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.

 

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.

 

Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients

Neurosurgery, Volume 85, (4), October 2019, 550–559

An understanding of the hearing outcomes is needed for treatment counseling for patients with vestibular schwannomas (VS).

OBJECTIVE: To determine long-term hearing results following stereotactic radiosurgery (SRS) for VS and identify any influential variables.

METHODS: Tertiary hospital retrospective cohort.

RESULTS: There were 579 tumors (576 patients) treated with SRS. Eighty-two percent (473) of tumors had ≥1 yr and 59% (344 ≥3 yr follow-up. In the 244 tumor ears, with measurable hearing before SRS who were followed ≥1 yr, 14% (31) had improved hearing, 13% (29) unchanged hearing, and 74% (158) had worsened hearing. In 175 patients with ≥3 yr followup and who had measurable hearing pretreatment, 6% (11 ears) improved hearing, 31% (54 ears) unchanged hearing, and 63% (110 ears) had worsened hearing. Patients with tumors with larger target volumes (P = 0.040) and with neurofibromatosis type 2 (NF2; P = 0.017) were associated with poorer hearing (P = 0.040). Patients with word recognition scores (WRS) of 50% or poorer had tumors with a larger volume (P = 0.0002), larger linear size (P=0.032),andNF2(P=0.045).TraditionallyreportedhearingoutcomesusingtheGardner RobertsonmaintenanceofPTA ≤50dborWRS≥50%were48%at3yr,whichoverestimates hearing outcomes compared to the above reporting standards.

CONCLUSION: Hearing declines over time in VS treated with SRS in a high proportion of cases. The frequency and magnitude of long-term hearing decline following SRS argues against prophylactic radiation for small tumors in hearing ears with undetermined growth behavior.

Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery, Volume 85, Issue 2, August 2019, Pages 257–263

The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial.

OBJECTIVE: To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group.

METHODS: A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox propor- tional hazards.

RESULTS: Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respec- tively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume param- eters predicted for death, neurologic death or toxicity.

CONCLUSION: SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

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.

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.

Radiation-Induced Changes After Stereotactic Radiosurgery for Brain Arteriovenous Malformations

Neurosurgery 83:365–376, 2018

Radiation-induced changes (RICs) are the most common complication of stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs), and they appear as perinidal T2-weighted hyperintensities on magnetic resonance imaging, with or without associated neurological symptoms.

OBJECTIVE: To determine the rates of RIC after AVM SRS and identify risk factors.

METHODS: A literature review was performed using PubMed and MEDLINE to identify studies reporting RIC in AVM patients treated with SRS. RICs were classified as radiologic (any neuroimaging evidence), symptomatic (any associated neurological deterioration, regardless of duration), and permanent (neurological decline without recovery). Baseline, treatment, and outcomes data were extracted for statistical analysis.

RESULTS: Based on pooled data from 51 studies, the overall rates of radiologic, symptomatic, and permanent RIC after AVMSRS were 35.5% (1143/3222 patients, 32 studies), 9.2% (499/5447 patients, 46 studies), and 3.8% (202/5272 patients, 39 studies), respectively. Radiologic RIC was significantly associated with lack of prior AVM rupture (odds ratio [OR] = 0.57; 95% confidence interval [CI]: 0.47-0.69; P < .001) and treatment with repeat SRS (OR = 6.19; 95% CI: 2.42-15.85; P < .001). Symptomatic RIC was significantly associated with deep AVM location (OR = 0.38; 95% CI: 0.21-0.67; P< .001).

CONCLUSION: Approximately 1 in 3 patients with AVMs treated with SRS develop radiologically evident RIC, and of those with radiologic RIC, 1 in 4 develop neurological symptoms. Lack of prior AVM hemorrhage and repeat SRS are risk factors for radiologic RIC, and deep nidus location is a risk factor for symptomatic RIC.

State of the Art Treatment of Spinal Metastatic Disease

Neurosurgery 82:757–769, 2018

Treatment paradigms for patients with spine metastases have evolved significantly over the past decade. Incorporating stereotactic radiosurgery into these paradigms has been particularly transformative, offering precise delivery of tumoricidal radiation doses with sparing of adjacent tissues. Evidence supports the safety and efficacy of radiosurgery as it currently offers durable local tumor control with low complication rates even for tumors previously considered radioresistant to conventional radiation.

The role for surgical intervention remains consistent, but a trend has been observed toward less aggressive, often minimally invasive, techniques. Using modern technologies and improved instrumentation, surgical outcomes continue to improve with reduced morbidity.

Additionally, targeted agents such as biologics and checkpoint inhibitors have revolutionized cancer care, improving both local control and patient survivals. These advances have brought forth a need for new prognostication tools and a more critical review of long-term outcomes. The complex nature of current treatment schemes necessitates a multidisciplinary approach including surgeons, medical oncologists, radiation oncologists, interventionalists, and pain specialists.

This review recapitulates the current state-of-the-art, evidence-based data on the treatment of spinal metastases, integrating these data into a decision framework, NOMS, which integrates the 4 sentinel decision points in metastatic spine tumors: Neurologic, Oncologic, Mechanical stability, and Systemic disease and medical co-morbidities.

Brainstem Cavernous Malformations: Surgical Indications Based on Natural History and Surgical Outcomes

World Neurosurg. (2018) 110:55-63

Cavernous malformations (CMs) are uncommon lesions occurring in the central nervous system, with an incidence of approximately 0.5% in the general population and constituting 5%e10% of all intracranial vascular malformations. Among CMs, prevalence within the brainstem as reported in the literature has ranged from 4% to 35%. With their precarious location and potentially devastating clinical events, brainstem CMs have attracted attention from neurosurgeons, and with these surgeons’ unrelenting efforts, the microsurgical techniques to treat these lesions in the brainstem have greatly improved in recent decades. Although surgical outcomes reported in the literature have been satisfying, surgical intervention has become increasingly contraindicated because of the tendency for a benign clinical course in brainstem CMs, after weighing this fact against the high risk of surgical morbidity. Thus, it is advisable to operate on patients with symptomatic lesions abutting the pial or ependymal surface of the brainstem or where lesions are accessible to safe entry zones, which have caused more than 1 significantly symptomatic hemorrhage and can be defined as aggressive. However, treatment remains controversial for deep-seated lesions away from the surface of the brainstem or lesions that are inaccessible to safe entry zones. Other treatments, such as radiosurgery and medication, are still debatable, which might be as an alternative for lesions amenable to but at high risk with surgery.

Long-term follow-up of multimodality treatment for multiple sclerosis-related trigeminal neuralgia

Acta Neurochir (2018) 160:135–144

The treatment for multiple sclerosis-related trigeminal neuralgia (MS-TN) is less efficacious and associated with higher recurrence rates than classical TN. No consensus has been reached in the literature on the choice procedure for MS-TN patients. The aim of this study was to assess the incidence and surgical outcomes of medically refractory MS-TN.

Methods Patient records were retrospectively reviewed for all Manitobans undergoing first procedure for medically refractory MS-TN between 2000 and 2014. Subsequent procedures were then recorded and analyzed in this subgroup of patients. The primary outcome measure was time to treatment failure.

Results The incidence of medically refractory MS-TN was 1.2/million/year. Twenty-one patients with 26 surgically treated sides underwent first rhizotomy including 13 GammaKnife and 13 percutaneous rhizotomies comprised of ten glycerol injections and three balloon compressions. Subsequent procedures were required on 23 sides (88%), including 24 GammaKnife, 19 glycerol injections, 25 balloon compressions, two microvascular decompressions, and four open partial surgical rhizotomies with a total of 99 surgeries on 26 sides (range, 1–12 each).

Conclusions The majority of MS-TN patients become medically refractory and require multiple repeat surgical procedures. MS-TN procedures were associated with high rates of pain recurrence and our data suggests reoperation within 1 year is often necessary. Optimal management strategy in this patient population remains to be determined. Patients need to be counseled on managing expectations as treatments commonly afford only temporary relief.

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.

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.

 

Volume-Staged Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations

Neurosurgery 80:543–550, 2017

Radiation-based treatment options of large intracranial arteriovenous malformations (AVM) must balance the likelihood of obliteration with the risk of adverse radiation effects (ARE).
OBJECTIVE: To analyze the efficacy and risks of volume-staged stereotactic radiosurgery (VS-SRS) for AVM.

METHODS: Retrospective study of 34 AVM patients having VS-SRS between 1997 and 2012. A median of 2 stages (range, 2-4) was used to treat a median AVM volume of 22.2 cm3 (range, 7.4-56.7). The median AVM margin dose was 16 Gy (range, 14-18); the median radiosurgery- based AVM score was 2.81 (range, 1.54-6.45). The median follow-up after VS-SRS was 8.2 years (range, 3-13.3).

RESULTS: Nidus obliteration was noted in 18 patients (53%) after VS-SRS. The rate of obliteration was 14% at 3 years, 54% at 5 years, and 75% at 7 years. Six patients (18%) had 11 bleeds after VS-SRS. Two patients (6%) remained neurologically stable, 2 (6%) patients had significant deficits, and 2 patients (6%) died. The actuarial risk of a first bleed after VS-SRS was 6% at 1 year, 12% at 3 years, and 19% at 7 years. Six patients (18%) underwent repeat SRS; all achieved nidus obliteration for an overall cure rate of 71%. Two patients (6%) had a permanent ARE after VS-SRS or repeat SRS.

CONCLUSION: VS-SRS permitted large volume intracranial AVM to be treated with a low rate of ARE. Further study is needed on dose escalation and decreasing the treatment volume per stage to determine if this will increase the rate of obliteration with this technique.

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.

 

Surgical management of medium and large petroclival meningiomas: a single institution’s experience of 199 cases with long-term follow-up

Surgical management of medium and large petroclival meningiomas

Acta Neurochir (2016) 158:409–425

Petroclival meningiomas (PCMs) were once regarded as ‘inoperable’ due to their complex anatomy and limited surgical exposure. This study aimed to evaluate the long-term outcomes of surgically treated PCMs larger than 2 cm.

Methods A series of 199 consecutive patients (137 females, 68.8 %) with PCMs larger than 2 cm from between 1993 and 2003 were included. The clinical charts, radiographs, and follow-ups were evaluated.

Results Gross total resection (GTR) was achieved in 111 (55.8 %) patients, subtotal resection (STR) in 65, and partial resection (PR) in 23. Cranial nerve dysfunctions were the most common complications and occurred in 133 (66.8 %) cases. The surgical mortality was 2.0 %. The Karnofsky Performance Scale (KPS) scores significantly decreased 1 month after the operations (preoperative KPS=76.8 and postoperative KPS = 64.8; p = 0.011, Paired-samples t test). Long-term follow-ups were obtained in 142 patients, the follow-up duration was 171.6 months, and the most recent KPS was 83.2. Permanent morbidities remained in 24 patients (18.9 %). Multivariate analysis revealed that brainstem edema and tumors larger than 4 cm in diameter were independent risk factors in terms of outcomes (KPS < 80). The recurrence/ progression rates were 14.5, 31.8, and 53.3 % for the GTR, STR, and PR cases, respectively (p =0.002, Pearson χ2 test). Gamma Knife radiosurgery for the remnants exhibited good tumor control.

Conclusions Favorable outcomes and low mortality were achieved with the microsurgical management of medium and large PCMs; however, the rates of cranial nerves dysfunction remained high. Radically aggressive resection might not be judicious in terms of postoperative morbidity. The preoperative evaluations and intraoperative findings were informative regarding the outcomes. The low follow-up rate likely compromised our findings, and additional consecutive studies were required.

Effect of Prior Embolization on Cerebral Arteriovenous Malformation Radiosurgery Outcomes

AVM

Neurosurgery 77:406–417, 2015

Embolization before stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVM) has been shown to negatively affect obliteration rates, but its impact on the risks of radiosurgery-induced complications and latency period hemorrhage is poorly defined.

OBJECTIVE: To determine, in a case-control study, the effect of prior embolization on AVM SRS outcomes.

METHODS: We evaluated a database of AVM patients who underwent SRS. Propensity score analysis was used to match the case (embolized nidi) and control (nonembolized nidi) cohorts. AVM angioarchitectural complexity was defined as the sum of the number of major feeding arteries and draining veins to the nidus. Multivariate Cox proportional hazards regression analyses were performed on the overall study population to determine independent predictors of obliteration and radiation-induced changes.

RESULTS: The matching process yielded 242 patients in each cohort. The actuarial obliteration rates were significantly lower in the embolized (31%, 49% at 5, 10 years, respectively) compared with the nonembolized (48%, 64% at 5, 10 years, respectively) cohort (P = .003). In the multivariate analysis for obliteration, lower angioarchitectural complexity (P , .001) and radiologically evident radiation-induced changes (P = .016) were independent predictors, but embolization was not significant (P = .744). In the multivariate analysis for radiologic radiation-induced changes, lack of prior embolization (P = .009) and fewer draining veins (P = .011) were independent predictors.

CONCLUSION: The effect of prior embolization on AVM obliteration after SRS may be significantly confounded by nidus angioarchitectural complexity. Additionally, embolization could reduce the risk of radiation-induced changes. Thus, combined embolization and SRS may be warranted for appropriately selected nidi.

Radiosurgery for symptomatic cavernous malformations: A multi‑institutional retrospective study in Japan

Gamma knife radiosurgery for brainstem cavernous malformations- should a patient wait for the rebleed?

Surg Neurol Int 2015;6:S249-57

A group study for symptomatic cavernous malformation (CM) treated with gamma knife (GK) surgery was performed.

Methods: A total of 298 cases collected from 23 GK centers across Japan were included. Hemorrhage was the most common manifestation, followed by seizures and neurological deficits. Most of the lesions were located in the brainstem and basal ganglia, followed by the cerebral or cerebellar hemispheres. The CMs, which had a mean diameter of 14.8 mm, were treated using GK surgery with a mean marginal dose of 14.6 Gy.

Results: In terms of hemorrhage‑free survival (HFS), a marked dissociation was confirmed between the hemorrhage and seizure groups, while no obvious difference was noted between sexes. Superficial CMs located in cerebellum or lobar regions responded to the treatment better than deeply located CMs in the basal ganglia or brainstem. No significant difference of dose‑dependent response was seen for three different ranges of marginal dose: Less than 15 Gy, between 15 and 20 Gy, and more than 20 Gy. Complications were more frequent after a marginal dose of over 15 Gy and in patients with lesions more than 15 mm in diameter. The rates of annual hemorrhage were estimated to be 7.4% during the first 2 years after radiosurgery and 2.8% thereafter. The overall hemorrhage rate after radiosurgery was 4.4%/year/patient.

Conclusion: The risk of hemorrhage is considerably reduced after GK treatment. The HFS as well as annual hemorrhage rate after GK treatment was apparently superior to that after conservative treatment for symptomatic CMs. To optimize the success of GK treatment, it is important to reduce the incidence of complications.

Stereotactic Radiosurgery for Intracranial Meningiomas: Current Concepts and Future Perspectives

Stereotactic Radiosurgery for Intracranial Meningiomas- Current Concepts and Future Perspectives

Neurosurgery 76:362–371, 2015

Meningiomas are among the most common adult brain tumors. Although the optimal management of meningiomas would provide complete elimination of the lesion, this cannot always be accomplished safely through resection. Therefore, other therapeutic modalities, such as stereotactic radiosurgery (as primary or adjunctive therapy), have emerged.

In the current review, we have provided an overview of the historical outcomes of various radiosurgical modalities applied in the management of meningiomas. Furthermore, we provide a discussion on key factors (eg World Health Organization grade, lesion size, and lesion location) that affect tumor control and adverse event rates. We discuss recent changes in our understanding of meningiomas, based on molecular and genetic markers, and how these will change our perspective on the management of meningiomas.

We conclude by outlining the areas in which knowledge gaps persist and provide suggestions as to how these can be addressed.

Using Higher Isodose Lines for Gamma Knife Treatment of 1 to 3 Brain Metastases Is Safe and Effective

Motor function after stereotactic radiosurgery for brain metastases in the region of the motor cortex

Neurosurgery 74:360–366, 2014

Higher isodose lines (IDLs) in Gamma Knife (GK) Perfexion treatment of brain metastases (BMet) could result in lower local control (LC) or higher radiation necrosis (RN) rates, but reduce treatment time.

OBJECTIVE: To assess the impact of the heterogeneity index (HI) and conformality index (CFI) on local failure (LF) for patients treated with GK for 1 to 3 BMet.

METHODS: From an institutional review board—approved database, 320 patients with 496 BMet were identified, treated for 1 to 3 BMet from July 2007 to April 2011 on GK Perfexion. Cox proportional hazards regression was used to analyze significance of HI, CFI, IDL, dose, tumor diameter, recursive partitioning analysis class, tumor radioresistance, primary, smoking history, metastasis location, and whole-brain radiation therapy (WBRT) history with LF and RN.

RESULTS: Median follow-up by lesion was 6.8 months (range, 0-49.6). The series median survival was 14.2 months. Per RECIST, 9.5% of lesions failed, 33.9% were stable, 38.3% partially responded, 17.1% responded completely, and 1.2% could not be assessed. The 12-month LC rate was 87.3%. On univariate analysis, a dose less than 20 Gy (hazard ratio [HR]: 2.940, P , .001); tumor size (HR: 1.674, P , .001); and cerebellum/brainstem location vs other (HR: 1.891, P = .043) were significant for LF. Non-small cell lung cancer (HR: 0.333, P = .0097) was associated with better LC. On multivariate analysis, tumor size (HR: 1.696, P , .001) and cerebellum/brainstem location vs other (HR: 1.959, P = .033) remained significant for LF. Variables not significant for LF included CI, IDL, and HI.

CONCLUSION: Our study of patients with 1 to 3 BMet treated with GK demonstrated no difference in LC or RN with varying HI, indicating that physicians can treat to IDL at 70% or higher IDL to reduce treatment time without increased LF or RN.