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Michael A. Garcia, Ann Lazar, Sai Duriseti, David R. Raleigh, Christopher P. Hess, Shannon E. Fogh, Igor J. Barani, Jean L. Nakamura, David A. Larson, Philip Theodosopoulos, Michael McDermott, Penny K. Sneed and Steve Braunstein

OBJECTIVE

High-resolution double-dose gadolinium-enhanced Gamma Knife (GK) radiosurgery-planning MRI (GK MRI) on the day of GK treatment can detect additional brain metastases undiagnosed on the prior diagnostic MRI scan (dMRI), revealing increased intracranial disease burden on the day of radiosurgery, and potentially necessitating a reevaluation of appropriate management. The authors identified factors associated with detecting additional metastases on GK MRI and investigated the relationship between detection of additional metastases and postradiosurgery patient outcomes.

METHODS

The authors identified 326 patients who received GK radiosurgery at their institution from 2010 through 2013 and had a prior dMRI available for comparison of numbers of brain metastases. Factors predictive of additional brain metastases on GK MRI were investigated using logistic regression analysis. Overall survival was estimated by Kaplan-Meier method, and postradiosurgery distant intracranial failure was estimated by cumulative incidence measures. Multivariable Cox proportional hazards model and Fine-Gray regression modeling assessed potential risk factors of overall survival and distant intracranial failure, respectively.

RESULTS

The mean numbers of brain metastases (SD) on dMRI and GK MRI were 3.4 (4.2) and 5.8 (7.7), respectively, and additional brain metastases were found on GK MRI in 48.9% of patients. Frequencies of detecting additional metastases for patients with 1, 2, 3–4, and more than 4 brain metastases on dMRI were 29.5%, 47.9%, 55.9%, and 79.4%, respectively (p < 0.001). An index brain metastasis with a diameter greater than 1 cm on dMRI was inversely associated with detecting additional brain metastases, with an adjusted odds ratio of 0.57 (95% CI 0.4–0.9, p = 0.02). The median time between dMRI and GK MRI was 22 days (range 1–88 days), and time between scans was not associated with detecting additional metastases. Patients with additional brain metastases did not have larger total radiosurgery target volumes, and they rarely had an immediate change in management (abortion of radiosurgery or addition of whole-brain radiation therapy) due to detection of additional metastases. Patients with additional metastases had a higher incidence of distant intracranial failure than those without additional metastases (p = 0.004), with an adjusted subdistribution hazard ratio of 1.4 (95% CI 1.0–2.0, p = 0.04). Significantly worse overall survival was not detected for patients with additional brain metastases on GK MRI (log-rank p = 0.07), with the relative adjusted hazard ratio of 1.07, (95% CI 0.81–1.41, p = 0.65).

CONCLUSIONS

Detecting additional brain metastases on GK MRI is strongly associated with the number of brain metastases on dMRI and inversely associated with the size of the index brain metastasis. The discovery of additional brain metastases at time of GK radiosurgery is very unlikely to lead to aborting radiosurgery but is associated with a higher incidence of distant intracranial failure. However, there is not a significant difference in survival.

▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class IV.

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Stephen T. Magill, David S. Lee, Adam J. Yen, Calixto-Hope G. Lucas, David R. Raleigh, Manish K. Aghi, Philip V. Theodosopoulos and Michael W. McDermott

OBJECTIVE

Skull base meningiomas are surgically challenging tumors due to the intricate skull base anatomy and the proximity of cranial nerves and critical cerebral vasculature. Many studies have reported outcomes after primary resection of skull base meningiomas; however, little is known about outcomes after reoperation for recurrent skull base meningiomas. Since reoperation is one treatment option for patients with recurrent meningioma, the authors sought to define the risk profile for reoperation of skull base meningiomas.

METHODS

A retrospective review of 2120 patients who underwent resection of meningiomas between 1985 and 2016 was conducted. Clinical information was extracted from the medical records, radiology data, and pathology data. All records of patients with recurrent skull base meningiomas were reviewed. Demographic data, presenting symptoms, surgical management, outcomes, and complications data were collected. Kaplan-Meier analysis was used to evaluate survival after reoperation. Logistic regression was used to evaluate for risk factors associated with complications.

RESULTS

Seventy-eight patients underwent 100 reoperations for recurrent skull base meningiomas. Seventeen patients had 2 reoperations, 3 had 3 reoperations, and 2 had 4 or more reoperations. The median age at diagnosis was 52 years, and 64% of patients were female. The median follow-up was 8.5 years. Presenting symptoms included cranial neuropathy, headache, seizure, proptosis, and weakness. The median time from initial resection to first reoperation was 4.4 years and 4.1 years from first to second reoperation. Seventy-two percent of tumors were WHO grade I, 22% were WHO grade II, and 6% were WHO grade III. The sphenoid wing was the most common location (31%), followed by cerebellopontine angle (14%), cavernous sinus (13%), olfactory groove (12%), tuberculum sellae (12%), and middle fossa floor (5%). Forty-four (54%) tumors were ≥ 3 cm in maximum diameter at the time of the first reoperation. In 100 reoperations, 60 complications occurred in 30 cases. Twenty of the 60 complications required surgical intervention (33%). Complications included hydrocephalus (12), CSF leak/pseudomeningocele (11), wound infection (9), postoperative hematoma (4), venous infarction (1), and pneumocephalus (1). Postoperative neurological deficits included new or worsened cranial nerve deficits (10) and hemiparesis (3). There were no perioperative deaths in this series. On multivariate analysis, posterior fossa location was significantly associated with complications (OR 3.45, p = 0.0472). The 1-, 2-, 5-, and 10-year overall survival rates according to Kaplan-Meier analysis after the first reoperation were 94%, 92%, 88%, and 76%, respectively. The median survival after the first reoperation was 17 years.

CONCLUSIONS

Recurrent skull base meningiomas are surgically challenging tumors, and reoperation is associated with high morbidity and complication rates. Despite these cautionary data, repeat resection of recurrent skull base meningiomas in appropriately selected patients provides excellent long-term survival.

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David R. Raleigh, Zachary A. Seymour, Bryan Tomlin, Philip V. Theodosopoulos, Mitchel S. Berger, Manish K. Aghi, Sarah E. Geneser, Devan Krishnamurthy, Shannon E. Fogh, Penny K. Sneed and Michael W. McDermott

OBJECTIVE

Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases.

METHODS

A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models.

RESULTS

The median age at surgery was 59 years (range 29.9–81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21–76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4–93), and the median activity was 0.73 mCi (range 0.34–1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0–22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02–13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05).

CONCLUSIONS

Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients.

▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

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Stephen T. Magill, Cecilia L. Dalle Ore, Michael A. Diaz, Daara D. Jalili, David R. Raleigh, Manish K. Aghi, Philip V. Theodosopoulos and Michael W. McDermott

OBJECTIVE

Recurrent meningiomas are primarily managed with radiation therapy or repeat resection. Surgical morbidity after reoperation for recurrent meningiomas is poorly understood. Thus, the objective of this study was to report surgical outcomes after reoperation for recurrent non–skull base meningiomas.

METHODS

A retrospective review of patients was performed. Inclusion criteria were patients with recurrent meningioma who had prior resection and supratentorial non–skull base location. Univariate and multivariate logistic regression and recursive partitioning analysis were used to identify risk factors for surgical complications.

RESULTS

The authors identified 67 patients who underwent 111 reoperations for recurrent supratentorial non–skull base meningiomas. The median age was 53 years, 49% were female, and the median follow-up was 9.8 years. The most common presenting symptoms were headache, weakness, and seizure. The WHO grade after the last reoperation was grade I in 22% of cases, grade II in 51%, and grade III in 27%. The tumor grade increased at reoperation in 22% of cases. Tumors were located on the convexity (52%), parasagittal (33%), falx (31%), and multifocal (19%) locations. Tumors involved the middle third of the sagittal plane in 52% of cases. In the 111 reoperations, 48 complications occurred in 32 patients (48%). There were 26 (54%) complications requiring surgical intervention. There was no perioperative mortality. Complications included neurological deficits (14% total, 8% permanent), wound dehiscence/infection (14%), and CSF leak/pseudomeningocele/hydrocephalus (9%). Tumors that involved the middle third of the sagittal plane (OR 6.97, 95% CI 1.5–32.0, p = 0.006) and presentation with cognitive changes (OR 20.7, 95% CI 2.3–182.7, p = 0.001) were significantly associated with complication occurrence on multivariate analysis. The median survival after the first reoperation was 11.5 years, and the 2-, 5-, and 10-year Kaplan-Meier survival rates were 91.0%, 68.8%, and 50.0%, respectively.

CONCLUSIONS

Reoperation for recurrent supratentorial non–skull base meningioma is associated with a high rate of complications. Patients with cognitive changes and tumors that overlap the middle third of the sagittal plane are at increased risk of complications. Nevertheless, excellent long-term survival can be achieved without perioperative mortality.

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William C. Chen, Stephen T. Magill, Ashley Wu, Harish N. Vasudevan, Olivier Morin, Manish K. Aghi, Philip V. Theodosopoulos, Arie Perry, Michael W. McDermott, Penny K. Sneed, Steve E. Braunstein and David R. Raleigh

OBJECTIVE

The goal of this study was to investigate the impact of adjuvant radiotherapy (RT) on local recurrence and overall survival in patients undergoing primary resection of atypical meningioma, and to identify predictive factors to inform patient selection for adjuvant RT.

METHODS

One hundred eighty-two patients who underwent primary resection of atypical meningioma at a single institution between 1993 and 2014 were retrospectively identified. Patient, meningioma, and treatment data were extracted from the medical record and compared using the Kaplan-Meier method, log-rank tests, multivariate analysis (MVA) Cox proportional hazards models with relative risk (RR), and recursive partitioning analysis.

RESULTS

The median patient age and imaging follow-up were 57 years (interquartile range [IQR] 45–67 years) and 4.4 years (IQR 1.8–7.5 years), respectively. Gross-total resection (GTR) was achieved in 114 cases (63%), and 42 patients (23%) received adjuvant RT. On MVA, prognostic factors for death from any cause included GTR (RR 0.4, 95% CI 0.1–0.9, p = 0.02) and MIB1 labeling index (LI) ≤ 7% (RR 0.4, 95% CI 0.1–0.9, p = 0.04). Prognostic factors on MVA for local progression included GTR (RR 0.2, 95% CI 0.1–0.5, p = 0.002), adjuvant RT (RR 0.2, 95% CI 0.1–0.4, p < 0.001), MIB1 LI ≤ 7% (RR 0.2, 95% CI 0.1–0.5, p < 0.001), and a remote history of prior cranial RT (RR 5.7, 95% CI 1.3–18.8, p = 0.03). After GTR, adjuvant RT (0 of 10 meningiomas recurred, p = 0.01) and MIB1 LI ≤ 7% (RR 0.1, 95% CI 0.003–0.3, p < 0.001) were predictive for local progression on MVA. After GTR, 2.2% of meningiomas with MIB1 LI ≤ 7% recurred (1 of 45), compared with 38% with MIB1 LI > 7% (13 of 34; p < 0.001). Recursive partitioning analysis confirmed the existence of a cohort of patients at high risk of local progression after GTR without adjuvant RT, with MIB1 LI > 7%, and evidence of brain or bone invasion. After subtotal resection, adjuvant RT (RR 0.2, 95% CI 0.04–0.7, p = 0.009) and ≤ 5 mitoses per 10 hpf (RR 0.1, 95% CI 0.03–0.4, p = 0.002) were predictive on MVA for local progression.

CONCLUSIONS

Adjuvant RT improves local control of atypical meningioma irrespective of extent of resection. Although independent validation is required, the authors’ results suggest that MIB1 LI, the number of mitoses per 10 hpf, and brain or bone invasion may be useful guides to the selection of patients who are most likely to benefit from adjuvant RT after resection of atypical meningioma.