Practical Radiation Oncology (2013) 3, 223–228
www.practicalradonc.org
Original Report
Radiation therapy for optic nerve sheath meningioma Jeffrey V. Brower MD, PhDa , Robert J. Amdur MDa,⁎, Jessica Kirwan MAa , William M. Mendenhall MDa , William Friedman MDb a
Department of Radiation Oncology, University of Florida, Gainesville, Florida Department of Neurosurgery, University of Florida, Gainesville, Florida
b
Received 8 May 2012; revised 14 June 2012; accepted 22 June 2012
Abstract Purpose: To explain the concepts that radiation oncologists should understand to manage patients with optic nerve sheath meningioma (ONSM). To accomplish this goal we first describe our institution's experience with the treatment of ONSM with radiation therapy and then use this data set as a framework for explaining the role of radiation therapy in the treatment of this uncommon tumor. Methods and Materials: We studied the outcomes of all 15 patients treated at our medical center with radiation therapy for ONSM between 1990 and 2006. The minimum follow-up was 5 years (median, 12 years). The median dose was 50.4 Gy at 1.8 Gy per treatment (range, 50-54 Gy). Results: No patient experienced tumor progression. The rates of local control, regional control, and relapse free-survival were all 100%. Radiographic tumor response after radiation therapy was as follows: No change in 93%; and a reduction in size in 7%. Vision status after radiation therapy was as follows: Stable in 60%; improved in 27%; and decreased in 13%. Vision was classified as “useful” at last follow-up in 86% of patients with useful vision at the time of radiation therapy. The only treatment complication was moderate retinopathy in 2 patients. At last follow-up, no patient had developed a second tumor. Conclusions: Radiation therapy with 50.4 Gy at 1.8 Gy per treatment prevents tumor growth and vision deterioration in most patients with ONSM. © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Optic nerve sheath meningioma (ONSM) is an uncommon tumor that develops from the arachnoid cap cells of the dural sheath surrounding the optic nerve.1 ONSM has the same etiology, histologic subgroups, and biologic behavior as meningiomas in other sites.2 Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology, University of Florida, 2000 SW Archer Rd, PO Box 100385, Gainesville, FL 32610–0385. E-mail address: [email protected]fl.edu (R.J. Amdur).
The challenge in treating patients with ONSMs is restoration or preservation of vision as well as preservation of the eye. The problem with surgery is that curative resection usually requires removal of the eye or causes vision loss when the eye remains in place.1,3 Multiple reports suggest that radiation therapy frequently prevents tumor growth and preserves vision for years after treatment.4-8 The purpose of this article is to report long-term follow-up results from patients treated with radiation therapy at our institution and to use this data set as a framework to explain the issues that radiation oncologists should understand to manage patients with this uncommon tumor.
1879-8500/$ – see front matter © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.06.010
224 Table 1
J.V. Brower et al
Practical Radiation Oncology: July-September 2013
Methods and materials
Patient characteristics
Characteristic Clinical presentation Visual acuity decline Proptosis Pain Incidental Age at diagnosis Female Affected side Left Right Tissue diagnosis RT for gross residual tumor Maximum tumor dimension at RT Tumor location Orbit and optic canal Optic canal and intracranial Orbit, optic canal and intracranial RT for progression a RT technique Stereotactic b Intensity modulated 2-dimensional 1-2 fields Delivered dose QD dose per treatment (14 patients) BID dose per treatment (1 patient)
Patients (n=15) 10 (67%) 1 (6.5%) 1 (6.5%) 3 (20%) Median, 52 y Range, 21-72 y 15 (100%) 8 (53%) 7 (47%) 8 (53%) 15 (100%) Median, 27 mm Range, 8-70 mm 5 1 9 5
(33.5%) (6.5%) (60%) (33.5%)
13 (87%) 1 (6.5%) 1 (6.5%) Median, 50.4 Gy Range, 49.4-54.4 Gy Median, 1.8 Gy Range, 1.7-1.8 Gy 1.2 Gy
QD, once a day; RT, radiation therapy. a RT for progression after surgery means that the patient underwent at least 1 surgical procedure with curative intent, was observed, and then referred for RT due to radiographic evidence of progression. b Stereotactic radiation therapy delivered with 5 noncoplanar beam angles, 6-MV photons, and no intensity modulation.
Data for this study were collected as part of an institutional review board-approved protocol and according to the Health Insurance Portability and Accountability Act. This is a 16-year experience spanning from January 1, 1990 to December 31, 2006. The last patient was treated 4 years before the date of analysis on December 31, 2010. Table 1 summarizes the main characteristics of our study population. The major features are that all 15 patients had gross tumor present at the time of radiation therapy and a third of these patients underwent radiation therapy for tumors that had recurred after at least 1 curative-intent resection. We do not know the importance of this, but all of our patients were female. Figure 1 shows images from a typical patient in this series. We defined tumor control to be no evidence of tumor progression. Tumor progression, stability, or regression was recorded in the following 2 ways: (1) at the time of the most recent computed tomography or magnetic resonance (MR) scan; and (2) at the time of last discussion of symptoms when scans were not done at the most recent follow-up evaluation. Vision was classified as “unchanged,” “improved,” or “decreased” compared with preradiation therapy status based on ophthalmologic values or our basic office examination when the patient was not followed by an ophthalmologist. Vision at last follow-up was classified as “useful” or “not useful” based on a qualitative assessment by a member of the radiation oncology department at the last follow-up evaluation. Toxicity that persisted or developed at least 1 year following radiation therapy was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.9 We did not attempt to record acute toxicity because this was not reliably recorded in the medical record.
Figure 1 Optic nerve sheath meningioma (ONSM). Axial (A) and coronal (B) magnetic resonance images with T1-weighted echo sequence, intravenous contrast, and fat suppression. In both images the ONSM is bright white compared to the fat in the orbit. In image (A), the arrows point to the anterior and posterior extent of the tumor. Image (B) is midway between the posterior edge of the globe and the orbital apex. The arrow points to the tumor. The small black dot surrounded by tumor is the optic vein or artery. This patient presented with 20/30 vision and was treated with approximately 50.4 Gy at 1.8 Gy per treatment using stereotactic radiation therapy involving 5 noncoplanar 6-MV photon beams. Five years after radiation therapy the tumor is unchanged on magnetic resonance scan and vision is unchanged from the pretreatment values.
Practical Radiation Oncology: July-September 2013
RT for optic nerve sheath meningioma Table 2
225
Vision following radiation therapy (RT)
Vision follow-up
No. of patients
Vision at last follow-up relative to vision at the start of RT Unchanged Improved Worse Retained “useful” vision a
9 of 15 (60%) 4 of 15 (27%) 2 of 15 (13%) 12 of 14 (86%)
Note: Median, 12 years (range, 4-19 years). a One patient was blind before radiation therapy (RT) and remained blind after RT. Both patients whose vision deteriorated after RT did not have useful vision in the treated eye at last follow-up.
Figure 2
Actuarial plot of tumor control and survival.
Discussion Presentation and diagnosis
Results No patient was lost to follow-up and all patients were alive at last follow-up. The median clinical and median radiographic follow-up was 12 years (range, 4-19 years). No patient underwent resection of ONSM following radiation therapy. No patient experienced tumor progression. In regard to radiographic tumor response, there was no change in 93% and a reduction in size in 7% (1 patient). Figure 2 is an actuarial plot of tumor control and absolute survival to 15 years. Table 2 summarizes vision outcome with a 12-year median follow-up. In the great majority of patients, vision in the treated eye was stable (60%) or improved (23%) following radiation therapy and 86% of patients retained useful vision at last follow-up. Two patients presented with problems other than decreased vision. The patient with symptoms from proptosis was asymptomatic within a year of completing radiation therapy. The patient who presented with headaches (possibly unrelated to her tumor) did not experience a change in the frequency or intensity of her discomfort following treatment. The only toxicities in our series were the 2 cases of vision deterioration following radiation therapy. In both of these patients vision in the treated eye deteriorated to the point that they could not use the treated eye for reading or watching television, and they both classified their vision as “not useful.” Both of these patients were evaluated by an ophthalmologist and the vision loss (b20/100) was attributed to retinopathy that did not respond to therapy. In the CTCAE version 4.0, this degree of retinopathy is classified as grade 4 toxicity from radiation therapy. The grade 4 toxicity rate was therefore 13% (2/15) in the total patient population and 14% (2/14) in the patients with useful vision prior to radiation therapy. No patient developed a second tumor (malignant or benign) in the brain or head and neck during the follow-up period.
At the time of presentation almost all patients reported some change in vision, with decreased visual acuity being the most prominent complaint.1,3 A minority of patients present with proptosis and orbital pain.1,7,8 The best imaging study for ONSM is an MR scan with a T1 echo sequence, fat suppression, and intravenous contrast. Fat suppression is important so that the tumor can be differentiated from the adjacent orbital fat. In this type of study the tumor is hyperechogenic (white). Figure 1 shows MR images of 1 of the patients in this series. Tissue diagnosis is not necessary and a biopsy should not be performed when the imaging and clinical setting is classic for ONSM because a biopsy often damages the optic nerve or other structure, thereby causing lasting morbidity. Nevertheless, biopsy is indicated when the imaging or clinical setting raises the question of other possibilities. The differential diagnosis of conditions that present with imaging similar to ONSM are optic nerve glioma, orbital schwannoma, orbital lymphoma, hemangiopericytoma, sarcoidosis, optic neuritis, leiomyosarcoma, and metastatic cancer to the orbit. In our series only 50% of the patients underwent a biopsy of the optic nerve lesions.
Literature review Table 3 summarizes published series that report on the outcomes of patients treated with radiation therapy for ONSMs. The remaining subsections will discuss the specific results. Tumor control The rate of tumor control ranges from 90% to 100% in most published series. All of these reports define tumor control, as we did in our series, as “no evidence of tumor progression.” No-growth is an appropriate endpoint for ONSM because benign tumors often do not shrink after radiation therapy.
226 Table 3
J.V. Brower et al
Practical Radiation Oncology: July-September 2013
Literature review
Series
Cases
Dose
Follow-up
Tumor control
Visual outcome
Toxicity
Turbin et al (2002)
18
40-55 Gy
8y
89%
44% improved 23% unchanged 33% worse
Narayan et al (2003)5
14
50-56 Gy
4y
100%
36% improved 50% unchanged 14% worse
Landert et al (2005)12
7 eyes
54 Gy
5y
—
Arvold et al (2009)8
22
45-59 Gy
3y
95%
Saeed et al (2010)6
34
45-54 Gy
5y
—
86% improved 14% worse 64% improved 32% unchanged 4% worse 41% improved 50% unchanged 9% worse
33% 4 retinopathy 1 iritis 1 temporal lobe 36% 1 retinopathy 1 orbital pain 1 xeropthalmia 2 iritis None
Metellus et al (2011)7
9
36-54 Gy
8y
100%
Abouaf et al (2012)10
10
21-66 Gy
4y
100%
Paulsen et al (2012)13
113 eyes
50-54 Gy
5y
96%
Present series
15
49-54 Gy
12 y
100%
3
78% 22% 60% 10% 30% 13% 75% 12%
improved unchanged improved unchanged worse improved unchanged worse
27% improved 60% unchanged 13% worse
None
29% 5 xeropthalmia 2 retinopathy 3 cataracts 11% 1 retinopathy 30% 2 retinopathy 1 cataract 46% 8 alopecia 26 pain 11 fatigue 7 hypoaesthesia 13% 2 retinopathy
Long-term follow-up is needed to have confidence in the ability of radiation therapy to prevent growth of an ONSM. While our series has the longest follow-up we have seen in the literature, many patients with ONSM will live for over 20 years following treatment. Life-time follow-up is needed to document the true value of radiation therapy in this setting.
Vision improvement or preservation In our series, 86% of the patients treated with radiation therapy retained useful vision at last follow-up and 23% experienced improvement in vision. These findings are consistent with the majority of reports from the literature with regard to vision stabilization and improvement, with similar outcomes at shorter follow-up periods.7,8,10
Radiographic tumor response In our study we assessed patients with imaging at follow-up to determine the radiographic response to radiation therapy. All patients in our study demonstrated either radiographic stabilization or regression following radiation therapy. A number of studies have documented variable radiographic findings at last follow-up after irradiation8,10,11 while some studies do not report the findings at all.4,6 Most recent studies demonstrate that irradiation of ONSMs leads to good overall radiographic control, with most studies demonstrating stabilization of lesions with some documented regression.7,8,10
Radiation therapy dose In our series, most patients received 50.4 Gy at 1.8 Gy per treatment with treatments given once daily. This dose is similar to those used by many of the major studies in the literature.3-5,7,8 Complication rate following radiation therapy In our series the only complication observed was retinopathy, resulting in vision deterioration in 13% of patients. According to the CTCAE guidelines, these patients experienced grade 4 toxicities. Many studies do not report the rate of complications reliably or
Practical Radiation Oncology: July-September 2013 Table 4
RT for optic nerve sheath meningioma
227
Treatment guidelines for optic nerve sheath meningioma
Diagnosis
Observation
Medical therapy Surgery Indication for RT
RT dose Target definition
RT technique
Follow-up
CT of magnetic resonance imaging scan is usually adequate. Tissue biopsy is not necessary in cases with classic imaging findings and a consistent clinical presentation. Biopsy should be avoided when possible due to the risk of visual impairment and high degree of uncertainty following histological analysis. T1 MRI with intravenous contrast and fat suppression is the imaging modality of choice for diagnosis. Main differential diagnosis: optic nerve glioma, orbital schwannoma, lymphoma, optic nerve metastasis. Reserved for individuals without visual symptoms and those with poor vision and a desire to keep their eye as well as individuals with life expectancy such that symptoms from tumor progression are unlikely in the future. No standard rule. Treatment with estrogen and progesterone antagonists, as well as hydroxyurea, have been mainly unsuccessful. Reserved for patients with pain from proptosis, mass effect, or individuals who have already lost vision in the affected eye. Visible tumor on CT or MRI in patient with vision symptoms or incidentally found tumors in which progression is expected. RT for patients with acceptable vision in affected eye with desire to preserve vision. 50.4 Gy at 1.8 GY QD or 1.2 Gy BID fractions. GTV = Visible tumor on MRI scan. CTV = GTV + 5 mm along length of optic nerve. PTV = CTV = 2-5 mm. 4-5 field noncoplanar 6-MV photon beams with no entry or exit through either eye. The number and location of beam angles depend on individual patient anatomy. IMRT should be used when it significantly improves plan quality, but in many cases a 3D conformal plan without IMRT is sufficient. We have not evaluated plans with volumetric modulated arc therapy, but this may be advantageous in some cases. MRI imaging yearly. Ophthamologic examination every 6-12 months.
3D, 3-dimensional; BID, twice a day; CT, computed tomography; CTV, clinical target volume; IMRT, intensity modulated radiation therapy; GTV, gross tumor volume; MRI, magnetic resonance imaging; PTV, planning target volume; QD, once a day; RT, radiation therapy.
systematically, so it is difficult to correlate findings universally. Of the studies that do report complication rates, our study is consistent with the reported findings.5,6,10 It is important to note that no patient in our study developed a secondary tumor of the head or neck.
Treatment guidelines Table 4 summarizes our treatment guidelines for ONSM.
Conclusions Radiation therapy with 50.4 Gy at 1.8 Gy per treatment prevents tumor growth and vision deterioration in most patients with ONSM. This article reviews the published literature and explains the issues that radiation oncologists should understand to manage patients with this uncommon tumor.
References 1. Miller NR. New concepts in the diagnosis and management of optic nerve sheath meningioma. J Neuroophthalmol. 2006;26:200-208.
2. Dutton JJ. Optic nerve sheath meningiomas. Surv Ophthalmol. 1992; 37:167-183. 3. Turbin RE, Thompson CR, Kennerdell JS, Cockerham KP, Kupersmith MJ. A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapy. Ophthalmology. 2002;109:890-900. 4. Liu JK, Forman S, Hershewe GL, Moorthy CR, Benzil DL. Optic nerve sheath meningiomas: visual improvement after stereotactic radiotherapy. Neurosurgery. 2002;50:950-957. 5. Narayan S, Cornblath WT, Sandler HM, Elner V, Hayman JA. Preliminary visual outcomes after three-dimensional conformal radiation therapy for optic nerve sheath meningioma. Int J Radiat Oncol Biol Phys. 2003;56:537-543. 6. Saeed P, Blank L, Selva D, et al. Primary radiotherapy in progressive optic nerve sheath meningiomas: a long-term follow-up study. Br J Ophthalmol. 2010;94:564-568. 7. Metellus P, Kapoor S, Kharkar S, et al. Fractionated conformal radiotherapy for management of optic nerve sheath meningiomas: long-term outcomes of tumor control and visual function at a single institution. Int J Radiat Oncol Biol Phys. 2011;80: 185-192. 8. Arvold ND, Lessell S, Bussiere M, et al. Visual outcome and tumor control after conformal radiotherapy for patients with optic nerve sheath meningioma. Int J Radiat Oncol Biol Phys. 2009;75: 1166-1172. 9. Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC). National Cancer Institute; 2009. Available at: http://ctep.cancer.gov/protocolDevelopment/ electronic_applications/ctc.htm. Accessed July 18, 2012.
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10. Abouaf L, Girard N, Lefort T, et al. Standard-fractionated radiotherapy for optic nerve sheath meningioma: visual outcome is predicted by mean eye dose. Int J Radiat Oncol Biol Phys. 2012;82: 1268-1277. 11. Stiebel-Kalish H, Reich E, Gal L, et al. Visual outcome in meningiomas around anterior visual pathways treated with linear accelerator fractionated stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 2012;82:779-788.
Practical Radiation Oncology: July-September 2013 12. Landert M, Baumert BG, Bosch MM, Lütolf UM, Landau K. The visual impact of fractionated stereotactic conformal radiotherapy on seven eyes with optic nerve sheath meningiomas. J Neuroophthalmol. 2005;25:86-91. 13. Paulsen F, Doerr S, Wilhelm H, Becker G, Bamberg M, Classen J. Fractionated stereotactic radiotherapy in patients with optic nerve sheath meningioma. Int J Radiat Oncol Biol Phys. 2012;82: 773-778.
www.practicalradonc.org
Original Report
Radiation therapy for optic nerve sheath meningioma Jeffrey V. Brower MD, PhDa , Robert J. Amdur MDa,⁎, Jessica Kirwan MAa , William M. Mendenhall MDa , William Friedman MDb a
Department of Radiation Oncology, University of Florida, Gainesville, Florida Department of Neurosurgery, University of Florida, Gainesville, Florida
b
Received 8 May 2012; revised 14 June 2012; accepted 22 June 2012
Abstract Purpose: To explain the concepts that radiation oncologists should understand to manage patients with optic nerve sheath meningioma (ONSM). To accomplish this goal we first describe our institution's experience with the treatment of ONSM with radiation therapy and then use this data set as a framework for explaining the role of radiation therapy in the treatment of this uncommon tumor. Methods and Materials: We studied the outcomes of all 15 patients treated at our medical center with radiation therapy for ONSM between 1990 and 2006. The minimum follow-up was 5 years (median, 12 years). The median dose was 50.4 Gy at 1.8 Gy per treatment (range, 50-54 Gy). Results: No patient experienced tumor progression. The rates of local control, regional control, and relapse free-survival were all 100%. Radiographic tumor response after radiation therapy was as follows: No change in 93%; and a reduction in size in 7%. Vision status after radiation therapy was as follows: Stable in 60%; improved in 27%; and decreased in 13%. Vision was classified as “useful” at last follow-up in 86% of patients with useful vision at the time of radiation therapy. The only treatment complication was moderate retinopathy in 2 patients. At last follow-up, no patient had developed a second tumor. Conclusions: Radiation therapy with 50.4 Gy at 1.8 Gy per treatment prevents tumor growth and vision deterioration in most patients with ONSM. © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Optic nerve sheath meningioma (ONSM) is an uncommon tumor that develops from the arachnoid cap cells of the dural sheath surrounding the optic nerve.1 ONSM has the same etiology, histologic subgroups, and biologic behavior as meningiomas in other sites.2 Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology, University of Florida, 2000 SW Archer Rd, PO Box 100385, Gainesville, FL 32610–0385. E-mail address: [email protected]fl.edu (R.J. Amdur).
The challenge in treating patients with ONSMs is restoration or preservation of vision as well as preservation of the eye. The problem with surgery is that curative resection usually requires removal of the eye or causes vision loss when the eye remains in place.1,3 Multiple reports suggest that radiation therapy frequently prevents tumor growth and preserves vision for years after treatment.4-8 The purpose of this article is to report long-term follow-up results from patients treated with radiation therapy at our institution and to use this data set as a framework to explain the issues that radiation oncologists should understand to manage patients with this uncommon tumor.
1879-8500/$ – see front matter © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.06.010
224 Table 1
J.V. Brower et al
Practical Radiation Oncology: July-September 2013
Methods and materials
Patient characteristics
Characteristic Clinical presentation Visual acuity decline Proptosis Pain Incidental Age at diagnosis Female Affected side Left Right Tissue diagnosis RT for gross residual tumor Maximum tumor dimension at RT Tumor location Orbit and optic canal Optic canal and intracranial Orbit, optic canal and intracranial RT for progression a RT technique Stereotactic b Intensity modulated 2-dimensional 1-2 fields Delivered dose QD dose per treatment (14 patients) BID dose per treatment (1 patient)
Patients (n=15) 10 (67%) 1 (6.5%) 1 (6.5%) 3 (20%) Median, 52 y Range, 21-72 y 15 (100%) 8 (53%) 7 (47%) 8 (53%) 15 (100%) Median, 27 mm Range, 8-70 mm 5 1 9 5
(33.5%) (6.5%) (60%) (33.5%)
13 (87%) 1 (6.5%) 1 (6.5%) Median, 50.4 Gy Range, 49.4-54.4 Gy Median, 1.8 Gy Range, 1.7-1.8 Gy 1.2 Gy
QD, once a day; RT, radiation therapy. a RT for progression after surgery means that the patient underwent at least 1 surgical procedure with curative intent, was observed, and then referred for RT due to radiographic evidence of progression. b Stereotactic radiation therapy delivered with 5 noncoplanar beam angles, 6-MV photons, and no intensity modulation.
Data for this study were collected as part of an institutional review board-approved protocol and according to the Health Insurance Portability and Accountability Act. This is a 16-year experience spanning from January 1, 1990 to December 31, 2006. The last patient was treated 4 years before the date of analysis on December 31, 2010. Table 1 summarizes the main characteristics of our study population. The major features are that all 15 patients had gross tumor present at the time of radiation therapy and a third of these patients underwent radiation therapy for tumors that had recurred after at least 1 curative-intent resection. We do not know the importance of this, but all of our patients were female. Figure 1 shows images from a typical patient in this series. We defined tumor control to be no evidence of tumor progression. Tumor progression, stability, or regression was recorded in the following 2 ways: (1) at the time of the most recent computed tomography or magnetic resonance (MR) scan; and (2) at the time of last discussion of symptoms when scans were not done at the most recent follow-up evaluation. Vision was classified as “unchanged,” “improved,” or “decreased” compared with preradiation therapy status based on ophthalmologic values or our basic office examination when the patient was not followed by an ophthalmologist. Vision at last follow-up was classified as “useful” or “not useful” based on a qualitative assessment by a member of the radiation oncology department at the last follow-up evaluation. Toxicity that persisted or developed at least 1 year following radiation therapy was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.9 We did not attempt to record acute toxicity because this was not reliably recorded in the medical record.
Figure 1 Optic nerve sheath meningioma (ONSM). Axial (A) and coronal (B) magnetic resonance images with T1-weighted echo sequence, intravenous contrast, and fat suppression. In both images the ONSM is bright white compared to the fat in the orbit. In image (A), the arrows point to the anterior and posterior extent of the tumor. Image (B) is midway between the posterior edge of the globe and the orbital apex. The arrow points to the tumor. The small black dot surrounded by tumor is the optic vein or artery. This patient presented with 20/30 vision and was treated with approximately 50.4 Gy at 1.8 Gy per treatment using stereotactic radiation therapy involving 5 noncoplanar 6-MV photon beams. Five years after radiation therapy the tumor is unchanged on magnetic resonance scan and vision is unchanged from the pretreatment values.
Practical Radiation Oncology: July-September 2013
RT for optic nerve sheath meningioma Table 2
225
Vision following radiation therapy (RT)
Vision follow-up
No. of patients
Vision at last follow-up relative to vision at the start of RT Unchanged Improved Worse Retained “useful” vision a
9 of 15 (60%) 4 of 15 (27%) 2 of 15 (13%) 12 of 14 (86%)
Note: Median, 12 years (range, 4-19 years). a One patient was blind before radiation therapy (RT) and remained blind after RT. Both patients whose vision deteriorated after RT did not have useful vision in the treated eye at last follow-up.
Figure 2
Actuarial plot of tumor control and survival.
Discussion Presentation and diagnosis
Results No patient was lost to follow-up and all patients were alive at last follow-up. The median clinical and median radiographic follow-up was 12 years (range, 4-19 years). No patient underwent resection of ONSM following radiation therapy. No patient experienced tumor progression. In regard to radiographic tumor response, there was no change in 93% and a reduction in size in 7% (1 patient). Figure 2 is an actuarial plot of tumor control and absolute survival to 15 years. Table 2 summarizes vision outcome with a 12-year median follow-up. In the great majority of patients, vision in the treated eye was stable (60%) or improved (23%) following radiation therapy and 86% of patients retained useful vision at last follow-up. Two patients presented with problems other than decreased vision. The patient with symptoms from proptosis was asymptomatic within a year of completing radiation therapy. The patient who presented with headaches (possibly unrelated to her tumor) did not experience a change in the frequency or intensity of her discomfort following treatment. The only toxicities in our series were the 2 cases of vision deterioration following radiation therapy. In both of these patients vision in the treated eye deteriorated to the point that they could not use the treated eye for reading or watching television, and they both classified their vision as “not useful.” Both of these patients were evaluated by an ophthalmologist and the vision loss (b20/100) was attributed to retinopathy that did not respond to therapy. In the CTCAE version 4.0, this degree of retinopathy is classified as grade 4 toxicity from radiation therapy. The grade 4 toxicity rate was therefore 13% (2/15) in the total patient population and 14% (2/14) in the patients with useful vision prior to radiation therapy. No patient developed a second tumor (malignant or benign) in the brain or head and neck during the follow-up period.
At the time of presentation almost all patients reported some change in vision, with decreased visual acuity being the most prominent complaint.1,3 A minority of patients present with proptosis and orbital pain.1,7,8 The best imaging study for ONSM is an MR scan with a T1 echo sequence, fat suppression, and intravenous contrast. Fat suppression is important so that the tumor can be differentiated from the adjacent orbital fat. In this type of study the tumor is hyperechogenic (white). Figure 1 shows MR images of 1 of the patients in this series. Tissue diagnosis is not necessary and a biopsy should not be performed when the imaging and clinical setting is classic for ONSM because a biopsy often damages the optic nerve or other structure, thereby causing lasting morbidity. Nevertheless, biopsy is indicated when the imaging or clinical setting raises the question of other possibilities. The differential diagnosis of conditions that present with imaging similar to ONSM are optic nerve glioma, orbital schwannoma, orbital lymphoma, hemangiopericytoma, sarcoidosis, optic neuritis, leiomyosarcoma, and metastatic cancer to the orbit. In our series only 50% of the patients underwent a biopsy of the optic nerve lesions.
Literature review Table 3 summarizes published series that report on the outcomes of patients treated with radiation therapy for ONSMs. The remaining subsections will discuss the specific results. Tumor control The rate of tumor control ranges from 90% to 100% in most published series. All of these reports define tumor control, as we did in our series, as “no evidence of tumor progression.” No-growth is an appropriate endpoint for ONSM because benign tumors often do not shrink after radiation therapy.
226 Table 3
J.V. Brower et al
Practical Radiation Oncology: July-September 2013
Literature review
Series
Cases
Dose
Follow-up
Tumor control
Visual outcome
Toxicity
Turbin et al (2002)
18
40-55 Gy
8y
89%
44% improved 23% unchanged 33% worse
Narayan et al (2003)5
14
50-56 Gy
4y
100%
36% improved 50% unchanged 14% worse
Landert et al (2005)12
7 eyes
54 Gy
5y
—
Arvold et al (2009)8
22
45-59 Gy
3y
95%
Saeed et al (2010)6
34
45-54 Gy
5y
—
86% improved 14% worse 64% improved 32% unchanged 4% worse 41% improved 50% unchanged 9% worse
33% 4 retinopathy 1 iritis 1 temporal lobe 36% 1 retinopathy 1 orbital pain 1 xeropthalmia 2 iritis None
Metellus et al (2011)7
9
36-54 Gy
8y
100%
Abouaf et al (2012)10
10
21-66 Gy
4y
100%
Paulsen et al (2012)13
113 eyes
50-54 Gy
5y
96%
Present series
15
49-54 Gy
12 y
100%
3
78% 22% 60% 10% 30% 13% 75% 12%
improved unchanged improved unchanged worse improved unchanged worse
27% improved 60% unchanged 13% worse
None
29% 5 xeropthalmia 2 retinopathy 3 cataracts 11% 1 retinopathy 30% 2 retinopathy 1 cataract 46% 8 alopecia 26 pain 11 fatigue 7 hypoaesthesia 13% 2 retinopathy
Long-term follow-up is needed to have confidence in the ability of radiation therapy to prevent growth of an ONSM. While our series has the longest follow-up we have seen in the literature, many patients with ONSM will live for over 20 years following treatment. Life-time follow-up is needed to document the true value of radiation therapy in this setting.
Vision improvement or preservation In our series, 86% of the patients treated with radiation therapy retained useful vision at last follow-up and 23% experienced improvement in vision. These findings are consistent with the majority of reports from the literature with regard to vision stabilization and improvement, with similar outcomes at shorter follow-up periods.7,8,10
Radiographic tumor response In our study we assessed patients with imaging at follow-up to determine the radiographic response to radiation therapy. All patients in our study demonstrated either radiographic stabilization or regression following radiation therapy. A number of studies have documented variable radiographic findings at last follow-up after irradiation8,10,11 while some studies do not report the findings at all.4,6 Most recent studies demonstrate that irradiation of ONSMs leads to good overall radiographic control, with most studies demonstrating stabilization of lesions with some documented regression.7,8,10
Radiation therapy dose In our series, most patients received 50.4 Gy at 1.8 Gy per treatment with treatments given once daily. This dose is similar to those used by many of the major studies in the literature.3-5,7,8 Complication rate following radiation therapy In our series the only complication observed was retinopathy, resulting in vision deterioration in 13% of patients. According to the CTCAE guidelines, these patients experienced grade 4 toxicities. Many studies do not report the rate of complications reliably or
Practical Radiation Oncology: July-September 2013 Table 4
RT for optic nerve sheath meningioma
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Treatment guidelines for optic nerve sheath meningioma
Diagnosis
Observation
Medical therapy Surgery Indication for RT
RT dose Target definition
RT technique
Follow-up
CT of magnetic resonance imaging scan is usually adequate. Tissue biopsy is not necessary in cases with classic imaging findings and a consistent clinical presentation. Biopsy should be avoided when possible due to the risk of visual impairment and high degree of uncertainty following histological analysis. T1 MRI with intravenous contrast and fat suppression is the imaging modality of choice for diagnosis. Main differential diagnosis: optic nerve glioma, orbital schwannoma, lymphoma, optic nerve metastasis. Reserved for individuals without visual symptoms and those with poor vision and a desire to keep their eye as well as individuals with life expectancy such that symptoms from tumor progression are unlikely in the future. No standard rule. Treatment with estrogen and progesterone antagonists, as well as hydroxyurea, have been mainly unsuccessful. Reserved for patients with pain from proptosis, mass effect, or individuals who have already lost vision in the affected eye. Visible tumor on CT or MRI in patient with vision symptoms or incidentally found tumors in which progression is expected. RT for patients with acceptable vision in affected eye with desire to preserve vision. 50.4 Gy at 1.8 GY QD or 1.2 Gy BID fractions. GTV = Visible tumor on MRI scan. CTV = GTV + 5 mm along length of optic nerve. PTV = CTV = 2-5 mm. 4-5 field noncoplanar 6-MV photon beams with no entry or exit through either eye. The number and location of beam angles depend on individual patient anatomy. IMRT should be used when it significantly improves plan quality, but in many cases a 3D conformal plan without IMRT is sufficient. We have not evaluated plans with volumetric modulated arc therapy, but this may be advantageous in some cases. MRI imaging yearly. Ophthamologic examination every 6-12 months.
3D, 3-dimensional; BID, twice a day; CT, computed tomography; CTV, clinical target volume; IMRT, intensity modulated radiation therapy; GTV, gross tumor volume; MRI, magnetic resonance imaging; PTV, planning target volume; QD, once a day; RT, radiation therapy.
systematically, so it is difficult to correlate findings universally. Of the studies that do report complication rates, our study is consistent with the reported findings.5,6,10 It is important to note that no patient in our study developed a secondary tumor of the head or neck.
Treatment guidelines Table 4 summarizes our treatment guidelines for ONSM.
Conclusions Radiation therapy with 50.4 Gy at 1.8 Gy per treatment prevents tumor growth and vision deterioration in most patients with ONSM. This article reviews the published literature and explains the issues that radiation oncologists should understand to manage patients with this uncommon tumor.
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