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Cheng-Chia Lee, Chun-Po Yen, Zhiyuan Xu, David Schlesinger, and Jason Sheehan

Object

The use of radiosurgery has been well accepted for treating small to medium-size metastatic brain tumors (MBTs). However, its utility in treating large MBTs remains uncertain due to potentially unfavorable effects such as progressive perifocal brain edema and neurological deterioration. In this retrospective study the authors evaluated the local tumor control rate and analyzed possible factors affecting tumor and brain edema response.

Methods

The authors defined a large brain metastasis as one with a measurement of 3 cm or more in at least one of the 3 cardinal planes (coronal, axial, or sagittal). A consecutive series of 109 patients with 119 large intracranial metastatic lesions were treated with Gamma Knife surgery (GKS) between October 2000 and December 2012; the median tumor volume was 16.8 cm3 (range 6.0–74.8 cm3). The pre-GKS Karnofsky Performance Status (KPS) score for these patients ranged from 70 to 100. The most common tumors of origin were non–small cell lung cancers (29.4% of cases in this series). Thirty-six patients (33.0%) had previously undergone a craniotomy (1–3 times) for tumor resection. Forty-three patients (39.4%) underwent whole-brain radiotherapy (WBRT) before GKS. Patients were treated with GKS and followed clinically and radiographically at 2- to 3-month intervals thereafter.

Results

The median duration of imaging follow-up after GKS for patients with large MBTs in this series was 6.3 months. In the first follow-up MRI studies (performed within 3 months after GKS), 77 lesions (64.7%) had regressed, 24 (20.2%) were stable, and 18 (15.1%) were found to have grown. Peritumoral brain edema as defined on T2-weighted MRI sequences had decreased in 79 lesions (66.4%), was stable in 21 (17.6%), but had progressed in 19 (16.0%). In the group of patients who survived longer than 6 months (76 patients with 77 MBTs), 88.3% of the MBTs (68 of 77 lesions) had regressed or remained stable at the most recent imaging follow-up, and 89.6% (69 of 77 lesions) showed regression of perifocal brain edema volume or stable condition. The median duration of survival after GKS was 8.3 months for patients with large MBTs. Patients with small cell lung cancer and no previous WBRT had a significantly higher tumor control rate as well as better brain edema relief. Patients with a single metastasis, better KPS scores, and no previous radiosurgery or WBRT were more likely to decrease corticosteroid use after GKS. On the other hand, higher pre-GKS KPS score was the only factor that showed a statistically significant association with longer survival.

Conclusions

Treating large MBTs using either microsurgery or radiosurgery is a challenge for neurosurgeons. In selected patients with large brain metastases, radiosurgery offered a reasonable local tumor control rate and favorable functional preservation. Exacerbation of underlying edema was rare in this case series. Far more commonly, edema and steroid use were lessened after radiosurgery. Radiosurgery appears to be a reasonable option for some patients with large MBTs.

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Douglas Kondziolka

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Beatriz E. Amendola and Aizik L. Wolf

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Mohamed Samy Elhammady and Roberto C. Heros

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David J. Salvetti, Tara G. Nagaraja, Carl Levy, Zhiyaun Xu, and Jason Sheehan

Object

Increasingly, meningiomas are detected incidentally, prior to symptom development. While these lesions are traditionally managed conservatively until symptoms develop or lesion growth occurs, it is conceivable that patients at high risk for symptom development may benefit from earlier intervention prior to the appearance of symptoms. However, little research has been performed to determine whether Gamma Knife surgery (GKS) can alter the rate of symptom development in such patients.

Methods

A retrospective case study was performed by screening the University of Virginia GKS database for patients treated for asymptomatic meningiomas. From the patient's medical records, pertinent demographic and treatment information was obtained. Yearly follow-up MRI had been performed to assess tumor control and detect signs of radiation-induced injury. Clinical follow-up via neurological examination had been performed to assess symptom development.

Results

Forty-two patients, 33 females (78.6%) and 9 males (21.4%), with 42 asymptomatic meningiomas were included in the analysis. The median age at GKS was 53 years. The most common lesion location was the cerebral convexities (10 lesions [23.8%]), and the median lesion size was 4.0 ml. The median duration of imaging and clinical follow-ups was 59 and 76 months, respectively. During the follow-up period, 1 tumor (2.4%) increased in size, 2 patients (4.8%) demonstrated symptoms, and 1 patient (2.4%) exhibited possible signs of radiation-induced injury. Thus, actuarial tumor control rates were 100%, 95.7%, and 95.7% for 2, 5, and 10 years, respectively. Actuarial symptom control at 5 and 10 years was 97% and 93.1%, respectively. Overall progression-free survival was 91.1% and 77.8% at 5 and 10 years, respectively.

Conclusions

Compared with published rates of symptom development in patients with untreated meningiomas, results in this study indicated that patients with asymptomatic lesions may benefit from prophylactic radiosurgery prior to the appearance of symptoms. Additionally, GKS is a treatment option that offers low morbidity.

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Douglas Kondziolka

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David J. Salvetti, Tara G. Nagaraja, Ian T. McNeill, Zhiyuan Xu, and Jason Sheehan

Object

It has been generally accepted that Gamma Knife surgery (GKS) is an effective primary or adjunct treatment for patients with 1–4 metastases to the brain. The number of studies detailing the use of GKS for 5 or more brain metastases, however, remains minimal. The aim of the current retrospective study was to elucidate the utility of GKS in patients with 5–15 brain metastases.

Methods

Patients were chosen for GKS based on prior MRI of these metastatic lesions and a known primary cancer diagnosis. Magnetic resonance imaging was used post-GKS to assess tumor control; patients were also followed up clinically. Overall survival (OS) from the date of GKS was used as the primary end point. Statistical analysis was performed to identify prognostic factors related to OS.

Results

Between 2003 and 2012, 96 patients were treated for a total of 704 metastatic brain lesions. The histology of these lesions varied among non–small cell lung cancer (NSCLC), breast cancer, melanoma, renal cancer, and other more rare carcinomas. At the initial treatment, 18 of the patients (18.8%) were categorized in Recursive Partitioning Analysis (RPA) Class 1 and 77 (80.2%) in RPA Class 2; none were in RPA Class 3. The median number of treated lesions was 7 (mean 7.13), and the median planned treatment volume was 6.12 cm3 (range 0.42–57.83 cm3) per patient. The median clinical follow-up was 4.1 months (range 0.1–40.70 months). Actuarial tumor control was calculated to be 92.4% at 6 months, 84.8% at 12 months, and 74.9% at 24 months post-GKS. The median OS was found to be 4.73 months (range 0.4–41.8 months). Multivariate analysis demonstrated that RPA class was a significant predictor of death (HR = 2.263, p = 0.038). Number of lesions, tumor histology, Graded Prognostic Assessment score, prior whole-brain radiation therapy, prior resection, prior chemotherapy, patient age, patient sex, controlled primary tumor, extracranial metastases, and planned treatment volume were not significant predictors of OS.

Conclusions

In patients with 5–15 brain metastases at presentation, the number of lesions did not predict survival after GKS; however, the RPA class was predictive of OS in this group of patients. Gamma Knife surgery for such patients offers an excellent rate of local tumor control.

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Yu-Hua Huang, Tao-Chen Lee, Tsung-Han Lee, Chen-Chieh Liao, Jason Sheehan, and Aij-Lie Kwan

Object

Decompressive craniectomy is a life-saving measure for patients who have sustained traumatic brain injury (TBI), but patients undergoing this procedure may still die during an early phase of head injury. The aim of this study was to investigate the incidence, causes, and risk factors of 30-day mortality in traumatically brain-injured patients undergoing decompressive craniectomy.

Methods

The authors included 201 head-injured patients undergoing decompressive craniectomy in this 3-year retrospective study. The main outcome evaluated was 30-day mortality in patients who had undergone craniectomy after TBI. Demographic and clinical data, including information on death, were obtained for subsequent analysis. The authors identified differences between survivors and nonsurvivors in terms of clinical parameters; multivariate logistic regression was used to adjust for independent risk factors of short-term death.

Results

The 30-day mortality rate was 26.4% in traumatically brain-injured patients undergoing decompressive craniectomy. The majority of deaths following decompression resulted from uncontrollable brain swelling and extensive brain infarction, which accounted for 79.2% of mortality. In the multivariate logistic regression mode, the 2 independent risk factors for 30-day mortality were age (OR 1.035 [95% CI 1.006–1.064]; p = 0.018) and Glasgow Coma Scale (GCS) score before decompressive craniectomy (OR 0.769 [95% CI 0.597–0.990]; p = 0.041).

Conclusions

There is a high 30-day mortality rate in traumatically brain-injured patients undergoing decompressive craniectomy. Most of the deaths are attributed to ongoing brain damage, even after decompression. Risk factors of short-term death, including age and preoperative GCS score, are important in patient selection for decompressive craniectomy, and these factors should be considered together to ensure the highest chance of surviving TBI.

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Stephen J. Monteith, Sagi Harnof, Ricky Medel, Britney Popp, Max Wintermark, M. Beatriz S. Lopes, Neal F. Kassell, W. Jeff Elias, John Snell, Matthew Eames, Eyal Zadicario, Krisztina Moldovan, and Jason Sheehan

Object

Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube.

Methods and Results

In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance.

Conclusions

The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.