Jeremy S. Slone

Training Global Oncologists: Addressing the Global Cancer Control Problem

The global incidence of cancer has increased by approximately 20% in the past decade, an increase mostly due to cases in low- and middle-income countries (LMICs) (1). By 2020, up to 70% of the 20 million annual new cancer cases are expected to occur in LMICs (2). The incidence of cancer in LMICs is increasing rapidly; however, many countries are not prepared to address this epidemic. Cancer survival rates in LMICs are often less than one-third of those in high-income countries (3). In addition to local capacity-building efforts, the involvement of the oncology community from high-income countries will be instrumental in changing the course of this impending global cancer crisis. There is a vital need to train global oncologists to work with colleagues in LMICs to develop sustainable capacity and infrastructure for clinical oncology care, research, and education. However, enumeration of specific goals and novel programs, and the path to implementing these programs, is not clear. Oncology programs in North America lack formal training or exposure to global oncology. Even without a formal curriculum, with the rise in global health (GH) oncology interest, several opportunities have developed for trainees committed to GH. We describe herein current opportunities and future directions for oncology trainees in the United States (US) who are interested in pursuing careers as global oncologists.

Mapping the Epidemiology of Kaposi Sarcoma and Non-Hodgkin Lymphoma Among Children in Sub-Saharan Africa: A Review

Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non‐Hodgkin lymphoma (NHL) compared to HIV‐negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub‐Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV‐infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV‐infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA.

Reply to “Childhood cancer in Africa”

To the Editor: We were pleased to see the recent comprehensive and informative review by Kruger et al. [1] entitled Childhood Cancer in Africa. However, we feel compelled to address an important omission that, per Figure 1 from Childhood Cancer in Africa, erroneously indicated there are no pediatric cancer services available in Botswana. In fact, Botswana has an active pediatric hematology/oncology program through partnership between its Ministry of Health (MOH), Baylor College of Medicine (BCM), Texas Children’s Cancer Center (TCCC), Baylor International Pediatric AIDS Initiative (BIPAI), and the Texas Children’s Hospital Global Health Service Corps. Partnership in pediatric HIV care between the MOH and BIPAI began in 1999 when Botswana had the highest adult prevalence of HIV in the world at 35.8% [2]. With assistance from Bristol-Myers Squibb, the Botswana-Baylor Children’s Clinical Centre of Excellence (BBCCOE) was later constructed and opened in 2003 in Gaborone on the campus of PrincessMarina Hospital (PMH), the country’s largest referral hospital. The BBCCOE was the first comprehensive pediatric HIV clinic in sub-Saharan Africa, served as a model for subsequent clinics, and still provides care to thousands of children. Currently, Botswana has the highest antiretroviral therapy coverage for HIV-positive children in subSaharan Africa [3]. With the benefit of the clinical infrastructure, existing partnership with the MOH, and evident need to treat both HIV-associated malignancies and other pediatric hematology/ oncology diagnoses, BIPAI, BCM, and TCCC have had a pediatric hematologist/oncologist in Botswana since 2007. This expanded a previously existing but small pediatric hematology–oncology program at PMH. With a fully nationalized health service, Botswana provides all health care free of charge for citizens including transportation to and from PMH for therapy. The Botswana model concurs with the World Health Organization (WHO) recommendation for universal coverage in low-income countries to promote and sustain health by providing timely access to care [4]. Thus, abandonment of pediatric oncology treatment is nearly non-existent, which differs significantly from rates reported in other resource-limited settings. Chemotherapy is provided free through the government formulary; surgical services are rendered by pediatric surgeons, orthopedic surgeons and neurosurgeons on the PMH staff; and radiation therapy is provided at a local private hospital through a guarantee of payment from the MOH. Additionally, a small number of children are referred to partner institutions in South Africa for interventions unavailable in Botswana. Numerous educational symposia, both in Botswana and in Houston, Texas, have created training opportunities for Batswana healthcare providers and have increased local capacity. A pediatric hematology–oncology fellowship training program is being planned to obviate the need for expatriate pediatric hematologist/oncologists. The program is also making significant scholarly contributions to the literature [5]. In their conclusion, Kruger et al. [1] suggest partnering with the established framework of the HIV/AIDS infrastructure in Africa to address pediatric cancer care. Botswana serves as a striking example of the feasibility and success of such collaboration.

Beyond Endemic Burkitt Lymphoma: Navigating Challenges of Differentiating Childhood Lymphoma Diagnoses Amid Limitations in Pathology Resources in Lilongwe, Malawi:

Background. Although Burkitt lymphoma (BL) is the most common childhood lymphoma in sub-Saharan Africa, Hodgkin lymphoma (HL) and other non-Hodgkin lymphomas occur. Diagnosing non-jaw mass presentations is challenging with limited pathology resources. Procedure. We retrospectively analyzed 114 pediatric lymphomas in Lilongwe, Malawi, from December 2011 to June 2013 and compared clinical versus pathology-based diagnoses over two time periods. Access to pathology resources became more consistent in 2013 compared with 2011-2012; pathology interpretations were based on morphology only. Results. Median age was 8.4 years (2.1-16.3). The most common anatomical sites of presentation were palpable abdominal mass 51%, peripheral lymphadenopathy 35%, and jaw mass 34%. There were 51% jaw masses among clinical diagnoses versus 11% in the pathology-based group (P < .01), whereas 62% of pathology diagnoses involved peripheral lymphadenopathy versus 16% in the clinical group (P < .01). The breakdown of clinical diagnoses included BL 85%, lymphoblastic lymphoma (LBL) 9%, HL 4%, and diffuse large B-cell lymphoma (DLBCL) 1%, whereas pathology-based diagnoses included HL 38%, BL 36%, LBL 15%, and DLBCL 11% (P < .01). Lymphoma diagnosis was pathology confirmed in 19/66 patients (29%) in 2011-2012 and 28/48 (60%) in 2013 (P < .01). The percentage of non-BL diagnoses was consistent across time periods (35%); however, 14/23 (61%) non-BL diagnoses were pathology confirmed in 2011-2012 versus 16/17 (94%) in 2013. Conclusions. Lymphomas other than Burkitt accounted for 35% of childhood lymphoma diagnoses. Over-reliance on clinical diagnosis for BL was a limitation, but confidence in non-BL diagnoses improved with time as pathology confirmation became standard. Increased awareness of non-BL lymphomas in equatorial Africa is warranted.

Lessons from pediatric HIV: A case for curative intent in pediatric cancer in LMICs

* Abbreviations: ALL — : acute lymphoblastic leukemia ARV — : antiretroviral medication BL — : Burkitt lymphoma CLHIV — : children living with HIV HIC — : high-income country LMIC — : low- and middle-income country Antiretroviral medications (ARVs) are now being provided to nearly 50% of children living with HIV (CLHIV) in low- and middle-income countries (LMICs), an increase of 30% in the past 5 years.1 The provision of ARVs in LMICs demonstrates that effective therapy can be delivered to children with complex medical issues. An estimated 96% of CLHIV and 80% of children <15 years of age living with cancer reside in LMICs, where 94 900 pediatric AIDS deaths and 120 000 pediatric cancer deaths occur annually.2,3 The health system infrastructure gains in the fight against HIV and other communicable diseases represent a promising platform for long-overdue, transformational cancer care in LMICs. Similar to combination antiretroviral therapy in the context of pediatric HIV, the advent of combination chemotherapy in the mid-1960s revolutionized pediatric cancer treatment. Before chemotherapy, pediatric cancer was uniformly fatal, and care was focused on palliation. By the 1970s, over half of children diagnosed with cancer in high-income countries (HICs) were cured. … Address correspondence to Henry Miller, Office of HIV/AIDS, United States Agency for International Development, 1300 Pennsylvania Ave, NW, Washington, DC 20523. E-mail: hmiller{at}usaid.gov

Increasing Numbers of New Kaposi Sarcoma Diagnoses in HIV-Infected Children and Adolescents Despite the Wide Availability of Antiretroviral Therapy in Malawi

To the Editor—It is with great interest that we read the recently published manuscript on Kaposi sarcoma (KS) risk in human immunodeficiency virus (HIV)–infected children worldwide [1]. The particularly high incidence rate of pediatric KS reported in eastern Africa is striking. The experience in our pediatric HIV-related malignancy program in Lilongwe, Malawi, is consistent with the epidemiologic data from the Pediatric AIDS-Defining Cancer Project Working Group. In eastern and central Africa— where human herpesvirus 8 (HHV-8) is endemic and prevalence rates are highest in the world—KS is among the 3 most common childhood cancers overall [2–5]. With the increased availability of combination antiretroviral therapy (cART) in sub-Saharan Africa over the past decade, it is important to determine trends in KS. Data from South Africa and Zambia demonstrate that in adults, the risk for KS and incidence rates remain high despite increased cART coverage [6, 7]. We retrospectively investigated trends in pediatric KS from 2006 to 2015 in our pediatric (<18 years of age) HIV-related malignancy program at the Baylor College of Medicine International Pediatric AIDS Initiative Center of Excellence in Lilongwe, Malawi. The scale-up in delivering cART to children in the Malawian national antiretroviral program began in 2005. Since then, >50 000 children have been initiated on cART, including 3964 at our center. Despite the substantial increase in cART coverage in Malawi, the annual number of new KS diagnoses in HIVinfected children and adolescents has steadily increased over the past decade (Figure 1). The average annual number of new pediatric KS diagnoses from 2006 to 2010 (n = 89) was 17.8 cases per year, compared to 25.2 cases per year from 2011 to 2015 (n = 126). We also compared numbers of new KS diagnoses in HIV-infected children and adolescents from our 2 published cohorts [8, 9]. In the recent cohort, 70 patients were diagnosed with KS over 34 months from 2010 to 2013. That represented 5.2% (70/1359) of all children initiated on cART at our center [9]. The historical control reported 72 patients with KS from 2003 to 2009 (total duration 80 months), representing 3.2% (72/2241) of cART initiations [8]. The older cohort averaged 0.9 new KS diagnoses per month vs 2.1 new KS diagnoses per month more recently. It is evident that the number of new pediatric KS diagnoses in Malawi is not yet decreasing despite wider availability of cART. Recent data from Blantyre, Malawi, reveal similar numbers [10]. Several factors that may contribute to the current increased numbers of pediatric KS diagnoses include improved referral networks via outreach to regional healthcare professionals, facilities, and patients through our Tingathe Community Outreach Program, improved infrastructure to establish definitive diagnoses via biopsies (especially in lymph node KS), and persistent gaps in access to cART. Despite great efforts to reduce the severe complications of pediatric HIV infection with cART, KS still remains an important complication in HHV-8– endemic regions of Africa. Our experience has demonstrated that long-term complete remission may be achieved in childhood KS with the combination of relatively moderate chemotherapy and

Maximizing the Impact of a Pediatric Hematology-Oncology Twinning Program

To the Editor: In 2007, Baylor College of Medicine (BCM) and the Texas Children’s Cancer and Hematology Centers (TXCH) established a comprehensive pediatric hematology-oncology program at Botswana’s primary government referral hospital, Princess Marina Hospital (PMH).[1] The PMH program remains the only center, public or private, that provides services to children with cancer and blood disorders in Botswana. The barriers to diagnosis, management, and survival of pediatric cancer in low and middle income countries (LMIC) have been described in many studies and include abandonment of treatment, late presentation, lack of diagnostic and treatment options, limited supportive care, and toxicity from treatment. Thus, survival from pediatric cancer in LMIC lags far behind high income countries. Creative approaches are necessary to achieve the best possible outcomes in LMIC as resources common in modern pediatric cancer centers are typically lacking. Since the program’s inception, the pediatric hematologyoncology program at PMH through BCM/TXCH has relied primarily on one full-time pediatric hematologist-oncologist (PHO) with periodic visiting PHOs. With high patient volumes in addition to various administrative, research and teaching responsibilities, interventions were necessary to maximize the impact of the twinning program at PMH with limited resources. In 2013, adapting a successful model from high income countries, the position of a Care Coordinator (CC)/Project Manager (PM) was created. The role of the CC is to organize patient care activities and facilitate appropriate healthcare services through the exchange of information among participants with the goal of achieving timely, high quality, and cost-effective healthcare with optimal outcomes. The PM role focuses on program development, patient education, and research infrastructure. In the 2 years since the establishment of the CC/PM position, many advances have been made including the following: creating referral and orders management systems to reduce abandonment of treatment or lost to follow-up of survivors; coordination of both local and international referrals for services unavailable at PMH; the development of patient educationmaterials for 13 malignancies and seven blood disorders and a handbook for all new oncology patients; creating standardized inpatient and outpatient clinical note forms; establishment of a comprehensive pediatric oncology database with enrollment of over 200 pediatric cancer patients for both clinical and research purposes that will soon provide the first data on pediatric cancer from the PMH program; editing a comprehensive pediatric hematology-oncology supportive care handbook that is nearing completion; liaising with philanthropists and non-governmental organizations offering support to patients and families; leading psycho-social efforts to decrease the negative impact of prolonged hospitalization; collaborating with colleagues at the twinning institution (BCM/TXCH) to appropriately leverage the twinning institution’s experience and resources; and education of local staff, especially nurses and dietitians, with limited pediatric cancer experience. The CC/PM has liaised with local benefactors for the donation of 14 televisions throughout PMH’s pediatric medical and surgical wards, wheelchairs to patients with disabilities, and recently, the donation of over 600 child-friendly pillow cases. Utilizing the role of the CC/PM, the above accomplishments were possible in spite of a growing clinical service that saw almost 25% increases in the average daily inpatient census and new patient referrals from 2013 to 2014. Pediatric oncology programs in high income countries are successful due to a multi-disciplinary approach with specialized staff including PHOs, nurses, social workers, care coordinators, child life specialists, and many other essential staff. A low cost and high impact option in LMIC is the employment of nurses and/or social workers in the non-clinical CC/PM role serving to maximize the impact of the twinning program.

Extramedullary hematopoiesis of the liver in a child with sickle cell disease: A rare complication

We present the case of a 7‐year‐old Cameroonian girl with sickle cell disease (SCD) who presented with progressive abdominal distension, fever, severe anemia, respiratory distress, and fatigue. Abdominal ultrasound showed a 15.3 cm × 11.5 cm × 15.5 cm solid echogenic mass within the left lobe of the liver. Fine‐needle aspiration showed features of extramedullary hematopoiesis (EMH). Despite transfusions, antibiotics, and initiation of hydroxyurea the patient died of respiratory failure during the hospital stay. There is a paucity of information on EMH in the pediatric sickle cell population, especially from resource‐limited settings such as western Africa. EMH, however, is a known complication of SCD and should be considered in patients presenting with mass lesions in the setting of chronic anemia. With limited therapeutic interventions for EMH, including radiation and hydroxyurea, the emphasis should be on improving overall treatment of patients with chronic and untreated hemolytic anemia, especially in low‐income countries.

Corrigendum: “Training Global Oncologists: Addressing the Global Cancer Control Problem”

[This corrects the article on p. 80 in vol. 5, PMID: 25905040.].

A 14-Year-Old Boy With Fevers, Cytopenias, and Neurocognitive Decline

A teenaged boy is admitted with 1 month of experiencing fever, cytopenias, and neurocognitive decline. How do you approach diagnostic workup and the management of this patient? A 14-year-old boy presented to our institution with a 1-month history of neurocognitive decline and intermittent fevers. His history was significant for fevers, headaches, and a 10-lb weight loss. Previous examinations by multiple medical providers were significant only for bilateral cervical lymphadenopathy. Previous laboratory workup revealed leukopenia, neutropenia, and elevated inflammatory markers. Despite improvement in his laboratory values after his initial presentation, his fevers persisted, and he developed slowed and “jerky” movements, increased sleep, slurred speech, delusions, visual hallucinations, and deterioration in his school performance. A brain MRI performed at an outside hospital before admission at our institution was concerning for patchy, increased T2 and fluid-attenuated inversion recovery signal intensity in multiple areas, including the basal ganglia. After transfer to our institution and admission to the pediatric hospital medicine team, the patient had an acute decompensation. Our subspecialists will discuss the initial evaluation, workup, differential diagnosis, definitive diagnosis, and subsequent management of this patient.