Top 25 Cited Gamma Knife® Surgery Articles - Volume 111

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Antoinette A. Chan, Aubrey Lau, Andrea Pirzkall, Susan M. Chang, Lynn J. Verhey, David Larson, Michael W. McDermott, William P. Dillon and Sarah J. Nelson

Object. The purpose of this study was to assess the differences in spatial extent and metabolic activity in a comparison of a radiosurgical target defined by conventional strategies that utilize the enhancing lesion and a metabolic lesion defined by proton magnetic resonance spectroscopy (MRS) imaging. The authors evaluated whether these differences manifest themselves in the clinical outcome of patients and assessed the value of incorporating 1H-MRS imaging—derived spatial information into the treatment planning process for gamma knife surgery (GKS).

Methods. Twenty-six patients harboring Grade IV gliomas who had previously been treated with external-beam radiation therapy were evaluated by comparing the radiosurgically treated lesion volume with the volume of metabolically active tumor defined on 1H-MRS imaging. The cohort was evenly divided into two groups based on the percentage of overlap between the radiosurgical target and the metabolic lesion volumes. Patients with a percentage of overlap greater than 50% with respect to the metabolic lesion volume were classified as low risk and those with an overlap less than 50% were classified as high risk.

Kaplan—Meier estimators were calculated using time to progression and survival as dependent variables. The metabolite levels within the metabolic lesion were significantly greater than those within the radiosurgical target (p ≤ 0.001). The median survival was 15.7 months for patients in the low-risk group and 10.4 months for those in the highrisk group. This difference was statistically significant (p < 0.01).

Conclusions. Analysis of the results of this study indicates that patients undergoing GKS may benefit from the inclusion of 1H-MRS imaging in the treatment planning process.

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Masahiro Shin, Keisuke Maruyama, Hiroki Kurita, Shunsuke Kawamoto, Masao Tago, Atsuro Terahara, Akio Morita, Keisuke Ueki, Kintomo Takakura and Takaaki Kirino

Object. A large number of clinical studies have been made on treatment outcomes of radiosurgery for arteriovenous malformations (AVMs), but the reported obliteration rates following this treatment vary significantly, perhaps reflecting the different methods and timings of the imaging studies used.

Methods. The authors retrospectively analyzed their experience with gamma knife surgery in 400 patients with AVMs (follow-up period 1–135 months, median 65 months), with special reference to the imaging modality used in each case. The calculated obliteration rates varied from 68.2 to 92%, depending on imaging modality and timing of evaluation. When only unquestionable imaging data such as demonstrations of a residual nidus on computerized tomography (CT) or magnetic resonance (MR) images or findings on angiograms were used in the calculation, the obliteration rates were 72% at 3 years and 87.3% at 5 years. Factors leading to a better obliteration rate were previous hemorrhage (p = 0.0084), smaller nidus (p = 0.0023), and higher radiation dose to the lesion's margin (p = 0.0495), as determined in a multivariate analysis. Factors leading to an earlier obliteration of the nidus were male sex (p = 0.0001), previous hemorrhage (p = 0.0039), smaller nidus diameter (p = 0.0006), and dose planning using angiography alone (p = 0.0201).

Conclusions. After the introduction of CT and MR images into dose planning, the conformity and selectivity of dosimetry improved remarkably, although the latency intervals until obliteration were prolonged. Imaging outcomes for AVMs should be evaluated using data provided by longer follow-up periods. The timing of additional treatments for residual AVMs should be decided cautiously, considering the size of the AVM, the patient age and sex, and the history of hemorrhage before radiosurgery.

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Ajay Jawahar, Ronnie E. Matthew, Alireza Minagar, Deepti Shukla, John H. Zhang, Brian K. Willis, Federico Ampil and Anil Nanda

Object. The objective of this retrospective study was to analyze the results of stereotactic radiosurgery performed using a gamma knife in the treatment of 44 consecutive patients with brain metastases from lung carcinoma.

Methods. Forty-four patients with lung carcinoma were treated for metastatic brain tumors by performing radiosurgery with a Leksell Gamma Knife. Twenty-one patients (47.7%) were women and 23 were men. The mean age of the patients was 56 years (range 35–77 years). Twenty-two patients (50%) had solitary tumors and the rest had multiple tumors (two—six lesions). Eighteen patients (40.9%) presented with a recurrent and/or progressive brain disease that previously had been treated with other modalities (surgery, external-beam radiotherapy, or both). Fifteen patients had controlled lung disease and 19 patients had systemic metastases (in lymph nodes, liver, and/or bones) at the time of radiosurgery.

The median follow-up period was 18.25 months. All patients were followed up for three different end points: 1) death caused by the disease; 2) clinical and/or radiological evidence of progression of the tumor that had been treated with radiosurgery; and 3) appearance of new lesions. At the last follow-up review, 17 patients (38.6%) were alive and 27 (61.4%) had died. Ten patients (22.7%) died as a result of brain disease (failure of local control or new metastases). Controlled primary disease at the time of detection of metastases and the ability to achieve local tumor control after radiosurgery significantly improved the patient survival (p < 0.01). Control of the treated tumor(s) was achieved in 32 of 44 patients (72 tumors) and 10 patients experienced treatment failure. In addition to the 44 patients comprising the study population, two other patients were treated, but died of lung disease too early in the follow-up period to have been assessed. As of the last follow-up review, no new brain metastasis had occurred in 36 patients (81.8% [includes surviving and nonsurviving patients]). The median duration of overall survival was 7 months, the median period of controlled brain disease was 21 months, and the median period of freedom from new brain metastases was 17 months (95% confidence interval 13–19 months).

Conclusions. Gamma knife surgery has significantly reduced the incidence of mortality from brain disease by effectively accomplishing local tumor control in patients with metastatic lung cancer. Local control and freedom from new brain metastases is not influenced by prior external-beam radiotherapy.

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Ronald Brisman

Object. The author presents a large series of patients with idiopathic trigeminal neuralgia (TN) who were treated with gamma knife surgery (GKS), at a maximum dose of 75 to 76.8 Gy, and followed up in a nearly uniform manner for up to 4.6 years.

Methods. Two hundred ninety-three patients were treated and followed up for at least 6 months (range 0.4–4.6 years, median 1.9 years). At the final follow-up review, there was complete (100%) pain relief without medicines in 64 patients (21.8%), 90% or greater relief with or without small doses of medicines in 86 (29.4%), between 75 and 89% relief in 31 (10.6%), between 50 and 74% relief in 19 (6.5%), and less than 50% relief in 23 patients (7.8%). Recurrent pain requiring a second procedure occurred in 70 patients (23.9%). Kaplan—Meier analysis showed that 100%, 90% or greater, and 50% or greater pain relief was obtained and maintained for 3.5 to 4.1 years in 5.6 , 23.7, and 50.4% patients, respectively. Of 31 patients who described pain relief ranging from 75 to 89%, 80% of patients described it as good and 10% as excellent; of 17 patients who reported between 50 and 74% pain relief, 53% described it as good and none as excellent (p = 0.014). Dysesthesia scores greater than 5 (scale of 0–10, in which a score of 10 represents excruciating pain) occurred in four (3.2%) of 126 patients who had not undergone prior surgery; all these patients obtained either good or excellent relief from TN pain. There were 36 patients in whom the TN had atypical features; these patients were less likely to attain at least 50% or at least 90% pain relief compared with those without atypical TN features (p = 0.001).

Conclusions. Gamma knife surgery is a safe and effective way to relieve TN. Patients who attain between 75 and 89% pain relief are much more likely to describe this outcome as good or excellent than those who attain between 50 and 74% pain relief.

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Nicolas Massager, José Lorenzoni, Daniel Devriendt, Françoise Desmedt, Jacques Brotchi and Marc Levivier

Object. Gamma knife surgery (GKS) has emerged as a suitable treatment of pharmacologically resistant idiopathic trigeminal neuralgia. The optimal radiation dose and target for this therapy, however, remain to be defined. The authors analyzed the results of GKS in which a high dose of radiation and a distal target was used, to determine the best parameters for this treatment.

Methods. The authors evaluated results in 47 patients who were treated with this approach. All patients underwent clinical and magnetic resonance imaging examinations at 6 weeks, 6 months, and 1 year post-GKS. Fifteen potential prognostic factors associated with favorable pain control were studied.

The mean follow-up period was 16 months (range 6–42 months). The initial pain relief was excellent (100% pain control) in 32 patients, good (90–99% pain control) in seven patients, fair (50–89% pain control) in three patients, and poor (< 50% pain control) in five patients. The actuarial curve of pain relief displayed a 59% rate of excellent pain control and a 71% excellent or good pain control at 42 months after radiosurgery. Radiosurgery-induced facial numbness was bothersome for two patients and mild for 18 patients. Three prognostic factors were found to be statistically significant factors for successful pain relief: a shorter distance between the target and the brainstem, a higher radiation dose delivered to the brainstem, and the development of a facial sensory disturbance after radiosurgery.

Conclusions. To optimize pain control and minimize complications of this therapy, we recommend that the nerve be targeted at a distance of 5 to 8 mm from the brainstem.

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Marco Losa, Micol Valle, Pietro Mortini, Alberto Franzin, Camillo Ferrari da Passano, Marco Cenzato, Stefania Bianchi, Piero Picozzi and Massimo Giovanelli

Object. Radiation therapy diminishes the risk of recurrence of incompletely removed nonfunctioning pituitary adenoma (NPA). The authors evaluated the efficacy and safety of gamma knife surgery (GKS) in patients with residual NPA following surgical debulking of the tumor.

Methods. Fifty-four patients, 26 men and 28 women, ranging in age from 29 to 72 years underwent gamma knife treatment. Baseline and follow-up studies involved magnetic resonance imaging, hormone evaluation, and neuroophthalmological examination 6 and 12 months after GKS and at yearly intervals thereafter. The mean follow up after GKS was 41.1 ± 3.1 months. Two of 52 patients undergoing follow up had a recurrence 40 and 49 months after GKS. In both of these patients the treated lesion had reduced in size, but a new lesion appeared in the contralateral side of the sella turcica. The recurrence-free interval at 5 years was 88.2% (95% confidence interval 72.6–100%). Tumor volume decreased from a baseline value of 2.3 ± 0.2 to 1.7 ± 0.2 cm3 at the last follow up (p < 0.001). Twenty-two patients (42.3%) had a 20% or greater reduction in tumor volume. The administered radiation dose had been significantly higher in patients who experienced tumor reduction. Visual function and motility did not deteriorate in any patient. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 12.5, 8.6, and 2.3%, respectively, of assessable patients at risk.

Conclusions. Gamma knife surgery was effective in controlling the growth of residual NPA after previously performed maximal surgical debulking. The major advantage of GKS compared with fractionated radiotherapy seems to be a lower risk of side effects, especially a lower risk of hypopituitarism.

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Keisuke Maruyama, Douglas Kondziolka, Ajay Niranjan, John C. Flickinger and L. Dade Lunsford

Object. Management options for arteriovenous malformations (AVMs) of the brainstem are limited. The long-term results of stereotactic radiosurgery for these disease entities are poorly understood. In this report the authors reviewed both neurological and radiological outcomes following stereotactic radiosurgery for brainstem AVMs over 15 years of experience.

Methods. Fifty patients with brainstem AVMs underwent gamma knife surgery between 1987 and 2002. There were 29 male and 21 female patients with an age range of 7 to 79 years (median 35 years). Anatomical locations of these AVMs included the midbrain (39 lesions), pons (20 lesions), and medulla oblongata (three lesions). The radiation dose applied to the margin of the AVM varied from 12 to 26 Gy (median 20 Gy). Forty-five patients were followed up from 5 to 176 months (mean 72 months). The angiographically confirmed actuarial obliteration rate was 66% at the final follow-up examination. Two patients experienced a hemorrhage before obliteration. The annual hemorrhage rate was 1.7% for the first 3 years after radiosurgery and 0% thereafter. Patients who had received irradiation at two or fewer isocenters had higher obliteration rates (80% compared with 44% for > two isocenters, p = 0.006), and this was related to a more spherical nidus shape. The rate of persistent neurological complications in patients treated using magnetic resonance imaging—based dose planning after 1993 was 7%, compared with 20% in patients treated before 1993. An older patient age, a lesion located in the tectum, and a higher radiosurgery-based score were significantly associated with greater neurological complications.

Conclusions. Stereotactic radiosurgery provided complete obliteration of AVMs in two thirds of the patients with a low risk of latency-interval hemorrhage. Better three-dimensional imaging studies and conformal dose planning reduced the risk of adverse radiation effects. Younger patients harboring more spherical AVMs that did not involve the tectal plate had the best outcomes.