Approach

Surgery is almost always performed, regardless of age, in order to:[2][11][14][28][29][30][31]

  • obtain tissue for definitive diagnosis

  • relieve mass effect on surrounding neural structures, or

  • treat hydrocephalus.

Surgery relieves raised intracranial pressure, if present (with or without cerebrospinal fluid [CSF] shunting), and may reverse visual compromise due to compression by tumor (improvement in nearly 40% of patients).

Surgery may include biopsy only, cyst aspiration, CSF shunting, or tumor resection (either partial or complete).

Contrast-enhanced brain imaging (magnetic resonance imaging [MRI]/computed tomography [CT]) helps determine the surgical approach and provides a baseline for evaluating residual disease and response to treatment.

Baseline endocrine and ophthalmologic evaluations with appropriate consults must be performed to aid in monitoring effects of surgery upon endocrine function.[6][8][9][24] However, detailed endocrinologic evaluation should not delay surgery in cases of rapid deterioration of vision.

Following primary surgery, radiation therapy may be required.[32] As endocrinopathies are common (both pre- and postoperatively), hormone replacement therapy is usually necessary, depending upon the specific endocrine deficiencies.[Figure caption and citation for the preceding image starts]: Craniopharyngioma: sagittal postcontrast MRIFrom the collection of Dr Marc C. Chamberlain [Citation ends].com.bmj.content.model.Caption@71b6d7f5[Figure caption and citation for the preceding image starts]: Craniopharyngioma (postoperative): sagittal postcontrast MRIFrom the collection of Dr Marc C. Chamberlain [Citation ends].com.bmj.content.model.Caption@3ecec395

Surgery

The extent of surgical resection and the potential risks of surgery depend on tumor size and location.[10][14][29][33][34]

Gross total resection should be achieved if possible; however, while maximizing resection, long-term side effects should also be minimized, bearing in mind the availability of adjuvant radiation therapy for subtotally resected lesions.

When adherent to nearby structures, such as the basilar artery, hypothalamus, or optic chiasm, surgery may be limited. In these cases, tissue biopsy for diagnosis and decompression of important anatomic structures is often attempted, without complete resection. Caution is required if intracystic therapies are used, as leakage carries toxicity to the optic structures and perforator vessels.

Surgical approach

Depends upon the anatomy (relationship to the sella, optic chiasm, and third ventricle) and size of the tumor as determined preoperatively by cranial MRI.[27] A number of surgical approaches may be used:

  • Transcortical or transcallosal approaches allow a transventricular (from above) approach, which is indicated for tumors that involve the third ventricle and are above the optic chiasm

  • Subfrontal and interhemispheric approaches (from underneath or between the frontal lobes) are indicated for tumors located anterior to the optic chiasm or just behind the lamina terminalis

  • Pterional approach (frontotemporal window, through the opened Sylvian fissure) is used for small tumors in close proximity to the optic chiasm

  • Transsphenoidal approach (either transnasal or sublabial) is utilized if the tumor is partly or totally intrasellar (pituitary fossa)

  • Endoscopic endonasal surgery is increasingly used (especially in children) for suprasellar as well as sellar tumors, due to a decreased risk of hypothalamic injury and higher chance of gross total resection.[35][36] It is typically transsphenoidal, with more expanded approaches used for larger craniopharyngiomas.

For multicompartmental tumors, a combined approach using two or more of these options may be used.[10][34]

Surgical complications include risk of arterial injury (anterior cerebral arteries and the basilar artery), pituitary dysfunction, diabetes insipidus, visual loss, and hypothalamic dysfunction. A higher incidence of hormone deficiency has been reported among pediatric patients undergoing complete resection compared with those managed with conservative surgery followed by adjuvant radiation therapy.[37]

Radiation therapy

Radiation therapy is typically used in the treatment of patients who have had either surgical biopsy only or incompletely resected tumors.[38][39][40][41]

Although complete resection remains the mainstay for select patients, data from retrospective studies suggest that long-term outcomes with subtotal resection followed by adjuvant radiation therapy continue to improve.[16][42] Advanced radiation therapy modalities serve to reduce adverse effects while maintaining high cure rates. No prospective randomized clinical trials have compared complete resection with subtotal resection followed by adjuvant radiation therapy.

Advances in radiation therapy technique have made this option more effective and safe, and definitive radiation therapy may be an option in some patients. Whilst this remains controversial, observational data suggest that outcomes with definitive radiation therapy (radiation therapy alone) are comparable to those of established craniopharyngioma treatment modalities.[43][44] Head-to-head prospective studies are required.

Modality

The radiation therapy technique used (conventional fractionated external beam radiation, conformal external beam radiation; or advanced techniques including intensity-modulated radiation, stereotactic radiosurgery, and proton beam therapy) is dependent upon the size of the residual tumor, its anatomic relationship to surrounding neural structures (in particular, the optic nerve and chiasm), and availability. Conventional fractionated external beam radiation therapy (photon-based) administered daily for 5 to 6 weeks with a median tumor dose of 54 Gy is considered the standard of care for most tumors.[40][41]

Stereotactic radiosurgery involves the delivery of a single large fraction, or several fractions, of radiation dosage, either via a linear accelerator (LINAC) or as multiple cobalt beams (Gamma Knife). Limited studies exist, although experience with other extra-axial intracranial tumors (e.g., meningiomas) suggests this is credible and effective therapy. The application of stereotactic radiosurgery is limited by tumor location in relation to the optic chiasm and nerve, and tumor size and geometry. The technique is best suited for the treatment of small (<2 cm), spherical tumors, or low-volume residual disease.[40][45][46][47][48]

Radiation therapy in many instances will result in hypopituitarism and consequently the need for hormone replacement therapy.[24][47][49] Other possible complications include loss of vision (secondary to a radiation-induced optic neuropathy), rarely radiation injury/necrosis of the anterior temporal lobes, radiation injury to the hypothalamus, and induction of neurocognitive deficits.[50][51]

Endocrine therapy

Endocrine replacement therapy depends upon the specific endocrine deficiency.[4][8][9][11][49][52][53] No improvement is seen in baseline endocrine dysfunction following surgery (with the possible exception of hyperprolactinemia). Indeed, the incidence increases following therapy as a consequence of surgery (lowest risk with transsphenoidal surgery).

Approximate prevalence of specific deficiencies includes growth hormone (75%), hypogonadotropic hypogonadism (75%), adrenocorticotropic hormone deficiency (25%), hypothyroidism (25%), and diabetes insipidus (>70% in children; 50% in adults).[4][8][9][49][52][53]

Management of recurrent/refractory disease

Recurrent or treatment refractory disease is established both clinically and radiographically. If present, repeat surgery may be indicated.[54] Radiation therapy may be used to treat recurrence, and observational data suggest that stereotactic radiosurgery is an effective, minimally invasive option in this context.[45]

Recurrences may manifest as a recalcitrant tumor cyst requiring surgical drainage (aspiration) and sometimes placement of an intratumoral cyst catheter and subgaleal reservoir. This allows repeated fluid aspiration and, if necessary, instillation of intracavitary radioactive colloidal phosphorus/yttrium.[55][56][57] Alternatively, chemotherapy agents may be placed; a variety of drugs have been utilized, including bleomycin, methotrexate, and cytarabine.[58] Caution is required if intracystic therapies are used, as leakage carries toxicity to the optic structures and perforator vessels.

In exceptional instances (e.g., tumor still present despite prior surgery/radiation therapy and no longer operable), patients may be treated with systemic chemotherapy.[54] However, data for chemotherapy in refractory craniopharyngioma are limited, and there is no standard systemic regimen.

Long-term sequelae

In addition to immediate management of the craniopharyngioma and endocrine deficiencies, the detection and management of the potential longer-term sequelae (such as delayed optic atrophy, hypopituitarism, obesity, hyperlipidemia, and diabetes mellitus) is essential, particularly in children.[49][59][60]

Quality of life is significantly impacted. Craniopharyngioma is best thought of as a chronic disease that is multidimensional.[61] Additionally, adults with craniopharyngioma have a substantially elevated risk of cardiovascular disease relative to the general population, added to the reduced health already common to these patients.[62]

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