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Childhood Brain Stem Glioma Treatment (PDQ®)

Health Professional Version
Last Modified: 01/28/2014
Table of Contents

General Information About Childhood Brain Stem Glioma

Cellular Classification of Childhood Brain Stem Glioma

Stage Information for Childhood Brain Stem Glioma

Treatment Option Overview for Childhood Brain Stem Glioma

Newly Diagnosed Childhood Brain Stem Glioma Treatment

Recurrent/Progressive Childhood Brain Stem Glioma Treatment

Changes to This Summary (01/28/2014)

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General Information About Childhood Brain Stem Glioma

Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis.

The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization (WHO) classification of nervous system tumors.[1,2] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.

The term brain stem glioma is a generic description that refers to any tumor of glial origin arising in the brain stem, inclusive of the midbrain, pons, and medulla. The following two histologies predominate:

  • Diffuse (infiltrating) astrocytomas centered in the pons, also called diffuse intrinsic pontine glioma (DIPG).

  • Pilocytic astrocytomas, which occur throughout the brain stem.

Incidence

Approximately 300 to 400 pediatric brain stem tumors are diagnosed each year in the United States. DIPG accounts for approximately 75% to 80% of pediatric brain stem tumors.[3] Most children with DIPG are diagnosed between the ages of 5 and 10 years. Focal pilocytic astrocytomas in the brain stem occur less frequently.[4]

Anatomy

Enlarge
Drawing of the inside of the brain showing  the lateral ventricle, third ventricle, and fourth ventricle, cerebrum, choroid plexus, hypothalamus, pineal gland, pituitary gland, optic nerve, tentorium, cerebellum,  brain stem, pons, medulla, and spinal cord.
Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain. The posterior fossa is the region below the tentorium, which separates the cortex from the cerebellum and essentially denotes the region containing the brain stem, cerebellum, and fourth ventricle.


Clinical Features

In children with DIPG, a classic triad of symptoms (cranial neuropathies, long tract signs, and ataxia) is often described. However, children often present with only one or two of these findings. Obstructive hydrocephalus due to expansion of the pons can also be a presenting symptom. Nonspecific symptoms may also occur, including behavioral changes and decreased school performance.

Focal pilocytic astrocytomas in the brain stem present in multiple ways depending on tumor location. Common presenting symptoms include the following:[4]

  • Raised intracranial pressure with associated hydrocephalus.
  • Unilateral hemiparesis.
  • Unilateral cranial neuropathies.
  • Ataxia.
Diagnosis

Primary tumors of the brain stem are most often diagnosed based on clinical findings and on neuroimaging studies using magnetic resonance imaging (MRI).[5] Histologic confirmation of presumed DIPGs is usually unnecessary. However, histologic confirmation is currently performed for research studies and may be more routinely recommended in the future.[6] Biopsy or resection may be indicated for brain stem tumors that are not diffuse and intrinsic or when there is diagnostic uncertainty based on imaging findings. New approaches with stereotactic needle biopsy may make biopsy safer.[7,8]

Children with neurofibromatosis type 1 (NF1) are at an increased risk of developing a brain stem glioma. They may present with a long history of symptoms or be identified by screening tests.

Prognosis and Prognostic Factors

The median survival for children with DIPGs is less than 1 year.[9] In contrast, focal pilocytic astrocytomas have a markedly improved prognosis, with 5-year overall survival exceeding 90%.[4]

Prognostic factors include the following:

  • Histology/grade of the tumor: Astrocytic tumors predominate in the brain stem. Pilocytic astrocytomas (WHO grade 1) have a favorable prognosis and can arise throughout the brain stem, including the tectum of the midbrain, focally within the pons, or at the cervicomedullary junction where they are often exophytic. In contrast, DIPGs are diffuse astrocytomas which, when biopsied at diagnosis or at postmortem evaluation, are often anaplastic astrocytoma (WHO grade 3) or glioblastoma (WHO grade 4). Low-grade fibrillary astrocytomas (WHO grade 2) can occur as focal tumors throughout the brain stem, with a good prognosis. Conversely, some children with imaging features supportive of a diagnosis of DIPG in whom tissue is eventually obtained may also show low-grade fibrillary histology.[10]

  • Age at diagnosis: Children younger than 3 years may have a more favorable prognosis, perhaps reflecting different biologic characteristics.[11]

  • NF1: Children with NF1 and brain stem gliomas may have a better prognosis than other patients who have intrinsic lesions.[12,13]

Follow-up After Treatment

For children with brain stem tumors and anticipated long-term survival, standard follow-up tends to include interval clinical assessments and periodic imaging with MRI. The required duration of follow-up with MRI varies; it largely depends on the presence or absence of residual imaging abnormalities and the original histology of the tumor after treatment.

References
  1. Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007. 

  2. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.  [PUBMED Abstract]

  3. Warren KE: Diffuse intrinsic pontine glioma: poised for progress. Front Oncol 2: 205, 2012.  [PUBMED Abstract]

  4. Klimo P Jr, Pai Panandiker AS, Thompson CJ, et al.: Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience. J Neurosurg Pediatr 11 (3): 274-81, 2013.  [PUBMED Abstract]

  5. Liu AK, Brandon J, Foreman NK, et al.: Conventional MRI at presentation does not predict clinical response to radiation therapy in children with diffuse pontine glioma. Pediatr Radiol 39 (12): 1317-20, 2009.  [PUBMED Abstract]

  6. Walker DA, Liu J, Kieran M, et al.: A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro Oncol 15 (4): 462-8, 2013.  [PUBMED Abstract]

  7. Cage TA, Samagh SP, Mueller S, et al.: Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children. Childs Nerv Syst 29 (8): 1313-9, 2013.  [PUBMED Abstract]

  8. Grill J, Puget S, Andreiuolo F, et al.: Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer 58 (4): 489-91, 2012.  [PUBMED Abstract]

  9. Cohen KJ, Pollack IF, Zhou T, et al.: Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol 13 (3): 317-23, 2011.  [PUBMED Abstract]

  10. Warren KE, Killian K, Suuriniemi M, et al.: Genomic aberrations in pediatric diffuse intrinsic pontine gliomas. Neuro Oncol 14 (3): 326-32, 2012.  [PUBMED Abstract]

  11. Broniscer A, Laningham FH, Sanders RP, et al.: Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 113 (3): 566-72, 2008.  [PUBMED Abstract]

  12. Pascual-Castroviejo I, Pascual-Pascual SI, Viaño J, et al.: Posterior fossa tumors in children with neurofibromatosis type 1 (NF1). Childs Nerv Syst 26 (11): 1599-603, 2010.  [PUBMED Abstract]

  13. Albers AC, Gutmann DH: Gliomas in patients with neurofibromatosis type 1. Expert Rev Neurother 9 (4): 535-9, 2009.  [PUBMED Abstract]

Cellular Classification of Childhood Brain Stem Glioma



Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)

The genomic characteristics of DIPGs appear to differ from those of most other pediatric high-grade gliomas and from those of adult high-grade gliomas. A number of chromosomal abnormalities have been reported for DIPG, including the following:

  • Histone H3 genes: Approximately 80% of DIPG tumors have a mutation in a specific amino acid in one of two histone H3 genes (H3F3A or HIST1H3B).[1] These mutations are less common in non–brain stem pediatric high-grade gliomas and are uncommon in adult high-grade gliomas.[1,2]

  • Receptor tyrosine kinase amplification: PDGFRA amplification occurs in approximately 30% of cases, with lower rates of amplification observed for some other receptor tyrosine kinases (e.g., MET and IGF1R).[3,4]

  • P53 deletion: DIPG tumors commonly show deletion of the P53 gene on chromosome 17p.[4]

The gene expression profile of DIPG differs from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas.[4]

References
  1. Wu G, Broniscer A, McEachron TA, et al.: Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44 (3): 251-3, 2012.  [PUBMED Abstract]

  2. Schwartzentruber J, Korshunov A, Liu XY, et al.: Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482 (7384): 226-31, 2012.  [PUBMED Abstract]

  3. Zarghooni M, Bartels U, Lee E, et al.: Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28 (8): 1337-44, 2010.  [PUBMED Abstract]

  4. Paugh BS, Broniscer A, Qu C, et al.: Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29 (30): 3999-4006, 2011.  [PUBMED Abstract]

Stage Information for Childhood Brain Stem Glioma

There is no generally applied staging system for childhood brain stem glioma.[1]

Brain stem gliomas are classified according to the following:

  • Location.
  • Radiographic appearance.
  • Histology (when obtained).

Brain stem gliomas may occur in the pons, midbrain, tectum, dorsum of the medulla at the cervicomedullary junction, or in multiple regions of the brain stem. The tumor may contiguously involve the cerebellar peduncles, cerebellum, the cervical spinal cord, and/or thalamus. The majority of childhood brain stem gliomas are diffuse astrocytomas that involve the pons (diffuse intrinsic pontine gliomas [DIPGs]), often with contiguous involvement of other brain stem sites.[2,3]

It is uncommon for these tumors to have spread outside the brain stem itself at the time of initial diagnosis. Spread of malignant brain stem tumors is usually contiguous, with metastasis via the subarachnoid space. Such dissemination may occur prior to local relapse but usually occurs simultaneously with or after local disease relapse.[4]

References
  1. Freeman CR, Farmer JP: Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 40 (2): 265-71, 1998.  [PUBMED Abstract]

  2. Laigle-Donadey F, Doz F, Delattre JY: Brainstem gliomas in children and adults. Curr Opin Oncol 20 (6): 662-7, 2008.  [PUBMED Abstract]

  3. Khatua S, Moore KR, Vats TS, et al.: Diffuse intrinsic pontine glioma-current status and future strategies. Childs Nerv Syst 27 (9): 1391-7, 2011.  [PUBMED Abstract]

  4. Sethi R, Allen J, Donahue B, et al.: Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma. J Neurooncol 102 (1): 121-7, 2011.  [PUBMED Abstract]

Treatment Option Overview for Childhood Brain Stem Glioma

Many of the improvements in survival in childhood cancer have been made as a result of clinical trials that have attempted to improve on the best available, accepted therapy. Clinical trials in pediatrics are designed to compare new therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms or by evaluating a single new treatment and comparing the results with those that were previously obtained with existing therapy.

Because of the relative rarity of cancer in children, all patients with brain tumors should be considered for entry into a clinical trial. To determine and implement optimum treatment, planning by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required. Radiation therapy (including 3-dimensional conformal radiation therapy) of pediatric brain tumors is technically very demanding and should be carried out in centers that have experience in that area in order to ensure optimal results.

Table 1. Standard Treatment Options for Childhood Brain Stem Gliomas
Stage Standard Treatment Options 
Newly diagnosed childhood brain stem gliomas:
Diffuse intrinsic pontine gliomasRadiation therapy
Focal or low-grade brain stem gliomasSurgical resection (with or without radiation therapy and chemotherapy)
Observation (with or without cerebrospinal fluid diversion)
Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors
Recurrent/progressive childhood brain stem gliomas:
Diffuse intrinsic pontine gliomasPalliative care
Focal or low-grade brain stem gliomasRepeat surgical resection
Radiation therapy
Chemotherapy

Newly Diagnosed Childhood Brain Stem Glioma Treatment



Standard Treatment Options for Diffuse Intrinsic Pontine Gliomas (DIPGs)

While numerous clinical trials are available for children with newly diagnosed DIPGs, the utility of any therapy besides radiation therapy in the treatment of patients with newly diagnosed DIPG remains unproven.[1-6]; [7,8][Level of evidence: 2A]; [9][Level of evidence: 3iiiA]

Currently, no chemotherapeutic strategy—including neoadjuvant, concurrent, postradiation therapy, or immunotherapy—when added to radiation therapy has led to long-term survival for children with DIPGs.[10-12]; [13][Level of evidence: 2A] This includes studies utilizing high-dose, marrow-ablative chemotherapy with autologous hematopoietic stem cell rescue, which have also been ineffective in extending survival.[14]

Standard treatment options for newly diagnosed DIPGs include the following:

  1. Radiation therapy.
Radiation therapy

Conventional treatment for children with DIPGs is radiation therapy to involved areas. The conventional dose of radiation ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions. Such treatment will result in transient benefit for most patients, but more than 90% of patients will die within 18 months of diagnosis.[15]

Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.[16]

Research studies evaluating the efficacy of hyperfractionated and hypofractionated radiation therapy and radiosensitizers have not demonstrated improved outcomes using these radiation techniques.

  1. Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 78 Gy have been completed. Evidence demonstrates that these increased radiation therapy doses do not improve the duration or rate of survival for patients with DIPGs, whether given alone [1,17] or in combination with chemotherapy.[3]

  2. Hypofractionated radiation therapy results in survival rates comparable to conventional fractionated radiation therapy techniques, possibly with less treatment burden.[15,18][Level of evidence: 2A]

  3. Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of radiation therapy have been undertaken but to date have failed to show any significant improvement in outcome.[1,3-5,19,20]

Chemotherapy only (infants)

Similar to the treatment of other brain tumors, radiation therapy is often omitted for infants with DIPGs, and chemotherapy-only approaches are utilized. However, published data supporting the utility of this approach is lacking.

Treatment options under clinical evaluation

Early-phase therapeutic trials may be available for selected patients. These trials may be available via Children’s Oncology Group phase I institutions, the Pediatric Brain Tumor Consortium, or other entities.

Standard Treatment Options for Focal or Low-Grade Brain Stem Gliomas

Standard treatment options for newly diagnosed focal or low-grade brain stem gliomas include the following:

  1. Surgical resection (with or without radiation therapy and chemotherapy).
  2. Observation (with or without cerebrospinal fluid diversion).
  3. Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors.
Surgical resection (with or without radiation therapy and chemotherapy)

In general, maximal surgical resection is attempted.[21,22]

Patients with residual tumor may be candidates for additional therapy, including 3-dimensional conformal radiation therapy approaches, with or without adjuvant chemotherapy.

Observation (with or without cerebrospinal fluid diversion)

Patients with small tectal lesions and hydrocephalus but no other neurological deficits may be treated with cerebrospinal fluid diversion alone and have follow-up with sequential neuroradiographic studies unless there is evidence of progressive disease.[21]

A period of observation may be indicated before instituting any treatment for patients with neurofibromatosis type 1.[23] Brain stem gliomas in these children may be indolent and may require no specific treatment for years.[24]

Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors

In selected circumstances, adjuvant therapy in the form of radiation therapy or chemotherapy can be considered in a child with a newly diagnosed focal or low-grade brain stem glioma.[25,26][Level of evidence: 3iDi] Decisions regarding the need for such therapy depend on the age of the child, the extent of resection obtainable, and associated neurologic deficits.

Alternative approaches for the treatment of inoperable brain stem gliomas include the following:

  • Stereotactic iodine I-125 brachytherapy approaches, with or without adjuvant chemotherapy.[27]

  • The use of BRAF inhibitors for tumors harboring a V600E mutation.[28]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Mandell LR, Kadota R, Freeman C, et al.: There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43 (5): 959-64, 1999.  [PUBMED Abstract]

  2. Jennings MT, Sposto R, Boyett JM, et al.: Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group. J Clin Oncol 20 (16): 3431-7, 2002.  [PUBMED Abstract]

  3. Allen J, Siffert J, Donahue B, et al.: A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 86 (6): 1064-9, 1999.  [PUBMED Abstract]

  4. Broniscer A, Leite CC, Lanchote VL, et al.: Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J Clin Oncol 18 (6): 1246-53, 2000.  [PUBMED Abstract]

  5. Doz F, Neuenschwander S, Bouffet E, et al.: Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Société Française d'Oncologie Pédiatrique. Eur J Cancer 38 (6): 815-9, 2002.  [PUBMED Abstract]

  6. Wolff JE, Westphal S, Mölenkamp G, et al.: Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87 (9): 945-9, 2002.  [PUBMED Abstract]

  7. Korones DN, Fisher PG, Kretschmar C, et al.: Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. Pediatr Blood Cancer 50 (2): 227-30, 2008.  [PUBMED Abstract]

  8. Cohen KJ, Heideman RL, Zhou T, et al.: Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group. Neuro Oncol 13 (4): 410-6, 2011.  [PUBMED Abstract]

  9. Jalali R, Raut N, Arora B, et al.: Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 77 (1): 113-8, 2010.  [PUBMED Abstract]

  10. Frappaz D, Schell M, Thiesse P, et al.: Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro Oncol 10 (4): 599-607, 2008.  [PUBMED Abstract]

  11. Frazier JL, Lee J, Thomale UW, et al.: Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 3 (4): 259-69, 2009.  [PUBMED Abstract]

  12. Hargrave D, Bartels U, Bouffet E: Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7 (3): 241-8, 2006.  [PUBMED Abstract]

  13. Warren K, Bent R, Wolters PL, et al.: A phase 2 study of pegylated interferon α-2b (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma. Cancer 118 (14): 3607-13, 2012.  [PUBMED Abstract]

  14. Bouffet E, Raquin M, Doz F, et al.: Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88 (3): 685-92, 2000.  [PUBMED Abstract]

  15. Janssens GO, Jansen MH, Lauwers SJ, et al.: Hypofractionation vs conventional radiation therapy for newly diagnosed diffuse intrinsic pontine glioma: a matched-cohort analysis. Int J Radiat Oncol Biol Phys 85 (2): 315-20, 2013.  [PUBMED Abstract]

  16. Liu AK, Macy ME, Foreman NK: Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 75 (4): 1148-54, 2009.  [PUBMED Abstract]

  17. Freeman CR, Krischer JP, Sanford RA, et al.: Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys 27 (2): 197-206, 1993.  [PUBMED Abstract]

  18. Negretti L, Bouchireb K, Levy-Piedbois C, et al.: Hypofractionated radiotherapy in the treatment of diffuse intrinsic pontine glioma in children: a single institution's experience. J Neurooncol 104 (3): 773-7, 2011.  [PUBMED Abstract]

  19. Freeman CR, Kepner J, Kun LE, et al.: A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas? Int J Radiat Oncol Biol Phys 47 (3): 561-4, 2000.  [PUBMED Abstract]

  20. Bradley KA, Zhou T, McNall-Knapp RY, et al.: Motexafin-gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a children's oncology group phase 2 study. Int J Radiat Oncol Biol Phys 85 (1): e55-60, 2013.  [PUBMED Abstract]

  21. Vandertop WP, Hoffman HJ, Drake JM, et al.: Focal midbrain tumors in children. Neurosurgery 31 (2): 186-94, 1992.  [PUBMED Abstract]

  22. Kestle J, Townsend JJ, Brockmeyer DL, et al.: Juvenile pilocytic astrocytoma of the brainstem in children. J Neurosurg 101 (1 Suppl): 1-6, 2004.  [PUBMED Abstract]

  23. Bilaniuk LT, Molloy PT, Zimmerman RA, et al.: Neurofibromatosis type 1: brain stem tumours. Neuroradiology 39 (9): 642-53, 1997.  [PUBMED Abstract]

  24. Molloy PT, Bilaniuk LT, Vaughan SN, et al.: Brainstem tumors in patients with neurofibromatosis type 1: a distinct clinical entity. Neurology 45 (10): 1897-902, 1995.  [PUBMED Abstract]

  25. Klimo P Jr, Pai Panandiker AS, Thompson CJ, et al.: Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience. J Neurosurg Pediatr 11 (3): 274-81, 2013.  [PUBMED Abstract]

  26. Ronghe M, Hargrave D, Bartels U, et al.: Vincristine and carboplatin chemotherapy for unresectable and/or recurrent low-grade astrocytoma of the brainstem. Pediatr Blood Cancer 55 (3): 471-7, 2010.  [PUBMED Abstract]

  27. Ruge MI, Kickingereder P, Simon T, et al.: Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome. J Neurooncol 109 (2): 273-83, 2012.  [PUBMED Abstract]

  28. Rush S, Foreman N, Liu A: Brainstem ganglioglioma successfully treated with vemurafenib. J Clin Oncol 31 (10): e159-60, 2013.  [PUBMED Abstract]

Recurrent/Progressive Childhood Brain Stem Glioma Treatment



Treatment Options for Recurrent Diffuse Intrinsic Pontine Gliomas (DIPGs)

Given the dismal prognosis for patients with DIPGs, progression of the pontine lesion is anticipated generally within 1 year of completing radiation therapy. In most cases, biopsy at the time of clinical or radiologic progression is neither necessary nor recommended. To date, no salvage regimen has been shown to extend survival. Patients should be considered for entry into trials of novel therapeutic approaches because there are no standard agents that have demonstrated a clinically significant activity.

Palliative Care

Palliative care is provided for these patients whether or not disease-directed therapy is administered.

Treatment options under clinical evaluation

Early-phase therapeutic trials may be available for selected patients. These trials may be available via Children’s Oncology Group phase I institutions, the Pediatric Brain Tumor Consortium, or other entities.

Treatment Options for Recurrent Focal or Low-Grade Brain Stem Gliomas

At the time of recurrence, a complete evaluation to determine the extent of the relapse may be indicated for selected low-grade lesions. Biopsy or surgical resection should be considered for confirmation of relapse when other entities such as secondary tumor and treatment-related brain necrosis, which may be clinically indistinguishable from tumor recurrence, are in the differential diagnosis. Other tests, including positron emission tomography, magnetic resonance spectroscopy, and single-photon emission computed tomography, have not yet been shown to be reliable in distinguishing necrosis from tumor recurrence in brain stem gliomas. Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.

Treatment considerations at the time of recurrence or progression are dependent on prior treatment. Treatment options for recurrent focal or low-grade brain stem gliomas include the following:

  1. Repeat surgical resection: The need for surgical intervention must be individualized on the basis of the initial tumor type, the location within the brain stem, the length of time between initial treatment, the appearance of the mass lesion, and the clinical picture.[1]

  2. Radiation therapy including 3-dimensional conformal radiation therapy.

  3. Chemotherapy: Chemotherapy with agents such as a carboplatin and vincristine may be effective in children with recurrent low-grade exophytic gliomas.[2,3]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Bowers DC, Krause TP, Aronson LJ, et al.: Second surgery for recurrent pilocytic astrocytoma in children. Pediatr Neurosurg 34 (5): 229-34, 2001.  [PUBMED Abstract]

  2. Packer RJ, Lange B, Ater J, et al.: Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11 (5): 850-6, 1993.  [PUBMED Abstract]

  3. Ater JL, Zhou T, Holmes E, et al.: Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol 30 (21): 2641-7, 2012.  [PUBMED Abstract]

Changes to This Summary (01/28/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was reformatted.

This summary was comprehensively reviewed and extensively revised.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

About This PDQ Summary



Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood brain stem glioma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Brain Stem Glioma Treatment are:

  • Kenneth J. Cohen, MD, MBA (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital)
  • Karen J Marcus, MD (Dana-Farber Cancer Institute/Boston Children's Hospital)
  • Roger J. Packer, MD (Children's National Medical Center)
  • Malcolm A. Smith, MD, PhD (National Cancer Institute)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Childhood Brain Stem Glioma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/child-brain-stem-glioma/HealthProfessional. Accessed <MM/DD/YYYY>.

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