Pediatric Craniopharyngioma Treatment & Management

Endocrine 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.

Tumor control

The use of chemotherapy in the treatment of craniopharyngioma is still under investigation. Chemotherapy can be considered for progressive disease that is unresectable and for which radiation therapy has already been used or is contraindicated. The use of systemic cytotoxic chemotherapy has not been shown to be of benefit in this disease.

Systemic use of interferon alpha has been attempted in a clinical trial. The rationale for use of this agent was based on the similar epithelial origin of craniopharyngiomas and squamous cell carcinomas, in which interferon alpha has shown some efficacy. In a phase II trial, Jakacki et al (2000) used interferon alpha at a dose of 8 million U/m² administered subcutaneously every day for a 16-week induction period and then the same dose 3 times/wk for 32 additional weeks in 15 patients with recurrent or progressive craniopharyngioma.^[9] 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.

Another, more tested chemotherapeutic modality is intracavitary/intracystic bleomycin, an antibiotic that induces DNA strand breaks and acts as an antineoplastic agent. First reported in 1985, this therapy involves placement of an Ommaya-type catheter into the cyst cavity.^[10] After confirming no leakage from the cavity after dye instillation, administration of bleomycin can commence (eg, 5 mg every other day until a total cumulative dose of 30 mg). Takahashi et al (2005), reported regression of the cystic cavities in 10 of 11 patients, with minimal adverse effects.^[10] Intratumoral therapy has also been performed using interferon alfa, with similar results. Despite the relative safety of these approaches, long-term vascular abnormalities such as moyamoya and aneurysms have been identified in pediatric patients with craniopharyngioma, especially in those who received both radiation therapy and intracystic therapy.^[11]

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.^[2]

One report described the use of carmustine (BCNU)–impregnated wafers (Gliadel: Guilford Pharmaceuticals, Inc; Baltimore, Maryland) in a patient with recurrent craniopharyngioma.^[12]

Given the morbidity of repeated surgeries for recurrent craniopharyngiomas after radiation therapy has failed, further research into other therapies for these locally invasive tumors is desperately needed.

Treatment options include radical surgery, conservative surgery with postoperative radiotherapy, and palliative surgery. Although reports suggest management of craniopharyngiomas with limited surgery or conventional external-beam radiotherapy alone, these methods are not widely used. Newer management options such as stereotactic radiosurgery or radiotherapy are promising but remain largely experimental.

Radical surgery

Historically, initial management of craniopharyngiomas has been surgical. Unfortunately, true complete resection of these tumors is challenging, even for experienced neurosurgeons who operate on several children with craniopharyngiomas each year.

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.

The postoperative mortality rate currently ranges from 0-20%, with the most recent series reporting rates of approximately 5-10%.

Perhaps most disheartening, gross total resection does not prevent recurrence. Following radical resection, local relapses are described in 0-60% 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.^[13]

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 (75-90% local progression is reported) and even greater morbidity because of the need for repeated resections for recurrences.

Conservative surgery with postoperative radiotherapy

Because limited surgery does not prevent recurrences and radical surgery carries unacceptable morbidity and mortality, 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.

Risk of parenchymal brain injury or second malignancy caused by radiation therapy is estimated to be less than 1-2%.

Some advocate postoperative radiation even after gross total resections, particularly if residual calcifications are noted on postoperative imaging studies (this carries 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.

Children younger than 3 years may not be candidates for such radiotherapy because they can develop unusually severe long-term adverse effects.

Palliative surgery

Conservative management with limited surgery and external-beam radiotherapy requires close monitoring of the neurologic status during treatment.

During or soon after radiotherapy, craniopharyngiomas can undergo cystic degeneration, which can lead to obstruction of cerebrospinal fluid outflow or compression of the optic apparatus, with potentially devastating consequences.

Fortunately, early recognition and appropriate surgical treatment followed by conventional full-dose radiotherapy are associated with good long-term outcome.

Obtain consultations from the following:

• Pediatric neurosurgeon
• Radiation oncologist
• Pediatric endocrinologist
• Pediatric hematologist/oncologist

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.