Neuro-Oncology Training for the Child Neurology Resident

Introduction/Background

Cancer is the leading cause of non-accidental death in children. In the United States, about 1 to 2 children per 10,000 are diagnosed with cancer each year.¹ The two most common types are leukemia and central nervous system (CNS) tumors, the latter being the most common solid tumor and the largest cause of childhood cancer-related mortality.² Over time, cure of pediatric cancers has been improving and now approaches 80%.³ With improvements in therapeutics and overall survival, both short and long-term neurologic adverse effects resulting from underlying disease and its treatments are better appreciated.⁴ Neuro-oncology is a rapidly evolving subspecialty that involves the management of patients with primary or metastatic central and peripheral nervous system neoplasms, as well as any other disorders or complications affecting the nervous system that result either directly or indirectly from CNS or systemic malignancies and related treatment (Table 1). Neurologists serve a critical role in the multidisciplinary management of these complex patients. As leaders of the Child Neurology Society Special Interest Group in Neuro-Oncology, we propose the following considerations to promote sufficient exposure, minimize knowledge gaps and optimize training experiences in neuro-oncology for child neurology residency programs.

Table 1.

Neurologic complications of cancer in children

Direct, Cancer-related toxicities	Indirect/Treatment related toxicities
Focal motor/sensory symptoms	Chemotherapy induced peripheral neuropathy
Seizure/Epilepsy	Seizure/Epilepsy
Headache	Headache
Hydrocephalus (obstructive/non-obstructive)	Vasculopathy
Movement disorder	Radiation necrosis
Visual acuity/visual fields changes	Drug specific toxicities (ie retinal changes)
Neuroendocrine dysfunction	Neuroendocrine dysfunction
Cognitive changes	Cognitive changes
Local compression/mass effect	Central nervous system infection
Metastatic/leptomeningeal disease	Paraneoplastic syndromes
Hearing loss	Hearing loss
	Posterior fossa syndrome

Current state of training

Current training models vary widely depending on whether the home institution has a dedicated pediatric neuro-oncology program and/or a dedicated child neurology subspecialist in neuro-oncology. At present, several training models exist. Child neurology residents can 1) rotate with a child neurology-trained neuro-oncologist at an institution with a neuro-oncology program, 2) rotate with different subspecialists at a hospital with a dedicated neuro-oncology program, 3) evaluate neuro-oncology patients through the neurology inpatient and outpatient services at a center without a dedicated neuro-oncology program. Hospitals with dedicated neuro-oncology programs generally have an infrastructure for residents to receive didactic lectures as well as attend multidisciplinary team meetings to discuss patient care. These tumor board meetings provide valuable education in neuroradiology, neuropathology and overall management in neuro-oncology. There are advantages to having the learning experience led by a child neurologist with expertise in neuro-oncology and to being at a hospital with a dedicated neuro-oncology program. These include education and experience provided from a neurological perspective with higher patient volumes and more diverse and complex cases that are often seen at these centers. A trainee’s experience may not be as integrated and comprehensive at institutions without a dedicated neuro-oncology program, but we propose ways to improve this learning experience.

Accreditation Council for Graduate Medical Education (ACGME) guidelines

As per the updated ACGME guidelines for child neurology (ACGME-approved focused revision: February 3, 2020; effective July 1, 2020), residents should receive teaching in neuro-oncology by faculty members or consultants with expertise in this field. In addition, as part of the general educational program, residents must have a broad range of structured didactic activities. ACGME competencies must be incorporated into the curriculum, specifically: professionalism, patient care and procedural skills, medical knowledge, practice based learning and improvement, interpersonal and communication skills and systems based practice. Residents are also required to receive instruction and experience in pain management, demonstrate knowledge in neuropathology, neuroimaging and neuropsychology, as well as demonstrate competence in the appropriate and compassionate use of palliative care. Exposure to neuro-oncology would fulfill many of the ACGME guidelines for child neurology.

The core competencies in Child Neurology related to training in Neuro-oncology

Patient care:

The possibility of a CNS tumor challenges skills in interviewing, developing and carrying forth patient management plans and counseling and education of families. This is particularly true in developing skills in approaching patients and parents with the discussion of a CNS tumor. The resident will be able to gather accurate and essential information from all sources, including medical interviews, physical examinations, medical records, and diagnostic/therapeutic experiences.

Medical knowledge:

This is a fertile area for residents to practice localization, pathologic investigation and diagnostic skills for primary and secondary brain and spinal cord tumors as well as treatment and the early and late neurologic sequelae.

Interpersonal and communication skills:

Residents will have the opportunity to develop and maintain compassionate therapeutic relationships that can help to guide families through diagnosis and treatment. In addition, they will learn to participate within the multidisciplinary team to improve and optimize care.

Professional issues:

Residents will learn to deal ethically and professionally with patients and families who have a wide range of understanding of neurologic issues and prognosis and with families who need additional information to make diagnostic decisions regarding the care of children whose prognoses may be poor. Training also includes the discussion of complex medical issues, treatment of disease, supporting children and their families during an acute medical crisis, and how to support them when there is a terminal diagnosis or a need for end-of-life care.

Systems-based practice:

Residents will recognize that the effective diagnosis and treatment of CNS tumors is based on collaboration with pathology, oncology, neurosurgery, rehabilitation medicine and other professionals. Increasing the interactions with and understanding of the complex system will allow residents to be effective advocates for their patients.

Proposed approaches to incorporate into current training

The child neurology resident should receive training and exposure to neuro-oncology which encompasses a common set of training experiences. This training should include principles of diagnosis and management of primary and secondary central and peripheral nervous system neoplasms, acute and long-term neurologic complications of cancer and related disorders, side effects of treatments and supportive care measures. Trainees should be familiar with hereditary disorders that predispose to CNS tumors.^5–8 These can be accomplished at all types of training programs by incorporating a didactic lecture series as well as expanding the residents’ clinical experiences by providing increased exposure to this patient population.

Medical Knowledge/Learning Objectives:

The core didactic and practical learning objectives for the child neurology trainee are delineated in Table 2. The didactic learning experience should consist of a core lecture series covering: 1) Overview of neuro-oncology including clinical presentation, diagnostic imaging, pathology, treatment, neurologic complications from tumor and treatment, 2) Neurocutaneous syndromes, 3) CNS tumors in familial cancer predisposition syndromes, 4) Cancer therapy induced neurotoxicity, 5) Long term neurologic sequelae from CNS tumors and associated therapy, 6) Goals of care, Delivering difficult news, end of life care. This lecture series could be integrated in the dedicated neuro-oncology rotation or as part of a broader lecture series provided throughout the year for child neurology residents.

Table 2.

Learning Objectives related to Neuro-oncology for the Child Neurology Trainee.

1.	Residents will demonstrate an understanding of the epidemiology of childhood CNS tumors and prognosis of the subtypes
2.	Residents will understand the typical presenting signs and symptoms of a primary or secondary CNS tumor
3.	Residents will obtain and document the history and physical examination of a child/adolescent with a primary or secondary CNS tumor, including neuroimaging and pathology
4.	Residents will demonstrate an understanding of the World Health Organization classification’s system, histopathology of CNS tumors, and will participate in neuropathologic review
5.	Residents will understand the application of neuroimaging
6.	Residents will learn to distinguish CNS tumors from potential mimickers such as demyelinating disease, vascular malformations and infections
7.	Residents will recognize the findings and associated tumor-related complications of neurocutaneous disorders, specifically neurofibromatosis type 1, neurofibromatosis type 2, tuberous sclerosis complex, von Hippel-Lindau disease
8.	Residents will attend outpatient neuro-oncology clinic and neurocutaneous clinic, if feasible. Other options include attending general neurology clinic, genetics clinic, and neurosurgery clinic
9.	Residents will provide consultation for neurologic issues, including seizures, raised intracranial pressure, headache, infection, peripheral neuropathy, and vasculopathy
10.	Residents will use a developmental framework to evaluation of children treated for a primary or secondary CNS tumor and refer when appropriate for hearing assessment, visual acuity/visual field testing, neuroendocrine testing, neurocognitive assessment, school-based assessments
11.	Residents will learn to diagnose and manage acute and long-term neurologic complications of the tumor and treatment
12.	Residents will gain competency in identifying patient populations at risk of specific long-term complications based on treatment intervention and age of treatment
13.	Residents will develop an understanding of issues related to families in crisis and end of life

Patient care:

The clinical experience must include practice in both the inpatient and outpatient areas. These experiences include the management of patients with primary neuro-oncologic problems and consultations requested by other services (ie oncology, pediatrics, neurology, ophthalmology, physical medicine and rehabilitation, neurosurgery, radiation oncology and neuropsychology). The ideal experience is one in which the resident provides supervised consultations of patients with primary CNS tumors and neurologic complications in children with systemic cancer, as well as those of stem cell transplant and cellular therapies, although the latter may not be feasible at all training sites. The neurologic issues can be divided roughly into two groups: direct cancer related toxicity and indirect neurologic effects of treatment (Table 1). At presentation, the most common symptoms of CNS tumors include headache, seizures, changes in vision, ataxia and altered mental status.⁹ Treatment related toxicities can occur from surgery, chemotherapy, radiation and immunotherapy and can occur at any time during or even many years after completion of therapy. The most common reasons for inpatient neurologic consultation in pediatric patients with cancer are altered mental status, seizures, pain and headache management and peripheral nervous system issues (sensory and motor).⁹ The spectrum of neurologic symptoms also includes diagnosis and treatment of toxic, nutritional or metabolic encephalopathy, chimeric antigen receptor T cell (CAR-T) therapy, CNS and systemic infections, cerebrovascular disease, increased intracranial pressure and paraneoplastic disease. As many novel therapies have only recently been used in the pediatric setting, the toxicities in children are not well known.

Residents could rotate through different specialties such as neuropathology, neuroradiology, radiation oncology, oncology, and neurosurgery to enhance their education in neuro-oncology. A rotation through neuropathology will supplement the teaching of basic histopathology, immunohistochemistry and molecular biology. Trainees will be expected to have an understanding of the classification and histopathology of CNS neoplasms. This should include a basic understanding of the molecular mechanisms that underlie the most common tumors, especially low and high grade gliomas, embryonal tumors and ependymomas. Many institutions have a tumor board patient review session for the multidisciplinary management of these patients which child neurology residents should attend. Through a rotation in neuroradiology, residents will be able to recognize the appropriate neurodiagnostic imaging needed for evaluation of CNS tumors. By rotating through neurosurgery, oncology and radiation oncology, trainees will gain basic knowledge in the general approach to the standard and experimental treatment of primary CNS tumors and a general overview of medical neuro-oncological therapies, including traditional treatments: surgery, radiation, chemotherapy, as well as novel therapies, among them molecularly targeted agents and immunotherapy. This will include participation in interdisciplinary management of patients with neuro-oncologic disorders. When feasible, the resident will gain exposure to clinical trial development and its relevance to the use of targeted and novel therapeutics.

Survivors of childhood cancer should be followed into adulthood and monitored for multisystemic effects of treatment. Long term neurologic sequelae include, but are not limited to, difficulties with cognitive function (in particular, difficulties with memory, processing speed and attention), hearing loss, visual field deficits, motor deficits, peripheral neuropathy, and sleep disorders (http://www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf).

Conclusions

The field of Neuro-oncology is a diverse and complex one. Neurologists serve a critical role in the multidisciplinary management of these complex patients, and it is important to optimize their specialized training to care for this population whether as a neuro-oncology subspecialist or general child neurologist. Training programs should use the opportunity to give residents exposure to these patients following a core content and common set of training experiences; potential approaches could be as described above. Neurology residents are often the first subspecialist a family may meet after presenting to the emergency room with an undiagnosed brain or spinal cord tumor tumor. Therefore, astute clinical acumen in localization and diagnosis, as well as ability to compassionately disclose findings on neuroimaging is critical to their training. Prompt recognition and diagnosis of neurologic symptoms in a patient with cancer may prevent permanent disability or death. No matter the timing, neurologic complications of cancer can be distressing and difficult for patients, families and caregivers and can substantially diminish the quality of life. The aim is to prepare the child neurology resident to provide compassionate care that optimizes patient function and quality of life.