Quality Assurance in Clinical Trials Requiring Radiation Therapy in Sub-Saharan Africa.

PURPOSE: Given the increasing availability of radiation therapy in sub-Saharan Africa, clinical trials that include radiation therapy are likely to grow. Ensuring appropriate delivery of radiation therapy through rigorous quality assurance is an important component of clinical trial execution. We reviewed the process for credentialing radiation therapy sites and radiation therapy quality assurance through the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center for AIDS Malignancy Consortium (AMC)-081, a multicenter study of cisplatin and radiation therapy for women with locally advanced cervical cancer living with HIV, conducted by the AIDS Malignancy Consortium at 2 sites in South Africa and Zimbabwe. METHODS AND MATERIALS: Women living with HIV with newly diagnosed stage IB2, IIA (>4 cm), IIB-IVA cervical carcinoma (per the 2009 International Federation of Gynecology and Obstetrics [FIGO] staging classifications) were enrolled in AMC-081. They received 3-dimensional conformal external beam radiation therapy (EBRT) to the pelvis (41.4-45 Gy) using a linear accelerator, high-dose-rate brachytherapy (6-9 Gy to point A with each fraction and up to 4 fractions), and concurrent weekly cisplatin (40 mg/m2). IROC reviewed EBRT and brachytherapy quality assurance records after treatment. RESULTS: All of the 38 women enrolled in AMC-081 received ±5% of the protocol-specified prescribed dose of EBRT. Geometry of brachytherapy applicator placement was scored as per protocol in all implants. Doses to points A and B, International Commission on Radiation Units and Measurements (ICRU) bladder, or ICRU rectum required correction by IROC in >50% of the implants. In the final evaluation, 58% of participants (n = 22) were treated per protocol, 40% (n = 15) had minor protocol deviations, and 3% (n = 1) had major protocol deviations. No records were received within 60 days of treatment completion as requested in the protocol. CONCLUSIONS: Major radiation therapy deviations were low, but timely submission of radiation therapy data did not occur. Future studies, especially those that include specialized radiation therapy techniques such as stereotactic or intensity-modulated radiation therapy, will require pathways to ensure timely and adequate quality assurance.

Model strategies to address barriers to cervical cancer treatment and palliative care among women in Zimbabwe: a public health approach.

BACKGROUND: Cervical cancer treatment and care remains limited in Zimbabwe despite the growing burden of the disease among women. This study was aimed at investigating strategies to address barriers in accessing treatment and care by women with cervical cancer in Harare, Zimbabwe. METHODS: A qualitative inquiry was conducted to generate evidence for this study. Eighty-four (84) participants were purposively selected for interviews and participation in focus group discussions. The participants were selected from cervical cancer patients, caregivers of cervical cancer patients, health workers involved in the care of cervical cancer patients as well as relevant policy makers in the Ministry of Health and Child Care. Participants were selected in such as a way as to ensure different of characteristics to obtain diverse perspectives about the issues under study. Discussion and interview guides were used as data collection tools and discussions/interviews were audio-recorded, transcribed and translated into English. Inductive thematic analysis was conducted using Dedoose software. RESULTS: Salient sub-themes that emerged in the study at the individual patient level were: provision of free or subsidized services, provision of transport to treating health facilities and provision of accommodation to patients undergoing treatment. At the societal level, the sub-themes were: strengthening of health education in communities and training of health workers and community engagement. Salient sub-themes from the national health system level were: establishment of more screening and treatment health facilities, increasing the capacities of existing facilities, decentralization of some services, building of multidisciplinary teams of health workers, development and rolling out of standardized guidelines and reformation of Acquired Immunodeficiency Virus (AIDS) levy into a fund that would finance priority disease areas. CONCLUSION: This study revealed some noteworthy strategies to improve access to cervical cancer treatment and care in low-income settings. Improved domestic investments in health systems and reforming health policies underpinned on strong political are recommended.

Education and training of clinical oncologists-experience from a low-resource setting in Zimbabwe.

As the burden of cancer increases worldwide, more so in low- and middle-income countries, one of the greatest challenges is human resource capacity development. Addressing this is critical in reducing the burden of cancer in the African continent. Other challenges include socio-economic demographics and disparities in the overall cancer care. Lack of sufficient numbers of qualified staff has been one of the obstacles in developing adequate and modern cancer treatment centres in Africa. Training in clinical oncology in Zimbabwe was established in 1990 through the collaboration between the Government of Zimbabwe and the WHO as a regional project. The training is offered by the University of Zimbabwe through the established Master of Medicine in Radiotherapy and Oncology (MMed Rad & Onco) postgraduate programme. Regional and local fellows have been trained, yielding more than 20 clinical oncologists over the years, who have initiated cancer treatment facilities in Africa and beyond. They have continued to train others, fulfilling the original WHO programme target of transfer of skills in sub-Saharan Africa. Collaborations with external partners have complemented efforts by the local faculty in addressing deficiencies in training, in areas where experts in the subject are lacking and in supporting nationals working abroad to come and teach newer technologies and techniques. The curriculum continues to evolve from knowledge-based training to competency-based training. However, there is a need to expand the current infrastructure to keep up with changing technology. Clinical oncology training in Zimbabwe continues and remains a regional resource. Emphasis on subspecialising seems to be the next natural step in progression. Strengthening of other disciplines, including surgical oncology and medical physics, would be complementary to the training. The programme is an example of a sustainable initiative born out of collaborative partnership and is sustained by local resources. The greater majority of qualified oncologists have remained in Africa.

Renal function impairment in cervical cancer patients treated with cisplatin-based chemoradiation: A review of medical records in a Zimbabwean outpatient department.

BACKGROUND: There is a potential increase in risk of renal function impairment among patients with invasive cervical cancer (ICC) who are HIV-positive and treated with cisplatin-based concurrent chemoradiation (CCRT). This concern is due to overlapping nephrotoxicity of the drugs, and nephropathy from the diseases themselves. There is limited literature available for the short-term renal outcomes for HIV-positive patients with ICC during routine clinical management. This study aimed to assess if HIV-infection increased the risk of renal impairment in ICC patients treated with CCRT, and explore the respective risk factors. MATERIALS AND METHODS: This was a retrospective review of records of ICC patients treated with at least one cycle of weekly cisplatin during CCRT at the Parirenyatwa Radiotherapy Center from January 2017-December 2018. The RIFLE criteria were used to classify renal impairment. Analyses were performed with Fisher's Exact tests, Wilcoxon rank sum tests. Odds ratios (OR) were generated using logistic regression. All statistical tests were 2-sided at a 5% level of significance. RESULTS: Seventy-two eligible patients were identified, 32 (44.44%) were HIV-positive. HIV-positive patients were younger (p = 0.002), had lower albumin levels (p = 0.014) and received lower cisplatin doses (p = 0.044). The mean percent reduction in estimated glomerular filtration rate (eGFR) from baseline was -19% (95% CI: -25.9% to -13.2%) for all patients. Thirty-one (43.1%) patients experienced renal impairment, 50% and 37.5% of HIV-positive and -negative patients respectively (p = 0.287). HIV-infection was associated with an adjusted OR of 1.16 (95% CI 0.35-3.43, p = 0.769). Baseline eGFR< 60ml/min was the only independent predictor of renal impairment, OR 0.25 (95% CI: 0.07-0.85). Baseline eGFR<60ml/min was also associated with receipt of lower cisplatin doses (p = 0.044). CONCLUSION: HIV-infection was not associated with elevated risk of renal impairment. Patients with an eGFR<60ml/min appear to be managed more cautiously reducing their risk for renal impairment during cisplatin therapy. The high prevalence of renal impairment in this population suggests the need for optimization of pre-treatment protocols.

Chemoradiation in Stage IIIB Cancer of the Uterine Cervix: A Review of the Zimbabwean Experience.

PURPOSE: Cervical cancer remains the leading cause of cancer morbidity and mortality among Zimbabwean women. Many patients present with stage IIIB disease. Although definitive concurrent chemoradiation (CCRT) is the standard of care, there is a paucity of data on the effect(s) of this intervention in resource-constrained and high HIV-prevalence settings. We investigated the differences in CCRT initiation practices, tolerability, and outcomes in this group. PATIENTS AND METHODS: We performed a retrospective analysis of data from hospital records for patients with stage IIIB disease who were treated over a 2-year period at Parirenyatwa Group of Hospitals. Outcome measures were documented treatment-related adverse events and early clinical tumor response. RESULTS: One hundred twenty-eight (37%) of 346 patients received CCRT, and 65 (51%) of 128 patients were infected with HIV. CCRT was prescribed mostly in patients with less extensive disease-not involving lower third vaginal walls, minimal pelvic sidewall involvement (P = .002), and higher CD4+ count (P = .02). Eighteen percent of recorded adverse events were high grade (≥ 3). One patient did not complete treatment, and 68.5% achieved complete clinical tumor response at 3 months post-CCRT. A higher proportion of complete clinical tumor response was noted in those patients who were young, HIV uninfected, had less extensive disease, CD4+ of 500 cells/mm3 or greater, received four or more cycles of chemotherapy, received brachytherapy, and had no treatment breaks. CONCLUSION: The study revealed that the use of CCRT to treat stage IIIB cervical cancer is low in Zimbabwe. Although several factors contribute, low CCRT uptake is mostly attributed to financial barriers. Well-selected patients tolerate the treatment and have good early clinical tumor response as expected. The role of CCRT for this patient group (and methods to make it available in resource-limited settings) must be further evaluated.

Cisplatin and radiation therapy in HIV-positive women with locally advanced cervical cancer in sub-Saharan Africa: A phase II study of the AIDS malignancy consortium.

PURPOSE: To determine the feasibility, safety, and tolerability of concomitant chemoradiotherapy administered at standard doses in HIV-infected women with locally-advanced cervical cancer (LACC) receiving antiretroviral therapy (ART). PATIENTS AND METHODS: Eligible participants had HIV infection and untreated, histologically-confirmed, invasive carcinoma of the uterine cervix, FIGO stages IB2, IIA (if tumor >4 cm), IIB, IIIA, IIIB, or IVA and met standard eligibility criteria. Subjects were prescribed 41.4-45 Gy external beam radiation therapy followed by high dose rate brachytherapy concomitant with up to six weekly doses of cisplatin 40 mg/m2 and were followed for 12 months. RESULTS: Sixty-four women were screened at two sites in sub-Saharan Africa, of whom 40 eligible participants were enrolled, for a screening ratio of 1.60. Of the 38 eligible participants who initiated study treatment, 31 (82%) completed treatment. By the 12-month follow-up visit, 7 women had died of disease and 29 of 31 (94%) returned for follow-up. One-year progression-free survival was 76.3% (95% CI, 59.4-86.9%), and did not significantly differ according to stage at entry (p = 0.581). Participant-reported adherence to ART was high; by 12 months, 93% of participants had an undetectable viral load. The most common grade 3 or 4 adverse event was decreased lymphocyte count that affected all treated participants. Non-hematologic serious adverse events were similar to those observed in women with LACC without HIV infection. CONCLUSIONS: The majority of HIV-infected women with LACC can complete concomitant chemoradiotherapy with the same cisplatin dose used in HIV-uninfected women with comparable tolerability and high ART adherence while on treatment.

American Society of Clinical Oncology Multidisciplinary Cancer Management Course: Connecting Lives, Cancer Care, Education, and Compassion in Zimbabwe-A Pilot for Efforts of Sustainable Benefit?

The burden of cancer in low- to middle-income countries is growing and is expected to rise dramatically while resources to manage this disease remain inadequate. All authorities for the management of cancer recommend multidisciplinary care. Educational efforts by international organizations to assist local professionals in caring for their patients tend to have a lasting impact because they empower local professionals and enhance their skills. A multidisciplinary cancer management course was designed by American Society of Clinical Oncology staff and local experts to provide a roadmap for cross-specialty interaction and coordination of care in Zimbabwe. The outcome of the course was measured through feedback obtained from participants and impact on local workforce. The cancer management course was relevant to daily practice and fostered long-lasting partnerships and collaborations. Furthermore, it resulted in a more motivated local workforce and strengthened existing multidisciplinary practices. Cancer care is in a critical state in low- to middle-income countries. Educational efforts and collaborative partnerships may provide a cost-effective strategy with sustainable benefits. A multidisciplinary approach to optimize therapy is desirable. Evaluation of the course impact after a period of 6 months to 1 year is needed to determine the sustainability and impact of such efforts.

Evaluation of the radiotherapy management of ocular surface squamous neoplasia in a high HIV prevalence setting- a retrospective review.

BACKGROUND: This article evaluates a single institute's radiotherapy management of OSSN, a previously regarded as rare malignancy, for possible future development of strategies to clearly define the role of adjuvant radiotherapy in improving treatment outcomes. MATERIALS AND METHODS: A retrospective review of 153 patients treated from January 2003 to December 2009. RESULTS: There was no difference in OSSN prevalence by gender (male to female ratio 1.07). Of 80/153 patients tested 79 (98.8 %) were HIV positive. Most patients (62.9 %) had prior orbital exenteration. Moderately and poorly differentiated grade (82.3 %) was associated with significantly higher stage and incidence of positive regional lymph nodes. External beam therapy dose mostly used was 60Gy in 30 fractions at 200 cGy per fraction in 5 fractions per week (34.8 %). (90)Strontium therapy was given to 13.5 % (60Gy in 6 fractions at 10Gy per fraction weekly). Favourable response (complete and partial) was seen in about 80 % of patients associated with higher total doses. Regional lymph node positivity was associated with poorer outcome. CONCLUSION: Adjuvant radiotherapy could have an important role in the management of patients presenting with locally advanced OSSN who are mostly HIV positive in developing countries. Prospective studies to evaluate the role of radiotherapy with or without chemotherapy in the management of OSSN in these settings are warranted.