The impact of unscheduled gaps and iso-centre sequencing on the biologically effective dose in Gamma Knife radiosurgery.

PURPOSE: Establish the impact of iso-centre sequencing and unscheduled gaps in Gamma Knife® (GK) radiosurgery on the biologically effective dose (BED). METHODS: A BED model was used to study BED values on the prescription iso-surface of patients treated with GK Perfexion™ (Vestibular Schwannoma). The effect of a 15 min gap, simulated at varying points in the treatment delivery, and adjustments to the sequencing of iso-centre delivery, based on average dose-rate, was quantified in terms of the impact on BED. RESULTS: Depending on the position of the gap and the average dose-rate profiles, the mean BED values were decreased by 0.1% to 9.9% of the value in the original plan. A heuristic approach to iso-centre sequencing showed variations in BED of up to 14.2%, relative to the mean BED of the original sequence. CONCLUSION: The treatment variables, like the iso-centre sequence and unscheduled gaps, should be considered during GK radiosurgery treatments.

A Retrospective Analysis of the Role of Single-Session Gamma Knife Stereotactic Radiosurgery in Sporadic Vestibular Schwannomas with Tumor Volumes Greater Than 10 cm3: Is It Worth Stretching the Boundaries?

OBJECTIVE: To evaluate the role of single-session Gamma Knife stereotactic radiosurgery (GK-SRS) in the treatment of vestibular schwannomas (VSs) with volumes of greater 10 cm3. METHODS: A retrospective analysis was performed of 103 patients treated with single-session GK-SRS between 1993 and 2011 with a mean follow-up of 6.2 years ± 4.4 SD. Treatment, clinical and outcome details were recorded and assessed. RESULTS: Eighty-one (78.6%) patients achieved radiological control with slow progression in a further 5 (4.9%) patients, who did not require further treatment. Linear measurements did not correlate well with volume, which can predict outcome following treatment more precisely. 2.9% of patients developed a new facial paresis, 5.8% trigeminal numbness and 2.9% facial pain. In all, 26 (25.2%) patients who were tested preserved some level of hearing following treatment. CONCLUSIONS: The overall radiological control rate in this study was 78.6%, while tumor volumes less than 20 cm3 can be safely treated with single-stage GK-SRS with an expected control rate of 83.2% without unacceptable morbidity rates. GK-SRS can be utilized as a first-line treatment option in patients with large-volume VSs especially in whom surgery is unattractive.

Repeat Radiosurgery Treatment After Cavernous Malformation Radiosurgery.

OBJECTIVE: Of cavernous malformations (CMs) treated with radiosurgery (RS), 5% bleed after 2-year initial latency period. This rate is similar to failure rate of RS for other pathologies, which often require repeat RS for favorable outcome. The aim of this pilot study was to define failure of CM RS and to assess safety of second RS. METHODS: Retrospective analysis was performed of 7 of 345 CMs retreated with RS; 6 CMs were deep-seated, and 1 was superficial. Median time between the 2 treatments was 8 years (range, 3-16 years), and median follow-up time after second RS was 3 years (range, 1-9 years). RESULTS: Following the 2-year latency period after RS, 6% of deep-seated and 5% of hemispheric CMs, and 6% of deep-seated and 2% of hemispheric lesions caused transient neurologic deficits without hemorrhage. A second treatment was indicated for rebleed in 5 cases and for recurrent transient neurologic deficits in 2 cases. Prescribed dose was 15 Gy (range, 12-20 Gy) at first treatment and 12 Gy (range, 12-18 Gy) at second treatment. Target volumes were 692 mm3 (range, 54-2400 mm3) and 935 mm3 (range, 150-1550 mm3) at first and second treatments, respectively, and treatment volumes were 811 mm3 (range, 79-2500 mm3) and 962 mm3 (range, 194-1750 mm3), respectively. Differences in treatment parameters were not significant. Reason for failure was inaccurate target definition in only 2 cases. There were no bleeds, morbidity, or mortality after second RS. CONCLUSIONS: Second RS applied to previously treated CMs is safe and may be effective. Further investigations are needed to verify these findings and assess long-term benefit of second RS.

Contemporary radiosurgery of cerebral cavernous malformations: Part 1. Treatment outcome for critically located hemorrhagic lesions.

OBJECTIVELong-term benefits of radiosurgery (RS) applying modern protocols to treat cavernous malformations (CMs) remain unclear as critics may consider the decrease in the rebleed rate generally observed 2 years after RS as a reflection of the lesion's natural history. The authors adopted an early intention-to-treat attitude since rehemorrhage from deep-seated CMs ultimately leads to stepwise neurological deterioration. The safety of this early policy was previously demonstrated. Here, the authors revisit their current practice in a larger population with a longer follow-up time to assess the long-term effects of RS in the context of current knowledge on the natural history of CMs.METHODSThe authors conducted a retrospective analysis of 210 patients with 210 hemorrhagic CMs located in the brainstem, thalamus, or basal ganglia and treated with Gamma Knife RS between 1995 and 2014. Two hundred six patients had available follow-up, which was a median of 5.5 years (range 1-20 years). The median age was 37 years (0.5-77 years) at presentation and 43 (2-78) at treatment. One hundred twenty-seven CMs had bled once and 83 had had multiple hemorrhages prior to treatment.RESULTSThe lifetime annual bleed rate of CMs having a single hemorrhage prior to treatment was 2.4% per lesion. The hemorrhage rate stabilized at 1.1% after a temporary increase of 4.3% within the first 2 years after RS. The annual pretreatment hemorrhage rate was 2.8% for the lesions having multiple bleeds prior to RS with a pretreatment rebleed rate of 20.7% and with a modest gradual decrease within the first 5 years and remaining stable at 11.55% thereafter. The rebleed rate fell to 7.9% for the first 2 years after RS and declined further to 1.3% thereafter, which was significantly lower than the long-term pretreatment rebleed risk. The rate of hemorrhage-free survival remained 86.4% and 75.1% (1 patient each) at 20 years after RS in the single- and multiple-bleed groups, respectively.Pretreatment hemorrhages resulted in permanent deficits in 48.8% of the cases with a single bleed and in 77.1% of the cases with multiple bleeds. Both the rate and severity of deficits were significantly lower in the first group. Only mild and a low rate of permanent neurological deficits were caused either by posttreatment hemorrhages (7.4%) or by radiation (7.2%). The rate of persistent morbidity in the single-bleed group remained significantly lower at the end of the study than pretreatment morbidity in the multiple-bleed group (OR 2.9, 95% CI 1.6-5.3). Lesion-specific mortality was < 1%.CONCLUSIONSThe hemorrhage rate of CMs after RS remained low after the first 2 years during the longer follow-up period. The benefit of early treatment appears to be confirmed by the study results as repeated hemorrhages carry the risk of significantly higher cumulative morbidity than the morbidity associated with RS.

Contemporary radiosurgery of cerebral cavernous malformations: Part 2. Treatment outcome for hemispheric lesions.

OBJECTIVEThe role of radiosurgery (RS) in treating superficial cavernous malformations (CMs) is insufficiently studied in part because of the disappointing results of early experimental attempts as compared to the mostly safe and effective microsurgery. Nonetheless, because of lesion- or treatment-specific factors, a therapeutic alternative may be required. In this study, the authors aimed to assess the safety of RS in treating superficial CMs and to analyze its long-term effect on hemorrhage rates and epilepsy control.METHODSThe authors conducted a retrospective analysis of 96 patients with 109 CMs located in the cerebral or cerebellar hemispheres and treated with RS between 1995 and 2014. A median of 15 Gy (range 10-25 Gy) was given to the 50% prescription isodose level, lesion volume was 604 mm3 (4-8300 mm3), and the prescription isodose volume was 638.5 mm3 (4-9500 mm3). Outcomes were compared to those of 206 deep-seated lesions reported on in another study. Ninety-five patients had available follow-up, which was a median of 7 years (1-21 years). Median patient age was 42 years (0.5-77) at presentation and 45 (3-80) at treatment. Seventy-one CMs presented with symptomatic hemorrhage, and 52 caused seizures.RESULTSIn the nonhemorrhagic group (37 lesions), one bleed occurred during the follow-up period, for an annual bleed rate of 0.4% per lesion. The lifetime annual bleed rate of CMs having a single hemorrhage prior to treatment was 2.5%. The rebleed rate in the single-bleed group decreased from 1.8% within the first 2 years after RS to 0.7% thereafter. The pretreatment rebleed rate for lesions having multiple bleeds prior to RS was 14.15%, which fell to 3.85% for the first 2 years after RS and declined to 1.3% thereafter. Multivariate analysis showed younger age, deep lesion location, and multiple pretreatment hemorrhages as significant predictors of posttreatment hemorrhage.Pretreatment hemorrhages led to permanent deficits in 41.4% of the cases with a single bleed and in 46.1% of cases with multiple bleeds. Only mild (modified Rankin Scale score 1) and a low rate of permanent neurological deficits were caused either by posttreatment hemorrhages (4.3%) or by radiation (2%).The rate of improvement in epilepsy was 84.9% after RS in patients with at least one seizure prior to treatment, not depending on the presence of hemorrhage or the time interval between presentation and treatment. Favorable outcome occurred in 81% of patients whose seizures were not controlled with antiepileptic medication prior to RS.CONCLUSIONSRadiosurgery for superficial CMs is safe and appears to be effective, offering a real treatment alternative to surgery for selected patients. Given their relatively benign natural history, superficial CMs require further study to verify the long-term benefit of RS over the lesions' natural history.

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

Background: 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 cm3 (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.

Gamma Knife radiosurgery for glomus jugulare tumors: a single-center series of 75 cases.

OBJECTIVE Glomus jugulare tumors are rare indolent tumors that frequently involve the lower cranial nerves (CNs). Complete resection can be difficult and associated with lower CN injury. Gamma Knife radiosurgery (GKRS) has established its role as a noninvasive alternative treatment option for these often formidable lesions. The authors aimed to review their experience at the National Centre for Stereotactic Radiosurgery, Sheffield, United Kingdom, specifically the long-term tumor control rate and complications of GKRS for these lesions. METHODS Clinical and radiological data were retrospectively reviewed for patients treated between March 1994 and December 2010. Data were available for 75 patients harboring 76 tumors. The tumors in 3 patients were treated in 2 stages. Familial and/or hereditary history was noted in 12 patients, 2 of whom had catecholamine-secreting and/or active tumors. Gamma Knife radiosurgery was the primary treatment modality in 47 patients (63%). The median age at the time of treatment was 55 years. The median tumor volume was 7 cm3, and the median radiosurgical dose to the tumor margin was 18 Gy (range 12-25 Gy). The median duration of radiological follow-up was 51.5 months (range 12-230 months), and the median clinical follow-up was 38.5 months (range 6-223 months). RESULTS The overall tumor control rate was 93.4% with low CN morbidity. Improvement of preexisting deficits was noted in 15 patients (20%). A stationary clinical course and no progression of symptoms were noted in 48 patients (64%). Twelve patients (16%) had new symptoms or progression of their preexisting symptoms. The Kaplan-Meier actuarial tumor control rate was 92.2% at 5 years and 86.3% at 10 years. CONCLUSIONS Gamma Knife radiosurgery offers a risk-versus-benefit treatment option with very low CN morbidity and stable long-term results.

Gamma knife surgery for pediatric arteriovenous malformations: a 25-year retrospective study.

OBJECT: The authors present their 25-year experience in treating pediatric arteriovenous malformations (AVMs) to allow comparisons with other historic studies and data in adults. METHODS: Data were collected from a prospectively maintained departmental database selected for age and supplemented by case note review and telephone interviews as appropriate. RESULTS: Three hundred sixty-three patients, ages 1-16 years (mean ± SD, 12 ± 3.2 years), underwent 410 treatments; 4 had planned 2-stage treatments and 43 were retreated subsequent to an initial partial response. Fifty-eight percent received general anesthesia for the procedure. Sixteen percent had previously undergone embolization. The most common presenting symptoms were as follows: hemorrhage (80.2%), epilepsy (8.3%; overall seizure prevalence 19.9%), and migrainous headaches (6.3%). Only 0.28% of the AVMs were incidental findings. The mean lesion volume was 3.75 ± 5.3 cm3 (range 0.01-32.8 cm3), with a median Spetzler-Martin grade of III (range I-V). The mean peripheral (therapeutic) dose was 22.7 ± 2.3 Gy (range 15-25 Gy), corresponding to a mean maximum dose of 43.6 ± 6 Gy (range 25-51.4 Gy). The obliteration rate was 71.3% in patients who received one treatment and 62.5% for retreated patients, with a mean obliteration time of 32.4 and 79.6 months, respectively. The overall obliteration rate was 82.7%. No follow-up data are as yet available for the 4 patients who underwent the staged treatments. Only 4 patients received peripheral doses below 20 Gy, and the AVM was obliterated in 3 of these patients. The other patients received 20, 22.5, or 25 Gy and had obliteration rates of 82.6%, 77.7%, and 86.3%, respectively. The bleeding rate postradiosurgery was 2.2%, and the cumulative complication rate was 3.6%, with radionecrosis being the most common complication (1.1%). CONCLUSIONS: Surprisingly, there was no correlation (p = 0.43) between outcome and radiosurgical dose when that dose was between 20 and 25 Gy, thus suggesting that the lower of these 2 doses may be effective. Radiosurgery for pediatric AVM is safe and effective.

Gamma Knife® radiosurgery for recurrent intracranial olfactory neuroblastoma (esthesioneuroblastoma): a case report.

BACKGROUND: We report the use of salvage radiosurgery to manage an aggressive olfactory neuroblastoma (esthesioneuroblastoma) with multiple recurrences and intracranial extension. CASE PRESENTATION: A 43-year-old Caucasian woman presented 11 years ago with progressive nasal blockage and headaches. A necrotic polyp originating in her left middle meatus and extending to the ethmoid air cells and cribriform plate (Kadish stage C) was radically resected via a craniofacial approach. Four years later, a local recurrence extending into her left cavernous sinus was identified and deemed inoperable. She received vincristine, ifosfamide, doxorubicin and etoposide chemotherapy (with minimal benefit) and external beam radiotherapy (60Gy in 30 fractions) to her skull base. Two years later, tumour extension in her left neck was treated with radical radiotherapy. She developed visual disturbances in her left eye, which progressed to blindness in the next two years. Having exhausted chemoradiotherapy, the left cavernous sinus esthesioneuroblastoma was treated with Gamma Knife® radiosurgery 2 years ago (20Gy at 50% isodose, tumour volume 7.5cm3). At one year, there was dramatic reduction in the tumour and no new symptoms; however, there were new tumour foci (in her left frontal lobe and above her right orbital apex). These were again treated with radiosurgery (20Gy at 50% isodose, total tumour volume 0.67cm3). Repeat imaging at six months showed no further disease progression. CONCLUSION: Whilst rare, olfactory neuroblastoma (esthesioneuroblastoma) can present management challenges and Gamma Knife® radiosurgery may prove a useful strategy in controlling intracranial spread.

Survival and complications following γ knife radiosurgery or enucleation for ocular melanoma: a 20-year experience.

BACKGROUND: We present our experience in treating ocular melanoma at the National Centre for Stereotactic Radiosurgery in Sheffield, UK over the last 20 years. METHOD: We analysed 170 patients treated with Gamma Knife radiosurgery, recorded the evolution of visual acuity and complication rates, and compared their survival with 620 patients treated with eye enucleation. Different peripheral doses (using the 50% therapeutic isodose) were employed: 50-70 Gy for 24 patients, 45 Gy for 71 patients, 35 Gy for 62 patients. FINDINGS: There was no significant difference in survival between the 35-Gy, 45-Gy and 50- to 70-Gy groups when compared between themselves (p = 0.168) and with the enucleation group (p = 0.454). The 5-year survival rates were: 64% for 35 Gy, 62.71% for 45 Gy, 63.6% for 50-70 Gy and 65.2% for enucleated patients. Clinical variables influencing survival for radiosurgery patients were tumour volume (p = 0.014) and location (median 66.4 vs 37.36 months for juxtapapillary vs peripheral tumours, respectively; p = 0.001), while age and gender did not prove significant. Regarding complications, using 35 Gy led to more than a 50% decrease, when compared with the 45-Gy dose, in the incidence of cataract, glaucoma and retinal detachment. Retinopathy, optic neuropathy and vitreous haemorrhage were not significantly influenced. Blindness decreased dramatically from 83.7% for 45 Gy to 31.4% for 35 Gy (p = 0.006), as well as post-radiosurgery enucleation: 23.9% for 45 Gy vs 6.45% for 35 Gy (p = 0.018). Visual acuity, recorded up to 5 years post-radiosurgery, was significantly better preserved for 35 Gy than for 45 Gy (p = 0.0003). CONCLUSIONS: Using 35 Gy led to a dramatic decrease in complications, vision loss and salvage enucleation, while not compromising patient survival.

Stereotactic radiosurgery for trigeminal schwannomas.

PURPOSE: Traditionally trigeminal schwannomas (TS) have been treated microsurgically; however, this is often associated with significant morbidity, and complete excision remains a challenge. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative in treating TS. We report on our cumulative experience of using SRS in the treatment of TS. MATERIALS AND METHODS: Seventy-four TS patients (four with NF2) were treated with SRS using the Leksell Gamma Knife. Mean age (±1 SD) at treatment was 47.1 (15.5) years with a mean interval between presentation and treatment of 30.9 months. Thirty (40.5%) patients had undergone previous surgery on average 47.3 months prior to SRS. The average target volume was 5.3 cm(3) (range 0.4-19.9 cm(3)) and was treated with a mean prescription dose of 16.4 (3.9) Gy to the tumour margin. RESULTS: Average follow-up was 48.2 months (range 6-168 months). Tumour size remained static in 58 (78.4%) patients and showed radiological evidence of shrinkage in 11 (14.9%). Tumour progression occurred in five (6.6%) patients on average 40 months after SRS (range 12-108). Progression-free survival (PFS) for all patients was 98.5% at 1 year, 92.7% at 5 years and 79.4% at 10 years. Log-rank analysis indicated a significantly worse outcome for NF2 patients (p = 0.001) who demonstrated a PFS of 100% at 1 year and 50% at 5 years. Seven patients developed adverse radiation effects whilst improvements in pre-treatment cranial nerve dysfunction were achieved in eight patients. CONCLUSIONS: SRS is an effective treatment option in patients with residual or newly diagnosed TS. In view of the results of this study we would advocate a more front-line role for the Gamma Knife in the treatment of this tumour group.

Stereotactic radiosurgery for trigeminal neuralgia: outcomes and complications.

Stereotactic radiosurgery is one of a number of recognised treatments for the management of trigeminal neuralgia refractory to drug therapy. The reported success of stereotactic radiosurgery in managing patients with trigeminal neuralgia varies in different units from 22 to 75%. This paper reports the outcomes of patients with trigeminal neuralgia who were treated at the National Centre for Stereotactic Radiosurgery in Sheffield, UK. The study reports the outcome of 72 patients treated consecutively between October 2004 and May 2008. Data were collected prospectively by a postal questionnaire sent to patients at 6, 12 and 24 months after treatment. The median age was 65.6 years (39 males: 33 females). Fourteen patients had secondary trigeminal neuralgia (eight multiple sclerosis). Fifteen of the patients included in the study were receiving a second treatment (an initial treatment having improved their pain significantly for at least 6 months). All radiosurgical procedures were performed using a single 4 mm collimator isocenter covering the region of the dorsal root entry zone with a maximal radiation dose of 80 Gy. The percentage of patients defined as having an excellent outcome (pain free without medication) was 39% after 6 months, 36% after 12 months and 64% after 24 months. The percentage of patients who reported being very satisfied with treatment was 71% after 6 months, 57% after 12 months and 53% after 24 months. Half the patients with secondary trigeminal neuralgia were pain free without medication after treatment, and 60% of patients who underwent a second treatment were pain free. A new trigeminal sensory deficit was reported by 31% of patients after radiosurgical treatment.

Stereotactic radiosurgery for arteriovenous malformations located in deep critical regions.

BACKGROUND: Radiosurgery is widely used to treat deep eloquent arteriovenous malformations (AVMs). OBJECTIVE: To evaluate how anatomic location, AVM size, and treatment parameters define outcome. METHODS: Retrospective analysis of 356 thalamic/basal ganglia and 160 brainstem AVMs treated with gamma knife radiosurgery. RESULTS: Median volume was 2 cm (range, 0.02-50) for supratentorial and 0.5 cm (range, 0.01-40) for brainstem AVMs; the marginal treatment doses were 17.5 to 25 Gy. After single treatment, obliteration was achieved in 65% of the brainstem, in 69% of the supratentorial, and 40% of the peritectal AVMs. Obliteration of lesions <4 cm was better in the brainstem (70%) and in the supratentorium (80%), but not in the peritectal region (40%). Complications were rare (6%-15%) and mild (≤ modified Rankin scale [MRS] 2). Rebleed rate increased with size, but was not higher than before treatment. AVMs >4 cm in the brainstem were treated with unacceptable morbidity and low cure rate. Obliteration of large supratentorial AVMs was 65% to 47% with more complications ≥ MRS3. Repeat radiosurgical treatment led to obliteration in 66% of the cases with minor morbidity. CONCLUSION: Deep eloquent AVMs <4 cm can be treated safely and effectively with radiosurgery. Obliteration of peritectal AVMs is significantly lower after a single treatment. However, morbidity is low, and repeat treatment leads to good obliteration. Radiosurgical treatment >4 cm in the brainstem is not recommended. Supratentorial deep AVMs >8 cm can be treated with radiosurgery with higher risk and lower obliteration rate. However, these lesions are difficult to treat with other treatment modalities, and a 50% success rate makes radiosurgery a good alternative even in this challenging group.

A historical analysis of single-stage γ knife radiosurgical treatment for large arteriovenous malformations: evolution and outcomes.

BACKGROUND: Large arteriovenous malformations (AVMs) remain challenging and difficult to treat, reflected by evolving strategies developed from simple radiosurgical plans, to encompass embolization and, recently, staged volume treatments. To establish a baseline for future practice, we reviewed our clinical experience. METHOD: The outcomes for 492 patients (564 treatments) with AVMs >10 cm(3) treated by single-stage radiosurgery were retrospectively analysed in terms of planning, previous embolization and size. RESULTS: Twenty-eight percent of the patients presented with haemorrhage at a median age of 29 years (range: 2-75). From 1986 to 1993 (157 patients) plans were simplistic, based on angiography using a median of 2 isocentres and a marginal dose of 23 Gy covering 45-70% of the AVM (median volume 15.7 cm(3)). From 1994 to 2000 (225 patients) plans became more sophisticated, a median of 5 isocentres was used, covering 64-95% of the AVM (14.6 cm(3)), with a marginal dose of 21 Gy. Since 2000, MRI has been used with angiography to plan for 182 patients. Median isocentres increased to 7 with similar coverage (62-94%) of the AVM (14.3 cm(3)) and marginal dose of 21 Gy. Twenty-seven percent, 30% and 52% of patients achieved obliteration at 4 years, respectively. The proportion of prior embolization increased from 9% to 44% during the study. Excluding the embolized patients, improvement in planning increased obliteration rates from 28% to 36% and finally 63%. Improving treatment plans did not significantly decrease the rate of persisting radiation-induced side effects (12-16.5%). Complication rate rose with increasing size. One hundred and twenty-three patients underwent a second radiosurgical treatment, with a 64% obliteration rate, and mild and rare complications (6%). CONCLUSIONS: Better visualization of the nidus with multimodality imaging improved obliteration rates without changing morbidity. Our results support the view that prior embolization can make interpretation of the nidus more difficult, reducing obliteration rate. It will be important to see how results of staged volume radiosurgery compare with this historical material.

Stereotactic radiosurgery for pineal tumours.

OBJECTIVES: Pineal tumours continue to present considerable clinical dilemmas and challenges. We were, therefore, interested to review our cumulative experience with a view to formulating a potential treatment strategy. METHODS: A retrospective analysis of all patients treated with Stereotactic radiosurgery (SRS) for pineal tumours in one centre between 1987 and 2009. Forty-four patients (66% male) were treated radiosurgically with a mean age(± 1 sd) of 33.6 (16.4) years. Eleven had biopsy-proven pineal parenchymal tumours (PPT), six astrocytomas, three ependymomas, two papillary epithelial tumours and two germ cell tumours. Twenty (45%) patients had no definitive histology despite attempted surgical biopsy in 11. Prior to radiosurgery, 17 had undergone craniotomy, 10 radiotherapy and four chemotherapy. Nine patients were referred for primary SRS. RESULTS: Fifty Gamma knife treatments were performed on 44 patients prescribing 18.1 (4.2) Gy with a treatment volume of 3.8 (3.8) cm( 3 ). Routine clinical and MRI assessments were reviewed to calculate control rates. Mean follow up was 62.5 (52.9) months. Five patients (two ependymomas and three PPT) died at 36.2 (36.7) months after initial radiosurgical treatment. Overall progression-free survival (PFS) results were 93% at 1 year, 77% at 5 years, 67% at 10 and 20 years. Log-rank analysis revealed that higher initial tumour grade (P = 0.04), previous radiotherapy (P = 0.002) and radiological evidence of necrosis (P = 0.03) were associated with worse outcomes. The 5-year PFS for patients who possessed these 'aggressive' features was 47.1% compared with 91% for those patients who did not have these features. No persistent complications were attributed to SRS. CONCLUSIONS: These results further demonstrate the increasingly significant role played by STRS in the treatment of pineal tumours. Based on our findings, we believe a re-examination of the role of more established therapies for this patient group may be warranted.

Stereotactic radiosurgery for deep-seated cavernous malformations: a move toward more active, early intervention. Clinical article.

OBJECT: The role of radiosurgery in the treatment of cavernous malformations (CMs) remains controversial. It is frequently recommended only for inoperable lesions that have bled at least twice. Rehemorrhage can carry a substantial risk of morbidity, however. The authors reviewed their practice of treating deep-seated inoperable CMs to assess the complication rate of radiosurgery, the impact that radiosurgery might have on rebleeding, and whether a more active, earlier intervention is justified in managing this condition. METHODS: The authors performed a retrospective analysis of 113 patients with 79 brainstem and 39 thalamic/basal ganglia CMs treated with Gamma Knife surgery. Lesions were stratified into 2 groups: those that might be lower risk with no more than 1 symptomatic bleed before radiosurgical treatment and those deemed high risk with multiple symptomatic hemorrhages before treatment. RESULTS: Forty-one CMs had multiple symptomatic hemorrhages before radiosurgery with a first-ever bleed rate of 2.9% per lesion per year, a rebleed rate of 30.5% per lesion per year, and a median time of 1.5 years between the first and second bleeds. In this group the rebleed rate decreased to 15% for the first 2 years after radiosurgery and declined further to 2.4% thereafter. Pretreatment multiple bleeds led to persistent deficits in 72% of the patients. Seventy-seven CMs had no more than 1 symptomatic bleed before radiosurgery, making for a lifetime bleed rate of 2.2% per lesion per year. The short period between the presenting bleed and treatment (median 1 year) makes the natural history in this group uncertain. The rate of hemorrhage in the first 2 years after treatment was 5.1%, and 1.3% thereafter. Pretreatment hemorrhages resulted in permanent deficits in 43% of the patients in this group, a rate significantly lower than in the multiple-bleeds group (p < 0.001). Posttreatment hemorrhages led to persistent deficits in only 7.3% of the patients. Permanent adverse radiation effects were rare (7.3%) and minor in both groups. CONCLUSIONS: Stereotactic radiosurgery is a safe management strategy for CMs in eloquent sites with the marked advantage of reducing rebleed risks in patients with repeated pretreatment hemorrhages. The benefit in treating CMs with a single bleed is less clear. Note, however, that repeated hemorrhage carries a significant risk of increased morbidity far in excess of any radiosurgery-related morbidity, and the authors assert that this finding justifies the early active management of deep-seated CMs.

Malignant transformation of acoustic neuroma/vestibular schwannoma 10 years after gamma knife stereotactic radiosurgery.

Only a handful of cases of de-novo malignancies of the vestibulocochlear nerve have been reported. Even rarer is the malignant transformation of a previously histologically diagnosed benign vestibular schwannoma. We present the case of a young adult who had combined operative/Gamma knife treatment for a benign vestibular schwannoma, followed by further surgery 2 years later. He represented 10 years after original diagnosis with facial numbness and ataxia, MRI showing gross tumor recurrence. After radical resection, histology showed malignant transformation to a malignant peripheral nerve sheath tumor. Within 3 months there was rapid, aggressive recurrence with brainstem compression, requiring further surgery for brainstem decompression. Histology confirmed further de-differentiation to an anaplastic sarcoma. While awaiting radiotherapy the tumor recurred again, the patient succumbing. The patient had no features of neurofibromatosis type 2. In the literature there are 13 other cases of malignant vestibular schwannomata. Only six had radiotherapy and of these only two had histological confirmation of a benign lesion preradiotherapy. Neither of these had neurofibromatosis. Three other cases had histological proof of malignancy postradiosurgery, but with no preradiotherapy histology; of these, two were positive for neurofibromatosis. The tumor biology of vestibular schwannomata as well as the radiobiology in the context of malignant transformation is discussed.

Radiosurgery for type II neurofibromatosis.

A summary of our radiosurgical experience treating type II neurofibromatosis (NF2) vestibular schwannomas (VSs), based on a retrospective consecutive series of 122 tumours in 92 patients, with an extended series of a further 22 patients (906 patient-years of follow-up) to investigate the risk of malignancy after radiosurgery. With current techniques, we estimate that 8 years after radiosurgery for NF2 VS, 20% of patients will have required further treatment, 50% will be well controlled, and in 30% there will have been some concern about control, but they will have been managed conservatively. Three years after treatment, approximately 40% retain their functional hearing, 40% have some deterioration, 20% becoming deaf in that ear. The risk of facial palsy was 5%. Two malignancies were recorded after radiosurgery, in one the malignant behaviour preceded treatment. This is less than the previously reported rate of spontaneously developing malignant gliomas in NF2. Whilst the clinical results are far worse than those achieved treating sporadic tumours, this applies equally to the results of surgery or observation when treating NF2 tumours. It is important therefore that these patients are given advice specific for NF2. Considering this, we believe that radiosurgery remains a valuable minimally invasive treatment option for selected NF2 patients.

The clinical course after stereotactic radiosurgical amygdalohippocampectomy with neuroradiological correlates.

OBJECTIVE: Radiosurgical ablation of the mesial temporal lobe structures can be used in the treatment of intractable temporal lobe epilepsy associated with mesial temporal sclerosis. In this study, we analyzed the magnetic resonance imaging (MRI) and spectroscopic changes that follow the treatment and report the clinical sequelae of the procedure. METHODS: Eight patients (five men and three women; age, 38 +/- 15 yr [mean +/- standard deviation]) with mesial temporal sclerosis were treated with radiosurgical amygdalohippocampectomy (25 Gy to the 50% isodose region with a mean target volume of 6.2 +/- 0.7 cm). MRI and magnetic resonance spectroscopy were performed sequentially during a 24-month period after treatment. RESULTS: Patients were followed up clinically for 24 to 53 months. MRI scans revealed changes of marked temporal lobe swelling, with often markedly elevated apparent diffusion coefficients in keeping with vasogenic edema that became apparent 6 to 12 months after stereotactic radiosurgery. Spectroscopy of the target area revealed a progressive loss of N-acetylaspartate (the late evolution of lactate) and a peak in the choline-to-creatine ratio that seemed to coincide with the peak of the vasogenic edema in the temporal lobe surrounding the target area. Clinically, all patients showed some reduction in seizure frequency, although in two patients, this reduction was modest. The MRI changes in those patients were also modest, and three patients ultimately became free of seizures. However, there was a latency of 18 to 24 months before improvements in seizure control occurred, and during this period, seizures worsened or changed in four patients. Two patients also developed symptoms of increased intracranial pressure with mild dysphasia, which responded to administration of corticosteroid medication. However, no long-term clinical verbal memory decline was identified in any patient. CONCLUSION: There are marked changes in MRI scans and magnetic resonance spectroscopic findings after patients undergo radiosurgery for temporal lobe epilepsy. Our initial findings suggest that some patients may have a period of distressing symptoms that accompany changes that are visualized on the MRI scans.