Sub specialization and centralization promote and thrive on a multidisciplinary team approach, in which all disciplines, including radiology, communicate with each other to ensure the most accurate and highest quality care (19). An effective radiology team is complex and expensive, as it includes radiologists, nuclear medicine physicians, imaging radiographers, technologists, medical physicists, and radiochemists, among others (20). Atun R et al. (21) noted the necessity of medical imaging as a cornerstone of many oncological services. Radiology is required in the diagnosis and treatment of cancer for accurate clinical management decision making by the multidisciplinary team and optimal outcomes for the patient (20). In many cancer types, early diagnosis and proper disease staging enhance the likelihood of survival (22). Unfortunately, misdiagnoses are not uncommon, causing patients to endure unneeded, and sometimes harmful, treatment, extra costs for the families and the hospitals, and even further delay of the correct diagnosis and appropriate treatment (23).

Sub specialization and centralization can help alleviate this common dilemma in oncology by working to ensure proper diagnostic imaging and earlier diagnosis. Studies have shown major differences between initial radiologist reports and subspecialty radiologist interpretations of imaging after referral (23, 24), indicating that a second opinion by a centralized radiology team has a positive impact on accurate diagnosis and patient care. This benefit may be even greater if done earlier in the course of illness. Additionally, sub specialization and centralization of pediatric oncology radiologists can decrease hospital costs by centrally reviewing images obtained at other institutions for patients who have been referred, instead of repeating the imaging examinations (23). The Institute of Medicine (25) reported that about 25% of patients undergo unnecessary repeated tests, including imaging (26), leading to inflated costs. Establishing a centralized team of specialty-trained pediatric radiologists can reduce such unnecessary costs. In large countries, like India, Indonesia, and Ethiopia, a network of different tier centers (primary, secondary, and tertiary) can be established, and utilization of telemedicine could help to address the issue.

Sub specialization and centralization of radiology also may increase patient volume from an increase in referrals (27), leading to a more reliable supply chain for imaging diagnostics (20), a more accurate perception of epidemiology of rare tumor subtypes not usually seen in smaller centers and improved collection and storage of imaging data, which helps with long-term follow-up (8). Additionally, by establishing centralized pediatric neuro-oncology specialized radiology, survival can be improved, as seen in a study on centralized neuroradiographic review in the United States (28). In a clinical trial of patients with average-risk medulloblastoma, 17% had images that, upon review, were considered incomplete or of poor quality, and when those patients’ survival was compared with that of patients with eligible, fully assessable images, those with incomplete or poor-quality images had poorer event-free survival (28). Additionally, 10% of the patients in the study were excluded after central radiologic review, because they had disseminated or residual disease. These patients were undertreated, which significantly decreased their probability of survival (28). A subspecialized and centralized pediatric neuro-oncology radiology center also positively influences surgical outcomes (20).

Many studies have shown that surgical procedures performed in high-volume centers have a higher survival rate and better outcomes, compared to those performed in low-volume centers (18, 29–36). The same has been found for individual surgeons who have performed high volumes of procedures and have more experience (29–31, 33, 35, 37). The centralization of pediatric surgical care in The Netherlands in Princess Máxima Center for Pediatric Oncology had a positive effect on both intraoperative and postoperative complications, mortality, and morbidity, when compared to pre-centralization data (18). Improvements in the care given at high-volume centers may be attributed to the skills of the staff, nursing team, and all related specialties, large number of operations, neurological intensive care unit, and high-quality advanced equipment (32). Additionally, sub specialization and centralization increase referrals, which in turn increases the experience of surgeons and hospital volume (32).

Sub specialization and high patient volume make acquiring equipment cost effective. For these reasons, surgical and radiological sub specialization and centralization should be linked because they enable hospitals to have better, more cost-effective resources (17). Another advantage of such an approach in high-volume centers is the networking among centers of excellence (32). In pediatric neuro-oncology, sub specialization and centralization of surgery offers a more aggressive approach towards many tumor resections; this is important in cancers in which survival is associated with complete resection (37, 38). One study comparing pediatric neurosurgery outcomes with surgeon experience/specialty found that the amount of residual tumor was related to the type of neurosurgeon (general, pediatric, or ASPN [American Society of Pediatric Neurosurgeons] member) who performed the procedure.

Pediatric neurosurgeons are more likely to extensively remove pediatric brain tumors than are general neurosurgeons. Additionally, lower neurological morbidity is associated with greater neurosurgical experience (e.g., ASPN members) (37). The mean number of operations performed by individual surgeons increased with sub specialization; individual general neurosurgeons perform fewer operations than do ASPN members (37).

Another study examined postoperative posterior fossa syndrome in patients with medulloblastoma; the authors found that younger age and having an operation in a low-volume center or by a low-volume surgeon increased the likelihood of posterior fossa syndrome (31). After sub specialization and centralization of pediatric brain tumor resections, mortality decreased (33). Additionally, lower rates of second brain tumor resection were associated with high surgical volumes, which can lead to lower costs in high-volume centers than in low-volume centers (34). Pediatric oncologic care (including surgery) is one of the most complex subspecialties of medical care; therefore, such cases favor centralization of care to surgical centers with high volume (34).

Pathologic assessment of tissue plays a vital role in diagnosis, staging, treatment, and prognosis (39, 40), and histopathologic evaluation of tumor tissue is typically required to confirm oncologic diagnosis (39). With increasingly smaller tissue samples needed for histopathologic examination, the centralized management of those specimens helps optimize the number of examinations that can be done on the tissue sample (41). This can be achieved through specialized standard operating procedures, policies, and protocols.

One study showed that after tissue-specific protocols were implemented, quality of care increased through improved and complete pathology reporting, which led to better interpretations of pathologic findings by the clinicians (42). Pathologists play a crucial role in communicating results with clinicians (40, 41, 43). Cancer diagnosis has changed from morphology-based classification, through microscopic examinations, to a molecular-based discipline (43). Many cancers are genetically driven, and over the last few decades, targeted therapies have been developed, forcing a more specific and stratified oncologic diagnosis (43). Successful treatment depends on pathologic diagnosis (44); furthermore, better outcomes are associated with accurate stratification of treatment (42). New high-throughput technologies are becoming essential for diagnosis of oncologic pathology (43, 45, 46). Sub specialization and centralization of pathology services can be an effective way for LMICs to access new, innovative technologies.

A useful strategy for resource-limited settings is seeking a second opinion, which can lower the risk of misdiagnosis and the necessity to later amend diagnoses (44, 47, 48). The accuracy of diagnosis can be evaluated by telepathology through twinning programs; the concordance rates of accuracy are similar in both static (pictures) and dynamic (real-time video) consultations (46). Sub specialization and centralization of pathology can be implemented into LMICs through collaborations with pathologists in HICs for intensive specialty training and second opinion telepathology (49).

One study demonstrated that in low-resource settings, an intensive 6-month training specifically tailored to local needs, as opposed to full subspecialty training, provided a sufficient foundation for accurate diagnoses of pediatric cancer (46). Neuro-oncological diagnoses have very specific histologic features that can be present due to genetic, environmental, or reactive causes, among others. One study in the United States found that after a central, independent pathologic review, 28% of high-grade glioma diagnoses were reclassified as low-grade glioma (50). Those 28% of children with low-grade glioma, whose follow-up after a near-complete resection should have been monitored only, received unnecessary chemotherapy and radiation therapy, which put them at risk of acute and long-term adverse late effects. In addition, the misdiagnoses added an unnecessary extra cost burden on health care systems.

Pediatric neuro-oncology is a nontechnical discipline, and the limited literature makes it difficult to quantify the impact of sub specialization and centralization of pediatric neuro-oncologists. Oncologists in LMICs typically have a heavy workload (42), with no extra time for fellowship training for sub specialization (46). Many academic hospitals in LMICs also do not have the resources to fund a full fellowship (46). An intensive 6-month specialty training was established in Brazil as a model for other low-resource settings (46). Although this model was used to train a general pathologist in pediatric cancer pathology, one can assume that it can also be used to train general oncologists to be pediatric neuro-oncologists.

The St. Jude Global Academy established the Neuro-Oncology Training Seminar as a multidisciplinary course on pediatric neuro-oncology for physicians in LMICs (51). Upon completion of the 9-week online course and the 7-day in-person workshop, physicians showed a significant improvement in comprehension of the core elements of pediatric neuro-oncology. In addition to this Academy, virtual clinical fellowship opportunities have been established through St. Jude Global and partners around the world (52). Using these novel approaches is important, because clinical fellows from LMICs who complete their medical training in HICs often decline the invitation to return to their country of origin, or they return but then leave after practicing for only a few years (53).

Radiation therapy is a vital element of the multidisciplinary clinical management of many pediatric cancers (54). The late adverse effects of radiation have been more clearly discerned as long-term survival of pediatric brain tumors has increased (55). Survivors of childhood brain tumors are at risk for neurocognitive, endocrine, and growth sequelae due, in part, to cranial radiation therapy (28, 54, 56). The amount and type of radiation administered are determined by the pathology, tumor location, disease progression, and age of the child (57). Large fields and high doses of radiation were used previously to treat pediatric brain tumors; however, severe late effects were seen in the first generation of survivors (55). Additionally, one study of patients with medulloblastoma showed that 71% of patients had at least one deviation in radiation, and seven patients did not receive the protocol-specified dose of radiation (58).

Because marginal deviations in radiation therapy are strongly correlated with risk of relapse (58), centralization and sub specialization are essential to ensure high quality treatment. Variations in outcome (54) indicate the need for sub specialization and centralization of radiation therapy for pediatric neuro-oncology patients; specific treatment protocols are not sufficient to positively affect quality of care without the presence of a multidisciplinary team. One important aim of radiation therapy in pediatric neuro-oncology has been to reduce the field of radiation and dose (55). Image-guided radiation therapy increases the accuracy of treatment by reducing the margin of healthy cells in the radiation beam and enabling increased dosage to the target area (54, 55). Having a specialized radiation oncologist makes this major advance possible because many technical skills are required (54).

These findings support the centralization of radiation treatment in cancer centers for an expansion of access to new, expensive resources in LMICs (59). Although 85% of the world’s population resides in LMICs, only about 33% of all radiation therapy facilities are in LMICs (60). Radiation therapy is cost-effective because of the high volume of patients a facility can treat and the long life of the equipment (21, 60). Twinning programs can also help establish radiation therapy centers and expertise in safe radiation therapy, while adapting to local and regional needs (21, 54).

Palliative care is a key component of comprehensive cancer care (59). It requires a broad, holistic, interdisciplinary approach for pain management, attending to suffering, home-based and hospice services, and bereavement (5, 10, 25, 59, 61, 62). Unfortunately, access to palliative care subspecialty is quite rare in LMICs, and if it is available, it is only at larger, more centralized locations (63). A major aspect of palliative care is to help clarify goals of treatment and care between clinicians and the patients and/or their families, which is vital throughout the illness experience (64, 65). The American Academy of Pediatrics recommends that pediatric palliative care begin at the time of the cancer diagnosis (5). Early involvement of palliative care is important for many reasons, including that children with malignant brain tumors commonly suffer from loss of their ability to communicate and present with severe symptoms at the end of life (25, 62, 66–68). Additionally, with early involvement of palliative care, advanced care planning improves, as discussions between the health care team and the patient and/or their family occur more frequently and earlier before death (69).

In patients with high-grade gliomas, palliative care consultations are associated with early change of code status to DNR (Do Not Resuscitate) and the increased use of hospice (70). Additionally, early integration promotes the continuation of relationships between the multidisciplinary team (including palliative care specialists) and the family, while avoiding the transfer of care or the introduction of new palliative care specialists during the last days of a child’s life (67). Palliative care consultations are associated with a shorter duration of stay in the hospital without any effect on mortality, and fewer deaths in the intensive care unit (64, 69). Integration of palliative care can also improve the quality of life by using less-aggressive treatment at the end of life and can improve survival (71). Interestingly, after the integration of palliative care, the number of hospital admissions at the end of life may be reduced (69); this was especially true for children with brain tumors (72). One study in Italy found that after the integration of palliative care, none of the patients with brain tumors had uncontrolled pain; almost 60% of patients received palliative sedation, and 44% died at home (66).

Pediatric palliative care includes patients and parents in clinical decision making; the wishes of the patient and/or parents are considered (65). Parents feel more comfortable discussing death with their child after consultations with the palliative care team (61). From the parents’ point of view, clear and honest communication from the doctor about their child’s prognosis is one of the strongest determinants of high-quality physician care (73). For parents of children with cancer, preparedness may be their only sense of control over unpredictable and devastating circumstances (73). Integrating palliative care aids in the grief and bereavement journey of surviving family members (68).

As the incidence and survival of pediatric brain tumors are increasing, supportive therapies, such as physical therapy, occupational therapy, speech therapy, neuropsychology, dental service, optometry, and audiometry, continue to be essential (74–77). Treatments for brain tumors can cause detrimental sequelae, including neurocognitive deficits, neurologic complications, endocrine abnormalities, gastrointestinal impairments, eye-related complications, and hearing loss (56, 74, 76, 78–81). For example, posterior fossa syndrome arises postoperatively in 40% of children with brain tumors located in the posterior fossa and presenting symptoms of impaired communication (often mutism), depressed mood, and loss of motor skills (82). Neuropsychological evaluations and interventions improve outcomes in pediatric neuro-oncology patients (56, 57, 83). Incorporating inpatient rehabilitation for patients with neurological disabilities due to brain tumors can also lead to functional improvement in activities of daily living (79, 84). Rehabilitation specialists in multiple disciplines (e.g., physical therapy, occupational therapy, and speech therapy) are required to optimize overall patient function (74). Early identification of these sequelae is vital to optimize normal speech, communication, language development, and social interactions for improved quality of life (85).

The Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health suggests integrating rehabilitation care from diagnosis and throughout the patient’s journey (86). The oncology team must screen patients for levels of function to ensure accurate and timely referral during the course of treatment and long-term follow-up (74, 77). Including rehabilitation providers on the multidisciplinary teams/rounds supports patients and families by ensuring consistent care providers throughout treatment (75), coordinated scheduling of rehabilitation services and anticancer treatment (74, 87), and improved discharge planning that can reduce the likelihood of re-admission to acute care (75, 87) and promote successful school transitions (88) (Table 1).