Jeremy Rowe

Management of the patient and family with neurofibromatosis 2: a consensus conference statement.

A consensus conference on neurofibromatosis 2 (NF2) was held in 2002 at the request of the United Kingdom (UK) Neurofibromatosis Association, with particular emphasis on vestibular schwannoma (VS) surgery. NF2 patients should be managed at specialty treatment centres, whose staff has extensive experience with the disease. All NF2 patients and their families should have access to genetic testing because presymptomatic diagnosis improves the clinical management of the disease. Some clinical manifestations of NF2, such as ocular abnormalities, can be detected in infancy; therefore, clinical screening for at-risk members of NF2 families can start at birth, with the first magnetic resonance (MRI) scan at 10u200a–u200a12 years of age. Minimal interference, maintenance of quality of life, and conservation of function or auditory rehabilitation are the cornerstones of NF2 management, and the decision points to achieve these goals for patients with different clinical presentations are discussed.

Risk of malignancy after gamma knife stereotactic radiosurgery.

OBJECTIVETo assess the risk of radiosurgery to cause malignant transformation in benign tumors or to induce new malignancies. METHODSA 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. RESULTSIn this material, a single new astrocytoma was diagnosed, whereas, based on national incidence figures, 2.47 cases would have been predicted. CONCLUSIONNo 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.

Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofibromatosis

Objective: To evaluate the results of stereotactic radiosurgery treating vestibular schwannomas secondary to type 2 neurofibromatosis. Methods: A retrospective review of 122 type 2 neurofibromatosis vestibular schwannomas consecutively treated in 96 patients. Tumour control was assessed by recourse to surgical intervention, by serial radiological imaging, and by the calculation of relative growth ratios in patients (n=29) habouring untreated contralateral tumours to act as internal controls. Hearing function was assessed with Gardner-Robertson grades and with averaged pure tone audiogram thresholds. Other complications are detailed. Results: Applying current techniques, eight years after radiosurgery it was estimated that 20% of patients will have undergone surgery for their tumour, 50% will have radiologically controlled tumours, and in 30% there will be some variable concern about tumour control, but up to that time they will have been managed conservatively. Relative growth ratios one and two years after treatment indicate that radiosurgery confers a significant (p=0.01) advantage over the natural history of the disease. Analysis of these ratios beyond two years was precluded by the need to intervene and radiosurgically treat the contralateral control tumours in more than 50% of the cases. This growth control was achieved with 40% of patients retaining their Gardner-Robertson hearing grades three years after treatment, (40% having some deterioration in grade, 20% becoming deaf). Pure tone audiogram results suggest some progressive long term hearing loss, although interpretation of this is difficult. Facial and trigeminal neuropathy occurred in 5% and 2%. Conclusions: Radiosurgery is a valuable minimally invasive alternative treatment for these tumours. For most patients, it controls growth or defers the need for surgery, or both. There is a price in terms of hearing function, although this may compare favourably with the deafness associated with the natural history of the disease, and with surgery. In deciding on therapy, patients should be aware of this treatment option.

Gamma knife stereotactic radiosurgery for unilateral acoustic neuromas

Objective:To evaluate the clinical results achievable using current techniques of gamma knife stereotactic radiosurgery to treat sporadic unilateral acoustic neuromas. Methods:A retrospective review of 234 consecutive patients treated for unilateral acoustic neuromas between 1996 and 1999, with a mean (SD) follow up of 35 (16) months. Tumour control was assessed with serial radiological imaging and by the need for surgical intervention. Hearing preservation was assessed using Gardner-Robertson grades. Details of complications including cranial neuropathies and non-specific vestibulo-cochlear symptoms are included. Results:A tumour control rate in excess of 92% was achieved, with only 3% of patients undergoing surgery after radiosurgery. Results were less good for larger tumours, but control rates of 75% were achieved for 35–45 mm diameter lesions. Of patients with discernible hearing, Gardner-Robertson grades were unchanged in 75%. Facial nerve function was adversely affected in 4.5%, but fewer than 1% of patients had persistent weakness. Trigeminal symptoms improved in 3%, but developed in 5% of patients, being persistent in less than 1.5%. Transient non-specific vestibulo-cochlear symptoms were reported by 13% of patients. Conclusions:Tumour control rates, while difficult to define, are comparable after radiosurgery with those experienced after surgery. The complications and morbidity after radiosurgery are far less frequent than those encountered after surgery. This, combined with its minimally invasive nature, may make radiosurgery increasingly the treatment of choice for small and medium sized acoustic neuromas.

The use of stereotactic radiosurgery in the management of meningiomas

This is a systematic review of a consecutive series of 309 meningiomas treated with gamma knife stereotactic radiosurgery between 1994 and 2000. There was an extreme selection bias towards lesions unfavourable for surgery, determined by the patients referred for treatment: 70% of tumours involved the skull base, 47% specifically the cavernous sinus: 15% of patients had multiple meningiomatosis or type 2 neurofibromatosis. Tumour histology was the main determinant of growth control (pu200a<u200a0.001), the 5-year actuarial control rates being 87% for typical meningiomas, 49% for atypical tumours and 0% for malignant lesions. Complications from radiosurgery were rare, occurring in 3% of tumours, and were most frequently trigeminal and eye movement disturbances treating cavernous sinus meningiomas. Given the problems inherent in managing these tumours, radiosurgery is a valuable strategy and adjuvant treatment for these meningiomas.

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.

Safety of Radiosurgery Applied to Conditions with Abnormal Tumor Suppressor Genes

OBJECTIVETo assess the risk of radiosurgery inducing malignancy in neurofibromatosis-2 (NF2) and von Hippel-Lindau disease. METHODSA retrospective cohort study of 118 NF2 and 19 von Hippel-Lindau disease patients, totalling 906 and 62 patient-years of follow-up data, respectively. RESULTSTwo cases of intracranial malignancy were identified, both of which occurred in NF2 patients. One of these was thought to have arisen before the radiosurgery; the other was a glioblastoma diagnosed 3 years after radiosurgery. CONCLUSIONBecause gliomas may occur in as many as 4% of NF2 patients, this may not represent an increased risk. We continue to offer radiosurgery treatment to selected NF2 and von Hippel-Lindau disease patients and consider that the late risk of malignancy arising after irradiation must be put in the context of the condition being treated, the treatment options available to these individuals, and their life expectancy.

Treatment options for von Hippel?-?Lindau's haemangioblastomatosis: the role of gamma knife stereotactic radiosurgery

Haemangioblastomas secondary to von Hippelu200a-u200aLindau (VHL) disease can be difficult to manage surgically, which has lead to an interest in the use of stereotactic radiosurgery. Retrospectively reviewed here are 30 tumours treated in 14 patients with a meanu200a±u200aSD follow-up of 34u200a±u200a24 months. During this time, three of the 14 patients (21%) died, two of generalized progressive disease. Before radiosurgery, the median time between interventions for cranial haemangioblastomas was 3 years (mean 3.9u200a±u200a5.0 years). After radiosurgery, the tendency for cranial disease progression was similar, 50% of patients developing further disease by 5 years. Local tumour control was achieved in the majority of cases and estimates of this are included. Radiosurgery is a useful palliative measure controlling the majority of haemangioblastomas, although its efficacy in these patients is limited by the tendency of further disease to develop or progress intracranially.

Stereotactic Radiosurgery for Type 2 Neurofibromatosis Acoustic Neuromas: Patient Selection and Tumour Size

Acoustic neuromas which are secondary to type 2 neurofibromatosis (NF2) respond less well to radiosurgery than unilateral sporadic disease. To refine the selection of these patients, a regression analysis was performed examining the response to radiosurgery of 114 NF2 tumours. The major determinant of outcome was tumour volume (p < 0.001). Calculating sensitivity and specificity values for different tumour volume limits gives a sensitivity value of 0.96 for a volume limit of 10 cm3. This suggests that the size constraints that apply to the radiosurgical management of NF2 acoustic neuromas differ and are more restricted than those which are accepted for acoustic neuromas in general.

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

BackgroundLarge 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.MethodThe outcomes for 492 patients (564 treatments) with AVMs >10xa0cm3 treated by single-stage radiosurgery were retrospectively analysed in terms of planning, previous embolization and size.ResultsTwenty-eight percent of the patients presented with haemorrhage at a median age of 29xa0years (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 23xa0Gy covering 45-70% of the AVM (median volume 15.7xa0cm3). From 1994 to 2000 (225 patients) plans became more sophisticated, a median of 5 isocentres was used, covering 64-95% of the AVM (14.6xa0cm3), with a marginal dose of 21xa0Gy. 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 (14.3xa0cm3) and marginal dose of 21xa0Gy. 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%).ConclusionsBetter 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.