Roberto Foroni

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 cm3, 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.

The role of Gamma Knife Radiosurgery in the management of cavernous sinus meningiomas

PURPOSE To evaluate the efficacy of Gamma Knife (GK) radiosurgery in terms of neurologic improvement and tumor growth control (TGC) in a large series of patients with cavernous sinus meningioma (CSM). METHODS AND MATERIALS One hundred thirty-eight patients with CSM (28 males, 110 females; mean age: 56.2 years) were treated with GK between February 1993 and February 2001. GK was used as a first-choice treatment in 68/138 patients and as postoperative adjuvant therapy in 70/138. In 32 patients, it was possible to compare the size of the planned treatment volume to tumor volume using the conformity index (CI); optimal CI values were taken to be < or =1.5 (range: 0.94-2.24). RESULTS A follow-up (FU) period of at least 12 months was available for 111 patients (median: 48.2 months, range: 12.1-84.5 months). Clinical conditions were improved or stable in 107/111 patients (96.5%). Neurologic recovery was observed in 76% of cases treated by GK alone and in 56.5% of adjuvant treatments (p < 0.03). Adequate TGC was documented in 108/111 tumors (97%), with shrinkage/disappearance in 70/111 (63%) and no variation in volume in 38/111 (34%); the overall actuarial progression-free survival rate at 5 years was 96%. Tumor size regression was observed in 79.5% of patients with FU >30 months, compared with 47.5% of patients with FU <30 months (p < 0.001). One hundred percent TGC was shown in treated patients with a CI < or =1.5 (20/32), compared with 92% TGC in cases with a CI >1.5 (p < 0.15, NS). Radiosurgical sequelae were transient in 4/111 cases (3.5%) and permanent in one case (1%). CONCLUSIONS For the FU period of our series (median: >4 years), GK radiosurgery seems to be both safe (permanent morbidity 1%) and effective (96% neurologic improvement/stability, 97% overall TGC, 96% actuarial TGC at 5 years) and might be considered as a first-choice treatment for selected patients with CSM.

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 cm3 (range, 1.5–13.4 cm3) 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 (≤ 20%) decreased in eight out of 20 patients. In one unusual case of a bulky cavernous sinus recurrence, neoplastic regression was particularly pronounced. CONCLUSION:Despite the constraints of the limited case material, considering the estimated doubling time of these rare tumors (4.2 yr), our preliminary results with GKR at a mid-term follow-up examination suggest an effective tumor growth control with negligible incidence of untoward sequelae.

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

OBJECTIVEGamma 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. METHODSOne 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. RESULTSIn 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. CONCLUSIONAccording 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.

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.

Gamma Knife Radiosurgery in Skull Base Meningiomas

Gamma Knife radiosurgery was performed on 50 patients (10 males and 40 females) with skull base meningiomas (SBMs) between February 1993 and September 1995. The patients ranged in age from 25 to 78 years (mean age 56 years). The location of the tumors was anterior fossa (n = 4), sphenoorbital (n = 2), sellar region (n = 5), cavernous sinus (n = 26), petroclival (n = 12), and occipital foramen (n = 1). The tumor volume ranged from 0.6 to 20 cm3 (mean 8.6 cm3). The mean values for dose planning were edge isodose (EI) 46.7%, edge dose (ED) 18.0 Gy, maximum dose 39.8 Gy, average dose (AD) 25.4 Gy, and average number of isocentres 5.7. The patients were analyzed for five parameters: tumor volume (< 7.5 vs. > or = 7.5 cm3); EI (< 50 vs. > or = 50%); ED (< 18 vs. > or = 18 Gy); AD (< 25 vs. > or = 25 Gy), and primary versus residual or recurrent tumors. The overall frequency of tumor growth control (TGC) was 98%, with 1- and 2-year TGC rates of 97% and 100%, respectively. The most favorable neurological results were obtained with a tumor volume < 7.5 cm3 (p < 0.05), EI > or = 50% (NS), ED > or = 18 Gy (NS) and with primary SBMs (p < 0.01). A favorable TGC was demonstrated at follow-up imaging examinations when the tumor volume was > or = 7.5 cm3 (100% TGC rate), EI < 50% (100%), ED > or = 18 Gy (100%), AD > 25 Gy (100%), in both primary SBMs (100%) and residual or recurrent SBMs (96.5%). To date, only 3 (6%) of the 50 patients have presented signs of neurological worsening related to the Gamma Knife radiosurgery. While no early complications were noted, neuroradiological follow-up did show delayed transient imaging complications (3 edema and 1 radionecrosis; 8% of all patients). In conclusion, our preliminary results seem to confirm that Gamma Knife radiosurgery is an effective and safe adjuvant or a feasible alternative primary treatment in controlling or preventing SBM progression.

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.

Stereotactic Radiosurgery of Uveal Melanomas: Preliminary Results with Gamma Knife Treatment

Twelve cases of uveal melanoma (T3N0M0:11 patients, T4N0M0:1 patient) treated with Gamma Knife stereotactic radiosurgery are reported. Our protocol includes preoperative ocular and systemic assessments with complete ocular examination, ophthalmoscopy, fundus photography, fluorangiography, standardized echography, CT and MRI, chest X-rays, liver echography and blood tests. The follow-up program is mainly based on echographic evaluation of tumor thickness and size. The procedures include fixation of the eye, application of the stereotactic Leksell frame G, CT/MRI localization of the melanoma, dose planning and treatment with the Gamma Knife (B type). A mean surface dose of 55 +/- 10 Gy was administered at the 60-90% isodose curve using 4- to 14-mm collimators and a number of shots ranging from 1 to 6. A significant reduction (10-41%) in echographic thickness of the tumor was shown in 6 cases with a follow-up of 3-12 months. In 4 patients, the tumor size was still unchanged after 1-10 months. The single high-dose radiation delivered to the target and the high spatial accuracy are the main advantages of stereotactic radiosurgery for the treatment of posterior uveal melanomas. A longer followup is needed to further validate this new application of Gamma Knife radiosurgery.

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.

Shape recovery and volume calculation from biplane angiography in the stereotactic radiosurgical treatment of arteriovenous malformations

PURPOSE A model for calculating the three-dimensional volume of arteriovenous malformations from biplane angiography. METHODS AND MATERIAL Three-dimensional (3D) volume reconstruction is easily feasible with axial, coronal, or sagittal computer tomography (CT) and nuclear magnetic resonance (NMR) scans. On the other hand, radiosurgical treatment of arteriovenous malformations (AVM) is exclusively based on two orthogonal stereotactic projections, obtained with angiographic procedures. Most commonly, AVM volumes have been calculated by assimilating the nidus volume to a prolate ellipsoid. We present an algorithm dedicated to 3D structure reconstruction starting from two orthogonal stereotactic projections. This has been achieved using a heuristic approach, which has been widely adopted in the artificial intelligence domain. RESULTS Tests on phantom of different complexity have shown excellent results. CONCLUSION The importance of the algorithm is considerable. As a matter of fact: (a) it allows calculations of complex structures far away from regular ellipsoid; (b) it permits shape recovery; (c) it provides AVM visualization on axial planes.