Tag: Stereotactic radiosurgery

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Stereotactic Radiosurgery With Versus Without Embolization for Brain ArteriovenousMalformations

Neurosurgery 88(2) 2021: 313–321

Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes.

OBJECTIVE: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features.

METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation.

RESULTS: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRSonly (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR)=1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post- SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts.

CONCLUSION: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

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Long-term pain outcomes in elderly patients with trigeminal neuralgia: comparison of first-time microvascular decompression and stereotactic radiosurgery

Neurosurg Focus 49 (4):E23, 2020

Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD) and stereotactic radiosurgery (SRS). The use of MVD in elderly patients has been described but has yet to be prospectively compared to SRS, which is well-tolerated and noninvasive. The authors aimed to directly compare long-term pain control and adverse event rates for first-time surgical treatments for idiopathic TN in the elderly.

METHODS A prospectively collected database was reviewed for TN patients who had undergone treatment between 1997 and 2017 at a single institution. Standardized collection of preoperative demographics, surgical procedure, and postoperative outcomes was performed. Data analysis was limited to patients over the age of 65 years who had undergone a first-time procedure for the treatment of idiopathic TN with at least 1 year of follow-up.

RESULTS One hundred ninety-three patients meeting the study inclusion criteria underwent surgical procedures for TN during the study period (54 MVD, 24 MVD+Rhiz, 115 SRS). In patients in whom an artery was not compressing the trigeminal nerve during MVD, a partial sensory rhizotomy (MVD+Rhiz) was performed. Patients in the SRS cohort were older than those in the MVD and MVD+Rhiz cohorts (mean ± SD, 79.2 ± 7.8 vs 72.9 ± 5.7 and 70.9 ± 4.8 years, respectively; p < 0.0001) and had a higher mean Charlson Comorbidity Index (3.8 ± 1.1 vs 3.0 ± 0.9 and 2.9 ± 1.0, respectively; p < 0.0001). Immediate or short-term postoperative pain-free rates (Barrow Neurological Institute [BNI] pain intensity score I) were 98.1% for MVD, 95.8% for MVD+Rhiz, and 78.3% for SRS (p = 0.0008). At the last follow-up, 72.2% of MVD patients had a favorable outcome (BNI score I–IIIa) compared to 54.2% and 49.6% of MVD+Rhiz and SRS patients, respectively (p = 0.02). In total, 0 (0%) SRS, 5 (9.3%) MVD, and 1 (4.2%) MVD+Rhiz patients developed any adverse event. Multivariate Cox proportional hazards analysis demonstrated that procedure type (p = 0.001) and postprocedure sensory change (p = 0.003) were statistically significantly associated with pain control.

CONCLUSIONS In this study cohort, patients who had undergone MVD had a statistically significantly longer duration of pain freedom than those who had undergone MVD+Rhiz or SRS as their first procedure. Fewer adverse events were seen after SRS, though the MVD-associated complication rate was comparable to published rates in younger patients. Overall, the results suggest that both MVD and SRS are effective options for the elderly, despite their advanced age. Treatment choice can be tailored to a patient’s unique condition and wishes.

 

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Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer

Neurosurgery 87:664–671, 2020

Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases.

OBJECTIVE: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). METHODS: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collectionwas performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazardmodels, Kaplan- Meier survival analysis, and competing risks analysis.

RESULTS: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005).

CONCLUSION: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brainmetastases and potentially challenge the standard application of WBRT in SCLC patients.

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Stereotactic Radiosurgery for Spetzler-Martin Grade I and II Arteriovenous Malformations: International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline

Neurosurgery 87:442–452, 2020

No guidelines have been published regarding stereotactic radiosurgery (SRS) in the management of Spetzler-Martin grade I and II arteriovenous malformations (AVMs).

OBJECTIVE: To establish SRS practice guidelines for grade I-II AVMs on the basis of a systematic literature review.

METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant search of Medline, Embase, and Scopus, 1986-2018, for publications reporting post-SRS outcomes in ≥ 10 grade I-II AVMs with a follow-up of ≥ 24 mo. Primary endpoints were obliteration and hemorrhage; secondary outcomes included SpetzlerMartin parameters, dosimetric variables, and “excellent” outcomes (defined as total obliteration without new post-SRS deficit).

RESULTS: Of 447 abstracts screened, 8 were included (n = 1, level 2 evidence; n = 7, level 4 evidence), representing 1102 AVMs, of which 836 (76%) were grade II. Obliteration was achieved in 884 (80%) at a median of 37 mo; 66 hemorrhages (6%) occurred during a median follow-up of 68 mo. Total obliteration without hemorrhage was achieved in 78%. Of 836 grade II AVMs, Spetzler-Martin parameters were reported in 680: 377 were eloquent brain and 178 had deep venous drainage, totaling 555/680 (82%) high-risk SRS-treated grade II AVMs.

CONCLUSION: The literature regarding SRS for grade I-II AVM is low quality, limiting interpretation. Cautiously, we observed that SRS appears to be a safe, effective treatment for grade I-II AVM and may be considered a front-line treatment, particularly for lesions in deep or eloquent locations. Preceding publications may be influenced by selection bias, with favorable AVMs undergoing resection, whereas those at increased risk of complications and nonobliteration are disproportionately referred for SRS.

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Biologically effective dose and prediction of obliteration of unruptured arteriovenous malformations treated by upfront Gamma Knife radiosurgery: a series of 149 consecutive cases

https://doi.org/10.3171/2020.4.JNS201250

Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs.

METHODS A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12–154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18–25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7–246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9–138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313–3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4–2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed.

RESULTS A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (−0.013689 × beam-on time) + (0.021 × age) − 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03).

CONCLUSIONS The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.

 

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Predictors of Local Control of Brain Metastasis TreatedWith Laser Interstitial Thermal Therapy

Neurosurgery 87:112–122, 2020

Laser Interstitial Thermal Therapy (LITT) has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS.

OBJECTIVE: To evaluate the predictive factors associated with local recurrence after LITT.

METHODS: Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence.

RESULTS: A total of 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence, and 31 radiation necrosis). Freedom from local recurrence at 6 mo was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 mo. Incompletely ablated lesions had a shorter median time for local recurrence (P < .001). Larger lesions (>6 cc) had shorter time for local recurrence (P = .03). Dural-based lesions showed a shorter time to local recurrence (P = .01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (P = .01). Patients receiving systemic therapy after LITT had longer time to local recurrence (P = .01). In multivariate Cox-regression model, the HR for incomplete ablated lesions was 4.88 (P < .001), 3.12 (P = .03) for recurrent tumors, and 2.56 (P = .02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%.

CONCLUSION: Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.

 

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Is There a Need for a 6-Month Postradiosurgery Magnetic Resonance Imaging in the Treatment of Vestibular Schwannoma?

Neurosurgery, Volume 86, Issue 2, February 2020, Pages 250–256

Stereotactic radiosurgery (SRS) is a common treatment modality for vestibular schwannoma (VS), with a role in primary and recurrent/progressive algorithms. At our institution, routine magnetic resonance imaging (MRI) is obtained at 6 and 12 mo following SRS for VS.

OBJECTIVE: To analyze the safety and financial impact of eliminating the 6-mo post-SRS MRI in asymptomatic VS patients. METHODS: A prospectively maintained SRS database was retrospectively reviewed for VS patients with 1 yr of post-treatment follow-up, 2005 to 2015. Decisions at 6-mo MRI were binarily categorized as routine follow-up vs clinical action—defined as a clinical visit, additional imaging, or an operation as a direct result of the 6-mo study.

RESULTS: A total of 296 patients met screening criteria, of whom 53 were excluded for incomplete follow-up and 8 for NF-2. Nine were reimaged prior to 6 mo due to clinical symptoms. Routine 6-mo post-SRS MRI was completed by 226 patients (76% of screened cohort), following from which zero instances of clinical action occurred.When scaled using national insurance database-derived financials—which estimated the mean per-study charge for MRI of the brain with and without contrast at $1767—the potential annualized national charge reduction was approximated as $1 611 504.

CONCLUSION: For clinically stable VS, 6-mo post-SRS MRI does not contribute significantly to management. We recommend omitting routine MRI before 12 mo, in patients without new or progressive neurological symptoms. If extrapolated nationally to the more than 100 active SRS centers, thousands of patients would be spared an inconvenient, nonindicated study, and national savings in health care dollarswouldbe on the order ofmillions annually.

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Long-term outcomes of high-dose single-fraction radiosurgery for chordomas of the spine and sacrum

J Neurosurg Spine 32:79–88, 2020

The current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS’s role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery.

METHODS Clinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery.

RESULTS In total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0–122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18–24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy.

CONCLUSIONS High-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.

 

 

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Stereotactic radiosurgery for arteriovenous malformations of the basal ganglia and thalamus: an international multicenter study

J Neurosurg 132:122–131, 2020

Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects.

METHODS The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation- induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome.

RESULTS The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044).

CONCLUSIONS SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

 

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An International Radiosurgery Research Foundation Multicenter Retrospective Study of Gamma Ventral Capsulotomy for Obsessive Compulsive Disorder

Neurosurgery, Volume 85, Issue 6, December 2019, Pages 808–816

Obsessive compulsive disorder (OCD) across its full spectrum of severity is a psychiatric illness affecting ∼2% to 3% of the general population and results in significant functional impairment. There are few large patient series regarding Gamma ventral capsulotomy (GVC).
OBJECTIVE: To evaluate clinical outcomes of severe medically refractory OCD treated with GVC.
METHODS: This is an international, multicenter, retrospective cohort study. Forty patients with pre-GVC Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores ≥ 24 (indicating severe OCD) were included. GVC was performed with 1 or 2 isocenters with a median maximum dose of 135 Gy (range, 120-180 Gy). Patients were deemed “responders” to GVC if there was ≥35% reduction of follow-up Y-BOCS scores, and considered in remission if their Y-BOCS scores were ≤16. The median follow-up was 36 mo (range, 6-96 mo).
RESULTS: The median pre-SRS Y-BOCS score was 35 (range, 24-40). Eighteen patients (45%) were considered “responders,” and 16 (40%) of them were in remission at their last follow-up. Nineteen patients (47.5%) remained stable with Y-BOCS of 33 (range, 26-36) following GVC, whereas 3 patients (7.5%) experienced worsening in Y-BOCS scores. Patients treated with 2 isocenters were more likely to have improvement in Y-BOCS score at 3 and 5 yr (P < .0005). Ten patients (25%) experienced post-GVC mood disturbance and neurological complications in 3 patients (7.5%). One patient developed radiation necrosis with edema that improved with steroids.
CONCLUSION: GVC serves as a reasonable treatment strategy for severe medical refractory OCD. Patients treated with 2 isocenters were more likely to have substantial improvement in OCD.

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Treatment Outcomes and Dose Rate Effects Following Gamma Knife Stereotactic Radiosurgery for Vestibular Schwannomas

Neurosurgery 85:E1084–E1094, 2019

Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored.

OBJECTIVE: To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas.

METHODS: We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression.

RESULTS: The study cohort included 227 patientswith available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rateswere 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044).

CONCLUSION:Whereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effectsmay impact post-treatment functional outcomes. Further research remains warranted.

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Comparing costs of microsurgical resection and stereotactic radiosurgery for vestibular schwannoma

J Neurosurg 131:1395–1404, 2019

Given rising scrutiny of healthcare expenditures, understanding intervention costs is increasingly important. This study aimed to compare and characterize costs for vestibular schwannoma (VS) management with microsurgery and radiosurgery to inform practice decisions and appraise cost reduction strategies.

METHODS In conjunction with medical records, internal hospital financial data were used to evaluate costs. Total cost was divided into index costs (costs from arrival through discharge for initial intervention) and follow-up costs (through 36 months) for 317 patients with unilateral VSs undergoing initial management between June 2011 and December 2015. A retrospective matched cohort based on tumor size with 176 patients (88 undergoing each intervention) was created to objectively compare costs between microsurgery and radiosurgery. The full sample of 203 patients treated with resection and 114 patients who underwent radiosurgery was used to evaluate a broad range of outcomes and identify cost contributors within each intervention group.

RESULTS Within the matched cohort, average index costs were significantly higher for microsurgery (100% by definition, because costs are presented as a percentage of the average index cost for the matched microsurgery group; 95% CI 93–107) compared to radiosurgery (38%, 95% CI 38–39). Microsurgery had higher average follow-up costs (1.6% per month, 95% CI 0.8%–2.4%) compared to radiosurgery (0.5% per month, 95% CI 0.4%–0.7%), largely due to costs incurred in the initial months after resection. A major contributor to total cost and cost variability for both resection and radiosurgery was the need for additional interventions in the follow-up period, which were necessary due to complications or persistent functional deficits. Although tumor size was not associated with increased total costs for radiosurgery, linear regression analysis demonstrated that, for patients who underwent microsurgery, each centimeter increase in tumor maximum diameter resulted in an estimated increase in total cost of 50.2% of the average index cost of microsurgery (95% CI 34.6%–65.7%) (p < 0.001, R 2 = 0.17). There were no cost differences associated with the proportion of inpatient days in the ICU or with specific surgical approach for patients who underwent resection.

CONCLUSIONS This study is the largest assessment to date based on internal cost data comparing VS management with microsurgery and radiosurgery. Both index and follow-up costs are significantly higher when tumors were managed with resection compared to radiosurgery. Larger tumors were associated with increased resection costs, highlighting the incremental costs associated with observation as the initial management.

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Repeat Gamma Knife radiosurgery versus microvascular decompression following failure of GKRS in trigeminal neuralgia: a systematic review and meta-analysis

J Neurosurg 131:1197–1206, 2019

Gamma Knife radiosurgery (GKRS) has emerged as a promising treatment modality for patients with classical trigeminal neuralgia (TN); however, considering that almost half of the patients experience post-GKRS failure or lesion recurrence, a repeat treatment is typically necessary. The existing literature does not offer clear evidence to establish which treatment modality, repeat GKRS or microvascular decompression (MVD), is superior. The present study aimed to compare the overall outcome of patients who have undergone either repeat GKRS or MVD after failure of their primary GKRS; the authors do so by conducting a systematic review and meta-analysis of the literature and analysis of data from their own institution.

METHODS The authors conducted a systematic review and meta-analysis of the PubMed, Cochrane Library, Web of Science, and CINAHL databases to identify studies describing patients who underwent either repeat GKRS or MVD after initial failed GKRS for TN. The primary outcomes were complete pain relief (CPR) and adequate pain relief (APR) at 1 year. The secondary outcomes were rate of postoperative facial numbness and the retreatment rate. The pooled data were analyzed with R software. Bias and heterogeneity were assessed using funnel plots and I 2 tests, respectively. A retrospective analysis of a series of patients treated by the authors who underwent repeat GKRS or MVD after postGKRS failure or relapse is presented.

RESULTS A total of 22 studies met the selection criteria and were included for final data retrieval and meta-analysis. The search did not identify any study that had directly compared outcomes between patients who had undergone repeat GKRS versus those who had undergone MVD. Therefore, the authors’ final analysis included two groups: studies describing outcome after repeat GKRS (n = 17) and studies describing outcome after MVD (n = 5). The authors’ institutional study was the only study with direct comparison of the two cohorts. The pooled estimates of primary outcomes were APR in 83% of patients who underwent repeat GKRS and 88% of those who underwent MVD (p = 0.49), and CPR in 46% of patients who underwent repeat GKRS and 72% of those who underwent MVD (p = 0.02). The pooled estimates of secondary outcomes were facial numbness in 32% of patients who underwent repeat GKRS and 22% of those who underwent MVD (p = 0.11); the retreatment rate was 19% in patients who underwent repeat GKRS and 13% in those who underwent MVD (p = 0.74). The authors’ institutional study included 42 patients (repeat GKRS in 15 and MVD in 27), and the outcomes 1 year after retreatment were APR in 80% of those who underwent repeat GKRS and 81% in those who underwent MVD (p = 1.0); CPR was achieved in 47% of those who underwent repeat GKRS and 44% in those who underwent MVD (p = 1.0). There was no difference in the rate of postoperative facial numbness or retreatment.

CONCLUSIONS The current meta-analysis failed to identify any superiority of one treatment over the other with comparable outcomes in terms of APR, postoperative facial numbness, and retreatment rates. However, MVD was shown to provide a better chance of CPR compared with repeat GKRS.

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Early postsurgical diffusivity metrics for prognostication of long-term pain relief after Gamma Knife radiosurgery for trigeminal neuralgia

J Neurosurg 131:539–548, 2019

Gamma Knife radiosurgery (GKRS) is an important treatment modality for trigeminal neuralgia (TN). Current longitudinal assessment after GKRS relies primarily on clinical diagnostic measures, which are highly limited in the prediction of long-term clinical benefit. An objective, noninvasive, predictive tool would be of great utility to advance the clinical management of patients. Using diffusion tensor imaging (DTI), the authors’ aim was to determine whether early (6 months post-GKRS) target diffusivity metrics can be used to prognosticate long-term pain relief in patients with TN.

METHODS Thirty-seven patients with TN treated with GKRS underwent 3T MRI scans at 6 months posttreatment. Diffusivity metrics of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were extracted bilaterally from the radiosurgical target of the affected trigeminal nerve and its contralateral, unaffected nerve. Early (6 months post-GKRS) diffusivity metrics were compared with long-term clinical outcome. Patients were identified as long-term responders if they achieved at least 75% reduction in preoperative pain for 12 months or longer following GKRS.

RESULTS Trigeminal nerve diffusivity at 6 months post-GKRS was predictive of long-term clinical effectiveness, where long-term responders (n = 19) showed significantly lower fractional anisotropy at the radiosurgical target of their affected nerve compared to their contralateral, unaffected nerve and to nonresponders. Radial diffusivity and mean diffusivity, correlates of myelin alterations and inflammation, were also significantly higher in the affected nerve of long-term responders compared to their unaffected nerve. Nonresponders (n = 18) did not exhibit any characteristic diffusivity changes after GKRS.

CONCLUSIONS The authors demonstrate that early postsurgical target diffusivity metrics have a translational, clinical value and permit prediction of long-term pain relief in patients with TN treated with GKRS. Importantly, an association was found between the footprint of radiation and clinical effectiveness, where a sufficient level of microstructural change at the radiosurgical target is necessary for long-lasting pain relief. DTI can provide prognostic information that supplements clinical measures, and thus may better guide the postoperative assessment and clinical decision-making for patients with TN.

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Low-Dose Gamma Knife Radiosurgery for Acromegaly

Neurosurgery, Volume 85, Issue 1, July 2019, Pages E20–E30

Remission rate is associated with higher dose of Gamma Knife Radio- surgery (GKRS; Gamma Knife: Elekta AB, Stockholm, Sweden) for acromegaly, but the dose ≥25 Gy is not always feasible when the functioning adenoma is close to optic apparatus

OBJECTIVE: To evaluate the efficacy and safety of low-dose (<25 Gy) GKRS in the treatment of patients with acromegaly.

METHODS: Single-center retrospective review of acromegaly cases treated with GKRS between June 1994 and December 2016. A total of 76 patients with the diagnosis of acromegaly who were treated with low-dose GKRS were selected for inclusion. Patients were treated with a median margin dose, isodose line, and treatment volume of 15.8 Gy, 57.5%, and 4.8 mL, respectively. Any identifiable portion of the optic apparatus was limited to a radiation dose of 10 Gy. All patients underwent full endocrine, ophthalmological, and imaging evaluation prior to and after GKRS treatments, and results of these were analyzed.

RESULTS: Biochemical remission was achieved in 33 (43.4%) patients. Actuarial remission rates were 20.3%, 49.9%, and 76.3% at 4, 8, and 12 yr, respectively. Absence of cavernous sinus invasion (P = .042) and lower baseline insulin-like growth factor-1 levels (P = .019) were significant predictors of remission. New hormone deficiencies were found in 9 (11.8%) patients. Actuarial hormone deficiency rates were 3%, 14%, and 22.2% at 4, 8, and 10 yr, respectively. Two (2.6%) patients who achieved initial remission experienced recurrence. No optic complications were encountered.

CONCLUSION: Reasonable remission and new hormone deficiency rates can be achieved with low-dose GKRS for acromegaly. These rates may be comparable to those with standard GKRS margin doses.

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Gamma Knife stereotactic radiosurgery for cavernous sinus meningioma: long-term follow-up in 200 patients

J Neurosurg 130:1799–1808, 2019

The authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM).

METHODS The authors retrospectively assessed treatment outcomes 5–18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22–83 years). In total, 120 (60%) patients underwent Gamma Knife SRS as primary management, 46 (23%) for residual tumors, and 34 (17%) for recurrent tumors after one or more surgical procedures. The median tumor target volume was 7.5 cm3 (range 0.1–37.3 cm3), and the median margin dose was 13.0 Gy (range 10–20 Gy).

RESULTS Tumor volume regressed in 121 (61%) patients, was unchanged in 49 (25%), and increased over time in 30 (15%) during a median imaging follow-up of 101 months. Actuarial tumor control rates at the 5-, 10-, and 15-year followups were 92%, 84%, and 75%, respectively. Of the 120 patients who had undergone SRS as a primary treatment (primary SRS), tumor progression was observed in 14 (11.7%) patients at a median of 48.9 months (range 4.8–120.0 months) after SRS, and actuarial tumor control rates were 98%, 93%, 85%, and 85% at the 1-, 5-, 10-, and 15-year follow-ups post-SRS. A history of tumor progression after microsurgery was an independent predictor of an unfavorable response to radiosurgery (p = 0.009, HR = 4.161, 95% CI 1.438–12.045). Forty-four (26%) of 170 patients who had presented with at least one cranial nerve (CN) deficit improved after SRS. Development of new CN deficits after initial microsurgical resection was an unfavorable factor for improvement after SRS (p = 0.014, HR = 0.169, 95% CI 0.041–0.702). Fifteen (7.5%) patients experienced permanent CN deficits without evidence of tumor progression at a median onset of 9 months (range 2.3–85 months) after SRS. Patients with larger tumor volumes (≥ 10 cm3) were more likely to develop permanent CN complications (p = 0.046, HR = 3.629, 95% CI 1.026–12.838). Three patients (1.5%) developed delayed pituitary dysfunction after SRS.

CONCLUSIONS This long-term study showed that Gamma Knife radiosurgery provided long-term tumor control for most patients with CSM. Patients who underwent SRS for progressive tumors after prior microsurgery had a greater chance of tumor growth than the patients without prior surgery or those with residual tumor treated after microsurgery.

 

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Trigeminal Nerve Atrophy Predicts Pain Recurrence After Gamma Knife Stereotactic Radiosurgery for Classical Trigeminal Neuralgia

Neurosurgery 84:927–934, 2019

Trigeminal nerve atrophy and neurovascular compression (NVC) are frequently observed in classical trigeminal neuralgia (CTN).

OBJECTIVE: To determine whether nerve characteristics contribute to Gamma Knife (ElektaAB, Stockholm, Sweden) surgery (GKS) outcomes in unilateral CTN without previous surgery.

METHODS: From 2006 to 2012, 67 patients with unilateral CTN without previous surgery received GKS with a maximal dose of 90 Gy delivered to the trigeminal nerve juxta brainstem. Two evaluators, blinded to the side of pain, analyzed the magnetic resonance images before GKS to obtain the parameters, including nerve cross-sectional area (CSA), vessel type of NVC, and site of NVC along the nerve. Correlations of the parameters with pain relief (Barrow Neurological Institute [BNI] grades I-IIIb) and recurrence (BNI grades VIV) were made by using Cox regression and Kaplan–Meier analyses.

RESULTS: The median CSA of the symptomatic nerves was significantly smaller than that of the asymptomatic nerves (4.95 vs 5.9 mm2, P < .001). After adjustment for age and sex, larger nerve CSA was associated with lower initial pain relief (hazard ratio 0.81, P=.03) and lower pain recurrence after initial response (hazard ratio 0.58, P= .02). Patients with nerve atrophy (CSA of ≤ 4.4 mm2 after receiver operating characteristic curve analysis) had a lower 5-yr probability of maintaining pain relief after initial response than those without nerve atrophy (65% vs 86%, P= .04).

CONCLUSION: Trigeminal nerve atrophy may predict pain recurrence in patients with initial post-GKS relief of CTN.Arterial and proximalNVCare not predictive ofGKS outcomes. Future studies are required to determine optimal treatments for long-term pain relief in patients with CTN and trigeminal nerve atrophy.

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Reconsidering an important subclass of high-risk dural arteriovenous fistulas for stereotactic radiosurgery

J Neurosurg 130:972–976, 2019

Aggressive dural arteriovenous fistulas (dAVFs) with cortical venous drainage (CVD) are known for their relatively high risk of recurrent neurological events or hemorrhage. However, recent natural history literature has indicated that nonaggressive dAVFs with CVD have a significantly lower prospective risk of hemorrhage. These nonaggressive dAVFs are typically diagnosed because of symptomatic headache, pulsatile tinnitus, or ocular symptoms, as in low-risk dAVFs. Therefore, the viability of stereotactic radiosurgery (SRS) as a treatment for this lesion subclass should be investigated.

METHODS The authors evaluated their institutional experience with SRS for dAVFs with CVD for the period from 1991 to 2016, assessing angiographic outcomes and posttreatment hemorrhage rates. They subsequently pooled their results with those published in the literature and stratified the results based on the mode of clinical presentation.

RESULTS In an institutional cohort of 42 dAVFs with CVD treated using SRS, there were no complications or hemorrhages after treatment in 19 patients with nonaggressive dAVFs, but there was 1 radiation-induced complication and 1 hemorrhage among the 23 patients with aggressive dAVFs. In pooling these cases with 155 additional cases from the literature, the authors found that the hemorrhage rate after SRS was significantly lower among the patients with nonaggressive dAVFs (0% vs 6.8%, p = 0.003). Similarly, the number of radiation-related complications was 0/124 in nonaggressive dAVF cases versus 6/73 in aggressive dAVF cases (p = 0.001). The annual rate of hemorrhage after SRS for aggressive fistulas was 3.0% over 164.5 patient-years, whereas none of the nonaggressive fistulas bled after radiosurgery over 279.4 patient-years of follow-up despite the presence of CVD.

CONCLUSIONS Cortical venous drainage is thought to be a significant risk factor in all dAVFs. In the institutional experience described here, SRS proved to be a low-risk strategy associated with a very low risk of subsequent hemorrhage or radiation-related complications in nonaggressive dAVFs with CVD.

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Does Stereotactic Radiosurgery Have a Role in the Management of Patients Presenting With 4 or More Brain Metastases?

Neurosurgery 84:558–566, 2019

Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) are effective treatments for management of brain metastases. Prospective trials comparing the 2 modal- ities in patients with fewer than 4 brain metastases demonstrate that overall survival (OS) is similar. Intracranial failure is more common after SRS, while WBRT is associated with neurocognitive decline. As technology has advanced, fewer technical obstacles remain for treating patients with 4 or more brain metastases with SRS, but level I data supporting its use are lacking.
Observational prospective studies and retrospective series indicate that in patients with 4 or more brain metastases, performance status, total volume of intracranial disease, histology, and rate of development of new brain metastases predict outcomes more accurately than the number of brain metastases.

It may be reasonable to initially offer SRS to some patients with 4 or more brain metastases. Initiating therapy with SRS avoids the acute and late sequelae of WBRT. Multiple phase III trials of SRS vs WBRT, both currently open or under development, are directly comparing quality of life and OS for patients with 4 or more brain metastases to help answer the question of SRS appropriateness for these patients.

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Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for the Treatment of Adults With Metastatic Brain Tumors: Executive Summary

Neurosurgery 84:550–552, 2019

The Congress of Neurological Surgeons systematic review and evidencebased clinical practice parameter guidelines for the treatment of adults with metastatic brain tumorswas first published in 2010. Because of the time elapsed since that publication, an update of this set of guidelines based on literature published since is now indicated.

OBJECTIVE: To establish the best evidence-based management of metastatic brain tumors over all commonly used diagnostic and treatment modalities in regularly encountered clinical situations.

METHODS: Literature searches regarding management of metastatic brain tumors with whole brain radiation therapy, surgery, stereotactic radiosurgery, chemotherapy, prophylactic anticonvulsants, steroids, instances of multiple brain metastases, and emerging and investigational therapies were carried out to answer questions designed by consensus of a multidisciplinary writing group.

RESULTS: Recommendations were created and their strength linked to the quality of the literature data available thus creating an evidence-based guideline. Importantly, shortcomings and biases to the literature data are brought out so as to provide guidance for future investigation and improvements in the management of patients with metastatic brain tumors.

CONCLUSION: This series of guidelines was constructed to assess the most current and clinically relevant evidence for management of metastatic brain tumors. They set a benchmark regarding the current evidence base for this management while also highlighting important key areas for future basic and clinical research, particularly on those topics for which no recommendations could be formulated.

The full guideline can be found here.

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