Journal of Neuro-Ophthalmology, September 1998, Volume 18, Issue 3

Anterior Visual Pathway Meningiomas Primarily Resected Between 1978 and 1988

The relapse rate, overall survival, and factors associated with a decreased recurrence-free survival rate in patients with anterior visual pathway (AVP) meningioma were compared with these features in patients who had meningiomas at other sites. Management of these patients is discussed. A review of the records of 581 consecutive patients who had primary resection of meningiomas between 1978 and 1988 identified 43 patients with AVP meningioma. Multiple clinical, surgical, and pathologic factors at the initial examination were analyzed to assess their association with recurrence, and the patients who had AVP meningioma were compared with patients who had non-AVP meningiomas to determine the factors that may influence recurrence. Recurrence-free and overall survival rates were determined. The AVP tumors were associated with a higher rate of recurrence. Subtotal resection was more common in the AVP tumors, but it alone was not associated with the decrease in recurrence-free or overall survival rates. Several factors that may explain the higher recurrence rate in patients with AVP meningioma were identified. Anterior visual pathway meningioma is associated with a higher rate of recurrence than are meningiomas at other sites. Operation remains the mainstay of treatment for symptomatic nonseeing eyes. Radiation therapy seems to be effective for managing recurrent tumor.

. hitmitil nl iXrtim- OiililhiilniiiliiHY ISt. h: 2lir, 21( 1, / w \ " ' I'WS I. ippincnll Williams X Wilkills. Philadelphia Anterior Visual Pathway Meningiomas Primarily Resected Between 1978 and 1988 The Mayo Clinic Rochester Experience Scott L. Stafford, M. D.. Arie Perry, M. D., Jacqueline A. Leavilt, M. D., James A. Garrity, M. D., Vera .1. Suman, Ph. D., Bernd W. Scheithauer, M. D., Christine M. Lohse. B. s., and Fredric B. Meyer, M. D. The relapse rale, overall survival, and faetors associated with a decreased recurrence- free survival rate in patients with anterior visual pathway ( AVP) meningioma were compared with these features in palienls who had meningiomas at other sites. Man­agement ol' these patients is discussed. A review of the records of 581 consecutive patients who had primary resection of me­ningiomas between 197S and 1988 identified 43 palienls with AVP meningioma. Multiple clinical, surgical, and pathologic factors at the initial examination were analyzed to assess their association with recurrence, and the patients who had AVP meningioma were compared with patients who had non- AVP meningiomas to determine the factors that may influence re­currence. Recurrence- free and overall survival rates were de­termined. The AVP tumors were associaled with a higher rate of recurrence. Subtotal resection was more common in the AVP tumors, but it alone was not associated with the decrease in recurrence- free or overall survival rales. Several factors that may explain the higher recurrence rate in patients with AVP meningioma were identified. Anterior visual pathway menin­gioma is associaled with a higher rate of recurrence than are meningiomas at other sites. Operation remains the mainstay of treatment for symptomatic nonseeing eyes. Radiation therapy seems to be effective for managing recurrent tumor. Key Words: . Anterior visual pathway meningioma- Meningioma Prognostic factors Surgery. Meningioma of the anterior visual pathway ( AVP) represents 2.. V/ to IS'/ ( I) of all meningiomas and as much its \( Y'/ c ( 2) of all primary orbital lumors. Ya-mashila et al. ( 3) have suggested that meningioma al this site is associated with a higher recurrence rate than me­ningiomas in other sites. We report the outcome of pa­tients who had primary resection of AVP meningioma at Manuscript received July IW7: accepted February l( W7. From the Division of Radiation Oncology ( S. 1.. S. I. I ) eparlineiil of Laboratory Medicine and Pathology ( A. I'.. U. W. S.). Department of Ophthalmology (. l. A. I... J. A. Ci. J, Section of Biosiatislies ( V. J. S.. C. M. I..), and the Department of Neurologic Surgery ( F. B. M.). Mayo Clinic and Mayo Foundation. Rochester. Minnesota. F. S. A. Supported in part by an unrestricted grant from Research to Prevent blindness. New York, New York, U. S.. A. Address correspondence and reprint requests to Dr. S. L. Stafford. Mavo Clinic. 200 Fust Street SYV. Rochester M. N ss')() s F. S. A. Mayo Clinic Rochester (. luring the years 1978 through 1988 and compare them with a group of 538 palienls who had non- AVP meningiomas that met Ihe same se­lection criteria. MKTHODS The study cohort consisted of 4.3 palienls identified from a group of 581 consecutive palienls with previously untreated primary meningiomas, all of whom underwent initial resection between January I, 1978, and December 31, 1988. All tumors involved the optic nerve intracra-nially. within the orbit, or both. They are collectively referred to as anterior visual pathway ( AVP) meningio­ma. The completeness of resection was defined by the operating surgeon and, when available, on Ihe basis of immediate postoperative imaging. The terms gross total resection ( GTR). radical subtotal or subtotal resection ( STR), and biopsy were used. Recurrence was defined radiographically as an increase in the size of an existing lumor or the reappearance of a tumor that had been com­pletely resected. Treatment at recurrence was defined as surgical or radiothcrapeulic intervention. The medical records were reviewed, and the clinical, surgical, and histopathologic findings in the AVP cases were compared with the same findings in the non- AVP cases. Clinical and surgical factors included sex. age. number of tumors, location, tumor laterality, time from diagnosis to operation, and extent of resection. The pres­ence or absence of en plaque tumor growth pattern at operation; invasion of bone, dura, brain parenchyma, soft tissue, or venous sinuses; and various histologic features were also compared ( Table I). The pathologic results were reviewed by one of the authors ( A. P.). and consultation was provided by another ( B. W. S.). Only meningiomas meeting the definition in the 1993 World Health Organization classification of central nervous system tumors ( 4) were included in the study. Specifically, meningeal hemangiopericytoma (" angioblaslic meningioma") and hemangioblastoma were excluded. Atypical meningiomas were defined as those with four or more mitotic figures/ 10 high- power 206 MENINGIOMA OF THE ANTERIOR VISUAL PATHWAY 207 TABLE 1. Comparison of clinical, surgical, and pathologic factors in patients with anterior visual pathway meningiomas and patients with meningiomas at other sites Factor Clinical Male sex Median age at diagnosis ( yr) Multiple lesions Side involved Left Right Mid- line Multiple Extent of surgery GTR Less than GTR Surgical En- plaque growth Bone invasion Dura invasion Involvement of soft tissue'' Venous sinus invasion Histologic Atypical Lack of cellular pleomorphism Nuclear atypia Macronucleoli Small cells Tumor sheeting Necrosis Increased mitotic rate Increased cellularity AVP group ( n = 41"), % 26 47 0 35 49 7 12 40 60 35 27 17 40 10 15 76 27 15 5 12 10 2 51 Non- AVP group (; i = 528"), % 34 58 3 46 40 7 8 83 17 5 4 9 7 9 19 48 57 28 15 18 16 9 54 P value 0.315 0.001 0.628 0.415 0.001 < 0.001 < 0.001 0.098 < 0.001 0.777 0.678 0.001 < 0.001 0.069 0.100 0.402 0.374 0.238 0.871 Abbreviations: AVP, anterior visual pathway; GTR, gross total re­section. " There was insufficient tissue to assess in 2 AVP tumors and 10 non- AVP tumors. '' Soft tissue invasion was defined as involvement of the carotid artery or other major arteries intracranially, involvement of the muscles of the orbil, or, in skull base tumors, extension into extracranial soft tissue by extension through the foramina of the skull base into the infratemporal/ pterygopalatine fossa. fields ( hpf) or the presence of at least three of the fol­lowing four variables: tumor sheeting, macronucleoli, small cells, and hypercellularity ( 5). Ten histologic vari­ables were assessed in each included patient's initially resected tumor. These factors were absence or presence of brain invasion, maximum mitotic rate per 10 hpf ( 1 hpf = 0 . 1 6 mm2), maximum cellularity, degree of pleo­morphism, cellular atypia, nuclear atypia, sheeting archi­tecture, small cell formation, macronucleoli, and extent of necrosis. Follow- up information was obtained from review of the medical record and from a detailed questionnaire sent to all patients known to be alive at last contact. All as­pects of the study were approved by the Mayo Institu­tional Review Board. Fisher's exact test was used to assess the association between the dichotomous histologic variables and the involvement of the AVP. Associations between continu­ous variables and the involvement of the AVP were ex­amined with the Wilcoxon rank- sum test. The distribu­tions of overall survival and recurrence- free survival were estimated with the Kaplan- Meier method ( 6). The log- rank test ( 7) was used to assess which clinical, sur­gical, or pathologic factors were univariately associated with an increased risk of recurrence. P =£ 0.05 was con­sidered to be statistically significant. RESULTS Of the 581 patients, 43 had AVP tumor and 538 had non- AVP tumors. The median age of the patients in the AVP group was 47 years ( range, 5- 79 years); 74% were female and 26% were male. The median duration of fol­low- up for both groups was 8.2 years ( range, 14 days to 15.5 years). Of the 43 AVP tumors, 9 involved the orbil only, 7 were intracranial only, and 27 were both orbital and intracranial. No patients in the AVP group had mul­tiple tumors. The initial surgical procedure in the AVP group was GTR in 40%, STR in 56%;, and biopsy in 5%. In comparison, in the non- AVP group, only 17% of pa­tients had STR, less than 1 % underwent biopsy, and 83% had GTR. Two patients with AVP tumor underwent post­operative radiation therapy after initial resection. Patients with AVP meningioma were observed until death, or a median of 8.3 years. In the AVP group, 5 patients died, and 23 had radiographically detected re­currences during follow- up. The clinical, surgical, and pathologic factors associated with AVP meningioma arc shown in Table 1. Recurrence- free survival at 5 years was 62% ( 95% confidence interval fCIJ, 49% to 70%) in the AVP group. Recurrence- free survival in the AVP group was significantly less than that in the non- AVP group ( Fig. 1; P < 0.001). The relative risk of recurrence in the AVP group compared with that in the non- AVP group was estimated to be 3.4 ( 95% CI, 2.1- 5.3). The overall survival of the patients with AVP tumor at 7.5 years was 92% ( range, 84- 100%). Unlike the non- AVP group, the AVP group had no decrease in over­all survival compared with an age- and sex- matched United States population ( Figs. 2 and 3). However, this % uu - 80- 60- 40- 20- 0- Non- AVP group AVP group " V _ 1 L _ - 0 1 2 3 4 5 6 7 8 Years FIG. 1. Recurrence- free survival rate in patients with meningioma of the anterior visual pathway ( AVP) and patients with meningi­omas at other sites ( non- AVP). ./ Neuw- Ophthalmol, Vol. IK No. .(, IVVX 208 S. L. STAFFORD ET AL. 100 60 % 40- AVP Expected 10 Years FIG. 2. Overall survival from date of operation in patients with meningioma of the anterior visual pathway and in an age- and sex- matched cohort from the United States population. finding may be a reflection of the small size of the AVP group compared with that of the non- AVP group. The age at diagnosis was younger in the AVP group ( P < 0.001). Patients with an AVP tumor were less likely to have undergone GTR ( F < 0.001). The AVP group also had a higher incidence of an en plaque pattern of tumor growth at the time of operation ( 35%) than the non- AVP group ( 5%). In contrast to the non- AVP group, STR was not asso­ciated with a decrease in recurrence- free survival among the patients with AVP tumor. Anterior visual pathway tumor was more likely to involve bone ( P < 0.001) and soft tissue ( as defined in Table l; P < 0.001) than non- AVP tumor. In addition, there was a trend toward an increased rate of dural involvement in the AVP group ( P = 0.098). A significantly larger proportion of AVP tu­mors were associated with the absence of cellular pleo-morphism and nuclear atypia ( P < 0.001). There was a trend toward a higher proportion of AVP tumors without macronucleoli ( P = 0.069). The rate of atypical menin­gioma was not increased in the AVP group ( Table 1). Treatment of patients with radiographically detected first recurrence included further observation ( that is, no intervention within 90 days; n = 9), radiation alone ( n = 2), operation alone ( n = 9), and operation with post­operative radiation ( « = 3). Six patients had a second recurrence. None of the patients who had had previous radiation therapy were known to have recurrence. Treat­ment at second recurrence was radiation alone ( w = 2), operation alone ( n = 3), and operation and radiation ( n = 1). One patient had a third recurrence after two op­erations and was then treated with operation and postop­erative radiation. In total, six patients in the AVP group were treated with radiation sometime during the course of their care. Two complications occurred in the patients with AVP meningioma treated with radiation. Radiation retinopa­thy occurred in one patient who received 5760 cGy for a massive frontal tumor involving both orbits. Dry eye required lubricating drops, but no further therapy was needed in one patient after receiving 6480 cGy for an orbital tumor with intracranial extension. This patient had undergone two resections before receiving radiation therapy. In the non- AVP group, 31 patients had radiation therapy sometime in the course of their treatment, and none have had a radiation- related complication. DISCUSSION Meningiomas of the AVP are an interesting group of tumors. In this series, this site was associated with sev­eral other factors that may account for the high incidence of recurrence. Multivariate analysis of the entire menin­gioma cohort indicates that age less than 40 years, male sex, less than GTR, AVP site, and four or more mitotic figures/ 10 hpf are independently associated with a de­creased rate of recurrence- free survival ( 8). Compared with meningiomas at other sites, AVP meningioma has a higher rate of STR, en plaque tumor growth, and a younger age at diagnosis, all of which may contribute to the higher recurrence rate. In many series, STR has been associated with an increased recurrence rate ( 3,9- 13). However, STR alone in our AVP group was not associ­ated with a decreased rate of recurrence- free survival. Again, this finding could be a reflection of a small num­ber of patients with AVP tumor. At least one other series ( 3) has shown that the AVP site is associated with a higher rate of recurrence than other locations. Other in­vestigators have attributed increased recurrence rates to other sites ( 3,14). Age has variably been shown to in­crease ( 15) or not to increase ( 16,17) the rate of recur­rence and was independently associated with a higher recurrence rate in our series ( 8). We did not find an increased rate of atypical histologic features that are as­sociated with higher recurrence rates in the AVP tumors. The only histologic finding associated with a propensity for a high recurrence rate is that of the papillary clear- cell subtypes ( 18,19). A combination of some or all of these factors will help guide the clinician in the appropriate selection of methods for treating individual patients. Historically, surgical management of symptomatic in­tracranial meningioma and observation, followed by sur­gical management of intraorbital or sheath tumor in the orbit, has been advocated, including meningioma involv- 100 - i<^-- 80- % 60 40 20 Non- AVP Expected Years FIG. 3. Overall survival from date of operation in patients with meningiomas at sites other than the anterior visual pathway and in an age- and sex- matched cohort from the United States popu­lation. J Nntm- Ophllmlnml, Vol. /< S', No. J. 1998 MENINGIOMA OF THE ANTERIOR VISUAL PATHWAY 209 ing the cavernous sinus ( 20,21). However, radiation therapy alone has been used effectively for intracranial meningioma at sites such as the cavernous sinus and optic nerve sheath ( 22,23), where the potential morbidity associated with operation is high ( 24- 26). Advances in imaging and treatment planning make it possible to use radiation therapy without a biopsy in selected cases in these high- risk surgical sites ( 27). Medial sphenoid, or parasellar, meningioma has been managed with opera­tion alone or with operation and radiation therapy ( 8,28) and has been the subject of a comprehensive review ( 29). Investigators have advocated stereotactic radiosurgery for meningioma not directly involving the optic nerve ( 30- 34); however, these series need longer follow- up for adequate assessment of local control with radiosurgery. Also, evidence indicates that external beam radiation alone should be considered in patients with seeing eyes who have optic nerve sheath meningioma ( 23,35). Mod­ern techniques using three- dimensional conformal treat­ment planning may limit morbidity ( 36). Although our sample was small, none of our patients in whom radia­tion therapy was a component of management have had recurrence. Other investigators have reported stable or improved visual function in patients who underwent STR for AVP meningioma and had radiation as part of the treatment ( 16 of 20 patients) ( 22). In a large, recently reported series including all sites, the rate of local control after STR and radiation therapy was 87% ( 37). When radiation therapy is used, regardless of technique, the normal structures that are treated must be considered, to minimize morbidity ( 38- 42). The timing of radiation therapy after STR is a controversial issue. Doses that control most of these tumors ( 4500 to 5300 cGy) cannot be used without assessing the risk of retinitis. Some re­cent data, however, indicate that postoperative radiation therapy not only has an impact on local control ( 37,43) but also may have a favorable impact on overall survival rates ( 37,44). These data are helpful but lack randomiza­tion, and each clinical situation is different. Whether ra­diation therapy is used immediately after first resection or at signs of first recurrence should be weighed with the potential for morbidity and the recent data from Condra et al. ( 37) It is our preference to use radiation in most postoperative eases at referral. These tumors are known to express progesterone and estrogen receptors ( 45), and various hormone therapies have been tried. Currently, the Southwest Oncology Group ( San Antonio, TX) is evaluating RU- 486 in a randomized trial. When the re­sults of this trial are known, we will have a better un­derstanding of the efficacy of hormonal therapy. In our series, none of the patients in the non- AVP group ( « = 31) had radiation- related complications. The two patients with complications in the AVP group were treated with doses deemed to be necessary for tumor control, with the realization that the complication rate may be higher with these doses ( 5760 cGy and 6480 cGy). CONCLUSIONS Anterior visual pathway meningioma is associated with a higher rate of recurrence than non- AVP tumor and is associated with clinical, surgical, and pathologic fac­tors that may explain this high rate. 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Role of radiotherapy in the treatment of meningioma. Bull Cancer Radiother I995; 82: 35- 9. 45. Rubinstein AB, Loven D, Geier A, Reichenthal E, Gadoth N. Hor­mone receptors in initially excised versus recurrent intracranial meningiomas. J Neurosurg 1994; 81: 184- 7. ./ Neitm- Ophllmhnol, Veil. 18. No. 3. 1998