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.

Vulvar cancer in Botswana in women with and without HIV infection: patterns of treatment and survival outcomes.

OBJECTIVES: Vulvar cancer is a rare gynecological malignancy. However, the incidence of human papillomavirus (HPV)-associated vulvar disease is increasing, particularly in low- and middle-income countries. HIV infection is associated with an increased risk of HPV-associated vulvar cancer. We evaluated treatment patterns and survival outcomes in a cohort of vulvar cancer patients in Botswana. The primary objective of this study was to determine overall survival and the impact of treatment modality, stage, and HIV status on overall survival. METHODS: Women with vulvar cancer who presented to oncology care in Botswana from January 2015 through August 2019 were prospectively enrolled in this observational cohort study. Demographics, clinical characteristics, treatment, and survival data were collected. Factors associated with survival including age, HIV status, stage, and treatment were evaluated. RESULTS: Our cohort included 120 women with vulvar cancer. Median age was 42 (IQR 38-47) years. The majority of patients were living with HIV (89%, n=107) that was well-controlled on antiretroviral treatment. Among women with HIV, 54.2% (n=58) were early stage (FIGO stage I/II). In those without HIV, 46.2% (n=6) were early stage (stage I/II). Of the 95 (79%) patients who received treatment, 20.8% (n=25) received surgery, 67.5% (n=81) received radiation therapy, and 24.2% (n=29) received chemotherapy, either alone or in combination. Median follow-up time of all patients was 24.7 (IQR 14.2-39.1) months and 2- year overall survival for all patients was 74%. Multivariate analysis demonstrated improved survival for those who received surgery (HR 0.26; 95% CI 0.08 to 0.86) and poor survival was associated with advanced stage (HR 2.56; 95% CI 1.30 to 5.02). Survival was not associated with HIV status. CONCLUSIONS: The majority of women with vulvar cancer in Botswana are young and living with HIV infection. Just under half of patients present with advanced stage, which was associated with worse survival. Improved survival was seen for those who received surgery.

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.

Cervix Cancer in Sub-Saharan Africa: An Assessment of Cervical Cancer Management.

PURPOSE: Underdeveloped nations carry the burden of most cervical cancer, yet access to adequate treatment can be challenging. This report assesses the current management of cervical cancer in sub-Saharan Africa to better understand the needs of underdeveloped nations in managing cervical cancer. METHODS: A pre- and postsurvey was sent to all centers participating in the Cervical Cancer Research Network's 4th annual symposium. The pre- and postsurvey evaluated human papillomavirus and HIV screening, resources available for workup and/or treatment, treatment logistics, outcomes, and enrollment on clinical trials. Descriptive analyses were performed on survey responses. RESULTS: Twenty-nine centers from 12 sub-Saharan countries saw approximately 300 new cases of cervical cancer yearly. Of the countries surveyed, 55% of countries had a human papillomavirus vaccination program and 30% (range, 0%-65%) of women in each region were estimated to have participated in a cervical cancer screening program. In the workup of patients, 43% of centers had the ability to obtain a positron emission tomography and computed tomography scan and 79% had magnetic resonance imaging capabilities. When performing surgery, 88% of those centers had a surgeon with an expertise in performing oncological surgeries. Radiation therapy was available at 96% of the centers surveyed, and chemotherapy was available in 86% of centers. Clinical trials were open at 4% of centers. CONCLUSION: There have been significant advancements being made in screening, workup, and management of patients with cervical cancer in sub-Saharan Africa; yet, improvement is still needed. Enrollment in clinical trials remains a struggle. Participants would like to enroll patients on clinical trials with Cervical Cancer Research Network's continuous support.

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.

Association Between CD4 Count and Chemoradiation Therapy Outcomes Among Cervical Cancer Patients With HIV.

BACKGROUND: In Botswana, nearly two-thirds of cervical cancer patients are HIV-positive. This study examined the relationship between CD4 count and chemoradiation therapy outcomes among cervical cancer patients with HIV. SETTING: A prospective cohort study of 231 HIV-positive women with locally invasive cervical cancer was conducted in Gaborone, Botswana from January 2015 to February 2018. METHODS: Primary outcome was survival, defined as time from scheduled end of chemoradiation therapy to death or last contact with patient. Nadir CD4 count was defined as lowest CD4 available before cancer diagnosis. Delta CD4 count was defined as improvement from nadir CD4 to CD4 at cancer diagnosis. Hazard ratio (HR) analyses were adjusted for presenting variables (age, baseline hemoglobin, cancer stage, and performance status) and treatment variables (chemotherapy cycles and radiation dose). RESULTS: Two hundred thirty-one patients were included in nadir CD4 analysis; 139 were included in delta CD4 analysis. Higher delta CD4 was significantly associated with reduced mortality after adjusting for presenting and treatment variables (CD4 100-249: HR 0.45, 95% CI: 0.21 to 0.95; CD4 ≥250: HR 0.45, 95% CI: 0.20 to 1.02). Higher nadir CD4 showed a trend toward reduced mortality after adjusting for presenting and treatment variables (HR 0.94, 95% CI: 0.84 to 1.06). CONCLUSIONS: Higher delta CD4 (greater improvement from nadir CD4 to CD4 at cervical cancer diagnosis) is significantly associated with lower mortality. Although not statistically significant, data suggest that higher nadir CD4 may reduce mortality. These results reinforce the importance of early HIV diagnosis and antiretroviral therapy initiation, as their effects influence cervical cancer outcomes years later.

Explaining disparities in oncology health systems delays and stage at diagnosis between men and women in Botswana: A cohort study.

PURPOSE: Men in Botswana present with more advanced cancer than women, leading to poorer outcomes. We sought to explain sex-specific differences in time to and stage at treatment initiation. METHODS: Cancer patients who initiated oncology treatment between October 2010 and June 2017 were recruited at four oncology centers in Botswana. Primary outcomes were time from first visit with cancer symptom to treatment initiation, and advanced cancer (stage III/IV). Sociodemographic and clinical covariates were obtained retrospectively through interviews and medical record review. We used accelerated failure time and logistic models to estimate standardized sex differences in treatment initiation time and risk differences for presentation with advanced stage. Results were stratified by cancer type (breast, cervix, non-Hodgkin's lymphoma, anogenital, head and neck, esophageal, other). RESULTS: 1886 participants (70% female) were included. After covariate adjustment, men experienced longer excess time from first presentation to treatment initiation (8.4 months) than women (7.0 months) for all cancers combined (1.4 months, 95% CI: 0.30, 2.5). In analysis stratified by cancer type, we only found evidence of a sex disparity (Men: 8.2; Women: 6.8 months) among patients with other, non-common cancers (1.4 months, 95% CI: 0.01, 2.8). Men experienced an increased risk of advanced stage (Men: 67%; Women: 60%; aRD: 6.7%, 95% CI: -1.7%, 15.1%) for all cancers combined, but this disparity was only statistically significant among patients with anogenital cancers (Men: 72%; Women: 50%; aRD: 22.0%, 95% CI: 0.5%, 43.5%). CONCLUSIONS: Accounting for the types of cancers experienced by men and women strongly attenuated disparities in time to treatment initiation and stage. Higher incidence of rarer cancers among men could explain these disparities.

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.

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.

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.

American Brachytherapy Society: Brachytherapy treatment recommendations for locally advanced cervix cancer for low-income and middle-income countries.

PURPOSE: Most cervix cancer cases occur in low-income and middle-income countries (LMIC), and outcomes are suboptimal, even for early stage disease. Brachytherapy plays a central role in the treatment paradigm, improving both local control and overall survival. The American Brachytherapy Society (ABS) aims to provide guidelines for brachytherapy delivery in resource-limited settings. METHODS AND MATERIALS: A panel of clinicians and physicists with expertise in brachytherapy administration in LMIC was convened. A survey was developed to identify practice patterns at the authors' institutions and was also extended to participants of the Cervix Cancer Research Network. The scientific literature was reviewed to identify consensus papers or review articles with a focus on treatment of locally advanced, unresected cervical cancer in LMIC. RESULTS: Of the 40 participants invited to respond to the survey, 32 responded (response rate 80%). Participants were practicing in 14 different countries including both high-income (China, Singapore, Taiwan, United Kingdom, and United States) and low-income or middle-income countries (Bangladesh, Botswana, Brazil, India, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). Recommendations for modifications to existing ABS guidelines were reviewed by the panel members and are highlighted in this article. CONCLUSIONS: Recommendations for treatment of locally advanced, unresectable cervical cancer in LMIC are presented. The guidelines comment on staging, external beam radiotherapy, use of concurrent chemotherapy, overall treatment duration, use of anesthesia, applicator choice and placement verification, brachytherapy treatment planning including dose and prescription point, recommended reporting and documentation, physics support, and follow-up.

HIV Infection and Survival Among Women With Cervical Cancer.

Purpose Cervical cancer is the leading cause of cancer death among the 20 million women with HIV worldwide. We sought to determine whether HIV infection affected survival in women with invasive cervical cancer. Patients and Methods We enrolled sequential patients with cervical cancer in Botswana from 2010 to 2015. Standard treatment included external beam radiation and brachytherapy with concurrent cisplatin chemotherapy. The effect of HIV on survival was estimated by using an inverse probability weighted marginal Cox model. Results A total of 348 women with cervical cancer were enrolled, including 231 (66.4%) with HIV and 96 (27.6%) without HIV. The majority (189 [81.8%]) of women with HIV received antiretroviral therapy before cancer diagnosis. The median CD4 cell count for women with HIV was 397 (interquartile range, 264 to 555). After a median follow-up of 19.7 months, 117 (50.7%) women with HIV and 40 (41.7%) without HIV died. One death was attributed to HIV and the remaining to cancer. Three-year survival for the women with HIV was 35% (95% CI, 27% to 44%) and 48% (95% CI, 35% to 60%) for those without HIV. In an adjusted analysis, HIV infection significantly increased the risk for death among all women (hazard ratio, 1.95; 95% CI, 1.20 to 3.17) and in the subset that received guideline-concordant curative treatment (hazard ratio, 2.63; 95% CI, 1.05 to 6.55). The adverse effect of HIV on survival was greater for women with a more-limited stage cancer ( P = .035), those treated with curative intent ( P = .003), and those with a lower CD4 cell count ( P = .036). Advanced stage and poor treatment completion contributed to high mortality overall. Conclusion In the context of good access to and use of antiretroviral treatment in Botswana, HIV infection significantly decreases cervical cancer survival.

Establishing and Delivering Quality Radiation Therapy in Resource-Constrained Settings: The Story of Botswana.

There is a global cancer crisis, and it is disproportionately affecting resource-constrained settings, especially in low- and middle-income countries (LMICs). Radiotherapy is a critical and cost-effective component of a comprehensive cancer control plan that offers the potential for cure, control, and palliation of disease in greater than 50% of patients with cancer. Globally, LMICs do not have adequate access to quality radiation therapy and this gap is particularly pronounced in sub-Saharan Africa. Although there are numerous challenges in implementing a radiation therapy program in a low-resource setting, providing more equitable global access to radiotherapy is a responsibility and investment worth prioritizing. We outline a systems approach and a series of key questions to direct strategy toward establishing quality radiation services in LMICs, and highlight the story of private-public investment in Botswana from the late 1990s to the present. After assessing the need and defining the value of radiation, we explore core investments required, barriers that need to be overcome, and assets that can be leveraged to establish a radiation program. Considerations addressed include infrastructure; machine choice; quality assurance and patient safety; acquisition, development, and retention of human capital; governmental engagement; public-private partnerships; international collaborations; and the need to critically evaluate the program to foster further growth and sustainability.