Establishing Cancer Treatment Programs in Resource-Limited Settings: Lessons Learned From Guatemala, Rwanda, and Vietnam

Purpose The global burden of cancer is slated to reach 21.4 million new cases in 2030 alone, and the majority of those cases occur in under-resourced settings. Formidable changes to health care delivery systems must occur to meet this demand. Although significant policy advances have been made and documented at the international level, less is known about the efforts to create national systems to combat cancer in such settings. Methods With case reports and data from authors who are clinicians and policymakers in three financially constrained countries in different regions of the world—Guatemala, Rwanda, and Vietnam, we examined cancer care programs to identify principles that lead to robust care delivery platforms as well as challenges faced in each setting. Results The findings demonstrate that successful programs derive from equitably constructed and durable interventions focused on advancement of local clinical capacity and the prioritization of geographic and financial accessibility. In addition, a committed local response to the increasing cancer burden facilitates engagement of partners who become vital catalysts for launching treatment cascades. Also, clinical education in each setting was buttressed by international expertise, which aided both professional development and retention of staff. Conclusion All three countries demonstrate that excellent cancer care can and should be provided to all, including those who are impoverished or marginalized, without acceptance of a double standard. In this article, we call on governments and program leaders to report on successes and challenges in their own settings to allow for informed progression toward the 2025 global policy goals.


INTRODUCTION
The global burden of cancer is expected to increase significantly by 2030; in that year alone, an estimated 21.4 million new cases and 13.2 million deaths will occur, and the vast majority of this burden will befall low-and middle-income countries. [1][2][3][4] In all regions of the world, formidable changes to health care delivery systems must occur to meet this demand. Although global goals and targets have been agreed upon at the international level, 5-11 less has been documented about the principles that underlie national efforts to grow cancer treatment programs. As such, implementation blueprints for a quality cancer system remain scarce, as clinicians and policy-makers are strapped by incommensurate human resource capacity, infrastructure, treatment options, financial support, and-often-political will. 12

WHO Building Block 1: Service Delivery
• Simultaneous centralization and decentralization: Centralization of comprehensive services to regionally distributed facilities; decentralization of basic services and diagnostic capacity for referrals • Focusing efforts on excellence of care (not accepting a double standard in delivery nor outcomes) • Building strong partnerships with academic medical centers in high-income countries (HICs) • Remote consults from oncologists and pathologists in HICs via tumor board or online systems • Respect for the cultural characteristics of the local population in developing programs

WHO Building Block 2: Health Workforce
• Retaining cancer specialists in country through policies or incentives • Welcoming volunteer experts to support program development according to national agenda • Creating regional training centers for oncologists, attracting talent and retaining skilled personnel • Offering continuing medical education at all levels of healthcare providers in cancer care • Developing training programs for non-MDs (eg, nursing oncology, cancer epidemiology) • Building and maintaining twinning programs with high-income countries for capacity transfer

WHO Building Block 3: Information
• Baseline national survey at initiation to assess needs and gaps in cancer care • Use of WHO's CANREG-5 to create national or hospital-based registry • Establishment of electronic, prospective records to monitor and document outcomes • Integrating implementation science into policy, strategic planning, and program development • Strengthening academic collaborations with centers in high income countries to advance education and build a joint research agenda that enables professional development on both sides

WHO Building Block 4: Medical Products, Vaccines, Technologies
• Collaboration with regional neighbors to leverage purchasing power for medicines • Adding essential antineoplastics to the national formulary for availability in the public sphere  16 New research also has produced priority advisement to reduce disparities in cancer control. 17,18 These advances, along with additional healthrelated gains from the international to the local levels, have laid the foundation for evidence-based policymaking and program development in cancer care and delivery.

Country Background
Guatemala is a mountainous nation in Central America that is home to more than 16 million people, half of whom live in rural areas. 19 The distribution of income is markedly unequal; 59% of the population lives below the national poverty line 20 ( on health care per capita (83% is out-of-pocket spending). Only 27% of the population is covered by public health insurance. 25 Signs of poverty are mirrored in high rates of maternal and infant mortality. 26,27 Half of children in Guatemala younger than age 5 years are chronically malnourished. 28 The intersection of malnutrition and malignancy as it pertains to survival outcomes and quality of life is vital. 29,30

Integration of Cancer Care Into the Health System
In the 1990s, a group of clinicians (including authors of this article) conducted a retrospective study on pediatric cancer outcomes between 1990 and 1995 at the two existing public tertiary care hospitals in Guatemala City: the Roosevelt Hospital and the San Juan de Dios Hospital. The findings were striking: only 100 patients were diagnosed with cancer each year, of 600 expected. 31 Also, adult oncologists were providing pediatric services, and the 2-year event-free survival rate was only 28% for many diseases now considered curable. 31 Existing facilities lacked diagnostic tools, systemic therapies, radiotherapy, interventions to treat sepsis, sufficient blood bank support, and appropriate nursing staff. With this needs assessment in hand, the clinicians created a targeted action plan for pediatric cancer care and invited the International  Two years later, this group formed the Fundación Ayúdame a Vivir (AYUVI), which led to the following achievements: (1) passing a decree in 1998 to create the Unidad Nacional de Oncología Pediátrica (UNOP; National Pediatric Cancer Unit) as the single center to provide cancer treatment to Guatemalan children; (2) an agreement between UNOP and SJCRH to establish a clinician twinning program to pair American and Guatemalan practitioners to advance care, education, and research 32,33 ; and (3) allowing AYUVI to serve as a foundation for advocacy and fundraising. UNOP opened in April 2000 as Gutatemala's first dedicated pediatric cancer hospital.
The annual budget of UNOP is supported by the AYUVI Foundation (64%) and the MOH (36%); AYUVI covers the infrastructure budget. UNOP reports to the MOH, but it remains a stand-alone facility self-operated and financed without external earmarking. Today, the SJCRH partnership provides 2% of the UNOP operating budget as well as substantial technical support for clinical care. 34 The number of cases at UNOP has more than quadrupled since its opening (524 patients younger than 18 years old in 2017). Two thousand pediatric patients are on active protocols. In addition, the treatment abandonment rate has been dramatically reduced (41% before UNOP 31 to 27% in 2001 35 to now less than 1%), which resulted in a more than doubling of the overall survival rate 36 ( Table 3).
UNOP provides diagnoses (imaging, pathology), treatments (surgery, chemotherapy, and radiation therapy), supportive care (infection, blood products, nutrition), and psychosocial support (housing, social services, transportation) free of charge. 32   Finally, a pediatric early-warning score program was incorporated to decrease inpatient morbidity and mortality, 37 and a hospital-based cancer registry has been incorporated into the MOH registry.
UNOP refers patients to external (but integrated) facilities for blood bank, radiotherapy, specific molecular studies, and imaging. Few delays have been recorded because of the strong relationship UNOP maintains with the external facilities. A purchasing manager organizes procurement of medicines from vendors, which has resulted in a stable supply chain. Guatemala is a signatory of the Pan American Health Organization Strategic Fund, which enables the public sector to purchase certain antineoplastic medicines on the WHO Model List of Essential Medicines, as well as supplies and consumables, at discounted rates. 38 Six data managers are responsible for recording and uploading outcomes data into a global pediatric oncology data base, which ultimately feeds back into UNOP strategic plans as well as to donors and the MOH. 39 UNOP is also an academic center where medical students from three Guatemalan universities and pediatric residents rotate. In 2003, UNOP and the Guatemalan School of Medicine of Francisco Marroquin University launched a regional fellowship training program with funding from SJCRH, with rotations in the United States, Italy, and Guatemala. This accredited 3-year fellowship program has graduated 21 pediatric hematologistoncologists from Central and South America. All have returned to their home countries to work in pediatric oncology units.
In Guatemala, the government has begun to implement a National Strategic Plan for Cancer and, in 2015, formed a National Commission of Chronic Nontransmissible Diseases. Separately, pediatric hematologist-oncologists in Guatemala and counterparts from six other Latin American countries launched the Asociación de Hemato-Oncología Pediátrica de Centro América, an organization that annually reviews and agrees upon treatment protocols for nearly a dozen pediatric malignancies. 40 In Guatemala, many challenges remain, including persistent late-stage diagnosis, suboptimal public sector investment, and limited health care personnel. To maximize efficacy and agility, UNOP solicits annual evaluations through the Asociación de Hemato-Oncología Pediátrica de Centro América, conducts a biweekly AYUVI-UNOP board meeting, and is finalizing its 5-year strategic plan.

Country Background
Rwanda is a landlocked East African country that is home to approximately 11.6 million people, 71% of whom live in rural areas. 41 The 1994 genocide against the Tutsi dismantled the nation, which resulted in one million lives lost, an entire generation of health care professionals gone or displaced, and a surge of infectious diseases as a result of the broken health care system. 42  Vaccination coverage went from less than 25% to more than 90%, and maternal mortality and mortality in children younger than age 5 years more than halved. These outcomes have been attributed to accessible national programs, the Rwandan community health worker network (45,000 strong), the enrollment of more than 90% of the population in public health insurance, and the opening of more than 500 health centers. 47 Yet, despite the exponential increase in the number of clinicians, only three oncologists (one clinical, one radiation, and one pediatric), two hematologists, and one oncoplastic surgeon currently practice in the country. 43,48

Integration of Cancer Care Into the Health System
Case documentation efforts in Rwanda in the 1960s to 1980s showed a predominance of cancers with infectious etiologies, but studies were observational, because treatment was not yet available. 49 The decision to open BCCOE in a rural area was rooted in an existing and strong academic and clinical partnership. The MOH was simultaneously planning to launch four additional cancer treatment units in district hospitals nationwide. The majority of patients at BCCOE initially seek care at their local health center and are referred to BCCOE from a district or referral hospital. A cancer pathology collaboration was introduced at BCCOE in 2012 and included training, anatomic telepathology, installment of new equipment, and expert volunteers. 60 Samples are processed and analyzed at BCCOE by Rwandan laboratory technicians and two pathologists, with support from DFCI colleagues. [61][62][63] In 2015, the MOH worked with DFCI to expand the national drug formulary alongside the WHO Essential Medicines List expansion, which increased the number of antineoplastic agents on its national formulary to 31. 64 The MOH and DFCI also prepared and approved standardized cancer treatment protocols (15 adult protocols and seven pediatric protocols). BCCOE offers outpatient and inpatient services, diagnosis, surgery, systemic treatment, palliation, and survivorship care, and it provides nutritional and transportation support for patients. Surgeries are performed in Butaro or other hospitals, and the majority of chemotherapy is administered in Butaro. To date, more than 4,000 children and adults have received care at BCCOE regardless of ability to pay. 55 A vital investment has been the development and refinement of an electronic medical records system to track patient outcomes, which allows for real-time monitoring, quality control, and prospective research. 65 A number of scientific articles have been published as a result, which document the patient outcomes at BCCOEimplementation science research is a priority of the MOH/DFCI/PIH partnership. 66,67 Although there are still no oncologists based at BCCOE, their partnerships have allowed for capacitybuilding and task-shifting. 56,68 The national Human Resources for Health Program, which jointly launched with the Clinton Health Access Initiative in 2012, also helped advance oncology training. 48 In addition, several Rwandan physicians currently are enrolled in oncology fellowship programs abroad (eg, Tanzania, Egypt) with contracts to return to Rwanda. In addition, 46 nurses have graduated from a 3-week nursing oncology program, and two have graduated from a 12-week program. 69 Three major hospitals have cancer pathology, imaging, surgical oncology, and palliative care programs. The main private hospital in the country, King Faisal Hospital, has additional services (ie, computed tomography, magnetic resonance imaging, and chemotherapy). Twenty district hospitals (of 42 total in Rwanda) and four university teaching hospitals are equipped for cervical cancer screening and same-day treatment of precancerous lesions with cryotherapy or loop electrosurgical excision procedure.
Rwanda still faces significant challenges-most notably, the financing of expanded services, such as radiation therapy (RT) and bone marrow transplantation. The Rwanda Military Hospital is opening the country's first RT facility in 2018. One stopgap solution has been to send patients abroad to receive RT while the MOH raises funds for an RT center. These patients are selected by a multidisciplinary review board on the basis of curative potential, but this selection is an extremely difficult clinical process. An additional challenge is the lack of a cancer registry, although one is in development. Overall, Rwanda has made important strides in the realm of cancer care and recently hosted the 11th International Conference on Cancer in Africa, of AORTIC (African Organization for Research and Training in Cancer).

Country Background
Vietnam is a small coastal nation in Southeast Asia with a population of 92.5 million, 67% of whom live in rural areas. The two major cities, Ha Noi and Ho Chi Minh City, are separated by more than 1,000 kilometers and serve as regional health care hubs. Vietnam endured a protracted and troubled history of occupation, colonization, and war. Similar to Rwanda, Vietnam's economic growth has been remarkable in the last 30 years. Although still considered a lower-to middle-income country, data demonstrate strong annual gross domestic product growth of 5% to 6% for the past two decades along with a steadily increasing life expectancy at birth, which reached 76 years in 2016.
The country's health care system provides four levels of care: national, provincial, district, and community facilities. This design allows for certain medical needs to be fast-tracked to the national level (eg, cancer care). The main public and private hospitals that are situated in Ha Noi and Ho Chi Minh City are consistently overcrowded; rates of capacity overload range from 150% to 250%. There are two hospital beds per 1,000 people and 1.2 doctors per 1,000 people. 70 Disparities in access to care vary widely by geography, which contributes greatly to treatment abandonment.

Cancer Care in Vietnam
According Although a system is in place for cancer treatment in Vietnam, the infrastructure and workforce required for the national burden of disease remain insufficient. Certain diagnostics-such as immunohistochemistry and molecular analysisare accessible only at a handful of Vietnam's hospitals, and the availability of pathologists is limited to a few hospitals. These insufficiencies lead to significant treatment delays and render individual cancer care planning extremely difficult. In addition, geographic disparities that result from the country's mountainous terrain present the need for a program dedicated to rural cancer detection. Minimal funding for cancer control and high costs of targeted and cytotoxic drugs (even when subsidized) are major challenges. Health insurance in Vietnam does not yet cover all fees, especially advanced technologies and targeted therapies.

DISCUSSION
The three country cases presented in this article demonstrate the feasibility of establishing cancer care programs in resource-constrained countries. Several principles that underpin the successes deserve highlighting. First, energy and drive from local leadership for the initial demonstrable response to an increasing cancer burden facilitate partner and stakeholder engagement. Second, each case describes the role of partnerships (public and private) and how these can be a vital catalyst to launch and sustain treatment cascades. Third, a focus on professional development that harnesses international expertise for training and education of the health workforce has embedded capacity building in these systems. Strengthening the local workforce and retaining staff are critical, especially given the global competition for skilled practitioners.
Last, all countries exemplify a commitment to geographic and financial access to care. These cases demonstrate the importance of giving early consideration to establishing the entry point into health care at the community level and at the same time to strengthen referral networks to specialty services. In Guatemala, access meant financial affordability and provision of comprehensive services in one facility as well as regional partnerships to leverage purchasing power and clinical expertise. In Rwanda, access meant nationwide interventions and policies, international collaborations to advance treatment options, and provision of treatment regardless of ability to pay. In Vietnam, access meant improvement in geographic equity by strengthening the two main public facilities in the north and south as well as engagement of a broad set of stakeholders in planning efforts. While Guatemala's case sheds light on progress driven through the public-private interface and nongovernmental actors, Rwanda's and Vietnam's examples highlight the progress of government-led health care delivery in nations recovering from immeasurable devastation. Finally, and perhaps most importantly, the policy decision that was engrained in each program from the start was the restoration of dignity in the care of patients with cancer. This is no small decision, although it is often overlooked. All three countries demonstrate that excellent cancer care can and should be provided to all, including those who are impoverished or marginalized, without acceptance of a double standard. It is our hope that this article provides a framework of evidence and the programmatic elements to other countries looking to create or grow their own initiatives.
Emerging robust models of care can inspire both national cancer planning and peers in other countries who may encounter related challenges. This only can happen, though, if such efforts are documented and publicized. Implementation research, research capacity building, and dissemination of findings will be critical to shape national cancer control planning over time. We call on governments and program planners to share their experiences to maximize knowledge sharing and to allow for informed progression toward the 2025 global goals. We are convinced that there is a future in which where you are diagnosed with cancer does not determine whether you survive, and we hope that this article will provide insights to countries who share this belief.