Pharmacogenetics and pharmacokinetics of tamoxifen in a Zimbabwean breast cancer cohort.

Tamoxifen is the most used hormonal therapy for oestrogen receptor-positive breast cancer. CYP2D6 is the main enzyme in the metabolic pathway of tamoxifen to endoxifen. Variations in endoxifen plasma concentrations are associated with CYP2D6 polymorphisms. This study aimed to determine the association between the CYP2D6 polymorphisms and endoxifen plasma concentrations in a cohort of Zimbabwean breast cancer patients (n = 40). TaqMan genotyping and copy number assays were done to determine CYP2D6 genotypes. Tamoxifen and metabolites were quantitated using LC-MS/MS. The population had high frequencies of the CYP2D6 reduced function alleles, *17 (15%) and *29 (18%). The median endoxifen concentration was 4.78 ng/mL, and in 55% of the patients, mostly intermediate metabolizers were below the endoxifen therapeutic threshold of 5.97 ng/mL. The CYP2D6 phenotypes and activity scores were significantly associated with endoxifen plasma concentrations (P = 0.0151) and with endoxifen to N-desmethyl-tamoxifen ratios (P = 0.0006).

Utilization and predictors of postmastectomy radiation receipt in an Oncology Center in Zimbabwe.

PURPOSE: Few sub-Saharan African studies have ascertained utilization for postmastectomy radiation (PMRT) for breast cancer, the second most common cancer among African women. We estimated PMRT utilization and identified predictors of PMRT receipt in Zimbabwe. METHODS: Retrospective patient cohort included non-metastatic breast cancer patients treated from 2014 to 2019. PMRT eligibility was assigned per NCCN guidelines. Patients receiving chemotherapy for non-metastatic disease were also included. The primary endpoint was receipt of PMRT, defined as chest wall with/without regional nodal radiation. Predictors of receiving PMRT were identified using logistic regression. Model performance was evaluated using the c statistic and Hosmer-Lemeshow test for goodness-of-fit. RESULTS: 201 women with localized disease and median follow-up of 11.4 months (IQR 3.3-17.9) were analyzed. PMRT was indicated in 177 women and utilized in 59(33.3%). Insurance coverage, clinical nodal involvement, higher grade, positive margins, and hormone therapy receipt were associated with higher odds of PMRT receipt. In adjusted models, no hormone therapy (aOR 0.12, 95% CI 0.043, 0.35) and missing grade (aOR 0.07, 95% CI 0.01, 0.38) were associated with lower odds of PMRT receipt. The resulting c statistic was 0.84, with Hosmer-Lemeshow p-value of 0.93 indicating good model fit. CONCLUSION: PMRT was utilized in 33% of those meeting NCCN criteria. Missing grade and no endocrine therapy receipt were associated with reduced likelihood of PMRT utilization. In addition to practice adjustments such as increasing hypofractionation and increasing patient access to standard oncologic testing at diagnosis could increase postmastectomy utilization.

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.

Gaps and opportunities for cervical cancer prevention, diagnosis, treatment and care: evidence from midterm review of the Zimbabwe cervical Cancer prevention and control strategy (2016-2020).

BACKGROUND: Cervical cancer is the fourth most common cancer amongst women globally and it accounts for the majority of cancer deaths among females in Zimbabwe. The objective of this midterm review analysis was to identify the gaps and opportunities for cervical cancer prevention, diagnosis, treatment, and care to inform the next cervical cancer strategy in Zimbabwe. METHODS: A mixed methods approach was used for the midterm review. Secondary data was collected from programme documents, published and grey literature. Primary data was collected in six provinces through key informant interviews with officials and focus group discussions with beneficiaries. After data analysis, a draft report was presented to a technical working group to validate the findings and to fill in any gaps. RESULTS: This midterm review revealed a myriad of gaps of the strategy particularly in diagnosis, treatment and care of cervical cancer and the primary focus was on secondary prevention. There was no data to quantify the level of awareness and advocacy for cervical cancer prevention. Our results revealed that there was no data on the proportion of women who ever tested for cervical cancer which existed nationally. Our findings suggest that some health facilities were screening women above 50 years old using VIAC, which is an inappropriate approach for those women. Quality control of VIAC and treatment of precancers were not part of the strategy. Pathological services were not efficient and effective due to lack of resources and additionally data on investigations were not routinely collected and available at the national level. Other gaps identified were limited funding, human resources, equipment, and commodities as well as lack of leadership at the national level to coordinate the various components of the cervical cancer programme. There are also numerous opportunities identified to build upon some successes realized to date. CONCLUSIONS: Our findings emphasized the importance of effective and holistic planning in cervical cancer screening programmes in low-resource settings. In addition, huge investments are required in cervical cancer programmes and governments need to take centre role in mobilizing the requisite resources.

Hypofractionation in Breast Cancer Radiotherapy Across World Bank Income Groups: Results of an International Survey.

PURPOSE: Hypofractionated breast radiotherapy has been found to be equivalent to conventional fractionation in many clinical trials. Using data from the European Society for Radiotherapy and Oncology Global Impact of Radiotherapy in Oncology survey, we identified preferences for hypofractionation in breast cancer across World Bank income groups and the perceived facilitators and barriers to its use. MATERIALS AND METHODS: An international, electronic survey was administered to radiation oncologists from 2018 to 2019. Demographics, practice characteristics, preferred hypofractionation regimen for specific breast cancer scenarios, and facilitators and barriers to hypofractionation were reported and stratified by World Bank income groups. Variables associated with hypofractionation were assessed using multivariate logistic regression models. RESULTS: One thousand four hundred thirty-four physicians responded: 890 (62%) from high-income countries (HICs), 361 (25%) from upper-middle-income countries (UMICs), 183 (13%) from low- and lower-middle-income countries (LLMICs). Hypofractionation was preferred most frequently in node-negative disease after breast-conserving surgery, with the strongest preference reported in HICs (78% from HICs, 54% from UMICs, and 51% from LLMICs, P < .001). Hypofractionation for node-positive disease postmastectomy was more frequently preferred in LLMICs (28% from HICs, 15% from UMICs, and 35% from LLMICs, P < .001). Curative doses of 2.1 to < 2.5 Gy in 15-16 fractions were most frequently reported, with limited preference for ultra-hypofractionation, but significant variability in palliative dosing. In adjusted analyses, UMICs were significantly less likely than LLMICs to prefer hypofractionation across all curative clinical scenarios, whereas respondents with > 1 million population catchments and with intensity-modulated radiotherapy were more likely to prefer hypofractionation. The most frequently cited facilitators and barriers were published evidence and fear of late toxicity, respectively. CONCLUSION: Preference for hypofractionation varied for curative indications, with greater acceptance in earlier-stage disease in HICs and in later-stage disease in LLMICs. Targeted educational interventions and greater inclusivity in radiation oncology clinical trials may support greater uptake.

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.

Patterns of Palliative Radiotherapy Utilization for Patients With Metastatic Breast Cancer in Harare, Zimbabwe.

PURPOSE: In sub-Saharan Africa, radiotherapy (RT) utilization and delivery patterns have not been extensively studied in patients with metastatic breast cancer. METHODS: A retrospective cohort study of female patients with metastatic breast cancer seen at Parirenyatwa Radiotherapy Centre in Zimbabwe from 2014 to 2018 was conducted. Demographics, pathology, staging, and treatment data were abstracted through chart review. Fisher's exact test and chi-squared test of independence were used to compare proportions, and independent two-sample t-tests were used to compare means. RESULTS: Of 351 patients with breast cancer, 152 (43%) had metastatic disease, median age 51 years (interquartile range: 43-61 years). Of those with metastatic disease, 30 patients (20%) received radiation to various metastatic sites: 16 spine; three nonspine bone metastases; six whole brain; and five chest wall or supraclavicular. Patients who received radiation were younger (46 v 52 years; P = .019), but did not differ significantly by performance status than those who did not. The most common dose prescription was 30 Gy in 10 fractions (33%). Five (17%) patients had treatment interruption and two (7%) had treatment noncompletion. Province of origin and clinical tumor stage were significant predictors of RT receipt (P = .002; and P = .018, respectively). CONCLUSION: A minority of patients with metastatic breast cancer received RT (20%), and these were likely to be younger, with advanced tumor stage, and resided in provinces where RT is available. Conventional courses were generally prescribed. There is a need to strongly consider palliative RT as an option for patients with metastatic breast cancer and use of hypofractionated courses (e.g. 8 Gy in one fraction) may support this goal.

Breast cancer in Zimbabwe: patterns of care and correlates of adherence in a national referral hospital radiotherapy center cohort from 2014 to 2018.

BACKGROUND: Breast cancer is the second most common cancer among women in Zimbabwe. Patients face socioeconomic barriers to accessing oncology care, including radiotherapy. We sought to understand patterns of care and adherence for women with breast cancer in sub-Saharan Africa (SSA) with radiotherapy access. METHODS: A retrospective cohort was created for women with breast cancer evaluated at the Parirenyatwa Hospital Radiotherapy and Oncology Center (RTC) from 2014 to 2018. Clinical data were collected to define patterns of care. Non-adherence was modeled as a binary outcome with different criteria for patients with localized versus metastatic disease. RESULTS: In total, 351 women presented with breast cancer with median age 51 at diagnosis (IQR: 43-61). Receptor status was missing for 71% (248). 199 (57%) had non-metastatic disease, and 152 (43%) had metastases. Of women with localized disease, 34% received post-mastectomy radiation. Of women with metastatic disease, 9.7% received radiotherapy. Metastatic disease and missing HIV status were associated with increased odds of study-defined non-adherence (aOR: 1.85, 95% CI: 1.05, 3.28; aOR: 2.13, 95% CI: 1.11, 4.05), while availability of ER/PR status was associated with lower odds of non-adherence (aOR: 0.18, 95% CI: 0.09, 0.36). CONCLUSIONS: Radiotherapy is likely underutilized for women with breast cancer, even in a setting with public sector availability. Exploring patient-level factors that influence adherence to care may provide clinicians with better tools to support adherence and improve survival. Greater investment is needed in multidisciplinary, multimodality care for breast cancer in SSA.

Global palliative radiotherapy: a framework to improve access in resource-constrained settings.

Radiotherapy is an essential component of cancer therapy. Lack of access to radiotherapy in less-developed countries prevents its use for both cure and symptom relief, resulting in a significant disparity in patient suffering. Several recent initiatives have highlighted the need for expanded access to both palliative medicine and radiotherapy globally. Yet, these efforts have remained largely independent, without attention to overlap and integration. This review provides an update on the progress toward global palliative radiotherapy access and proposes a strategic framework to address further scale-up. Synergies between radiotherapy, palliative medicine, and other global health initiatives will be essential in bringing palliative radiotherapy to patients around the globe.

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.

Survival of cervix cancer patients in Harare, Zimbabwe, 1995-1997.

The survival experience of 284 patients with cancer of the cervix uteri registered by the population-based Zimbabwe National Cancer Registry in 1995-1997 is described. The vital status of these subjects was established by linkage with death registration and by retrieval of patient files from medical records departments. Untraced patients were contacted at home. Of the 284, 177 (62.3%) were dead and 76 (26.8%) were alive at the closing date of the study (31 December 1999), with only 31 cases (10.9%) lost to follow-up. Overall observed and relative survival at 3 years were 44.2% and 45.2%, respectively. Half of the cases (139) had been referred and treated in the radiotherapy department. Survival was significantly greater in the first 3 years for patients who received radiotherapy treatment compared to those that had not, but this difference had disappeared by the fourth year of follow-up. Many cases presented late (distant metastasis), and extent of disease was an important determinant of survival; cases with metastases had a risk of death some 3 times that of patients with localized disease. The results demonstrate the importance of earlier diagnosis and availability of effective treatment in the African context.

Cancer survival in a southern African urban population.

This paper provides the first comprehensive population based cancer survival estimates from the African continent. Five-year absolute and relative survival estimates are presented for black and white Zimbabwean patients diagnosed with cancer in Harare, Zimbabwe between the years 1993 and 1997. The survival of black Zimbabwean cancer patients are among the lowest ever reported from population based cancer registries. For most cancer sites, white Zimbabwean patients have much higher survival than black Zimbabweans, except for lung and colorectal cancer, for which the estimates are similarly poor. Race specific comparisons to cancer patients in the United States show that Zimbabwean patients have much lower survival than American cancer patients and that the gap between black Zimbabwean patients and black American patients is broader than between white Zimbabwean and white American patients. Access to and the ability to pay for medical care may be a very important barrier to better survival for the majority of black Zimbabwean patients and the most important cause for the very low cancer survival in this population.