Landert, Monika MD; Baumert, Brigitta G MD, PhD; Bosch, Martina M MD; Lütolf, Urs M MD; Landau, Klara MD
Optic nerve sheath meningiomas (ONSM) represent 1% to 2% of all meningiomas diagnosed in the general population (1), 95% of which are unilateral (2). Primary optic nerve sheath meningiomas develop from meningothelial cap cells of arachnoid villi along the intracanalicular or intraorbital portions of the optic nerve. Visual loss and visual field defects tend to be slowly progressive and long-term survival is common (2). Secondary ONSM arise from a neighboring intracranial site and extend into the subdural and/or subarachnoid spaces of the optic nerve sheath (3).
The formerly controversial issue of management of primary ONSM, with recommendations ranging from simple observation to surgery and radiotherapy, is now being revised. There is an accumulating literature in support of radiation (4-16). Because of the low incidence of this tumor, however, outcome measurements of radiation therapy are limited and no prospective studies have yet been published.
Conventional radiotherapy has been used to treat ONSM with some success (1,17-19). A large retrospective comparative series by Turbin et al (16) showed a more favorable outcome for conventional fractionated radiation therapy than for surgery or observation. Newer treatment techniques of radiotherapy are able to tailor or, conform, dose better to the tumor itself while sparing surrounding non-tumoral healthy tissue. These techniques are known as three-dimensional conformal radiotherapy, which is based on three-dimensional patient data, treatment planning, and treatment delivery. Stereotactic radiotherapy represents a highly accurate form of three-dimensional conformal radiotherapy. Eight studies have suggested short-term beneficial results from three-dimensional conformal radiotherapy (12) or the more precise fractionated stereotactic conformal radiotherapy (SCRT) (4-7,10,14,15). Of the seven studies of SCRT, only the two by Andrews et al (4) and by Saeed et al (15) compared radiation treatment to observation alone.
In the current study, we report the outcome of seven eyes with ONSM treated by fractionated SCRT at the University Hospital of Zurich and compare it to a similar group of six eyes that were not treated.
Only cases presenting clinically and radiologically with primary, rather than secondary, ONSM were included. Between 1989 and 2000, 18 cases were referred to the Department of Ophthalmology at the University Hospital of Zurich with the diagnosis of primary ONSM. Three patients were excluded because of previous surgical treatment, one because of neurofibromatosis type 2 with multiple meningiomas, and one because of previous conventional radiotherapy. One patient who received SCRT with no light perception before treatment was excluded because visual improvement after irradiation could not be expected.
Diagnosis was based on the clinical findings and the characteristic appearance on magnetic resonance imaging (20). The 12 cases included in the study had repeated magnetic resonance imaging studies, the last of which was performed at the end of the follow-up period. All cases had detailed orbital investigations using high spatial-resolution pre-contrast and post-contrast T1-weighted images with fat saturation, which allow improved visualization of meningiomas (21).
Thirteen eyes of twelve cases met entry criteria. Seven tumors were located on the right side and four on the left. One case had bilateral ONSM, one symptomatic, the other discovered incidentally with magnetic resonance imaging. Seven eyes were treated with SCRT (treated group). Six eyes were managed by observation only (untreated group). The single case with bilateral optic nerve sheath meningiomas was represented in both groups. Indications for treatment were deterioration of visual function with or without radiologically documented tumor growth. Untreated patients included three with satisfactory and stable visual function and three who did not wish to be irradiated despite progressive visual loss (Table 1). All treated patients gave informed consent before therapy. Our seven treated patients have been previously reported in a multicenter study published in a radiation oncology journal with emphasis on treatment technique and clinical outcome (5).
Patient Baseline Characteristics
There were 10 women (83%) and two men (17%). The female predominance prevailed in both treatment groups (Table 1). The mean age of the entire patient group at the time of presentation was 44.7 years (range: 13-76). Treated patients were older than untreated patients. The mean and median age in the treated group was 46.6 and 46 years, respectively; the mean and median age in the untreated group was 39.5 and 34 years, respectively.
In general, visual acuity at the time of diagnosis was better in the treated group than in the untreated group. All treated patients presented with 20/40 or better visual acuity immediately before treatment started. At initial presentation, half of the untreated eyes had a visual acuity ranging from 20/40 to 20/100, whereas the other half had normal vision.
Seven cases were treated with highly focused irradiation in the form of fractionated SCRT at the Department of Radiation Oncology, University Hospital of Zurich. The median total dose was 54 Gray (50-54 Gray) with fractions of 1.7/1.8 Gray daily over 6 weeks. Patients were immobilized and scanned in a relocatable stereotactic mask with integrated custom-made bite-block. The gross tumor volume was defined as visible tumor mass on the planning computed tomography scan and was expanded by 3 mm three-dimensionally for the calculation of the planning target volume. Irradiation was performed with non-coplanar fixed beams conformed to the treatment volume.
Critical structures (contralateral optic nerve, optic chiasm, lens, central retina) were identified to keep the radiation dose to these structures below the organ-specific critical dose. This was achieved by the use of dose restrictions that were defined by the maximum reported tolerance dose for a defined organ. For example, in a given case, the accepted dose was the minimum possible for the contralateral optic nerve, and for the optic chiasm it was aimed to be kept as low as possible but not exceeding 50 Gy. In general, maximum dose used was lower than usual, because ONSMs are benign tumors. The irradiation and planning techniques are described in detail elsewhere (5). The dose to the chiasm, the contralateral optic nerve, and the contralateral eyeball were always less than 20% of the prescription dose.
Main Outcome Measures
Baseline and follow-up assessments of visual acuity were performed by the same experienced neuro-ophthalmologist (K.L.). Best-corrected visual acuity was measured using Snellen charts and noted in a 20/20 ratio equivalent. At least three out of four letters had to be correctly identified for the patient to be given full credit for that line. If worse than 20/200, visual acuity was graded as counting fingers, hand motions, light perception, or no light perception.
In the treated group, visual acuity was recorded at 3 months after treatment in six of seven eyes and at the last follow-up visit (“final VA”) in all seven eyes. The visual field was tested either by Goldmann kinetic perimetry or by automated static perimetry with the Octopus program G2.
A change in visual function was defined as change in visual acuity or visual field. A change in visual acuity consisted of improvement or worsening by two or more lines. A change in visual field consisted of an expansion or contraction of 20 degrees or more in the V-4-e isopter on Goldmann perimetry or a change of at least 5 dB in mean deviation (MD) on automated fields (22). The mean follow-up time was 57 months (range: 21-142) in the treated group, and 61 months (range: 16-118) in the untreated group. The mean follow-up time after radiotherapy in the treated group was 23 months (range: 8-40).
Changes in visual function were classified as improvement, stabilization, or worsening. The treatment groups were compared with each other by the Mann-Whitney U test.
Among the seven treated eyes, six experienced improvement in visual function. Five eyes had an increase in visual acuity of three lines or more; one eye improved by one Snellen line. At 3 months after treatment, visual acuity had improved in five out of the six eyes in which it was recorded. One eye lost two lines of visual acuity. Visual field improved in four eyes, remained stable in two, and deteriorated in one.
Among the six untreated eyes, four showed moderate to severe worsening of vision. In three eyes with initial visual acuities ranging from 20/20 to 20/100, visual acuity declined to hand motion and no light perception, and one eye declined from 20/40 to 20/70. Two eyes with initially normal visual acuity maintained normal acuity over the follow-up period. Visual field deteriorated in three eyes and remained unchanged in three eyes.
Non-parametric statistical analysis revealed significantly better visual outcome for the treated group than the untreated group (p = 0.012).
Imaging Characteristics and Outcome
Three meningiomas were confined to the orbit, three involved the optic canal, and seven involved the intracranial space (Fig. 1). There was no difference in these patterns of involvement between the two groups (Table 1). Slight reduction in tumor size was noted in one treated patient. In the untreated group, one patient had enlargement of the tumor that extended both towards the globe and from the canal towards the chiasm. There were no long-term side effects of SCRT. One patient had acute eyelid edema and was treated with low-dose corticosteroids with subsequent symptom resolution.
The main finding in our series of 13 eyes with primary ONSM was a statistically significant improvement of visual function in the treated group as compared with the untreated group. Six of seven treated eyes (86%) experienced prompt improvement in visual acuity, visual field, or both. Five of those eyes (71%) had an increase in visual acuity of three lines or more and remained stable over a mean follow-up period of 23 months after SCRT. By contrast, three of six untreated eyes had profound visual loss.
Consistent with other series, our results show that stereotactic conformal radiotherapy in patients with progressive optic neuropathy caused by primary ONSM is superior to observation in preserving visual function. This improvement appears to be greater than found in previous studies. For example, the percentage of eyes with an improvement in visual acuity of at least three Snellen lines is higher than that reported by Pitz et al (14) and Narayan et al (12). Pitz et al (14) found functional improvement in 7 (44%) of 16 eyes (defined as improvement of visual acuity of two or more lines or change of at least 8% of visual field) over a mean follow-up period of 37 months, but only one eye (6%) gained more than two Snellen lines. Narayan et al (12) reported a three-line or greater visual acuity improvement in 5 (36%) of 14 patients treated with three-dimensional conformal radiation therapy with a mean observation time of 51.3 months.
The relatively low rate of visual improvement in these reports might be a reflection of an under-representation of eyes with pre-treatment mild or moderate visual loss. Our patients with marked improvement all had pretreatment visual acuities ranging from 20/40 to 20/30, which may allow a greater potential for good treatment results. Based on our interval visual acuity data, improvement in visual function appears to occur early after treatment initiation, resembling rapid visual recovery after surgical decompression in compressive optic neuropathy (23).
The number of eyes included in our study was small and our follow-up was short. Thus, no firm conclusions with regard to long-term risks of irradiation, visual preservation, or containment of tumor growth can be made. Our untreated group had worse baseline visual function than our treated group, so that conclusions about the beneficial effect of treatment must also be tempered.
Despite these weaknesses, our study supports the accumulating data on the efficacy of SCRT for primary ONSMs (4-6,10,14). We further confirm that without treatment, vision declines substantially in some cases (2,15,16,24) but remains stable in others (24). Our findings support SCRT for eyes with primary ONSM in which progression of optic neuropathy has been documented, but before severe visual loss occurs.
The authors thank Burkhardt Seifert, PhD, Department of Biostatistics, University of Zurich, Switzerland, for his expert statistical consultation.
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