Heyoung McBride

The impact of adjuvant stereotactic radiosurgery on atypical meningioma recurrence following aggressive microsurgical resection

OBJECT Patients with atypical meningioma often undergo gross-total resection (GTR) at initial presentation, but the role of adjuvant radiation therapy remains unclear. The increasing prevalence of stereotactic radiosurgery (SRS) in the modern neurosurgical era has led to the use of routine postoperative radiation therapy in the absence of evidence-based guidelines. This study sought to define the long-term recurrence rate of atypical meningiomas and identify the value of SRS in affecting outcome. METHODS The authors identified 228 patients with microsurgically treated atypical meningiomas who underwent a total of 257 resections at the Barrow Neurological Institute over the last 20 years. Atypical meningiomas were diagnosed according to current WHO criteria. Clinical and radiographic data were collected retrospectively. RESULTS Median clinical and radiographic follow-up was 52 months. Gross-total resection, defined as Simpson Grade I or II resection, was achieved in 149 patients (58%). The median proliferative index was 6.9% (range 0.4%-20.6%). Overall 51 patients (22%) demonstrated tumor recurrence at a median of 20.2 months postoperatively. Seventy-one patients (31%) underwent adjuvant radiation postoperatively, with 32 patients (14%) receiving adjuvant SRS and 39 patients (17%) receiving adjuvant intensity modulated radiation therapy (IMRT). The recurrence rate for patients receiving SRS was 25% (8/32) and for IMRT was 18% (7/39), which was not significantly different from the overall group. Gross-total resection was predictive of progression-free survival (PFS; relative risk 0.255, p < 0.0001), but postoperative SRS was not associated with improved PFS in all patients or in only those with subtotal resections. CONCLUSIONS Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection. This analysis of the largest patient series to date suggests that close observation remains reasonable in the setting of aggressive microsurgical resection. Although postoperative adjuvant SRS did not significantly affect tumor recurrence rates in this experience, a larger cohort study with longer follow-up may reveal a therapeutic benefit in the future.

Gamma Knife radiosurgery for posterior fossa meningiomas: a multicenter study.

OBJECT Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa. METHODS At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12-89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm(3), and a median margin dose of 13.6 Gy (range 8-40 Gy) was delivered to the tumor. RESULTS At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30-4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69-15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01-1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01-1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05-3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively. CONCLUSIONS Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation for patients with posterior fossa meningiomas. Those with a smaller tumor volume and no prior radiation therapy were more likely to have a favorable response after radiosurgery. Rarely, additional procedures may be required for hydrocephalus or tumor progression.

Stereotactic radiosurgery for intracranial hemangioblastomas: a retrospective international outcome study

OBJECT The purpose of this study was to evaluate the role of stereotactic radiosurgery (SRS) in the management of intracranial hemangioblastomas. METHODS Six participating centers of the North American Gamma Knife Consortium and 13 Japanese Gamma Knife centers identified 186 patients with 517 hemangioblastomas who underwent SRS. Eighty patients had 335 hemangioblastomas associated with von Hippel-Lindau disease (VHL) and 106 patients had 182 sporadic hemangioblastomas. The median target volume was 0.2 cm(3) (median diameter 7 mm) in patients with VHL and 0.7 cm(3) (median diameter 11 mm) in those with sporadic hemangioblastoma. The median margin dose was 18 Gy in VHL patients and 15 Gy in those with sporadic hemangioblastomas. RESULTS At a median of 5 years (range 0.5-18 years) after treatment, 20 patients had died of intracranial disease progression and 9 patients had died of other causes. The overall survival after SRS was 94% at 3 years, 90% at 5 years, and 74% at 10 years. Factors associated with longer survival included younger age, absence of neurological symptoms, fewer tumors, and higher Karnofsky Performance Status. Thirty-three (41%) of the 80 patients with VHL developed new tumors and 17 (16%) of the106 patients with sporadic hemangioblastoma had recurrences of residual tumor from the original tumor. The 5-year rate of developing a new tumor was 43% for VHL patients, and the 5-year rate of developing a recurrence of residual tumor from the original tumor was 24% for sporadic hemangioblastoma patients. Factors associated with a reduced risk of developing a new tumor or recurrences of residual tumor from the original tumor included younger age, fewer tumors, and sporadic rather than VHL-associated hemangioblastomas. The local tumor control rate for treated tumors was 92% at 3 years, 89% at 5 years, and 79% at 10 years. Factors associated with an improved local tumor control rate included VHL-associated hemangioblastoma, solid tumor, smaller tumor volume, and higher margin dose. Thirteen patients (7%) developed adverse radiation effects (ARE) after SRS, and one of these patients died due to ARE. CONCLUSIONS When either sporadic or VHL-associated tumors were observed to grow on serial imaging studies, SRS provided tumor control in 79%-92% of tumors.

Gamma Knife radiosurgery for sellar and parasellar meningiomas: a multicenter study.

OBJECT Parasellar and sellar meningiomas are challenging tumors owing in part to their proximity to important neurovascular and endocrine structures. Complete resection can be associated with significant morbidity, and incomplete resections are common. In this study, the authors evaluated the outcomes of parasellar and sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an adjunct to microsurgical removal or conventional radiation therapy and as a primary treatment modality. METHODS A multicenter study of patients with benign sellar and parasellar meningiomas was conducted through the North American Gamma Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors identified all patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were also required to have a minimum of 6 months of imaging and clinical follow-up after GKRS. Factors predictive of new neurological deficits following GKRS were assessed via univariate and multivariate analyses. Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. RESULTS The authors identified 763 patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were assessed clinically and with neuroimaging at routine intervals following GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of 56 years (range 8-90 years). Three hundred fifty-five patients (50.7%) had undergone at least one resection before GKRS, and 3.8% had undergone prior radiation therapy. The median follow-up after GKRS was 66.7 months (range 6-216 months). At the last follow-up, tumor volumes remained stable or decreased in 90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10 years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery, prior radiation therapy, or a tumor margin dose < 13 Gy significantly increased the likelihood of tumor progression after GKRS. At the last clinical follow-up, 86.2% of patients demonstrated no change or improvement in their neurological condition, whereas 13.8% of patients experienced symptom progression. New or worsening cranial nerve deficits were seen in 9.6% of patients, with cranial nerve (CN) V being the most adversely affected nerve. Functional improvements in CNs, especially in CNs V and VI, were observed in 34% of patients with preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6% of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome with tumor growth and accompanying neurological decline was statistically more likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior surgery (p = 0.021). CONCLUSIONS Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients.

Skull base chondrosarcoma radiosurgery: report of the North American Gamma Knife Consortium

OBJECT Stereotactic radiosurgery (SRS) is a potentially important option for patients with skull base chondrosarcomas. The object of this study was to analyze the outcomes of SRS for chondrosarcoma patients who underwent this treatment as a part of multimodality management. METHODS Seven participating centers of the North American Gamma Knife Consortium (NAGKC) identified 46 patients who underwent SRS for skull base chondrosarcomas. Thirty-six patients had previously undergone tumor resections and 5 had been treated with fractionated radiation therapy (RT). The median tumor volume was 8.0 cm3 (range 0.9-28.2 cm3), and the median margin dose was 15 Gy (range 10.5-20 Gy). Kaplan-Meier analysis was used to calculate progression-free and overall survival rates. RESULTS At a median follow-up of 75 months after SRS, 8 patients were dead. The actuarial overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. Local tumor progression occurred in 10 patients. The rate of progression-free survival (PFS) after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with shorter PFS. Eight patients required salvage resection, and 3 patients (7%) developed adverse radiation effects. Cranial nerve deficits improved in 22 (56%) of the 39 patients who deficits before SRS. Clinical improvement after SRS was noted in patients with abducens nerve paralysis (61%), oculomotor nerve paralysis (50%), lower cranial nerve dysfunction (50%), optic neuropathy (43%), facial neuropathy (38%), trochlear nerve paralysis (33%), trigeminal neuropathy (12%), and hearing loss (10%). CONCLUSIONS Stereotactic radiosurgery for skull base chondrosarcomas is an important adjuvant option for the treatment of these rare tumors, as part of a team approach that includes initial surgical removal of symptomatic larger tumors.

Gamma knife radiosurgery for cerebellopontine angle meningiomas: A multicenter study

BACKGROUND Resection of cerebellopontine angle (CPA) meningiomas may result in significant neurological morbidity. Radiosurgery offers a minimally invasive alternative to surgery. OBJECTIVE To evaluate, in a multicenter cohort study, the outcomes of patients harboring CPA meningiomas who underwent Gamma Knife radiosurgery (GKRS). METHODS From 7 institutions participating in the North American Gamma Knife Consortium, 177 patients with benign CPA meningiomas treated with GKRS and at least 6 months radiologic follow-up were included for analysis. The mean age was 59 years and 84% were female. Dizziness or imbalance (48%) and cranial nerve (CN) VIII dysfunction (45%) were the most common presenting symptoms. The median tumor volume and prescription dose were 3.6 cc and 13 Gy, respectively. The mean radiologic and clinical follow-up durations were 47 and 46 months, respectively. Multivariate regression analyses were performed to identify the predictors of tumor progression and neurological deterioration. RESULTS The actuarial rates of progression-free survival at 5 and 10 years were 93% and 77%, respectively. Male sex (P = .014), prior fractionated radiation therapy (P = .010), and ataxia at presentation (P = .002) were independent predictors of tumor progression. Symptomatic adverse radiation effects and permanent neurological deterioration were observed in 1.1% and 9% of patients, respectively. Facial spasms at presentation (P = .007) and lower maximal dose (P = .011) were independently associated with neurological deterioration. CONCLUSION GKRS is an effective therapy for CPA meningiomas. Depending on the patient and tumor characteristics, radiosurgery can be an adjuvant treatment to initial surgical resection or a standalone procedure that obviates the need for resection in most patients.

Long-term radiosurgical control of subtotally resected adult pineocytomas

OBJECT The optimal management of pineocytomas remains controversial. Although the value of complete microsurgical removal is well accepted, gross-total resection is not always feasible. Data regarding the role of postoperative adjuvant stereotactic radiosurgery (SRS) for residual disease is limited and conflicting. Here, the authors review the largest single-institution experience with multimodal pineocytoma management in an effort to quantify the utility of adjuvant radiosurgical treatment of residual disease. METHODS The medical records and radiographic studies for all patients with histologically confirmed pineocytoma at the Barrow Neurological Institute between 1999 and 2011 were retrospectively reviewed. Clinical and radiographic data, including the volumetric extent of resection, were collected retrospectively, and Kaplan-Meier analysis was used to identify progression-free survival. RESULTS Fourteen adults with newly diagnosed pineocytomas were surgically treated in the period from 1999 to 2011. The median clinical and radiographic follow-ups were 44 and 53 months, respectively. Twelve patients (86%) underwent microsurgical removal and 2 (14%) underwent endoscopic biopsy. Five patients (36%) had complete resections and 9 (64%) demonstrated residual disease. Three patients (21%) presented with radiographic recurrence at a median interval of 43 months after initial treatment (range 13-83 months). At the time of recurrence, the median preoperative tumor volume was 2.6 cm(3). Adjuvant SRS was used to treat 3 subtotally resected tumors (33%) following initial presentation and 2 (66%) at the time of recurrence. Among patients with subtotally resected tumors, progression-free survival was significantly longer (p < 0.05) for those who did as compared with those who did not undergo adjuvant radiosurgery. To date, no patient who underwent adjuvant radiosurgery has demonstrated radiographic or clinical evidence of disease progression. CONCLUSIONS Microsurgical removal remains the definitive treatment for pineocytomas, yet residual disease can be effectively controlled using adjuvant SRS.