Role of Stereotactic Radiosurgery

Role of Stereotactic Radiosurgery


Keywords: meningioma, radiation, skull base, stereotactic radiosurgery


Gautam U. Mehta, Jeyan Kumar, Mohana Rao Patibandla, Jason P. Sheehan



Abstract


Stereotactic radiosurgery (SRS) is an important component of a multimodality approach to primary and metastatic tumors of the brain. In this chapter, we will discuss the role of SRS in the treatment of skull base meningiomas. To date, clinical studies have largely demonstrated durable tumor control for meningiomas treated with SRS. Compared to convexity meningiomas, radiosurgical management of meningiomas at the skull base requires specific pretreatment considerations, given the proximity to critical neurovasculature and the potential for cerebrospinal fluid outlet obstruction with posterior fossa lesions. As surgical treatment of skull base lesions may also carry increased risk, careful patient selection is essential, and factors such as patient age, tumor location, tumor size, distance from cranial nerves, and medical comorbidities must be considered. Further research is necessary to better understand the long-term outcomes of SRS in order to define optimal management of skull base meningiomas.


7.1 Introduction


SRS is a neurosurgical procedure that delivers radiation that is highly conformal, allowing high treatment doses to selected targets. Unlike fractionated radiotherapy or fractionated stereotactic radiotherapy, SRS is most frequently performed in a single session. The first clinical applications of SRS for meningioma were performed by Lars Leksell in the 1970s and with modern applications in the 1980s, with the advent of postcontrast MRI. 1,​ 2 Because meningiomas of the skull base can be challenging to resect, these tumors are more frequently referred for radiation than those at other locations. Although convexity meningiomas have similar biology to those of the skull base, similar to skull base resection, SRS of skull base meningiomas presents with unique challenges. Despite steep radiation dose falloff with SRS, minimizing radiation doses to neurovascular structures at the base of the brain becomes critical. Furthermore, management and patient selection require special considerations, which will be discussed in this chapter.


7.2 Radiobiology of Skull Base Meningiomas


Initial understanding of the radiobiology of intracranial meningiomas was largely based on initial clinical results with nonstereotactic radiation therapy reported in the 1970s. Despite lack of modern neuroimaging to assess tumor response, patients with subtotal resection of meningiomas and postoperative irradiation were found to have prolonged survival in these early studies. 3 Unlike these clinical results, in vitro study of radiation for meningiomas has demonstrated modest to equivocal results, likely due to the slow proliferative rate of these tumors in culture. 4 More sophisticated recent models have shown that radiation inhibits angiogenesis in murine models of these tumors. 5


Large series of SRS for meningiomas over the past two decades have helped further elucidate the radiobiology of these tumors. Initial results with the first large series published at the University of Pittsburgh in 1991. 6 Kondziolka and colleagues demonstrated that Gamma Knife radiosurgery could result in a 96% actuarial control at 2 years, with reduction in tumor volume in 17 of 50 patients (34%). 6 Margin doses in this initial study were relatively high, with 96% of patient receiving 12 Gy or higher and 48% of patients receiving 18 Gy or higher. Later studies analyzing the effect of margin dose found that a margin dose greater than or equal to 12 Gy was effective in tumor control of these patients. 7 Of 10 patients treated with 10 Gy or less, 4 tumors increased in size and 6 tumors were stable. Of 11 tumors treated with 12 Gy or more, 7 tumors were stable and 4 decreased in size. The largest study to date of meningiomas treated by SRS was performed by the European Gamma Knife Society. 8 This included 4,565 patients treated with SRS using a median margin dose of 14 Gy. The authors found that SRS resulted in a 5- and 10-year progression-free survival of 95.2 and 88.6%, respectively.


7.3 Outcomes of Stereotactic Radiosurgery for Skull Base Meningiomas


7.3.1 Radiological Response


Over the past two decades, several studies on the treatment outcomes for SRS of skull base meningiomas have been reported. In 1996, Nicolato and colleagues reported the results of Gamma Knife radiosurgery for 50 patients with skull base meningiomas. 9 This included 26 patients with cavernous sinus meningiomas. Mean tumor volume was 8.6 cm3 and mean margin dose was 18 Gy. 49 patients had tumor control at last follow-up, however, only 3 patients had follow-up of at least 2 years in this study. Two modern, single-center studies with more than 200 patients using a mean and/or median margin dose of 14 Gy, resulted in a 5-year progression-free survival of 96 to 98.5%. 10,​ 11 Median tumor volume was 6.5 cm3 in one study and mean tumor volume was 5 cm3 in another. Another study of SRS for foramen magnum meningiomas, demonstrated a 5-year progression-free survival of 97% (▶ Fig. 7.1). Because increased tumor volume has been associated with worse SRS outcomes for skull base meningioma, separate studies have looked at the outcomes of SRS for larger skull base meningiomas. 12 We previously analyzed the results of SRS for skull base meningiomas greater than 8 cm3 (which corresponds to a diameter of approximately 2.5 cm). 13 Among 75 patients, we found 5- and 10-year progression-free survivals of 88.6 and 77.2%, respectively. Patients with tumors greater than 14 cm3 were more likely to progress (hazard ratio 6.86, 95% confidence interval [CI] 0.88–53.36).



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Fig. 7.1 Kaplan-Meier analysis of tumor control after stereotactic radiosurgery in 57 foramen magnum meningiomas demonstrates 5- and 10-year progression free survival of 97 and 92%, respectively. Dashed lines represent 95% confidence intervals. (Reproduced from Mehta G. U., Zenonos G., Patibandla M. R., et al. Outcomes of stereotactic radiosurgery for foramen magnum meningiomas: an international multicenter study. 2017; in press.)


7.3.2 Cranial Neuropathy


Cranial neuropathies associated with SRS of skull base meningiomas are largely dependent on the location of the meningioma treated. Regardless, studies that have combined the results of all skull base meningiomas have demonstrated a rate of new or progressive cranial neuropathy in 1.5 to 8.6% of patients. 10 The risks of cranial neuropathies based on tumor location are detailed in ▶ Table 7.1. The cranial neuropathy risks associated with SRS for larger meningiomas may be greater than for small- to medium-volume tumors. Bledsoe and colleagues, who analyzed large (> 10 cm3) meningiomas at all sites, reported a 23% complication rate, with an 8% rate of cranial neuropathy. 12 Looking at only skull base meningiomas, we previously found that new or worsened cranial neuropathy occurred in 14% of patients who had SRS for tumors greater than 8 cm3. Hypofractionated SRS may be an option for patients with larger skull base meningiomas and help to mitigate complications associated with single-session SRS for large targets.





















































Table 7.1 Outcomes of some large series of skull base meningiomas by location

Author/Date


Location


Patients


Mean/median volume


Mean/median margin dose


Progression-free survival (PFS)


Adverse radiation effects


Skeike et al/2010 14


Cavernous


100


7.39 cm3


12.4 Gy


5 year: 94


10 year: 92


Optic neuropathy (2%)


Sheehan et al/2014 15


Sellar/parasellar


763


8.8/6.7 cm3


13.2/13 Gy


5 year: 95%


10 year: 82%


New/worsening CN deficits (9.6%)


Starke et al/2014 16


Petroclival


254


7.8 ± 6.6 cm3


13.4 ± 2.4 Gy


5 year: 93%


10 year: 84%


Hydrocephalus (2.8%)


Mehta et al/in press 37


Foramen magnum


57


Median: 2.9 cm3


Median: 12.5 Gy


5 year: 97%


10 year: 92%


Hearing loss/numbness in one patient (2%)


7.3.3 Brainstem Toxicity


As skull base meningiomas may be directly adjacent to or compressing the brainstem, radiation exposure with SRS is often unavoidable. Because of the steep radiation falloff with SRS and shielding strategies, this radiation burden can be significantly minimized. 17 The American Society for Radiation Oncology (ASTRO) funded a review of the maximum tolerated dosages of radiation on normal tissue called Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC). 18 The brainstem-specific study for this initiative reviewed prior reports of radiation therapy and radiosurgery for lesions adjacent to the brainstem. 19 This review found that brainstem doses of less than or equal to 12.5 Gy were associated with less than 5% risk of complications. Clinical evidence of brainstem toxicity is rare. A multicenter study of SRS for 675 posterior fossa meningiomas did not demonstrate any cases with apparent brainstem toxicity. 20


7.3.4 Other Complications


Vascular injury is a potential complication of SRS, particularly at the skull base, but the risk of major injury to a cerebrovascular structure from radiosurgery for a skull base meningioma is quite rare. Bledsoe and colleagues noted vascular infarct in 2 of 91 patients with skull base meningiomas who were treated with Gamma Knife radiosurgery. 12 After SRS, tumor swelling may result in ventricular outlet obstruction and hydrocephalus. In the previously described study of 675 patients treated with SRS for posterior fossa meningiomas, 2.1% developed hydrocephalus on imaging and 1.7% required surgery for cerebrospinal fluid diversion. 20


7.4 Management of Skull Base Meningiomas and Indications for Stereotactic Radiosurgery


7.4.1 General Indications


Patient selection is critical for effective utilization of SRS for skull base meningiomas. As many such tumors are found incidentally, observation is an important option for these patients, particularly with older patients or those with nongrowing, asymptomatic tumors. For growing and symptomatic tumors, most patients should consider treatment. In general, the procedural morbidity of SRS is significantly less than open surgical resection. This includes risks associated with general anesthesia, as well as surgery. This is particularly important in the management of meningiomas of the skull base as open surgical resection may require lengthy surgery with dissection around or manipulation of cranial nerves, the brainstem, and major arteries and veins. Therefore, patients who are older, and who carry greater medical comorbidities may be better suited for SRS (▶ Table 7.1). With young patients, and with tumors that are amenable to complete resection, open surgical options provide the possibility of histological confirmation of the tumor and grade and long-lasting, curative therapy. Regardless, even in the modern, microsurgical era, Simpson’s grade I resections are associated with some small risk of recurrence. 21,​ 22 Several studies have suggested that gross total tumor resection at the expense of subtotal resection with neurologic preservation, followed by radiosurgery, may be a more valid approach in the contemporary era. 23 Others have concluded that tumor control and recurrence-free survival are comparable for Simpson’s grade I resected patients and those treated with radiosurgery for a World Health Organization (WHO) grade I meningioma. 24


The risks and benefits of radiosurgery compared with observation are largely dependent on the natural history of meningiomas. Several natural history studies of asymptomatic meningiomas have been reported, demonstrating growth in only 11 to 37% of patients over more than 5 years follow-up. 25,​ 26,​ 27 These rates of quiescence may be comparable to the rates of tumor stability seen with some studies of SRS. However, the natural history of meningiomas is rarely tumor regression while tumor regression is seen frequently after SRS. In a recent survey in the United Kingdom, SRS was found to be the preferred approach for incidental but progressive meningiomas of the skull base. 28 To more clearly understand the tumor control benefits of SRS, future observational studies will be required with matched untreated controls.


7.4.2 Specific Tumor Locations


Although meningiomas of the skull base share a common proximity to critical neurovascular structures, the benefits and risks of radiosurgery may be unique to specific locations. The risks of cranial neuropathy documented in the previous section are clearly related to tumor location. In particular, proximity to the optic apparatus may be particular to certain meningiomas of the anterior cranial base. Likewise, the risk of brainstem toxicity is an important consideration for tumors of the posterior fossa. Therefore, it is critical to analyze the results of SRS, specific to these tumor locations to more clearly understand risk–benefit profile compared with observation or surgery (▶ Table 7.2). Furthermore, within various locations, some skull base meningiomas may be more amenable to surgery than others (lateral vs. middle or medial sphenoid wing, posterior vs. anterior or anterolateral foramen magnum). These factors should be considered in a patient-based and lesion-specific approach to management.

















Table 7.2 Factors favoring stereotactic radiosurgery and surgical resection of skull base meningiomas

Treatment modality


Stereotactic radiosurgery


Surgical resection


Preoperative factors


Older age


Greater medical comorbidities


Smaller tumor size


Distant from optic apparatus


Younger age


Few medical comorbidities


Larger tumor size


Compressing optic apparatus


Symptomatic mass effect


Despite these considerations, the radiobiology of tumors of different locations may be similar. Based on large, retrospective cohort data, several authors have suggested that meningiomas may be less likely to be atypical or anaplastic in skull base locations than over the convexity. 29,​ 30,​ 31 These data from retrospective studies may be limited by factors related to symptom development as small, slow-growing convexity meningiomas may go undetected due to their location. Specific tumor locations within the skull base, however, have not been reported to predispose to more aggressive phenotypes.


7.4.3 Primary, Residual, and Recurrent Disease


SRS for meningioma can be performed either for previously untreated tumors with radiological findings consistent with meningioma, with no histological confirmation, or for residual or recurrent disease. The comparative results of SRS for these different indications may be difficult to determine as most studies combine these groups in their analysis. However, in the European Gamma Knife Society, report on SRS for benign meningiomas, multivariate analyses found that radiological tumor control was better for those patients who had not undergone prior surgery (p < 0.001). 8 For some patients with tumor adherent to critical neurovascular structures, gross total resection may not be possible. In such instances, a paradigm of maximal operative resection followed by SRS of residual disease may be reasonable. Recurrent disease after resection of meningiomas may occur even after Simpson’s grade I resection. 22 In select cases of recurrence, without significant mass effect, SRS may be a viable alternate treatment option.


7.4.4 Atypical and Anaplastic Meningiomas


Atypical and anaplastic meningiomas likely represent a larger proportion of all meningiomas (> 20%) than previously recognized. 32 In a study of 140 meningiomas, 117 of the benign tumors had 5-year overall survival of 85% compared to 23 atypical or anaplastic tumors with 58%. 33 Aichholzer and colleagues studied 46 patients with skull base meningiomas with mean follow-up of 40 months found survival rates of 97.5% in benign tumors and 83% for malignant tumors. 34 SRS for these tumors is performed after resection and histological identification of a high-grade tumor. Milker-Zabel and colleagues found local tumor failure after SRS was significantly greater in WHO grade II tumors versus grade I (p < 0.002). 35 In this study, they also demonstrated that patients treated with SRS at recurrence had worse progression-free survival than patients treated with SRS immediately following resection or biopsy. Also, higher radiosurgical doses are certainly required to treat grade II and III meningiomas. In our review of 647 cases of grades II and III meningiomas, margin doses were typically 16 to 20 Gy for grade II and 18 to 22 Gy for grade III meningiomas. 36 Despite these higher doses, the median 5-year progression-free survival rates for grades II and III meningiomas were 59 and 13%, respectively. While SRS affords low rates of tumor control for WHO grades II and III meningiomas, radiosurgery does appear to represent a valuable tool in the multimodality management often required for patients harboring such tumors. Future prospective study will be required to compare the natural history of higher-grade meningiomas to those treated with SRS.


7.4.5 Case Example


A 63 year-old woman presented with gradually progressive changes in taste, decreased sensation on the left side of her face, and diminished hearing in the left ear. MRI showed a well-defined, extra-axial mass in the left cerebellopontine angle consistent with a meningioma. The tumor was 1.2 cm3 upon presentation in November 2008 (▶ Fig. 7.2a).



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Fig. 7.2 MRI of a cerebellopontine angle meningioma treated with Gamma Knife stereotactic radiosurgery (SRS). (a) Axial postcontrast T1-weighted MRI at presentation in November 2008 revealed a tumor volume of 1.2 cm3. (b) By July 2010, the tumor had grown to 3.8 cm3, at which point it was treated with Gamma Knife SRS (treatment isodose line denoted in yellow). (c) At last follow-up in April 2016, the tumor had diminished in size to 0.95 cm3.

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Jul 31, 2019 | Posted by in NEUROSURGERY | Comments Off on Role of Stereotactic Radiosurgery
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