Radiation Oncology/CNS/Meningioma

Epidemiology Most common benign brain tumor Approximately 95% Represents 20% of primary intracranial neoplasms. Occur mostly in age group 40-70 yrs old, increasing in incidence with age, and peaking at 70. F>M 2:1 Risk Factors Prior radiation therapy Treatment of tinea capitis with radiation is classic scenario of radiation induced meningioma. PCI increases incidence of meningioma by 10X baseline rate. Median interval between radiation treatment and development of meningioma is ~20 yrs. Type II Neurofibromatosis Hormone replacement therapy in women Mayo Clinic; 2008 (1993-2003) 18182668 -- "Is there an association between meningioma and hormone replacement therapy?" (Blitshteyn S, J Clin Oncol. 2008 Jan 10;26(2):279-82.) Retrospective. 1390 women with meningioma, 11% current/past HRT users Outcome: OR for HRT use and meningioma 2.2 (SS) Conclusion: Positive association between HRT use and diagnosis for meningioma Imaging CT Well-defined extra-axial mass that displaces normal brain. Smooth in contour, sometimes calcified About 60% hyperdense with normal brain without contrast About 70% brightly and homogenously enhance with contrast (less frequent in malignant or cystic meningiomas) MRI Preferred imaging because it can show dural origin Dural tail sign seen in about two-thirds: characteristic marginal thickening that tapers peripherally along the dura Isointense on T1, hyperintense (usually homogeneously) on T2, strong enhancement with IV contrast PET May have a role in predicting aggressiveness of meningioma: more aggressive tumors appear to have significantly higher mean rate of glucose utilization WHO Classification Benign (Grade I) - (90%) - meningothelial, fibrous, transitional, psammomatous, angioblastic (most aggressive) Atypical (Grade II) - (7%) - choroid, clear cell, atypical Anaplastic/Malignant (Grade III) - (2%) - papillary, rhabdoid, anaplastic Korea; 2007 (1986-2004) 17766430 -- "Atypical and anaplastic meningiomas: prognostic implication of clinicopathological features." (Yang SY, J Neurol Neurosurg Psychiatry. 2007 Aug 31) Retrospective. 74 patients with high grade (33 atypical, 41 anaplastic). Reclassified according to 2000 WHO. Mean F/U 4.8 years Outcome: OS atypical 11.9 years vs. anaplastic 3.3 years; RFS atypical 11.5 years vs. anaplastic 2.7 years If atypical, brain invasion and RT didn't improve survival; if anaplastic, prognostic factors were brain invasion, adjuvant RT, p53 overexpression, extent of resection Conclusion: 2000 WHO classification better than previous criteria Treatment Overview Treatment can range from conservative management to definitive surgery, adjuvant radiation or definitive radiation/radiosurgery. Patients with small asymptomatic meningiomas found incidentally can be observed until they grow or become symptomatic. Indications for adjuvant radiation therapy: incomplete resection and high grade tumor. Tx to dose of 54 Gy for Grade I and 60 Gy for Grade II-III. Cavernous sinus meningioma represent a scenario where SRS is particularly useful given the potential morbidity of surgical resection in that region. UpToDate recommendations (version 15.2, 4/2007) Small, asymptomatic meningioma: careful observation with re-imaging in 3-6 months If no growth at first F/U, routine imaging q1 year If tumor growth, active treatment Young patients with asymptomatic meningioma: consider surgery Symptomatic, large, infiltrative, or edematous lesions should be treated with surgery and/or RT If anatomically accessible: attempt surgical resection Simpson Grade I: no adjuvant therapy Simpson Grade II-III and benign: no adjuvant therapy Simpson Grade II-III and atypical/malignant: adjuvant RT Simpson Grade IV: adjuvant RT For patients who are unresectable, not surgical candidates, or refuse surgery, offer primary RT Observation Majority (~2/3) of asymptomatic, incidentally found meningiomas are stable on imaging. If they progress, the rate of growth tends to be 2-4 mm per year and tumor doubling time is on average 20 years Calcified and hypointense on T2 meningiomas appear less likely to progress; elderly patients appear to have slower growth rates Reasonable to consider observation for asymptomatic meningiomas, particularly in elderly patients or patients with skull-base (high operative risk) tumors. If so, MRI at 3 months, then 6 months later, then annually is considered reasonable For younger patients and patients with non-calcified tumors, consider treatment due to higher expected growth rates Tel Aviv; 2004 (Israel)(1989-1999) 15452322 -- "Natural history of conservatively treated meningiomas." (Herscovici Z, Neurology. 2004 Sep 28;63(6):1133-4.) Retrospective. 43 patients, 51 meningiomas Outcome: 63% no growth, 37% growth (mean growth rate 4 mm / year) Predictors: younger age, sphenoid ridge location, non calcified, hyperintense on MRI T2 predicted for growth Hannover; 2003 12823874 -- "The natural history of incidental meningiomas." (Nakamura M, Neurosurgery. 2003 Jul;53(1):62-70; discussion 70-1.) Retrospective. 47 asymptomatic patients reviewed. 41 (87%) managed conservatively, 6 surgery Outcome: volumetric growth mean 0.8 cm3 / year, 66% growth rates <1 cm3 / year; tumor doubling mean 22 years (1.3 - 143 years). Higher growth rates in younger patients. No correlation between initial size and doubling time. Less likely to progress if calcified Conclusion: Majority of incidental meningiomas minimal growth; can be managed conservatively Mayo; 1998 9855530 -- "The natural history of asymptomatic meningiomas in Olmsted County, Minnesota." (Go RS, Neurology. 1998 Dec;51(6):1718-20.) Retrospective. 35 asymptomatic patients found incidentally. Mean F/U 6.2 years Outcome: 88% stable, 12% progressed, 3% (1 patient) developed symptoms. Less likely to progress if calcified Northwestern; 1997 9153494 -- "Meningiomas: the decision not to operate." (Braunstein JB, Neurology. 1997 May;48(5):1459-62.) Retrospective. 12 patients managed conservatively in 100 consecutive meningiomas, either with no symptoms or high operative risk. Mean F/U 8.8 years Outcome: growth in 1/12 patients Illinois; 1995 7616265 -- "The natural history and growth rate of asymptomatic meningiomas: a review of 60 patients." (Olivero WC, J Neurosurg. 1995 Aug;83(2):222-4.) Retrospective. 60 patients diagnosed with asymptomatic meningioma. 45 patients follow up scans at 3 months, 9 months, then q 1 year. Average F/U 2.7 years (0.5-15). Outcome: 67% no growth (average F/U 2.4 years, max 6 years); 22% tumor growth (2.4 mm per year, range 2 mm - 1 cm) Conclusion: Need for close follow-up to rule out rapidly enlarging tumors Surgical Management Frequently considered for symptomatic patients, younger patients, and patients with expanding/infiltrating tumors Complications: range 2-30% depending on location and type Mortality: range 1-14%; worse in elderly Resectability plays an important role: Completeness of resection - Simpson Grade 13406590 - predicts for likelihood of local recurrence Gross total resection (Grade I-III) in ~80%, leading to 10-year PFS of ~80% Subtotal resection typically in cavernous sinus, petroclival region, posterior superior sagittal sinus, and optic nerve sheath tumors; have 4.2x relative excess death risk compared to complete resection Simpson Grade Completeness of Resection 10-year Recurrence Grade I complete removal including resection of underlying bone and associated dura 9% Grade II complete removal + coagulation of dural attachment 19% Grade III complete removal w/o resection of dura or coagulation 29% Grade IV subtotal resection 40% Grade is also important: 15-year OS benign 80% vs. atypical/anaplastic 51%, risk of death 4.6x Helsinki; 1992 (Finland)(1953-1980) 1641106 -- "Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma." (Kallio M, Neurosurgery. 1992 Jul;31(1):2-12.) Retrospective. 935 patients treated with surgery. Outcome: 1-year DSS 91%, 15-year DSS 78%; subtotal resection 4.2x risk of death; malignant histology 4.6x risk of death Adjuvant Radiation Germany (1985-2009) -- Atypical and malignant meningiomas 62 pts w/ atypical and 23 pts w/ malignant meningiomas, s/p RT (60% after surgical resection, 19% at disease progression, 8% as primary treatment). Average dose 57.6 Gy in 1.8-3 Gy fx. 2012 22137023 -- "Long-term outcome after radiotherapy in patients with atypical and malignant meningiomas--clinical results in 85 patients treated in a single institution leading to optimized guidelines for early radiation therapy." (Adeberg S, Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):859-64.) 5-yr OS: 81% atypical and 53% malignant. PFS: 95% and 50% (at 2 and 5 yrs) for atypical, and 63% and 13% for malignant. Conclusion: "RT resulted in improvement of preexisting clinical symptoms; outcome is comparable to other series reported in the literature." France (1999-2006) -- Atypical and malignant meningiomas 19 pts w/ atypical and 5 pts w/ malignant meningiomas, s/p RT. Treatment at Centre de Protontherapie d'Orsay (CPO). Median total RT dose 68 CGE (34 Gy photons + 34 CGE protons). 2009 19203844 -- "Combined proton and photon conformal radiotherapy for intracranial atypical and malignant meningioma." (Boskos C, Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):399-406.) Survival associated with dose > 60 Gy. Conclusion: "Postoperative combination of conformal radiotherapy with protons and photons for atypical and malignant meningiomas is a well-tolerated treatment producing long-term tumor stabilization." UC San Francisco Atypical meningiomas; 2009 (1993-2004) 19145156 -- "Long-term recurrence rates of atypical meningiomas after gross total resection with or without postoperative adjuvant radiation." (Aghi MK, Neurosurgery. 2009 Jan;64(1):56-60; discussion 60.) Retrospective. 108 atypical meningioma, gross total resection. Adjuvant radiation in 8 patients. Outcome: recurrence rate 28%, mean time to recurrence 3 years. No recurrence with the 8 patients who received adjuvant RT. Patients with recurrences underwent RT, and average 2.7 craniotomies/patient. Tumor-related mortality after recurrence 30% Conclusion: High recurrence rate for atypical meningiomas after GTR without adjuvant radiation; causing numerous reoperations and shortened survival Subtotal resection; 1994 (1967-90) 8283256 -- "Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990," (Goldsmith BJ, J Neurosurg. 1994 Feb;80(2):195-201.) Retrospective. 140 pts (117 benign, 23 malignant) treated with adjuvant RT. RT median dose 54 Gy, benign margin 1-2cm, malignant margin 1-3cm. Median FU 3.3 years Outcome: 5-year OS benign 85% vs. malignant 58% (SS); 10-year benign PFS and OS 77% (no 10 year outcomes for malignant) RT dose: 10-year PFS <52 Gy 65% vs. >52 Gy 93% (SS); malignant 5-year PFS <53 Gy 17% vs. >53 Gy 63% (SS) Toxicity: no secondary CNS tumors; 4% blindness, 1% (2 patients) cerebral necrosis, 1 leading to death Conclusion: RT for subtotally resected meningioma effective and safe. Recommend 54 Gy for benign and 60 Gy for malignant meningioma Subtotal resection; 1987 (1968-78) 3587542 -- "Radiation therapy in the treatment of partially resected meningiomas," (Barbaro NM, Neurosurgery. 1987 Apr;20(4):525-8. Retrospective. 51 pts w/ GTR and no xrt, 30 pts w/ STR and no xrt, 54 pts w/ STR + xrt Recurrence rate: GTR 4%, STR alone 60%, STR + adjuvant RT 32% Conclusion: adjuvant RT decreases recurrence rate Gainesville (1964-85) 3403313 -- Taylor WB et al. "The meningioma controversy: postoperative radiation therapy," Int J Radiat Oncol Biol Phys. 1988 Aug;15(2):299-304. 132 pts w/ benign intracranial meningioma w/ minimum 2 yr FU. Local control at 10 yrs: STR alone (18%), STR + xrt (82%), GRT (77%) Princess Margaret (1966-90) 8598358 -- Milosevic MF et al. "Radiotherapy for atypical or malignant intracranial meningioma," Int J Radiat Oncol Biol Phys. 1996 Mar 1;34(4):817-22. 59 pts w/ atypical or malignant meningioma. 17 had GTR, 35 had STR, others had bx or other. All pts received xrt (median dose 50 Gy). 5yr OS was 28%, 5yr CSS was 34% Age < 58, xrt dose > 50 Gy were independent predictors of higher CSS on multivariate analysis. Cleveland Clinic (1979-95) 10656373 -- Goyal LK et al. "Local control and overall survival in atypical meningioma: a retrospective study," Int J Radiat Oncol Biol Phys. 2000 Jan 1;46(1):57-61. 22 atypical meningioma, 8 received xrt in the range of 54 Gy (35-59.4), 15 had GTR Pts w/ GTR had 5 and 10 yr OS of 87% and 87%; Pts w/ STR had 5 and 10 yr OS of 100% and 75% MGH (1981-96) 11121635 -- Wenkel E et al. "Benign meningioma: partially resected, biopsied, and recurrent intracranial tumors treated with combined proton and photon radiotherapy," Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1363-70. 46 pts w/ subtotally resected, bx'd, or recurrent meningioma tx'd w/ combined photon/proton xrt (9 w/ STR, 8 w/ bx only, 29 w/ recurrence after surg). Median dose 59 CGE. 5 yr OS was 93% and 10 yr OS was 77% 8 pts had severe long term toxicity and 1 pt died of brainstem necrosis. Toxicity appeared dose related. Stereotactic Radiosurgery Prague; 2007 (1992-1999) 17695387 -- "Gamma Knife surgery for benign meningioma." (Kollova A, J Neurosurg. 2007 Aug;107(2):325-36.) Retrospective. 368 patients with 400 meningiomas. Median margin dose 12.5 Gy at 50% isodose (6.5-24 Gy). Median F/U 5 years 5-year outcome: decreased volume 70%, stable 28%, increased 2%; actuarial local control 98%; worse in men and when RT dose <12 Gy Toxicity: temporary 10%, permanent 6%; perilesional edema 15%, worse when dose >16 Gy Conclusion: SRS safe and effective, therapeutic window 12-16 Gy to 50% isodose at tumor margin University of Maryland, 2005 (1992-2000) 15590183 -- DiBiase SJ et al. "Factors predicting local tumor control after gamma knife stereotactic radiosurgery for benign intracranial meningiomas," Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1515-9. 137 pts w/ benign meningioma; 62% tx'd definitively, while remaining had previous resection. Median 14 Gy to 50% isodose. Prognostic factors associated w/ worse prognosis were conformity index < 1.4, male sex, and size >10 cc. Mayo Clinic, 2003 (1990-97) 12605979 -- Pollock BE et al. "Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas," Int J Radiat Oncol Biol Phys. 2003 Mar 15;55(4):1000-5. 198 adult meningioma <3.5 cm tx'd w/ either surgery (136) or SRS (62); for SRS, mean margin dose of 17.7 Gy w/ mean max dose of 34.9 Gy. No statistically significant difference b/w Simpson Grade I resections and SRS tx'd pts in terms of PFS (100% vs 96% respectively). Pittsburgh, 1999 (1987-92) 10389879 -- "Long-term outcomes after meningioma radiosurgery: physician and patient perspectives," (Kondziolka D, J Neurosurg. 1999 Jul;91(1):44-50.) Retrospective. 99 consecutive pts w/ SRS (57% had prior resection, 5 received prio fx'd xrt). 89% skull base tumors. Median margin dose 16 Gy to 50% isodose (9-25 Gy) Outcome: decrease in 59% at 3 years, 69% at 5 years, 73% at 7 years and 88% at 9 years; local control 95%, progression related to prior resection and multiple meningiomas Toxicity: new or worsened symptoms 9% Patient survey satisfaction: 79% response rate, 96% considered it a "success" Proton Therapy PSI; 2004 (1997-2002) 15172139 -- "Spot-scanning proton radiation therapy for recurrent, residual or untreated intracranial meningiomas." (Weber DC, Radiother Oncol. 2004 Jun;71(3):251-8.) Retrospective. 16 patients (8 skull base). 13 patients adjuvant RT or salvage RT after surgical recurrence; 3 patients radical RT. Benign meningioma 52.2-56 CGE based on prognostic factors, atypical meningioma 64 CGE at 1.8-2.0 CGE/fx. Median F/U 2.8 years Outcome: 3-year LC 92%, DFS 92%, OS 93%. No deaths from recurrence. Toxicity: 3-year toxicity 24% (radiation induced optic neuropathy Grade 3 in 1 patient, retinopathy Grade 2 in 1 patient, symptomatic brain necrosis Grade 4 in 1 patient 7.2 months after treatment). No hypothalamic/pituitary dysfunction Conclusion: Spot-scanned PT effective; ophthalmologic toxicity dose-related Special Sites Cavernous Sinus Meningioma Verona, Italy, 2002 (1992-2002) 12383360 -- Nicolato A et al. "Radiosurgical treatment of cavernous sinus meningiomas: experience with 122 treated patients," Neurosurgery. 2002 Nov;51(5):1153-9; discussion 1159-61. 156 pts w/ cavernous sinus meningioma that were either inoperable, symptomatic, progressive. All tumors were <2cm but >2mm from optic pathways. 5yr PFS was 96.5%; regression in 80% if followed for >30 mo's, but only 43.5% if followed for <30 mo's. 1% permanent radiosurgical sequellae. Pittsburgh, 2002 12134934 -- Lee JY et al. "Stereotactic radiosurgery providing long-term tumor control of cavernous sinus meningiomas," J Neurosurg. 2002 Jul;97(1):65-72. 159 pts w/ cavernous sinus meningioma tx'd w/ SRS. 52% tx'd w/ definitive SRS, 48% tx'd after 1 or more attempts at resection. Median dose to tumor margin 13 Gy. 29% w/ improvement of neurologic status, 62% w/ stabilization of neuro status, 9% w/ worsening. Actuarial tumor control rate 93%. Marseille, France, 2000 (1992-1998) 11143266 -- Roche PH et al. "Gamma knife radiosurgery in the management of cavernous sinus meningiomas," J Neurosurg. 2000 Dec;93 Suppl 3:68-73. 80 pts w/ cavernous sinus meningioma where gamma knife was used as definitive tx (50) or adjuvant tx for microsurgery (30) 5yr PFS 92.8% 15 of 54 pts w/ oculomotor deficit improved, 8 recovered, 1 worsened. 1 case of transient optic neuropathy reported. Optic Nerve Sheath Brower; 2012 (1990-2006) (University of Florida) 24674368 -- "Radiation therapy for optic nerve sheath meningioma." (Brower J, PRO. 2013 Volume 3, Issue 3 , Pages 223-228) Retrospective. 15 patients. Median age 52 years. RT for gross residual tumor, 1/3 underwent radiation therapy for tumors that had recurred within 1 year of surgery, minimum f/u 5 years, median 12yrs, Target definition is GTV= Visible tumor on MRI scan, CTV= GTV+5mm along length of ON, PTV= CTV+ 2 to 5mm magin Outcome: No patient experienced tumor progression, LC/RC/RFF all 100%, vision status after radiation therapy: Stable 60%, Improved in 27%, Decreased 13%, Moderate retinopathy in 2 patients Conclusion: RT with 50.4Gy at 1.8Gy per treatment prevents tumor growth and vision deterioration Tubingen; 2006 (1981-2002) (Germany) 16191463 -- "The role of surgery in meningiomas involving the optic nerve sheath." (Roser F, Clin Neurol Neurosurg. 2006 Jul;108(5):470-6.) Retrospective. 24 patients. Female 7:1 male, mean age 44 years. Surgery pterional craniotomy, intra/extradural subtotal excision, bony decompression Outcome: Low morbidity, preserved/improved vision in 50% patients. Long-term vision loss due to recurrence in 20% Conclusion: RT should be primary treatment option as it prolongs time to functional loss; surgery for intracranial extension, disfiguring proptosis, and rapid visual deterioration