 years (range 53 – 55 years) . No difference was detected in disease phenotype when stage at presentation (p=0.7874), histological subtype (p=0.3375), grade of differentiation (p=0.8297), nodal involvement (p=0.0998) or hormone-receptor positivity (p=0.6285) was considered. Completion rates for systemic chemotherapy were excellent (>90%) regardless of HIV-status and no statistically significant toxicity was observed. The median CD4 count at diagnosis was 477 cells/μL (range 234 – 807 cells/μL), with a nadir value of 333 cells/μL (range 62 – 713 cells/μL), representing a decrease of 30.2% during treatment. One case of suspected treatment-related mortality was recorded. Conclusion: This retrospective study confirmed that women infected with HIV had a younger age at breast cancer diagnosis when compared to women with a negative HIV-status. No difference in disease phenotype could be demonstrated for women with HIV, denoting the coexistence of two common chronic diseases. Chemotherapy was tolerated well, but caused a median decline in CD4-count of 30% during treatment.
Cell biological responses of prostatic tumour cell lines to irradiation and anticancer drugs
(Stellenbosch : Stellenbosch University, 2003-12) Serafin, Antonio Mendes; Bohm, E. L. J. F.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Radiation Oncology.
ENGLISH ABSTRACT: The "classic" prostate cell lines, DU145, PC-3 and LNCaP, have served as a valuable cell biological model for research into prostate cancer. However, their relevance may be limited because they derive from metastatic, and not from primary normal and tumour epithelium. The cell lines (1532T, 1535T, 1542T, 1542N and BPH-l) have been derived from primary benign and malignant human tumour prostate epithelium and may be more representative. Using these cell lines I have examined the role of basic cell damage responses (repair, checkpoint activation, apoptosis and associated signalling proteins, and the influence of androgen status) in cell inactivation, and its relevance to treatment. Numerous studies have suggested that loss of p53 function leads to resistance to chemotherapeutic agents and irradiation. It is shown here that the p53-inactive cell lines are, in fact, the most sensitive to chemotherapeutic agents such as etoposide, vinblastine and estramustine, whilst the p53 wild-type cell line, LNCaP, is the most radiosensitive. Notwithstanding the effects of p53 degradation by the HPV -16 E6 viral protein, the results on chemosensitivity raises the possibility that different chemotherapeutic agents may have different p53-dependent effects in different tumour cells. Androgen deprivation is demonstrated to sensitise prostate cancer cells to chemotherapeutic agents and it is shown that the hormone independent cell lines are the most chemosensitive. The LNCaP cell line displayed an increased resistance to apoptosis induced by etoposide and gamma irradiation, suggesting that androgens are capable of protection against both these DNA damaging agents. The major factors determining radiosensitivity in human tumour cell lines are known to be DNA double-strand break (dsb) induction and repair. In the prostate cell lines I find that cellular radiosensitivity correlates with the number of DNA double-strand breaks measured within 2 hours of irradiation, and that the more radioresistant cell lines show better repair competence. Conclusions as to the influence of androgen dependence on radiosensitivity and repair are not possible at this stage since only the LNCaP cell line was androgen sensitive. The fact that the 2 hour repair period can separate radiosensitive from radioresistant cells in 2 groups of human tumour cell lines highlights the role of non-homologous end-joining repair. This has implications for therapy, and is consistent with the clinical observation that prostate tumours can be successfully controlled by low dose rate-brachytherapy. To evaluate the role of apoptosis, cells were exposed to TD50 concentrations of chemotherapeutic drugs, and 60Co y-irradiation. Apoptosis was found to be low, overall, and ranged from 0.1% - 12.1%,3.0% - 6.0% and 0.1% - 8.5% for etoposide, estramustine and vinblastine, respectively. The percentage of cells undergoing druginduced apoptosis was, on average, higher in the tumour cell lines than in the normal cell lines. Gamma irradiation-induced apoptosis levels ranged from 1.3% - 7%. The LNCaP cell line yielded the lowest percentage of apoptotic cells after exposure. The l532T cell line yielded the highest percentage of apoptotic cells after exposure. Apoptotic propensity did not rank the cell lines according to their radiosensitivity. Immunoblotting demonstrated that the apoptosis-associated proteins, bax and bcl-2, are expressed at a basal level in all the cell lines tested, but no increase was detected after exposure to TD50 doses of etoposide, vinblastine and estramustine. The ratio of bax and bcl-2 also was not altered by DNA damage. No evidence was found that a correlation may exist between reproductive cell death and the expression of genes which control apoptosis. My results show that apoptosis is not a major mechanism of drug- or radiation-induced cell death in prostate cell lines. In conclusion, loss of p53 function and loss of androgen dependence was not found to be correlated with resistance of tumours to chemotherapeutic drugs. Cellular radiosensitivity was found to be correlated with the number of DNA double-strand breaks remaining after 2 hours of repair. The more radioresistant cell lines showed better repair competence. Apoptosis and genes affecting apoptosis, such as p53 and members of the bcl-2 family, do not seem to contribute significantly to the sensitivity of prostate cancer cells to anticancer drugs and irradiation.
Chemotherapy administration standards and guidelines : the development of a resource document
(AOSIS, 2018-08-13) Eedes, David J.; Bailey, Belinda; Burger, Henriette
There are no nationally recognised guidelines for the handling and administration of chemotherapy in South Africa. The Independent Clinical Oncology Network’s Chemotherapy Administration Standards and Guidelines Resource Documentwas developed over 2 years and first introduced at a South African international oncology conference in 2017. A working group consisting of oncologists and oncology nurses was set up to address this deficiency. Pragmatic guidelines suitable to a wide range of local chemotherapy administration practices were developed using an iterative, multidisciplinary, collaborative process. The consensus was that these guidelines should be appropriate to the South African context. Safety, standard operational procedures, recommended professional competencies and training were central to the document. Guidelines for prescribing, storing, mixing, dispensing, administering and disposing of chemotherapy were included. Patient consent and involvement, patient and staff safety, recommended professional competencies, management of accidents and errors, error reporting and local legal requirements are dealt with in detail. The hope is that these guidelines will be used as a resource document for South African chemotherapy practices, both public and private. The document is supported by standard operating procedures and action steps. These were developed to promote the use of the guidelines and to support pragmatic quality assurance measures at practice level. These standards and guidelines will be regularly updated, based on needs identified and deficiencies noted.
Descriptive epidemiological study of head and neck cancers at a single institution in Southern Africa
(Stellenbosch : Stellenbosch University, 2019-12) Naidoo, Komeela; Simonds, Hannah M.; Afrogheh, A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiation Oncology.
ENGLISH SUMMARY : Head and Neck Cancers (HNCs) constitute a major public health concern worldwide. The incidence is approximately two times more in less-developed regions as compared to more developed regions. The estimated incidence in sub-Saharan Africa is 27593 per 100000 with a cumulative risk of 0.66. We evaluated patient demographics, risk factors, tumours characteristics, prognostic factors, disease stage, treatment intent and treatment modality in a cohort of patients with HNC in Cape Town, SA. Records of all HNC patients that presented to Tygerberg Hospital oncology department between 1 January 2015 and 31 December 2017 were reviewed. The following variables were described: patient demographics, which include age, sex, HIV status, and socio-economic status as well as tumour characteristics, risk factors, treatment intent and treatment modalities. Data was collected from 854 patients seen between 2015 and 2017. There were 603 (71%) male and 251 (29%) female. The male to female ratio was 2.4:1. The age range was 10-89 years (median age 58 years). Smoking was a risk factor in 737 (86.3%) and alcohol in 634 (74.2%) of patients. Of the 167 patients with oropharyngeal primaries, 16 (9.58%) patients had p16 positive, 78 (46.70%) were p16 negative and the p16 status was unknown in 73 (43.7%). The most common site was the oral cavity (n=320) and the most common sub-site was the anterior tongue (n=137). Eleven patients had two separate primaries at the time of diagnosis. In total, 466 patients (53.87%) presented with locally advanced, stage IVA disease. The median age of diagnosis, the most predominate primary site; histological subtype and stage at presentation were consistent with that reported in the literature. We have demonstrated that the majority of patients present at a late stage, with locally advanced disease. This together with the predominate risk factors of smoking and alcohol consumption is a potential target for health campaigns and awareness programmes. This cohort will be followed up for treatment outcomes and survival rates.
Establishing a multidisciplinary AIDS-associated Kaposi’s sarcoma clinic : patient characteristics, management and outcomes
(Health & Medical Publishing Group, 2018-12) Burger, H.; Ismail, Z.; Taljaard, J. J.
Background: Kaposi’s sarcoma (KS) typically occurs in the setting of immunodeficiency and specifically in the presence of HIV infection, when it is called AIDS-associated KS (AIDS-KS). In spite of impressive gains in the South African (SA) antiretroviral therapy (ART) roll-out programme since 2004, AIDS-KS still causes significant morbidity and mortality, and the treatment of advanced disease can be challenging owing to the centralisation of oncology services and the high incidence of concurrent infections. In 2014, a multidisciplinary AIDS-KS clinic (MKSC) was established at Tygerberg Hospital, Cape Town, with the goal of optimising management of AIDS-KS patients. Objectives: To report on the characteristics and outcomes of patients seen during the first 6 months after the inception of the MKSC. Methods: A retrospective observational study was performed of all new cases referred to the MKSC from February to August 2014. Results: Forty-two patients were included in the study. The median age was 34 years (range 20 - 60). Forty-one patients were on ART at time of diagnosis or were initiated by a median of 3 months after diagnosis. The median CD4+ count before diagnosis was 147 cells/µL (range 4 - 811). The HIV viral load was undetectable in 22 cases (52.4%). Thirty-eight patients (90.5%) were classified as AIDS Clinical Trials Group (ACTG) poor risk, 10 patients (23.8%) had visceral KS, 14 patients (33.3%) were on tuberculosis (TB) treatment at time of presentation, and 22 patients (52.4%) received oncological therapy in addition to ART. After median follow-up of 25.6 months, 2-year overall survival (OS) was 61.1%. On univariate analysis, factors significantly associated with poor 2-year OS included ACTG S1 stage (S = systemic illness), visceral KS, being on TB treatment, and Eastern Cooperative Oncology Group performance status score >2. In the T1 (T = tumour extent) subgroup, receiving chemotherapy was significantly associated with improved 2-year OS. Conclusions: Advanced AIDS-KS significantly affects young people in the Western Cape Province of SA despite 10 years of ART roll-out. There is a high prevalence of concomitant TB infection that could adversely affect adherence and response to treatment. Despite advanced disease at presentation and palliative treatment intent, survival outcomes are encouraging and seem to be positively affected by the increased use of chemotherapy. A multidisciplinary approach to diagnosis, staging and treatment and the exploration of prognostic indices specific to the sub-Saharan setting would be valuable in designing appropriate treatment algorithms.
Examination of irradiated neuroblastoma and neuroepithelial cell lines for the interrelationship between cell survival, micronucleation, apoptosis and DNA repair
(Stellenbosch : Stellenbosch University, 2000-12) Akudugu, John Mbabuni; Bohm, E. L. J. F.; Slabbert, J. P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiation Oncology.
ENGLISH ABSTRACT: Predictive assays are of key importance in clinical radiotherapy, chemotherapy and toxicology. Prior to exposing malignant tissues to irradiation or drugs in the clinic, a good understanding of the damage response to the cytotoxic agent is required. Such information is necessary for effective planning and treatment. Regrettably however the methods which detect DNA damage, namely micronucleus, apoptosis and DNA repair assays do not rank cells according to their intrinsic survival response to cytotoxic agents. The application of predictive assays based on micronuclei and apoptosis in the clinic therefore remains unreliable. Using a panel of 7 neuroblastoma and 6 neuroepithelial cell lines, it is shown that damage assays also do not rank cell lines according to cell survival. However, radiosensitivity can be reconstructed from micronuclei formation and apoptosis, and a new parameter, cell death due to small deletions, chromosome aberrations and misrepair. The interrelationships between radiation-induced micronuclei, apoptosis and repair is complex and varies between cell lines. Micronuclei formation and apoptosis are exponentially interrelated. This suggests that these cell inactivation pathways are strongly correlated. Evidence exists to show that the expression of apoptosis and micronuclei is influenced by the extent of DNA double-strand break repair within the first 2 hours after irradiation. Cell lines which repair more damage in the first 2 hours express more micronuclei and less apoptosis. Micronuclei formation and apoptosis and are not significantly correlated with the 20 hours slow repair component. There is however a strong correlation between 20 hours of repair and radiosensitivity, with the more radioresistant cell lines being more repair proficient. This suggests that the 2 hours (fast) DNA repair component is more error prone, and that cells lines repairing more damage late after irradiation tend to show better survival. In conclusion, micronuclei formation, apoptosis and DNA repair are strictly cell type specific and are not suitable for predicting radiosensitivity in terms of cell survival. However, these assays are very useful for studies on the influences of dose modifying agents i.e. oxygen tension, radiation modality, pH, cytotoxic sensitisers and radiation protectors which alter cellular responses and provide insight into damage mechanisms.
Fully automatic treatment planning for external-beam radiation therapy of locally advanced cervical cancer : a tool for low-resource clinics
(American Society of Clinical Oncology, 2019) Kisling, Kelly; Zhang, Lifei; Simonds, Hannah M.; Fakie, Nazia; Yang, Jinzhong; McCarroll, Rachel; Balter, Peter; Burger, Hester; Bogler, Oliver; Howell, Rebecca; Schmeler, Kathleen; Mejia, Mike; Beadle, Beth M.; Jhingran, Anuja; Court, Laurence
PURPOSE: The purpose of this study was to validate a fully automatic treatment planning system for conventional radiotherapy of cervical cancer. This system was developed to mitigate staff shortages in low-resource clinics. METHODS: In collaboration with hospitals in South Africa and the United States, we have developed the Radiation Planning Assistant (RPA), which includes algorithms for automating every step of planning: delineating the body contour, detecting the marked isocenter, designing the treatment-beam apertures, and optimizing the beam weights to minimize dose heterogeneity. First, we validated the RPA retrospectively on 150 planning computed tomography (CT) scans. We then tested it remotely on 14 planning CT scans at two South African hospitals. Finally, automatically planned treatment beams were clinically deployed at our institution. RESULTS: The automatically and manually delineated body contours agreed well (median mean surface dis- tance, 0.6 mm; range, 0.4 to 1.9 mm). The automatically and manually detected marked isocenters agreed well (mean difference, 1.1 mm; range, 0.1 to 2.9 mm). In validating the automatically designed beam apertures, two physicians, one from our institution and one from a South African partner institution, rated 91% and 88% of plans acceptable for treatment, respectively. The use of automatically optimized beam weights reduced the maximum dose signiﬁcantly (median, −1.9%; P , .001). Of the 14 plans from South Africa, 100% were rated clinically acceptable. Automatically planned treatment beams have been used for 24 patients with cervical cancer by physicians at our institution, with edits as needed, and its use is ongoing. CONCLUSION: We found that fully automatic treatment planning is effective for cervical cancer radiotherapy and may provide a reliable option for low-resource clinics. Prospective studies are ongoing in the United States and are planned with partner clinics.
Gestational trophoblastic neoplasm and women living with HIV and/or AIDS
(AOSIS Publishing, 2015-07-03) Barnardt, Pieter; Relling, Martha
The 2011 World Health Organization global report on HIV and/or AIDS estimated that sub-Saharan Africa comprised 67% of the global HIV burden, with a current estimate of 5.9 million cases in South Africa. Since the introduction of antiretroviral therapy, there has been an increase in the incidence of non-AIDS-defining cancers. Gestational trophoblastic neoplasm (GTN) is a rare pregnancy-related disorder with an incidence ranging from 0.12–0.7/1000 pregnancies in Western nations. The overall cure rate is about 90%. Response to treatment for GTN is generally favourable; but the sequelae of HIV and/or AIDS, the resultant low CD4 counts, comorbidities, poor performance status and the extent of metastatic disease in patients receiving chemotherapy, compromise the prognosis and survival.
Hypofractionation and prostate cancer : a good option for Africa?
(AOSIS, 2017-08-29) Incrocci, Luca; Heijmen, Ben; Kupelian, Patrick; Simonds, Hannah M.
Cancer is an emerging public health problem in Africa. According to the World Health Organization, the numbers will be doubled by 2030 because of the ageing and the growth of the population. Prostate cancer is the most common cancer among men in most African countries. Radiotherapy machines are extremely limited in Africa and therefore prostate cancer in Africa is mostly managed by urologists. However, for a large proportion of prostate cancer patients, external-beam radiotherapy (EBRT) will be the treatment of choice in Africa because of limitations of surgical expertise in many countries. The disparity between the α/β ratio for late complications and the low α/β ratio for prostate cancer widens the therapeutic window when treating prostate cancer with hypofractionation. Because of the reduced number of treatment days, hypofractionation offers economic and logistic advantages, reducing the burden of the very limited radiotherapy resources in most African countries. It also increases patient convenience. A misleading assumption is that high-level radiotherapy is not feasible in low-income countries. The gold standard option for hypofractionation includes daily image-guided radiotherapy with 3–4 implanted gold fiducials. Acceptable methods for image guidance include ultrasound and cone-beam computed tomography (CT). CT-based treatment planning with magnetic resonance imaging fusion allows for accurate volume delineation. Volumetric modulated arc therapy or inversely planned intensity modulated radiotherapy is the ideal for treatment delivery. The most vital component is safe delivery, which necessitates accurate quality assurance measures and on-board imaging. We will review the evidence and potential utilisation of hypofractionated EBRT in Africa.
The influence of pentoxifylline on damage responses in tumour cells
(Stellenbosch : Stellenbosch University, 2000-04) Theron, Catherina S; Bohm, E. L. J. F.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiation Oncology.
ENGLISH ABSTRACT: Pentoxifylline enhances the toxicity of radiation and has emerged as an effective modulator of the radiation response of tumour cells. The molecular mechanisms involved in the enhancement of radiotoxicity by pentoxifylline have not yet been elucidated. Cell cycle blocks, DNA repair and programmed cell death (apoptosis) are all pert of the cellular response to DNA damage and as such must be considered as targets of the drug. In this study, the influence of pentoxifylline on radiosensitisation, G2 block abrogation, DNA repair inhibition and the induction of apoptosis have been investigated in 8e11 and MeWo melanoma and 4197 and 4451 squamous cell carcinoma (SCC) cell lines. The influence of pentoxifylline on radiation-induced apoptosis in Jurkat J5 T-lymphocytic leukemia cells has also been assessed. Hela cervical carcinoma cells were used to investigate the molecular events involved in the abrogation of the G2 block by pentoxifylline. It is shown that pentoxifylline preferentially sensitises the TP53 mutant MeWo and 4451 cell lines and enhances radiotoxicity by factors of up to 14.5. In the MeWo melanoma, but not in the 4451 SCC cell line, radiosensitisation is accompanied by inhibition of DNA repair. No significant enhancement of radiation-induced apoptosis was observed in MeWo melanoma and 4451 SCC cells. However, Jurkat J5 cells showed an increase in apoptosis after irradiation in the presence of the drug. In irradiated Hela cervical carcinoma cells, pentoxifylline affects the expression of the two components of the mitosis promoting factor (MPF), namely cyclin 81 and p34cdC2, and rapidly restores cyclin 81/p34cdC2 ratios to control levels. Analysis of cyclin 81 expression in whole cells and isolated nuclei furthermore reveals an influence of the drug on the subcellular translocation of the MPF. It is concluded that G2 block abrogation is not the only mechanism involved in the radiosensitisation of tumour cells by pentoxifylline, but that DNA repair inhibition plays a role in certain cell types. Although pentoxifylline induces apoptosis in Jurkat J5 thymocytes, radiation-induced apoptosis plays no role in the radiosensitisation of the two TP53 mutant melanoma and sec cell lines. Abrogation of the G2 block by pentoxifylline, which sensitises tumour cells to a second irradiation or chemotherapeutic challenge, involves a modulation of the levels of cyclin 81 and p34cdC2, and the subcellular location of the MPF. These results are of utmost importance for the clinical potential of pentoxifylline as a dose modifier in cancer therapy.
Long-term complications of pelvic radiotherapy
(South African Society of Gynaecologic Oncology, 2010) Simonds, Hannah
Complications following pelvic radiation are frequently under-reported and inadequately addressed. This overview examines the nature and the intensity of complications encountered by cancer survivors; it focuses specifically on gastrointestinal and vaginal complications, and the problems surrounding the methods of recording and assessing toxicities.
Malignant peripheral nerve sheath tumours and neurofibromatosis 1 : a case series and recommendations for care
(AOSIS, 2018-08-20) Burger, Henriette; Bezuidenhout, Heidre; Sher-Locketz, Candice; Baatjes, Karin; Van Wyk, Jacques; Bonthuys, Anita
Background: The incidence of malignant peripheral nerve sheath tumours (MPNST) in patients with neurofibromatosis 1 (NF1) is significantly higher than that of the general population. NF1-associated MPNST occur at a younger age and carry a worse prognosis than sporadic MPNST. Aim: This case series describes four cases of MPNST in patients with NF1. Setting: The study was performed in a public academic hospital in the Western Cape province of South Africa. Method: Demographics, disease status, histopathology, treatment and outcome data were collected retrospectively from medical charts and through review of histological slides. Results: The median age was 36.5 years. All tumours were > 5 cm at presentation and located on the trunk. One patient presented with metastatic disease. There was a mean delay of 3.5 months from presentation to initiation of treatment. Three patients underwent wide excision, with one receiving adjuvant chemotherapy and radiotherapy. At a median follow-up of 20 months from histological diagnosis only one patient was alive in clinical remission. Two patients had succumbed to progressive disease at 8 and 16 months from diagnosis and one patient with terminal metastatic disease was lost to follow-up. Conclusion: In this series the patients presented with advanced, often unresectable lesions for which single modality therapy was not curative. An adult NF1 health surveillance guideline for resource-constrained environments could lead to early diagnosis and treatment of MPNST and other complications in NF1 patients.
Managing AIDS-related Kaposi’s sarcoma and pregnancy
(AOSIS Publishing, 2013-05) Barnardt, Pieter
An estimated 30 - 40% of HIV-infected patients are likely to develop cancer during the progression of their disease. The occurrence of malignancy among these patients represents a difficult challenge in their care. Kaposi’s sarcoma (KS) – currently the most common tumour observed with an estimated incidence of 15 - 20% – represents the first manifestation of AIDS in 30 - 40% of patients. Any organ may be involved, but the gastrointestinal tract and lung remain the most frequently involved locations. The case described here presented a clinical and ethical dilemma where visceral KS, pregnancy and medical complications required multi-disciplinary management.
Managing gestational trophoblastic neoplasm (GTN) and people living with HIV (PLWH)
(MedPharm Publications, 2019) Barnardt, Pieter
The 2017 World Health Organization (WHO) global report on HIV/AIDS estimated that sub-Saharan Africa comprised 64% of the global HIV burden, with a current estimate of 19.4 million cases in Eastern and Southern Africa. Since the introduction of antiretroviral therapy (ART) there has been a 30–40% increase in the incidence of non-AIDS malignancies. Gestational trophoblastic disease comprises of a spectrum of pregnancy-related disorders with an overall cure rate of 90%. The response to treatment is generally favourable but the associated complications of HIV, comorbidities, poor performance status and extent of metastatic disease in gestational trophoblastic neoplasm patients receiving chemotherapy, compromises the outcome and survival.
Medical students' perceptions on euthanasia and physician-assisted suicide : are they fully informed?
(Health & Medical Publishing Group, 2018) Burger, H.; Gwyther, L.; Krause, R.; Ratshikana-Moloko, M.; Hellenberg, D.
No abstract available
Morphine and chronic cancer pain
(Health & Medical Publishing Group, 2001-10) Smit, B. J.
Cancer pain can be broken down into the following categories: (i),pain caused by the cancer process itself, i.e. bony invasion or nerve compression or infiltration that is likely to present with the features of acute pain; (ii) pain arising from the treatment for the cancer process and likely to present as chronic pain - this might include pain resulting from radical surgery, chemotherapy or radiation therapy; and (hi) bedsores, chronic infection or constipation, which may become part of the pain syndrome.
Morphine for cancer pain
(Health & Medical Publishing Group, 1994) Smit, B. J.
[No abstract available]

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