Craniopharyngiomas are histologically benign but clinically aggressive tumors that primarily involve the sellar/suprasellar region. The clinical management can be quite complex owing to the adjacent anatomical structures, so a greater understanding of the anatomy and clinical course is critical to optimizing the treatment of these lesions. Additional insights have also resulted from genetic studies. Clinical management involves a multidisciplinary approach that includes neurosurgery, endocrinology, ophthalmology, and possibly oncology. Surgical management remains the mainstay of treatment. Newer, less invasive therapies continue to be developed that can aid in the more comprehensive management of these tumors.
Craniopharyngiomas are particularly difficult intracranial neoplasms to remove and are associated with high recurrence rates. These tumors are theorized to originate from degeneration of the epithelial remnants of Rathke’s pouch and the craniopharyngeal duct. As a result, craniopharyngiomas can involve the length of the craniopharyngeal duct from the sella, parasellar, and suprasellar areas. These locations along the cranial base, coupled with the propensity of the tumor to adhere to critical structures such as the hypothalamus, optic chiasm, and neurovasculature, necessitates a well-planned and well-executed surgical resection to minimize complications. Overall gross total resection rates have benefited greatly from the introduction of minimally invasive skull base techniques that use an endoscopic endonasal approach to enrich the viewing angles, facilitating more maximal resection while minimizing complications. Despite this operative advancement, the overall treatment of craniopharyngiomas still requires a multidisciplinary team that includes neurosurgery, otolaryngology, endocrinology, neuro-oncology, and radiation oncology.
40.2 Incidence and Epidemiology
Craniopharyngiomas are benign World Health Organization (WHO) grade I intracranial tumors that originate from the remnants of Rathke’s pouch. Although craniopharyngiomas constitute less than 1% of all primary central nervous system tumors, they are the most common nonglial tumor in children.1 The incidence of craniopharyngiomas is estimated at 0.13 per 100,000 person-years, with a bimodal age distribution between 5 to 14 years and 65 to 74 years and a higher prevalence in childhood.2 There is no gender or race predilection.
Two pathological types of craniopharyngiomas have been described. The adamantinomatous subtype is more common in children, accounting for 5 to 10% of pediatric intracranial malignancies, whereas the papillary form occurs almost exclusively in adults.
Craniopharyngiomas are most commonly found in the suprasellar region but can extend along the entire length of the craniopharyngeal duct into the sella and parasellar regions. Pan et al described five growth patterns of craniopharyngiomas based on their relationship to the arachnoid sleeve that surrounds the pituitary stalk.3 Three basic growth patterns have been observed—infradiaphragmatic (sellar), subarachnoid extraventricular, and subpial intraventricular (third ventricle)—based on their origin from infrasellar, infradiaphragmatic, transinfundibular, suprasellar, subarachnoid, or subpial ventricular locations.
Craniopharyngiomas are epithelial neoplasms believed to form from the squamous epithelial rests or the remnants of the primitive craniopharyngeal duct, most commonly found at the level of the infundibulum. Traditionally, two histological types of craniopharyngiomas are described: adamantinomatous and papillary. Adamantinomatous craniopharyngiomas may develop from remnants of Rathke’s pouch. These tumors are grossly characterized as a spongy mass with cystic components that contain dark fluid with lipid and polarized cholesterol crystals. Histologically, adamantinomatous craniopharyngiomas are defined by the presence of nests and trabeculae of epithelium within a loose fibrous stroma. They also contain areas of wet keratin, calcifications, and cholesterol clefts. Papillary craniopharyngiomas are characterized as a solid tumor consisting of well-differentiated, monomorphic squamous epithelial cells that form distinct papillae within a fibrovascular core. This subtype can easily be differentiated from its counterpart by the lack of cystic spaces filled with “motor oil” fluid, wet keratin, calcifications, or xanthogranulomatous change.
Genetic studies for craniopharyngiomas have shown promise in developing targeted therapies. Comparative genetic studies have indicated an overexpression of CTNNB1 and BRAF V600E mutations in more than 90% of adamantinomatous and papillary craniopharyngiomas, respectively.4 , 5 , 6 BRAF V600E mutations are known to cause other cancers via the constitutive activation of MAPK signaling pathway, which promotes cell proliferation. A phase II clinical trial is under way to determine the utility of BRAF inhibitors in the treatment of papillary craniopharyngiomas. CTNNB1 mutations are also associated with other cancers, because accumulation of nuclear B-catenin leads to activation of the Wnt signaling pathway and cellular proliferation.7 Overactivation of the Wnt/B-catenin pathway has been demonstrated to induce craniopharyngioma formation in the mouse model.7 Further characterization of the Wnt/B-catenin pathway and its role in the progression of adamantinomatous craniopharyngiomas may prove critical to the development of additional targeted therapies.8
Immunohistochemistry has traditionally been of limited utility owing to the poor understanding of the genetic alterations associated with craniopharyngiomas. In general, craniopharyngiomas stain positive for cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. Adamantinomatous craniopharyngiomas are also positive for beta-catenin. However, in light of recent findings of the high incidence of genetic mutations for CTNNB1 and BRAF V600E, immunohistochemistry will most likely play an increasingly significant role in diagnosis and treatment. In 2015, BRAF mutation status was used to successfully differentiate papillary craniopharyngioma from Rathke’s cleft cyst.9 The presence of B-catenin can also be used to differentiate between the adamantinomatous and papillary subtypes.
Recent genomic and transcriptomic studies have yielded additional insights into the molecular drivers.10 In addition to the Wnt/B-catenin pathway, adamantinomatous craniopharyngiomas were found to also have dysregulation of the epidermal growth factor receptor (EGFR) and sonic hedgehog (SHH) signaling pathways. These studies point to a multifactorial involvement driving tumor progression and necessitate further studies to develop effective targeted therapies.
The decision to intervene is largely dependent on a combination of clinical and radiographic factors. Despite advancements in the nonoperative treatment of craniopharyngiomas, surgical resection remains the mainstay of intervention, with radiation and chemotherapy serving adjuvant roles.11 The extent of surgical resection and overall prognosis are largely a function of the tumor growth pattern as it relates to the adjoining critical neurovascular structures. Several studies have offered topographical classification schemes based on the tumor location and its association to surrounding structures, such as the diaphragma sella, optic chiasm, pituitary stalk, and third ventricle. These schemes can aid in operative planning, including surgical approach and expected morbidity.
Surgical intervention in the case of a newly diagnosed craniopharyngioma is dependent on symptoms, tumor size, and evidence of growth with serial imaging. Although asymptomatic patients who have large suprasellar lesions may be observed, many surgeons advocate for early surgical resection to optimize complete removal at the outset, the better to prevent a limited removal in the future.12 Regardless, a multisystem neurologic, ophthalmologic, and endocrinologic comprehensive assessment is necessary to determine the sequelae of this tumor.
40.5 Preoperative Assessment
40.5.1 Clinical Assessment
The initial work-up includes a comprehensive neurologic, endocrinologic, and visual assessment. Additionally, consultation with otolaryngology should be pursued for preoperative planning if an endoscopic endonasal approach is considered. In general, the clinical sequelae of craniopharyngiomas can be divided into five categories:
Endocrine: Hypopituitarism occurs in up to 82% of patients who have craniopharyngiomas, secondary to compression of the pituitary gland, infundibulum, or hypothalamus.12 , 13 , 14 Growth hormone deficiency is the most common hormonal deficit, the clinical manifestations of which can vary depending on age.15 In the prepubescent population, short stature and delayed sexual development are common. Hypocortisolemia occurs in up to 62% of patients and can be potentially fatal.12 , 13 , 16 Additional manifestations may include infertility, amenorrhea, and galactorrhea as a result of hyperprolactinemia due to stalk effect, occurring in up to 55% of patients. Diabetes insipidus is much less common preoperatively. A complete pituitary serologic panel should be obtained, including luteinizing hormone, follicle-stimulating hormone, estrogen, testosterone, thyroid-stimulating hormone, free thyroxine, adrenocorticotrophic hormone, cortisol, growth hormone, insulin growth factor-1, and prolactin levels. About 82% of patients will have evidence of endocrine deficiency in one or more axes.15 , 17
Ophthalmologic: Deficits in visual acuity and visual fields, most often bitemporal hemianopia, are common manifestations resultant from direct compression of the optic nerves and chiasm by craniopharyngiomas, occurring in up to 84% of patients.18 , 19 , 20 Objective findings of optic nerve atrophy and papilledema may result either from direct compression or, secondarily, from hydrocephalus. Comprehensive testing by an ophthalmologist or optometrist is necessary preoperatively. Visual deficits can often stabilize or recover from surgical decompression, with the likelihood of visual recovery dependent on the duration and severity of the visual deficit.14
Hypothalamic: Manifestations of hypothalamic dysfunction are mainly in the form of hyperphagia and obesity but can also include daytime sleepiness, behavioral changes, and imbalances in homeostasis (blood pressure, temperature, heart rate, thirst). Preoperative weight gain is quite common.21 , 22 , 23 There is no current effective treatment for hypothalamic obesity, but careful nutrition and exercise may help. Hyperphagia and obesity may also occur postoperatively as a result of hypothalamic injury.24
Hydrocephalus: Obstructive hydrocephalus occurs in up to 30% of patients and commonly indicates tumor extension into the third ventricle with obstruction of the foramen of Monro.25 A retrochiasmatic origin is often implicated.1 Symptoms may include nausea/vomiting and papilledema, but headaches are by far the most common complaint.12 The presence of symptomatic hydrocephalus may necessitate preoperative spinal fluid diversion in the form of an external ventricular drain or ventriculoperitoneal shunt.
Frontotemporal effects: Large craniopharyngiomas can result in mass effect and edema in the frontal and temporal lobes, which can cause behavioral changes and altered mentation.18 , 19 In extreme cases, apathy, urinary incontinence, and hypersomnia can also be present.
40.5.2 Radiographic Assessment
Preoperative CT and MRI studies provide important insights for preoperative planning. The CT is optimal for bony anatomy and can yield critical insights with which to guide the surgical approach when endonasal techniques are used, such as septal deviations, concha bullosa, sphenoethmoidal air cells, and the location of sphenoid septations as they relate to the carotid artery. Craniopharyngiomas are also known to contain calcifications, which also can be best appreciated on CT scan. MRI is critical for preoperative planning and is excellent for characterization of the degree of tumor extension, including by identifying encasement of surrounding neurovascular structures, such as the optic nerves/chiasm, internal carotid arteries, anterior cerebral arteries, pituitary gland, and infundibulum. It may also be useful for predicting the degree of involvement of the hypothalamus as evidenced by fluid-attenuated inversion recovery (FLAIR) hyperintensity. These considerations can often guide the surgical approach, because an open transcranial approach is traditionally favored for tumors with a large degree of lateral extension, a postfixed chiasm, or a small intercarotid distance. Aside from these exceptions, the extended endoscopic approach is a robust procedure that has provided excellent outcomes in our experience.26 , 27
A thorough understanding of skull base anatomy is critical for operative success. Several classification schemes have been described to guide the choice of operative approach. The earliest classification scheme included the Hoffman classification, which described the location of the craniopharyngioma relative to the optic chiasm.28 Yasargil et al further differentiated the tumor location relative to the diaphragma sella, whereas Samii et al described a classification scheme based on the vertical projection of the tumor.29 , 30 In the era of endoscopic approaches, Kassam et al developed a classification scheme centered on the location of the infundibulum.31
More recently, a comprehensive anatomical classification system was developed to guide aggressive surgical resection.32 This scheme classified craniopharyngiomas based on tumor origin into four possible groups: intrasellar, prechiasmatic, retrochiasmatic, and intraventricular types (Fig. 40.1).
Consistent with the previous classification scheme by Kassam et al, lesions that have significant extension into the third ventricle were considered suboptimal for an endoscopic approach and alternative transcranial approaches such as the interhemispheric or translamina terminalis approach were recommended.31 Ideal locations for endonasal craniopharyngioma resection include the intrasellar and prechiasmatic types without lateral extension. The orbitozygomatic and transpetrosal approaches were advocated for prechiasmatic tumors with lateral extension and the retrochiasmatic craniopharyngiomas, respectively. Although technically more difficult, in our experience and others, retrochiasmatic lesions can be approached endoscopically with great success once a learning curve is overcome.27 , 33 , 34 , 35 , 36 , s. Literatur
Preoperative characterization of tumor adherence and attachment to surrounding structures, specifically the hypothalamus, are gaining greater attention.38 The determination of hypothalamic involvement preoperatively is critical both in determining the limits of resection and counseling of the patient regarding postoperative risk for hypothalamic dysfunction (hyperphagia, obesity, behavioral dysfunction), which can be a debilitating consequence and result in significant reduction in quality of life.39 Van Gompel et al identified T2 signal change and irregular contrast enhancement as predictors of hypothalamic involvement.40 Puget et al developed a grading scheme centered on hypothalamic preservation at the cost of gross total resection for tumors that clearly involved the hypothalamus. They were able to achieve good functional outcomes and tumor control using adjuvant radiotherapy.39 These scoring systems were recently externally validated in a separate cohort and point to the importance of examining the preoperative MRI for prognostication.41
40.6 Postoperative Considerations
It is of critical importance to discuss with the patient the possible postoperative complications that can be life-changing. The patient should be counseled on the potential for hypothalamic dysfunction with symptoms of obesity and hyperphagia and endocrine dysfunction, including diabetes insipidus and panhypopituitarism. The outcome of these preoperative conversations can guide intraoperative management decisions.
The current treatment paradigm for craniopharyngiomas is multidisciplinary, with surgery remaining the cornerstone of treatment. Surgical intervention can be extremely challenging due to the infiltration and adherence of the tumor to surrounding critical structures such as the hypothalamus, vasculature, and cranial nerves.38 The ideal treatment goal is gross total surgical resection resulting in disease cure with functional preservation, but the involvement of neurovascular structures often necessitates subtotal resection and subsequent adjuvant therapies to maintain function and quality of life. The following six factors should be taken into consideration when intervention is necessary.
40.7.1 Management of Hydrocephalus
Hydrocephalus is present in up to 30% of patients at diagnosis. The initial triage step involves differentiation of acute versus chronic hydrocephalus and determination of the severity of symptoms. In the setting of acute hydrocephalus with severe symptoms, immediate cerebral spinal fluid diversion is necessary using either a perioperative external ventricular drain or a staged surgical procedure with initial placement of an ventriculoperitoneal shunt. In the setting of chronic hydrocephalus or absence of acute symptoms, surgical resection of the tumor alone will typically result in the resolution of hydrocephalus.
40.7.2 Perioperative Endocrine Management
Preoperative hypocortisolemia is uncommon but if present will necessitate preoperative stress dosing with hydrocortisone or dexamethasone, which can also aid in control of vasogenic edema and aseptic meningitis. Perioperative fluid balance should be maintained, as a small proportion of patients experience diabetes insipidus preoperatively. In patients who have volume depletion, mannitol or other diuretic agents should not be administered. Patients should otherwise be maintained on their outpatient endocrine replacement medications as scheduled.
40.7.3 Management of Tumor-Related Cysts
Not infrequently, craniopharyngiomas may exist primarily in a cystic form or be composed of both solid and cystic elements. Significant tumor extension superiorly into the lateral ventricle or laterally toward the sylvian fissure may necessitate a transcranial approach for adequate access. This is especially true for the cystic component, with lateral extension limiting complete removal endoscopically. Adjuvant procedures to address a residual or recurrent cyst may include stereotactic needle aspiration or Ommaya reservoir placement. The placement of the reservoir can facilitate future aspirations as needed, as well as possible intratumoral administration of colloidal radioisotopes or chemotherapeutic agents.42
40.7.4 Presence of Calcifications
Calcifications are observed in 45 to 57% of craniopharyngiomas.15 The location of calcifications relative to surrounding neurovascular structures is an important consideration for preventing iatrogenic injury when resecting the calcifications intraoperatively. This may also limit the ability to achieve a gross total resection.
40.7.5 Relationship to Surrounding Structures
The degree of infiltration into the third ventricle can dictate the surgical approach. A tumor that is entirely isolated within the body of the third ventricle or the optic recess with an intact floor of the third ventricle is suboptimal for the endoscopic endonasal route, so a craniotomy route would be recommended.31
An appreciation of the degree of tumor invasion of the hypothalamus is critical to minimize postoperative morbidity. Muller et al differentiated the anterior and posterior hypothalamus using the mammillary bodies as the landmark.43 The presence of a clear cerebrospinal fluid (CSF) cleft signifies absence of hypothalamic invasion but is an infrequent finding. Other determinants of hypothalamic invasion, including T2 or FLAIR hyperintensity, may be associated with a difficult surgical dissection plane along the walls of the hypothalamus.40 However, intraoperative assessment remains the gold standard, necessitating careful and limited dissection in this area to minimize irreversible complications.
The optic nerves and chiasm can be displaced and compressed by the tumor. It is important to appreciate the location of these structures on preoperative imaging and as early as possible during the operation in order to minimize iatrogenic injury. Preservation of the vasculature supplying the optic chiasm and nerves is critical during tumor dissection. Several classification schemes already mentioned underscore the importance of considering the location of the tumor relative to the chiasm as prechiasmatic or retrochiasmatic.28 , 32
The location of the infundibulum is a very important consideration in guiding the surgical approach and counseling the patient regarding potential postoperative development of diabetes insipidus and endocrinopathy. Retroinfundibular lesions are suboptimal for an endoscopic approach if preservation of the infundibulum is of primary importance, but stalk preservation may be accomplished through greater bony removal of the sellar floor.31 , 33 , 34 Oftentimes, craniopharyngiomas invade or originate from the pituitary stalk. In these settings, radical resection requires sacrifice of the infundibulum and often results in permanent diabetes insipidus and hypopituitarism.
It is important to appreciate the location of the internal carotid arteries and their branches, including the anterior cerebral arteries and posterior communicating arteries, preoperatively. Dense adherence of craniopharyngiomas to the large arteries of the skull base is a common reason for subtotal resection. However, with careful dissection, an arachnoid plane can often be identified and developed, facilitating separation of these vessels from the capsule of the tumor.
40.7.6 Degree of Lateral Extension
Significant extension of the tumor lateral to the internal carotid artery or optic nerve can prohibit effective resection via an endonasal approach, and tumors exhibiting these significant lateral extensions are more suitable for a transcranial approach.
Surgical success is contingent on detailed preoperative planning and recognition of possible anatomical limitations intraoperatively. If necessary to avoid injury to critical neurovascular structures, subtotal resection should be performed with a plan for adjuvant therapy. The extent of surgical resection necessary for long-term control is highly debatable. Some surgeons advocate for aggressive surgical resection to minimize recurrence, cyst formation, and improve overall survival, whereas others report that subtotal removal and adjuvant radiation provides similar long-term tumor control to that possible through gross total resection, with less surgical risk.44 , 45
40.8 Surgical Approaches
The options for the surgical approach for resection of craniopharyngiomas can be broadly divided into transcranial and endoscopic endonasal techniques (Fig. 40.2). The specific surgical approach is governed by the location of the pathology in combination with the surgeon’s experience.
40.8.1 Transcranial Approaches
This approach is used primarily for suprasellar lesions. The addition of a transbasal translamina terminalis extension provides greater exposure to the anterior third ventricle.46 , 47 A recent retrospective study highlighted the strength of the subfrontal approach in providing exposure along the vertical axis from the sella to the third ventricle, with gross total resection achieved in 91% of cases.48
This is the workhorse approach and as such is familiar to nearly all neurosurgeons. This approach provides access to the sellar/parasellar region through the opticocarotid and oculomotor–carotid triangles. The assumption is that the tumor will have increased the spaces within these triangles, which are otherwise narrow. The advantages with this approach are its ability to provide direct access to the lateral portion of the tumor and to facilitate direct optic nerve decompression via an anterior clinoidectomy and unroofing of the optic canal. In addition, injuries to major vascular structures are better managed by this approach. A key extension is an orbital osteotomy to improve basal visualization. Additional variants are the supraorbital and minipterional approaches, which have not been extensively studied.49
This approach is used for craniopharyngiomas that exhibit significant extension within the third ventricle or through the foramen of Monro to the lateral ventricles.
This lateral approach is typically used for retrochiasmatic tumors that have extension into the third ventricle and interpeduncular fossa. It allows for excellent visualization of the hypothalamus and pituitary stalk. The major disadvantages are retraction on the temporal lobe and the need to traverse neurovascular structures and cranial nerves during the dissection.
Intracavitary Therapy/Cyst Aspiration
This approach is typically considered in the setting of large predominantly cystic tumors with the goals of decreasing mass effect and improving endocrinopathy. As expected, simple cyst drainage is associated with higher rates of recurrence than other surgical interventions are.42 As an important adjunct, or alternative, to surgical resection in select cystic cases, the catheter can be placed in the cyst and used for injection of radioisotopes or chemotherapeutic agents.
40.8.2 Endoscopic Approach
Endoscopic Endonasal Transtuberculum/Transplanum Approach
This approach is largely indicated for midline lesions between the carotid arteries and medial to the optic nerves with limited lateral extension. Intrasellar, preinfundibular, and prechiasmatic lesions are optimal but not required. Relative contraindications include tumors located exclusively in the third ventricle, but even these lesions can be approached with sufficient experience.22
The expanded endoscopic endonasal approach carries many advantages over traditional transcranial approaches. The approach accesses natural corridors to provide direct visualization to the tumor without the need for brain retraction. There is, however, a steep learning curve that requires a unique skill set. Although reliable repair of skull base defects had traditionally plagued the success of endoscopic approaches, contemporary techniques using multilayered closures have dramatically reduced the incidence of CSF leaks to less than 5% at experienced centers.
40.9 Adjuvant Therapies
Various options are available for the treatment of residual or recurrent craniopharyngiomas.
Stereotactic radiation is a commonly employed therapy for craniopharyngiomas and may be delivered as radiotherapy or radiosurgery.
Radiotherapy is delivered through various methodologies, such as photon stereotactic radiotherapy and proton beam therapy. There is currently no class I data to suggest superiority of any modality for the treatment of craniopharyngiomas, but each method has its theoretical advantage. The advantage of stereotactic radiotherapy is that it is delivered in multiple fractions, which reduces the impact of the radiation on radiosensitive normal structures such as the optic apparatus. This is an especially important feature in the context of craniopharyngiomas due to the proximity to the chiasm. Intensity-modulated radiation therapy provides the capability to conform treatment plans to irregular shapes or volumes by modulating the intensity of the individual beams, thereby limiting radiation exposure to critical structures and providing improved dose homogeneity. Proton beam therapy can deliver large doses of radiation with limited exit dose to surrounding tissues, which is advantageous when near critical structures. Some complications of radiotherapy include endocrinopathy, vasculitis, neurobehavioral changes, and visual deficits.
Stereotactic radiosurgery is defined by the delivery of a single high-dose fraction of conformal radiation to the target. Accordingly, its application is limited by the target’s proximity to critical structures, with the radiation delivery dose to the optic chiasm ideally limited to less than 8 to 10 Gy. Leskell Gamma Knife (Elekta) and linear accelerators are the most common devices for this type of photon delivery. This technique is optimal for smaller targets with sufficient distance between the tumor and critical radiation-sensitive structures. A major disadvantage with radiosurgery is the observation that treatment can result in an increase in the size of the cystic component, which can require subsequent interventions for cyst decompression.50 , 51 , 52 As with all radiation therapies, radiosurgery may result in delayed development of endocrinopathy, vasculitis, neurobehavioral changes, and visual deficits.
40.9.2 Intracavitary Radiation
Stereotactic delivery of a colloidal radioisotope into the cystic component of craniopharyngiomas has been extensively reported without a general consensus on the optimal therapeutic agent.53 , 54 , 55 , 56 , 57 The two most commonly used radioisotopes are yttrium-90 and phosphorus-32, which are beta-emitting isotopes. These two radioisotopes have similarly limited penetrance to surrounding tissues.
Systemic chemotherapy has not been studied extensively and is considered a last-line therapy for aggressive craniopharyngiomas refractory to alternative therapies. Various regimens of chemotherapy have been reported but have not been extensively studied.58 , 59 Systemic administration of interferon-α for the treatment of craniopharyngiomas has also been reported.
Intracavitary chemotherapy is an accepted alternative for the treatment of the cystic component of craniopharyngiomas. The two most common agents are bleomycin and interferon-α.
40.9.4 Targeted Therapies
Recent studies into the genetic underpinnings of craniopharyngiomas have yielded promising avenues for targeted treatments. The papillary type of craniopharyngioma is strongly associated with BRAF V600E mutations. Targeted therapies for this specific mutation have previously been successful for other types of cancers.6 A recent case report identified a successful response using BRAF and MEK inhibitors for a patient who had recurrent papillary-type craniopharyngioma.60 This study points to a promising treatment modality for papillary-type craniopharyngiomas with BRAF inhibitors such as vemurafenib and dabrafenib. As of 2019, a phase II clinical trial is in process to evaluate the benefit of BRAF inhibitors for papillary craniopharyngiomas. Targeted therapies for the Wnt pathway are currently in development. A recent in vitro study did find an impact of inhibition of the EGFR pathway in sensitizing adamantinomatous craniopharyngiomas to radiation.61
40.10 Outcomes and Prognosis
Surgical intervention remains the cornerstone of treatment for craniopharyngiomas and offers the best opportunity for a cure. Successful surgical resection is largely dependent on tumor consistency, presence of arachnoid dissection planes, and degree of adherence to surrounding critical neurovascular structures, including hypothalamus. A multitude of surgical approaches are available to achieve the goal of maximal resection, yet class I and II data assessing comparative outcomes using these approaches are lacking. However, a large body of comparative literature does exist in the form of retrospective reviews and meta-analyses that has yielded some insight as it relates to outcomes. A major confounder of these studies is the divergence in the goals of surgery. Some have advocated for a radical surgical resection, even at the risk of increasing morbidity, to improve progression-free survival, whereas others have promoted a more conservative resection complemented by adjuvant therapies to preserve quality of life.32 , 62 , 63 , s. Literatur
40.10.1 Comparison of Surgical Approaches
Patient selection is a critical step to achieving successful surgical resection. Certain craniopharyngiomas are suboptimal for an endoscopic endonasal approach—namely, those with lateral extension beyond the internal carotid artery, complete vascular encasement, and isolated location in the third ventricle. These lesions are often best approached via a transcranial route. Given these exceptions, a multitude of studies have compared the traditional transcranial to endoscopic approaches. The advent of the endoscopic endonasal approaches has greatly facilitated the resection of properly selected craniopharyngiomas with decreased morbidity and at least equivalent tumor-control rates compared with transcranial approaches, but the learning curve to successfully employing endoscopic approaches can be steep.27 , 65 The primary advantage of the endoscopic approach is the direct line of sight provided along the long axis of the tumor without the need for brain retraction. The inferior optic chiasm and retrochiasmatic regions are also well visualized, which minimizes potential blind spots and allows for early decompression of these structures. The greatest disadvantage of the endoscopic approaches has been postoperative CSF leakage, although CSF leak rates have dramatically improved with the advent of multilayered closures and use of the nasoseptal flap. In contrast, transcranial approaches are versatile, with a multitude of options to attack complex lesions. The disadvantages with the traditional transcranial approaches are brain injury from retraction and small operative corridors between critical neurovascular structures that can increase the risk of visual deficits and vascular injury.65 A blind spot underneath the optic chiasm can also increase the likelihood of residual tumor.
In 2012, Komotar et al performed a large systematic review of the literature comparing endoscopic endonasal approaches with both transsphenoidal microscopic and transcranial approaches.65 The endoscopic approaches resulted in higher rates of gross total resection (67% vs. 43%) and postoperative improvement in vision compared with the transcranial cohort. However, the CSF leak rate was also higher in the endoscopic cohort (18.4%) than in the transsphenoidal microscopic (9.0%) and transcranial (2.6%) groups. Jeswani et al found in their institutional experience equivocal outcomes comparing endoscopic with transcranial approaches.66
More recently, Wannemuehler et al published their single-institution comparison of transcranial approaches with the extended endoscopic approach, which found similar resection rates (gross total resection rate [GTR] about 55%) but associated significantly improved visual outcomes with the endoscopic approach.67 Additional morbidities, including diabetes insipidus and endocrinopathy, were similar between the groups, at about 50%. Although postoperative CSF leakage was observed only in the endonasal group, this result did not meet statistical significance. For craniopharyngiomas that can be treated using either approach, the endoscopic approach was more likely to result in gross total resection (90% vs. 40%), visual recovery, and overall fewer complications than with the transcranial approaches.36 Prospective randomized comparisons are needed to determine the definitive advantage of one surgical approach over the other, but the data at least indicate the noninferiority of endoscopic approaches to transcranial approaches.