Approach Considerations
The optimal treatment for craniopharyngiomas remains controversial. Decisions regarding the care of a patient with craniopharyngioma should be made in a multidisciplinary setting that includes neurosurgery, neuro-oncology, radiation oncology, ophthalmology, and endocrinology.
Medical Care
Medical management can be divided into two components: achieving tumor control and management of treatment complications.
Tumor Control
The utility of pharmacologic agents in the management of pediatric craniopharyngioma remains controversial and randomized controlled trials are needed.
The evidence for administration of systemic agents in pediatric craniopharyngioma is limited, however, some data suggests it may be useful in progressive or recurrent craniopharyngioma patients who are not candidates for resection or radiation therapy. Interferon alpha-2a, chosen for its efficacy in cancers with a similar epithelial origin, was administered in a phase II trial in recurrent or progressive pediatric craniopharyngioma. [16] Although an objective radiographic response was seen in only 3 of 12 patients who were able to be evaluated, the time until radiation therapy was required was delayed in those patients. However, 60% experienced moderately severe toxicities (eg, hepatic, neurologic, cutaneous), but these were all reversible with discontinuation or dose reduction. The same group more recently administered pegylated interferon-alpha-2b in a small series of 5 patients demonstrating the feasibility of this approach, however larger, more robust investigations are clearly needed. [17]
Intracystic or intratumoral administration has demonstrated some benefit. [18] Bleomycin, an antibiotic that induces DNA strand breaks and acts as an antineoplastic agent, has been successfully administered by an Ommaya-type catheter into the cyst with subsequent regression of cystic cavities in many patients. [19] However, in a large meta-analysis, no definitive conclusions could be made about the effectiveness of intratumoral Bleomycin in the treatment of pediatric craniopharyngioma. [20] Intratumoral interferon alpha has also been administered with similar results. [21] Complications from intratumoral administration, including those from inappropriate intratumoral catheter placement and leak of the pharmacologic agent outside of the cyst, have been described. One report described the use of carmustine (BCNU)–impregnated wafers (Gliadel: Guilford Pharmaceuticals, Inc; Baltimore, Maryland) in a patient with recurrent craniopharyngioma. [22]
Management of Treatment Complications
Long-term hormone replacement is the primary medical treatment associated with childhood craniopharyngiomas and includes the administration of intranasal vasopressin (desmopressin acetate [DDAVP]), corticosteroids, thyroid hormones, growth hormones, and sex hormones.
Perioperative care includes attention to frequently associated multiple hormone deficiencies.
Frequently, perioperative corticosteroid administration (stress doses) is required.
Surgical Care
Surgical management when feasible is the treatment of choice in pediatric craniopharyngioma. Surgical options include radical surgery or conservative surgery with postoperative radiotherapy.
Radical Surgery
Radical surgery with gross total resection was historically the preferred surgical approach. However, due to the significant morbidity and lack of evidence to suggest a lower recurrence rate, radical surgery is now only recommended when the tumor is favorably localized and does not intimately involve the hypothalamic or optic regions.
Both transcranial and transsphenoidal approaches have been described. No surgical technique has been identified as superior in the pediatric population. Transsphenoidal approaches were more commonly associated with nonendocrine complications in 7-12 year olds in one analysis. [23] Another study comparing transcranial and transsphenoidal approaches in 314 pediatric craniopharyngioma patients found that transsphenoidal surgery was associated with a higher incidence of cerebrospinal fluid leak, but shorter length of stay. [24]
True complete resection of these tumors is challenging, even for experienced neurosurgeons who operate on several children with craniopharyngiomas each year. [25, 26] Frequently, these tumors densely adhere to the optic chiasm, pituitary stalk, and internal carotid artery and often invade the region of the third ventricle; therefore, not surprisingly, radical surgery frequently causes significant morbidity including panhypopituitarism, neurologic deficits (cranial nerve palsies, hemiparesis, aphasia), and visual field deficits or blindness. Recently, the perioperative mortality rate has been reported as low as 3%; however, perioperative morbidity remains an issue, ranging from 8-14%. [27, 28]
In addition, gross total resection does not prevent recurrence. Following radical resection, local relapses have been described in 10-50% of patients. One series reported that complete excision was achieved in only 63% of patients treated with radical surgery, and one half of the tumors believed to be completely excised subsequently recurred. [29]
Conservative Surgery Alone
Morbidity and mortality associated with radical surgery led neurosurgeons to attempt lesser resections; unfortunately, limited surgery alone resulted in worse local control with rates of local progression as high as 75-90%, and even greater morbidity due to repeated resections after recurrences.
Conservative Surgery and Postoperative Radiotherapy
Because both radical and conservative surgical approaches have limitations, postoperative external-beam radiotherapy has been added to limited surgery in an effort to improve local control. The literature seems to support this approach, with a reported long-term control of approximately 80-95% at 5-20 years and a low risk of long-term morbidity. [30]
Some advocate postoperative radiation even after gross total resections, particularly if residual calcifications are noted on postoperative imaging studies since this portends a poor prognosis.
In general, radiotherapy is administered using field arrangements similar to those used for pituitary adenomas (>2 fields, narrow margin around gross tumor volume). A dose response for craniopharyngiomas has been reported; thus, the total tumor dose is generally 5000-5500 cGy in 25-30 fractions.
Radiation therapy may also be of benefit as a salvage therapy in patients with failed surgical resection or progressive or recurrent craniopharyngioma. [31] Radiosurgery has also been used in pediatric craniopharyngioma both as an adjunct in postoperative residual disease and as salvage for recurrent or progressive disease. [32] Intracavitary irradiation (brachytherapy) has also been attempted in patients with recurrent craniopharyngioma. The local radiation doses ranged from 200-267 Gy, and complete or partial cyst resolution was seen in 71-88% of cases. However, the appropriate isotope to use and whether intracavitary brachytherapy has any impact on overall outcome remains unclear. [13]
Children younger than 3 years may not be candidates for such radiotherapy because they can develop unusually severe long-term adverse effects.
Risk of parenchymal brain injury or second malignancy caused by radiation therapy is estimated to be less than 1-2%.
Consultations
Obtain consultations from the following:
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Pediatric neurosurgeon
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Radiation oncologist
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Pediatric endocrinologist
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Pediatric hematologist/oncologist
Diet
Attention to special neurologic and endocrinologic concerns is prudent. Weight gain can be dramatic and a significant long-term problem. Nutritional consultation can be helpful.
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This MRI sequence was obtained following the intravenous administration of gadolinium contrast. Observe the relatively homogeneous and cystic mass arising from the sella turcica and extending superiorly and posteriorly with compression of normal regional structures. Note that the lesion is sharply demarcated and smoothly contoured. This fluid-filled mass is consistent with a typical craniopharyngioma.
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This axial CT scan image demonstrates a cystic lesion in the typical location of a craniopharyngioma. Although most of the lesion is fluid filled, a rim of enhancing soft tissue is observed following the administration of intravenous contrast.
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Non-contrast Head CT with peripheral calcifications around a bi-lobed craniopharyngioma.
