Continent
Countries included/submitted data
PBCR included/submitted data
Geographic coverage by continent (%)
Population coverage in millions (%)
Africa
5/14
5/16
31
8.8 (1 %)
Asia
15/18
44/77
57
152.3 (4 %)
Europe
29/30
100/120
83
238.8 (33 %)
North America
2/2
54/58
93
258.5 (80 %)
Oceania
4/6
11/13
85
23 (73 %)
South and Central America
8/11
11/29
38
22.7 (4.3 %)
Available data suggest a low incidence of CNS tumor in countries with limited resources. While the incidence of pediatric brain tumor in the CBTRUS (Central Brain Tumor Registry of the United States) was 4.92/100,000 person-years for children less than 15 years during the period 2004–2008 [5], Manoharan et al. reported an incidence of 0.9/100,000 in the Delhi Population Based Cancer Registry (PBCR) for the period 2003–2007 [6]. In Colombia, a country with a population of 47,000,000, there is a rough estimate of 400 new pediatric brain tumors per year. Whether this lower incidence is real or related to other factors is unknown. One common proposed cause of lower reported incidence of childhood cancer in general in low-income countries is the high mortality rate in young children (under the age of 5 years) that may lead to early death before the child develops cancer. However, there is no statistical reason that this high rate of premature death should influence the overall incidence of childhood cancer. Using data from the International Agency for Cancer Research (IARC), Howard et al. reported a close correlation between the reported incidence of childhood leukemia and the mean annual per capita gross national income [7]. There is no similar study for childhood brain tumors. However, it is very likely that in many low-income countries, children with brain tumor die before diagnosis.
Delay in the Diagnosis of CNS Tumors
Despite advances in neuroimaging, timely diagnosis of CNS tumors remains a problem in high-income countries. There are no specific studies that have analyzed differences in the delay to diagnosis of CNS tumors between high- and low-income countries. However, the issue of late diagnosis of CNS tumors is obvious for neurosurgeons and oncologists who practice in these countries. Beyond the usual challenges of nonspecific symptoms such as vomiting, failure to thrive, hypoactivity, headaches, or visual disturbance that are usual factors involved in delayed diagnosis [8], access to neuroimaging facilities is the main obstacle that patients and families face. The limited number of CT or MRI scans; long waiting lists, particularly when sedation is needed; and in many places the prohibitive cost of these tests are among the many reasons that delay or prevent the diagnosis of brain tumor in children in these countries. In most places, the imaging study will be limited to the brain and it is exceptional to have preoperative imaging of the spine when a malignant brain tumor such as medulloblastoma is suspected. Once a brain tumor is diagnosed on imaging, then confirmation of the correct diagnosis would mean a referral to a specialized center able to take care of these children.
Most developing countries lack specialized centers whether due to unavailability of experienced staff or shortage of equipment [9], and even when they have one, families from rural areas often face difficulties to access these specialized centers due to financial costs and difficulties in transportation, which will also complicate future compliance during treatment and follow-up.
In some countries like Panama, programs have been developed to increase awareness of early signs and symptoms of pediatric brain tumors for primary care physicians. The primary objective is to increase early diagnosis and referral of these patients. Programs like this one are being currently developed in other countries like Colombia, addressing the most common malignancies in childhood.
Cultural Barriers
Cancer is a condition that relates to fate, myths, and beliefs. The diagnosis of brain tumor is a devastating event for the families; often they tend to seek help from local “healers” or use complementary and alternative medicine. As a result, this may affect the natural history of the disease and delay the diagnosis of cancer even more [10]. A classical example is the increased incidence of blindness associated with optic pathway gliomas seen in countries with limited resources.
Brain tumor diagnosis has in some cultures a negative perception and stigmatization. Families may refuse to be referred to a cancer center, trying to avoid the risk of marginalization associated with this condition. Stigma like the belief that cancer equates death or mental and physical disability and cultural myths might also influence parental or family decisions including treatment abandonment. Because the social stigmata of cancer can be so powerful, social barriers must be fully understood before any strategy is implemented in low-income countries.
Some cultural choices, like treating boys over girls, may affect incidence, survival, and mortality data of cancer in some cultural contexts [11]. Other social factors are critical, such as financial and transportation difficulties that have been identified as major sources of abandonment of treatment [12].
Management of Pediatric Brain Tumors in Countries with Limited Resources
Neurosurgery
With a few exceptions, neurosurgical management is generally the first step in the treatment of pediatric brain tumors. Neurosurgeons in low-income countries are overloaded with work and neurosurgical units are generally understaffed. Neurosurgery in these countries faces two main challenges, i.e., quality and quantity in both resources and qualified personnel [9]. The World Health Organization African Subcommittee conducted a survey on African neurosurgical services in the late 1990s. This survey reported a ratio of one African neurosurgeon per 1,352,000 individuals compared to 1/121,000 in Europe and 1/81,000 in North America [13]. Similar figures are described in the South Asian continent.
In addition, there are a limited number of neurosurgeons with a pediatric expertise in low-income countries, and thus, general neurosurgeons, when available, are expected to operate on children. In such conditions, specific knowledge of the principles of pediatric neuro-oncology is important and unfortunately many general neurosurgeons are not familiar with this specialty. As a result, in most places, surgical intervention is limited to the insertion of ventriculoperitoneal shunts for the management of hydrocephalus. Attempt to complete or near complete surgical resection is not a common practice, and surgery is usually limited to a biopsy to allow histological diagnosis. Unfortunately, less than gross total resection greatly impact survival of children with brain tumor like ependymoma or/and would upgrade risk status for some other tumors like medulloblastoma.
Neuronavigation and the use of intraoperative microscope are known to facilitate surgery and to improve tumor resection; however, these equipments are scarce in low-income countries or are only available in selected private practices; trained neurosurgeons with the expertise to use these techniques are limited. A recurrent challenge in this context is the management of children who underwent incomplete tumor resection. Most often, neurosurgeons consider that there is no role for further surgery and they refer the child to radiation oncologists or pediatric oncologists for adjuvant treatment. While local oncologists are often unsuccessful in trying to convince referring neurosurgeons to proceed to second look surgery in the context of an incomplete resection, telemedicine experiences that involve a contact between neurosurgeons appear to offer a unique opportunity to discuss such technical issues and to optimize the quality of surgical management [14].
Postoperative intensive care with good monitoring of intracranial pressure, fluids, and electrolyte balance is crucial when caring with brain tumor patients especially when hormonal problems are expected like in craniopharyngioma surgery. The lack of such specialized multidisciplinary care will increase perioperative morbidity and mortality.
Another issue identified in some of the twinning programs is the lack of communication between neurosurgeons and pediatric oncologist. Often, these patients are not referred for further adjuvant therapy and frequently a suboptimal surgical resection is the only treatment modality. This seems to be a more prevalent issue, if the surgical management is performed by a non-pediatric neurosurgeon and at an institution where appropriate pediatric oncology or radiation therapy is not available.
Neuropathology
Experienced pathologists able to differentiate subtypes of pediatric neurological tumors are absent in many developing countries. The lack of trained personnel and inadequate technical equipment are therefore limiting the possibility to achieve a timely and accurate diagnosis in many places. Often, clinicians are faced with long turnover times—sometimes exceeding 1 month—before a diagnosis is proposed [15]. Availability of some important staining techniques may also compromise the possibility to accurately identify tumor types. A classical example is the availability of the BAF47 staining. This staining that has now become part of the standard battery of immunohistochemical staining performed in the context of embryonal tumors of the central nervous system.
In a report on a telemedicine twinning experience between Canada and Jordan in pediatric neuro-oncology between two multidisciplinary programs, the most common recommendation was a review of the neuropathology, resulted in several cases in a change in the initial diagnosis or in the grading of the tumor with significant consequences in term of subsequent management [14]. Those results have been replicated in the ongoing twining program between Canada and Colombia. However, a number of factors are limiting this practice that would greatly benefit pediatric neuro-oncology programs in countries with limited resources. In this context, it is likely that a significant number of children are treated without an adequate diagnosis.
Radiation and Radiotherapy Services
Radiation therapy is a critical component of treatment of many central nervous system tumors in children; however, limited radiotherapy machines and personnel make them available only at large centers with long waiting lists. There is evidence that delay in starting radiotherapy has a negative impact on survival in medulloblastoma and there is no doubt that the extent of neurological recovery will be closely dependent on the time to initiate radiation in patients with diffuse intrinsic pontine glioma (DIPG).
Radiation indications, treatment volumes, and doses are determined by tumor histology, extent of disease, anticipated pattern of spread, and expected pattern of failure. In malignant CNS tumors such as medulloblastoma and ependymoma, excellent survival rates have been reported, particularly in patients with average risk features (complete resection and absence of metastatic disease and no anaplastic features). Survival rates are above 90 % in patients with pure germinoma, regardless of metastatic stage, with a combination of chemotherapy and radiation. However, access to radiation oncology services is a prerequisite for successful outcome and the number of functioning radiotherapy machines available in most countries with limited resources is the main barrier to optimal patient care. It is clear that pediatric neuro-oncology programs cannot be developed or implemented in countries, which have no radiation oncology services. A survey of radiotherapy equipments in Africa conducted in 1998 reported that 9/56 countries had no radiotherapy at all, 24 had orthovoltage facilities only, and 2/3 of the megavoltage equipments available in the continent were located in two countries (Egypt and South Africa) [16]. The supply of radiation equipments available in the continent represented at that time 18 % of the estimated needs. Appropriate maintenance of the radiation equipment is also an issue in countries where there is only one radiotherapy machine; the treatment could get interrupted for an undetermined period of time or waiting times can increase considerably if the machine goes out of service.
As a consequence, access to radiation is a major issue in most countries with limited resources, and delay in initiation and/or continuation of radiation treatment is a common problem.
In several places, pediatric oncologists are trying to overcome this problem by designing protocols that offer postoperative chemotherapy prior to radiation, in particular for medulloblastoma patients. Although this is not an ideal option, this approach may help prevent early recurrence or dissemination following initial surgery. Another limiting factor in the management is the number of well-qualified personnel with an expertise in CNS radiation techniques and more specifically in pediatrics. Craniospinal radiotherapy (CSI), which is commonly used in the management of medulloblastoma patients, is one of the most complex radiotherapy techniques, and evidence from several medulloblastoma trials has suggested that the quality of CSI impacts outcome. Some groups have started to address specific issues related to the availability of radiation machines. In particular, a group in Cairo has run a randomized trial that has shown similar survival between patients with DIPG treated with normal fractionation (30 sessions at 1.8 Gy each) and hypofractionation (13 sessions of 3 Gy each) [17]. The results of this trial may benefit DIPG patients in countries that face limitations in the access to radiation services.
Ideally, the radiotherapeutic management of children with CNS tumor in countries with limited resources would benefit from a central referral system that would review and validate indications and facilitate timely access to the most appropriate equipment. Hopefully, cooperative groups and support groups will be able to advocate for the development of such process.
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