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The optimal management of cavernous malformations (CMs) remains controversial. Over the past decade, stereotactic radiosurgery (SRS) has gained wider acceptance in the management of CMs, especially in those with deep location, eloquence, and where surgery is of high risk. Unlike arteriovenous malformations (AVMs), there is no imaging surrogate endpoint to confirm CM obliteration. Clinical response to SRS can only be gauged by a reduction in long-term CM hemorrhage rates. There is concern that the long-term benefits of SRS and the reduced rehemorrhage rate after a latency period of 2 years may only be a reflection of natural history. Of further concern is the development of adverse radiation effects (AREs), which were significant in the early experimental studies. The lessons learnt from that era have led to the progressive development of well-defined, lower marginal dose treatment protocols that have reported less toxicity (5%-7%) and consequently reduced morbidity. Currently, there is at least Class II, Level B evidence for use of SRS in solitary CMs with previous symptomatic hemorrhage in eloquent areas with high surgical risk. Recent prospective cohort studies observing untreated brainstem and thalamic CMs report significantly higher hemorrhage rates and neurological sequelae than the rates reported from contemporary pooled large natural history meta-analyses. Furthermore, this strengthens our recommendation for early proactive SRS in symptomatic deep-seated CMs due to the higher morbidity associated with observation and microsurgery. The key to successful outcomes for any surgical intervention is patient selection. We hope that our precis on contemporary SRS techniques in the management of CMs will assist this process.

Introduction Primary chordomas and chondrosarcomas of the skull base are difficult tumours to treat successfully. Despite advances in surgical techniques, a gross total resection is often impossible to achieve. In addition, some patients may be deemed unsuitable or not wish to undergo extensive surgery for these conditions. This study examines the role of Gamma Knife Stereotactic Radiosurgery (GKRS) in the treatment of these difficult cases. Methods All patients harbouring either a chordoma or chondrosarcoma treated at the National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK, between 1985 and 2018, were reviewed with regard to their clinical presentations, pre- and post-treatment imaging, GKRS prescriptions and outcomes. Results In total, 24 patients with a mean tumour volume of 13 cm 3 in the chordoma group ( n =15) and 12 cm 3 in the chondrosarcoma group ( n =9) underwent GKRS. The 5- and 10-year overall survival rates for the chordoma group were 67% and 53% respectively, while for the chondrosarcoma group, they were 78% at both time points. The tumour control rates at 5 and 10 years in the chordoma group were 67% and 49% and for the chondrosarcoma group 78% at both time points. Patients with tumour volumes of less than 7 cm 3 before GKRS treatment demonstrated a statistically significant longer overall survival rate ( p =0.03). Conclusions GKRS offers a comparable option to proton beam therapy for the treatment of these tumours. Early intervention for tumour volumes of less than 7 cm 3 gives the best long-term survival rates.

Abstract 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.

Abstract 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 cm3 (range, 0.02–50) for supratentorial and 0.5 cm3 (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 cm3 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 cm3 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 cm3 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 cm3 in the brainstem is not recommended. Supratentorial deep AVMs >8 cm3 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.

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.

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.

To assess the risk of radiosurgery to cause malignant transformation in benign tumors or to induce new malignancies. A retrospective cohort study comparing the Sheffield, England, radiosurgery patient database with national mortality and cancer registries. This data set comprises approximately 5000 patients and 30,000 patient-years of follow-up, with more than 1200 patients having a follow-up period longer than 10 years. In this material, a single new astrocytoma was diagnosed, whereas, based on national incidence figures, 2.47 cases would have been predicted. No increased risk of malignancy was detected in this series, supporting the safety of radiosurgery. Pragmatically, in advising patients, the risks of malignancy would seem small, particularly if such risks are considered in the context of the other risks faced by patients with intracranial pathologies requiring radiosurgical treatments.

PurposeAcromegaly has high morbidity and mortality when growth hormone secretion remains uncontrolled. Stereotactic radiosurgery (SRS) may be used when pituitary surgery is not suitable or unsuccessful, but there are few very long-term safety data available, especially for significant adverse events such as stroke.Methods118 patients with acromegaly were treated with SRS between 1985 and 2015, at the National Centre for Stereotactic Radiosurgery, Sheffield, UK. Data were gathered from case notes, hospital databases, and patient questionnaires. Stroke incidence in comparison to the normal population was quantified using the standardised incidence ratio (SIR), and visual complications assessed.Results88% (104/118) had complete morbidity follow up data for analysis. The mean follow-up was 134 months, and median SRS dose was 30 Gy. 81% of tumours had cavernous sinus invasion. There was no excess stroke rate relative to that seen in two age- and sex-matched large population studies (SIR = 1.36, 95% CI 0.27–3.96; SIR = 0.52, 95% CI 0.06–1.89). In 68/104 patients who had MRI-guided SRS with no further radiation treatment (SRS or fractionated radiotherapy) there was no loss of visual acuity and 3% developed ophthalmoplegia. There was a positive correlation between > 1 radiation treatment and both ophthalmoplegia and worsening visual acuity.ConclusionStroke rate is not increased by SRS for acromegaly. Accurate MRI-based treatment planning and single SRS treatment allow the lowest complication rates. More than one radiation treatment (SRS or fractionated radiotherapy) was associated with increased visual complications.

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.

In the brain, they can cause haemorrhagic stroke1 and epileptic seizures,2 and in the spinal cord, they can bleed and cause myelopathy.3 Despite the availability of microsurgical excision and stereotactic radiosurgery for cavernoma treatment and known genetic causes of most familial forms of cavernoma,4 uncertainties remain about cause, diagnosis, prognosis, treatment, and care. [...]to prioritise these uncertainties about brain and spine cavernomas for researchers and funding agencies,5 we undertook a James Lind Alliance priority setting partnership.