Josef Vymazal

Gamma knife radiosurgery for acromegaly – long‐term experience

Objective  The Leksell gamma knife (LGK) is one of the treatment options for pituitary adenomas. We report on our long‐term experience treating acromegaly using LGK.

Arteriovenous malformations after Leksell gamma knife radiosurgery: Rate of obliteration and complications - Commentary

OBJECTIVEAlthough relevant information exists regarding the chance of obliterating arteriovenous malformations (AVMs) using radiosurgery, the overall chance of cure after gamma knife radiosurgery is usually only extrapolated from a portion of all monitored patients. This chance and the risks involved in radiosurgery, including repeat treatment when necessary in a defined population of treated patients, were analyzed in our study. METHODSBetween October 1992 and June 2000, gamma knife radiosurgery was performed on 330 patients with AVMs. The volume of the AVM nidus ranged from 0.15 to 28.6 cm3 (median, 3.9 cm3). When complete obliteration was not achieved within 3 years, repeat radiosurgery was performed on 76 patients. The volume of the nidus for the second treatment ranged from 0.09 to 16.8 cm3 (median 2.9 cm3). The result was reviewed in 300 (91%) patients after the first round of treatment and in 68 (89.5%) after the second round of treatment. RESULTSAVM obliteration was achieved in 222 (74%) patients after the first round of radiosurgery and in 47 (69%) after the second. The overall chance of cure was 92% (269 patients). Final angiography verified complete obliteration by 12 to 96 months (median, 25 mo) after initial radiosurgery. Smaller volume AVMs and the application of a higher radiation dose resulted in a higher chance of obliteration. The risk of rebleeding after radiosurgery was 2.1% annually until full obliteration, and the overall mortality from rebleeding was 1%. The risk of permanent morbidity after the first and second radiosurgery treatments were 2.7 and 2.9%, respectively. The cumulative risk of morbidity in both groups of patients was 3.4%. CONCLUSIONAlthough one-quarter of the patients required that the treatment be repeated, gamma knife radiosurgery can offer a high cure rate for patients treated for AVMs with a low risk of morbidity and mortality from rebleeding during the latent period.

Gamma Knife Radiosurgery of Meningiomas in the Cavernous Sinus Region

Summary For 6 years (1992–1998) we have treated 67 patients with cavernous sinus meningioma using the Leksell gamma knife in the Hospital Na Homolce, Prague. The age of the patients ranged between 19–82 years, median 57 years. Radiosurgery was the primary treatment in 64,2% of the patients, in the rest a microsurgical resection preceded. The volume of the tumour ranged from 0,9–31,4 cm3, median 7,8 cm3. The meningioma was distant from the optic tract in 58% of the cases, in 12% of the cases there was a contact with the tumour and the optic tract without its compression and in 30% of the cases there was a compression of the optic tract caused by the meningioma. The dose to the tumour margin ranged from 10–14 Gy, median 12 Gy. The follow up was available in 53 patients, in intervals of 2–60 months, median 19 months. There was no change in the tumour volume in 48% of the cases, in 52% of the cases a decrease of the tumour volume occurred. No increase of the tumour volume was observed. Clinical symptoms and signs improved in 35,8% of the patients, temporary morbidity was 3,8%. The mortality of the treatment was zero. Hitherto, the results of gamma knife radiosurgery of cavernous sinus meningioma have proved its safety and efficiency, although long term experience with a large group of patients is missing. Advances in neuroradiology and radiosurgical technique have allowed us to treat tumours with a closer contact to the optic tract and nerves compared with the past.

Thrombus imaging with fibrin-specific gadolinium-based MR contrast agent EP-2104R: results of a phase II clinical study of feasibility.

Purpose:To determine the feasibility of detecting thrombi using a fibrin-specific gadolinium-based magnetic resonance imaging contrast agent, EP-2104R. Methods:Subjects with confirmed thrombus in the venous system (n = 14), or in the heart, or arterial system (n = 38) were enrolled. Patients were imaged before and at various times following a 4 μmol/kg intravenous bolus injection of EP-2104R: <1 hour (N = 16), 2 to 6 hours (N = 36), and/or 20 to 36 hours (N = 33). Images were assessed by investigators at each site and by a single reader not affiliated with the sites to determine whether thrombi were visible, not visible, or further enhanced with EP-2104R. A subset of data was analyzed quantitatively by measuring a signal intensity relative to background tissue. Results:Overall, 29 thrombi were visible before contrast administration, 3 of 14 in the venous system, and 26 of 38 in the arteries and heart. Thrombi generally enhanced in signal after EP-2104R injection, and an additional 7 were visualized. After contrast, 4 of 14 thrombi were visible in the venous system, and 32 of 38 in the arteries and heart. Thrombi were more conspicuous when imaged at 2 to 6 hours post EP-2104R compared with within 1 hour, because of lower blood background. Quantitatively, the post: pre signal intensity ratio was 1.90 at 2 to 6 hours post injection (standard deviation = 1.08, N = 20, P < 0.001); and 2.04 (standard deviation = 1.29, N = 19, P < 0.0025) for the 20 to 36 hours time point. There were no serious adverse events considered related to study drug. Conclusion:EP-2104R enhanced magnetic resonance imaging detects thrombi not readily visible in precontrast screening and gives additional enhancement of thrombi that are visible in precontrast imaging.

Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields)

BackgroundThe present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial.MethodsCell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients.ResultsThe efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index ≤ 1). The sensitivity to chemotherapeutic treatment was increased by 1–3 orders of magnitude by adjuvant TTFields therapy (dose reduction indexes 23 – 1316). Similar findings were seen in an animal tumor model. Finally, 20 GBM patients were treated with TTFields for a median duration of 1 year. No TTFields related systemic toxicity was observed in any of these patients, nor was an increase in Temozolomide toxicity seen in patients receiving combined treatment. In newly diagnosed GBM patients, combining TTFields with Temozolomide treatment led to a progression free survival of 155 weeks and overall survival of 39+ months.ConclusionThese results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity.

Treatment of essential trigeminal neuralgia with gamma knife surgery

OBJECT The authors present the long-term follow-up results (minimum 5 years) of patients with essential trigeminal neuralgia (TN) who were treated with gamma knife surgery (GKS). METHODS One hundred seven patients (61 females and 46 males) underwent GKS. The median follow up was time was 60 months (range 12-96 months). The target was the trigeminal root, and the maximum dose was 70 to 80 Gy. Repeated GKS was performed in 19 patients for recurrent pain, and the same dose was used. Initial successful results were achieved in 96% of patients, with complete pain relief in 80.4%. Relief was achieved after a median latency of 3 months (range 1 day-13 months). Gamma knife surgery failed in 4% of patients. Pain recurred in 25% of patients after a median latent interval of 36 months (6-94 months). The initial success rate after a second GKS was 89% and 58% of patients were pain free. Pain relapse occurred in only one patient in this group. Hypesthesia was observed in 20% of patients after the first GKS and in 32% after the second GKS. The median interval to hypaesthesia was 35 months (range 3-94 months) after one treatment and 21 months (range 1-72 months) after a second treatment. CONCLUSIONS The initial success rate of pain relief was high and comparable to that reported in other studies. A higher than usual incidence of sensory impairment after GKS could be the long duration of follow-up study and due to the detailed neurological examination.

Magnetic resonance imaging of brain iron in health and disease

Brain iron is a major contributor to magnetic resonance imaging (MRI) contrast in normal gray matter, and its role in the pathogenesis of different neurological disorders has also become apparent. Non-heme brain iron is present in the brain mainly in the form of ferritin. The unique magnetic properties of ferritin determine different signal changes on both T1- and T2-weighted images, and the T2 relaxation rates have a linear dependence on applied field strength. This finding is typical for ferric oxyhydroxide cores. The resulting T2-shortening also depends on echo-spacing used in the imaging sequence as well as on the water diffusion coefficient and the size of the ferritin cluster. Quantitation of non-heme brain iron by MRI aids in the diagnosis and monitoring of different neurological diseases.

Gamma Knife Treatment of Trigeminal Neuralgia: Clinical and Electrophysiological Study

Between October 1995 and October 1996, we treated 49 patients suffering from trigeminal neuralgia with Gamma Knife radiosurgery. There were 23 males and 26 females. The mean age was 68 (range 38–94 years) The root of the trigeminal nerve close to brain stem was chosen as the target. The maximum dose was 70 Gy in 24 cases and 80 Gy in 25 cases. A single shot with the 4-mm collimator was used. 13 patients underwent Gamma Knife treatment of trigeminal nerve root without any previous surgical procedures. 31 patients suffered from an essential neuralgia (EN), while 7 had neuralgia related to multiple sclerosis (MS). Three had atypical neuralgia (AN) and 8 patients had postherpetic neuralgia (PN). Patients were divided into five groups according to pain reduction. The success rate of pain relief (excellent, very good and good responses) in these patients was: EN 77% of patients, MS 43%, AN 33% and PN 38% of patients. Pain relief occurred after latent intervals of between 1 day and 8 months (median 2 months and mean 2.8 months). Clinically detected complications after radiosurgery occurred only in the form of tactile hypesthesia in 6%. In a selected group of 18 patients, we observed slight electrophysiological changes in 2 patients (11%) after Gamma Knife treatment.

Gamma knife radiosurgery for endocrine-inactive pituitary adenomas

SummaryBackground. The goal of nonsecreting pituitary adenoma radiosurgery is to halt tumour growth and to maintain normal performance of the hypophysis and the functionally important structures around the sella. The effectiveness of gamma knife radiosurgery was evaluated. Method. Over a period of 10 years (1993–2003), 140 patients with nonsecreting pituitary adenoma were treated by Leksell gamma knife at our Centre. Seventy-nine of them were followed up for longer than 3 years. Their age range was 24–73 years, with a median of 54 years. Eighty-five percent of them had previous open surgery. Fifteen patients had adenoma contact with the optic tract. Fourteen patients had a normally functioning hypophysis, 48 patients had complete panhypopituitarism, while the rest retained partial functions of the normal hypophysis. Adenoma volumes ranged between 0.1 and 31.3, the median being 3.45 ccm. The marginal dose ranged between 12 and −35 Gy, with a median of 20 Gy. Findings. The follow-up ranged from 36 to 122 months, with a median of 60 months. No adenoma growth was detected; 89% of treated adenomas decreased in size, with a median volume reduction of 61%. There was no perimeter vision impairment after radiosurgery, while 4 out of 52 patients with abnormal perimeter vision reported improvement. There was no impairment of oculomotor nerve function. Impairment of hypophysis function was observed in 2 patients. Conclusions. Radiosurgery has a reliable antiproliferative effect on nonsecreting pituitary adenomas. It is a safe treatment with a low risk of morbidity. Short contact between a nonsecreting pituitary adenoma and the optic pathway is not an absolute contraindication for Gamma knife radiosurgery.

Gamma knife surgery of brain cavernous hemangiomas

OBJECT The authors conducted a study to record more detailed information about the natural course and factors predictive of outcome following gamma knife surgery (GKS) for cavernous hemangiomas. METHODS One hundred twelve patients with brain cavernous hemangiomas underwent GKS between 1993 and 2000. The median prescription dose was 16 Gy. One hundred seven patients were followed for a median of 48 months (range 6-114 months). The rebleeding rate was 1.6%, which is not significantly different with that prior to radiosurgery (2%). An increase in volume was observed in 1.8% of cases and a decrease in 45%. Perilesional edema was detected in 27% of patients, which, together with the rebleeding, caused a transient morbidity rate of 20.5% and permanent morbidity rate of 4.5%. Before radiosurgery 39% of patients suffered from epilepsy and this improved in 45% of them. Two patients with brainstem cavernous hemangiomas died due to rebleeding. Rebleeding was more frequent in female middle-aged patients with a history of bleeding, a larger lesion volume, and a prescription dose below 13 Gy. Edema after GKS occurred more frequently in patients who had surgery, a larger lesion volume, and in those in whom the prescription dose was more than 13 Gy. CONCLUSIONS Gamma knife surgery of cavernous hemangiomas can produce an acceptable rate of morbidity, which can be reduced by using a lower margin dose. Lesion regression was observed in many patients. Radiosurgery seems to remain a suitable treatment modality in carefully selected patients.