Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data.

Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an "incisionless" treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data. Methods: A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018-December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review. Results: The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature. Conclusion: We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years.

Surgical Management of Adverse Radiation Effects After Gamma Knife Radiosurgery for Cerebral Arteriovenous Malformations: A Population-Based Cohort Study.

OBJECTIVE: The goal of this study is to report our experience in the surgical treatment of cerebral arteriovenous malformations (cAVMs) related permanent symptomatic adverse radiation effects (PSAREs), to clarify an appropriate surgical management and to identify the risk factors related to their development. METHODS: We evaluated 549 patients treated with Gamma Knife radiosurgery (GKRS) for cAVMs with a follow-up of at least 8 years. Univariate and multivariate analyses were used to test different risk factors related to the development of PSARE. We retrospectively reviewed the records of these patients to analyze the clinical outcome. RESULTS: Fourteen patients (2.5%) developed PSARE and were submitted to surgery. Higher average treated volume represents a significant risk factors for the development of PSARE (P < 0.05); on the other hand, older age and higher average dose reduce the risk of PSARE (P < 0.05). A favorable clinical outcome was achieved in 13 patients (93%) after surgery; in 1 patient, the unfavorable outcome was due to hemorrhage that occurred months after GKRS. Serial MRI scans following either surgical removal of the nodule or Ommaya reservoir positioning showed progressive reduction of brain edema in all cases. CONCLUSIONS: The management of PSARE is controversial, especially for cAVMs treated with SRS. Surgical removal is rarely needed, but-if unavoidable-it can be a valuable option in experienced hands. A careful preoperative planning is always necessary to detect pathologic blood flow through the PSARE.

Leksell Gamma Knife for pediatric and adolescent cerebral arteriovenous malformations: results of 100 cases followed up for at least 36 months.

OBJECT: The goal of this study was to evaluate advantages, risks, and failures of Gamma Knife radiosurgery (GKRS) in a large series of pediatric and adolescent patients with cerebral arteriovenous malformations (cAVMs) who were followed up for at least 36 months. METHODS: Since February 1993, 100 pediatric and adolescent patients (≤ 18 years of age) with cAVMs have undergone GKRS at the authors' institution and were followed up for at least 36 months. Forty-six patients were boys and 54 were girls; the mean age was 12.8 years (range 3-18 years). Hemorrhage, either alone or combined with seizure, was the clinical onset in 70% of cases. The mean pre-GK cAVM volume was 2.8 ml; 92% of cAVMs were Spetzler-Martin (S-M) Grades I-III. Most lesions (94%) were in eloquent or deep-seated brain regions, according to S-M classification. The parameters for mean and range in treatment planning were prescription isodose 53.8% (40%-90%); prescription dose (PD) 20.2 Gy (9.0-26.4 Gy); maximal dose (MD) 37.8 Gy (18-50 Gy); and number of shots 4.7 (1-17). On the day of GKRS, stereotactic CT or stereotactic MRI and digital subtraction angiography were used. RESULTS: Obliteration rate (OR) was angiographically documented in 75 of 84 cases (89.3%) after single-session GKRS, with actuarial ORs at 3 and 5 years of 68.0% and 88.1%, respectively. A repeat treatment was performed in 7 patients (6 with obliteration), and 16 patients with cAVMs underwent staged treatment (9 of them were angiographically cured). Thus, the overall OR was 90%, with actuarial ORs at 3, 5, and 8 years of 59.0%, 76.0%, and 85.0%, respectively. Permanent symptomatic GK-related complications were observed in 11% of cases, with surgical removal of enlarged mass seen on post-RS imaging needed in 5 cases. Hemorrhage during the latency period occurred in 9% of patients, but surgical evacuation of the hematoma was required in only 1 patient. One patient died due to rebleeding of a brainstem cAVM. Radiosurgery outcomes varied according to cAVM sizes and doses: volumes ≤ 10 ml and PDs > 16 Gy were significantly associated with higher ORs and lower rates of permanent complication and bleeding during the latency period. CONCLUSIONS: The data from this study reinforce the conclusion that GKRS is a safe and effective treatment for pediatric and adolescent cAVMs, yielding a high OR with minimal permanent severe morbidity and no mortality. The very low frequency of severe hemorrhages during the latency period further encourages a widespread application of RS in such patients. Univariate analysis found that modified RS-based cAVM score, nidus volume, PD, integral dose, S-M grade, and preplanned treatment (the last 2 parameters were also confirmed on multivariate analysis) significantly influenced OR. Lower S-M grades and single-session planned treatments correlated with shorter treatment obliteration interval on univariate analysis. This statistical analysis suggests that a staged radiosurgical treatment should be planned when nidus volume > 10 ml and/or when the recommended PD is ≤ 16 Gy.

The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: Chronic stimulation of the human subthalamic nucleus (STN) is gradually becoming accepted as a long-term therapeutic option for patients with advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI) improves contrast resolution in basal ganglia nuclei containing high levels of iron, because of magnetic susceptibility effects that increase significantly as the magnetic field gets higher. This phenomenon can be used for better visualization of the STN and may reduce the time necessary for detailed microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity. OBJECTIVE: The objective of this retrospective study is to analyze a population of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided into two groups in which different targeting methods were used. METHODS: Mean age was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean follow-up was 12 months (range 6 to 36 months). Patients were divided into two groups: Group A contained 6 patients who underwent STN targeting using 1T stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B consisted of 14 patients who underwent STN targeting using 3T nonstereotactic (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For statistical analysis, we compared (five different parameters in both (matched) groups: Unified Parkinson's disease rating scale (UPDRS) score reduction (medication off before surgery against stimulation on/medication off after surgery), postoperative drug reduction, duration of surgery, the "central preoperative track" chosen as final implantation track during surgery, and correspondence between the targeted STN and the intraoperative neurophysiologic data. RESULTS: Mean UPDRS III score reduction (medication off/stimulation on versus preoperative medication off) was 69% in Group A and 74% in Group B (p = 0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment was reduced by 66% in Group A and 75% in Group B (p = 0.006, log-rank test). The preoperative "central" track (which corresponds to ideal STN targeting) proved to be the most clinically effective in 2/12 leads for Group A versus 21/28 for Group B (p < 0.001).Neurophysiologic data confirmed these results; the hypothetical target was confirmed by MER data in 76% of tracks in Group A, and in 75% of tracks in Group B (p < 0.001, univariate and multivariate analysis). CONCLUSION: 3T MRI appears to be a useful tool in STN-DBS preoperative targeting. Neurophysiologic testing remains fundamental to determine lead deepness (and prevent clinical side effects.

Radiosurgical options in neuro-oncology: a review on current tenets and future opportunities. Part II: adjuvant radiobiological tools.

Stereotactic radiosurgery (SRS) is currently a well-established, minimally invasive treatment for many primary and secondary tumors, especially deep-sited lesions for which traditional neurosurgical procedures were poorly satisfactory or not effective at all. The initial evolution of SRS was cautious, relying on more than 30 years of experimental and clinical work that preceded its introduction into the worldwide medical community. This path enabled a brilliant present, and the continuous pace of technological advancement holds promise for a brighter future. Part II of this review article will cover the impact of multimodal adjuvant technologies on SRS, and their input to the crucial role played by neurosurgeons, radiation oncologists and medical physicists in the management and care of fragile neuro-oncological patients.

The use of electrical source imaging in targeting lesional mesial temporal epilepsy for radiosurgical treatment.

Gamma knife radiosurgery (GK-RS) is a technique applied in selected cases of mesial-temporal epilepsy, although still limited to centres with adequate instrumentation and expertise. Here, we report a case of radio surgery targeted with the aid of electrical source imaging that localizes the cortical area generating the scalp epileptic discharges. The patient, a 39-year-old male, presented with a right mesio-temporal lesion; electrical source imaging localization partially overlapped with the lesional area but showed an important activation of the omolateral frontal area, concordant with the epileptic network. The patient underwent GK-RS, with good neurosurgical and clinical results. A radiosurgical ellipsoidal treatment volume area of 2 × 2 × 2 cm³, located over the right temporo-mesial region within a centre showing abnormal signal intensity, was considered. Seven months after treatment, the patient developed brain oedema that gradually resolved after one year. After three years of follow-up, the patient was seizure-free (Engel class I). Our very preliminary experience suggests that electrical source imaging appears to be a useful supporting tool for the definition of the radiosurgical treatment volume in selected patients with temporo-mesial lesional epilepsy.

Radiosurgical options in neuro-oncology: a review on current tenets and future opportunities. Part I: therapeutic strategies.

Stereotactic radiosurgery can nowadays be considered not only as a potential adjuvant to surgical treatment of several neuro-oncological pathologies, including primary tumors and metastatic lesions, but in some cases also as a valuable alternative tailored option. In Part I of the review, we propose a dissertation focused on the different irradiation stereotactic radiosurgery techniques to date available for clinical indications more relevant to oncologists and oncologic surgeons, such as high-grade and low-grade gliomas, metastases and meningiomas. It is noteworthy that the most recent body of literature correlated with this topic shows that the therapeutic results presently achievable are revolutionizing the way patients are diagnosed and managed worldwide. As we sought to shed light on the current potentialities of stereotactic radiosurgery, we must consider that to exploit all the benefits provided by this shift in clinical practice, a profound awareness by all practitioners involved in the care of neoplastic patients is certainly warranted.

A framework for the objective assessment of registration accuracy.

Validation and accuracy assessment are the main bottlenecks preventing the adoption of image processing algorithms in the clinical practice. In the classical approach, a posteriori analysis is performed through objective metrics. In this work, a different approach based on Petri nets is proposed. The basic idea consists in predicting the accuracy of a given pipeline based on the identification and characterization of the sources of inaccuracy. The concept is demonstrated on a case study: intrasubject rigid and affine registration of magnetic resonance images. Both synthetic and real data are considered. While synthetic data allow the benchmarking of the performance with respect to the ground truth, real data enable to assess the robustness of the methodology in real contexts as well as to determine the suitability of the use of synthetic data in the training phase. Results revealed a higher correlation and a lower dispersion among the metrics for simulated data, while the opposite trend was observed for pathologic ones. Results show that the proposed model not only provides a good prediction performance but also leads to the optimization of the end-to-end chain in terms of accuracy and robustness, setting the ground for its generalization to different and more complex scenarios.

Integration of functional neuroimaging in CyberKnife radiosurgery: feasibility and dosimetric results.

OBJECT: The integration of state-of-the-art neuroimaging into treatment planning may increase the therapeutic potential of stereotactic radiosurgery. Functional neuroimaging, including functional MRI, navigated brain stimulation, and diffusion tensor imaging-based tractography, may guide the orientation of radiation beams to decrease the dose to critical cortical and subcortical areas. The authors describe their method of integrating functional neuroimaging technology into radiosurgical treatment planning using the CyberKnife radiosurgery system. METHODS: The records of all patients who had undergone radiosurgery for brain lesions at the CyberKnife Center of the University of Messina, Italy, between July 2010 and July 2012 were analyzed. Among patients with brain lesions in critical areas, treatment planning with the integration of functional neuroimaging was performed in 25 patients. Morphological and functional imaging data sets were coregistered using the Multiplan dedicated treatment planning system. Treatment planning was initially based on morphological data; radiation dose distribution was then corrected in relation to the functionally relevant cortical and subcortical areas. The change in radiation dose distribution was then calculated. RESULTS: The data sets could be easily and reliably integrated into the Cyberknife treatment planning. Using an inverse planning algorithm, the authors achieved an average 17% reduction in the radiation dose to functional areas. Further gain in terms of dose sparing compromised other important treatment parameters, including target coverage, conformality index, and number of monitor units. No neurological deficit due to radiation was recorded at the short-term follow-up. CONCLUSIONS: Radiosurgery treatments rely on the quality of neuroimaging. The integration of functional data allows a reduction in radiation doses to functional organs at risk, including critical cortical areas, subcortical tracts, and vascular structures. The relative simplicity of integrating functional neuroimaging into radiosurgery warrants further research to implement, standardize, and identify the limits of this procedure.

Gamma Knife surgery in vestibular schwannomas: impact on the anterior and posterior labyrinth.

OBJECT: During the past decades, in small-to-medium size vestibular schwannomas, Gamma Knife surgery (GKS) has become a reliable therapeutic option because of either excellent local tumor control or minimal morbidity, with cranial neuropathy becoming increasingly rare. Although still insufficiently analyzed in larger cohorts of patients with long-term follow-ups, adequate chances of hearing preservation and vestibular sparing seem clinically guaranteed. However, deeper investigations are needed in this regard, expanding the number of cases and the follow-up period. METHODS: A small group of patients with vestibular schwannomas (74 patients, including 41 men and 33 women) treated between 2003 and 2009 using GKS at the authors' institution were analyzed--both before and after GKS--with computerized static stabilometry and electronystagmography for balance disorders, vertigo, and ataxia on 1 side and pure tone average, vocal speech discrimination score, auditory brainstem response, and so forth for hearing impairment and tinnitus on the other side. Eligibility criteria for this prospective study included previously untreated unilateral lesions and a Gardner-Robertson hearing class of I-III. Dosimetry plans had been programmed at the lower effective dosages for these tumors (median surface dose 12.4 Gy, range 10-13 Gy), carefully avoiding even minimal toxic dosages on the most vulnerable targets: the cochlea (never > 6 Gy) and the vestibular canals (< 7.5 Gy). RESULTS: To date, tumor growth control rates remain satisfactory; at a mean follow-up of 50 months, the rate was 96%. The overall level of hearing preservation was 72%, with 81% having Gardner-Robertson Class I hearing. Tinnitus decreased, from 52% to 28% of patients (p < 0.01). Significant improvements were also observed in vestibular symptoms, with computerized static stabilometry abnormalities decreasing from 62% to 32% (p < 0.001) and electronystagmography abnormalities reducing from 48% to 14% (p < 0.001). CONCLUSIONS: Using appropriate radiodosimetry planning, GKS seems to guarantee not only adequate tumor growth control rates, but also better levels of hearing preservation, with a documented, long-lasting improvement in vestibular functions.

Validation through accuracy prediction in neuroimage registration.

Validation and accuracy assessment are the main bottlenecks preventing the adoption of many medical image processing algorithms in the clinical practice. In the classical approach, a-posteriori analysis is performed based on some predefined objective metrics. The main limitation of this methodology is in the fact that it does not provide a mean to estimate what the performance would be a-priori, and thus to shape the processing workflow in the most suitable way. In this paper, we propose a different approach based on Petri Nets. The basic idea consists in predicting the accuracy that will result from a given processing on a given type of data based on the identification and characterization of the sources of inaccuracy intervening along the whole chain. Here we propose a proof of concept in the specific case of image registration. A Petri Net is constructed after the detection of the possible sources of inaccuracy and the evaluation of their respective impact on the estimation of the deformation field. A training set of five different synthetic volumes is used. Afterward, validation is performed on a different set of five synthetic volumes by comparing the estimated inaccuracy with the posterior measurements according to a set of predefined metrics. Two real cases are also considered. Results show that the proposed model provides a good prediction performance. An extended set of clinical data will allow the complete characterization of the system for the considered task.

Gamma knife radiosurgery for trigeminal neuralgia: results and potentially predictive parameters--part I: Idiopathic trigeminal neuralgia.

OBJECTIVE: Gamma knife radiosurgery (GKR) is an increasingly used, minimally invasive treatment option for patients with trigeminal neuralgia (TN) refractory to medical therapy. This retrospective study evaluates the long-term results and side effects of GKR in the treatment of TN focusing on potentially predictive factors. METHODS: One hundred sixty patients with TN were included in this study (minimum follow-up, >6 mo; mean, 37.4 mo; range, 6-144 mo). In 92 patients, GKR represented the first nonmedical option ("primary GKR"). In 68 patients, invasive treatments had been previously attempted. All patients were treated using a single 4-mm collimator shot targeting the pontine trigeminal root entry zone with a maximal dose of 75 to 95 Gy. Brainstem dose exposure never exceeded 15 Gy. Treatment outcome results were classified as Grade I (pain-free with no pharmacological treatment), Grade II (pain-free with pharmacological treatment), and Grade III (no result). Data were analyzed using the log-rank test for univariate analysis and the ordered logit model for multivariate analysis. RESULTS: In the overall series, 98 (61%) out of 160 patients reached a Grade I outcome, 45 (29%) reached a Grade II outcome, and 17 (10%) patients had no results from GKR. These results were encouraging for patients with typical facial pain features and for patients treated by a "primary" gamma knife. Considering the global outcome, the most effective and safest dose was found to be in the 80 to 90 Gy range. CONCLUSION: According to our experience, GKR represents a reliable second-line therapeutic approach for TN after pharmacological failure. Favorable prognostic factors include "primary GKR" and maximal GKR dose ranging between 80 and 90 Gy.

Glomus jugulare tumors: the option of gamma knife radiosurgery.

OBJECTIVE: Glomus jugulare tumors are generally considered slow-growing, benign lesions. However, their pronounced local aggressiveness frequently results in severe neurological deficits. Surgical removal is rarely radical and is usually associated with morbidity. There is increasing evidence that stereotactic radiosurgery, particularly gamma knife radiosurgery (GKR), may play a relevant role as a therapeutic option in these tumors. METHODS: Between 1996 and 2005, we used GKR to treat 20 patients bearing growing glomus jugulare tumors, mostly classified as Glasscock-Jackson Grade IV or Fisch Stage D1. Follow-up (mean, 50.85 mo) data was available for 20 patients (four men, 16 women; mean age, 56 yr): eight out of 20 tumors were surgical recurrences, three out of 20 patients had GKR as the primary treatment, and 11 out of 20 patients previously underwent endovascular embolization. Regarding the radiosurgical dose planning, the average tumor volume was 7.03 cm (range, 1.5-13.4 cm) and the mean marginal dose was 17.3 Gy (range, 13-24 Gy). RESULTS: Neurological signs and symptoms were unchanged in 13 out of 20 patients. An improvement of cranial nerve function was observed in five patients and hearing deterioration was observed in two patients. Tumor volume was unchanged in 11 out of 20 patients and was slightly (

Gamma Knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part II: Differences in obliteration rates, treatment-obliteration intervals, and prognostic factors.

PURPOSE: To evaluate and compare obliteration rates (OBRs) and treatment-obliteration intervals (TOIs) for cerebral arteriovenous malformations (cAVMs) treated with Gamma Knife radiosurgery in children/adolescents and adults; and to determine factors predicting the OBR and TOI in these two populations. METHODS AND MATERIALS: This study concerned 62 children/adolescents and 193 adults observed for > or = 3 years. Fisher exact two-tailed and Wilcoxon rank-sum tests, multiple logistics, and Cox proportional hazard models were used for statistical analysis. RESULTS: The overall OBR was 85.5% in children/adolescents and 87.6% in adults (p = 0.671), but children/adolescents showed higher 36-month actuarial OBRs (69.35%) and shorter median TOIs (25.7 months) than adults (66.84% and 28.2 months; p = 0.006 and p = 0.017, respectively). In children/adolescents, lower Spetzler-Martin grades (p = 0.043) and younger age (p = 0.019) correlated significantly with OBRs, and lower Spetzler-Martin grades (p = 0.024) and noneloquent cAVM locations (p = 0.046) with TOIs. In adults, low flow through the cAVM and < 6.2-cm3 volume were associated with both OBR and TOI (p = 0.012 and p = 0.002, respectively). CONCLUSIONS: The differences in OBRs within 3 years and TOIs, although slight, seem to show that pediatric cAVMs behave differently from those in adults after Gamma Knife radiosurgery.

Gamma knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part I: Differences in epidemiologic, morphologic, and clinical characteristics, permanent complications, and bleeding in the latency period.

PURPOSE: To compare the epidemiologic, morphologic, and clinical characteristics of 92 children/adolescents (Group A) and 362 adults (Group B) with cerebral arteriovenous malformations (cAVMs) considered suitable for radiosurgery; to correlate radiosurgery-related permanent complication and post-radiosurgery bleeding rates in the 75 children/adolescents and 297 adults available for follow-up. METHODS AND MATERIALS: Radiosurgery was performed with a model C 201-source Co60 Leksell Gamma Unit (Elekta Instruments, Stockholm, Sweden). Fisher exact two-tailed, Wilcoxon rank-sum, and two-sample binomial exact tests were used for statistical analysis. RESULTS: There were significant differences between the two populations in sex (p = 0.015), clinical presentation (p = 0.001), and location (p = 0.008). The permanent complication rate was lower in younger (1.3%) than in older patients (5.4%), although the difference was not significant (p = 0.213). The postradiosurgery bleeding rate was lower in Group A (1.3%) than in Group B (2.7%) (p = 0.694), with global actuarial bleeding rates of 0.56% per year and 1.15% per year, respectively. CONCLUSIONS: The different characteristics of child/adolescent and adult cAVMs suggest that they should be considered two distinct vascular disorders. The similar rates of radiosurgery-related complications and latency period bleeding in the two populations show that gamma knife radiosurgery does not expose young patients to a higher risk of sequelae than that for older patients.

Estimating the growth kinetics of experimental tumors from as few as two determinations of tumor size: implications for clinical oncology.

Clinical information on tumor growth is often limited to a few determinations of the size of the tumor burden taken at variable time. As a consequence, fitting of growth equations to clinical data is hampered by the small number of available data. On the other hand, characterising the tumor growth kinetics in terms of clinically relevant parameters, such as the doubling time of the tumors, is increasingly required to optimize and personalise treatments. A computational method is presented which can estimate the growth kinetics of tumors from as few as two determinations of its size taken at two successive time points, provided the size at which tumor growth saturates is known. The method is studied by using experimental data obtained in vitro with multicell tumor spheroids and in vivo with tumors grown in mice, and its outputs are compared to those obtained by fitting of experimental data with the Gompertz growth equation. Under certain assumptions and limitations the method provides comparable estimates of the doubling time of tumors with respect to the classical nonlinear fitting approach. The method is then tested against simulated tumor growth trajectories spanning the range of tumor sizes observed in the clinics. The simulations show that a relative classification of tumors on the basis of their growth kinetics can be obtained even if the size at which tumor growth saturates is not known. This result opens the possibility to classify patients bearing fast or slow growing tumors and, hence, to adapt therapeutic regimens under a more rationale basis.

Analysis of long-term outcomes and prognostic factors in patients with non-small cell lung cancer brain metastases treated by gamma knife radiosurgery.

OBJECT: The authors conducted a study to evaluate the long-term outcomes and prognostic factors for survival in a large series of patients treated by gamma knife surgery (GKS) for non-small cell lung cancer (NSCLC) brain metastases. METHODS: The study is based on the retrospective analysis of clinical and radiological records obtained during a 10-year period (1993-2003), concerning 836 lesions in 504 patients. The lesions were primary in 86% and recurrent 14% of the cases; they were solitary in 31%, single in 29%, and multiple in 40%. The mean follow-up period was 16 months (range 4-113 months). The most common histological types were adenocarcinoma (51%) and squamous cell carcinoma (27%). Dose planning parameters were as follows: mean target volume 6.2 cm3 (range 0.06-22.5 cm3); mean prescription dose 21.4 Gy (range 15.5-28 Gy); and mean number of isocenters 6.7 (range one-18). Progression-free and actuarial survival curves were calculated using the Kaplan-Meier method. The main factors affecting survival were determined by unimultivariate analysis (log-rank test and Cox proportional hazard models). Analysis of long-term outcomes seemed to confirm that GKS is a primary therapeutic option in these patients. The 1-year local tumor control rate was 94%. The overall median survival was 14.5 months, with extremely rewarding quality of life indices. The recursive partitioning analysis classification was the dominant prognostic factor. CONCLUSIONS: Gamma knife surgery is a useful treatment for brain metastases from NSCLC.

Leksell gamma knife radiosurgery for cerebral arteriovenous malformations in pediatric patients.

OBJECTS: The authors report their experience of gamma knife radiosurgery (GKR) in a large series of pediatric cerebral arteriovenous malformations (cAVMs). The advantages, risks and failures of this approach are presented and discussed. METHODS: Gamma knife radiosurgery was performed on 63 children aged < or =16 years. Haemorrhage was the clinical onset in 50 out of 63 cases. The mean pre-GK cAVM volume was 3.8 cm(3). Fifty-eight out of 63 cAVMs were Spetzler-Martin grades I-III. Most lesions (47 out of 63) were in eloquent or deep-seated brain regions. CONCLUSION: Gamma knife radiosurgery-related complications occurred in 2 out of 47 cases with an available follow-up (1 had transient and 1 permanent morbidity). No bleeding occurred during the latency period. In 39 children with >36-month follow-up, complete cAVM occlusion was angiographically documented in 31, with a 3- and 4-year actuarial obliteration rate of 72 and 77% respectively. High rates of complete obliteration and very low frequency of permanent morbidity with no bleeding during the latency period encourage widespread application of GKR in the treatment of pediatric cAVMs.

The role of gamma knife radiosurgery in the treatment of primary and metastatic brain tumors.

With the widespread diffusion of stereotactic radiosurgical procedures, GKR treatments have gained considerable momentum as a major therapeutic option for patients harboring primary or metastatic brain tumors. Present results in high grade gliomas indicate a potential palliative role of this technique. The overall low radiosensitivity of these oncotypes and their infiltrative nature-with the resulting problems in properly defining the tumor target-are still a major obstacle to further development of the approach. In this regard, useful contributions are expected from advances in molecular neurobiology and functional neuroimaging as shown by preliminary investigations with MR spectroscopy. Surgery maintains a dominant role in the therapeutic armamentarium for low grade gliomas. However, in unfavorable cases (unresectable tumors, recurrences), GKR seems to be an effective alternative to conventional radiochemotherapy. In grade 2 astrocytomas and specifically in grade 1 pilocytic forms, short-to-mid-term reported studies have documented encouraging 70 to 93% local tumor control rates, with minimal cerebral toxicity. Finally, during the last decade, GKR has become a primary treatment choice for patients harboring small-to-medium-size brain metastases, with reasonable life expectancy and no impending intracranial hypertension. Focal tumor responses are consistently elevated, even in the most radioresistant oncotypes (melanoma, renal carcinoma); median and actuarial survival rates are far better than with conventional radiation treatments and are comparable to those observed in accurately selected surgical-radiation series.

Radiosurgical treatment of cavernous sinus meningiomas: experience with 122 treated patients.

OBJECTIVE: To evaluate the efficacy of gamma knife (GK) radiosurgery, in terms of neurological improvement and tumor growth control (TGC), for a large series of patients with cavernous sinus meningiomas. METHODS: Between February 1993 and January 2002, 156 patients with cavernous sinus meningiomas (35 male and 121 female patients; mean age, 56.1 yr) were treated with GK radiosurgery in our department. GK radiosurgery was used as a first-choice treatment for 75 of 156 patients and as postoperative adjuvant therapy for 81 of 156 patients (all with Grade I meningiomas). Eligibility criteria for radiosurgery were as follows: symptomatic meningiomas and/or documented tumor progression on magnetic resonance imaging scans, conditions of high operative risk, patient refusal of microsurgery or reoperation, tumor volume of <20 cm(3), and location no less than 2 mm from the optic pathways. RESULTS: Follow-up data for at least 12 months were available for 122 patients (median follow-up period, 48.9 mo). Clinical conditions were improved or stable for 118 of 122 patients (97%). Neurological recovery was observed for 78.5% of patients treated with GK radiosurgery alone and for 60.5% of patients treated with adjuvant therapy (P < 0.05). Adequate TGC was documented for 119 of 122 tumors (97.5%), with shrinkage/disappearance in 75 of 122 cases (61.5%) and no variation in volume in 44 of 122 cases (36%); the overall actuarial progression-free survival rate at 5 years was 96.5%. Tumor size regression was observed for 80% of patients with follow-up periods of more than 30 months, compared with 43.5% of patients with follow-up periods of less than 30 months (P < 0.0002). Radiosurgical sequelae were transient in 4 of 122 cases (3.0%) and permanent in 1 case (1%). CONCLUSION: For the follow-up periods in our series (median, >4 yr), GK radiosurgery seems to be both safe (permanent morbidity rate, 1%) and effective (97% neurological improvement/stability, 97.5% overall TGC, and 96.5% actuarial TGC at 5 yr). GK radiosurgery might be considered a first-choice treatment for selected patients with cavernous sinus meningiomas.