In low-income countries (LIC) when children with cancer are referred to tertiary institutions, they are often grouped with children with other diagnoses, amidst adults with cancer, or both; wards may be overcrowded and/or have substandard hygienic facilities (lacking hand washing stations, hand sanitizers, individual toilets, etc.). Knowing that in the absence of reliable and accessible laboratory services most children with leukemia will die of infection before leukemia is diagnosed and that in the absence of chemotherapy or radiotherapy, solid tumors are exclusively surgical diseases, the absence of separate pediatric oncology wards in some LIC is no surprise. Furthermore, when standards of living are poor and health systems are fragmented or inadequate, pediatric cancer may either not seem to occur (because they are not diagnosed), present to medical attention for surgical interventions only (due to presence of a mass), or present to medical attention severely ill (due to advanced disease or sepsis). The reasons overcrowded settings prevail in LIC are likely multifactorial and variable from one place to another. Lack of space, staff, drugs, or expertise, as well as fatalism or a sense of futility of treatment, among others, may serve as explanations. It is through improvement of standards of living and health care infrastructure that children with cancer are able to reach medical care, be diagnosed with cancer, and stimulate the mobilization of resources towards the offering of cancer-directed therapy. Once the need to address pediatric cancer is acknowledged and more patients are diagnosed, expertise is built, and fundamental barriers to oncology care such as access to chemotherapy and safe handling of chemotherapy are addressed, clinicians building a PCU and looking to improve pediatric cancer outcomes must devise strategies for expanding towards the effective delivery of multimodal therapy (treatment that incorporates medical, psychosocial, supportive, surgical, and/or radiation oncology services).

PCUs often aim to cohort children with cancer. The justification for grouping children with cancer together and separating them from patients with other diagnoses, stems primarily from the desire to protect them [1]. However, this practice also creates several important opportunities that deserve to emphasized. From an organizational stand point, the introduction of chemotherapy, the infectious risks imposed by it, the need for close monitoring of toxicities, and the need for safe handling of chemotherapy and waste products often triggers the desire to separate cancer patients from others. Therefore, chemotherapy availability and administration can become the catalyst for physical creation of pediatric oncology wards. However, as mentioned before, a PCU is more than its infrastructure or physical space and can look differently in different parts of the world. Therefore, conceptualizing, creating, restructuring, or building a PCU creates opportunities for development of expertise by nurses, physicians, and surgeons (among other staff); standardization of care; education of dedicated staff in safe handling of chemotherapy; tracking of outcomes; prevention of infections; prevention or early management of toxicity; building of care teams; and provision of multidisciplinary patient-centered care (Fig. 5.1).

In the absence of dedicated space and staff, the quality of care provided to children with cancer can suffer [1, 2]. Some practical examples include the following. Without specialized PCUs, general physicians and nurses may not be able to build the expertise to guide development and implementation of treatment guidelines (or protocols). Without standardization of care, outcomes cannot be reliably measured and the need or areas to improve may be overlooked or neglected. When cancer patients need to share rooms or beds with other patients, they may be exposed to infectious diseases (respiratory, diarrheal, or other) that are mild to moderate in the normal host but can lead to death in them due to their immunosuppressed status. Without specialized nursing (generated by experience or formal curriculum), toxic effects of chemotherapy and complications may not be recognized and managed promptly, leading to morbidity or death. Furthermore, if standard procedures to protect staff during administration of chemotherapy and to handle and dispose of potentially dangerous materials are not developed, health professionals and family members are unnecessarily exposed to potentially toxic substances. Finally, in the absence of a sense of unity, respect, and common purpose among providers, decision making about care and communication with patients and families can be heavily fragmented.

Key Components, Human Resources: The spectrum of human resources needed at the PCU depends on the diagnoses being treated, the volume of patients seen at the center, and its economic supports. As adapted from the St. Jude Children’s Research Hospital International Outreach Program in their “Guide to Establishing a Pediatric Oncology Twinning Program” [3], ideally human resources at the PCU include a medical director, other physicians (generalists, pediatricians, pediatric oncologists) trained and designated to care of children with cancer, nurses and nurse educator, data managers, and administrators, along with specialists in infectious disease and infection control, pathology, radiology, radiation oncology, surgery (general or pediatric oncologic, orthopedic, and neurologic), pharmacy, pain, palliative and psychosocial services, child life, nutrition, and rehabilitation. Some staff, such as physicians and nurses, are ideally dedicated to the PCU and do not work at other locations. Other staff is likely shared with other departments or institutions depending on the volume of patients at the PCU.

Key Components, Other: In conceptualizing a PCU, the natural reaction is to focus on diagnostics, therapeutics, and supportive care. However, a multitude of biologic `and nonbiologic factors likely influence pediatric cancer outcomes at the PCU (see Fig. 5.2). Biologic factors include genetics, exposures, clinical characteristics, and molecular characteristics of the cancer. However, by the time the patient arrives to the PCU and is diagnosed, biologic factors are for the most part not modifiable. Nonbiologic factors include social and economic context, oversight and support, referral and surveillance capacities, infrastructure availability, and the functionality of the care team at the PCU. In LMC, nonbiologic factors and their influence on outcomes need to be studied in more detail because nonbiologic factors are likely most influential, prevalent, and actionable among barriers to improvement of pediatric cancer outcomes. A comprehensive linear and ecologic model of nonbiologic factors that influence pediatric cancer outcomes in a PCU is presented in Fig. 5.3.

International Society of Pediatric Oncology and International Network for Cancer Treatment and Research (SIOP and INCTR) Recommendations: In 1991, the SIOP Working Committee on Standards of Care and Training and Working Committee on Psychosocial Issues in Pediatric Oncology put forward recommendations for the organization of a PCU [4]. This consensus document recommended that all children with cancer should be offered child-oriented diagnosis, treatment, aftercare, and follow-up and gave basic guidelines for the development of PCUs. With progressive improvement in the standard of care in many countries resulting in improved survival, it was recognized that the guidelines for development of a PCU needed to be updated. In 2008, the first revised document was presented at the SIOP Pediatric Oncology in Developing Countries (PODC) meeting, which was further revised at consecutive meetings, and consensus was obtained. In 2010 the SIOP guidelines were further modified by the members of the INCTR Pediatric Oncology Working Group, many of whom were active SIOP PODC members. Table 5.2 shows the joint SIOP/INCTR recommendations for the development of a PCU [58].

Certification or Needs Assessment Program for PCUs: No consensus exists regarding the need for certification or periodic assessment of a PCU. In the SIOP/INCTR recommendations, it was suggested that programs that had international collaborations or twinning programs could use those resources for guidance and improvement. However, there was consensus that a process of certification, though voluntary, could be used to obtain support and additional services from governmental agencies or supporting NGOs.

Eighty percent (80 %) of the children with cancer live in low- and middle-income (LMC) [5]. Although regional variations in the incidence of childhood cancers have been reported [6, 7], the high proportion of pediatric cancer in LMC stems primarily from the fact that most of the world’s population under 18 years of age lives in LMC [8]. The etiology of childhood cancers remains predominantly unknown [6, 7] and increases in incidence of childhood cancer in LMC are usually a reflection of improved detection rates [2, 5]. Mortality from childhood cancer on the other hand is significantly higher in LMC compared to HIC, with a survival gap >50 % between some LMC and HIC [2]. Therefore, the highest burden of pediatric cancer in LMC and the centerpiece of cancer disparities between HIC and LMC does not result from high or changing incidence, but from differences in cancer-related mortality. In order to address this burden, PCUs in LMC can focus on reducing the risk of cancer-related death by promoting early diagnosis, delivering effective care, reducing the risk of treatment-related death, and reducing treatment abandonment (Fig. 5.4).

What about LIC or extreme resource-limited settings (ERLS)? What can clinicians do to address pediatric cancer in these settings? While providing an answer, experts in HIC sometimes struggle with envisioning pediatric cancer care without the full spectrum of technologies routinely used for diagnosis, monitoring, and treatment. In contrast, clinicians in LIC or ERLS struggle with how not to address pediatric cancer despite known human resource scarcity, equipment shortages, and high workloads. Clinicians in LMC are witnesses to how, as standards of living improve and health systems are strengthened, the burden of cancer becomes more noticeable and the need to address it imperative [9].

When addressing pediatric cancer in LMC, clinicians should keep in mind pediatric cancer is a heterogeneous group of diseases. Therefore centers in LMC, even those in ERLS, can make valuable contributions to the burden of childhood cancer in their settings. In this section we summarize four key examples of optimization of resources: the case-by-case approach; protocol development and prioritization; comprehensive integration of pain, palliative, and psychosocial services; and capacity building and education through twinning.

The Case-by-Case Approach: Epidemiologists seek to understand patterns, causes, and consequences of childhood cancer; pediatric oncology collaborative groups seek to standardize care and study and compare best strategies; and public health departments seek to address prevention, screening, and delivery of care at the population level. However, ultimately, cancer occurs at the level of the individual and must be addressed case by case. Even in pediatric oncology centers of excellence in HIC where access and standardization are the norm, the fit between open collaborative trials, standards of care, patient and family’s goals of therapy, and the patient’s diagnosis and clinical situation is made case by case. When making decisions about pediatric oncology treatment, centers in LMC, including ERLS, must consider factors such as the patient’s status, proposed therapeutic plan, resources available, and nonbiologic factors (see Table 5.3).