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The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization 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.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification.
|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.|
|3.||Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.|
Incidence and Presentation
Craniopharyngiomas are relatively rare pediatric tumors, accounting for about 6% of all intracranial tumors in children.[1,2,3] They are believed to be congenital in origin, arising from ectodermal remnants, Rathke cleft, or other embryonal epithelium in the sellar and/or parasellar area. No predisposing factors have been identified.
Because craniopharyngiomas occur in the region of the pituitary gland, endocrine function and growth may be affected. Additionally, the close proximity of the tumor to the optic nerves and chiasm may result in vision problems. Some patients present with obstructive hydrocephalus due to tumor obstruction of the third ventricle. Extremely rarely, the tumor may predominate in the posterior fossa with presenting symptoms of headache, diplopia, ataxia, and hearing loss.
Long-term survival for children with craniopharyngioma is generally very good. Regardless of the treatment modality, long-term survival is approximately 85% in children [2,3] with 5- and 10-year overall survival rates greater than 90%.[5,6,7]
|1.||Bunin GR, Surawicz TS, Witman PA, et al.: The descriptive epidemiology of craniopharyngioma. J Neurosurg 89 (4): 547-51, 1998.|
|2.||Karavitaki N, Wass JA: Craniopharyngiomas. Endocrinol Metab Clin North Am 37 (1): 173-93, ix-x, 2008.|
|3.||Garnett MR, Puget S, Grill J, et al.: Craniopharyngioma. Orphanet J Rare Dis 2: 18, 2007.|
|4.||Zhou L, Luo L, Xu J, et al.: Craniopharyngiomas in the posterior fossa: a rare subgroup, diagnosis, management and outcomes. J Neurol Neurosurg Psychiatry 80 (10): 1150-4, 2009.|
|5.||Muller HL: Childhood craniopharyngioma. Recent advances in diagnosis, treatment and follow-up. Horm Res 69 (4): 193-202, 2008.|
|6.||Müller HL: Childhood craniopharyngioma--current concepts in diagnosis, therapy and follow-up. Nat Rev Endocrinol 6 (11): 609-18, 2010.|
|7.||Sanford RA, Muhlbauer MS: Craniopharyngioma in children. Neurol Clin 9 (2): 453-65, 1991.|
Craniopharyngiomas are histologically benign and do not metastasize to remote brain locations or to areas outside the sellar region except by direct extension. They may be invasive, however, and may recur locally. They may be classified as adamantinomatous or squamous papillary, with the former being the predominant form in children. They are typically composed of both a solid portion with an abundance of calcification, and a cystic component which is filled with a dark, oily fluid. Recent evidence suggests that adamantinomatous craniopharyngiomas are locally more aggressive with a significantly higher rate of recurrence compared with the squamous papillary subtype.
|1.||Karavitaki N, Wass JA: Craniopharyngiomas. Endocrinol Metab Clin North Am 37 (1): 173-93, ix-x, 2008.|
|2.||Pekmezci M, Louie J, Gupta N, et al.: Clinicopathological characteristics of adamantinomatous and papillary craniopharyngiomas: University of California, San Francisco experience 1985-2005. Neurosurgery 67 (5): 1341-9; discussion 1349, 2010.|
The results of imaging studies (computerized tomography scans and magnetic resonance imaging [MRI] scans) are often diagnostic for childhood craniopharyngiomas, with most demonstrating intratumoral calcifications and a solid and cystic component. The most common location is suprasellar, with an intrasellar portion. Craniopharyngiomas without calcification may be confused with other tumor types, such as germinoma or hypothalamic/chiasmatic astrocytoma, and biopsy may be required. MRI of the spinal axis is not routinely performed.
Apart from imaging, patients often undergo formal visual examination including visual field evaluation and endocrine testing.
|1.||Rossi A, Cama A, Consales A, et al.: Neuroimaging of pediatric craniopharyngiomas: a pictorial essay. J Pediatr Endocrinol Metab 19 (Suppl 1): 299-319, 2006.|
There is no generally applied staging system for childhood craniopharyngiomas. Patients are classified as having newly diagnosed or recurrent disease.
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
There is no consensus as to the optimal treatment of newly diagnosed craniopharyngioma. Little data exist to compare the different modalities in terms of recurrence rate or quality of life. For this reason, treatment is individualized.
Because these tumors are histologically benign, it may be possible to remove all the visible tumor resulting in long-term disease control.[Level of evidence: 3iA]; [Level of evidence: 3iiiB]; [Level of evidence: 3iiiC] A 5-year progression-free survival (PFS) rate of about 65% has been reported. Many surgical approaches have been described, and the route should be determined by the size, location, and extension of the tumor. A transsphenoidal approach may be possible in some small tumors located entirely within the sella,[Level of evidence: 3iiiC] but this is not usually possible in children, in which case a craniotomy is usually required.
Gross total resection is technically challenging because the tumor is surrounded by vital structures, including the optic nerves and chiasm, the carotid artery and its branches, the hypothalamus, and the third cranial nerve. The tumor may be adherent to these structures, which may cause complications, and may limit the ability to remove the entire tumor. The surgeon often has limited visibility in the region of the hypothalamus and in the sella, and portions of the mass may be left in these areas, accounting for some recurrences. Almost all craniopharyngiomas have an attachment to the pituitary stalk, and of the patients who undergo radical surgery, virtually all will require life-long pituitary hormone replacement with multiple medications.[2,6]
Complications of radical surgery include the need for hormone replacement, obesity (which can be life threatening), severe behavioral problems, blindness, seizures, spinal fluid leak, false aneurysms, and difficulty with eye movements. Rare complications include death from intraoperative hemorrhage, hypothalamic damage, or stroke.
If the surgeon feels that tumor remains, or if postoperative imaging reveals residual craniopharyngioma that was not resected, radiation therapy may be recommended to prevent early progression.[Level of evidence: 3iiiDiii] Periodic surveillance magnetic resonance imaging is performed for several years after radical surgery because of the possibility of tumor recurrence.
Surgery with Cyst Drainage
For large cystic craniopharyngiomas, particularly in children younger than 3 years and in those with recurrent cystic tumor after initial surgery, stereotactic or open implantation of an intracystic catheter with a subcutaneous reservoir may be a valuable alternative treatment option. The benefits of this procedure include temporary relief of fluid pressure by serial drainage, and in some cases, for intracystic instillation of sclerosing agents as a means to prolong the interval to or obviate the need for radiation. This procedure may also be helpful in allowing the surgeon to perform a two-staged approach, whereby first the cyst is drained by the implanted catheter to relieve pressure and complicating symptoms, followed by tumor resection.
Limited Surgery and Radiation Therapy
The goal of limited surgery is to establish a diagnosis, drain any cysts, and decompress the optic nerves. No attempt is made to remove tumor from the pituitary stalk or hypothalamus in an effort to minimize certain late effects associated with radical surgery. The surgical procedure is followed by radiation therapy with a 5-year PFS rate of about 70%.[4,10] Conventional radiation is fractionated external-beam radiation with a recommended dose of 54 Gy to 55 Gy in 1.8 Gy fractions. Surgical complications are less likely than with radical surgery. Complications of radiation include loss of pituitary hormonal function, cognitive dysfunction, development of late strokes and vascular malformations, delayed blindness, development of second tumors, and, rarely, malignant transformation of the primary tumor within the radiation field.[12,13] Newer radiation technologies such as intensity-modulated proton therapy may reduce scatter whole-brain and whole-body irradiation and result in the sparing of normal tissues. It is unknown whether such technologies result in decreased late effects from irradiation.[14,15] Tumor progression remains a possibility, and it is usually not possible to repeat the radiation dose. In selected cases, stereotactic radiation therapy can be delivered as a single large dose of radiation to a very small field.[Level of evidence: 3iC] Proximity of the craniopharyngioma to vital structures, particularly the optic nerves, limits this to very small tumors that are in the sella.[Level of evidence: 3iiiDiii]
Intracavitary Radiation Therapy and/or Chemotherapy
Some craniopharyngiomas with a large cystic component may be treated by stereotaxic delivery of P-32 or other radioactive compounds.[18,19]; [Level of evidence: 3iiiDiii] Nonradioactive agents such as bleomycin and interferon-alpha have also been used.[21,22,23]; [Level of evidence: 2C] These strategies have been found to be useful in certain cases and are with low reported risk of complications. However, none have shown efficacy against solid portions of the tumor.
|1.||Mortini P, Losa M, Pozzobon G, et al.: Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series. J Neurosurg 114 (5): 1350-9, 2011.|
|2.||Elliott RE, Hsieh K, Hochm T, et al.: Efficacy and safety of radical resection of primary and recurrent craniopharyngiomas in 86 children. J Neurosurg Pediatr 5 (1): 30-48, 2010.|
|3.||Zhang YQ, Ma ZY, Wu ZB, et al.: Radical resection of 202 pediatric craniopharyngiomas with special reference to the surgical approaches and hypothalamic protection. Pediatr Neurosurg 44 (6): 435-43, 2008.|
|4.||Yang I, Sughrue ME, Rutkowski MJ, et al.: Craniopharyngioma: a comparison of tumor control with various treatment strategies. Neurosurg Focus 28 (4): E5, 2010.|
|5.||Locatelli D, Massimi L, Rigante M, et al.: Endoscopic endonasal transsphenoidal surgery for sellar tumors in children. Int J Pediatr Otorhinolaryngol 74 (11): 1298-302, 2010.|
|6.||Sands SA, Milner JS, Goldberg J, et al.: Quality of life and behavioral follow-up study of pediatric survivors of craniopharyngioma. J Neurosurg 103 (4 Suppl): 302-11, 2005.|
|7.||Müller HL, Gebhardt U, Teske C, et al.: Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up. Eur J Endocrinol 165 (1): 17-24, 2011.|
|8.||Lin LL, El Naqa I, Leonard JR, et al.: Long-term outcome in children treated for craniopharyngioma with and without radiotherapy. J Neurosurg Pediatr 1 (2): 126-30, 2008.|
|9.||Schubert T, Trippel M, Tacke U, et al.: Neurosurgical treatment strategies in childhood craniopharyngiomas: is less more? Childs Nerv Syst 25 (11): 1419-27, 2009.|
|10.||Winkfield KM, Tsai HK, Yao X, et al.: Long-term clinical outcomes following treatment of childhood craniopharyngioma. Pediatr Blood Cancer 56 (7): 1120-6, 2011.|
|11.||Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28 (4): E10, 2010.|
|12.||Ishida M, Hotta M, Tsukamura A, et al.: Malignant transformation in craniopharyngioma after radiation therapy: a case report and review of the literature. Clin Neuropathol 29 (1): 2-8, 2010 Jan-Feb.|
|13.||Aquilina K, Merchant TE, Rodriguez-Galindo C, et al.: Malignant transformation of irradiated craniopharyngioma in children: report of 2 cases. J Neurosurg Pediatr 5 (2): 155-61, 2010.|
|14.||Beltran C, Roca M, Merchant TE: On the benefits and risks of proton therapy in pediatric craniopharyngioma. Int J Radiat Oncol Biol Phys 82 (2): e281-7, 2012.|
|15.||Boehling NS, Grosshans DR, Bluett JB, et al.: Dosimetric comparison of three-dimensional conformal proton radiotherapy, intensity-modulated proton therapy, and intensity-modulated radiotherapy for treatment of pediatric craniopharyngiomas. Int J Radiat Oncol Biol Phys 82 (2): 643-52, 2012.|
|16.||Kobayashi T: Long-term results of gamma knife radiosurgery for 100 consecutive cases of craniopharyngioma and a treatment strategy. Prog Neurol Surg 22: 63-76, 2009.|
|17.||Hasegawa T, Kobayashi T, Kida Y: Tolerance of the optic apparatus in single-fraction irradiation using stereotactic radiosurgery: evaluation in 100 patients with craniopharyngioma. Neurosurgery 66 (4): 688-94; discussion 694-5, 2010.|
|18.||Julow J, Backlund EO, Lányi F, et al.: Long-term results and late complications after intracavitary yttrium-90 colloid irradiation of recurrent cystic craniopharyngiomas. Neurosurgery 61 (2): 288-95; discussion 295-6, 2007.|
|19.||Barriger RB, Chang A, Lo SS, et al.: Phosphorus-32 therapy for cystic craniopharyngiomas. Radiother Oncol 98 (2): 207-12, 2011.|
|20.||Zhao R, Deng J, Liang X, et al.: Treatment of cystic craniopharyngioma with phosphorus-32 intracavitary irradiation. Childs Nerv Syst 26 (5): 669-74, 2010.|
|21.||Ierardi DF, Fernandes MJ, Silva IR, et al.: Apoptosis in alpha interferon (IFN-alpha) intratumoral chemotherapy for cystic craniopharyngiomas. Childs Nerv Syst 23 (9): 1041-6, 2007.|
|22.||Linnert M, Gehl J: Bleomycin treatment of brain tumors: an evaluation. Anticancer Drugs 20 (3): 157-64, 2009.|
|23.||Steinbok P, Hukin J: Intracystic treatments for craniopharyngioma. Neurosurg Focus 28 (4): E13, 2010.|
|24.||Cavalheiro S, Di Rocco C, Valenzuela S, et al.: Craniopharyngiomas: intratumoral chemotherapy with interferon-alpha: a multicenter preliminary study with 60 cases. Neurosurg Focus 28 (4): E12, 2010.|
Recurrence of craniopharyngioma occurs in approximately 35% of patients regardless of primary therapy. Management is determined in large part by prior therapy. Repeat attempts at gross total resection are difficult and long-term disease control is less often achieved.[Level of evidence: 3iiiDi] Complications are more frequent than with initial surgery.[Level of evidence: 3iiiDi] External-beam radiation therapy is an option if this has not been previously employed, including consideration of radiosurgery in selected circumstances.[Level of evidence: 3iiiDiii] Cystic recurrences may be treated with intracavitary instillation of radioactive P-32, bleomycin,[Level of evidence: 3iiiDiii] or interferon-alpha,[Level of evidence: 3iiiB] and a reservoir may be placed to permit intermittent outpatient aspiration. Chemotherapy is generally not utilized.
|1.||Yang I, Sughrue ME, Rutkowski MJ, et al.: Craniopharyngioma: a comparison of tumor control with various treatment strategies. Neurosurg Focus 28 (4): E5, 2010.|
|2.||Vinchon M, Dhellemmes P: Craniopharyngiomas in children: recurrence, reoperation and outcome. Childs Nerv Syst 24 (2): 211-7, 2008.|
|3.||Jang WY, Lee KS, Son BC, et al.: Repeat operations in pediatric patients with recurrent craniopharyngiomas. Pediatr Neurosurg 45 (6): 451-5, 2009.|
|4.||Xu Z, Yen CP, Schlesinger D, et al.: Outcomes of Gamma Knife surgery for craniopharyngiomas. J Neurooncol 104 (1): 305-13, 2011.|
|5.||Hukin J, Steinbok P, Lafay-Cousin L, et al.: Intracystic bleomycin therapy for craniopharyngioma in children: the Canadian experience. Cancer 109 (10): 2124-31, 2007.|
|6.||Cavalheiro S, Di Rocco C, Valenzuela S, et al.: Craniopharyngiomas: intratumoral chemotherapy with interferon-alpha: a multicenter preliminary study with 60 cases. Neurosurg Focus 28 (4): E12, 2010.|
Quality-of-life issues are important in this group of patients, and are difficult to assess due to various treatment modalities. Whereas intelligence quotient is usually maintained, behavioral issues and memory deficits attributed to the frontal lobe and hypothalamus are common. Other common problems include visual loss, obesity (which can be life threatening), and the almost universal need for life-long endocrine replacement with multiple pituitary hormones.[2,3,4][Level of evidence: 3iiiC] Vasculopathies and secondary tumors may also result from local irradiation. A recent report indicated that adults on long-term growth hormone replacement secondary to childhood craniopharyngioma involving the hypothalamus were at increased cardiovascular risk.
Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.
|1.||Winkfield KM, Tsai HK, Yao X, et al.: Long-term clinical outcomes following treatment of childhood craniopharyngioma. Pediatr Blood Cancer 56 (7): 1120-6, 2011.|
|2.||Vinchon M, Weill J, Delestret I, et al.: Craniopharyngioma and hypothalamic obesity in children. Childs Nerv Syst 25 (3): 347-52, 2009.|
|3.||Dolson EP, Conklin HM, Li C, et al.: Predicting behavioral problems in craniopharyngioma survivors after conformal radiation therapy. Pediatr Blood Cancer 52 (7): 860-4, 2009.|
|4.||Kawamata T, Amano K, Aihara Y, et al.: Optimal treatment strategy for craniopharyngiomas based on long-term functional outcomes of recent and past treatment modalities. Neurosurg Rev 33 (1): 71-81, 2010.|
|5.||Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28 (4): E10, 2010.|
|6.||Holmer H, Ekman B, Björk J, et al.: Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy. Eur J Endocrinol 161 (5): 671-9, 2009.|
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.
Revised text to state that 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.
Treatment Options for Newly Diagnosed Childhood Craniopharyngioma
Revised text to state that complications of radiation include loss of pituitary hormonal function, cognitive dysfunction, development of late strokes and vascular malformations, delayed blindness, development of second tumors, and, rarely, malignant transformation of the primary tumor within the radiation field. Also added text to state that newer radiation technologies such as intensity-modulated proton therapy may reduce scatter whole-brain and whole-body irradiation and result in the sparing of normal tissues. It is unknown whether such technologies result in decreased late effects from irradiation (cited Beltran et al. and Boehling et al. as references 14 and 15, respectively).
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.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood craniopharyngioma. 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:
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 Craniopharyngioma Treatment are:
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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.
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National Cancer Institute: PDQ® Childhood Craniopharyngioma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/child-cranio/healthprofessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2012-10-05
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