OBJECTIVO Nos países africanos lusófonos, a formação em oncologia é uma necessidade não resolvida. O conhecimento em oncologia detido pelas diversas especialidades que compõem a equipa multidisciplinar de oncologia é, em grande medida, diminuta. Por esse motivo nos diversos encontros promovidos pelos PALOPs os temas educação e treino têm sido amplamente discutidos. Pretende-se encontrar consensos no sentido de que os currículos, as metodologias sejam semelhantes, respondam às carências identificadas e o reconhecimento nacional e pelos países da região, dos quadros formados, possa ter lugar.
METODOLOGIA Auscultação pelo representante dos PALOPs no Comité de educação e treino e de investigação da AORTIC dos responsáveis pela política oncológica de Angola, Cabo Verde e Moçambique, responsáveis pelas unidades de saúde dedicadas à oncologia e internos de especialidade desses países em reunião a 9 de Abril de 2019, em Portugal, com o com o objetivo de identificar aspetos importantes e propor um programa de ação para formação em Oncologia para os países integrantes.
RESULTADOS Conclui-se que a formação em oncologia deverá integrar os programas curriculares dos cursos pré-graduados das distintas licenciaturas da área de saúde. A nível das ordens profissionais deve-se desenvolver ações que visem a formação especializada em oncologia. Promover o debate com o objetivo de apoiar a formação em oncologia cirúrgica, médica e radio-oncologia em cada país. Este, apoiará os colégios já existentes, na organização de competências ou sub-especialidades de oncologia. Deve-se manter a formação não formal em oncologia em todas as áreas mas reconhecida pelas autoridades nacionais e pela AORTIC. Os PALOPS devem divulgar as actividades formativas para que haja cooperação e usufruto por todos os países. Deverão ser elaborados manuais em conjunto de apoio ao ensino da oncologia.
CONCLUSÕES A formação em oncologia foi definida como uma actividade estratégica a integrar os Planos Oncológicos dos PALOPs.

OBJECTIVE System dynamics (SD) modeling is a robust systems science methodology still under-used in clinical and translational science. We demonstrate the utility of SD modeling by simulating a multi-centre cohort study of prostate cancer (PrCa) survival, using PrCa patients enrolled in an on-going PrCa genetics study in a Pan-African sample [U01CA184374, Rebbeck, PI; Men of African Descent Cancer of the Prostate Consortium (MADCaP)].
METHODS Working in collaboration with MADCaP investigators, we built a SD model to simulate a cohort study of African men presenting to hospital for PrCa diagnosis and treatment. Key parameters in our SD model included study enrolment start and end dates; case accrual and refusal rates; lost-to-follow up rates; Gleason score distribution (<=6, 7, 8-10); survival time by Gleason score; and PrCa-specific and other death proportion. The resultant SD model was a working set of algebraic and ordinary differential equations, depicted as a ‘stock-and-flow’ diagram. Dimensions (units) of stocks, flows, and auxiliary variables were checked. Major endpoints of interest (stocks) represented in the SD model included: (1) Enrolment, (2) PrCa-specific deaths, (3) non-PrCa deaths, and (4) cases lost-to-follow-up. Simulated output showed change-over-time (months) for variables in the model, displayed as time series vectors or as ‘behaviour-over-time’ graphs. With estimates of Gleason score distribution at enrolment and with survival time by Gleason score based upon available parent study data, we simulated likely enrollment trajectories and major endpoints, stratified by Gleason score.
RESULTS A ‘base case’ scenario was simulated that replicated case enrolment and known endpoints for the parent study, from inception to date (April 2019; N=1,918). Output over a period of 96 months (follow-up through 2024), which simulated design dynamics beyond the original study period and over the planned cohort study period, revealed distinctive patterns of mortality stratified by Gleason score. Gleason 8-10 cases were most prevalent but generated a similar proportion of surviving cases compared to cases with Gleason 7 by study end. Also, sensitivity analyses showed that if the lost-to-follow up rate in the simulated cohort study could be reduced from 8% to 5% per year, recruitment rates would meet sample size expectations, powered to an expected PrCa-specific morality rate of 72%.
CONCLUSION Planning and implementing complex study protocols in resource-limited settings is challenging. Simulation-supported research design can help researchers, study staff, and other stakeholders ‘see’ short-term and long-term pitfalls in participant outreach, recruitment, data collection, retention and other aspects of study management.

OBJECTIVES Cervical cancer is the leading cause of cancer deaths among women in Tanzania. To increase access to screen and treat services, Jhpiego with Tanzania Ministry of Health (MOH) through USAID funded Cervical Cancer Prevention Program has worked since 2014 to strengthen systems at national and regional levels for delivery of sustainable cervical cancer screening and treatment services. The purpose of this paper is to describe key sustainability lessons at program level from Njombe and Iringa Regions in strengthening cervical cancer screening and treatment services beyond donor support.
METHODS Using WHO health systems building blocks consisting of community mobilization, policy enabling environment, human resource capacity building; and strengthening service delivery; referral and data management systems, Jhpiego worked with the MOH in Iringa and Njombe Regions to strengthen systems for sustainable cervical cancer screening services. Emphasizing Single Visit Approach (SVA), which consists of screening with visual inspection with acetic acid (VIA) followed by immediate treatment of pre cervical cancer lesions the program supported Regional Health Management Team and Regional Referral Hospital capacity building to ensure sustainability beyond donor support.
RESULTS A total of 91 program managers knowledge and 95 health care provider’s skills strengthened for delivery of quality cervical cancer prevention services. 13 District Councils budget plans incorporated cervical cancer screening activities for sustainability. 38,389 women were screened using VIA with VIA positivity rate of 7%. 98% of women with pre-cancerous lesions were treated on the same day with cryotherapy. 20% of women screened were HIV infected.
CONCLUSIONS Experience shows that implementing functional Cervical Cancer Prevention Program using stakeholder’s engagement and health systems strengthening approach contributes for sustainability of cervical cancer prevention program. Lessons learned point to the importance of: political commitments, partnership, appropriate resource allocation, competence-based training, monitoring and quality assurance in order to achieve long-term sustainability. However, limited funding is a great barrier to sustainability and scaling up.

INTRODUCTION AND OBJECTIVE Because of their massive use by 80-85% of African population, medicinal preparations from known plants used traditionally against cancer in Africa need to be evaluated for their efficacy using reverse pharmacology approach.
MATERIAL AND METHODS Forty (40) HIV/AIDs patients with cancer associated with HIV/AIDs were divided into 2 groups.and treated by trained traditional healers using for each group one of the following two plant extracts (Cancer bush (CB, Sutherlandia fructescens) and Devil's Claw (DEV, Harpagophytum procumbens) used for a long period of time in Southern Africa in the traditional treatment of those diseases. Analytical and biological previously conducted, demonstrated their scavenging capacity on free radical generation and their chemo preventive/anti-inflammatory and anti-metastasic activities using molecular techniques. Biological tests: CD4 count viral load and liver enzymes: Aspartate amino transferase (AST), Alanine amino transferase (ALT) and y Glutamyl transpeptidase (y GT).have been performed throughout the progression of the disease before and after the administration of plant preparations. Regular adjustment of doses was performed for quality control and standardisation purpose based on active compounds present in each of the plant extracts.
RESULTS Our data demonstrated that Cancer bush and Devil’s Claw used as medicinal plants in South Africa possess all at some stages, antioxidant activities. A significant chemopreventive/anti-inflammatory activity detected by inhibition of TPA-stimulated COX-2 expression in MCF-10A cells in vitro and in mouse in vivo was observed with both plant extracts. An immune-boosting activity against HIV/AIDS and a disappearance of malignancies associated with HIV/AIDS disease were observed after six-month treatment of these patients by these herbal preparations. Extract from DEV has reduced more the malignant lesions because of its substantial anti-metastatic activity on MMP-7 mRNA in HT-29 cells.
CONCLUSION This type of “reverse pharmacology” approach can help to improve patient health status and to achieve rapidly a programme of transferring promising plants into clinical settings.

OBJECTIVE Burkitts Lymphoma (BL) is common in sub-Saharan Africa (SSA). In high-income countries, BL is highly curable with chemotherapy. However, there are few prospective studies from SSA describing non-pediatric BL and no regional standard of care. We present here a summary of BL outcomes under local standard-of-care therapy in Malawi.
METHODS Thirty-five participants aged ≥15 years with newly diagnosed BL from 2013-2018 in Malawi were enrolled. Chemotherapy was administered according to local institutional guidelines, with concurrent antiretroviral therapy (ART) if HIV-infected.
RESULTS Median age was 21 (range 15-61) and 15 (43%) participants were HIV-infected. Twenty-seven (77%) participants had stage III/IV disease and 19 (54%) had ECOG performance status (PS) >1. Among HIV-infected, median CD4 count was 130 (range 29-605), and ten (67%) had suppressed HIV viral load. Four (11%) patients died before chemotherapy initiation. First-line chemotherapy consisted of CHOP in 22 (71%), infusional EPOCH in four (13%), high-dose methotrexate-based chemotherapy in four (13%), and rituximab+CHOP in one (3%). Among 28 evaluable participants, fourteen (50%) achieved a complete response and six (21%) achieved a partial response. Median overall survival (OS) was seven months; one-year OS was 40% (95% CI 24-56%). 16/22 (73%) deaths were from disease progression. Death was associated with worse PS, lower BMI, higher stage, higher LDH, and higher creatinine. Compared with CHOP, more intensive chemotherapy was associated with decreased mortality (HR 0.24 [0.05-1.02], p=0.05).
CONCLUSIONS This is among the best characterized prospective cohorts of non-pediatric BL in SSA. Most deaths resulted from progressive BL. Patients who received more intensive therapy appeared to have better outcomes. Defining optimal approaches is an urgent priority in SSA.

BACKGROUND Kaposi sarcoma (KS) is highly associated with immunosuppression, and evidence suggests that KS oncogenesis is associated with loss of T-cell mediated control of human herpesvirus-8 (HHV-8). KS is a complex tumour, characterized histologically by spindle-like tumour cells infected with HHV-8 and marked inflammatory infiltrate. Identifying the elements that comprise the KS tumour, the phenotypic and translational state of these cell types, and how these cellular components interact in vivo will advance our understanding of KS tumorigenesis and guide the development of new targeted therapies.
METHODS We evaluated KS tumor and normal skin samples obtained from treatment-naïve HIV-positive and HIV-negative adults with KS enrolled in an ongoing study at the Uganda Cancer Institute in Kampala, Uganda. RNA was extracted from tissue that had been snap frozen or preserved in RNALater, and sequencing was performed on Illumina HiSeq 2500. Leukocyte composition within each biopsy was estimated using CIBERSORT, an analytic platform used to characterize cellular gene expression profiles. Single-cell suspensions of a subset of KS tumours were sorted and evaluated using targeted multiplex RT-PCR with primers specific for 24 genes relevant to immune cell lineage, function, proliferation, and exhaustion.
RESULTS CIBERSORT analysis of 39 KS tumours revealed that CD4 and CD8 T cells, monocytes, and macrophages represent the majority of intratumoral hematopoietic cells. To date, 2 cryopreserved single-cell suspensions have been analyzed. Candidate KS tumor cells with a CD34+/VEGFR3+/LYVE-1+ surface phenotype comprised 1.54% and 0.35% of cells from HIV+KS and HIV-KS subjects, respectively. Flow cytometric sorting showed populations of immune cells, including CD4/CD8, monocytes, and macrophages. Targeted transcriptional profiling of the single CD8+ T cells revealed significant heterogeneity in the expression of various genes, but uniformly low expression of genes associated with proliferation and functional activation, such as Ki-67, granzyme B, and TNFa (Figure). Analysis of additional KS tumour single cell suspensions is ongoing.
CONCLUSIONS Our findings to date indicate that the immune infiltrate in KS tumors is dominated by T-cells and macrophages. Initial analyses suggest that the transcriptional profile of immune cells in KS tumors is consistent with an “exhausted” profile, which may have implications for the use of anti-PD1 or other immunotherapies targeting T-cell exhaustion in the treatment of KS.

OBJECTIVE Delays and inaccuracies limit histopathologic diagnosis of Kaposi sarcoma (KS) in Sub-Saharan Africa. We hypothesized that quantification of DNA from the etiologic agent of KS, Kaposi sarcoma-associated herpesvirus (KSHV), could distinguish KS from non-KS and be developed into a point-of-care diagnostic test.
METHODS We performed skin punch biopsies among consecutive patients with skin lesions suspected clinically to be KS in Uganda. Histopathologic evaluation of the biopsies was done in Uganda and by up to 3 pathologists in the US. DNA from KSHV ORF 26 from the biopsy tissue was quantified by polymerase chain reaction (PCR), performed by conventional methods, and by loop-mediated isothermal amplification (LAMP), performed in a novel portable device named Tiny Isothermal Nucleic Acid Quantification System (TINY). Using consensus of the US histopathology as gold standard and receiver operating characteristics curves, we estimated the performance of PCR and LAMP via TINY for the diagnosis of KS.
RESULTS Among 506 participants with skin biopsies, consensus US pathology revealed that 330 biopsies were KS, 149 not KS and 27 indeterminate. Compared to gold standard pathology, sensitivity of African pathology was 95% and specificity 70%. Quantification of KSHV DNA by PCR found an area under the curve (AUC) of 0.96; at one optimal cut-point, sensitivity for KS was 98% and specificity was 90%. In the first 262 biopsies evaluated in TINY, AUC was 0.94, with an optimal cut-point yielding 86% sensitivity and 85% specificity. In this same 262 biopsies, AUC for PCR was identical, and an optimal cut-point yielded 87% sensitivity and 87% specificity.
CONCLUSIONS Quantification of KSHV DNA from skin lesions, using both PCR and a new portable device employing LAMP, can accurately distinguish a high fraction of cases of KS from non-KS in Africa. The findings set the stage for development of a point-of-care diagnostic test for KS.

BACKGROUND We report on the quantitative and functional analysis of immune reconstitution in HIV+ patients treated with autologous stem cell transplant (AHCT) on BMT-CTN-0803/AMC-071 phase II study.
METHODS Immunome analysis was performed by 5 colour flow cytometry. Comparisons were made between HIV+ (n=40, lymphoma, BEAM conditioning) and HIV- (n=30, myeloma, melphalan conditioning) AHCT, age-matched recipients at 56, 180, and 365 days post-AHCT and 72 healthy controls (HC). Unsupervised PCA examined differences in immune cell proportions across 18 cell subsets for 3 cohorts, and across 108 cell subsets comparing HIV+ AHCT recipients to HC. Independent unsupervised analysis with importance index (IN) identified contributions of cell populations expressing immune markers to the differences between HIV+ and control immunomes. Wilcoxon rank-sum tests compared absolute counts of cell subsets. Functional responsiveness of was evaluated by Elispot.
RESULTS PCA analysis across 18 immune marker combinations showed HIV+ and HIV- AHCT recipients clustered away from HC and from each other at Day 56 and approached HC by Day 365. PCA performed across 106 markers showed increasing similarity between HIV+ and HC over time. IN identified the following subsets as significantly impacting differences between HIV+AHCT recipients and controls, (confirmed by Wilcoxon tests): activated T cells (higher HIV+); cytotoxic memory T cells (higher HIV+); effector cytotoxic T cells (higher HIV+); naïve T helper (lower HIV+); memory T helper cells (lower HIV+). HIV+ patient T cells showed higher production of INFγ with HIV and EBV pepmixes compared to controls.
CONCLUSIONS Analysis of immune recovery showed HIV+ AHCT patients exhibit lymphocyte profiling seen with chronic HIV infection and respond robustly to antigen recall. Differences included pro-inflammatory changes with increased markers of immune-activation, cytotoxic T cell numbers, depletion of naïve and expansion of memory T cells observed in chronic, treated HIV infection.

OBJECTIVE One of the main challenges facing health care organizations in Africa is insufficient trained personnel. To bridge this gap, Ampath Oncology Institute adopted an innovative non-profit–private-public sector partnership model.
METHODS Ampath Oncology Institute is a non-profit organization based in Eldoret, Kenya a low- and middle-income country (LMIC) in East Africa. Since 2017, employee volunteer fellows from Takeda pharmaceutical’s oncology research and development (R&D) team have worked alongside counterparts at Ampath. Depending on locally identified unmet needs, volunteers including biostatisticians, clinical scientists, outcomes researchers and project managers have provided support for Ampath projects. Takeda’s R&D fellows share their knowledge and technical expertise to help build capacity in areas including research, data management, education, survivorship care, and pharmacovigilance. This knowledge sharing is provided virtually and on-site and the partnership operates under project-specific governance structures led by AMPATH with goals, objectives and deliverables.
RESULTS The collaboration has provided mentorship for numerous employees at Ampath in areas including data collection, clinical research and support of a retrospective and prospective lymphoma standard of care study. There has also been the establishment of a patient navigation program to improve patient coordination and strengthen survivorship care through support groups for oncology patients. Educational materials on lymphomas for health care providers and community volunteers have been developed to increase disease awareness. Pharmacovigilance has also been improved through the development of standard operating procedures and standardization of medication forms. Employees from both organizations have enhanced their leadership skills and expanded their global health perspectives.
CONCLUSION The creation of an integrated project teams which involve multiple stakeholders is an effective strategy to address gaps in cancer health care and ensure sustainable support in low middle-income countries.

OBJECTIVE The factors that determine whether and how childhood cancer is prioritized in national health agendas and integrated into health systems remain poorly understood. We investigated the political, social, and economic factors that influence health system priority-setting on childhood cancer care (CCC) in a range of low- and middle-income countries (LMIC).
METHODS Based on in-depth qualitative case studies, we analysed the determinants of priority-setting for CCC in El Salvador, Guatemala, Ghana, India, and the Philippines using a conceptual framework that evaluates the impact of political contexts, actor power, ideas, and issue characteristics on political prioritization. Data derived from interviews (n=68) with key informants involved in CCC policies and programs, supplemented by academic literature and policy documents.
RESULTS Political priority for childhood cancer varies widely across the countries studied and is most influenced by political context and actor power dynamics. Ghana has placed relatively little national priority on CCC, due to competing priorities and a lack of stakeholder cohesion. In El Salvador and Guatemala, actor power has played a central role in generating national priority for CCC, where civil society organizations have disrupted legacies of fragmented governance to shape policy agendas. In India, an empowered private actor was instrumental in establishing priority and sustained channels of financing for CCC. In the Philippines, the childhood cancer community capitalized on a window of opportunity to expand access to CCC through the political prioritization of UHC and NCDs in health system reforms.  
CONCLUSIONS Actor power emerged as a critical enabler of CCC prioritization in LMIC. Responsiveness to political contexts – in particular, priority placed on NCDs and UHC – is also crucial to place CCC firmly on national health agendas. Governments must be convinced of the potential for health system strengthening and the capability of networked actors to amplify public sector investments and catalyse change on the ground.