Massimo Gerosa

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.

Prognostic factors in low-grade supratentorial astrocytomas: A uni-multivariate statistical analysis in 76 surgically treated adult patients

A retrospective uni-multivariate statistical analysis was performed on 32 prognostic factors to investigate their importance in predicting survival in a series of 76 adult patients with low-grade supratentorial astrocytomas treated over a 13-year period. The end point used for this study was the length of survival. The median survival time was 40 months. Overall actuarial survival at 2, 5, and 10 years was 69%, 38%, and 22%, respectively. Radical resection of the neoformation, a higher preoperative Karnofsky performance status (KPS) score, and an age younger than 50 years are strongly correlated with survival; postoperative radiotherapy appears to be associated with increased survival only in patients under 50 years of age.

Surgery for intramedullary spinal cord tumors: the role of intraoperative (neurophysiological) monitoring

In spite of advancements in neuro-imaging and microsurgical techniques, surgery for intramedullary spinal cord tumors (ISCT) remains a challenging task. The rationale for using intraoperative neurophysiological monitoring (IOM) is in keeping with the goal of maximizing tumor resection and minimizing neurological morbidity. For many years, before the advent of motor evoked potentials (MEPs), only somatosensory evoked potentials (SEPs) were monitored. However, SEPs are not aimed to reflect the functional integrity of motor pathways and, nowadays, the combined used of SEPs and MEPs in ISCT surgery is almost mandatory because of the possibility to selectively injury either the somatosensory or the motor pathways. This paper is aimed to review our perspective in the field of IOM during ISCT surgery and to discuss it in the light of other intraoperative neurophysiologic strategies that have recently appeared in the literature with regards to ISCT surgery. Besides standard cortical SEP monitoring after peripheral stimulation, both muscle (mMEPs) and epidural MEPs (D-wave) are monitored after transcranial electrical stimulation (TES). Given the dorsal approach to the spinal cord, SEPs must be monitored continuously during the incision of the dorsal midline. When the surgeon starts to work on the cleavage plane between tumor and spinal cord, attention must be paid to MEPs. During tumor removal, we alternatively monitor D-wave and mMEPs, sustaining the stimulation during the most critical steps of the procedure. D-waves, obtained through a single pulse TES technique, allow a semi-quantitative assessment of the functional integrity of the cortico-spinal tracts and represent the strongest predictor of motor outcome. Whenever evoked potentials deteriorate, temporarily stop surgery, warm saline irrigation and improved blood perfusion have proved useful for promoting recovery, Most of intraoperative neurophysiological derangements are reversible and therefore IOM is able to prevent more than merely predict neurological injury. In our opinion combining mMEPs and D-wave monitoring, when available, is the gold standard for ISCT surgery because it supports a more aggressive surgery in the attempt to achieve a complete tumor removal. If quantitative (threshold or waveform dependent) mMEPs criteria only are used to stop surgery, this likely impacts unfavorably on the rate of tumor removal.

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.

AGE-RELATED CHEMOSENSITIVITY OF STEM CELLS FROM HUMAN MALIGNANT BRAIN TUMOURS

After radiation therapy and chemotherapy for malignant glioma, patients aged 50 or under survive longer than patients over 50. Data from Brain Tumor Study Group trials show that, without treatment, these age groups have similar survival; therefore unperturbed tumour growth does not account for the difference. Sixteen consecutive patients with malignant glioma were studied, half of whom were less than or equal to 50 years of age; none had been treated before initial surgery, and all were subsequently treated with radiation and chemotherapeutic agents (in all but two patients, with nitrosoureas). Median survival of those aged greater than 50 was less than or equal to 50 years was 54 + weeks whereas that of those aged greater than 50 was 37 weeks. The longer survival for younger patients could not be attributed to tumour type, size, or location, pretreatment Karnofsky status, or mode of treatment. In-vitro sensitivity testing of clonogenic cells obtained from biopsy specimens showed that tumour cells from seven of eight patients aged less than or equal to 50 years were sensitive to 1,3-bis (2-chloroethyl)-1-nitrosourea (greater than 40% cell kill at clinically achievable concentrations) compared with only one patient with sensitive cells out of eight older patients. Patient age was inversely correlated with in-vitro cell kill, and patients with sensitive cells were significantly younger than those with resistant cells. Therefore influence of age on survival after treatment of malignant gliomas is probably due to inherent differences in the sensitivity of clonogenic cells to radiation and/or chemotherapeutic agents.

Gamma Knife Stereotactic Radiosurgery for Uveal Melanoma: Clinical Results after 2 Years

We report on 36 cases of uveal melanoma treated at our center between March 1993 and September 1995. There were 16 men and 20 women, aged 57 +/- 11 years. The choroid was affected in 35 patients and the ciliary-body in 1. The same preoperative and follow-up protocol was adopted for all cases. The procedure included fixation and positioning of the eye with a retrobulbar injection of long-lasting anesthetic and two extraocular muscle sutures, application of the frame, computed tomography scan localization, dose planning and treatment with the Gamma Knife. The patients were divided into three groups. Group A: 10 patients with a follow-up of 24 +/- 4 months, treated with a high dose (surface dose 58 +/- 9 Gy, maximum dose 81 +/- 15 Gy, mean dose 66 +/- 11 Gy). Group B: 9 patients with a follow-up of 16 +/- 2 months, treated with a lower dose (surface dose 41 +/- 3 Gy, maximum dose 76 +/- 10 Gy, mean dose 53 +/- 11 Gy). Group C: 17 patients with a follow-up of 6 +/- 3 months, treated with a lower dose (surface dose 42 +/- 3 Gy, maximum dose 72 +/- 16 Gy, mean dose: 54 +/- 6 Gy). In group A, we observed marked tumor regression in 9 cases, tumor recurrence in 1 case and severe complications in 5 cases (neovascular glaucoma and/or radiation retinopathy and/or radiation optic neuropathy). In group B, significant local control of the tumor was obtained with minor complications (cotton wool spots hard exudates, intraretinal hemorrhages). In group C, to date we have observed a regression of the tumor in 7 cases and 1 severe complication (neovascular glaucoma). Our data show that uveal melanomas may be adequately controlled by a high radiosurgical dosage (50-70 Gy), though there are significant side effects. Comparable levels of local tumor control may be obtainable using lower doses (40-45 Gy) which would hopefully reduce the rate of complications. However, a longer follow-up is needed for further validation of these results.

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.

Integration of the metabolic data of positron emission tomography in the dosimetry planning of radiosurgery with the gamma knife: early experience with brain tumors. Technical note.

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

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.