Significance of HIV status in cervical cancer patients receiving curative chemoradiation therapy, definitive radiation alone, or palliative radiation in Botswana.

BACKGROUND: Cervical cancer associated with human papillomavirus has the highest cancer incidence and mortality for women in Botswana because of a high HIV prevalence and limited screening. This study investigates the significance of HIV on the overall survival (OS) of patients with locally advanced cervical cancer by various treatment categories (curative chemoradiation, definitive radiation [RT] alone, or palliative RT alone). METHODS: This study included patients diagnosed with cervical cancer between 2013 and 2020, prospectively enrolled in the Botswana Prospective Cancer Cohort. OS based on HIV status and completion of planned treatment regimen was estimated by the Kaplan-Meier method. Comparisons of 2-year OS by HIV status was performed by the log-rank test, univariate and multivariable Cox analyses adjusting for cancer stage, RT dose, number of chemotherapy cycles, and baseline hemoglobin levels. RESULTS: Of 1131 patients diagnosed with stage IB-IVB cervical cancer, 69.8% were women living with HIV (n = 789). For patients receiving curative chemoradiation, HIV status was not significantly associated with OS in unadjusted (p = .987) and adjusted (p = .578) analyses. For RT only treatment and definitive (high-dose) RT alone, HIV status was significantly associated with OS in unadjusted analysis (HR = 1.77, p = .002; HR = 1.95, p = .014), but not in adjusted analysis (p = .227, p = .73). For patients receiving palliative (low-dose) RT, HIV status was not associated with OS in unadjusted (p = .835) or adjusted analysis (p = .359). CONCLUSIONS: In Botswana, a resource-limited setting, HIV status had no significant effect on 2-year OS in patients with cervical cancer with well-managed HIV receiving chemoradiation, RT alone, or palliative RT. This demonstrates that patients living with HIV receiving antiretroviral treatment can receive clinically appropriate treatment with no evidence that HIV may lead to poorer outcomes.

Delays in Cervical Cancer Treatment Initiation for Patients Living With or Without HIV in Botswana: An Observational Cohort Analysis (2015-2019).

PURPOSE: To assess delays in treatment initiation of chemoradiation or radiation alone for patients with advanced stage cervical cancer in Botswana. METHODS AND MATERIALS: Females with locally advanced cervical cancer (stages IB2-IVB) were prospectively enrolled in an observational cohort study from 2015 to 2019. We evaluated delays at 30, 60, 90, 120, 150, and 180 or greater days between the date of diagnosis and treatment initiation. Factors associated with overall survival were modeled with multivariable Cox proportional hazards regression (aHR). Associations between delays in cervical cancer treatment initiation were evaluated via univariable logistic regression. RESULTS: Among the 556 patients included (median age = 47.9 years), 386 (69.4%) were females living with HIV with a median CD4 count of 448.0 cells/µL (IQR, 283.0-647.5 cells/µL) at diagnosis. Most patients had stages 2 (38.1%) or 3 (34.5%) cervical cancer. Early-stage patients experienced longer delays in treatment initiation compared to late-stage patients (P = .033). Early-stage patients with delays ≥90 days and pathology diagnosis between 2016 and 2019 (aHR, 0.34; P < .001) versus <90 days had a decreased risk of mortality, and those with delays ≥90 days and pathology diagnosis before 2016 (aHR, 5.67; P = .022) versus <90 days had an increased risk of mortality. Late-stage patients with delays ≥120 days and pathology diagnosis between 2018 and 2019 (aHR, 1.98; P = .025) versus <120 days had an increased risk of mortality. Early-stage patients with pathology diagnosis between 2016 and 2019 (odds ratio, 2.32; P = .043) versus before 2016 were more likely to experience delays ≥90 days, and late-stage patients who traveled >100 km to the treatment facility (odds ratio, 2.83; P < .001) versus <100 km were more likely to experience delays ≥120 days. CONCLUSIONS: Delays in care are common in Botswana, particularly for those living farther from the treatment clinic and at advanced stages. This paper is among the first to show an association between treatment delays and worsened overall survival at advanced stages of cervical cancer, highlighting the need for interventions to help patients receive timely care in global settings.

Benchmarking of the Cervical Cancer Care Cascade and Survival Outcomes After Radiation Treatment in a Low- and Middle-Income Country Setting.

PURPOSE: Timely radiation treatment (RT) is critical in cervical cancer treatment, but patients in low- and middle-income countries (LMICs) in sub-Saharan Africa often face barriers that delay care. Time to care was benchmarked in a multidisciplinary team (MDT) setting in Botswana. METHODS: Time intervals between steps in care were recorded for 230 patients reviewed at MDT between January 2016 and July 2018. Associations between RT delay and overall survival (OS) were evaluated using Kaplan-Meier curves and multivariable Cox proportional hazards models. RESULTS: For patients who received RT (n = 187; 81.3%), the median biopsy to pathology reporting interval was 25 (IQR, 19-36) days and was 57 (IQR, 28-68) days for patients who did not (P = .003). Intervals in care did not differ between patients who did and did not receive RT. Among treated patients, the uppermost quartile interval from pathology reporting to RT initiation was ≥111 days and that from RT simulation to initiation was ≥12 days. Among patients receiving a RT dose of ≥65 Gy (n = 100), the delay from RT simulation to initiation of >12 days was associated with worse median OS (2.0 v 4.6 years; P = .048); this association trended toward, although did not meet, statistical significance on multivariable analysis (hazard ratio, 2.35; 95% CI, 0.95 to 5.85; P = .07). CONCLUSION: The MDT-coordinated care model allows for systematic benchmarking of the patient treatment cascade. Barriers to timely treatment exist for this cohort in Botswana, and RT delay may be associated with OS of patients receiving curative treatment. Interventions to accelerate the timing of the radiation oncology care cascade may improve clinical outcomes in this LMIC setting.

Patterns of care and outcomes for endometrial and ovarian cancers in botswana 2015-2021.

Purpose: Endometrial and ovarian cancers are leading causes of cancer death among women. However, there is little data on these patients from low- and middle-income countries including Botswana, a country in sub-Saharan Africa. This study reports data on demographics, treatment, and outcomes for patients with endometrial and ovarian cancer in Botswana. Methods: This prospective cohort study included all prospectively enrolled patients with endometrial or ovarian cancer who presented to Princess Marina or Gaborone Private Hospital between May 2015 and May 2021. Demographic, treatment, and survival data were analyzed. Results: 99 patients with endometrial and 38 patients with ovarian cancer were included. Median age at diagnosis was 64 for patients with endometrial cancer and 57 for patients with ovarian cancer. Just over half of patients with endometrial cancer (52.6%) presented with FIGO stages I and II, whereas most patients with ovarian cancer (65.8%) presented with stages III and IV. 24.2% of patients with endometrial cancer received chemotherapy, 32.3% received radiotherapy, 74.7% received surgical treatment, and 16.2% received no treatment; of patients with ovarian cancer, 42.1% received chemotherapy, 2.6% received radiotherapy, 52.6% received surgical treatment, and 31.6% of patients received no treatment. 1-and 2-year overall survival probabilities were 76.9% and 59.7% for patients with endometrial cancer and 62.8% and 43.7% for patients with ovarian cancer, respectively. Conclusion: This study demonstrates that a large proportion of patients with ovarian and endometrial cancer in Botswana are diagnosed at an advanced stage, and many do not receive standard-of-care treatment. Further inquiry is required to characterize challenges to diagnosis and treatment of ovarian and endometrial cancers in Botswana.

Stage and outcomes of invasive cervical cancer patients in Botswana: A prospective cohort study from 2013 to 2020.

Objective: To present the stage distribution, patterns of care, and outcomes of patients from Botswana with invasive cervical cancer, living with or without HIV. Methods: Between 2013 and 2020, women with cervical cancer were prospectively enrolled in an observational cohort study. Results: A total of 1,043 patients were enrolled; 69% were women living with HIV. The median age of the cohort was 47 years (interquartile range [IQR] 40-58 years), with women living with HIV presenting at a younger age compared to women without HIV (44 versus 61 years, p < 0.001). Among women living with HIV, the median CD4 count at the time of cancer diagnosis was 429.5 cells/µL (IQR 240-619.5 cells/µL), 13% had a detectable viral load, and 95% were on antiretroviral therapy. In regard to treatment, 6% (n = 58) underwent surgery, 33% (n = 341) received radiation therapy, 51% (n = 531) received chemoradiation, and 7% (n = 76) did not receive treatment. Stage distribution in the cohort was as follows: I 17% (n = 173), II 37% (n = 388), III 35% (n = 368), and IV 8% (n = 88). For all patients, 2-year OS was 67%. In multivariable Cox regression, worse OS was associated with stage: II (HR 1.91, p = 0.007), III (HR 3.99, p < 0.001), and IV (HR 5.06, p < 0.001) compared to stage I. Improved OS was associated with hemoglobin > 10 g/dL (HR 0.51, p < 0.001) compared to Hb ≤ 10 g/dL. Conclusions: Among women in Botswana with cervical cancer, most patients presented with stage II or III disease warranting radiation therapy or chemoradiation. While two-thirds of cervical cancer patients were women living with HIV, HIV did not impact OS.

Relative Dose Intensity and Pathologic Response Rates in Patients With Breast Cancer and With and Without HIV Who Received Neoadjuvant Chemotherapy.

PURPOSE: Patients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT). METHODS: This was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding. RESULTS: In total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy. CONCLUSION: Patients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes.

Five-year overall survival following chemoradiation therapy for locally advanced cervical carcinoma in women living with and without HIV infection in Botswana.

PURPOSE: To compare updated prospective 5-year survival outcomes of cervical cancer patients living with and without human immunodeficiency virus (HIV) infection who initiated curative chemoradiation therapy (CRT) in a resource-limited setting. METHODS & MATERIALS: Women in Botswana with locally advanced cervical cancer were enrolled in a prospective, observational, cohort study from July 2013 through January 2015. Survival outcomes were analyzed after 5 years of follow-up. RESULTS: This cohort included 143 women initiating curative CRT. Sixty-seven percent (n = 96) of cohort were women living with HIV (WLWH), all of whom were receiving antiretroviral therapy (ART) at the time of treatment initiation and boasted a median CD4 count of 481 cells/µL (IQR, 351-579 µL). The 5-year overall survival (OS) rates were 56.8% (95% CI, 40.0-70.5%) for patients without HIV infection and 55.1% (95% CI, 44.2-64.7%) for WLWH (p = 0.732). Factors associated with superior 5-year OS on multivariate analyses included baseline hemoglobin > 10 g/dL (hazard ratio (HR) 0.90, 95% CI, 0.83-0.98, p = 0.015), lower stage at diagnosis (stage I and II vs. III and IV) (HR 1.39, 95% CI 1.09-1.76, p = 0.007), and higher EQD2 (HR 0.98, 95% CI 0.97-0.99, p = 0.001). CONCLUSIONS: Five-year OS was not impacted by HIV status in this population of WLWH with well-managed infection who initiated curative treatment for cervical cancer in Botswana. Regardless of HIV status, hemoglobin levels and stage at diagnosis were associated with survival. These findings suggest that treatment for cervical cancer in WLWH with well-controlled infection need not be altered solely due to HIV status.

Chemoradiation versus radiation alone in stage IIIB cervical cancer patients with or without human immunodeficiency virus.

OBJECTIVE: Cervical cancer remains the most common cancer among women in sub-Saharan Africa and is also a leading cause of cancer related deaths among these women. The benefit of chemoradiation in comparison with radiation alone for patients with stage IIIB disease has not been evaluated prospectively in women living with human immunodeficiency virus (HIV). We assessed the survival of chemoradiation versus radiation alone among stage IIIB cervical cancer patients based on HIV status. METHODS: Between February 2013 and June 2018, patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIB cervical cancer with or without HIV and treated with chemoradiation or radiation alone, were prospectively enrolled in an observational cohort study. Overall survival was evaluated using the Kaplan-Meier method. Cox proportional hazards modeling was used to analyze associations with survival. RESULTS: Among 187 patients, 63% (n=118) of women had co-infection with HIV, and 48% (n=69) received chemoradiation. Regardless of HIV status, patients who received chemoradiation had improved 2 year overall survival compared with those receiving radiation alone (59% vs 41%, p<0.01), even among women living with HIV (60% vs 38%, p=0.02). On multivariable Cox regression analysis, including all patients regardless of HIV status, 2 year overall survival was associated with receipt of chemoradiation (hazard ratio (HR) 0.63, p=0.04) and total radiation dose ≥80 Gy (HR 0.57, p=0.02). Among patients who received an adequate radiation dose of ≥80 Gy, adjusted overall survival rates were similar between chemoradiation versus radiation alone groups (HR 1.07; p=0.90). However, patients who received an inadequate radiation dose of <80 Gy, adjusted survival was significantly higher in chemoradiation versus radiation alone group (HR 0.45, p=0.01). CONCLUSIONS: Addition of chemotherapy to standard radiation improved overall survival, regardless of HIV status, and is even more essential in women who cannot receive full doses of radiation.

Management of Head and Neck Cancers With or Without Comorbid HIV Infection in Botswana.

OBJECTIVES/HYPOTHESIS: Head and neck cancer (HNC) is the fifth most common malignancy in sub-Saharan Africa, a region with hyperendemic human immunodeficiency virus (HIV)-infection. HIV patients have higher rates of HNC, yet the effect of HIV-infection on oncologic outcomes and treatment toxicity is poorly characterized. STUDY DESIGN: Prospective observational cohort study. METHODS: HNC patients attending a government-funded oncology clinic in Botswana were prospectively enrolled in an observational cohort registry from 2015 to 2019. Clinical characteristics were analyzed via Cox proportional hazards and logistic regression followed by secondary analysis by HIV-status. Overall survival (OS) was evaluated via Kaplan-Meier. RESULTS: The study enrolled 149 patients with a median follow-up of 23 months. Patients presented with advanced disease (60% with T4-primaries), received limited treatment (19% chemotherapy, 8% surgery, 29% definitive radiation [RT]), and had delayed care (median time from diagnosis to RT of 2.5 months). Median OS was 36.2 months. Anemia was associated with worse survival (HR 2.74, P = .001). Grade ≥ 3 toxicity rate with RT was 30% and associated with mucosal subsite (OR 4.04, P = .03) and BMI < 20 kg/m2 (OR 6.04, P = .012). Forty percent of patients (n = 59) were HIV-infected; most (85%) were on antiretroviral therapy, had suppressed viral loads (90% with ≤400 copies/mL), and had immunocompetent CD4 counts (median 400 cells/mm3 ). HIV-status was not associated with decreased receipt or delays of definitive RT, worse survival, or increased toxicity. CONCLUSIONS: Despite access to government-funded care, HNC patients in Botswana present late and have delays in care, which likely contributes to suboptimal survival outcomes. While a disproportionate number has comorbid HIV infection, HIV-status does not adversely affect outcomes. LEVEL OF EVIDENCE: 2c Laryngoscope, 131:E1558-E1566, 2021.

Report of clinico-pathological features of breast cancer in HIV-infected and uninfected women in Botswana.

BACKGROUND: To characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status. METHODS: This was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records. RESULTS: A total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44-66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%, p < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER-/PR-/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER-/PR-/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals. CONCLUSIONS: Majority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana.

HIV infection is not associated with the initiation of curative treatment in women with cervical cancer in Botswana.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Sub-Saharan Africa. The risk of developing cancer is increased for women living with human immunodeficiency virus (HIV) infection. It is unknown which factors predict the initiation of curative chemoradiotherapy (CRT) in resource-limited settings and whether HIV is associated with initiating curative CRT in settings with a high HIV burden. METHODS: All women living with and without HIV infection who were initiating curative and noncurative CRT for locally advanced cervical cancer in Botswana were prospectively enrolled in an observational study. The factors associated with receiving CRT were evaluated in all patients and the subgroup of women living with HIV. RESULTS: Of 519 enrolled women, 284 (55%) initiated CRT with curative intent. The curative cohort included 200 women (70.4%) who were living with HIV and had a median CD4 count of 484.0 cells/µL (interquartile range, 342.0-611.0 cells/µL). In the noncurative cohort, 157 of 235 women (66.8%) were living with HIV and had a median CD4 count of 476.5 cells/µL (interquartile range, 308.0-649.5 cells/µL). HIV status was not associated with initiating curative CRT (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.58-1.56). The factors associated with receiving curative CRT treatment on multivariable analysis in all patients included baseline hemoglobin levels ≥10 g/dL (OR, 1.80; 95% CI, 1.18-2.74) and stage I or II versus stage III or IV disease (OR, 3.16; 95% CI, 2.10-4.75). Women aged >61 years were less likely to receive curative treatment (OR, 0.43; 95% CI, 0.24-0.75). Among women who were living with HIV, higher CD4 cell counts were associated with higher rates of CRT initiation. CONCLUSIONS: The initiation of CRT with curative intent does not depend on HIV status. Significant predictors of CRT initiation include baseline hemoglobin level, disease stage, and age.

A retrospective review of patients with Kaposi's sarcoma in Botswana.

BACKGROUND: Despite widespread antiretroviral coverage in Botswana, Kaposi's sarcoma (KS) remains among the most common malignancies. To date, adult KS in Botswana is not well characterized. The diagnosis relies on clinical suspicion that is often confirmed by histopathology given the implications of treatment; however, this poses a significant resource burden. METHODS: We conducted a retrospective review of the cohort of patients biopsied for possible KS at Princess Marina Hospital, the main dermatology referral site in Botswana, from September 2008 through June 2015 to describe the demographics, human immunodeficiency virus (HIV) characteristics, and clinical presentations of these patients. Histopathologic diagnoses were reviewed, and positive predictive value (PPV) was used to characterize the accuracy of clinical suspicion of KS. RESULTS: A total of 441 patients received 450 biopsies where KS was on the differential diagnosis, and 239 patients (54%) were ultimately diagnosed with KS. The KS cohort was more likely to be male (58% vs. 37%, P < 0.001), HIV positive (94% vs. 85%, P < 0.05), and have lower CD4 counts at the time of biopsy (274 cells/µl vs. 362 cells/µl, P < 0.05). The PPV of clinical suspicion of KS was 58%. When KS was not histopathologically diagnosed, clinically benign diseases were found in 17%, medically significant conditions requiring alternative therapies in 78%, and life-threatening diseases in 5%. DISCUSSION: Our study reinforces the risk factors in development of KS. The poor PPV supports the important role of histology in KS diagnosis to both ensure appropriate treatment and prevent overtreatment. Improved accessibility to biopsy and augmentation of local dermatopathologic services would likely improve diagnostic accuracy and treatment.

Building research capacity through programme development and research implementation in resource-limited settings - the Ipabalele study protocol: observational cohort studies determining the effect of HIV on the natural history of cervical cancer in Botswana.

INTRODUCTION: The global burden of cancer continues to increase in low- and middle-income countries, particularly in sub-Saharan Africa (SSA). Botswana, a middle-income country in SSA, has the second highest prevalence of HIV worldwide and has seen an increase in human papillomavirus (HPV)-associated cervical cancer over the last decade in the setting of improved survival of HIV-infected women. There is an urgent need to understand more clearly the causes and consequences of HPV-associated cervical cancer in the setting of HIV infection. We initiated the Ipabalele ('take care of yourself' in Setswana) programme to address this need for new knowledge and to initiate long-term research programme capacity building in the region. In this manuscript, we describe the components of the programme, including three main research projects as well as a number of essential cores to support the activities of the programme. METHODS AND PROCEDURES: Our multidisciplinary approach aims to further current understanding of the problem by implementing three complementary studies aimed at identifying its molecular, behavioural and clinical determinants. Three participant cohorts were designed to represent the early, intermediate and late stages of the natural history of cervical cancer.The functional structure of the programme is coordinated through programmatic cores. These allow for integration of each of the studies within the cohorts while providing support for pilot studies led by local junior investigators. Each project of the Ipabalele programme includes a built-in capacity building component, promoting the establishment of long-lasting infrastructure for future research activities. ETHICS AND DISSEMINATION: Institutional review board approvals were granted by the University of Pennsylvania, University of Botswana and Ministry of Health and wellness of Botswana. Results will be disseminated via the participating institutions and with the help of the Community Advisory Committee, the project's Botswana advisory group.

Breast Cancer Pathology Turnaround Time in Botswana.

PURPOSE: Quality pathology is critical for timely diagnosis and management of breast cancer. Few studies have analyzed pathology turnaround time (TAT) in sub-Saharan Africa. The purpose of this study was to quantify TAT for breast cancer specimens processed by the National Health Laboratory and Diagnofirm Laboratory in Gaborone, Botswana, and additionally compare TAT before and after 2012 to evaluate the effect of pathology scale-up interventions by the Ministry of Health and Wellness. METHODS: Retrospective analyses of TAT were performed for breast specimens submitted to the two laboratories from 2011 to 2015. TAT was calculated as the time from specimen collection and receipt in the laboratory to the date of final report sign-out. Descriptive statistics and rank sum test were used to compare temporal trends in TAT before and after 2012. RESULTS: A total of 158 breast biopsy, 219 surgical, and 218 immunohistochemistry (IHC) specimens were analyzed. The median TAT in 2015 was 6 and 7 days for biopsy and IHC specimens, respectively, and 57.5 days for surgical specimens. There was a significant decrease in median TAT for biopsy specimens from 21.5 days in 2011 to 2012 compared with 8 days in 2013 to 2015 ( P < .001). There was also a significant decrease in median TAT for IHC specimens during the same period ( P < .001). However, there was no significant decline in median TAT for surgical specimens. CONCLUSION: The scale-up of pathology personnel and infrastructure by the Ministry of Health and Wellness significantly reduced median TAT for biopsy and IHC specimens. TAT for surgical specimens remains suboptimal. Efforts are currently under way to decrease TAT for surgical specimens to 7 days.

Availability of WHO Essential Medicines for Cancer Treatment in Botswana.

PURPOSE: Stock outs of cancer drugs are potentially fatal but have not been systematically studied in low- and middle-income countries. The aim of this study was to determine the availability and alignment of the Botswana National Essential Medicines List (NEML) for cancer drugs with the WHO's Essential Medicines List (EML). METHODS: The availability and cost of cancer drugs were analyzed using data from a weekly stock catalog sent by Botswana's Central Medical Store to all pharmacy departments in government hospitals. Comparative data were extracted from the WHO EML and the "International Drug Price Indicator Guide-2014" from the Management Sciences for Health. Interviews with key informants were used to collect data on the Botswana NEML and the drug supply chain in the public sector. RESULTS: The 2015 Botswana NEML for cancer had 80.5% alignment with the WHO EML. At least 40% of essential drugs were out of stock for a median duration of 30 days in 2015. Stock outs affected chemotherapy drugs included in first-line regimens for treating potentially curable diseases such as cervical, breast, and colorectal cancer and were not associated with buyer price of therapy. Analyses showed that the median price ratio for procured drugs was greater than 1 for 61% of the NEML drugs, which suggests inefficiency in procurement in the public sector. CONCLUSIONS: Botswana has one of the highest alignments of NEML to the WHO EML in the sub-Saharan African region, which is consistent with investment in the health care system evident in other clinical spheres. Better quantification of chemotherapy requirements using data from the National Cancer Registry and resource-sensitive treatment guidelines can help reduce stock outs and facilitate more effective and efficient procurement processes.

Methodology to Forecast Volume and Cost of Cancer Drugs in Low- and Middle-Income Countries.

PURPOSE: In low- and middle-income countries (LMICs), frequent outages of the stock of cancer drugs undermine cancer care delivery and are potentially fatal for patients with cancer. The aim of this study is to describe a methodologic approach to forecast chemotherapy volume and estimate cost that can be readily updated and applied in most LMICs. METHODS: Prerequisite data for forecasting are population-based incidence data and cost estimates per unit of drug to be ordered. We used the supplementary guidelines from the WHO list of essential medicines for cancer to predict treatment plans and ordering patterns. We used de-identified aggregate data from the Botswana National Cancer Registry to estimate incident cases. The WHO Management Sciences for Health International Price Indicator was used to estimate unit costs per drug. RESULTS: Chemotherapy volume required for incident cancer cases was estimated as the product of the standardized dose required to complete a full treatment regimen per patient, with a given cancer diagnosis and stage, multiplied by the total number of incident cancer cases with the respective diagnosis. The estimated chemotherapy costs to treat the 10 most common cancers in the public health care sector of Botswana is approximately 2.3 million US dollars. An estimated 66% of the budget is allocated to costs of rituximab and trastuzumab alone, which are used by approximately 10% of the cancer population. CONCLUSION: This method provides a reproducible approach to forecast chemotherapy volume and cost in LMICs. The chemotherapy volume and cost outputs of this methodology provide key stakeholders with valuable information that can guide budget estimation, resource allocation, and drug-price negotiations for cancer treatment. Ultimately, this will minimize drug shortages or outages and reduce potential loss of lives that result from an erratic drug supply.

Strengthening palliative care delivery in developing countries: a training workshop model in Botswana.

BACKGROUND: The persistent global unmet need for palliative care continues to be felt acutely in Sub-Saharan Africa, where the volume is growing and access to palliative services remains underdeveloped. Recognizing the increasing urgency of bolstering palliative care infrastructure, several countries, such as Botswana, have established national policies and strategies to enhance care delivery. Given that education and training are essential components in pursuing this goal, we present a model for a training workshop that was successful in increasing the palliative care knowledge base and skill set in a group of nurses. METHODS: A 2-day palliative care workshop was conducted for 15 nurses in Gaborone, Botswana in October 2014. Ten nurses completed pre- and post-workshop tests consisting of 21 questions spanning palliative care topics and delivery skills. RESULTS: The survey category with the highest pre-test score of 70% was principles of palliative care. Ninety percent of participants demonstrated statistically significant improvement in post-test scores in comparison to pre-test results. The greatest increase in scores were observed in the categories of communication, end-of-life care and syringe driver use for administration of analgesic medications. The lowest post-test score category was spirituality, though it consisted of one survey question. CONCLUSIONS: Here we provide quantitative data that supports the success of the training workshop model presented. Improvement in palliative care knowledge and treatment skills, as evidenced by the increased scores from pre- to post-test results, suggests the efficacy of this 2-day training program in advancing palliative care education of nurses. Given the unmet need for healthcare workers trained in palliative care, this model could serve as a valuable tool for expanding and strengthening the delivery of care in settings where patients have limited access to palliative care services.

Impact of Human Immunodeficiency Virus Infection on Survival and Acute Toxicities From Chemoradiation Therapy for Cervical Cancer Patients in a Limited-Resource Setting.

PURPOSE: To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting. METHODS AND MATERIALS: Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January 2015. RESULTS: Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P = .70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10 g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P = .003), total radiation dose ≥75 Gy (HR 0.52, 95% CI 0.27-0.97, P = .04), and age <40 years versus 40-59 years (HR 2.17, 95% CI 1.05-4.47, P = .03). CONCLUSIONS: Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status.