General Information About Childhood Craniopharyngioma

Primary brain tumors, including craniopharyngiomas, 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.

Craniopharyngiomas are uncommon pediatric brain tumors. They are believed to be congenital in origin, arising from ectodermal remnants, Rathke cleft, or other embryonal epithelium, and often occur in the suprasellar region with an intrasellar portion. Magnetic resonance imaging (MRI) and computed tomography (CT) imaging are used to diagnose craniopharyngiomas, but histologic confirmation is generally required before treatment. The treatment of newly diagnosed craniopharyngiomas may include a combination of surgery, radiation therapy, cyst drainage, and/or intracystic interferon-alpha. The treatment of recurrent craniopharyngiomas depends on the initial treatment used. Regardless of treatment given, the 5-year and 10-year survival rates exceed 90%.

The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization classification of nervous system tumors.[1 ] 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.

Incidence

Craniopharyngiomas are relatively uncommon, accounting for about 6% of all intracranial tumors in children.[2 ,3 ]

No predisposing factors have been identified.

Anatomy

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 tentorium separates the cerebrum from the cerebellum. The infratentorium (posterior fossa) is the region below the tentorium that contains the brain stem, cerebellum, and fourth ventricle. The supratentorium is the region above the tentorium and denotes the region that contains the cerebrum.

Clinical Presentation

Craniopharyngiomas occur in the region of the pituitary gland, and endocrine function may be affected. Additionally, their closeness to the optic nerves and chiasm may result in vision problems. Some patients present with obstructive hydrocephalus caused by tumor growth within the third ventricle. Rarely, tumors may extend into the posterior fossa, and patients may present with headache, diplopia, ataxia, and hearing loss.[4 ]

Diagnostic Evaluation

CT scans and MRI scans are often diagnostic for childhood craniopharyngiomas, with most tumors demonstrating intratumoral calcifications and a solid and cystic component. MRI of the spinal axis is not routinely performed.

Craniopharyngiomas without calcification may be confused with other tumor types, including germ cell tumors, hypothalamic/chiasmatic astrocytomas, or Langerhans cell histiocytosis. Biopsy or resection is required to confirm the diagnosis.[5 ]

Apart from imaging, patients often undergo endocrine testing and formal vision examination, including visual-field evaluation.

Prognosis

Regardless of the treatment modality, long-term event-free survival is approximately 65% in children,[2 ,3 ] with 5-year and 10-year overall survival rates higher than 90%.[6 ,7 ,8 ]

References:

1. Louis DN, Ohgaki H, Wiestler OD: WHO Classification of Tumours of the Central Nervous System. 4th rev.ed. Lyon, France: IARC Press, 2016.
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. 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.
6. Muller HL: Childhood craniopharyngioma. Recent advances in diagnosis, treatment and follow-up. Horm Res 69 (4): 193-202, 2008.
7. Müller HL: Childhood craniopharyngioma--current concepts in diagnosis, therapy and follow-up. Nat Rev Endocrinol 6 (11): 609-18, 2010.
8. Zacharia BE, Bruce SS, Goldstein H, et al.: Incidence, treatment and survival of patients with craniopharyngioma in the surveillance, epidemiology and end results program. Neuro Oncol 14 (8): 1070-8, 2012.

Histopathologic Classification of Childhood Craniopharyngioma

Craniopharyngiomas are histologically benign and often occur in the suprasellar region, with an intrasellar portion. They may be locally invasive and typically do not metastasize to remote brain locations.

Craniopharyngiomas are classified as one of the following:

• Adamantinomatous: Adamantinomatous craniopharyngioma is the type found most frequently in children.[1 ] These tumors are typically composed of a solid portion formed by nests and trabeculae of epithelial tumor cells, with an abundance of calcification, and a cystic component that is filled with a dark, oily fluid. Wet keratin is also characteristic. Adamantinomatous craniopharyngiomas are more locally aggressive than are papillary tumors and have a significantly higher rate of recurrence.[2 ] Activating beta-catenin (CTNNB1) gene mutations are found in most adamantinomatous tumors.[3 ,4 ,5 ]
• Papillary: Papillary craniopharyngiomas occur primarily in adults. BRAF V600E mutations are observed in nearly all papillary craniopharyngiomas.[4 ,5 ]

References:

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.
3. Sekine S, Shibata T, Kokubu A, et al.: Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol 161 (6): 1997-2001, 2002.
4. Brastianos PK, Taylor-Weiner A, Manley PE, et al.: Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet 46 (2): 161-5, 2014.
5. Goschzik T, Gessi M, Dreschmann V, et al.: Genomic Alterations of Adamantinomatous and Papillary Craniopharyngioma. J Neuropathol Exp Neurol 76 (2): 126-134, 2017.

Stage Information for Childhood Craniopharyngioma

There is no generally applied staging system for childhood craniopharyngiomas. For treatment purposes, patients are grouped as having newly diagnosed or recurrent disease.

Treatment Option Overview for Childhood Craniopharyngioma

Table 1 describes the treatment options for newly diagnosed and recurrent childhood craniopharyngioma.

Table 1. Treatment Options for Childhood Craniopharyngioma

Treatment Group	Treatment Options
Newly diagnosed childhood craniopharyngioma	Complete resection with or without radiation therapy
	Subtotal resection with radiation therapy
	Primary cyst drainage with or without radiation therapy
	Intracystic interferon-alpha
Recurrent childhood craniopharyngioma	Surgery
	Radiation therapy, including radiosurgery
	Intracavitary instillation of radioactive phosphorus P 32, bleomycin, or interferon-alpha, for those with cystic recurrences
	Systemic interferon

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[1 ] Childhood and adolescent cancer survivors require close monitoring 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.)

References:

1. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.

Newly Diagnosed Childhood Craniopharyngioma Treatment

Treatment Options for Newly Diagnosed Childhood Craniopharyngioma

There is no consensus on the optimal treatment for newly diagnosed craniopharyngioma, in part because of the lack of prospective randomized trials that compare the different treatment options. Treatment is individualized on the basis of factors that include the following:

• Tumor size.
• Tumor location.
• Extension of the tumor.
• Potential short-term and long-term toxicity.

Treatment options for newly diagnosed childhood craniopharyngioma include the following:

1. Complete resection with or without radiation therapy.
2. Subtotal resection with radiation therapy.
3. Primary cyst drainage with or without radiation therapy.
4. Intracystic interferon-alpha.

Complete resection with or without radiation therapy

It may be possible to remove all visible tumor and achieve long-term disease control.[1 ][Level of evidence: 3iA]; [2 ][Level of evidence: 3iiiB]; [3 ][Level of evidence: 3iiiC] A 5-year progression-free survival (PFS) rate of about 65% has been reported.[4 ] Gross-total resection is often 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. These structures may limit the ability to remove the entire tumor.

Many surgical approaches have been described, and the choice is determined by tumor size, location, and extension. Surgical approaches include the following:

• Transsphenoidal approach: A transsphenoidal approach may be possible for some small tumors located entirely within the sella.[5 ][Level of evidence: 3iiiC] The development of expanded endonasal techniques with endoscopic visualization have allowed increased use of this approach, even for sizeable childhood tumors, which is similar to the experience in adults.[6 ] When an endonasal approach is not possible, a craniotomy is required.
• Craniotomy: As noted above, gross-total resection may be technically challenging because the tumor is surrounded by vital structures. The surgeon often has a limited view of the hypothalamic and sellar regions, and portions of the mass may remain after surgery, accounting for some recurrences. An understanding of the complex variations in how the tumors grow anatomically may help facilitate gross-total resection.[7 ] Nonetheless, almost all craniopharyngiomas have an attachment to the pituitary stalk, and of the patients who undergo complete resection, virtually all will require lifelong pituitary hormone replacement with multiple medications.[2 ,8 ]

  Complications of complete resection include the following:

  • Obesity, which can be life-threatening.[9 ]
  • Need for hormone replacement therapy.[10 ]
  • Severe behavioral problems.[10 ]
  • Blindness.
  • Seizures.
  • Spinal fluid leak.
  • False aneurysms.
  • Difficulty with eye movements.
  • Death from intraoperative hemorrhage, hypothalamic damage, or stroke (rare).

If the surgeon indicates that the tumor was not completely removed or if postoperative imaging reveals residual craniopharyngioma, radiation therapy may be recommended to prevent early progression (refer to the Subtotal resection with radiation therapy section of this summary for more information).[11 ][Level of evidence: 3iiiDiii]

Periodic surveillance using magnetic resonance imaging is performed for several years after complete resection because of the possibility of tumor recurrence.

Subtotal resection with 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 the late effects associated with complete resection.[12 ]

The surgical procedure is often followed by radiation therapy, with a 5-year PFS rate of about 70% to 90% [4 ,13 ]; [14 ][Level of evidence: 3iDiii] and 10-year overall survival rates exceeding 90%.[15 ][Level of evidence: 3iiA]; [16 ][Level of evidence: 3iiiDiii] The standard approach to radiation therapy involves fractionated external-beam radiation, with a recommended dose of 50 Gy to 54 Gy, in 1.8-Gy fractions, restricting the optic chiasm dose to 54 Gy.[17 ,18 ,19 ,20 ] Transient cyst enlargement may be noted soon after radiation therapy but generally resolves without further intervention.[21 ][Level of evidence: 3iDiv]

A systematic review of 109 reports that described extent of resection found that subtotal resection plus radiation therapy was associated with rates of tumor control similar to those for gross-total resection. It was also reported that both approaches were associated with PFS rates higher than those for subtotal resection alone.[16 ][Level of evidence: 3iiiDiii]

Surgical complications with a subtotal resection are less likely than with complete resection. Complications of radiation therapy include the following:

• Loss of pituitary hormonal function.
• Cognitive dysfunction.
• Development of late strokes and vascular malformations.
• Delayed blindness.
• Development of second tumors.
• Malignant transformation of the primary tumor within the radiation field (rare).[22 ,23 ]

Newer radiation technologies such as intensity-modulated photon therapy and proton therapy may reduce the radiation dose to uninvolved parts of the brain and spare normal tissue. When these highly conformal radiation treatments are employed, interim imaging is commonly performed to detect changes in cyst volume, with treatment plans modified as appropriate.[20 ,24 ,25 ] It is unknown whether such technologies reduce late effects from radiation.[14 ,20 ,25 ,26 ]

Tumor progression remains a concern, and it is usually not possible to repeat a full course of standard fractionated radiation. In selected cases, stereotactic radiation therapy can be delivered as a single large dose of radiation to a small field.[27 ][Level of evidence: 3iC] Proximity of the craniopharyngioma to vital structures, particularly the optic nerves, limits this to small tumors within the sella.[28 ][Level of evidence: 3iiiDiii]

Primary cyst drainage with or without radiation therapy

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 viable alternative treatment option. Benefits include temporary relief of fluid pressure by serial drainage, and in some cases, allowance for intracystic instillation of sclerosing agents as a means to postpone or obviate radiation treatment. This procedure may also allow the surgeon to use a two-stage approach: first draining the cyst via the implanted catheter, to relieve pressure and complicating symptoms; and then later resecting the tumor or employing radiation therapy.[29 ]

Intracystic interferon-alpha

Intracystic interferon-alpha may also be a treatment option for primary cystic lesions, after ensuring the integrity of the cyst wall, to delay the need for alternative therapies.[30 ]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

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. Chivukula S, Koutourousiou M, Snyderman CH, et al.: Endoscopic endonasal skull base surgery in the pediatric population. J Neurosurg Pediatr 11 (3): 227-41, 2013.
7. Morisako H, Goto T, Goto H, et al.: Aggressive surgery based on an anatomical subclassification of craniopharyngiomas. Neurosurg Focus 41 (6): E10, 2016.
8. 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.
9. 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.
10. Clark AJ, Cage TA, Aranda D, et al.: Treatment-related morbidity and the management of pediatric craniopharyngioma: a systematic review. J Neurosurg Pediatr 10 (4): 293-301, 2012.
11. 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.
12. Elowe-Gruau E, Beltrand J, Brauner R, et al.: Childhood craniopharyngioma: hypothalamus-sparing surgery decreases the risk of obesity. J Clin Endocrinol Metab 98 (6): 2376-82, 2013.
13. 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.
14. Merchant TE, Kun LE, Hua CH, et al.: Disease control after reduced volume conformal and intensity modulated radiation therapy for childhood craniopharyngioma. Int J Radiat Oncol Biol Phys 85 (4): e187-92, 2013.
15. Schoenfeld A, Pekmezci M, Barnes MJ, et al.: The superiority of conservative resection and adjuvant radiation for craniopharyngiomas. J Neurooncol 108 (1): 133-9, 2012.
16. Clark AJ, Cage TA, Aranda D, et al.: A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma. Childs Nerv Syst 29 (2): 231-8, 2013.
17. Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28 (4): E10, 2010.
18. Harrabi SB, Adeberg S, Welzel T, et al.: Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects. Radiat Oncol 9: 203, 2014.
19. Lo AC, Howard AF, Nichol A, et al.: Long-term outcomes and complications in patients with craniopharyngioma: the British Columbia Cancer Agency experience. Int J Radiat Oncol Biol Phys 88 (5): 1011-8, 2014.
20. Bishop AJ, Greenfield B, Mahajan A, et al.: Proton beam therapy versus conformal photon radiation therapy for childhood craniopharyngioma: multi-institutional analysis of outcomes, cyst dynamics, and toxicity. Int J Radiat Oncol Biol Phys 90 (2): 354-61, 2014.
21. Shi Z, Esiashvili N, Janss AJ, et al.: Transient enlargement of craniopharyngioma after radiation therapy: pattern of magnetic resonance imaging response following radiation. J Neurooncol 109 (2): 349-55, 2012.
22. 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.
23. 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.
24. Winkfield KM, Linsenmeier C, Yock TI, et al.: Surveillance of craniopharyngioma cyst growth in children treated with proton radiotherapy. Int J Radiat Oncol Biol Phys 73 (3): 716-21, 2009.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. Kilday JP, Caldarelli M, Massimi L, et al.: Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN. Neuro Oncol 19 (10): 1398-1407, 2017.

Recurrent Childhood Craniopharyngioma Treatment

Treatment Options for Recurrent Childhood Craniopharyngioma

Recurrence of craniopharyngioma occurs in approximately 35% of patients regardless of primary therapy.[1 ]

Treatment options for recurrent childhood craniopharyngioma include the following:

1. Surgery.
2. Radiation therapy, including radiosurgery.
3. Intracavitary instillation of radioactive phosphorus P 32 (32P), bleomycin, or interferon-alpha, for those with cystic recurrences.
4. Systemic interferon.

The management of recurrent craniopharyngioma is determined largely by previous therapy. Repeat attempts at gross-total resections are difficult, and long-term disease control is achieved less often.[2 ][Level of evidence: 3iiiDi] Complications are more frequent than with initial surgery.[3 ][Level of evidence: 3iiiDi] If not previously employed, external-beam radiation therapy is an option, including consideration of radiosurgery in selected circumstances.[4 ][Level of evidence: 3iiiDiii]

Cystic recurrences may be treated with intracavitary instillation of varying agents via placement of an Ommaya catheter.[5 ] These agents have included radioactive 32P or other radioactive compounds,[6 ,7 ,8 ]; [9 ][Level of evidence: 2A] bleomycin,[10 ]; [11 ][Level of evidence: 3iiiDiii] or interferon-alpha.[12 ]; [13 ][Level of evidence: 3iiiB]; [14 ][Level of evidence: 3iiiDi] These strategies have been found to be useful in certain cases, and a low risk of complications has been reported. However, none of these approaches have shown efficacy against solid portions of the tumor.

Although systemic therapy is generally not utilized, a small series has shown that the use of subcutaneous peginterferon alpha-2b to manage cystic recurrences can result in durable responses.[15 ][Level of evidence: 3iiiDiii] In addition, case reports demonstrating dramatic tumor response to BRAF inhibitors in adults with papillary craniopharyngiomas suggest that there may be a role for BRAF inhibitor therapy in the rare setting of a child with a papillary craniopharyngioma.[16 ,17 ]

Treatment Options Under Clinical Evaluation for Recurrent Childhood Craniopharyngioma

Early-phase therapeutic trials may be available for selected patients. These trials may be available via the Children's Oncology Group (COG), the Pediatric Brain Tumor Consortium, or other entities. Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

• APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

  Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.

References:

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. Steinbok P, Hukin J: Intracystic treatments for craniopharyngioma. Neurosurg Focus 28 (4): E13, 2010.
6. 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.
7. Barriger RB, Chang A, Lo SS, et al.: Phosphorus-32 therapy for cystic craniopharyngiomas. Radiother Oncol 98 (2): 207-12, 2011.
8. Maarouf M, El Majdoub F, Fuetsch M, et al.: Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children. Strahlenther Onkol 192 (3): 157-65, 2016.
9. Kickingereder P, Maarouf M, El Majdoub F, et al.: Intracavitary brachytherapy using stereotactically applied phosphorus-32 colloid for treatment of cystic craniopharyngiomas in 53 patients. J Neurooncol 109 (2): 365-74, 2012.
10. Linnert M, Gehl J: Bleomycin treatment of brain tumors: an evaluation. Anticancer Drugs 20 (3): 157-64, 2009.
11. 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.
12. 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.
13. 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.
14. Kilday JP, Caldarelli M, Massimi L, et al.: Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN. Neuro Oncol 19 (10): 1398-1407, 2017.
15. Yeung JT, Pollack IF, Panigrahy A, et al.: Pegylated interferon-α-2b for children with recurrent craniopharyngioma. J Neurosurg Pediatr 10 (6): 498-503, 2012.
16. Aylwin SJ, Bodi I, Beaney R: Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor. Pituitary 19 (5): 544-6, 2016.
17. Roque A, Odia Y: BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. CNS Oncol 6 (2): 95-99, 2017.

Late Effects in Patients Treated for Childhood Craniopharyngioma

Quality-of-life issues are important in this group of patients and are difficult to generalize because of the various treatment modalities. In one series of 261 patients diagnosed with craniopharyngiomas before 2000, hypothalamic involvement was associated with lower overall survival (OS), impaired quality-of-life, and severe obesity.[1 ][Level of evidence: 3iA]

Late effects of treatment for childhood craniopharyngioma include the following:

• Behavioral issues and memory deficits. Although intelligence quotient is usually maintained, behavioral issues and memory deficits attributed to the frontal lobe and hypothalamus commonly occur.[2 ] Patients with hypothalamic involvement showed impairment in memory and executive functioning.[3 ]
• Visual disturbances, including visual field and acuity defects.[4 ][Level of evidence: 3iiiC]
• Endocrine abnormalities. Endocrine abnormalities result in the almost universal need for lifelong endocrine replacement with multiple pituitary hormones.[5 ,6 ,7 ][Level of evidence: 3iiiC] A report indicated that adults, despite being treated with long-term growth hormone replacement after childhood-onset craniopharyngioma involving the hypothalamus, were at increased risk of developing cardiovascular disease.[8 ]
• Decreased height. Growth hormone replacement initiated in childhood results in increases in height without impact on OS and progression-free survival when compared with children who did not receive growth hormone.[9 ][Level of evidence: 3iiiC] Growth hormone administration beginning 1 year after diagnosis may be associated with early improvements in quality of life when measured at 3 years postdiagnosis.[10 ][Level of evidence: 3iC]
• Obesity, which can be life-threatening, and the development of metabolic syndrome, including nonalcoholic fatty liver disease.[11 ,12 ] Children who undergo complete resection or subtotal resection may develop obesity, suggesting that a predilection to obesity may be a component of the disease itself, as opposed to the result of direct hypothalamic injury.[13 ][Level of evidence: 3iC]
• Vasculopathies and stroke. Vasculopathies and subsequent strokes may result from local irradiation.[14 ,15 ] One cross-sectional cohort study observed a trend suggesting that long-term growth hormone replacement may reduce the risk of stroke.[15 ]
• Subsequent neoplasms. Subsequent neoplasms may result from local irradiation.[14 ]

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.

References:

1. Sterkenburg AS, Hoffmann A, Gebhardt U, et al.: Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes. Neuro Oncol 17 (7): 1029-38, 2015.
2. 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.
3. Özyurt J, Thiel CM, Lorenzen A, et al.: Neuropsychological outcome in patients with childhood craniopharyngioma and hypothalamic involvement. J Pediatr 164 (4): 876-881.e4, 2014.
4. Wan MJ, Zapotocky M, Bouffet E, et al.: Long-term visual outcomes of craniopharyngioma in children. J Neurooncol 137 (3): 645-651, 2018.
5. Vinchon M, Weill J, Delestret I, et al.: Craniopharyngioma and hypothalamic obesity in children. Childs Nerv Syst 25 (3): 347-52, 2009.
6. 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.
7. 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.
8. 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.
9. Boekhoff S, Bogusz A, Sterkenburg AS, et al.: Long-term Effects of Growth Hormone Replacement Therapy in Childhood-onset Craniopharyngioma: Results of the German Craniopharyngioma Registry (HIT-Endo). Eur J Endocrinol 179 (5): 331-341, 2018.
10. Heinks K, Boekhoff S, Hoffmann A, et al.: Quality of life and growth after childhood craniopharyngioma: results of the multinational trial KRANIOPHARYNGEOM 2007. Endocrine 59 (2): 364-372, 2018.
11. Elowe-Gruau E, Beltrand J, Brauner R, et al.: Childhood craniopharyngioma: hypothalamus-sparing surgery decreases the risk of obesity. J Clin Endocrinol Metab 98 (6): 2376-82, 2013.
12. Hoffmann A, Bootsveld K, Gebhardt U, et al.: Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma. Eur J Endocrinol 173 (3): 389-97, 2015.
13. Tan TS, Patel L, Gopal-Kothandapani JS, et al.: The neuroendocrine sequelae of paediatric craniopharyngioma: a 40-year meta-data analysis of 185 cases from three UK centres. Eur J Endocrinol 176 (3): 359-369, 2017.
14. Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28 (4): E10, 2010.
15. Lo AC, Howard AF, Nichol A, et al.: A Cross-Sectional Cohort Study of Cerebrovascular Disease and Late Effects After Radiation Therapy for Craniopharyngioma. Pediatr Blood Cancer 63 (5): 786-93, 2016.

Changes to This Summary (04 / 02 / 2020)

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.

Late Effects in Patients Treated for Childhood Craniopharyngioma

Added text to include decreased height as a late effect of treatment for childhood craniopharyngioma. Growth hormone replacement initiated in childhood results in increases in height without impact on overall survival and progression-free survival when compared with children who did not receive growth hormone (cited Boekhoff et al. as reference 9 and level of evidence 3iiiC). Also added that growth hormone administration beginning at 1 year after diagnosis may be associated with early improvements in quality of life when measured at 3 years postdiagnosis (cited Heinks et al. as reference 10 and level of evidence 3iC).

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 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:

• 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 Craniopharyngioma Treatment are:

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

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. 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.

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Craniopharyngioma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/brain/hp/child-cranio-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389330]

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Last Revised: 2020-04-02