Josef Novotný

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 surgery for benign meningioma.

OBJECT Meningioma is the most frequent benign tumor treated with Gamma Knife surgery (GKS); however, the assessment of its efficacy and safety in slow-growing tumors is an ongoing process, requiring analysis of long-term results. METHODS Three hundred sixty-eight patients harboring 400 meningiomas treated between 1992 and 1999 at Na Homolce Hospital were evaluated. The median patient age was 57 years (range 18-84 years). The median tumor volume was 4.4 cm3 (range 0.11-44.9 cm3). The median tumor margin dose to the 50% isodose line was 12.55 Gy (range 6.5-24 Gy). Descriptive analysis was performed in 331 patients (90%); 325 patients had a follow-up longer than 24 months (median 60 months), and six patients were included because of posttreatment complications. The volume of treated tumors decreased in 248 cases (69.7%), remained the same in 99 (27.8%), and increased in nine (2.5%). The actuarial tumor control rate was 97.9% at 5 years post-GKS. Perilesional edema after radiosurgery was confirmed on neuroimaging in 51 patients (15.4%). The temporary and permanent morbidity rates after radiosurgery were 10.2 and 5.7%, respectively. RESULTS A significantly higher incidence of tumor volume increase was observed in men compared with women and in tumors treated with a margin dose lower than 12 Gy. Significant risk factors for edema included an age greater than 60 years, no previous surgery, perilesional edema before radiosurgery, a tumor volume greater than 10 cm3, a tumor location in the anterior fossa, and a margin dose greater than 16 Gy. CONCLUSIONS Stereotactic radiosurgery is a safe method of treatment for meningiomas. A minimum margin dose of 12 to 16 Gy seems to represent the therapeutic window for benign meningiomas with a high tumor control rate in a mid-term follow-up period.

Radiation Tolerance of Functioning Pituitary Tissue in Gamma Knife Surgery for Pituitary Adenomas

OBJECTIVEThis study is intended to contribute to a determination of the sensitivity of preserved hypophyseal function to focal radiation in pituitary adenomas. METHODSWe compared two subgroups of patients followed up for a median of 5 years after gamma knife surgery (GKS). Subgroup 1 (n = 30) showed postirradiation hypopituitarism. Subgroup 2 (n = 33) was continually eupituitary. These subgroups were taken from a previously published study relating to a larger group of 163 patients with pituitary adenomas treated by GKS and evaluated after a median follow-up period of 2 years. A relatively high treatment dose was used in this larger group (median, 20 Gy to the tumor margin for growth control in nonfunctioning adenomas; median, 35 Gy for hypersecreting adenomas). Early results approached those of microsurgery, and there were only a few side effects. In the present study, we compared 16 different variables in the same two subgroups to discover the relationships that caused a delayed appearance of postirradiation hypopituitarism. The main pretreatment and treatment parameters were measured on reconstructed treatment plans. This database was used for statistical evaluation. RESULTSThe relationship between the mean dose and the volume of functioning hypophysis was stronger in terms of worsening of pituitary function than that of the spot dose to different intrasellar structures. We found that for our group of patients, the safe mean dose of radiation to the hypophysis was 15 Gy for gonadotropic and thyrotropic functions and 18 Gy for adrenocorticotropic function. The worsening of pituitary function was also significantly dependent on the dose to different anatomic levels of the infundibulum, but we did not succeed in fully characterizing this relationship. In addition, we discovered significant levels of dependency of postirradiation pituitary damage to different pretreatment and treatment variables. CONCLUSIONKnowledge of the radiation tolerance of functioning pituitary structures subjected to GKS can ensure better preservation of pituitary function after irradiation. This is valid for the group of patients we studied. Our study’s findings can be used as a guideline for GKS treatment of new patients with pituitary adenomas, and it can serve for comparison with the experience of other gamma knife centers.

Brain metastases after stereotactic radiosurgery using the Leksell gamma knife: can FDG PET help to differentiate radionecrosis from tumour progression?

Abstract. Stereotactic radiosurgery (SRS) using the Leksell gamma knife promotes acute and chronic local changes in glucose metabolism. We have been able to find very few papers on Medline on the subject of assessment of metastases by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) after SRS. The aim of this work was to specify the additional value of FDG PET, in comparison with magnetic resonance imaging (MRI), in differentiating SRS-induced radionecrosis from viable brain metastasis in a clinical setting. Fifty-seven metastases in 25 patients were treated by SRS. An average of 33 weeks later, all the patients underwent FDG PET. At the same time (SD=2 weeks) all the patients underwent MRI. The sensitivity, specificity and accuracy of both FDG PET and MRI examinations were calculated with reference to clinical and radiological follow-up or biopsies. The additional value derived from use of FDG PET after MRI was assessed and progression-free survival rates were compared. The difference in progression-free survival rates between the negative and positive subgroups was significant (P=0.0005) for MRI and even more so (P<0.00001) for FDG PET. Sensitivity, specificity and accuracy were 75% (6/8), 93.9% (46/49) and 91.2% (52/57) for FDG PET, and 100% (8/8), 65.3% (32/49) and 70.2% (40/57) for MRI. In the subgroup of patients with positive or non-diagnostic MRI, the probability of presence of a viable tumour was only 32% (8/25). This probability increased to 100% (5/5) when subsequent FDG PET was positive and decreased to 11.1% (2/18) when FDG PET was negative. The frequency of a viable neoplasm was significantly different (P=0.001) in the FDG PET negative and positive subgroups. MRI and FDG PET both have an important predictive value for persistent viable metastases after treatment by SRS. Neither sensitive but non-specific MRI nor specific but insensitive FDG PET is reliable on its own. While FDG PET significantly improved the diagnostic accuracy in the subgroup of patients with positive and non-diagnostic MRI, it provided no additional value in the MRI-negative subgroup.

Quality control of the stereotactic radiosurgery procedure with the polymer-gel dosimetry

PURPOSE To assess the entire geometric and dosimetric (relative) uncertainties of the radiosurgery procedure with the Leksell gamma knife. MATERIALS AND METHODS The entire Leksell gamma knife stereotactic radiosurgery treatment procedure was simulated with the use of a special water filled head phantom and polymer-gel dosimeter evaluated by nuclear magnetic resonance (NMR). A test vessel filled with the polymer-gel dosimeter was fixed in the head phantom. The phantom underwent stereotactic NMR imaging, treatment planning and then irradiation according to the treatment plan prepared exactly the same way as in the ordinary treatment procedure for a patient. The treatment plan was represented by one isocenter positioned approximately centrally in the head phantom. This procedure was subsequently repeated for all four collimators (4, 8, 14, 18mm) used on the Leksell gamma knife. Evaluation of dosimeters was performed on a Siemens EXPERT 1T NMR scanner. Dose profiles in X, Y and Z axes through the ellipsoidal shaped dose distribution were obtained to compare experimental results from the irradiated phantom with the treatment planning system calculations. RESULTS Reasonable agreement was observed between the treatment planning system calculations of relative dose distribution and the measured data. The maximum observed deviation in the spatial position between the center of the measured and calculated dose profiles was 0.6mm. The maximum observed difference in full width of half maximum between calculated and measured profiles was 1.2mm. CONCLUSIONS The use of polymer-gel dosimetry for a verification of stereotactic procedures has some unique advantages that can be summarized as follows: the dosimeter itself is tissue equivalent, three-dimensional dose distributions can be measured and the dosimeter allows simulation of the patients procedures without any limitations.

Transportation Dose and Doses to Extracranial Sites during Stereotactic Radiosurgery with the Leksell Gamma Knife

Two dosimetric aspects of Leksell Gamma knife (LGK) treatment have been investigated in this study: (a) measurement of the small dose (transportation dose) which is absorbed during the patients transportation into and out of the treatment position within the ionization chamber, and (b) measurements of the doses absorbed by the eyes, thyroid, breast, abdomen, gonads, knee and ankle during the treatment using thermoluminescent dosimetry (TLD). The transportation dose was 0.253 +/- 0.003 Gy, which represented 8.4% of the dose rate (3.005 Gy/min) during measurements. In vivo TLD measurements have been performed on 51 patients. The doses measured in organs and sites of interest were 0.223 +/- 0.168 Gy for the eyes, 0.081 +/- 0.050 Gy for the thyroid, 0.049 +/- 0.033 Gy for the breast, 0.024 +/- 0.18 Gy for the abdomen, 0.012 +/- 0.008 Gy for the gonads, 0.003 +/- 0.002 Gy for the knee and 0.002 +/- 0.002 Gy for the ankle. During LGK radiosurgery, doses to extracranial sites and organs depend mainly on the total target dose and the number of shots used for the treatment. These doses are generally low; the maximum dose was measured for the eyes (approximately 0.7% of the maximum target dose), and the doses to other body organs decrease with increasing distance from the isocenter of the LGK radiation unit.

The Role of Gamma Knife Radiosurgery in Arteriovenous Malformation with Aneurysms

A review of 217 patients treated with Gamma knife radiosurgery (GKRS), at Hospital Na Homolce, Prague, between October 1992 and January 1998 for arteriovenous malformation (AVM) is presented. Forty-one patients (18.9%) with an AVM and associated aneurysm are the subjects of special interest for this study. The nidus volume in the presence of an aneurysm lying close to the nidus or within it was significantly larger than the nidus volume in cases where the AVMs had no associated aneurysm, suggesting that an increased flow in a larger AVM may be an important factor for aneurysm formation. The association of an arterial aneurysm with an AVM significantly increased the chance of hemorrhage when compared to the group with AVM and no aneurysm. Ten patients out of 14, who had an aneurysm close to or within the nidus, showed a complete obliteration of their AVM and aneurysm, although the latter was not always included within the irradiated volume. Thus, this study indicates that radiosurgery alone could be the method of choice for the treatment of a combination of AVM and aneurysm, if the aneurysm is close to or within the nidus.

Evaluation of Geometric and Dosimetric Inaccuracies of Stereotactic Irradiation in the Rat Brain

Objective: To evaluate geometric and dosimetric inaccuracies in the irradiation of the rat brain with the Leksell Gamma Knife. Materials and Methods: Altogether three types of dosimeters were employed for these measurements: (a) a thermoluminescent dosimeter, (b) a semiconductor detector and (c) a polymer gel dosimeter. The thermoluminescent dosimeter and the semiconductor detector were calibrated using an ion chamber and then implanted in the brain of a rat cadaver and used for absolute dose determination. A special glass phantom mimicking exactly the shape of the rat body filled with the polymer gel was used for measurements of the relative dose distribution and evaluation of geometric inaccuracies during the stereotactic irradiation in the rat brain. Results: Both thermoluminescent and semiconductor detectors, due to their size, measured mean doses. The observed results demonstrated that the Leksell GammaPlan can be employed for the calculation of absorbed doses in irradiation of experimental animals. In our case, it was necessary to apply a correction factor of 1.078 for the absolute absorbed dose to obtain reliable results. A comparison of calculated dose profiles using the treatment planning system in all three axes with those measured by the polymer gel dosimeter demonstrated a very good geometric agreement with the mean deviation in profile position of 0.5 mm. Conclusion: The results indicate that this technique can effectively check the geometric and dosimetric accuracy of stereotactic irradiation in the rat brain. The Leksell GammaPlan can be employed for the calculation of absorbed doses, but the correction factor of 1.078 had to be applied for the absolute dose calculations in our irradiation geometry.

Ocular and Orbital Lesions

Technological advances in medical imaging, treatment planning, and radiation dose delivery have led to dramatic improvements in all treatment capabilities including radiosurgery. It is now possible to recognize intraocular tumors and other ophthalmologic diseases at an early stage because physicians are generally more aware and because of the availability and use of both direct and indirect ophthalmoscopy, fluorescein angiography, ultrasonography, and magnetic resonance imaging. The basic advantage of radiosurgery is the possibility of applying relatively high doses in a single session to well-defined intracranial targets.

Verification of dose volume histograms in stereotactic radiosurgery and radiotherapy using polymer gel and MRI

In this work we focus on dose volume histograms (DVHs) measurement in stereotactic radiosurgery (SR) performed with the Leksell gamma knife (ELEKTA Instrument AB, Stockholm, Sweden) and stereotactic radiotherapy (SRT) performed with linear accelerator 6 MV Varian Clinac 2100 C/D (Varian Medical Systems, Palo Alto, USA) in conjunction with BrainLAB stereotactic system (BrainLAB, Germany) using modified BANG gel and magnetic resonance imaging (MRI). The aim of the experiments was to investigate a method for acquiring entire dose volume information from irradiated gel dosimeter and calculate DVHs.