Management of Recurrent Skull Base Meningiomas

Management of Recurrent Skull Base Meningiomas

Keywords: anaplastic, atypical, chemotherapy, endoscopic surgery, meningioma, microsurgery, minimally-invasive, radiosurgery, recurrence, skull base

Sheri K. Palejwala, Garni Barkhoudarian, Walavan Sivakumar, Daniel F. Kelly


Skull base meningiomas, due to their frequent investment or encasement of critical neurovascular structures, are challenging to resect in their entirety, both with initial resection and reresection. Up to one-third of such meningiomas will recur or progress after initial surgery. Given their complex and varied spectrum of location and growth pattern, such meningiomas pose a significant management challenge. They are typically best treated with judicious use of maximal surgical reresection, and/or stereotactic radiotherapy (SRT) or radiosurgery (SRS), with the aim of reversing neurological deficits and slowing or stopping tumor progression. While complete surgical excision remains the strongest prognosticator for recurrence free-survival, independent of the frequency of recurrence, SRT and SRS remain key treatment options for many recurrent meningiomas. Depending upon the tumor location, focused radiation with SRS or SRT has shown comparable outcomes to surgery when used alone, and with good tumor control rates when used as an adjuvant, with both subtotal and complete resection, as well as with some high-grade (atypical) and multiply recurrent tumors. Beyond repeat surgery and radiation, multiple chemotherapeutic and hormonal therapies have been trialed, and some demonstrate limited efficacy, but without evidence of lasting regression or remission. Ultimately, recurrent or progressive meningiomas of the skull base are best managed with a team approach that offers multimodality therapies including a combination of traditional and endoscopic keyhole surgical approaches for maximal safe resection, focused radiation treatments with SRS and SRT, and a continued search for effective targeted medical therapies based on tumor genetics and biomarkers.

18.1 Introduction

Meningiomas account for over one-third of all brain tumors, making them the most common primary brain tumor in the United States, with a lifetime risk of approximately 1%. According to the 2016 World Health Organization (WHO) Classification guidelines, roughly 70 to 80% of all meningiomas are WHO grade I, while 20 to 25% are WHO grade II and 1 to 6% WHO grade III. Incidence of meningioma increases steadily with age, with a median presentation age of 65 years, and a 2 to 3-fold increased likelihood in females. 1 Given the overall prevalence of meningiomas, and that up to 30% may be higher grade, the lifetime risk of recurrence after initial treatment is significant. For purposes of this chapter, skull base meningiomas include those of the sella and parasellar spaces, olfactory groove, tuberculum, sphenoid, petrous ridge, and the foramen magnum. Skull base meningiomas are more likely to recur than other subtypes, and their relationship to critical neurovascular structures makes their management more challenging.

18.2 Recurrence

Up to 20% of benign meningiomas and 70% of atypical meningiomas that were initially treated with gross total surgical resection recur. 1,​ 2 Recurrence depends on several variables especially the extent of initial resection, intracranial tumor location, initial tumor histopathology and molecular genetics, the use of upfront adjuvant therapy (before recurrence or treatment failure), and the unique situations of meningiomas associated with radiation or genetic syndromes. Skull base meningiomas, which make up approximately 20 to 30% of meningiomas, are particularly prone to progression and recurrence given that these tumors are invested in and around the critical neurovascular structures of the cranial base making complete resection less feasible. 3

18.2.1 Presentation

Most recurrent skull base meningiomas are diagnosed with follow-up magnetic resonance imaging (MRI) or computed tomography (CT), as long-term follow-up with serial imaging for distant recurrence surveillance has become common practice. 1,​ 4 In contrast, some patients may present with focal deficit due to compression of neurovascular structures, especially when located along the skull base or causing parenchymal mass effect. This presentation is more likely when the tumor is rapidly growing, such that the surrounding structures do not have adequate time to compensate for the relatively brisk growth rate.

18.2.2 Extent of Resection

Since initially described by Simpson in 1957, extent of resection has been held as the most important indicator of meningioma recurrence, and duration of recurrence-free survival (▶ Table 18.1). The greatest likelihood of recurrence prevention is an initial complete or Simpson grade I–II resection. 5,​ 6,​ 7 However, grade I resection is often not possible to achieve for skull base meningiomas, given the involvement of critical neurovascular structures. Nevertheless, even achieving grade II or III resection is associated with decreased rates of recurrence and increased rates of recurrence-free survival. 6,​ 7,​ 8 Hence, the likelihood of obtaining a complete, and potentially curative resection is more likely on initial resection than in the setting of recurrence, but should remain the goal of surgical resection if possible, even with multiple recurrences. However, in many recurrent skull base meningiomas, curative resection is not a reasonable goal and instead bony decompression and safe but effective debulking with adjuvant radiotherapy or radiosurgery offer the best treatment options. 9,​ 10,​ 11,​ 12

Table 18.1 Simpson grading of meningioma extent of resection 7

Simpson grade

Extent of resection


Complete macroscopic tumor resection, surrounding bone and dura


Complete macroscopic tumor resection, with excision of involved dura, not bone


Complete macroscopic tumor resection, without bone or dura resection


Subtotal resection with macroscopic residual


Biopsy alone

18.2.3 Location

Intracranial meningiomas are often divided into skull base lesions and those located along the cranial convexities. Skull base meningiomas are more likely to recur than convexity meningiomas, irrespective of tumor grade, as most atypical and anaplastic meningiomas occur along the cranial convexity. The higher rate of recurrence in cranial base meningiomas is attributable primarily to the challenges of resection in proximity to critical neurovascular structures. 5,​ 6,​ 13 Parasagittal meningiomas, however, should be considered separately than their convexity counterparts, as involvement or frank invasion of the superior sagittal sinus poses similar surgical constraints as those presented by the cranial nerves. This is especially true of falcine and parafalcine meningiomas adjacent to sensorimotor cortex. 1,​ 5 In these cases, complete surgical resection can be unduly morbid, especially in the setting of an otherwise benign disease process, and Simpson I resection is, by definition, impossible without significant and unwarranted morbidity and even mortality. As a result, skull base and parasagittal meningiomas are associated with significantly higher rates of tumor regrowth, recurrence, and decreased overall survival. 1,​ 2,​ 5,​ 6,​ 13

18.2.4 Histopathology

The WHO recognizes 15 subtypes of meningiomas and divides them into three cohorts: WHO grade I, WHO grade II (atypical), and WHO grade III (anaplastic) meningiomas, with increasing rates of recurrence and invasion. 1 As a result of the 2016 grading criteria, the subset of atypical, WHO grade II, meningiomas has grown from 6 to 10% of all meningiomas, to 20 to 25%, while the outcomes of WHO grade I meningiomas are improved and more reflective of a benign disease process. 1,​ 6 Tumor histology plays a significant role in the likelihood of tumor recurrence. Although WHO grade III tumors are far less common, they are much more likely to recur in short interval, than their more benign counterparts. When they do occur, they are more aggressive and locally invasive, and in late stages, even present with extracranial metastases. ▶ Table 18.2 outlines an overview of meningioma incidence, survival, and recurrence, stratified by WHO grades. Based on several large studies, skull base meningiomas in general do not appear to have a higher proportion of grade II or III meningiomas relative to other locations. 1,​ 13,​ 14

Table 18.2 Meningioma incidence, progression-free and overall survival, and recurrence rate based on World Health Organization grade

WHO grade

Incidence (%)

Progression-free Survival (%)

Overall survival (%)

Recurrence rate* (%)


























*After gross total resection (Simpson grade I–II)

 Hormone Receptor Status

Estrogen receptors, though seldom expressed in meningiomas, are more likely to be present with WHO grade I meningiomas. Progesterone receptor presence is strongly correlated with grade I meningiomas, and are nearly absent in atypical meningiomas. Progesterone receptor presence, however, has not been shown to be an independent predictor of a more favorable outcome. 1 Some studies have shown a greater Ki-67 in progesterone receptor-negative meningiomas, however, this cannot be used to imply a causative relationship between receptor status and tumor aggression, as receptor status is correlative with a number of confounding variables, the most significant of which is histologic grade. 15

18.2.5 Radiation-induced Meningiomas

Radiation is the only known environmental risk factor for meningioma formation, and meningiomas are the most common cerebral neoplasms caused by radiation. 1,​ 16 Radiation-induced meningiomas are roughly six times more likely to demonstrate multiplicity, occurring in 5 to 19% of cases. Also, radiation-induced meningiomas are much more likely to be atypical or anaplastic, with a high incidence of nuclear atypia, pleomorphism, cellularity, necrosis, local invasion, and mitoses. 16,​ 17 As expected from these higher-grade tumors, recurrence rates are significantly higher with radiation-induced meningiomas at 25.6% as opposed to 11.4% in sporadic meningiomas, when looking across all subtypes, WHO grades, and variable degrees of resection. Multiple recurrences also occurred in 11.6% of all treated radiation-induced menigniomas. 16,​ 17,​ 18

The treatment of choice for radiation-induced meningiomas is no different than for their genetic or sporadic counterparts, complete surgical resection. However, due to their local invasiveness and multiplicity, this presents additional challenges. When considering surgical resection, it is important to consider not only prior exposures as well as the devascularized, radiated scalp and soft tissue. 16 In these situations, minimally invasive and endoscopic-assisted techniques could play an essential role in minimizing the surgical impact, optimizing wound healing and expediting recovery. Given that radiation-induced meningiomas are more likely to be higher grade and locally invasive, more aggressive surgical excision with wide dural and bony margins is recommended when possible. Expectedly, skull base and parafalcine radiation-induced meningiomas have higher recurrence rates than those located on the convexity due to the same anatomical constraints on aggressive resection in these locations as with sporadic menigniomas. 16,​ 17 Paradoxically, radiation therapy or radiosurgery may also serve as an important adjunct in the management of these tumors, and has often times been used successfully both as adjuvant therapy or as the sole treatment. 16,​ 18

18.2.6 Adjuvant Therapy of De Novo Meningiomas

Some groups advocate the use of upfront adjuvant radiosurgery after initial subtotal resection of even WHO grade I tumors or for atypical and higher-grade meningiomas, before evidence of regrowth or recurrence. In cases of tumors invading the cavernous sinus or other critical neurovascular structures of the skull base, treatment might be staged, with the intent of resecting what is safely accessible and using adjuvant radiosurgery for the more invasive and less surgically accessible portions. 19

Using this paradigm of radiation for anything other than the complete resection of a WHO grade I meningioma, the recurrence or residual growth rate is 4 to 8%, though a few have a transient growth period. 20 One argument against this practice is the early execution of one of the major tools in the surgeon’s armamentarium for the management of tumor recurrence. The premature use of radiosurgery for “disease control” of residual tumor, or radiating the tumor bed of higher-grade tumors can leave the brain vulnerable to adverse radiation effects if future radiation becomes necessary.

18.2.7 Multiple Recurrences

Multiple recurrences are more common in the setting of atypical meningiomas, where the average patient has 3 to 4 instances of tumor recurrence. Initial recurrences (1–3) are strongly correlated with extent of resection whereas subsequent recurrences (≥4) are independent of the initial treatment modality (surgery vs. radiation or radiosurgery) as well as extent of resection or radiation dose. Furthermore, initial recurrences are more likely to be local, while subsequent recurrences are progressively peripheral then distant to initial tumor location. 13

Genetic analysis of patients with more than or equal to three meningiomas showed the same copy of chromosome X was inactivated or the same NF2 mutation was present. This supports the widely-purported hypothesis that multiple meningiomas are still clonal and arise via dural spread. 1 Similarly, pathologic studies have shown evidence of meningothelial cell nests in peritumoral and even distant strips of otherwise unremarkable dura. 21 As mentioned previously, multiple recurrences are more common in the setting of familial syndromes with germline mutations and radiation-induced tumors, essentially, higher-grade meningiomas. It is intuitive that frequency of tumor recurrence is a clear demonstration of tumor aggression and, in turn, increases the likelihood of future recurrence, with progressively shorter intervals between recurrences.

18.3 Management

The management of recurrent or progressive skull base meningiomas present the surgeon, his/her team, and the patient with the same basic options as for management of the initial tumor: surveillance, repeat surgical resection through the same or a different approach, stereotactic radiotherapy (SRT) or radiosurgery (SRS), adjuvant medical therapies, or in many cases, some combination of these therapies. The decision-making process should be individualized based on the patient’s age, comorbidities, recurrence location, tumor histology and their prior surgical and nonsurgical treatments. For example, a meningioma with cranial nerve or vascular investment that has been previously debulked without SRT or SRS, and now shows progressive growth, may be best treated with SRS or SRT alone (▶ Case 1). In contrast, a progressively growing previously operated parasellar meningioma (from a lateral approach) with new brainstem compression, may be best treated with endonasal transclival bony decompression and tumor debulking, followed by imaging and/or SRT (▶ Case 3). In some patients with multiple comorbidities and an aggressive, highly invasive skull base meningioma that has already had reasonable surgical debulking and SRS/SRT, more unproven therapies such as chemotherapy or hormonal therapy (e.g., mifepristone) may be considered. It is also important for the patient to understand that while surgical resection and radiation with SRS or SRT are standard and proven effective therapies for managing skull base meningiomas, other therapies such as chemotherapy and hormonal therapies are considered experimental. Setting appropriate expectations is critical in these challenging patients.

18.3.1 Surveillance

Surveillance with serial imaging is always a viable option especially in the setting of small recurrences, low-grade tumors, asymptomatic tumors, high-risk patients, proximity to critical structures, and less readily accessible lesions. This is especially true in the early stages of regrowth when it can be challenging to differentiate tumor recurrence from postsurgical and/or postradiation changes. It is important to note that although a higher proportion of WHO grade II–III meningiomas recur, most meningiomas are WHO grade I, which remain slow-growing tumors that can often be safely followed with serial MRIs, particularly in the elderly patient population or those with significant comorbidities. In most patients with an asymptomatic but slowly enlarging meningioma (particularly in older patients), it is reasonable to perform surveillance MRIs at 6-month intervals. If mass effect or symptoms develop, then reresection, SRS/SRT, or other adjuvant therapies can be considered at that time.

18.3.2 Surgical Resection

A majority of patients with a symptomatic recurrence of a skull base meningioma will be best served by reresection, as will those patients without symptoms but with progressive tumor growth and mass effect seen on serial imaging. Many if not most of these patients will also benefit at some point from subsequent SRS or SRT given that a complete removal will often not be possible, particularly for invasive skull base meningiomas with vascular and/or cranial nerve encasement. As such, these patients should be counseled prior to reresection that such multimodality treatment will likely be needed.

As with the initial resection, the single most important factor in preventing further recurrence and improving both recurrence-free and overall survival is the extent of resection. 13 While some have recommended radical resection, even at the risk of transient morbidity such as cranial nerve palsies or cerebrospinal fluid (CSF) leak, due to the poor prognosis associated with multiple recurrences, 5 others including our group, advocate for maximal but safe reresection with the primary goal being neurological preservation and restoring or maintaining quality of life. 12

 Goals of Surgery

Surgical goals in the treatment of recurrent skull base meningiomas can vary from maximal resection to decompression of critical neurovascular structures. Early radical resection has been shown to portend a survival benefit in the setting of recurrence. Furthermore, radical Simpson grade I–II resection is particularly advocated for surgically accessible tumors and symptomatic patients. 13 It is important to note that radical reresection is not as effective as initial complete resection, but still remains the greatest predictor of disease-free survival. 5 Conversely, patients’ quality of life can be significantly compromised with significant morbidity following overzealous reresection, often without a corresponding survival advantage. As always, the goals of surgery should be a realistic understanding of the feasibility of radical resection weighed against the potential neurologic deficits and/or other complications incurred by such a surgery.


The optimal surgical approach for a recurrent skull base meningioma is primarily dependent on tumor location, the prior approach used, the recurrence growth pattern, anatomical constraints imposed by cranial nerves and vasculature surrounding the tumor, and if the patient had prior SRS or SRT. Given that many if not most recurrent skull base meningiomas arise in or near the midline, several approach options are often possible including using a traditional lateral skull base approach, a retromastoid approach as well as somewhat newer keyhole approaches that incorporate endoscopy such as the supraorbital eyebrow approach, mini-pterional approach and endonasal endoscopic approach. 11,​ 12,​ 13,​ 22,​ 23

The aims in selecting a surgical approach is ensuring access to the tumor mass, gaining adequate control of the relevant vasculature, decompressing vital structures, obtaining a wide resection of dural margins when possible, and avoiding unnecessary manipulation of vital neurovascular structures.

Same Approach

Using the same approach as the initial resection is beneficial in the setting of local recurrence that does not extend beyond the previous exposure. However, residual left in the initial resection from limited visualization is likely to be similarly obscured on repeat resection, and the use of endoscopy, for example, might be beneficial. Additionally, there is increased risk to critical neurovascular structures that have been previously manipulated surgically and/or radiated. Anatomical landmarks can also be obscured from fibrosis and scar, which can also increase the likelihood of cranial nerve palsies and vascular injuries. Finally, wound healing can also become troublesome with repeat surgery and previous radiation. This is especially relevant in the setting of radiation-induced meningioma recurrence, where patients may require tissue grafts to ensure adequate scalp closure. 16 With respect to endonasal approaches, reconstruction can be particularly challenging as some autologous local tissue grafts such as nasoseptal mucosa may no longer be available, and risk of CSF leak, especially with previous radiation, is higher.

Different Approach

A different approach might be indicated for distant recurrences or regrowth of residual tumor, which was inaccessible with the initial approach. Added benefits of using a different approach, when possible, include avoidance of scar tissue, as clearly demarcated landmarks will allow for reliable identification of critical structures, and may decrease the incidence of complications. Many skull base meningiomas lend themselves to multiple approaches from the offset, including transcranial and/or endoscopic endonasal approaches. An anterior cranial fossa floor or olfactory groove meningioma, for example, could be approached via a subfrontal or expanded endoscopic approach. In these instances, the area of tumor recurrence may have been at the limits of the previous exposure, lending the regrowth to the other approach, or the alternative approach may simply be advantageous due to the avoidance of scar tissue.

Similarly, suprasellar meningiomas can be approached from a transphenoidal or transcranial (pterional/orbitozygomatic) approach. The supraorbital craniotomy to the suprasellar space is an underutilized approach that provides a direct trajectory to the tumor while largely avoiding scar tissue from previous approaches and allowing access for decompression of the optic apparatus. Endoscopy can be added to traditional microsurgical techniques in order to safely maximize tumor removal, in the setting of a less invasive approach (▶ Fig. 18.1). Using an eyebrow incision, the tissue is less likely to be previously radiated, minimizing postoperative wound complications, and CSF leak. McLaughlin et al describe seven patients who underwent the supraorbital approach, with endoscopy, for the resection of meningiomas with recurrence or delayed progression, where all patients had adequate tumor removal and two-thirds had improvement in their visual acuity. 24


Fig. 18.1 Illustration of surgical access afforded by a supraorbital eyebrow craniotomy with addition of an endoscope

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Jul 31, 2019 | Posted by in NEUROSURGERY | Comments Off on Management of Recurrent Skull Base Meningiomas
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