Chondrosarcoma of the skull base

INTRODUCTION — 

Chondrosarcomas are a heterogeneous group of malignant bone tumors that can arise anywhere in the axial or appendicular skeleton. They most commonly involve the femur, pelvis, or humerus. Chondrosarcomas involving the skull base are less common and pose unique management challenges related to their proximity to neurovascular structures.

The clinical presentation, diagnosis, and management of chondrosarcoma of the skull base is presented here. Chondrosarcomas in other locations are discussed separately. (See "Chondrosarcoma".)

EPIDEMIOLOGY — 

Chondrosarcomas of the skull base are rare tumors. They represent approximately 1 percent of chondrosarcomas and 0.15 percent of intracranial neoplasms [1].

The majority are located in the middle cranial fossa and arise from within the spheno-petrosal, petro-occipital (petroclival), or spheno-occipital synchondroses. The most common locations are petrous bone (38 percent), clivus (24 percent), petroclival synchondrosis (20 percent), sphenoid bone (12 percent), and supra- or parasellar (7 percent) [1]. There is a predilection for the right skull base for reasons that are not known. Less commonly, chondrosarcomas in the nasal cavity secondarily involve the skull base and intracranial compartment [1-4].

The median age at diagnosis is 43 years (range 18 to 85 years) [1]. There is a slight female predominance [1,3,5,6].

Most chondrosarcomas are sporadic tumors in patients without identifiable risk factors. Genetic predisposition syndromes and other risk factors are reviewed separately. (See "Pathogenetic factors in soft tissue and bone sarcomas".)

PATHOLOGY — 

More than 80 percent of chondrosarcomas of the skull base are classified as conventional chondrosarcomas (picture 1). Myxoid, mesenchymal, clear cell, and dedifferentiated subtypes are much less common, making up approximately 13, 3, 0.4, and 0.7 percent of cases, respectively [1-6].

A World Health Organization (WHO) histologic grade of 1 to 3 is assigned based on nuclear size, staining pattern, mitotic activity, and degree of cellularity (picture 1) [2]. Most skull base chondrosarcomas are WHO grade 1 (60 percent) or grade 2 (38 percent) [1]. Grade 3 tumors are rare (2.5 percent).

Additional information on pathologic classification of chondrosarcomas is presented separately. (See "Chondrosarcoma".)

CLINICAL PRESENTATION — 

The clinical presentation of chondrosarcoma of the skull base varies based on tumor location and extent. Most patients have symptoms for several months or more before diagnosis [1].

Diplopia is the most common presenting symptom. This is often due to compression of the abducens nerve (cranial nerve VI) in Dorello's canal by a petroclival tumor. Diplopia can also occur due to cavernous sinus involvement leading to abducens and/or oculomotor nerve palsies [1,7,8].

Headaches are very common and may be caused by local mass effect or obstructive hydrocephalus. Facial pain and trigeminal neuropathy may occur due to involvement of the trigeminal nerve at the petrous apex [1,8].

Extra-axial compression or invasion is present in approximately half of tumors, most commonly involving brainstem (50 percent), cavernous sinus (42 percent), optic apparatus (38 percent), and/or temporal lobe (22 percent) [1]. Larger tumors may cause decreased visual acuity or visual field defects from impingement on the optic nerves, chiasm, or optic tracts. Conductive hearing loss may arise from compression of the eustachian tube as it extends inferiorly from the foramen lacerum. Sensorineural hearing loss can be caused by direct involvement of the inner ear or the vestibulocochlear nerve, which can also be associated with vertigo.

Hypopituitarism may arise due to mass effect on the pituitary gland or stalk, manifesting as generalized weakness or fatigue, susceptibility to infections, reproductive dysfunction, or galactorrhea [1,8].

DIAGNOSTIC EVALUATION — 

A preoperative diagnosis of chondrosarcoma of the skull base can often be made with imaging. Laboratory studies can point to an alternative diagnosis in certain cases. A biopsy is usually unnecessary and is often avoided because it can interfere with definitive resection and reconstruction.

Imaging — Chondrosarcomas have specific imaging characteristics that help differentiate them from other pathologies involving the skull base. Both computed tomography (CT) and magnetic resonance imaging (MRI) are typically obtained since they provide complementary information on bone and soft tissue.

●CT features – On noncontrast CT, skull base chondrosarcomas usually exhibit low attenuation but contain internal calcifications that appear as rings or arcs, often called a "chondroid pattern" (image 1). This pattern can sometimes be appreciated even on plain skull radiographs.

A key feature, particularly in tumors that are not very large, is that they expand the synchondrosis they originated from, displacing surrounding structures rather than encircling them. Encirclement is more common with other tumors such as chordoma or prolactinoma. Chondrosarcomas often displace the carotid artery and carotid canal or the eustachian tube [9]. Additionally, smaller tumors may respect the cortical bone of the synchondrosis they arise in. They are usually eccentric to one side (often the right side) [1].

Lager/invasive tumors are more osteodestructive and can envelop the carotid artery [10]. In such cases, CT angiography is useful to determine whether there is constriction of the lumen, which can increase surgical risk.

●MRI features – Contrast-enhanced MRI is often diagnostic for skull base chondrosarcoma (image 1). Chondrosarcomas are usually T2-hyperintense, T1-hypointense, and enhancing after administration of contrast. The pattern of enhancement can vary from solidly enhancing to a more heterogeneous, lacy, "arabesque-like" pattern [11]. Intratumor calcifications can appear as granular hypointensities on susceptibility-weighted sequences.

Chondrosarcomas are usually less cellular than other tumors such as chordomas or metastases, resulting in higher apparent diffusion coefficient (ADC) values [11,12]. Dynamic contrast-enhanced (DCE) MRI and MRI-based radiomics show promise in helping to discriminate chondrosarcomas from other skull base lesions [12,13].

●Angiography – For patients at high risk for vascular injury with resection, a catheter-based angiogram with or without a balloon test occlusion is sometimes performed preoperatively to evaluate the collateral circulation and the implications of vascular compromise in the case of carotid injury.

Differential diagnosis — Other tumors with a predilection for the skull base can usually be distinguished from chondrosarcoma by location and imaging features.

●Chordoma of the skull base – Most skull base chordomas are midline lesions centered in the clivus (image 2); chondrosarcomas are usually eccentric. Chordomas tend to spread within the venous plexus of the skull base and encircle rather than displace surrounding structures such as the carotid artery. They tend to be more cellular and therefore generally have lower ADC values on MRI than chondrosarcomas. Although calcifications can be present, they are less frequent than with chondrosarcomas. (See "Chordoma of the skull base", section on 'Imaging'.)

●Pituitary tumors – Pituitary adenomas usually have an epicenter within the sella. They are typically homogenously enhancing and usually do not have calcifications. Among pituitary tumors, lactotroph adenomas (prolactinomas) are more likely to be extensive and invasive in a way that may be confused with chondrosarcoma (image 3). In such cases, elevated serum prolactin (>200 ng/mL) can make the diagnosis noninvasively [14]. (See "Causes, presentation, and evaluation of sellar masses", section on 'Hormonal hypersecretion'.)

●Metastases – Metastases have a variable appearance on imaging. The most useful radiographic differences are that they are unlikely to have internal calcifications and are more osteodestructive than chondrosarcomas. They are also associated with lower ADC values compared with chondrosarcoma. Metastases usually have a more aggressive clinical course and can be associated with significant edema within the brain parenchyma. Perineural spread can be seen, which is not characteristic of chondrosarcoma. A systemic staging evaluation usually reveals other lesions.

●Meningioma – Skull base meningiomas are usually homogeneously enhancing and associated with hyperostosis of bone (image 4), in contrast with the osteodestructive nature of chondrosarcomas. A dural tail can be useful if present. (See "Epidemiology, pathology, clinical features, and diagnosis of meningioma", section on 'Neuroimaging'.)

●Sinonasal malignancies – Sinonasal cancers are usually centered in the nasal cavity. Internal calcifications are unusual. They can be associated with perineural spread. (See "Tumors of the nasal cavity".)

●Hematologic malignancies – Lymphoma, plasmacytoma, and multiple myeloma can involve the skull base in various locations, often with a more acute clinical course. Compared with chondrosarcoma, they are more likely to be homogeneously enhancing and do not have internal calcifications (image 5). They are usually hypercellular and have low ADC values. Plasmacytoma and myeloma may be associated with monoclonal gammopathy. (See "Solitary plasmacytoma of bone" and "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis".)

Laboratories — Selective laboratory investigation is indicated depending on the differential diagnosis and tumor location. Testing for hormonal hypersecretion (eg, serum prolactin, insulin-like growth factor-1 [IGF-1], and plasma corticotrophin [ACTH]) is useful for tumors with pituitary/sellar involvement and can be diagnostic of an adenoma. We obtain a serum protein electrophoresis (SPEP) with immunofixation and serum free light chain assay when there is radiographic suspicion for plasmacytoma or multiple myeloma.

Limited role of biopsy — In contrast with bone and soft tissue tumors in other sites, a biopsy is rarely necessary before definitive surgery for suspected chondrosarcoma of the skull base. The diagnosis is usually evident from imaging, and biopsy can be challenging and potentially harmful. Certain biopsy approaches can compromise reconstructive options for definitive resection.

Nonetheless, a biopsy is appropriate when the diagnosis is in question and the differential includes tumors for which operative management is not immediately indicated. Such tumors include high-grade sinonasal malignancies, lymphoma, and plasmacytoma.

Extent of disease evaluation and staging — The evaluation for metastatic disease is tailored to tumor grade and subtype. In patients with grade 1 or 2 conventional chondrosarcoma of the skull base, body imaging is not routinely performed given the low rate of metastases. In patients with grade 3 tumors and those with mesenchymal or dedifferentiated histology, we obtain a staging CT of the chest with contrast to evaluate for lung metastases. As with other sarcomas, lung is the main site of metastatic disease.

Although chondrosarcomas may be staged according to tumor, node, metastasis (TNM) system for primary malignant tumors of bone (table 1), this system has not been widely adopted for clinical use. Under the TNM system, skull base chondrosarcomas are considered together with appendicular, trunk, and facial tumors.

MANAGEMENT

Resectable tumors — Surgical management of chondrosarcoma offers the best chance for cure. Obtaining clear margins in the base of skull is challenging, however, and adjuvant radiation therapy is often required for local disease control. Chondrosarcomas are poorly responsive to systemic therapies.

Surgery — All operative candidates should be offered maximal safe resection. Beyond removal of the grossly abnormal appearing tumor, resection of the surrounding infiltrated bone to normal-appearing bone should be the goal whenever possible. This is often referred to as a "supratotal" resection. An en bloc "wide local excision," a term often used for chondrosarcomas in other parts of the body, is usually not possible in the base of the skull. Proximity to critical neurovascular structures often poses significant limitations, and overzealous resections can be associated with significant morbidity [1,4,15-18].

Patients should be referred for consultation at high-volume neurosurgical centers with oncologic skull base expertise. Surgery can be performed with a conventional and/or endoscopic approach. Selected tumors, particularly those that are confined to the area medial to the cranial nerves, can be removed completely by endoscopic endonasal surgery [15]. Advanced endoscopic techniques (eg, far/extreme medial and contralateral transmaxillary approaches) have improved resectability while decreasing morbidity (picture 2) [19-21]. Nonetheless, conventional or combined techniques are often still required [18]. Across studies, the rate of gross total resection for newly diagnosed tumors ranges from 23 to 38 percent [1,6].

Retrospective data in patients with skull base chondrosarcoma suggest that gross total resection is associated with improved progression-free survival. As an example, in a retrospective single-institution study of 37 patients with new or recurrent skull base chondrosarcomas who underwent maximal safe resection, gross total resection was associated with prolonged progression-free survival compared with subtotal resection (112 versus 43 months), although results were not statistically significant (p = 0.2) [16]. Forty-eight percent of patients received adjuvant radiation therapy. Overall survival was not reported because median overall survival was not reached with a median follow-up of 5.6 years. In other studies and systematic reviews, gross total resection has not been consistently associated with improved overall survival [1,6].

Important limitations of the existing data are heterogeneity (most series are a mix of tumor subtypes and grades, and use of adjuvant therapy is nonstandardized), small studies with variable follow-up, and the potential for selection bias. Tumors that are amenable to a complete resection are usually smaller and are not intimately associated with sensitive structures that would preclude radical removal. In addition, patients able to undergo surgery are generally younger, healthier, and at lower risk for surgical complications. These factors must be considered when weighing the benefits and risks of surgery.

Potential complications of surgery include cerebrospinal fluid (CSF) leaks, transient or permanent cranial neuropathies, intracranial hemorrhage, and vascular injury [1,15,18]. In a systematic review of 33 retrospective studies that included 1307 patients with skull base chondrosarcoma, the most common surgical complications were transient cranial neuropathies (16 percent), persistent cranial neuropathies (6.7 percent), CSF leak (6.5 percent), intracerebral hemorrhage (1.4 percent), and ischemic stroke (0.7 percent) [1].

Adjuvant radiation therapy

Residual or high-grade disease — For patients with residual disease after maximal surgical resection of a grade 1 or 2 conventional chondrosarcoma and all patients with high-grade tumors, we suggest adjuvant radiation therapy. Particle-based therapy (proton or carbon ion) is often favored when available because it facilitates safer delivery of high doses of radiation to the skull base. Newer photon technologies are increasingly achieving equivalent and sometimes superior radiation delivery, however, and selection of a specific technique is individualized.

Supporting evidence for the use of radiation therapy to improve local control after subtotal resection consists primarily of retrospective case series from single institutions [16]. Studies are limited by small size and heterogeneity in tumor characteristics and treatment approaches. In a systematic review of 22 observational studies in 1388 patients with new or recurrent skull base chondrosarcoma, progression-free survival rates with adjuvant radiation therapy (provided in most cases to patients with subtotal or partial resections) ranged from 87 to 96 percent at 3 years, 57 to 100 percent at 5 years, and 67 to 100 percent at 10 years [22]. Most patients received proton therapy (64 percent), carbon ion therapy (18 percent), or a combination of proton and photon therapy (12 percent).

Given the limitations in the data, it has been difficult to determine whether adjuvant radiation therapy improves overall survival. In an analysis of 718 patients with skull base chondrosarcoma in the National Cancer Database (NCDB) for whom overall survival and treatment data were available, 44 percent of patients received radiation therapy (traditional or proton) and 54 percent of patients did not [6]. In a multivariable regression analysis that adjusted for multiple factors including age, tumor size, histology, and extent of resection, receipt of radiation therapy was not associated with a difference in survival in the overall cohort (hazard ratio [HR] 1.10, 0.67-1.81) or in any subgroup (eg, complete versus partial resection). In an exploratory univariate analysis of radiation modality and dose, high-dose radiation (>60 Gy) was associated with improved overall survival compared with no or low-dose radiation (<30 Gy; HR 0.33, 95% CI 0.15-0.71), and proton therapy was associated with improved overall survival compared with no radiation therapy with borderline statistical significance (HR 0.42, 95% CI 0.17-1.05).

Chondrosarcomas are radioresistant tumors that require high doses of radiation (≥70 Gy) to achieve tumor control. Delivery of such high doses is challenging in the skull base, particularly for larger treatment fields that encroach on the brainstem, cranial nerves, pituitary gland, and temporal lobes. Particle-based therapies (eg, proton beam and carbon ion) have been favored historically for this purpose, since they achieved greater avoidance of normal tissue radiation dose than the available photon-based techniques [1,22-25]. Several advanced photon technologies now achieve comparable precision to particle-based therapies, however, and selection of a specific technique should be based on a case-specific evaluation.

Administration of radiation therapy varies by technique:

●Proton therapy – Typical doses for proton therapy for skull base chondrosarcoma range from 70 to 78.4 Gy(RBE) (Gray-relative biological effectiveness), fractionated over 30 to 56 sessions. Hypofractionated regimens (eg, 35 Gy[RBE] in five fractions) are also being investigated [26]. Five-year control rates with proton therapy for skull base chondrosarcoma range from 75 to 97 percent [22,25,27].

●Carbon ion radiotherapy – Typical doses range from 70 to 80 Gy(RBE), although even higher doses (up to 95 Gy[RBE]) have been used [24]. There is less experience with carbon ion therapy (not available in the United States) compared with proton therapy, but availability internationally is increasing.

●Photon-based radiation – Photon radiation therapy can also be used to treat skull base chondrosarcomas, but contemporary highly conformal techniques are required to achieve adequate dosing. Intensity-modulated radiation therapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) are increasingly used for this purpose [28].

Single-fraction stereotactic radiosurgery (SRS) may be appropriate for treating small volumes. Reported local control rates for SRS using doses of 16 to 18 Gy range from 67 to 83 percent at 10 years [17,29].

Even with particle-based therapy and highly conformal techniques, adverse radiation effects are a major cause of short- and long-term morbidity. Common adverse effects include hypopituitarism (31 percent); hearing loss (7 percent); radiation necrosis, most commonly the temporal lobe or brainstem (image 6) (4 percent); cranial nerve neuropathies including blindness (2 percent); osteoradionecrosis (1 percent); and secondary malignancies (<1 percent) [1,29-31]. (See "Delayed complications of cranial irradiation".)

Gross total resection — We suggest observation for most patients who undergo gross total resection of a grade 1 or 2 chondrosarcoma of the skull base. There is a lack of consensus, however, and some experts suggest adjuvant radiation therapy for all patients [17]. Shared decision-making is particularly important in these cases after review of individual factors including tumor location, the surgeon's intraoperative impression of microscopic residual disease, the radiation field, risks of reoperation, and patient preferences.

There have been no randomized trials or well-designed observational studies comparing observation with adjuvant radiation therapy for completely resected low-grade chondrosarcomas of the skull base. One systematic review of the literature identified six eligible retrospective studies on the long-term outcomes of a total of 157 patients managed with surgery alone (gross total resection in approximately 60 percent of cases) for low-grade skull base chondrosarcoma [22]. With median follow-up ranging from 39 to 86 months, progression-free survival ranged from 84 to 93 percent at 3 years, 60 to 93 percent at 5 years, and 58 to 64 percent at 10 years. The available data did not permit separate estimates for gross total resection versus subtotal resection.

Data on outcomes after gross total resection alone are even more limited. In one of the larger individual retrospective studies of 37 patients with detailed reporting of treatment and outcomes, all seven patients with grade 1 conventional chondrosarcoma were alive and progression-free after surgery alone (gross total resection in five, subtotal resection in two) with a median follow-up of 5.6 years [16].

Poor operative candidates — For patients who are not candidates for a meaningful resection based on older age or comorbidities, primary radiation therapy can be considered. However, observation and supportive care may be more appropriate for very frail patients, as they are at higher risk for treatment toxicity and have worse overall survival regardless of treatment modality [5].

In systematic reviews of the efficacy of adjuvant radiation therapy for skull base chondrosarcoma, approximately 5 to 10 percent of included patients have undergone biopsy alone [6,22,27]. Outcomes and administration of radiation therapy are reviewed above. (See 'Residual or high-grade disease' above.)

Locally recurrent disease — The management of recurrent skull base chondrosarcomas often requires a multidisciplinary approach [32]. Considerations include the following:

●Repeat surgery is generally preferred for recurrent tumors that can be removed completely with low morbidity. Radiation therapy is typically administered postoperatively in patients who are radiation-naïve. Particle-based therapies are preferred for larger treatment fields.

●Repeat surgery is also indicated to relieve compressive symptoms or to debulk large tumors and/or separate them from sensitive structures (eg, optic nerves or the brainstem). Such procedures facilitate subsequent radiation therapy.

●Reirradiation is possible in selected patients who have received prior radiation therapy. Eligibility depends on multiple factors including the location and size of the recurrent tumor and the timing and dose of prior therapy. SRS has been successfully used as a salvage therapy in cases of re-irradiation [32].

●For high-grade tumors and more aggressive subtypes (eg, mesenchymal and dedifferentiated histologies), systemic therapies should be considered, although chondrosarcomas are generally poorly responsive to available therapies [33]. (See "Chondrosarcoma".)

Metastatic disease — The approach to patients with metastatic chondrosarcoma is reviewed separately. (See "Chondrosarcoma".)

PROGNOSIS — 

Chondrosarcomas of the skull base are slow-growing but locally invasive tumors, and local recurrences are common [1,3-6,10]. Morbidity and mortality are largely driven by local recurrences and complications of therapy. Five- and ten-year overall survival rates are approximately 85 and 75 percent, respectively [1,3-6,10].

Prognosis varies based on patient age, tumor grade and subtype, and tumor size and location:

●Age and performance status – Younger patients have better progression-free and overall survival compared with older patients [1,3,6,10]. In data on 205 patients with skull base chondrosarcoma in the Surveillance, Epidemiology, and End Results (SEER) database, five-year survival was 93 percent for patients 15 to 44 years of age and 71 percent for those 65 to 74 years of age [3]. Frailty and comorbidities have been associated with worse outcomes [5].

●Histology and grade – Progression-free survival and overall survival are significantly lower for high-grade chondrosarcomas of the skull base, including World Health Organization (WHO) grade 3 conventional chondrosarcomas and mesenchymal and dedifferentiated subtypes [1,3,4]. In a National Cancer Database (NCDB) study that included 736 cases of sinonasal and skull base chondrosarcomas, five-year overall survival for low-, intermediate-, and high-grade tumors was 90, 87, and 69 percent, respectively, and 10-year overall survival was 81, 79, and 62 percent [4].

Mesenchymal and dedifferentiated subtypes have an increased risk of distant metastases, although absolute risk in patients with skull base chondrosarcoma is difficult to estimate given the rarity of these tumors. In a systematic review that included 718 patients with skull base chondrosarcoma, the rate of distant metastases was 1.5 percent, and no patient with metastases at the time of diagnosis survived longer than five years [6]. Data in chondrosarcoma more generally indicate that the metastatic potential of grade 3 tumors is high (>30 percent). (See "Chondrosarcoma".)

●Tumor size and location – Larger tumors and certain locations, such as those with a sublacerum epicenter, have been associated with worse prognosis [6,10].

●Arterial encasement – Encasement of multiple major arteries, such as the carotid or basilar artery, confers worse outcomes. In a study of 41 patients with skull base chondrosarcoma, the four patients with encasement of three or four arteries had significantly lower median progression-free survival compared with all other patients (1.8 versus 10.2 years) [10].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bone sarcomas".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Chondrosarcoma (The Basics)" and "Patient education: Bone cancer (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Skull base chondrosarcomas are rare malignant bone tumors that are usually slow-growing and locally invasive. They represent approximately 1 percent of chondrosarcomas and 0.15 percent of intracranial neoplasms. (See 'Epidemiology' above.)

●Pathology – Conventional chondrosarcoma is the predominant type found in the skull base. Most are World Health Organization (WHO) grade 1 or grade 2. Grade 3 conventional chondrosarcoma and high-grade histologic subtypes (eg, mesenchymal, dedifferentiated) are less common. (See 'Pathology' above.)

●Clinical presentation – Diplopia and headaches are the most common presenting symptoms. Most patients have symptoms for several months or more before diagnosis. (See 'Clinical presentation' above.)

●Diagnostic evaluation – Chondrosarcomas have specific imaging features (image 1) that help differentiate them from other pathologies involving the skull base, including chordoma (image 2), pituitary adenoma (image 3), metastatic disease, meningioma (image 4), and plasmacytoma (image 5). (See 'Differential diagnosis' above.)

On CT and MRI, chondrosarcomas typically show enlargement of the synchondrosis, internal calcifications, displacement of surrounding structures, and an eccentric location (image 1). (See 'Imaging' above.)

A preoperative diagnosis can often be made with imaging. A biopsy is usually unnecessary and is often avoided because it can interfere with definitive resection and reconstruction. (See 'Limited role of biopsy' above and 'Laboratories' above.)

●Management – Surgical management of chondrosarcoma offers the best chance for cure. Obtaining clear margins in the base of skull is difficult, however, and adjuvant radiation therapy is often required for local disease control.

•Surgery – All operative candidates should be offered maximal safe resection. Wide local excision rather than less extensive surgery is the goal, but proximity to critical neurovascular structures often poses significant limitations. (See 'Surgery' above.)

•Adjuvant radiation therapy – For patients with residual grade 1 or 2 conventional chondrosarcoma and all patients with high-grade tumors, we suggest adjuvant radiation therapy (Grade 2C). Particle-based therapy (proton or carbon ion) or advanced photon delivery techniques are typically required to deliver sufficiently high doses of radiation to the tumor while sparing adjacent structures in the skull base. (See 'Residual or high-grade disease' above.)

For most patients who undergo gross total resection of a grade 1 or 2 conventional chondrosarcoma, we suggest observation rather than adjuvant radiation therapy (Grade 2C). (See 'Gross total resection' above.)

Primary radiation therapy may be considered for patients who are poor surgical candidates because of age or comorbidities. (See 'Poor operative candidates' above.)

•Locally recurrent or metastatic disease – Reoperation and salvage radiation therapy are used to treat locally recurrent disease. Systemic therapies for metastatic chondrosarcoma are reviewed separately. (See 'Locally recurrent disease' above and "Chondrosarcoma".)

●Prognosis – Chondrosarcomas of the skull base are slow-growing but locally invasive tumors, and local recurrences are common. Ten-year progression-free and overall survival is approximately 65 and 75 percent, respectively. (See 'Prognosis' above.)