Linear accelerator radiosurgery for cavernous sinus meningiomas.
Kimball MM Stereotact Funct Neurosurg. 2009;87(2):120-7. Epub 2009 Feb 27.

Department of Neurosurgery, University of Florida, Gainesville, FL 32610, USA.
OBJECTIVE: In this paper, the authors review the results of a single-center experience using linear accelerator (LINAC) radiosurgery for the treatment of cavernous sinus meningiomas. METHODS: This is a retrospective analysis with a median follow-up of 50 months. All patients were treated on an outpatient basis. Fifty-five patients were treated and 6 patients were lost to follow-up. Changes in preradiosurgery cranial nerve deficits and symptoms as well as actuarial local tumor control were evaluated. RESULTS: The actuarial local tumor control was 100% at 5 years and 98% at 10 years. One patient had enlargement of tumor. Sixty-five percent had improvement in preradiosurgery cranial nerve deficits, 31% were unchanged and 1 patient (3.5%) was worse. Only 1 patient developed a new neurologic deficit. CONCLUSIONS: This is the largest LINAC radiosurgery experience for cavernous sinus meningiomas reported to date. Radiosurgery appears to offer greatly superior tumor control and much lower morbidity than surgical resection of cavernous sinus meningiomas.
 

Long-term follow-up of meningiomas of the cavernous sinus after surgical treatment alone.
Sindou M, Wydh E, Jouanneau E, Nebbal M, Lieutaud T. J Neurosurg. 2007 Nov;107(5):937-44Department of Neurosurgery, Hopital Neurologique Pierre Wertheimer, University Claude-Bernard of Lyon, France.

OBJECT: The authors report on the long-term outcome in 100 consecutive patients with meningiomas arising from the cavernous sinus (CS) with compressive extension outside the CS. The treatment in all cases was surgery alone without adjuvant radiosurgery or radiotherapy. The aim of this study was to evaluate the percentage of patients in whom surgery alone was able to produce long-term tumor control. METHODS: All 100 patients harbored meningiomas with supra- and/or laterocavernous extension, and 27 had petroclival extension. Surgery was performed via frontopterionotemporal craniotomy associated with orbital and/or zygomatic osteotomy in 97 patients. Proximal control of the internal carotid artery at the foramen lacerum was undertaken in 65 patients; the paraclinoid carotid segment was exposed extradurally at the space made by the anterior clinoidectomy in 81 patients. For the petroclival tumor extension, a second-stage surgery was performed via a presigmoid-retrolabyrinthine or retrosigmoid approach in 13 and 14 patients, respectively. RESULTS: The mortality rate was 5% and two patients had severe hemiplegic or aphasic sequelae. The creation or aggravation of disorders in vision, ocular motility, or trigeminal function occurred in 19, 29, and 24% of patients respectively, with a significantly higher rate of complications when resection was performed inside the CS (p < 0.05). Gross-total removal of both the extra- and intracavernous portions was achieved in 12 patients (Group 1), removal of the extracavernous portions with only a partial resection of the intracavernous portion in 28 patients (Group 2), and removal only of the extracavernous portions was performed in 60 patients (Group 3). The follow-up period ranged from 3 to 20 years (mean 8.3 years). There was no tumor recurrence in Group 1. In the 83 surviving patients in Groups 2 and 3 combined, the tumor remnant did not regrow in 72 patients (86.7%); regrowth was noted in 11 (13.3%). CONCLUSIONS: The results suggest that there is no significant oncological benefit in performing surgery within the CS. Because entering the CS entails a significantly higher risk of complications, radiosurgical treatment should be reserved for remnants with secondary growth and clinical manifestations.

Long-term outcomes of Gamma Knife surgery for cavernous sinus meningioma.
Hasegawa T, Kida Y, Yoshimoto M, Koike J, Iizuka H, Ishii D. J Neurosurg. 2007 Oct;107(4):745-51.

Department of Neurosurgery, Gamma Knife Center, Komaki City Hospital, Komaki, Japan. h-toshi@komakihp.gr.jp

OBJECT: The aim of this study was to evaluate long-term outcomes, including tumor control and neurological function, in patients with cavernous sinus meningiomas treated using Gamma Knife surgery (GKS). METHODS: One hundred fifteen patients with cavernous sinus meningiomas, excluding atypical or malignant meningiomas, were treated with GKS between 1991 and 2003. Forty-nine patients (43%) underwent GKS as the initial treatment. The mean tumor volume was 14 cm3, and the mean maximum and margin doses applied to the tumor were 27 and 13 Gy, respectively. The median follow-up period was 62 months. During the follow-up, 111 patients were able to be evaluated with neuroimaging. RESULTS: The actuarial 5- and 10-year progression-free survival rates were 87 and 73%, respectively. Similarly, the actuarial 5- and 10-year focal tumor control rates were 94 and 92%, respectively. Regarding functional outcomes, 43 patients (46%) experienced some degree of improvement, 40 (43%) remained stable, and 11 (12%) had worse preexisting or newly developed symptoms. Patients who underwent GKS as the initial treatment experienced significant improvement of their symptoms (p = 0.006). CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment over the long term in selected patients with cavernous sinus meningiomas. Tumor progression is more likely to occur from the lesion margin outside the treatment volume. In small to medium-sized tumors, GKS is an excellent alternative to resection, preserving good neurological function. For relatively large-sized tumors, low-dose radiosurgery (< or = 12 Gy) is acceptable for the prevention of tumor progression

Evaluation of fractionated radiotherapy and gamma knife radiosurgery in cavernous sinus meningiomas: treatment strategy.
Metellus P, Regis J, Muracciole X, Fuentes S, Dufour H, Nanni I, Chinot O, Martin PM, Grisoli F. Neurosurgery. 2005 Nov;57(5):873-86; discussion 873-86.

Department of Neurosurgery, Timone Hospital, University of Aix-Marseille II, Marseille, France

OBJECTIVE: To investigate the respective role of fractionated radiotherapy (FR) and gamma knife stereotactic (GKS) radiosurgery in cavernous sinus meningioma (CSM) treatment. METHODS: The authors report the long-term follow-up of two populations of patients harboring CSMs treated either by FR (Group I, 38 patients) or GKS radiosurgery (Group II, 36 patients). There were 31 females with a mean age of 53 years in Group I and 29 females with a mean age of 51.2 years in Group II. In 20 patients (Group I) and 13 patients (Group II), FR and GKS radiosurgery were performed as an adjuvant treatment. In 18 patients (Group I) and in 23 patients (Group II), FR and GKS radiosurgery were performed as first line treatment. In our early experience with GKS radiosurgery (1992, date of gamma knife availability in the department), patients with tumors greater than 3 cm, showing close relationship with the optic apparatus (<3 mm) or skull base dural spreading, were treated by FR. Secondarily, with the advent of new devices and our growing experience, these criteria have evolved. RESULTS: The median follow-up period was 88.6 months (range, 42-168 mo) for Group I and 63.6 months (range, 48-92 mo) for Group II. According to Sekhar's classification, 26 (68.4%) patients were Grade III to IV in Group I and 10 (27.8%) patients in Group II (P < 0.05); 23 (60.5%) patients had extensive lesions in Group I and 7 (19.4%) patients in Group II (P < 0.05). Mean tumor volume was 13.5 cm in Group I and 5.2 cm in Group II (P < 0.05). Actuarial progression-free survival was 94.7% and 94.4% in Group I and II, respectively. Clinically, improvement was seen for 24 (63.2%) patients in Group I and for 21 (53.8%) patients in Group II (P > 0.05). Radiologically, 11 (29%, Group I) patients and 19 (Group II, 52.7%) patients showed tumor shrinkage (P = 0.04). Transient morbidity was 10.5% in Group I and 2.8% in Group II. Permanent morbidity was 2.6% in Group I and 0% in Group II. CONCLUSION: FR and GKS radiosurgery are safe and efficient techniques in treatment of CSMs, affording comparable satisfactory long-term tumor control. However, GKS radiosurgery provides better radiological response, is far more convenient, and fits into most patients lives much better than FR. Therefore, in the authors' opinion, GKS radiosurgery should be advocated in first intention for patients with CSMs, whereas conventional radiotherapy should be reserved for cases that are not amenable to this technique, thus making these two therapeutic modalities not alternative but complementary tools in CS meningioma treatment strategy.

Results of stereotactic radiosurgery for patients with imaging defined cavernous sinus meningiomas.
Pollock BE, Stafford SL. Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1427-31.
 

Department of Neurological Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. pollock.bruce@mayo.edu

The purpose of this study was to evaluate the efficacy and safety of stereotactic radiosurgery as primary management for patients with imaging defined cavernous sinus meningiomas. METHODS: Between 1992 and 2001, 49 patients had radiosurgery for dural-based masses of the cavernous sinus presumed to be meningiomas. The mean patient age was 55.5 years. The mean tumor volume was 10.2 mL; the mean tumor margin dose was 15.9 Gy. The mean follow-up was 58 months (range, 16-144 months). RESULTS: No tumor enlarged after radiosurgery. Twelve of 38 patients (26%) with preexisting diplopia or facial numbness/pain had improvement in cranial nerve function. Five patients (10%) had new (n = 3) or worsened (n = 2) trigeminal dysfunction; 2 of these patients (4%) underwent surgery at 20 and 25 months after radiosurgery despite no evidence of tumor progression. Neither patient improved after partial tumor resection. One patient (2%) developed an oculomotor nerve injury. One patient (2%) had an ischemic stroke related to occlusion of the cavernous segment of the internal carotid artery. Event-free survival was 98%, 85%, and 80% at 1, 3, and 7 years after radiosurgery, respectively. Univariate analysis of patient and dosimetric factors found no analyzed factor correlated with postradiosurgical morbidity. CONCLUSIONS: Radiosurgery was an effective primary management strategy for patients with an imaging defined cavernous sinus meningioma. Except in situations of symptomatic mass effect, unusual clinical presentation, or atypical imaging features, surgery to confirm the histologic diagnosis is unlikely to provide clinical benefit.

Introduction 

The management of patients with cavernous sinus meningiomas has changed significantly over the past 30 years. In the 1970s, many patients with cavernous sinus meningiomas went undiagnosed and their symptoms of diplopia or trigeminal dysfunction were attributed to other causes. However, the advent of magnetic resonance imaging (MRI) permitted the detection of even small tumors and surgical excision was frequently attempted using newly developed skull base techniques. Despite the enthusiasm attached to these improved surgical approaches, the morbidity of cavernous sinus surgery was not insignificant. Moreover, it was recognized that meningiomas could invade the adjacent neurovascular structures making complete resection impossible  In the late 1980s and early 1990s, stereotactic radiosurgery emerged as an alternative to surgical removal for patients with cavernous sinus meningiomas Since that time, several articles have documented that radiosurgery provides high tumor control rates with a low chance of cranial nerve injury for these patients. As a result, radiosurgery is now commonly considered the best treatment for the majority of patients with cavernous sinus meningiomas. However, between 26 and 82% of the patients in these series had undergone prior surgery and often had sustained iatrogenic neurologic morbidity. To better understand the outcomes after primary radiosurgical management of cavernous sinus meningiomas, we reviewed patients having radiosurgery for an imaging defined cavernous sinus meningioma.

Radiosurgery was performed with the Leksell Gamma Knife (Elekta Instruments, Norcross, GA). Magnetic resonance imaging was the imaging used for dose planning in all cases. Dose planning was performed to cover the enhancing tumor as conformally as possible without segmentation of the images to establish the desired target volume. As a result, determination of the ratio of prescription isodose volume to the target volume was not performed. The mean number of isocenters used was 12.1 (range, 6–24). Forty-four tumors (90%) were treated at the 50% isodose line, four tumors (8%) were treated at the 40% isodose line, and one tumor (2%) was treated at the 45% isodose line. The mean prescription isodose volume was 10.2 mL (range, 1.3–35.4 mL). Besides tumor volume, the maximum calculated dose to the adjacent optic nerves or chiasm was determined and frequently influenced dose prescription. The general goal was to keep the maximum dose to these structures below 10.0 Gy. The mean maximum dose to the optic apparatus was 7.7 Gy (range, 3.3–13.1 Gy). The mean dose to the tumor margin was 15.9 Gy (range, 12–20 Gy); the mean maximum radiation dose was 32.4 Gy (range, 24–40 Gy).

Four significant changes occurred in Spring 1997 that altered how patients having radiosurgery before 1997 (n = 21) were managed compared with patients having radiosurgery after 1997 (n = 28) despite being of similar age (58.0 years vs. 53.7 years, p = 0.30) and having similarly sized tumors (10.8 mL vs. 9.7 mL, p = 0.62). First, in March 1997, the Gamma Knife was upgraded from a model U to a model B. Second, the MRI sequence for dose planning was changed from two-dimensional 3 mm T1-weighted post-gadolinium spin echo imaging to three-dimensional 1-mm spoiled grass post-gadolinium sequences. This sequence provides more accurate stereotactic localization (15) and permits better visualization of adjacent structures such as the optic nerves and chiasm. Third, the average number of isocenters used increased from 10.6 to 13.2 (p = 0.01). Fourth, the mean tumor margin dose decreased form 17.5 Gy to 14.8 Gy (p < 0.001).

Discussion 

Over the past 5 years, the results of radiosurgery for more than 500 patients with cavernous sinus meningiomas have been reported. Although tumor margin doses ranged from 12 to 18 Gy in these series, the majority of patients received between 13 and 14 Gy. At follow-up times ranging from 19 to 49 months, the 5-year actuarial progression-free survival is between 93% and 100%. Complication rates have ranged from 3% to 10%, with most being cranial nerve deficits. In our series, no tumor enlarged at a mean follow-up interval of 58 months; the mean tumor margin dose was 15.9 Gy. The most common complication was new or worsened trigeminal dysfunction (10%). One patient (2%) developed an oculomotor nerve injury. One patient (2%) had an ischemic stroke related to occlusion of the cavernous segment of the internal carotid artery. Event-free survival was 98%, 85%, and 80% at 1, 3, and 7 years after radiosurgery, respectively. Moreover, 12 of 38 patients (26%) with preexisting diplopia or facial numbness/pain had improvement in cranial nerve function. Consequently, unless the patient has a large tumor with extension into the middle or posterior fossa and symptomatic mass effect, radiosurgery can be safely and effectively performed as the primary treatment for patients with cavernous sinus meningiomas.

Several points must be remembered when discussing the results of cavernous sinus meningioma radiosurgery. First, meningioma recurrence or progression may occur decades after surgical resection or radiation therapy. Therefore, studies with a minimum follow-up of 10 years and more are needed to adequately assess this technique. Although some studies have included patients with follow-up more than 10 years after meningioma radiosurgery, a recent study has reported tumor control for 285 consecutive patients with a having radiosurgery for benign intracranial tumors between 1987 and 1992. The median follow-up in this series was 10 years. Seventy-nine of 85 meningioma patients (93%) had either smaller (n = 45) or stable (n = 34) tumors. The mean tumor margin dose for these patients was 16.5 Gy. Consequently, continued diligent follow-up of a large number of patients receiving tumor margin doses of 14 Gy or less is still needed. Second, late complications after radiosurgery are now being described and include injury to large intracranial arteries. At our center, we have documented internal carotid artery stenosis or occlusion in 4 patients (meningiomas, n = 2; pituitary adenomas, n = 2) after radiosurgery. Two patients had cavernous sinus meningiomas (1 previously operated and therefore was not included in this series): both patients suffered permanent neurologic deficits from related ischemic events. Roche et al. reported a patient who developed a temporary central facial palsy 14 months after radiosurgery of a cavernous sinus meningioma and was discovered to have occlusion of her intracavernous internal carotid artery. The estimated dose to the affected artery was 36 Gy. Based on these reports and our own experience, we now minimize the radiation dose to major arteries whenever possible. It is possible that Linac-based radiosurgery could have a lower rate of neurovascular complications compared to Gamma Knife radiosurgery secondary to greater dose homogeneity and lower maximum radiation doses within the dose plan. However, only a few reports have focused on Linac-based radiosurgery of cavernous sinus meningiomas, whereas many more articles have detailed the results of gamma knife radiosurgery of cavernous sinus meningiomas ). Therefore, a fair comparison of neurovascular complications between the different techniques will only be possible after a large number of patients are followed for extended periods after Linac-based cavernous sinus meningioma radiosurgery. Third, as more patients undergo radiosurgery based on neuroimaging alone without histologic conformation, a small percentage of patients will actually have other tumor types or potentially nonneoplastic lesions such as sarcoid. Although errors of this sort cannot be completely eliminated, insistence on a tissue based diagnosis remains mandatory for patients with unusual presenting symptoms or neuroimaging inconsistent with a benign, slow-growing tumor.

It is not uncommon that meningiomas involving the cavernous sinus can extend upward and compress the optic nerves or chiasm. Although none of our patients had visual loss before radiosurgery, a brief discussion of this subject as it relates to the management of patients with skull base meningiomas is worthwhile. Surgical excision is the accepted treatment for meningioma patients who present with visual loss secondary to compression of the optic apparatus. Resection provides rapid decompression of the optic nerves, and improvement in visual function is common. However, tumor removal alone frequently does not provide long-term protection against tumor regrowth. Klink et al. noted that 18 of 29 patients (62%) undergoing “nonradical” surgery of parasellar and cavernous sinus meningiomas had tumor recurrence/progression within a mean follow-up interval of 13.6 years. Eight of nine patients (89%) followed more than 15 years showed tumor progression. Therefore, we typically advocate surgical resection followed by planned, postoperative radiosurgery or radiation therapy for these patients. It is important not to confuse patients with visual loss from compression by skull base meningiomas and patients having optic nerve sheath meningiomas. For patients with optic nerve sheath meningiomas, fractionated radiation therapy is being increasingly recognized as an alternative to surgical excision. Radiation therapy has been demonstrated as a method to not only preserve but also potentially improve visual function for patients with optic nerve sheath meningiomas.

Conclusions 

Radiosurgery was an effective primary management strategy for patients with an imaging defined cavernous sinus meningioma. Except in situations of symptomatic mass effect, unusual clinical presentation, or atypical imaging features, there is little benefit in performing surgery to confirm the histologic diagnosis

 

Gamma knife radiosurgery for tumors involving the cavernous sinus.
Liu AL, Wang C, Sun S, Wang M, Liu P. Stereotact Funct Neurosurg. 2005;83(1):45-51. Epub 2005 Apr 28.
 

Gamma Knife Center, Beijing Neurosurgical Institute, Beijing, People's Republic of China. alilius@public3.bta.net.cn

OBJECTIVE: To study the features of diagnosis and radiosurgery of tumors involving the cavernous sinus. METHODS: From December 1994 to the end of 2000, 175 patients with cavernous sinus lesions were treated by Leksell gamma knife (GK) in our Institute. Ninety patients (51.4%) had had open surgery previously. Our experience of treating cavernous sinus tumors by GK was analyzed retrospectively. RESULTS: A Hundred and forty-four (82.3%) patients were followed from 1 to 84 months (median 32.5 months); total tumor control rate was 94%. Surgery was performed after radiosurgery in 3 patients because of tumor enlargement. Metastatic tumor in the cavernous sinus was highly sensitive to irradiation. These lesions shrunk markedly on MRI 2-3 months after GK surgery. The median survival time was 12.2 months, and patients died of noncavernous sinus lesions. CONCLUSION: With high tumor control rate and few complications, GK surgery could become a main option for small benign or residual tumors involving the cavernous sinus. It is also very useful as part of comprehensive therapy for metastatic tumors in the cavernous sinus.