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.

 

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.

Gamma Knife Radiosurgery for Multiple Sclerosis-Associated Trigeminal Neuralgia

 

Neurosurgery 85:E933–E939, 2019

Trigeminal neuralgia in the setting of multiple sclerosis (MS-TN) is a challenging condition to manage that is commonly treated with Gamma Knife radiosurgery (GKRS; Elekta AB). However, data regarding the efficacy of this treatment are somewhat limited, particularly for repeat GKRS.

OBJECTIVE: To report outcomes of GKRS for MS-TN from a cohort study.

METHODS: Retrospective review of our GKRS database identified 77 cases of unilateral MS-TN (UMSTN) in 74 patients treated with GKRS between 2001 and 2016, with 37 cases undergoing repeat GKRS. Background medical history, treatment outcomes and complications, and dosimetric data were obtained by retrospective chart reviews and telephone interviews.

RESULTS:Eighty two percent of UMSTN cases achieved Barrow Neurological Institute (BNI) IIIb or better pain relief following initial GKRS for a median duration of 1.1 yr. Estimated rates ofpainreliefat1,3,and5yr were 51,39,and29% respectively.Eighty-eightpercentachieved BNI IIIb or better pain relief after repeat GKRS for a median duration of 4.0 yr. Estimated rates of pain relief at 1 and 3 yr were 70 and 54%, respectively. Median doses for initial and repeat GKRS were 85 and 80 Gy to the 100% isodose line, respectively. Those with MS-TN had a shorter duration of BNI IIIb or better pain relief after initial (4.6 vs 1.1 yr), but not repeat GKRS (3.8 vs 4.0 yr) compared to a historical cohort from our institution.

CONCLUSION: GKRS is an effective, well-tolerated treatment for patientswith MS-TN. More durable relief is often achieved with repeat GKRS.

 

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.

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.

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.

 

The emerging role of gamma knife radiosurgery in the management of glossopharyngeal neuralgia

Neurosurg Rev (2019) 42:31–38

Glossopharyngeal neuralgia (GPN) represents a rare craniofacial disorder accounting for about 1% of all craniofacial pain syndromes. GPN shares several pathophysiologic and clinical features with the more common trigeminal neuralgia. Medical therapy and microvascular decompression, in case of vascular nerve compression, represented the mainstay of GPN management. Other ablative therapies have been reported to date; however, few data are available because of the rarity of this pain syndrome. Among the ablative procedures, gamma knife radiosurgery (GKRS) has been recently introduced in the management of GPN with good pain control and low complication rates.

Authors performed a systematic review of the published literature about GKRS in the management of GPN. Radiosurgical treatment data, pain control and recurrence rate have been analysed and compared.

GKRS represented a valuable and effective treatment option for the management of GPN. Pain control and complication rates are better than those reported by other ablative procedures and microvascular decompression; however, future studies should be focused on the long-term efficacy of GKRS.

Stereotactic Radiosurgery for Intracranial Ependymomas: An International Multicenter Study

Neurosurgery 84:227–234, 2019

Stereotactic radiosurgery (SRS) is a potentially important option for intracranial ependymoma patients.

OBJECTIVE: To analyze the outcomes of intracranial ependymoma patients who underwent SRS as a part of multimodality management.

METHODS: Seven centers participating in the International Gamma Knife Research Foundation identified 89 intracranial ependymoma patients who underwent SRS (113 tumors). The median patient age was 16.3 yr (2.9-80). All patients underwent previous surgical resection and radiation therapy (RT) of their ependymomas and 40 underwent previous chemotherapy. Grade 2 ependymomas were present in 42 patients (52 tumors) and grade 3 ependymomas in 48 patients (61 tumors). The median tumor volume was 2.2 cc (0.03-36.8) and the median margin dose was 15 Gy (9-24).

RESULTS: Forty-seven (53%) patients were alive and 42 (47%) patients died at the last follow-up. The overall survival after SRSwas 86% at 1 yr, 50% at 3 yr, and 44% at 5 yr. Smaller total tumor volume was associated with longer overall survival (P = .006). Twenty-two patients (grade 2: n = 9, grade 3: n = 13) developed additional recurrent ependymomas in the craniospinal axis. The progression-free survival after SRSwas 71%at 1 yr, 56% at 3 yr, and 48% at 5 yr. Adult age, female sex, and smaller tumor volume indicated significantly better progression-free survival. Symptomatic adverse radiation effects were seen in 7 patients (8%).

CONCLUSION: SRS provides another management option for residual or recurrent progressive intracranial ependymoma patients who have failed initial surgery and RT.

Radiosurgery and fractionated radiotherapy for cavernous sinus meningioma: a systematic review and meta-analysis

Acta Neurochirurgica (2018) 160:2367–2378

Radiosurgery (RS) and fractionated radiotherapy (FRT) are part of the therapeutic armamentarium for the management of cavernous sinus meningiomas. We propose a systematic review of the local tumor control and clinical outcomes after monofractionated radiosurgical treatment, including gamma knife radiosurgery (GKRS) and linear accelerator (Linac RS), or fractionated radiotherapy.

Materials and Methods: The current review and meta-analysis adhered to the PRISMA guidelines. We performed a search in PubMed, Embase, and Medline based on the following mesh terms, used alone or in diverse combinations, in both title and abstract: “cavernous sinus”, “meningioma”, “radiosurgery”, “gamma knife”,”linac”, “cyberknife” and “radiotherapy”. We screened 425 studies. We selected 36 studies, matching all selection criteria: 24 for GK, 5 for Linac, and 7 for FRT.

Results: Were included 2817 patients (GKRS, n = 2047, LinacRS, n = 350, FRT, n = 420). Half of patients benefited from upfront RS or FRT; the other half benefited from adjuvant RS or FRT (combined approach or tumor recurrence). The mean gross target volume (GTV) was smaller for RS as compared to FRT (p = 0.07). The median marginal doses were 13.9 Gy (range, 11 to 28) for GKRS and 14 Gy (range, 12.8 to 17.7) for LinacRS. For FRT, patients received a mean dose of 51.2 Gy (25.5 fractions, 1.85 Gy each). The mean overall follow-up values were 48 months (range, 15 to 89) for GKRS, 69 months (range, 46 to 87) for Linac, and 59.5 months (range, 33 to 83) for FRT. PFS at 5 years for GKRS, LinacRS, and FRT were respectively 93.6%, 95.6%, and 97.4% (p = 0.32, the Kruskal-Wallis). Monofractionated treatments (GKRS and LinacRS) induced more tumor volume regression than FRT (p = 0.001). Tumor recurrence or progression ranged between 3 and 5.8%, without statistically significant differences between modalities (p > 0.05). Trigeminal symptoms improved in approximately 54%, and III-IV-VI cranial nerves (CN) palsies improved in approximately 45%. After GKRS, visual acuity improved in 21% (not enough data available for other modalities). De novo deficits occurred in 5 to 7.5%. Adverse radiation effects appeared in 4.6 to 9.3% (all techniques pooled).

Conclusion: RS achieved a twice-higher rate of tumor volume regression than FRT. GKRS series reported an improvement in visual acuity in 21% of the cases. GKRS, Linac, and FRT provided similar clinical post therapeutic outcomes for the trigeminal and oculomotor CN.

Gamma Knife radiosurgery for large vestibular schwannomas greater than 3 cm in diameter

J Neurosurg 128:1380–1387, 2018

Stereotactic radiosurgery (SRS) is an important alternative management option for patients with small and medium-sized vestibular schwannomas (VSs). Its use in the treatment of large tumors, however, is still being debated. The authors reviewed their recent experience to assess the potential role of SRS in larger-sized VSs.

METHODS Between 2000 and 2014, 35 patients with large VSs, defined as having both a single dimension > 3 cm and a volume > 10 cm3, underwent Gamma Knife radiosurgery (GKRS). Nine patients (25.7%) had previously undergone resection. The median total volume covered in this group of patients was 14.8 cm3 (range 10.3–24.5 cm3). The median tumor margin dose was 11 Gy (range 10–12 Gy).

RESULTS The median follow-up duration was 48 months (range 6–156 months). All 35 patients had regular MRI followup examinations. Twenty tumors (57.1%) had a volume reduction of greater than 50%, 5 (14.3%) had a volume reduction of 15%–50%, 5 (14.3%) were stable in size (volume change < 15%), and 5 (14.3%) had larger volumes (all of these lesions were eventually resected). Four patients (11.4%) underwent resection within 9 months to 6 years because of progressive symptoms. One patient (2.9%) had open surgery for new-onset intractable trigeminal neuralgia at 48 months after GKRS. Two patients (5.7%) who developed a symptomatic cyst underwent placement of a cystoperitoneal shunt. Eight (66%) of 12 patients with pre-GKRS trigeminal sensory dysfunction had hypoesthesia relief. One hemifacial spasm completely resolved 3 years after treatment. Seven patients with facial weakness experienced no deterioration after GKRS. Two of 3 patients with serviceable hearing before GKRS deteriorated while 1 patient retained the same level of hearing. Two patients improved from severe hearing loss to pure tone audiometry less than 50 dB. The authors found borderline statistical significance for post-GKRS tumor enlargement for later resection (p = 0.05, HR 9.97, CI 0.99–100.00). A tumor volume ≥ 15 cm3 was a significant factor predictive of GKRS failure (p = 0.005). No difference in outcome was observed based on indication for GKRS (p = 0.0761).

CONCLUSIONS Although microsurgical resection remains the primary management choice in patients with VSs, most VSs that are defined as having both a single dimension > 3 cm and a volume > 10 cm3 and tolerable mass effect can be managed satisfactorily with GKRS. Tumor volume ≥ 15 cm3 is a significant factor predicting poor tumor control following GKRS.

Stereotactic radiosurgery in the treatment of parasellar meningiomas: long-term volumetric evaluation

J Neurosurg 128:362–372, 2018

Parasellar meningiomas tend to invade the suprasellar, cavernous sinus, and petroclival regions, encroaching on adjacent neurovascular structures. As such, they prove difficult to safely and completely resect. Stereotactic radiosurgery (SRS) has played a central role in the treatment of parasellar meningiomas. Evaluation of tumor control rates at this location using simplified single-dimension measurements may prove misleading. The authors report the influence of SRS treatment parameters and the timing and volumetric changes of benign WHO Grade I parasellar meningiomas after SRS on long-term outcome.

METHODS Patients with WHO Grade I parasellar meningiomas treated with single-session SRS and a minimum of 6 months of follow-up were selected. A total of 189 patients (22.2% males, n = 42) form the cohort. The median patient age was 54 years (range 19–88 years). SRS was performed as a primary upfront treatment for 44.4% (n = 84) of patients. Most (41.8%, n = 79) patients had undergone 1 resection prior to SRS. The median tumor volume at the time of SRS was 5.6 cm3 (0.2–54.8 cm3). The median margin dose was 14 Gy (range 5–35 Gy). The volumes of the parasellar meningioma were determined on follow-up scans, computed by segmenting the meningioma on a slice-by-slice basis with numerical integration using the trapezoidal rule.

RESULTS The median follow-up was 71 months (range 6–298 months). Tumor volume control was achieved in 91.5% (n = 173). Tumor progression was documented in 8.5% (n = 16), equally divided among infield recurrences (4.2%, n = 8) and out-of-field recurrences (4.2%, n = 8). Post-SRS, new or worsening CN deficits were observed in 54 instances, of which 19 involved trigeminal nerve dysfunction and were 18 related to optic nerve dysfunction. Of these, 90.7% (n = 49) were due to tumor progression and only 9.3% (n = 5) were attributable to SRS. Overall, this translates to a 2.64% (n = 5/189) incidence of direct SRS-related complications. These patients were treated with repeat SRS (6.3%, n = 12), repeat resection (2.1%, n = 4), or both (3.2%, n = 6). For patients treated with a margin dose ≥ 16 Gy, the 2-, 4-, 6-, 8-, 10-, 12-, and 15-year actuarial progression-free survival rates are 100%, 100%, 95.7%, 95.7%, 95.7%, 95.7%, and 95.7%, respectively. Patients treated with a margin dose < 16 Gy, had 2-, 4-, 6-, 8-, 10-, 12-, and 15-year actuarial progressionfree survival rates of 99.4%, 97.7%, 95.1%, 88.1%, 82.1%, 79.4%, and 79.4%, respectively. This difference was deemed statistically significant (p = 0.043). Reviewing the volumetric patient-specific measurements, the early follow-up volumetric measurements (at the 3-year follow-up) reliably predicted long-term volume changes and tumor volume control (at the 10-year follow-up) (p = 0.029).

CONCLUSIONS SRS is a durable and minimally invasive treatment modality for benign parasellar meningiomas. SRS offers high rates of growth control with a low incidence of neurological deficits compared with other treatment modalities for meningiomas in this region. Volumetric regression or stability during short-term follow-up of 3 years after SRS was shown to be predictive of long-term tumor control.

 

Prospective comparison of long-term pain relief rates after first-time microvascular decompression and stereotactic radiosurgery for trigeminal neuralgia

J Neurosurg 128:68–77, 2018

Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD), stereotactic radiosurgery (SRS), and radiofrequency ablation (RFA). Although the efficacy of each procedure has been described, few studies have directly compared these treatment modalities on pain control for TN. Using a large prospective longitudinal database, the authors aimed to 1) directly compare long-term pain control rates for first-time surgical treatments for idiopathic TN, and 2) identify predictors of pain control.

METHODS The authors reviewed a prospectively collected database for all patients who underwent treatment for TN between 1997 and 2014 at the University of California, San Francisco. Standardized collection of data on preoperative clinical characteristics, surgical procedure, and postoperative outcomes was performed. Data analyses were limited to those patients who received a first-time procedure for treatment of idiopathic TN with > 1 year of follow-up.

RESULTS Of 764 surgical procedures performed at the University of California, San Francisco, for TN (364 SRS, 316 MVD, and 84 RFA), 340 patients underwent first-time treatment for idiopathic TN (164 MVD, 168 SRS, and 8 RFA) and had > 1 year of follow-up. The analysis was restricted to patients who underwent MVD or SRS. Patients who received MVD were younger than those who underwent SRS (median age 63 vs 72 years, respectively; p < 0.001). The mean follow-up was 59 ± 35 months for MVD and 59 ± 45 months for SRS. Approximately 38% of patients who underwent MVD or SRS had > 5 years of follow-up (60 of 164 and 64 of 168 patients, respectively). Immediate or short-term (< 3 months) postoperative pain-free rates (Barrow Neurological Institute Pain Intensity score of I) were 96% for MVD and 75% for SRS. Percentages of patients with Barrow Neurological Institute Pain Intensity score of I at 1, 5, and 10 years after MVD were 83%, 61%, and 44%, and the corresponding percentages after SRS were 71%, 47%, and 27%, respectively. The median time to pain recurrence was 94 months (25th–75th quartiles: 57–131 months) for MVD and 53 months (25th–75th quartiles: 37–69 months) for SRS (p = 0.006). A subset of patients who had MVD also underwent partial sensory rhizotomy, usually in the setting of insignificant vascular compression. Compared with MVD alone, those who underwent MVD plus partial sensory rhizotomy had shorter pain-free intervals (median 45 months vs no median reached; p = 0.022). Multivariable regression demonstrated that shorter preoperative symptom duration (HR 1.005, 95% CI 1.001–1.008; p = 0.006) was associated with favorable outcome for MVD and that post-SRS sensory changes (HR 0.392, 95% CI 0.213–0.723; p = 0.003) were associated with favorable outcome for SRS.

CONCLUSIONS In this longitudinal study, patients who received MVD had longer pain-free intervals compared with those who underwent SRS. For patients who received SRS, postoperative sensory change was predictive of favorable outcome. However, surgical decision making depends upon many factors. This information can help physicians counsel patients with idiopathic TN on treatment selection.

Stereotactic Radiosurgery for Brainstem Arteriovenous Malformations

Neurosurgery 81:910–920, 2017

The management of brainstem arteriovenous malformations (bAVMs) is a formidable challenge. bAVMs harbor higher morbidity and mortality compared to other locations.

OBJECTIVE: To review the outcomes following stereotactic radiosurgery (SRS) of bAVMs in a multicenter study.

METHODS: Six medical centers contributed data from 205 patients through the International Gamma Knife Research Foundation. Median age was 32 yr (6-81). Median nidus volume was 1.4 mL (0.1-69 mL). Favorable outcome (FO) was defined as AVM obliteration and no post-treatment hemorrhage or permanent symptomatic radiation-induced complications.

RESULTS: Overall obliteration was reported in 65.4% (n = 134) at a mean follow-up of 69 mo. Obliteration was angiographically proven in 53.2% (n = 109) and on MRA in 12.2% (n=25). Actuarial rate of obliteration at 2, 3, 5, 7, and 10 yr after SRS was 24.5%, 43.3%, 62.3%, 73%, and 81.8% respectively. Patients treated with a margin dose >20 Gy were more likely to achieve obliteration (P = .001). Obliteration occurred earlier in patients who received a higher prescribed margin dose (P = .05) and maximum dose (P = .041). Post-SRS hemorrhage occurred in 8.8% (n = 18). Annual post gamma knife latency period hemorrhage was 1.5%. Radiation-induced complications were radiologically evident in 35.6% (n = 73), symptomatic in 14.6% (n=30), and permanent in 14.6% (n=30, which included long-tract signs and new cranial nerve deficits). FO was achieved in 64.4% (n = 132). Predictors of an FO were a higher Virginia radiosurgery AVM scale score (P = .003), prior hemorrhage (P = .045), and a lower prescribed maximum dose (P = .006).

CONCLUSION: SRS for bAVMs results in obliteration and avoids permanent complications in the majority of patients.

Efficacy and outcomes of facial nerve–sparing treatment approach to cerebellopontine angle meningiomas

J Neurosurg 127:1231–1241, 2017

Advanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patient’s life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC).

METHODS Medical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve–sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated.

RESULTS According to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes.

CONCLUSIONS CPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.

Stereotactic radiosurgery for cerebellar arteriovenous malformations: an international multicenter study

J Neurosurg 127:512–521, 2017

Cerebellar arteriovenous malformations (AVMs) represent the majority of infratentorial AVMs and frequently have a hemorrhagic presentation. In this multicenter study, the authors review outcomes of cerebellar AVMs after stereotactic radiosurgery (SRS).

METHODS: Eight medical centers contributed data from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65% presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent radiation-induced complications (RICs). Patients were followed clinically and radiographically, with a median follow-up of 60 months (range 7–325 months).

RESULTS: The overall actuarial rates of obliteration at 3, 5, 7, and 10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session SRS. Obliteration and a favorable outcome were more likely to be achieved in patients treated with a margin dose greater than 18 Gy (p < 0.001 for both), demonstrating significantly better rates (83.3% and 79%, respectively). The rate of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable outcome.

CONCLUSIONS: SRS results in successful obliteration and a favorable outcome in the majority of patients with cerebellar AVMs. Most patients will require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical and not microsurgical scales were predictive of clinical outcome after SRS.

Cystic Vestibular Schwannomas Respond Best to Radiosurgery

Neurosurgery 81:490–497, 2017

Vestibular schwannomas (VS) have a well-documented response to Gamma Knife R  (Elekta AB, Stockholm, Sweden) Stereotactic radiosurgery (SRS). However, there are limited data available regarding the volumetric response of cystic tumors.

OBJECTIVE: This report correlates the radiographic appearance of VS before radiosurgery with the delayed volumetric response.

METHODS: This study reviewed our SRS experience with 219 VS patients between 2003 and 2013. Patients were treatment naïve and had a significant extracanalicular tumor volume. Magnetic resonance imaging at the time of SRS identified 42 contrast-enhancing macrocystic tumors, 45 contrast-enhancing microcystic tumors, and 132 homogeneously enhancing tumors with no intratumoral cyst formation. The median follow-up was 49.1 months. The median tumor volume was 2.6 cm3 (0.70-16.1 cm3) and the median dose was 12.5 Gy (11-13 Gy).

RESULTS: The actuarial tumor control rate was 99.4% at 2 years and 96.4% at 5 years. A volumetric reduction of >20% occurred in 85.4% of macrocystic tumors, 76.1% of microcystic tumors, and 62.8% of homogeneously enhancing VS. The median volume decrease per year for macrocystic, microcystic, and homogenous tumors was 17.2%, 7.5%, and 7.9% per year respectively (P < .001). A 2:1 blinded volumetric case match showed a significant size reduction in macrocystic tumors compared to noncystic tumors (P = .007). Serviceable hearing was maintained in 61.5% of patients that had Gardner-Robertson grade I-II hearing before treatment. Surgical resection or repeat radiosurgery was performed in 8 patients (3.6%) who had sustained tumor progression.

CONCLUSION: SRS provided VS tumor control in >95% of patients, regardless of radiographic characteristics. Tumor volume regression was most evident in patients with cystic tumors.

Preserving normal facial nerve function and improving hearing outcome in large vestibular schwannomas with a combined approach

Acta Neurochir (2017) 159:1197–1211

To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal functional outcome for facial and cochlear nerves.

Methods Patient characteristics, surgical and dosimetric features, and outcome were collected prospectively at the time of treatment and during the follow-up.

Results A consecutive series of 32 patients was treated between July 2010 and June 2016. Mean follow-up after surgery was 29 months (median 24, range 4–78). Mean presurgical tumor volume was 12.5 cm3 (range 1.47–34.9). Postoperative status showed normal facial nerve function (House– Brackmann I) in all patients. In a subgroup of 17 patients with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained serviceable hearing. Among them, 13 had normal hearing (Gardner–Robertson class 1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean duration between surgery and GKRS was 6.3 months (range 3.8–13.9). Mean tumor volume at GKRS was 3.5 cm3 (range 0.5–12.8), corresponding to mean residual volume of 29.4% (range 6– 46.7) of the preoperative volume. Mean marginal dose was 12 Gy (range 11–12). Mean follow-up after GKRS was 24 months (range 3–60). Following GKRS, there were no new neurological deficits, with facial and hearing functions remaining identical to those after surgery in all patients. Three patients presented with continuous growth after GKRS, were considered failures, and benefited from the same combined approach a second time.

Conclusion Our data suggest that large VS management, with planned subtotal resection followed by GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve and a high level of cochlear nerve functions to be retained. Our functional results with this approach in large VS are comparable with those obtained with GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.

 

Radiosurgery for Unruptured Brain Arteriovenous Malformations: An International Multicenter Retrospective Cohort Study

Neurosurgery 80:888–898, 2017

The role of intervention in the management of unruptured brain arteriovenous malformations (AVM) is controversial.

OBJECTIVE: To analyze in a multicenter, retrospective cohort study, the outcomes following radiosurgery for unruptured AVMs and determine predictive factors.

METHODS: We evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes.

RESULTS: The unruptured AVM cohort comprised 938 patients with a median age of 35 yr. The median nidus volume was 2.4 cm3, 71% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 57%. The median radiosurgical margin dose was 21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 9% and 3%, respectively. Favorable outcome was achieved in 61%. In the multivariate logistic regression analysis, smaller AVM maximum diameter (P = .001), the absence of AVM-associated arterial aneurysms (P = .001), and higher margin dose (P = .002) were found to be independent predictors of a favorable outcome. A margin dose ≥ 20 Gy yielded a significantly higher rate of favorable outcome (70% vs 36%; P < .001)

CONCLUSION: Radiosurgery affords an acceptable risk to benefit profile for patients harboring unruptured AVMs. These findings justify further prospective studies comparing radiosurgical intervention to conservative management for unruptured AVMs.

 

Staged-Volume Radiosurgery of Large Arteriovenous Malformations Improves Outcome by Reducing the Rate of Adverse Radiation Effects

Neurosurgery 80:180–192, 2017

The treatment of large arteriovenous malformations (AVMs) remains challenging. Recently, staged-volume radiosurgery (SVRS) has become an option.

OBJECTIVE: To compare the outcome of SVRS on large AVMs with our historical, single- stage radiosurgery (SSRS) series.

METHODS: We have been prospectively collecting data of patients treated by SVRS since 2007. There were 84 patients who had a median age of 37 years (range, 9-62 years) who were treated until July 2013. The outcomes of 76 of those who had follow-ups available were analyzed and compared with the outcomes of 122 patients treated with the best SSRS technique.

RESULTS: There were 21.5% of AVMs that were deep seated, and 44% presented with hemorrhage resulting in 45% fixed neurological deficit. There were 14% of patients who had undergone embolization before radiosurgery. The median nidus treatment volume was 19.7 cm 3 (6.65-68.7) and 17.5 Gy (13-22.5) prescription isodose was given. Of the 44 lesions having radiological follow-up at 4 years, 61.4% were completely obliterated. Previous embolization (50% with and 63% without) and higher Spetzler-Martin grades appeared to be the negative factors in successful obliteration, but treatment volume was not. Within 3 years after radiosurgery, the annual bleed rates of unruptured and previously ruptured AVMs were 3.2% and 5.6%, respectively. Three bleeds were fatal and 2 resulted in significant modified Rankin scale 3 morbidity. These rates differ little from SSRS. Temporary adverse radiation effects (AREs) did not change significantly, but permanent AREs dropped from 15% to 6.5% (P = .03) compared with SSRS.

CONCLUSION: Obliteration and hemorrhage rates of large AVMs treated by SVRS are similar to historical SSRS. However, SVRS offers a lower rate of AREs.

 

Long-Term Results of Stereotactic Radiosurgery for Skull Base Meningiomas

Long-Term Results of Stereotactic Radiosurgery for Skull Base Meningiomas

Neurosurgery 79:58–68, 2016

Gamma knife radiosurgery (GKRS) is well established in the management of inaccessible, recurrent, or residual benign skull base meningiomas. Most series report clinical outcome parameters and complications in the short intermediate period after radiosurgery. Reports of long-term tumor control and neurological status are still lacking.

OBJECTIVE: To report the presentation, treatment, and long-term outcome of skull base meningiomas after GKRS.

METHODS: From a prospectively collected institutional review board-approved database, we selected patients with a World Health Organization grade I skull base meningioma treated with a single-session GKRS and a minimum of 60 months follow-up. One hundred thirty-five patients, 54.1% males (n = 73), form the cohort. Median age was 54 years (19-80). Median tumor volume was 4.7 cm3 (0.5-23). Median margin dose was 15 Gy (7.5-36). Median follow-up was 102.5 months (60.1-235.4). Patient and tumor characteristics were assessed to determine the predictors of neurological function and tumor progression.

RESULTS: At last follow-up, tumor volume control was achieved in 88.1% (n = 119). Post- GKRS clinical improvement or stability was reported in 61.5%. The 5-, 10-, and 15-year actuarial progression-free survival rates were 100%, 95.4%, and 68.8%, respectively. Favorable outcome (both tumor control and clinical preservation/improvement) was attained in 60.8% (n = 79). Pre-GKRS performance status (Karnofsky Performance Scale) was shown to influence tumor progression (P = .001) and post-GKRS clinical improvement/preservation (P = .003).

CONCLUSION: GKRS offers a highly durable rate of tumor control for World Health Organization grade I skull base meningiomas, with an acceptably low incidence of neurological deficits. The Karnofsky Performance Scale at the time of radiosurgery serves as a reliable long-term predictor of overall outcome.