Andras A. Kemeny

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.

A phantom study to assess the accuracy of stereotactic localization, using T1-weighted magnetic resonance imaging with the Leksell stereotactic system.

This phantom study assesses the accuracy of stereotactic localization using the Leksell G frame (Elekta Instruments AB, Stockholm, Sweden) with T1-weighted magnetic resonance imaging (Siemens 1.5 T Magnetom; Erlangen, Germany). The coordinates of an array of solid perspex rods were determined and compared with measured values in a series of transverse, coronal, and sagittal images. The maximum absolute errors observed (X = 2.7 mm, Y = 7.0 mm, Z = 8.0 mm) were discouraging. However, the more reasonable mean errors (X = 0.4 mm, Y = 0.7 mm, Z = 1.3 mm) reflect considerable variation in accuracy throughout the volume assessed and limitation of maximum errors to specific areas. We present details of the spatial variation and discuss possible mechanisms for improving accuracy. The overall results are of direct relevance only to the scanner used. These results are, however, an indication of the need to approach with caution stereotactic localization using magnetic resonance imaging and to emphasize the requirement for quality assurance and for a comprehensive study of the scanners characteristics.

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 radiosurgery of the glomus jugulare tumour - early multicentre experience.

Summary¶ Leksell Gamma Knife was used to treat 66 patients with glomus jugulare tumour at 6 European sites between 1992–1998. The age of the patients ranged between 18–80 years (median 54 years). Gamma Knife radiosurgery was a primary treatment in 30 patients (45.5%). Open surgery preceded radiosurgery in 24 patients (36.4%), embolisation in 14 patients (21.2%) and fractionated radiotherapy in 5 patients (7.6%). The volume of the tumour ranged 0.5–27 cm3 (median 5,7 cm3). The minimal dose to the tumour margin ranged between 10–30 Gy (median 16.5 Gy). After radiosurgery 52 patients were followed, the follow up period was 3–70 months (median 24 months). Neurological deficit improved in 15 patients (29%) and deteriorated in 3 patients (5,8%), one transient and two persistant. Neuroradiological follow up using MRI or CT was performed in 47 patients 4–70 months (median 24 months) after radiosurgery. Tumour size decreased in 19 patients (40%) while in the remaining 28 patients (60%) no change in the tumour volume was observed. None of the tumours increased in volume during the observation period. Control angiography was performed in 6 patients. Pathological vascularisation completely disappeared in one patient, reduced in two and there was no change in the remaining three. Radiosurgery proves to be a safe treatment for glomus jugulare tumour with no mortality and no acute morbidity. Because of its naturally slow growth rate, up to 10 years of follow up will be necessary to establish a cure rate after radiosurgery for these lesions.

Radiosurgery for Epilepsy Associated with Cavernous Malformation: Retrospective Study in 49 Patients

OBJECTIVEMicrosurgical resection of a cavernous malformation (CM) with or without associated cortical resection can provide efficient treatment of drug-resistant associated epilepsy. To explore the potential alternative role of radiosurgery and to evaluate its safety and efficacy for this indication, we conducted a retrospective multicenter study. METHODSWe retrospectively reviewed the files of patients with long-lasting drug-resistant epilepsy, presumably caused by CM, who were treated by gamma knife (GK) surgery for the control of their epilepsy in five centers (Marseilles, Komaki City, Prague, Graz, and Sheffield). A satisfactory follow-up was available for 49 patients (mean follow-up period, 23.66 ± 13 mo). The mean duration of epilepsy before the GK procedure was 7.5 (±9.3) years. The mean frequency of seizures was 6.9/month (±14). The mean marginal radiation dose was 19.17 Gy ± 4.4 (range, 11.25–36). Among the 49 patients, 17 (35%) had a CM located in or involving a highly functional area. RESULTSAt the last follow-up examination, 26 patients (53%) were seizure-free (Engel’s Class I), including 24 in Class IA (49%) and 2 patients with occasional auras (Class IB, 4%). A highly significant decrease in the number of seizures was achieved in 10 patients (Class IIB, 20%). The remaining 13 patients (26%) showed little or no improvement. The mediotemporal site was associated with a higher risk of failure. One patient bled during the observation period, and another experienced radiation-induced edema with transient aphasia. Postradiosurgery excision was performed in five patients, and a second radiosurgical treatment was carried out in one patient. CONCLUSIONThis series is the first to specifically evaluate the capability of GK surgery to safely and efficiently treat epilepsy associated with CM. Seizure control can be reached when a good electroclinical correlation exists between CM location and epileptogenic zone. Although we do not recommend GK surgery for prevention of bleeding for a CM that has not bled previously, our findings suggest that GK surgery can be proposed for the treatment of epilepsy when the CM is located in a highly functional area.

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.

Long-term Tumor Control of Benign Intracranial Meningiomas After Radiosurgery in a Series of 4565 Patients

BACKGROUND Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS Median tumor volume was 4.8 cm3, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P < .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P < .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.

Slow Hyperpolarization in Cortical Neurons: A Possible Mechanism Behind Vagus Nerve Simulation Therapy for Refractory Epilepsy?

Summary: Purpose: Recent studies have shown that chronic, intermittent stimulation of the left vagus nerve (VNS) decreases the frequency, duration, and/or intensity of seizures in some patients with medically refractory focal seizures. Although VNS is being used in an increasing number of patients, the neuronal mechanism behind VNS therapy of refractory epileptic seizures is yet unclear.

The potential role of myofibroblasts in the obliteration of arteriovenous malformations after radiosurgery.

OBJECTIVES To examine the structural changes in arteriovenous malformations (AVMs) after stereotactic radiosurgery and to identify the cytoskeletal antigen phenotype of the proliferating cells to gain information about the possible mechanism of obliteration. METHODS We conducted immunohistochemical and electromicroscopic investigations of surgical material that was removed from seven patients. The patients were harboring cerebral AVMs that had been previously treated with gamma knife irradiation, and they experienced subsequent bleeding 10 to 52 months after treatment. RESULTS Light microscopy revealed spindle-shaped cell proliferation in the connective tissue stroma and in the subendothelial region of the vessels. The ultrastructural and immunohistochemical characteristics of these spindle cells were identical to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Whereas in nonirradiated specimens of AVMs, similar cells expressed vimentin and desmin positivity, in irradiated cases, alpha-smooth muscle actin activity was also observed. CONCLUSION In view of the contractile activity of myofibroblasts, the proliferation generated by irradiation and the transformation of the resting cells into an activated form could be relevant to the shrinking process and eventual occlusion of AVMs after radiosurgery.

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 (p < 0.001), 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.