Overview of the management of central nervous system tumors in children

INTRODUCTION — Primary malignant central nervous system (CNS) tumors are the second most common childhood malignancies, after hematologic malignancies, and are the most common pediatric solid organ tumor (table 1) [1]. They are the leading cause of death from childhood cancer, surpassing the mortality rate of acute lymphoblastic leukemia [2]. Although advances in surgical intervention, radiation therapy, and chemotherapy have improved the survival rates in children with CNS tumors, mortality and morbidity associated with these disorders persist, especially with malignant brain tumors.

A general overview of the management and prognosis of CNS tumors in children will be reviewed here. An overview of the clinical manifestations, diagnosis, and epidemiology of CNS tumors in children is presented separately. (See "Clinical manifestations and diagnosis of central nervous system tumors in children" and "Epidemiology and classification of central nervous system tumors in children".)

The management and prognosis of specific CNS tumors that occur in children are discussed in greater detail separately:

●Low-grade gliomas (see "Treatment and prognosis of IDH-mutant astrocytomas in adults")

●Malignant gliomas (see "Clinical presentation, diagnosis, and initial surgical management of high-grade gliomas")

●Brainstem glioma (see "Diffuse intrinsic pontine glioma" and "Focal brainstem glioma")

●Optic glioma (see "Optic pathway glioma")

●Medulloblastoma (see "Clinical presentation, diagnosis, and risk stratification of medulloblastoma" and "Histopathology, genetics, and molecular groups of medulloblastoma" and "Treatment and prognosis of medulloblastoma")

●Craniopharyngioma (see "Craniopharyngioma")

●Ependymoma (see "Intracranial ependymoma and other ependymal tumors")

●Focal brainstem glioma (see "Focal brainstem glioma")

●Germ cell tumors (see "Intracranial germ cell tumors")

●Intradural nerve sheath tumors, such as schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (see "Intradural nerve sheath tumors")

●Meningioma (see "Management of known or presumed benign (WHO grade 1) meningioma")

●Spinal cord tumors (see "Spinal cord tumors")

●Tuberous sclerosis (see "Tuberous sclerosis complex: Clinical features")

●Other tumors, including neuronal and neuronoglial tumors, choroid plexus tumors, atypical teratoid/rhabdoid tumors, ependymoblastoma, and medulloepithelioma (see "Uncommon brain tumors")

MANAGEMENT STRATEGY — The mainstay of management in CNS tumors includes a multimodal approach of surgery, radiation therapy, and chemotherapy. The confirmation of a CNS tumor warrants a referral to a neurosurgeon for further evaluation, tissue biopsy, and gross total resection where possible. Radiation therapy and chemotherapy are used as adjunct measures based on the histology of the tumor.

SURGERY — An open surgical procedure is the preferred approach to obtain tissue for a histologic diagnosis and bulk removal of the tumor where possible. A pediatric neurosurgeon should be involved, if possible, as they are best able to perform tumor resection with limited long-term morbidity [3]. In most cases, near-total resection can be achieved. However, complete resection is generally limited by the inability to remove the tumor with surrounding clear margins of normal tissue because of the risk of producing permanent neurologic deficits, and to remove scattered tumor cells that have infiltrated beyond the margins of the resection [4]. Adjunct therapy (ie, radiation therapy and chemotherapy) is required.

Deep-seated tumors, such as diffuse infiltrative brainstem and chiasmatic gliomas, are associated with a high risk of irreversible neurologic sequelae in an open surgical approach. In these cases, tissues for histologic diagnosis can be obtained using stereotactic biopsy techniques guided by magnetic resonance imaging (MRI) or computed tomography (CT) [4,5]. Endoscopic biopsy is another option for intraventricular or periventricular tumors [6].

Surgical approaches and techniques — The major risk of extensive tumor resection is injury to the surrounding tissue, especially in functionally critical parts of the brain, which can result in long-term neurologic impairment. Advances in operative microscopy with better visualization of the interface between the tumor and the surrounding normal tissue have resulted in safer surgical resection and lower neurologic morbidity.

In cases where the tumor is in a functionally critical site and/or there is poor demarcation of the tumor from its surroundings, the following techniques have been used to minimize injury to the adjacent normal tissue:

●Preoperative stereotactic imaging to guide the surgical approach in order to minimize manipulation of normal tissue and maximize tumor resection [7]

●Intraoperative MRI, including functional MRI to aid in intraoperative decision making [5,7]

●Intraoperative neurophysiologic monitoring of visual, auditory, and somatosensory pathways in cases that involve functionally critical zones to minimize injury to normal tissue [7,8]

Postoperative imaging, preferably by MRI, is performed within the first 24 to 72 hours to determine the extent of tumor resection. This information is useful in the planning of subsequent therapy, including the need for repeat surgery.

Preoperative and perioperative considerations — In addition to deciding the optimal surgical approach and technique to adopt for a child with a CNS tumor, the following preoperative and perioperative complications have to be addressed:

●Increased intracranial pressure (ICP) including obstructive hydrocephalus

●Seizures

●Endocrine abnormalities

Elevated intracranial pressure — Elevated ICP is a common finding in children with CNS tumors and can be caused by mass effect of the tumor and/or obstructive hydrocephalus. Patients who have radiographic and/or clinical signs of elevated ICP require urgent neurosurgical intervention (eg, tumor resection and/or placement of a shunt to relieve hydrocephalus, if present) to prevent serious morbidity and death.

Although tumor resection may lead to resolution of hydrocephalus, preoperative shunting is often performed to temporarily relieve the increased ICP, reducing the potential risk of herniation. Shunting is usually performed by placing an external ventricular drain (figure 1) just prior to craniotomy for tumor resection. Postoperatively, the shunt allows drainage of bloody cerebrospinal fluid (CSF) and debris. It is usually removed within a few days after normal CSF flow is reestablished following tumor resection. In cases with persistent obstruction of CSF flow, a long-term CSF shunting procedure may be required (eg, a ventriculoperitoneal shunt or endoscopic third ventriculostomy, in which a perforation is made to connect the third ventricle to the subarachnoid space). These procedures are discussed in greater detail separately. (See "Hydrocephalus in children: Management and prognosis", section on 'CSF diversion procedures'.)

Patients with elevated ICP due to CNS tumors are typically treated with glucocorticoid therapy (eg, dexamethasone) in the perioperative period to reduce peritumor edema associated with the surgical procedure. Intravenous or oral dexamethasone (0.25 to 0.5 mg/kg administered every six hours with a maximum dose of 16 mg per day) is given preoperatively and is continued intraoperatively and during the early postoperative period. In most cases, dexamethasone can be discontinued after a few days because tumor volume is reduced following resection. However, children with tumors that are not amenable to resection (eg, brainstem lesions) may require protracted dexamethasone therapy and are at risk for its side effects. The use of dexamethasone in this setting is supported by indirect evidence in studies involving adult patients with symptomatic primary and metastatic brain tumors [9]. These data are discussed in a separate topic review. (See "Management of vasogenic edema in patients with primary and metastatic brain tumors", section on 'Initiation of glucocorticoids'.)

Seizures — Seizures are common in patients with brain tumors, and epileptogenesis is probably multifactorial [10]. In one study, the following factors were associated with increased risk of seizure perioperatively at the time of brain tumor resection [11]:

●Supratentorial tumor location

●Young age (<2 years)

●Hyponatremia

Tumor pathology and tumor size did not appear to be associated with increased risk of seizure [11].

●Treatment of seizures – Anticonvulsant therapy is indicated for patients with CNS tumors complicated by seizures. Agents that are commonly used include phenytoin, levetiracetam, valproic acid, lamotrigine, topiramate, gabapentin, and pregabalin.

Drug interactions are important to consider in selecting an antiseizure medication in patients with brain tumors:

•Phenytoin induces the cytochrome P450 enzymes, increasing the clearance and decreasing the effectiveness of chemotherapeutic agents that are metabolized through this system (eg, nitrosoureas, paclitaxel, cyclophosphamide, etoposide, topotecan, irinotecan, thiotepa, doxorubicin, methotrexate, and corticosteroids) [10]. Phenytoin levels should be monitored closely in patients treated concomitantly with dexamethasone (particularly during tapering and after discontinuation) because dexamethasone can alter the blood concentration of phenytoin [10].

•Valproic acid inhibits hepatic enzyme expression, reducing metabolism of some chemotherapeutic drugs, leading to increased risk of toxicity. Toxic effects of nitrosoureas, given alone or with cisplatin and etoposide, have been reported with concomitant administration of valproic acid [10].

•Other anticonvulsants that affect P450 enzymes include phenobarbital and carbamazepine.

•Many chemotherapeutic agents induce coenzymes of the cytochrome P450 pathway and change the plasma concentration of concomitantly prescribed antiseizure medications.

More information on specific drug interactions is available through the drug interactions program included within UpToDate.

●Prophylactic antiseizure medication – Based upon the available evidence, we recommend not using prophylactic anticonvulsants in patients without a history of seizures. The exception is the use of postoperative seizure prophylaxis at the discretion of the neurosurgeon. This approach is consistent with the consensus statement from the Quality Standards Subcommittee of the American Academy of Neurology [12].

Clinical trials in adult patients with brain tumors without history of prior seizures have demonstrated that prophylactic anticonvulsants do not reduce the frequency of seizures and are associated with increased risk of adverse events [13]. Although most studies are of adult patients with brain tumors, the results are most likely applicable to pediatric patients as well. (See "Seizures in patients with primary and metastatic brain tumors", section on 'Indications for antiseizure medication therapy'.)

Endocrine abnormalities — Patients with lesions located in the hypothalamus or pituitary gland may present with endocrine abnormalities, such as growth failure due to either hypothyroidism or growth hormone deficiency. One example is craniopharyngioma, which often presents with endocrine abnormalities due to its location near the optic chiasm and pituitary axis (see "Craniopharyngioma"). Tumor resection can exacerbate endocrine dysfunction. For example, patients whose posterior pituitary gland is injured or resected during surgery may have impaired fluid and electrolyte regulation with an initial phase of transient arginine vasopressin deficiency (AVP-D, previously called central diabetes insipidus), followed by a period of inappropriate antidiuretic hormone release, and a final persistent phase of AVP-D. (See "Craniopharyngioma" and "Arginine vasopressin deficiency (central diabetes insipidus): Etiology, clinical manifestations, and postdiagnostic evaluation".)

Management of the specific endocrine abnormalities may require hormonal replacement therapy.

RADIATION THERAPY — Radiation therapy plays an integral role in the treatment of CNS tumors in children. The use of radiation therapy is dependent on the histologic diagnosis of the tumor, whether there is an effective chemotherapeutic alternative, and the age of the child. Radiation therapy is usually avoided in children <3 years old because of the risk of severe neurocognitive sequelae. (See "Delayed complications of cranial irradiation", section on 'Neurocognitive effects'.)

When radiation therapy is selected, planning the target volume (local versus craniospinal) and the dose of radiation therapy takes into consideration the tumor location, stage and subtype of the tumor, expected patterns of spread, availability of effective chemotherapy, and age of the patient.

Radiation therapy is generally delivered by conventional external beam. Other techniques include three-dimensional conformal radiation therapy (targeting the radiation to conform to the size and shape of the tumor) and stereotactic radiosurgery. The different techniques of radiation therapy administration are discussed in greater detail separately. (See "General principles of radiation therapy for head and neck cancer" and "Stereotactic cranial radiosurgery".)

Although an effective adjunct, radiation therapy is associated with both acute and long-term complications, particularly in infants and young children whose nervous systems are still developing. The complications of cranial radiation can be categorized into three phases and are summarized as follows. A more detailed discussion of the complications of cranial radiation is provided in separate topic reviews. (See "Acute complications of cranial irradiation" and "Delayed complications of cranial irradiation".)

●Acute reactions occur during treatment and are caused by injury to the brain that results in inflammation and edema. Symptoms include headache, nausea, drowsiness, focal neurologic deficits, and fever.

●Early-delayed reactions occur from a few weeks to three months after radiation treatment and are thought to be due to a combination of tumor response, peritumor edema, and demyelination. Findings include transient focal neurologic deficits, somnolence syndrome (characterized by extreme sleepiness and signs of increased intracranial pressure [ICP], such as headache, nausea, vomiting, anorexia, and irritability), and asymptomatic magnetic resonance imaging (MRI) contrast enhancement, which may be difficult to distinguish from tumor progression.

●Late reactions occur >90 days after radiation treatment and generally are irreversible. They are due to radiation-induced brain necrosis at or near the site of the tumor that has received the highest radiation dose, diffuse white matter injury (ie, leukoencephalopathy), secondary malignancies, and vasculopathy. General findings include impaired neurocognitive function, and social and behavioral deficits. In a retrospective study of 101 children with brain tumors treated with cranial radiation, 5 percent developed radiation necrosis [14].

Depending on the location of the tumor and field of radiation, other complications, such as hearing impairment, hypothalamic and pituitary endocrinopathies, and visual impairment secondary to cataracts, optic neuropathy, retinopathy, or cortical blindness, may arise.

Various strategies, such as decreasing the radiation dose for patients with relatively lower-risk disease and three-dimensional conformal radiation therapy, have been adopted to minimize the long-term complications associated with radiation therapy. The latter minimizes radiation to adjacent normal tissue by customizing the treatment to deliver maximum radiation within the contour of the tumor volume, regardless of its shape. Proton beam therapy also minimizes the harmful effects of radiation to neighboring normal tissues because of its unique ability of depositing most of its energy (proton) at the targeted area with minimal exit dose. (See "Stereotactic cranial radiosurgery" and "General principles of radiation therapy for head and neck cancer".)

Proton radiation therapy has emerged as a treatment of choice in some brain tumors. Compared with standard photon-based radiation therapy, proton therapy decreases low-dose radiation exposure to uninvolved brain and to structures anterior to the craniospinal axis. In the short term, these features of proton therapy may increase tolerance of concurrent and adjuvant chemotherapy by decreasing hematologic and gastrointestinal side effects [15]. In the long term, proton therapy may reduce the risk of neurocognitive, endocrine, vascular, and developmental sequelae of radiation therapy, as well as the risk of radiation-induced second malignancies [15]. This is particularly important for young children who require radiation therapy as part of their treatment plan. (See "Radiation therapy techniques in cancer treatment", section on 'Proton beam'.)

CHEMOTHERAPY — The role of chemotherapy in the treatment of CNS tumors is dependent on the type of tumor and the patient's age.

Chemotherapy is routinely used in the following clinical settings:

●Older children with embryonal tumors (eg, medulloblastomas, ependymomas, high-grade astrocytomas) in combination with surgery and radiation therapy.

●Young children and infants with embryonal tumors, low-grade gliomas, and optic glioma after surgical resection. The goal of chemotherapy in this setting is to delay or replace radiation therapy. This reduces or eliminates the long-term effects of radiation (ie, neurocognitive impairment, developmental delay, and endocrine abnormalities) in this vulnerable population.

See the relevant reviews on specific histologic types of tumors for more detailed information on chemotherapy. (See 'Introduction' above.)

The use of chemotherapy for CNS tumors poses a challenge to oncologists. The presence of the blood-brain barrier limits the penetration of most systemically administered chemotherapeutic agents. The following approaches are used to administer these agents and are discussed in greater detail separately.

●High-dose or combination systemic therapy

●Intrathecal chemotherapy

●Intratumoral chemotherapy with direct administration of the chemotherapy into the tumor bed

●Systemic administration with disruption of the blood-brain barrier by infusions of hypertonic arabinose or mannitol

An increased understanding of the molecular pathways involved in signal transduction, angiogenesis, and cell growth has led to the development of targeted agents in the treatment of malignant gliomas and other tumors. For example, drugs have been developed that disrupt the vascular endothelial growth factor (VEGF) pathway, which is involved in the formation of the abnormal vasculature observed in malignant gliomas and other tumors. These agents include monoclonal antibodies that bind VEGF, inhibitors of tyrosine kinases within the VEGF pathway, and inhibitors of protein kinase C, a major component of the VEGF pathway. Other new drugs target additional molecular pathways involved in tumor pathogenesis, such as the epidermal growth factor, platelet derived growth factor, integrin, sonic hedgehog, and histone deacetylase systems/pathways.

Biologic agents, such as interferons (IFN alpha and beta) and gene therapy, have also shown promise in the treatment of malignant gliomas and other CNS tumors.

PALLIATIVE CARE — Certain brain tumors (eg, high-grade gliomas) have a poor prognosis, with five-year survival rates <20 percent (see 'Prognosis' below). In such cases, early involvement of a palliative care team at the time of diagnosis can help support family and caregivers and assist in establishing realistic treatment goals for the patient. Children with brain tumors at the end of life have progressive neurologic deterioration, including loss of the ability to communicate [16]. End-of-life care for these patients needs to provide early anticipatory guidance for families and comfort measures that address the distinct issues in the care of a dying child with a brain tumor. (See "Pediatric palliative care".)

PROGNOSIS

Survival — Survival after diagnosis with a primary brain or other CNS tumor varies considerably, depending on the age of the child and the type of tumor. Based on data from the Central Brain Tumor Registry of the United States (2011 to 2015), pilocytic astrocytoma was the tumor type with the highest survival rates after diagnosis (five-year survival rate of 97 percent), whereas atypical teratoid/rhabdoid tumors, diffuse intrinsic pontine glioma (DIPG), and high-grade gliomas had the lowest survival rates after diagnosis [17,18]. Five-year survival for glioblastoma is only 18 percent [17,18], while two-year survival for DIPG is only around 2 percent. In the United States, CNS tumors account for one-fourth of all cancer deaths in children [19].

Survival has improved, in part due to advances in diagnostic techniques and histologic classification of tumors, improvement in neurosurgical and radiation oncology techniques, and the utilization of new single and combination chemotherapeutic agents. Despite advances in the care of children with CNS tumors, mortality and morbidity associated with these disorders persist. Improvement in survival and durable remissions has been slower in patients with CNS tumors compared with other cancers, particularly leukemias and lymphomas.

Late mortality occurs in 15 to 25 percent of patients who survive beyond five years [20,21]. Late mortality is most commonly due to tumor recurrence or progression [20,21]. Other causes of death include secondary malignant tumor and secondary medical conditions [20]. (See 'Secondary neoplasms' below.)

Long-term morbidity — Pediatric survivors with CNS tumors often have neurologic, cognitive, psychological, and endocrine complications that are due to damage from the tumor itself, its treatment (surgery, radiation, and/or chemotherapy), or subsequent secondary malignancy. The risk of these complications is increased in patients who are younger at the time of diagnosis and treatment (less than three years of age), have hydrocephalus, and/or are treated with cranial radiation [22-24]. (See "Treatment and prognosis of medulloblastoma", section on 'Neurocognitive impairment'.)

In the Childhood Cancer Survivor Study, 82 percent of the 2821 five-year survivors of childhood brain tumors reported having at least one chronic medical condition [21]. Compared with their siblings, survivors had an increased risk of developing a new endocrine condition (hazard ratio [HR] 19.8, 95% CI 14.5-27.1), sensory deficit (eg, hearing loss; HR 12.5, 95% CI 8.9-17.6), and neurologic problem (HR 5.6, 95% CI 4.8-6.7). Cranial radiation therapy was associated with an increased risk of subsequent malignancy and neurocognitive impairment.

Secondary neoplasms — Patients treated for CNS tumors in childhood are at risk of developing secondary neoplasms decades beyond the primary cancer treatment [21,25,26]. Based upon long-term follow-up studies of survivors of childhood CNS tumors, the cumulative incidence of secondary neoplasms 20 years after diagnosis is approximately 10 percent [21,25]. The most common subsequent neoplasms include basal cell carcinoma, meningioma, malignant CNS tumors (eg, glioma and astrocytoma), soft tissue sarcomas, and thyroid cancers. The risk of developing a secondary CNS neoplasm is associated with the maximum cranial radiation dose given [21,27]. The risk does not appear to be higher after exposure to multimodal therapy compared with radiation alone for medulloblastoma [25]. (See "Delayed complications of cranial irradiation", section on 'Secondary tumor formation'.)

Neurocognitive effects — Neurocognitive impairment is a common complication in children with CNS tumors [28-30]. Younger age at diagnosis and treatment is the most consistently identified risk factor; others include cranial radiotherapy, neurosurgical resection, perioperative complications, and ototoxicity [31].

Scholastic impairment was illustrated in a study from the Finnish Cancer Registry that compared school performance at age 16 years of patients with CNS tumors with age-matched controls [28]. Although 94 percent of patients were able to finish their education at the usual age, patients had lower grades in all school subjects compared with controls, with the greatest difference in foreign language. In particular, brain tumor survivors who were diagnosed as preschoolers had 18-fold higher odds (95% CI 15.0-23.5) of a special education history than did those in the sibling group.

In a report from the Children's Oncology Group of 93 patients with a low-grade brain tumor who were treated only with surgical excision, patients were more likely to have below-average scores compared with published normative scores in intelligence quotient (IQ), academic performance, visual and motor skills, and adaptive behavior (55 percent compared with the expected normative rate of 25 percent) [29].

Late neurocognitive complications of cranial irradiation are discussed in greater detail separately. (See "Delayed complications of cranial irradiation", section on 'Neurocognitive effects'.)

Cerebrovascular disease — Survivors of childhood CNS tumors treated with radiation therapy are at increased risk for late-occurring cerebrovascular complications including stroke [32-34]. Late cerebrovascular complications of cranial irradiation are discussed separately. (See "Delayed complications of cranial irradiation", section on 'Cerebrovascular effects'.)

Endocrine abnormalities — The hypothalamic-pituitary-adrenal (HPA) axis may be injured by cranial irradiation, which may lead to endocrine abnormalities, including thyroid disease, growth delay, obesity, abnormal puberty, and infertility [35,36]. In a report from the Childhood Cancer Survivor Study group, adult survivors of childhood brain tumors compared with their siblings are at increased risk for endocrine abnormalities, including growth hormone deficiency (relative risk [RR] 278, 95% CI 111-694), the need for medications to induce puberty (RR 86, 95% CI 31-238), and hypothyroidism (RR 14.3, 95% CI 9.7-21.0) [22].

Weight gain and obesity affect approximately one-third of survivors [36]. Contributing factors include HPA axis dysfunction as well as impaired mobility, visual impairment, disrupted sleep, medication side effects, and reduced physical activity [37,38]. In one large cohort of brain tumor survivors between 4 and 20 years of age (median 15 years), 29 percent were overweight or obese, a rate approximately twice as high as expected for the general population [36].

In female survivors, radiation therapy and diagnosis before four years of age are associated with an increased risk for menarche abnormalities, including both late and early menarche [39]. (See "Endocrinopathies in cancer survivors and others exposed to cytotoxic therapies during childhood" and "Delayed complications of cranial irradiation", section on 'Endocrinopathies'.)

Psychological effects — In a study from the Childhood Cancer Survivor Study group, adult survivors of childhood brain cancer compared with their siblings had an increased rate of symptoms of physiologic distress, particularly depression [40]. Multivariate analyses of risk factors demonstrated no association of distress with any treatment-related variable.

Social effects — Compared with age- and sex-matched controls or siblings, adult survivors of brain tumors are less likely to be married and are at risk for lower rates of employment, lower education and income levels, and high health care costs [41,42]. Some of these associations may be mediated by deficits in social cognition and executive function [43].

SURVIVORSHIP — Specific long-term follow-up guidelines for survivors of childhood CNS tumors have been published by the Children's Oncology Group [44].

Additional topics related to cancer survivorship in children and adolescents include:

●Psychosocial needs (see "Overview of cancer survivorship in adolescents and young adults")

●Fertility and parenthood (see "Overview of infertility and pregnancy outcome in cancer survivors")

●Screening for subsequent cancers (see "Overview of cancer survivorship care for primary care and oncology providers", section on 'Screening for subsequent primary cancers')

SUMMARY AND RECOMMENDATIONS

●Surgery and diagnostic confirmation – An open surgical procedure is the preferred approach for most childhood brain tumors to obtain tissue for a histologic diagnosis and bulk removal where possible. Stereotactic biopsy is used for tumors deeply located in the brain, which are not amenable to open surgical intervention because of the high risk of irreversible neurologic impairment. Intraventricular and periventricular lesions can be biopsied endoscopically. (See 'Management strategy' above and 'Surgery' above.)

●Management of complications

•Increased intracranial pressure – Patients with clinical and/or neuroimaging evidence of elevated intracranial pressure (ICP) require urgent neurosurgical intervention (eg, tumor resection and/or placement of a shunt to relieve hydrocephalus). In addition, for most children undergoing surgery for tumor resection, we suggest perioperative glucocorticoid therapy to reduce peritumoral edema (Grade 2C). A typical regimen consists of dexamethasone 0.25 to 0.5 mg/kg given orally or intravenously every six hours (maximum dose 16 mg per day). (See 'Elevated intracranial pressure' above and "Management of vasogenic edema in patients with primary and metastatic brain tumors", section on 'Initiation of glucocorticoids'.)

•Seizures – Patients with brain tumors commonly experience seizures, which may require antiseizure medication. The choice of agent is based on drug interactions, safety profile, and clinician and patient preference. (See "Seizures in patients with primary and metastatic brain tumors".)

We suggest not using prophylactic anticonvulsants in patients without a history of seizures (Grade 2C). However, some neurosurgeons may reasonably choose to provide seizure prophylaxis in the perioperative setting if the patient is deemed to be at high risk of postoperative seizures based on the location of the tumor and/or extent of resection. (See 'Seizures' above.)

•Endocrine dysfunction – Children with certain brain tumors (eg, lesions located in the hypothalamus or pituitary gland) may present with endocrine abnormalities, including growth failure, hypothyroidism, and arginine vasopressin deficiency (AVP-D). Management focuses on treating the specific endocrine abnormalities and may require hormonal replacement therapy. (See 'Endocrine abnormalities' above.)

●Adjunctive therapies

•Radiation therapy – The use of radiation therapy is dependent on the histologic diagnosis of the tumor. Although radiation therapy is an effective adjunct, it is associated with both acute and long-term complications. The timing, dose, and field of radiation are based on the histology, tumor location and size, stage of the tumor, expected patterns of spread, and availability of effective chemotherapy agents. (See 'Radiation therapy' above and "Delayed complications of cranial irradiation".)

•Chemotherapy – The use of chemotherapy is dependent on the underlying tissue histology. It is routinely used in combination with surgery and radiation therapy for older children to treat embryonal tumors (eg, medulloblastoma). In young children and infants with embryonal tumors, low-grade gliomas, and optic glioma, chemotherapy is used after surgical resection to delay or avoid the need for radiation therapy. (See 'Chemotherapy' above.)

●Prognosis – Survival after diagnosis with a primary brain or other CNS tumor varies considerably, depending on the age of the child and the type of tumor. Survivors of pediatric CNS tumors are at risk for secondary neoplasms and neurologic, cognitive, endocrine, social, and psychological sequelae. (See 'Prognosis' above.)

For children with life-threatening tumors, pediatric palliative care is an important component of management. (See "Pediatric palliative care".)