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Purpose: Delays in diagnosis and treatment of cancers can lead to poor survival. These delays represent a multifaceted problem attributable to patient, provider, and systemic factors. We aim to quantify intervals from symptom onset to treatment start among patients with cancer in Botswana and to understand potential risk factors for delay. Patients and Methods: From December 2015 to January 2017, we surveyed patients seen in an oncology clinic in Botswana. We calculated proportions of patients who experienced delays in appraisal (between detecting symptoms and perceiving a reason to discuss them with provider, defined as > 1 month), help seeking (between discussing symptoms and first consultation with provider, defined as > 1 month), diagnosis (between first consultation and receiving a diagnosis, defined as > 3 months), and treatment (between diagnosis and starting treatment, defined as > 3 months). Results: Among 214 patients with cancer who completed the survey, median age at diagnosis was 46 years, and the most common cancer was cancer of the cervix (42.2%). Eighty-one percent of patients were women, 60.7% were HIV infected, and 56.6% presented with advanced cancer (stage III or IV). Twenty-six percent of patients experienced delays in appraisal, 35.5% experienced delays help seeking, 63.1% experienced delays in diagnosis, and 50.4% experienced delays in treatment. Patient income, education, and age were not associated with delays. In univariable analysis, patients living with larger families were less likely to experience a help-seeking delay (odds ratio [OR], 0.31; P =.03), women and patients with perceived very serious symptoms were less likely to experience an appraisal delay (OR, 0.45; P =.032 and OR, 0.14; P =.02, respectively). Conclusion: Nearly all patients surveyed experienced a delay in obtaining cancer care. In a setting where care is provided without charge, cancer type and male sex were more important predictors of delays than socioeconomic factors. [ABSTRACT FROM AUTHOR]

Purpose: Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)--an AIDS-defining cancer--in the country. Patients and Methods: This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed. Results: One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P = .001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P = .008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P = .33; adjusted analysis, HR, 0.57; P = .14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P = .001). Conclusion: Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival. [ABSTRACT FROM AUTHOR]

Purpose: Delays in diagnosis and treatment of cancers can lead to poor survival. These delays represent a multifaceted problem attributable to patient, provider, and systemic factors. We aim to quantify intervals from symptom onset to treatment start among patients with cancer in Botswana and to understand potential risk factors for delay. Patients and Methods: From December 2015 to January 2017, we surveyed patients seen in an oncology clinic in Botswana. We calculated proportions of patients who experienced delays in appraisal (between detecting symptoms and perceiving a reason to discuss them with provider, defined as > 1 month), help seeking (between discussing symptoms and first consultation with provider, defined as > 1 month), diagnosis (between first consultation and receiving a diagnosis, defined as > 3 months), and treatment (between diagnosis and starting treatment, defined as > 3 months). Results: Among 214 patients with cancer who completed the survey, median age at diagnosis was 46 years, and the most common cancer was cancer of the cervix (42.2%). Eighty-one percent of patients were women, 60.7% were HIV infected, and 56.6% presented with advanced cancer (stage III or IV). Twenty-six percent of patients experienced delays in appraisal, 35.5% experienced delays help seeking, 63.1% experienced delays in diagnosis, and 50.4% experienced delays in treatment. Patient income, education, and age were not associated with delays. In univariable analysis, patients living with larger families were less likely to experience a help-seeking delay (odds ratio [OR], 0.31; P =.03), women and patients with perceived very serious symptoms were less likely to experience an appraisal delay (OR, 0.45; P =.032 and OR, 0.14; P =.02, respectively). Conclusion: Nearly all patients surveyed experienced a delay in obtaining cancer care. In a setting where care is provided without charge, cancer type and male sex were more important predictors of delays than socioeconomic factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)—an AIDS-defining cancer—in the country. Patients and Methods: This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed. Results: One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P =.001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P =.008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P =.33; adjusted analysis, HR, 0.57; P =.14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P =.001). Conclusion: Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: People living with HIV (PLWH) experience increased risk of Hodgkin lymphoma (HL) despite effective initiation of antiretroviral therapy (ART). In high-income countries, outcomes following HIV HL have been reported to be non-differential, or inferior for PLWH. We sought to assess the effect of HIV on HL survival in Botswana, an African country with a generalized HIV epidemic and high ART coverage, to describe a context more reflective of global HIV populations., Patients and Methods: In the Thabatse Cancer Cohort, consenting participants initiating treatment for HL at one of four cancer centers in Botswana were enrolled from 2010 to 2020. Patients were followed quarterly for up to 5 years. The impact of HIV on survival following treatment initiation was assessed using an inverse probability-weighted Cox marginal structural model adjusted for age, performance status, and disease stage., Results: Seventy-eight new HL cases were enrolled, 47 (60%) were PLWH and 31 (40%) were HIV-uninfected. Baseline characteristics were similar between groups. The majority (61%) of patients presented with regional disease (stage I or II) with no statistically significant difference by HIV status ( P = .38). Nearly all (87%) PLWH participants were on ART before their HL diagnosis (median ART duration 42 months), and median CD4 count was 413 cells/μL (interquartile range 253-691). Survival, in unadjusted analyses, was lower among patients without HIV compared with PLWH (log rank P = .021). In adjusted analysis, HIV infection was not significantly associated with survival in inverse probability-weighted Cox model (hazard ratio 0.43; 95% CI, 0.16 to 1.16; P = .094)., Conclusion: In this cohort of patients treated for HL in Botswana, survival in PLWH (87% on long-standing ART) was at least as good as in individuals without HIV., Competing Interests: Aliyah SohaniConsulting or Advisory Role: AbbVie, MersanaExpert Testimony: Levin Papantonio Jason EfstathiouConsulting or Advisory Role: Blue Earth Diagnostics, AstraZeneca, Boston Scientific, Roivant, Merck, Myovant Sciences Philippe ArmandHonoraria: Merck, Bristol Myers SquibbConsulting or Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, ADC Therapeutics, Celgene, Daiichi Sankyo, C4 Therapeutics, GenMab, Miltenyi Biotec, Enterome, Tessa Therapeutics, MorphoSys, Regeneron, Genentech/Roche, EpizymeResearch Funding: Merck Sharp & Dohme (Inst), Bristol Myers Squibb (Inst), Roche (Inst), Adaptive Biotechnologies (Inst), Affimed Therapeutics (Inst), Genentech (Inst), IGM (Inst), Kite, a Gilead Company (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme Scott Dryden-PetersonPatents, Royalties, Other Intellectual Property: Royalties received from UpToDate, Inc for article on HIVNo other potential conflicts of interest were reported.

Purpose: With intense HIV epidemics, southern African countries have a high burden of classic Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL). However, suboptimal access to pathology resources limits subtype classification. We sought to assess the diagnostic accuracy of specimens classified as lymphoma and to determine association between discordant pathologic diagnosis and overall survival., Methods: Seventy patients with CHL or NHL and treated at three Botswana hospitals from 2010 to 2016 were analyzed. Local pathologic assessment relied primarily on morphology. All cases underwent secondary US hematopathology review, which is considered gold standard., Results: The median follow-up was 58 months. The overall reclassification rate was 20 of 70 cases (29%). All 20 CHL cases were correctly classified in Botswana, and mixed cellularity was the most common subtype, diagnosed in 11 (55%) cases. Of 47 confirmed NHL cases, diffuse large B-cell lymphoma was the final US diagnosis in 28 cases (60%), another aggressive B-cell NHL in nine (19%), an indolent B-cell NHL in six (13%), and T-cell NHL in four (9%). Common types of diagnostic discordance included NHL subtype reclassification (11 of 20, 55%) and CHL reclassified as NHL (7 of 20, 35%). Concordant versus discordant diagnosis after secondary review was associated with improved 5-year overall survival (60.1% v 26.3%, P = .0066). Discordant diagnosis was independently associated with increased risk of death (adjusted hazard ratio 2.733; 95% CI, 1.102 to 6.775; P = .0300) even after stratifying results by CHL versus NHL., Conclusion: In this single prospective cohort, discordant pathologic diagnosis was associated with a nearly three-fold increased risk of death. Limited access to relatively basic diagnostic techniques impairs treatment decisions and leads to poor patient outcomes in low-resource countries., Competing Interests: Jason A. EfstathiouConsulting or Advisory Role: Blue Earth Diagnostics, AstraZeneca, Boston Scientific, Roivant, Merck, Myovant Sciences Bruce A. ChabnerStock and Other Ownership Interests: Alnylam, Loxo, PharmaMar, Blueprint Medicines, GlaxoSmithKline, Biomarin, Seattle Genetics, SpringWorks Therapeutics, Constellation PharmaceuticalsHonoraria: Bristol Myers SquibbConsulting or Advisory Role: PharmaMar, EMD Serono, Cyteir, Chugai PharmaExpert Testimony: LillyTravel, Accommodations, Expenses: PharmaMar Jeremy AbramsonConsulting or Advisory Role: Celgene, Novartis, AbbVie, Kite, a Gilead company, Genentech, EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol Myers Squibb, C4 Therapeutics¸ BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MorphoSys, MustangBio, Ono Pharmaceutical, RegeneronResearch Funding: Seattle Genetics (Inst), AI Therapeutics (Inst), Bristol Myers Squibb/Celgene (Inst) Scott L. Dryden-PetersonPatents, Royalties, Other Intellectual Property: Royalties received from UpToDate, Inc for article on HIV Aliyah R. SohaniConsulting or Advisory Role: AbbVie, MersanaExpert Testimony: Levin PapantonioNo other potential conflicts of interest were reported.

Purpose: We evaluated a clinical breast examination (CBE) screening program to determine the prevalence of breast abnormalities, number examined per cancer diagnosis, and clinical resources required for these diagnoses in a middle-income African setting., Methods: We performed a retrospective review of a CBE screening program (2015-2018) by Journey of Hope Botswana, a Botswana-based nongovernmental organization (NGO). Symptomatic and asymptomatic women were invited to attend. Screening events were held in communities throughout rural and periurban Botswana, with CBEs performed by volunteer nurses. Individuals who screened positive were referred to a private tertiary facility and were followed by the NGO. Data were obtained from NGO records., Results: Of 6,120 screened women (50 men excluded), 452 (7.4%) presented with a symptom and 357 (5.83%) were referred for further evaluation; 257 ultrasounds, 100 fine-needle aspirations (FNAs), 58 mammograms, and 31 biopsies were performed. In total, 6,031 were exonerated from cancer, 78 were lost to follow-up (67 for ≤ 50 years and 11 for > 50 years), and 11 were diagnosed with cancer (five for 41-50 years and six for > 50 years, 10 presented with symptoms). Overall breast cancer prevalence was calculated to be 18/10,000 (95% CI, 8 to 29/10,000). The number of women examined per breast cancer diagnosis was 237 (95% CI, 126 to 1910) for women of age 41-50 years and 196 (95% CI, 109 to 977) for women of age > 50 years. Median time to diagnosis for all women was 17.5 [1 to 32.5] days. CBE-detected tumors were not different than tumors presenting through standard care., Conclusion: In a previously unscreened population, yield from community-based CBE screening was high, particularly among symptomatic women, and required modest diagnostic resources. This strategy has potential to reduce breast cancer mortality.

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.

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.