Scott L. Stafford

Meningioma grading: an analysis of histologic parameters.

Histologic grading of meningiomas has prognostic and sometimes therapeutic implications, but diagnostic criteria for atypical meningioma are vague, and the significance of brain invasion in the determination of malignancy remains controversial. We reviewed our experience with 581 patients whose meningiomas were resected at Mayo Clinic during the years 1978 through 1988. All patients were followed until death or a median of 9.0 years. Ten histologic parameters were assessed and compared with recurrence-free survival. On univariate analysis, six variables were associated with recurrence, although most were statistically significant only in the subset of patients having undergone gross total tumor resection. On multivariate analyses, the most significant parameters were histologic brain invasion (when assessable) and maximal mitotic rate of at least four per 10 high-power fields (HPF). Also significant were combinations of at least three of the following four parameters: hypercellularity, architectural sheeting, macronucleoli, and small cell formation. Proposed grading criteria based on these findings yielded 81% classic, 15% atypical, and 4% brain invasive meningiomas with respective 5-year recurrence rates of 12%, 41%, and 56%. There was no association between histologic grade and either extent of surgical resection or patient age. However, male sex was associated with high-grade (atypical/brain invasive) tumors. Too few frankly anaplastic meningiomas were encountered for statistical analysis. Brain invasion and an increased mitotic index (at least four per 10 HPF) are the most powerful histologic factors prognostic for recurrence in meningiomas. We propose an objective definition for atypical meningioma based on our data. Because the difference in recurrence rates for brain invasive and atypical meningiomas was not statistically significant, it could not be determined whether brain invasion alone warrants a designation of malignancy. Likewise, we were unable to determine what constitutes histologic anaplasia due to the rarity of such cases.

Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients.

OBJECTIVETo determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. METHODSOne hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20–90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1–5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm3 (range, 0.5–50.5 cm3), and the median tumor margin dose was 16 Gy (range, 12–36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. RESULTSOverall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. CONCLUSIONRadiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.

A study on the radiation tolerance of the optic nerves and chiasm after stereotactic radiosurgery

PURPOSE To evaluate the risk of clinically significant radiation optic neuropathy (RON) for patients having stereotactic radiosurgery of benign tumors adjacent to the optic apparatus. METHODS AND MATERIALS We reviewed the dose plans and clinical outcomes of 218 gamma knife procedures (215 patients) for tumors of the sellar and parasellar region (meningiomas, n = 122; pituitary adenomas, n = 89; craniopharyngiomas, n = 7 patients). Previous surgery or radiation therapy was performed in 156 (66%) and 24 (11%) patients, respectively. Median follow-up was 40 months (range 4-115). RESULTS The median maximum radiation dose to the optic nerve was 10 Gy (range 0.4-16.0). Four patients (1.9%) developed RON at a median of 48 months after radiosurgery. All had prior surgery, and 3 of 4 had external beam radiotherapy (EBRT) in their management either before (n = 2) or adjuvantly (n = 1). The risk of developing a clinically significant RON was 1.1% for patients receiving 12 Gy or less. Patients receiving prior or concurrent EBRT had a greater risk of developing RON after radiosurgery (p = 0.004). CONCLUSION RON occurred in less than 2% of our patients, despite the majority (73%) receiving more than 8 Gy to a short segment of the optic apparatus. Knowledge of the dose tolerance of these structures permits physicians to be more aggressive in treating patients with sellar or parasellar tumors, especially those with hormone-producing pituitary adenomas that appear to require higher doses to achieve biochemical remission.

Primarily Resected Meningiomas: Outcome and Prognostic Factors in 581 Mayo Clinic Patients, 1978 Through 1988

OBJECTIVE To establish prognostic factors for recurrence and outcome of surgical treatment, with or without postoperative radiation therapy, in patients with meningiomas. MATERIAL AND METHODS From 1978 through 1988, 581 patients underwent initial resection of a previously untreated primary meningioma at Mayo Clinic Rochester. In this study cohort, the outcome and prognostic factors associated with radiographic progression-free survival were analyzed. RESULTS Gross total resection (GTR) of the meningioma was accomplished in 80% of patients; the other 20% underwent less than GTR. Perioperative mortality within 10 days was 1.6%. Overall survival was significantly decreased from that for an age- and sex-matched cohort from the US white population. Progression-free survival at 5 and 10 years was 88% and 75%, respectively, in patients who underwent GTR and 61% and 39%, respectively, in those who underwent less than GTR. Multivariate analysis showed that age younger than 40 years, male sex, less than GTR, optic nerve involvement, and 4 or more mitotic figures per 10 high-power fields were associated with decreased progression-free survival. The 581 patients had 106 first recurrences. A trend toward improved progression-free survival was noted after first recurrence when irradiation with or without operation was used in comparison with only surgical treatment (P = 0.058). CONCLUSION With only operative treatment of meningioma, the 10-year recurrence rate was 25% in patients who had GTR and 61% in those who had less than GTR. These results emphasize the need for long-term follow-up and for consideration of adjuvant radiation therapy. Patients treated at the time of recurrence seem to benefit from radiation therapy with or without surgical resection. Factors associated with recurrence were (1) less than GTR, (2) involvement of the anterior visual pathway, (3) age younger than 40 years, and (4) increased mitotic index.

Stereotactic radiosurgery provides equivalent tumor control to simpson grade 1 resection for patients with small- to medium-size meningiomas

PURPOSE To compare tumor control rates after surgical resection or stereotactic radiosurgery for patients with small- to medium-size intracranial meningiomas. MATERIALS AND METHODS Between 1990 and 1997, 198 adult meningioma patients treated at our center underwent either surgical resection (n = 136) or radiosurgery (n = 62) as primary management for benign meningiomas <35 mm in average diameter. Tumor recurrence or progression rates were calculated by the Kaplan-Meier method according to an independent radiographic review. The mean follow-up was 64 months. RESULTS The tumor resections were Simpson Grade 1 in 57 (42%), Grade 2 in 57 (42%), and Grade 3-4 in 22 (16%). The mean margin and maximal radiation dose at radiosurgery was 17.7 Gy and 34.9 Gy, respectively. Tumor recurrence/progression was more frequent in the surgical resection group (12%) than in the radiosurgical group (2%; p = 0.04). No statistically significant difference was detected in the 3- and 7-year actuarial progression-free survival (PFS) rate between patients with Simpson Grade 1 resections (100% and 96%, respectively) and patients who underwent radiosurgery (100% and 95%, respectively; p = 0.94). Radiosurgery provided a higher PFS rate compared with patients with Simpson Grade 2 (3- and 7-year PFS rate, 91% and 82%, respectively; p <0.05) and Grade 3-4 (3- and 7-year PFS rate, 68% and 34%, respectively; p <0.001) resections. Subsequent tumor treatments were more common after surgical resection (15% vs. 3%, p = 0.02). Complications occurred in 10% of patients after radiosurgery compared with 22% of patients after surgical resection (p = 0.06). CONCLUSIONS The PFS rate after radiosurgery was equivalent to that after resection of a Simpson Grade 1 tumor and was superior to Grade 2 and 3-4 resections in our study. If long-term follow-up confirms the high tumor control rate and low morbidity of radiosurgery, this technique will likely become the preferred treatment for most patients with small- to moderate-size meningiomas without symptomatic mass effect.

High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction.

OBJECTIVE: Stereotactic radiosurgery is being used with more frequency in the management of patients with trigeminal neuralgia. To improve facial pain outcomes, many centers have increased the prescribed radiation dose to the trigeminal nerve. METHODS: Between April 1997 and December 1999, 68 patients underwent radiosurgery for trigeminal neuralgia with use of the Leksell gamma knife (Elekta Instruments, Norcross, GA) and a single 4-mm isocenter of radiation. Twenty-seven patients (40%) received 70 Gy (low dose) of irradiation and 41 patients (60%) received 90 Gy (high dose). The groups were similar with regard to age, sex, duration of pain, number of prior surgeries, and preexisting trigeminal deficits. The primary facial pain outcomes for analysis were excellent (pain-free, no medications) and good (pain-free, reduced medications). The mean length of follow-up after radiosurgery was 14.4 months (range, 2-36 mo). RESULTS: At last follow-up examination, 11(41 %) of the 27 patients with low-dose radiosurgery remained pain-free compared with 25 (61 %) of the 41 patients with high-dose radiosurgery (P = 0.17). Additional surgery was performed in 12 low-dose patients (44%) and 8 high-dose patients (20%) (P = 0.05). High-dose radiosurgery was associated with an increased rate of permanent trigeminal nerve dysfunction (54% versus 15%, P = 0.003). Bothersome dysesthesias occurred in 13 high-dose patients (32%), whereas only 1 low-dose patient had this complication (P = 0.01). Three high-dose patients (8%) developed corneal numbness after radiosurgery. Pain recurred with more frequency in patients not developing trigeminal nerve dysfunction after radiosurgery (9 of 22 patients, 41 %) compared with those who sustained facial numbness, paresthesias, or dysesthesias (4 of 27 patients, 15%); however, the difference was not statistically significant (P = 0.08). CONCLUSION: Higher doses of radiation may correlate with better facial pain outcomes after radiosurgery for trigeminal neuralgia. However, the incidence of significant trigeminal nerve dysfunction is markedly increased after radiosurgery for patients receiving high-dose radiosurgery. Because of the nonselective nature of this ablative technique, dose prescription should be limited to less than 90 Gy.

Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? a prospective double-blind, randomized study

PURPOSE To test the hypothesis that increasing the nerve length within the treatment volume for trigeminal neuralgia radiosurgery would improve pain relief. METHODS AND MATERIALS Eighty-seven patients with typical trigeminal neuralgia were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal dose with 4-mm diameter collimators) using either one (n = 44) or two (n = 43) isocenters. The median follow-up was 26 months (range 1-36). RESULTS Pain relief was complete in 57 patients (45 without medication and 12 with low-dose medication), partial in 15, and minimal in another 15 patients. The actuarial rate of obtaining complete pain relief (with or without medication) was 67.7% +/- 5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain relapsed in 30 of 72 responding patients. Facial numbness and mild and severe paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one-isocenter patients, respectively (p = 0.23). Improved pain relief correlated with younger age (p = 0.025) and fewer prior procedures (p = 0.039) and complications (numbness or paresthesias) correlated with the nerve length irradiated (p = 0.018). CONCLUSIONS Increasing the treatment volume to include a longer nerve length for trigeminal neuralgia radiosurgery does not significantly improve pain relief but may increase complications.

Rhabdoid meningioma : an aggressive variant

It is has been suggested that rhabdoid morphology is associated with a poor prognosis, regardless of tumor histogenesis. We report a series of 15 meningiomas with rhabdoid features. Nine patients had undergone multiple resections. In six, the rhabdoid component was histologically apparent only in recurrences. Rhabdoid morphology was defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Ultrastructurally, the latter consisted of whorls of intermediate filaments often entrapping lysosomes or other organelles. Meningothelial features included whorl formation and nuclear pseudoinclusions, immunohistochemical coexpression of vimentin and epithelial membrane antigen, and the ultrastructural finding of interdigitating cell membranes and intercellular junctions. At the histologic level, a conventional meningioma component was noted in most tumors; only four lesions were entirely rhabdoid. Histologic malignancy (brain invasion or anaplasia) was observed in nine cases, another two tumors being considered malignant on the basis of extracranial metastasis. In the majority, increased cell proliferation was evidenced by a high mitotic rate or MIB-1 LI. At last follow-up, 13 patients (87%) had experienced at least one recurrence and 8 (53%) were dead of disease. Median time to death was 5.8 years after initial surgery and 3.1 years after the first appearance of rhabdoid morphology. Our findings corroborate those from a smaller series recently reported by Kepes et al. on the same entity (Kepes JJ, Moral LA, Wilkinson SB, Abdullah A, Llena JF. Rhabdoid transformation of tumor cells in meningiomas: A histologic indication of increased proliferative activity. Report of four cases. Am J Surg Pathol 1998;22:231-8). They further suggest that rhabdoid meningiomas are highly aggressive tumors and that the rhabdoid phenotype represents a marker of malignant transformation in meningiomas.

Orbital lymphoma: radiotherapy outcome and complications

BACKGROUND AND PURPOSE Orbital non-Hodgkins lymphomas (NHL) have traditionally been treated with radiation. Forty-eight patients presenting with orbital NHL were treated with radiation and were evaluated for local control, overall survival, cause-specific survival, and complications. MATERIALS AND METHODS Forty-five patients had low-grade and 3 patients had intermediate-grade histologic findings. Orbit-only disease occurred in 22 patients, the conjunctiva in 16, both in five, and lacrimal gland only in five. Patient age ranged from 35 to 94 years (median, 68). Ann Arbor stages were cIEA (34), cIIEA (six), cIIIEA (two), and cIVEA (six). Radiation doses ranged between 15 and 53.8 Gy (median, 27.5 Gy). RESULTS Follow-up ranged from 0.14 to 18.23 years (median, 5.35). Median overall survival and cause-specific survival were 6.5 and 15.5 years, respectively. Patients with clinical stage I or II disease had significantly better overall and cause-specific survival than patients with stage III or IV disease. Ten-year relapse-free survival in 41 patients with stage I or II disease was 66%. However, there was continued downward pressure on relapse-free survival out to 18 years. One local failure occurred. Twenty-five patients sustained acute complications. There were 17 minor and four major late complications. All major late complications occurred with doses more than 35 Gy. CONCLUSIONS Excellent local control with radiation doses ranging from 15 to 30 Gy is achieved. Patients with stage I or II disease have better overall and cause-specific survival than patients with stage III or IV disease. Late relapse occurs in sites other than the treated orbit, even in patients with early-stage disease. Doses 35 Gy or higher result in significant late complications and are therefore not indicated for patients with low-grade tumors.

Glomus jugulare tumor: Tumor control and complications after stereotactic radiosurgery

We evaluated toxicity and long‐term efficacy of stereotactic radiosurgery in patients with symptomatic or progressive glomus jugulare tumors.