Tumors involving the foramen magnum are rare, Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas.

Transcription

1 J Neurosurg 117: , 2012 Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas Clinical article Georgios Zenonos, M.D., 1 Douglas Kondziolka, M.D., 1,3 John C. Flickinger, M.D., 1,2 Paul Gardner, M.D., 1 and L. Dade Lunsford, M.D. 1,3 Departments of 1 Neurological Surgery and 2 Radiation Oncology, and 3 Center for Image-Guided Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Object. Microsurgical management of foramen magnum meningiomas (FMMs) can be associated with significant morbidity and mortality. Stereotactic radiosurgery may be an efficient and safe alternative treatment modality for such tumors. The object of this study was to increase the documented experience with Gamma Knife surgery (GKS) for FMMs and to delineate its role in an overall management paradigm. Methods. The authors report on their experience with 24 patients harboring FMMs managed with GKS. Twelve patients had primary symptomatic tumors, 5 had asymptomatic but enlarging primary tumors, and 7 had recurrent or residual tumors after a prior surgery. Results. Follow-up clinical and imaging data were available in 21 patients at a median follow-up of 47 months (range months). Ten patients had measurable tumor regression, which was defined as an overall volume reduction > 25%. Eleven patients had no further tumor growth. Two patients died as a result of advanced comorbidities before follow-up imaging. One patient was living 8 years after GKS but had no clinical evaluation. Ten of 17 symptomatic patients with at least 6 months of follow-up had symptom improvement, and 7 remained clinically stable. Smaller tumors were more likely to regress. No patient suffered an adverse radiation effect after radiosurgery. Conclusions. Gamma Knife surgery was a safe management strategy for small, minimally symptomatic, or growing FMMs as well as for residual tumors following conservative microsurgical removal. ( Key Words meningioma foramen magnum case series Gamma Knife surgery outcome oncology stereotactic radiosurgery Tumors involving the foramen magnum are rare, constituting no more than 1% of all intracranial tumors. 14,37 Despite their benign nature, FMMs can be technically challenging to resect, as their usual anterolateral location places them close to osteoarticular structures, the nervous system, and vascular structures that pose potential morbidity for the patient. 1 5,7,10,13,14,17 19,21,24 27,29 32,37 Stereotactic radiosurgery has been proposed as an effective tool that could supplement and complement microsurgery in the treatment of these lesions. 6,8,9,15,23,28,33 Although 3 small studies have demonstrated encouraging results without morbidity or death, 9,23,33 additional experience is needed. In the current analysis, we review our experience over the last 21 years with the use of GKS in the care of FMMs. Based on this experience and a review of previously published literature, we propose an integrated treatment paradigm. Abbreviations used in this paper: FMM = foramen magnum meningioma; GKS = Gamma Knife surgery. Methods This retrospective analysis was performed with approval from the University of Pittsburgh institutional review board. Medical records and imaging results were prospectively collected, and physicians who had not participated in the care of the patients independently retrospectively reviewed the collected data. Clinical follow-up data were supplemented with a telephone interview, conducted by one of the authors (G.Z.) at the time that this report was prepared, as well as with outcome data provided by current physicians or family members. For survival statistics, the social security death index was used at the time that the current paper was prepared to determine whether patients were still living or to learn the exact date of death if they had already died. Review of the Literature A review of the literature in PubMed was performed using the MeSH terms Gamma knife radiosurgery, 864 J Neurosurg / Volume 117 / November 2012

2 Gamma Knife surgery for foramen magnum meningioma Meningioma, Foramen Magnum, Management, Surgery, Assessment, patient outcomes. The reference lists of reviewed clinical articles were further screened for available data not included in our initial search. Statistical Analysis Microsoft Excel 2010 (Microsoft Corp.) and SPSS version 16.0 (SPSS, Inc.) were used for data management, descriptive statistics, and statistical comparisons. A 2-tailed Student t-test was used to compare the means of interval data. The alpha criterion of 0.05 was chosen for statistical significance. Results Diagnosis of Meningioma The diagnosis of meningioma was based on either tissue pathology obtained at a prior operation (7 patients) or characteristic imaging findings of a dura-based mass located at the foramen magnum (17 patients). These latter findings included uniform contrast enhancement on CT or MRI, often associated with signal characteristics of intratumoral calcification. Patients were included in this study if their tumor was confined to the following anatomical sites: 1) anteriorly, from the lower third of the clivus and upper edge of the body of C-2; 2) laterally, by the jugular tubercles and superior aspect of the C-2 lamina; and 3) posteriorly, by the anterior edge of the squamous occipital bone and C-2 spinous process, according to previous reports. 11,13 Patient Population Between January 1990 and December 2007 at our center, 24 patients (17 women and 7 men) underwent GKS for meningiomas involving the foramen magnum. The median patient age at presentation was 69 years (range years). A detailed description of these patients is featured in Table 1, and patient signs and symptoms are provided in Table 2. Twelve patients presented neurological signs and symptoms that gradually progressed over intervals of time ranging from several months to several years. All 7 patients who had undergone initial microsurgical approaches had one or more postoperative deficits, including hydrocephalus (2 patients), ataxia (1 patient), prolonged coma (1 patient), and CSF leakage (1 patient). Five patients had worsening lower cranial nerve deficits after an initial surgery, and myelopathy developed in 1 patient. Five patients had a history of multiple intracranial tumors. One patient had an acoustic neuroma, 1 had a pituitary adenoma, and 3 had multiple intracranial meningiomas. Indications for Radiosurgery Gamma knife surgery was performed in patients with residual (2 patients) or recurrent (5 patients) lesions after previous resections. Twelve had newly diagnosed symptomatic tumors. Five patients underwent GKS because of progressive tumor growth during observation (Table 1). Radiosurgery was recommended to patients J Neurosurg / Volume 117 / November 2012 who had tumor progression despite prior surgery and to patients whose age or associated medical conditions significantly increased the risk of major postoperative morbidity. Contraindications to radiosurgery included larger tumor volumes (average diameter > 35 mm) and disabling symptomatic tumors causing brainstem compression. In such patients, an initial surgical decompression was recommended. For patients with residual or recurrent tumors after an initial surgery, the average time between microsurgery and GKS was 85 months (median 35 months, range months). Radiosurgical Technique Radiosurgery was performed in a single session after administering a local anesthetic supplemented by mild intravenous conscious sedation (midazolam and fentanyl) as necessary. After applying the Leksell stereotactic frame, high-resolution volume-acquisition MR images were obtained. Before 1991, or in patients with contraindications for MRI, we performed radiosurgery using stereotactic CT guidance. Image-integrated isodose plans were created to enclose the tumor borders (Fig. 1). Given the irregular geometry of the tumors, multiple isocenters were often used (average 6.7, range 2 14). A radiosurgery team consisting of a neurosurgeon, a radiation oncologist, and a medical physicist selected maximum and margin radiation doses. Tumor margin isodose curves of 50% were generally used, delivering a mean 13 Gy of radiation to the tumor margin (median dose 13 Gy, range Gy). The mean maximum dose was 26.5 Gy (median 26 Gy, range Gy), and the mean tumor volume was 5.7 cm 3 (median 4.1 cm 3, range cm 3 ). Dose prescription was individually determined based on the tumor volume and the goal of keeping spinal cord and lower brainstem doses at 8 12 Gy. Details regarding specific Gamma Knife models (U, B, C, and Perfexion, Elekta Instruments, Inc.) and radiosurgical procedure details for each case are listed in Table 1. Immediately after radiosurgery, all patients were given a single intravenous dose of methylprednisolone. All patients not hospitalized for additional medical comorbidity care were discharged within 24 hours after GKS. Clinical Response Clinical outcome analysis was based on the 23 patients for whom we had follow-up data. The median clinical follow-up to evaluate symptom progression was 62 months. Overall, the last clinical follow-up constituted a visit to the neurosurgery outpatient offices for 10 patients, correspondence with the patient (follow-up telephone calls or letters) in 5 cases, correspondence with other physicians caring for the patient in 6, and clinical evaluation while in the hospital in the 2 who died shortly after GKS. The mean follow-up from GKS to the last time that patients were censored with the social security death index was 106 months (median 107 months; Table 1). Overall, among 21 patients with at least 6 months of clinical follow-up after GKS, 10 patients had improvement of at least 1 of their symptoms. Eleven patients remained clinically stable. No asymptomatic patient treated 865

3 G. Zenonos et al. TABLE 1: Demographic, radiosurgical procedure, and imaging outcome details* Case No. Age (yrs), Sex Prior Treatment Reason For GKS Lesion Vol (cm 3 ) Max Dose (Gy) Margin Dose (Gy)/Isodose (%) No. of Isocenters Used Collimator (mm) Leksell GKS Model Period From GKS to Last Imaging FU (mos) Outcome on FU Imaging Alive or Dead (mos of FU) 1 70, F no incidental finding / , 2 14 B 66 lesion regressed D (101) 2 69, F GTR, STR adjuvant therapy / , 4 8 U 10 lesion stable A (210) 3 74, F no incidental finding / B 15 lesion regressed D (42) 4 80, F GTR recurrence / , 6 8 B 7 lesion stable D (112) 5 83, F no symptomatic / C NA patient died after 3 mos D (3) 6 44, F no incidental finding / C NA patient lost to FU A (92) 7 62, M GTR, XRT recurrence / , 2 14, 1 18 U 26 lesion stable A (134) 8 77, F no symptomatic / (8 sectors), 3 4 (8 sectors) Perfexion 6 lesion regressed A (42) 9 83, F no symptomatic / C 7 lesion stable D (107) 10 80, M GTR recurrence / C NA patient died after 2 wks D (0.4) 11 83, F no symptomatic / , 2 18 U 44 lesion stable D (145) 12 53, F no symptomatic / , 8 8 C 3 lesion stable A (63) 13 58, F no symptomatic / , 4 8 B 86 lesion regressed A (156) 14 69, M no incidental finding / , 5 8 B 49 lesion regressed A (147) 15 77, F STR recurrence / , 3 8 C 36 lesion stable D (107) 16 67, M no symptomatic / , 4 4 C 90 lesion stable A (100) 17 82, M STR recurrence / U 73 lesion stable D (70) 18 39, F STR adjuvant therapy / , 5 8 B 82 lesion regressed A (186) 19 35, F no symptomatic / , 2 4 B 128 lesion regressed A (137) 20 67, M no symptomatic / C 6 lesion stable D (96) 21 61, F no symptomatic / , 1 14 B 61 lesion stable A (163) 22 72, F no symptomatic / , 4 8 C 55 lesion regressed A 117) 23 55, F no incidental finding / , 3 14 C 78 regressed A (116) 24 65, M no symptomatic / C 47 regressed A (88) * Location of FMM in relation to the dentate ligament was anterior in all cases except for Case 6, in which it was posterior. Abbreviations: A = alive; D = dead; FU = follow-up; GTR = gross-total resection; NA = not available; STR = subtotal resection; XRT = fractionated radiation therapy. 866 J Neurosurg / Volume 117 / November 2012

4 Gamma Knife surgery for foramen magnum meningioma TABLE 2: Progression of symptoms after GKS in 24 patients* Symptom (total no. of patients for group) No. (%) Immediately After GKS (30 days) 6 Mos After GKS Pre-GKS Worse Same Better Worse Same Better patients w/ primary disease (17) headaches/neck pain 8 (47) 0 8 (47) (13) 6 (40) lower CN deficits 3 (18) 0 3 (18) (7) 1 (7) myelopathy 6 (35) 0 6 (35) (13) 3 (20) other 3 (18) 0 3 (18) (7) 1 (7) none 5 (29) patients w/ residual/recurrent disease (7) headaches/neck pain 1 (14) 0 1 (14) (17) lower CN deficits 5 (71) 0 5 (71) (67) 0 myelopathy 3 (42) 0 3 (42) (33) 1 (17) other 1 (14) 0 1 (14) (17) 0 none all patients (24) headaches/neck pain 9 (38) 0 9 (38) (10) 7 (33) lower CN deficits 8 (33) 0 8 (33) (24) 1 (5) myelopathy 9 (38) 0 9 (38) (19) 4 (19) other 4 (17) 0 4 (17) (10) 1 (5) none 5 (21) * Some patients presented with more than 1 symptom. Percentages refer to the total percentage of patients in each of the 3 groups (primary disease, residual/recurrent, and total). Abbreviation: CN = cranial nerve. Two patients died before the 6-month follow-up time point, and 1 patient was lost to follow-up. These 3 patients are not included in this column. Therefore, the numbers and percentages of patients in each group are reduced accordingly in this column. For the primary disease group, the number of patients is 15; for the recurrent or residual disease group, the number of patients is 6; and the total number of patients is 21. Other symptoms included vertigo, noncardiogenic syncopal episodes, and ataxia. for a growing tumor had any new neurological signs or symptoms after radiosurgery. A detailed analysis of symptom progression in this series of patients is provided in Table 2 and Fig. 2. Among the 17 symptomatic patients with at least 6 months of follow-up, 10 had amelioration of at least 1 symptom, and 9 had improvement in all symptoms. Patients whose condition improved presented, on average, with smaller tumors (mean 3.7 ± 3.2 cm 3, mean ± SD) than those who remained neurologically stable (mean 9.3 ± 3.8 cm 3 ). This difference was statistically significant (p = ). An analysis of symptom progression in relation to initial tumor size is presented in Fig. 2. The mean tumor volume in symptomatic patients was 6.34 ± 4.44 cm 3, whereas in asymptomatic patients it was 3.2 ± 2.5 cm 3. As evident in Table 2, the most common presenting symptom in primarily treated patients was headache or neck pain (8 of 17 patients), followed by myelopathy (6 of 17 patients). Conversely, lower cranial deficits were the most common symptom in residual or recurrent tumor cases (5 of 7 patients). The most common symptom to resolve after GKS was headache or neck pain (7 of 9 patients), followed by myelopathy (4 of 9 patients). Only 1 of 8 patients with lower cranial deficits experienced improvement after GKS. J Neurosurg / Volume 117 / November 2012 Imaging Response Follow-up imaging studies were requested every 6 months for the first 2 years, and then at 4, 8, and 12 years after radiosurgery. Imaging was performed at other intervals if new neurological signs or symptoms were detected. The median imaging follow-up was 47 months (range months). Three patients did not have follow-up imaging data: 2 patients died of intercurrent illness within 6 months of radiosurgery, and 1 patient was lost to followup. Six patients had their last imaging study < 1 year after GKS, 1 between 1 and 2 years, 6 between 2 and 5 years, and 8 after 5 years (Tables 1 and 3). Tumor progression, stability, or regression was based on a review of imaging studies and the measurement of tumor diameters. Volumes were determined by multiplying measurements in 3 planes and then dividing by 2. Tumor regression was defined as an overall tumor volume reduction > 25%. Tumor control was maintained in all 21 evaluable patients. Ten patients had tumor regression, and all had stable lesion volumes at a median of 47 months after GKS (range months). Generally, as the duration of follow-up increased, tumor regression was more likely to be detected. A detailed analysis of the radiographic response of tumors according to the time to the last imaging fol- 867

5 G. Zenonos et al. Fig. 1. Axial and sagittal MR images with contrast showing a left FMM. Images without (A, 1 6) and with (B, 1 6) the radiosurgical dose plan are shown. This tumor received a margin dose of 11.5 Gy and a maximum dose of 23 Gy. low-up is provided in Table 3. Tumor progression was not documented in any evaluable patient. In a comparison of patients whose tumors had regressed versus those with stable tumors at a minimum of 2 years after radiosurgery, we were unable to detect any difference in the maximum radiation doses used (27.3 ± 2.5 vs 28.2 ± 3.9 Gy, respectively, p = 0.605), mean tumor margin doses used (13.6 ± 1.3 vs 13 ± 0.9 Gy, respectively, p = 0.327), and mean number of isocenters used (7.1 ± 2.3 vs 6.5 ± 4 isocenters, respectively, p = 0.719). However, the mean tumor volume at presentation was significantly smaller in patients whose tumors had regressed by 2 years (patients with tumor regression, 4.1 ± 2.2 cm 3 ; patients with stable tumors, 9.4 ± 4.8 cm 3 ; p = 0.018; Fig. 2). All 5 asymptomatic patients with previously untreated but growing tumors had long-term tumor regression. One of the patients with residual tumor after microsurgery had tumor regression, and 1 remained stable. Patient Survival Eleven patients still living at the time of the last follow-up (46% of all patients) were on average 11 years away from radiosurgery (median 11 years, range years). Average age at the time of GKS in these patients was 59 years (median 62 years, range years), and average age at the time of this writing was 78 years (median 74 years, range years). Of note, the 1 patient lost to follow-up was still living 8 years after GKS according to the social security death index. Ten of the 24 patients died during the follow-up interval, that is, the period from treatment to the writing of this paper. The mean age at death in these patients was J Neurosurg / Volume 117 / November 2012

6 Gamma Knife surgery for foramen magnum meningioma TABLE 3: Radiographic tumor progression in relation to the time to the last follow-up imaging study Last FU Imaging Study No. of Patients Stable Tumor No. (% of FU group) Tumor Regression Tumor Progression Fig. 2. Bar graph demonstrating radiographic tumor progression and symptom progression in patients with at least 6 months of follow-up imaging data in relation to the initial tumor size. Tumor regression was defined as > 25% reduction in tumor volume. The average follow-up interval was similar in the 3 groups (< 3 cm 3 group: 52 months, 3 6 cm 3 group: 45 months, > 6 cm 3 group: 47 months). Asymptomatic lesions were not included in the symptom progression analysis. Dark gray bars represent tumor regression; light gray bars, improved symptoms. years (median 85 years, range years). The mean age at the time of GKS was 79 years (median 81 years, range years), and the mean survival after GKS treatment was 6.5 years (median 8 years, range 20 days 12 years). Of note, 2 patients died at 20 days and 3 months, respectively, after GKS. Both of these patients were severely disabled, nonambulatory octogenarians with multiple comorbidities and initially hospitalized for profound malnutrition (> 40% below ideal body weight) due to a difficulty in managing secretions. Both patients had multiple lower cranial nerve deficits, with 1 of the 2 having an absent gag reflex bilaterally. The other patient also suffered from advanced Parkinson disease. Despite significant brainstem compression, it was considered highly unlikely that they would survive surgical decompression. The families opted for conservative care, and GKS was recommended as the only reasonable alternative. Excluding these 2 patients, average survival after GKS was 8.5 years (median 9 years, range years), with a mean age of 86 years at the time of death (median 87 years, range years). The exact cause of death in the remaining 8 patients is unknown. Notably, all deceased patients had outlived their life expectancies calculated at birth according to United Nations World Population Prospects (75.6 years for men and 80.8 years for women). 34 On average, these patients were 6.4 years beyond their life expectancy at the time of death. Adverse Effects Although 2 patients died early in the follow-up as a result of advanced comorbidities, none of the patients experienced early or late adverse radiation effects. More specifically, we documented no adverse T2 changes and no patients requiring the additional use of corticosteroids. J Neurosurg / Volume 117 / November 2012 none total 3 primary 1 residual/recurrent 2 <24 mos total 7 5 (71) 2 (28) 0 primary residual/recurrent mos total 6 3 (50) 3 (50) 0 primary residual/recurrent >60 mos total 8 3 (38) 5 (62) 0 primary residual/recurrent Discussion Meningiomas of the foramen magnum remain challenging clinical entities. Their rarity adds to the complexity of their management, as most of the information regarding their treatment comes from case studies with limited numbers of patients and spanning many decades. 1 8,10,13 20,24 32,35,36 Microsurgical removal is considered definitive and the standard of care. However, even at institutions with highly experienced personnel, surgery can be associated with significant morbidity, mortality, and long-term recurrence. 1 8,10,13,15 20,24 32,35,36 To date, limited evidence suggests radiosurgery as an alternative tool that leads to tumor control with a favorable safety profile in selected cases in which surgery is either contraindicated or declined by the patient. 9,23,33 Based on available microsurgical and radiosurgical data, we propose an integrated treatment paradigm that incorporates radiosurgery in the armamentarium of neurosurgeons who care for patients with these lesions. Review of Microsurgical Literature Over the past century, outcomes of microsurgical removal of FMMs have improved. Yaşargil and Curcic 36 reviewed the published outcomes of 114 patients who had undergone surgery between 1924 and Overall mortality was 13%, although it was as high as 45% in some series. Furthermore, classifying survivors in a 3-tiered system, they found that 69% of treated patients had a good outcome, 8% had a fair outcome, and 10% had a poor outcome. 36 During the past 20 years up to 2011, approximately 400 surgically treated cases of FMM have been documented in the literature. 1 8,10,13,16 20,24 32,35 The various surgical approaches have included the posterolateral, far lateral (either retro- or transcondylar), 4,5,17,25,28 anterolateral or extreme lateral, 3,30,32 transoral and transclival approach, 10,19 as well as the lateral and posterior suboccipital 869

7 G. Zenonos et al. approaches. 5,19,31 Many authors have described variations in these approaches, such as the transposition of vertebral arteries, 2,3,17,26,28,30,32 resection of the jugular tubercle, 3,5,32 or partial mastoidectomy. 3,30,32 Overall, advances in microneurosurgical techniques over the last 2 decades have resulted in an average mortality rate that has decreased to 6.2% (range 0% 25%), neurological improvement in 70% 100% of patients, neurological stability in 2.5% 20% of patients, and neurological decline in 7.5% 10% of patients in published series. 1 8,10,13,15 19,24 32,35 Major morbidity has varied anywhere from 0% to 60% of patients and is mainly associated with lower cranial nerve deficits leading to aspiration and pneumonia, CSF leaks, myelopathy, infection, and hydrocephalus. 4 24,26,27,29,36,37 Infections and CSF leaks are more commonly reported with the transoral transclival approach. 10,19 The far lateral approach 4,5,17,25,28 seems to be associated with decreased rates of lower cranial nerve deficits and overall morbidity, as compared with rates in the extreme lateral and lateral suboccipital approaches. 3,5,19,30 32 Factors associated with a more challenging surgical procedure and higher procedural morbidity include an anterior tumor location, 13,31 tumor extension into the lower clivus, 16 small tumor size (smaller lesions can be more difficult to resect because of the limited surgical corridor), tumor invasiveness, extradural extension, 13 vertebral artery encasement, 14 absence of an arachnoidal sheath, 4,12,36 and adherences in recurrent lesions. 3,4,31,32 Complete resection rates have varied from 0% to 100%, while recurrence rates have varied from 0% to 33% in surgical series published in the last 2 decades. 1 5,7,10, 13,17 19,24 27,29 32 The reason behind this wide variability lies not only in the heterogeneity of the tumors, but also in the aggressiveness with which these lesions were approached. Some authors have attempted complete resections even at the cost of potential morbidity, 2 whereas others argue for a more conservative approach to minimize complications. 4,13 Factors associated with incomplete resections and recurrences include encasement of the vertebral arteries, 31 tumor invasiveness (as evident from the extradural component of the tumors), 13,22 and adherences to vital structures, especially in recurrent lesions. 2,31,32 Review of Radiosurgery Studies in the Literature At the time of this review, we found only 3 small studies specifically addressing the management of FMMs with radiosurgery via Gamma Knife 23,33 or Cyberknife 9 technology. Permanent morbidity or mortality after radiosurgery was not observed in any of these studies, and nearly all patients had long-term tumor control. 9,23,33 Muthukumar et al. 23 described our early experience in In that study, 5 patients with FMMs were treated with GKS; 3 had newly diagnosed tumors, and 2 had recurrent tumors. Average age at the time of radiosurgery was 80 years (range years). After a mean followup of 36 months (range months), 1 patient died of an intercurrent illness, but all others remained stable. Follow-up imaging studies revealed a reduction in tumor volume in 1 patient, and no further lesion growth in the other 4 patients. Starke et al. 33 recently reported their experience in 5 patients with FMMs. One lesion increased in size following GKS, requiring a second treatment, which resulted in size stabilization. By the last followup, all meningiomas demonstrated either no growth (4 patients) or a reduction in size (1 patient). No patients experienced any postradiotherapy complications. Using the Cyberknife, Cheshier et al. 9 treated 9 patients with tumors near the foramen magnum. Of these 9 tumors, 6 regressed, 2 remained stable, and 1 increased in size during follow-up. Indications for Radiosurgery After Reviewing the Literature and Results of the Current Study The most important finding in the present study is that all patients with available follow-up imaging had either tumor regression or tumor control at a median follow-up of 47 months. No patient experienced any permanent morbidity directly attributed to GKS treatment. All patients with at least 6 months of clinical follow-up either had improvement of their symptoms or remained clinically stable at their last follow-up. These favorable results concur with outcomes in the 3 radiosurgery studies described above 9,23,33 and further validate the value of radiosurgery in managing these lesions. However, we certainly believe that further long-term follow-up is necessary in patients who undergo radiosurgery. We observed that smaller tumors were more likely to regress and that patients with smaller tumors were more likely to have symptom improvement. Patients with growing but as yet asymptomatic tumors had excellent lesion control and no long-term treatment-related morbidity. These results seem to support a relatively aggressive approach using GKS for newly diagnosed small asymptomatic or nondisabling symptomatic tumors. Given the suggested favorable safety profile of GKS, as well as the technical challenges that accompany the surgical excision of small FMMs, we recommend close follow-up for stable asymptomatic lesions and early GKS over surgical excision once the lesions are found to progress on imaging. Furthermore, we recommend early GKS over surgical excision for small minimally symptomatic lesions. In patients with significant surgical comorbidities or an older age or in patients who decline surgery, GKS can be seen as an alternative to surgery for nondisabling symptomatic lesions without significant brainstem compression. Based on our limited experience, we believe that severely disabled or malnourished patients, usually those with larger tumors causing significant brainstem compression, do not benefit from GKS. Surgical decompression is preferable for disabling symptomatic lesions causing significant brainstem compression if the procedure seems feasible. In our opinion, the goal of microsurgery should be to avoid morbidity while achieving the maximal resection that can be safely performed, and GKS can be used for any residual tumor. Furthermore, given the increased surgical risk associated with the microsurgical removal of recurrent tumors, we advocate GKS for recurrent tumors without significant brainstem compression. Unfortunately, because of their slow-growing nature, FMMs are not often recognized until they have already grown significantly, at which point patients have signs or 870 J Neurosurg / Volume 117 / November 2012

8 Gamma Knife surgery for foramen magnum meningioma symptoms of mass effect, cranial neuropathy, or myelopathy. 1,2,4,6 8,15,16,19,20,25,28,36 For this reason, microsurgery, which currently represents the standard of care, will likely be the treatment of choice in the majority of patients. It is possible, however, that the wider availability of MRI may enable earlier diagnosis of FMM, and thus primary treatment with GKS may become more feasible. The inferior location of such tumors in the past has posed a potential technical difficulty for radiosurgery. The Leksell Gamma Knife Perfexion unit circumvents this limitation. Definition of Goals and Limitations of the Current Study The goal in the current study was not to directly compare radiosurgery and microsurgery, but rather to propose an integrated management paradigm that utilizes radiosurgery as a complementary modality for treating the spectrum of tumors defined as FMMs. In this spectrum, since the more common lesions are large tumors with profound brainstem compression, radiosurgery is more likely to supplement microsurgery and observation rather than replace them. This retrospective study has a number of limitations. As in most retrospective studies, a potential selection bias should be considered. For example, patients referred for radiosurgery who had growing tumors but minimal symptoms may have had lower-grade tumors, which were less likely to lead to recurrences. Moreover, because of a referral bias, lesions treated with radiosurgery in this report are probably different from the average surgically treated FMM, and thus this study should not be perceived as a direct comparison of radiosurgery with microsurgery. In addition, although this study currently represents the largest FMM radiosurgery series, the number of cases is still relatively small, and therefore the study is probably underpowered for extensive statistical analyses. Furthermore, even though we elected to present all of our cases for transparency and completeness, not all cases had significant long-term follow-up. For all of the above reasons, the proposed management paradigm reflects our personal understanding and recommendations after interpreting the presented information, rather than an evidence-based management algorithm that is substantiated by robust data. Naturally, given the variety of experiences, preferences, and biases, interpretation of the same data could lead to different conclusions and recommendations by different readers. Our proposed management paradigm has yet to be validated with additional cases or compared with other proposed paradigms to follow. We generally prefer radiosurgery to standard or hypofractionated radiotherapy for FMMs, as they are extraaxial tumors in critical locations with a radiobiological response profile consistent with slow-growing tumors, for which fractionation may have a lesser response. And although stereotactic radiosurgery is our personal preference, there are no comparison studies of fractionated radiotherapy. Furthermore, it is unclear whether a specific tumor volume, patient age, performance status, or tumor histology (for example, WHO Grade I, II, or III) would favor one modality over the other, although we recommend combined radiosurgery and radiotherapy in the setting of malignant meningiomas. Proposed Management Algorithm Despite advances in microneurosurgical techniques, the surgical removal of FMMs continues to be a challenge. The present study provides additional evidence that GKS is an effective and safe treatment alternative that could supplement and complement microsurgery and Fig. 3. Proposed management algorithm for FMMs. J Neurosurg / Volume 117 / November

9 G. Zenonos et al. observation in selected lesions. Based on this evolving knowledge and our personal understanding of the treatment of these lesions, we suggest the following (Fig. 3): 1) periodic imaging and clinical assessment of patients with asymptomatic lesions and early GKS once tumor progression is documented; 2) early GKS rather than surgical excision for small minimally symptomatic lesions; 3) early GKS for nondisabling symptomatic lesions without significant brainstem compression; 4) surgical decompression for disabling symptomatic tumors associated with significant brainstem compression in patients with a reasonable surgical risk profile, with the goal of a maximal safe resection; 5) subsequent GKS for tumors that remain after initial decompression; 6) early GKS for recurrent tumors without significant brainstem compression; and 7) supportive medical management of elderly and medically infirm patients with significant brainstem compression (since the risk profile of surgery is too poor and the benefit of GKS is unsubstantiated). Disclosure Both Drs. Lunsford and Kondziolka are consultants for AB Elekta, and Dr. Lunsford has direct stock ownership in AB Elekta. Author contributions to the study and manuscript preparation include the following. Conception and design: Zenonos. Acquisition of data: Zenonos. Analysis and interpretation of data: Zenonos. Drafting the article: Zenonos. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Zenonos. Statistical analysis: Zenonos. Study supervision: Kondziolka, Lunsford. References 1. Akalan N, Seçkin H, Kiliç C, Ozgen T: Benign extramedullary tumors in the foramen magnum region. Clin Neurol Neurosurg 96: , Arnautović KI, Al-Mefty O, Husain M: Ventral foramen magnum meninigiomas. J Neurosurg 92 (1 Suppl):71 80, Babu RP, Sekhar LN, Wright DC: Extreme lateral transcondylar approach: technical improvements and lessons learned. 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10 Gamma Knife surgery for foramen magnum meningioma 32. Sen CN, Sekhar LN: An extreme lateral approach to intradural lesions of the cervical spine and foramen magnum. Neurosurgery 27: , Starke RM, Nguyen JH, Reames DL, Rainey J, Sheehan JP: Gamma knife radiosurgery of meningiomas involving the foramen magnum. J Craniovertebr Junction Spine 1:23 28, United Nations: World Population Prospects, the 2010 Revision. New York: Department of Economic and Social Affairs, Population Division ( tab-sorting_mortality.htm) [Accessed August 16, 2012] 35. Wu Z, Hao S, Zhang J, Zhang L, Jia G, Tang J, et al: Foramen magnum meningiomas: experiences in 114 patients at a single institute over 15 years. Surg Neurol 72: , Yaşargil MG, Curcic M: Meningiomas of basal posterior cranial fossa, in Krayenbuhl H (ed): Advances and Technical Standards in Neurosurgery. Vienna: Springer-Verlag, vol 7, 1 115, Yasuoka S, Okazaki H, Daube JR, MacCarty CS: Foramen magnum tumors. Analysis of 57 cases of benign extramedullary tumors. J Neurosurg 49: , 1978 Manuscript submitted September 2, Accepted August 7, Portions of this work were presented as an electronic poster at the AANS Annual Scientific Meeting in Miami, Florida, April 14 18, Please include this information when citing this paper: published online September 14, 2012; DOI: / JNS Address correspondence to: Georgios Zenonos, M.D., Department of Neurological Surgery, 200 Lothrop Street, Suite B400, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania zenonosg@upmc.edu. J Neurosurg / Volume 117 / November