Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24-233). Median tumour volume was 6.2 cc (+/-7), and the median marginal dose was 14 Gy (+/-3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6-233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

First German Guideline on Diagnostics and Therapy of Clinically Non-Functioning Pituitary Tumors.

Although non-functioning pituitary tumors are frequent, diagnostic and therapeutic concepts are not well standardized. We here present the first German multidisciplinary guideline on this topic. The single most important message is to manage the patients by a multidisciplinary team (consisting at least of an endocrinologist, a neurosurgeon, and a (neuro-) radiologist). The initial diagnostic work-up comprises a detailed characterization of both biochemical (focusing on hormonal excess or deficiency states) and morphological aspects (with magnetic resonance imaging of the sellar region). An ophthalmological examination is only needed in presence of symptoms or large tumors affecting the visual system. Asymptomatic, hormonally inactive tumors allow for a 'wait and scan' strategy. In contrast, surgical treatment by an experienced pituitary surgeon is standard of care in case of (impending) visual impairment. Therapeutic options for incompletely resected or recurrent tumors include re-operation, radiotherapy, and observation; the individual treatment plan should be developed multidisciplinary. Irrespective of the therapeutic approach applied, patients require long-term follow-up. Patient with larger pituitary tumors or former surgery/radiotherapy should be regularly counseled regarding potential symptoms of hormonal deficiency states.

Acute necrosis after Gamma Knife surgery in vestibular schwannoma leading to multiple cranial nerve palsies.

We discuss a rare acute complication after Gamma Knife therapy (Elekta AB, Stockholm, Sweden) in a single patient. A 52-year-old woman presented with vertigo, facial weakness and hearing loss emerging 48hours following Gamma Knife radiosurgery for a right-sided vestibular schwannoma. Neurological examination 6days after symptom onset showed right-sided facial palsy, spontaneous left-beating nystagmus and pathologic head-impulse testing to the right. Pure-tone audiogram revealed right-sided sensorineural hearing loss. A diagnosis of acute vestibulocochlear and facial neuropathy was made. Brain MRI demonstrated focal contrast sparing within the schwannoma, likely related to acute radiation necrosis. Acute multiple cranial neuropathies of the cerebellopontine angle after Gamma Knife treatment should raise suspicion of acute tissue damage within the schwannoma and should result in urgent MRI. Treatment with steroids may be considered based on accompanying swelling and edema.

Comparing the cost-effectiveness of two brain metastasis treatment modalities from a payer's perspective: stereotactic radiosurgery versus surgical resection.

OBJECTIVES: This study aims to identify the cost-effectiveness of two brain metastatic treatment modalities, stereotactic radiosurgery (SRS) versus surgical resection (SR), from the perspective of Germany's Statutory Health Insurance (SHI) System. METHODS: Retrospectively reviewing 373 patients with brain metastases (BMs) who underwent SR (n=113) and SRS (n=260). Propensity score matching was used to adjust for selection bias (n=98 each); means of survival time and survival curves were defined by the Kaplan-Meier estimator; and medical costs of follow-up treatment were calculated by the Direct (Lin) method. The bootstrap resampling technique was used to assess the impact of uncertainty. RESULTS: Survival time means of SR and SRS were 13.0, 18.4 months, respectively (P=0.000). Medians of free brain tumor time were 10.4 months for SR and 13.8 months for SRS (P=0.003). Number of repeated SRS treatments significantly influenced the survival time of SRS (R(2)=0.249; P=0.006). SRS had a lower average cost per patient (€9964 - SD: 1047; Skewness: 7273) than SR (€11647 - SD: 1594; Skewness: 0.465), leading to an incremental cost effectiveness ratio of €-3740 per life year saved (LYS), meaning that using SRS costs €1683 less than SR per targeted patient, but increases LYS by 0.45 years. CONCLUSION: SRS is more cost-effective than SR in the treatment of brain metastasis (BM) from the SHI perspective. When the clinical conditions allow it, early intervention with SRS in new BM cases and frequent SRS repetition in new BM recurrent cases should be advised.

Gamma Knife surgery for central neurocytomas.

OBJECT: The optimal management of central neurocytoma (CN) remnants and recurrences is still not clear. To date no large series of patients treated with Gamma Knife surgery (GKS) for CNs has been published. For that reason the authors decided to combine data from 5 different centers so that they could analyze the largest population of patients treated with GKS for CN currently available. METHODS: Data obtained in 42 patients who were treated for CN with GKS before July 1, 2010, were retrospectively collected and analyzed. The median prescribed dose was 13 Gy (range 11-25 Gy). The follow-up time in these patients ranged from 0.5 to 14.7 years (mean 6.1 years, median 4.9 years). Eleven patients were followed up for 5-10 years and 9 patients for more than 10 years. All patients were alive and well at the closing of the study except 1 patient, who died of injuries sustained in a traffic accident. RESULTS: Two cases of local tumor progression and 2 cases of distant tumor recurrence occurred among the patient population, yielding 5- and 10-year tumor control rates of 91% and 81%, respectively. No permanent complications occurred. The findings were in line with results reported in earlier publications. Despite the high tumor control rate, enlargement of part of or the whole ventricular system was seen in 45% of patients. CONCLUSIONS: The high tumor control rate and the low complication rate following GKS indicate that GKS is the preferred treatment for CN tumor remnants or recurrences following microsurgery. However, data from longer follow-up times in more patients are needed before this conclusion can be validated. The patients need to be closely monitored and potential hydrocephalus managed despite tumor control.

Long-term tumor control of benign intracranial meningiomas after radiosurgery in a series of 4565 patients.

BACKGROUND: Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE: To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS: From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS: Median tumor volume was 4.8 cm³, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P < .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P < .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION: Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.

Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of gamma knife radiosurgery.

OBJECTIVE: The most important treatment options for meningiomas are microsurgery, radiotherapy, and gamma knife radiosurgery (GKRS). The efficacy of GKRS in terms of local tumor control and tumor volume (TV) reduction can best be determined by accurate analysis of changes in tumor size in pre- and post-GKRS images. In this prospective study, we set the focus on evaluating TV changes and treatment outcome of meningiomas using a quantitative volumetric follow-up protocol after GKRS. METHODS: Consecutive patients with World Health Organization Grade I and II meningiomas were included in this study. Most patients underwent a microsurgical TV reduction before being treated with GKRS. Follow-up examinations were performed according to a standardized protocol and included magnetic resonance imaging and quantitative volumetric tumor analyses as well as thorough neurological examinations. RESULTS: Complete follow-up data was available for 211 patients (243 tumors) with a mean age of 57.9 years. TVs ranging from 0.1 to 48.3 cm3 were treated with GKRS using prescription doses ranging from 10 to 22 Gy. The achieved overall tumor control rate determined with quantitative TV analyses after GKRS was 93.4%; a mean TV reduction of 42.1% was achieved in 74.5% of all treated patients. CONCLUSION: Results of this study show that a quantitative volumetric follow-up study of meningiomas is a useful method to demonstrate the efficacy of GKRS for meningiomas. Statistically significant TV reductions with a low rate of side effects can be achieved with GKRS.

Volumetric follow up of brain metastases: a useful method to evaluate treatment outcome and predict survival after Gamma Knife surgery?

OBJECT: Brain metastases are diagnosed in 20 to 40% of all cancer patients and are associated with a considerable drop in life expectancy and often also in quality of life for these patients. Several treatment options are available including surgery, chemotherapy, whole-brain radiotherapy, stereotactic radiotherapy, stereotactic radiosurgery, and Gamma Knife surgery (GKS). However, management of brain metastases still presents a challenge and there is no general consensus on the best treatment strategy. The aim of the authors' study was to further evaluate the efficacy of GKS in the treatment of brain metastases and to evaluate the predictive value of volumetric tumor follow-up measurement. METHODS: Consecutive patients with controlled systemic cancer and variable numbers of brain metastases were included in this prospective study. Patients with severe symptoms of brain compression underwent surgery before GKS. Each follow-up examination included a thorough neurological examination and a neuroradiological quantitative volumetric tumor analysis. A total of 300 consecutive patients (mean age 58 years) with 703 brain metastases were treated between December 1998 and October 2005. The mean total tumor volume (TTV) was 2.1 cm3. The overall local tumor control rate was 84.5%. In 79% of all treated metastases a mean TTV reduction of 84.7% was achieved using a mean prescription dose of 21.8 Gy. Only few, mostly mild, side effects were observed during the mean follow-up period of 12.7 months. The overall mean progression-free survival period was 9.4 months. There was a statistically significant difference in survival of patients with one compared with multiple metastases, regardless of the histological type and preceding treatment. CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for patients with brain metastases regardless of the history of treatment and histological tumor type. It achieves excellent tumor control, significant TTV reduction without causing severe side effects, and accordingly, preserves quality of live. Volume changes after GKS did not serve as a predictor for treatment outcome and survival.

Intracranial glomus jugulare tumors: volume reduction with Gamma Knife surgery.

OBJECT: Glomus jugulare tumors (GJTs) are slow-growing benign tumors arising from paraganglion cells of the superior vagal ganglion. Involvement of cranial nerves and extensive erosion of the jugular foramen and petrous bone are typically seen in patients with GJTs. Advances in microsurgical techniques have improved patient outcomes, but tumors involving the petrous bone remain difficult to treat effectively. The aim of our study was to further evaluate the role of Gamma Knife surgery (GKS) in the management of intracranial GJTs. METHODS: Twelve consecutive patients (mean age 51.7 years) with intracranial GJTs were included in this study. The treatment strategy was either multimodal, with microsurgical tumor volume reduction followed by GKS in patients suffering from brainstem compression, or GKS as the only treatment. Follow-up examinations included thorough neurological examinations and neuroradiological quantitative volumetric tumor analysis. Five patients (41.6%) underwent microsurgery before GKS. Tumor volumes ranging from 1.6 to 24.8 cm3 were treated using prescription doses of 14 to 20 Gy (nine-28 isocenters). The achieved overall tumor control rate after GKS was 100% (33 months mean follow up) with only mild side effects observed. A tumor volume reduction (mean 41.1%; 3.2 cm3) was achieved in all patients. CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for intracranial GJTs. The tumor volume reductions achieved are comparable to those achieved using microsurgery but with a much lower rate of side effects. More studies with longer follow-up times are necessary to confirm these very promising results.

Gamma Knife surgery for multiple brain metastases from a malignant schwannoma of the penis.

The occurrence of brain metastases from a malignant schwannoma of the penis is extremely rare. In patients with a single brain metastasis, microsurgical extirpation is the treatment of choice and verifies the diagnosis. In cases of multiple or recurrent metastases, radiosurgery is an effective and safe therapy option. Gamma Knife surgery was performed in a patient who had previously undergone tumor resection and who presented with recurrence of the lesion and three de novo brain metastases. This first report on brain metastasis from a malignant penile schwannoma illustrates the efficacy and safety of radiosurgical treatment for these tumors.

Evaluation of a new concept for the management of skull base chordomas and chondrosarcomas.

OBJECT: Chordomas and chondrosarcomas of the skull base are rare locally invasive tumors associated with high recurrence rates. The aim of this study was to evaluate the concept of microsurgical tumor volume reduction followed by early gamma knife surgery (GKS). METHODS: Thirteen patients with 15 tumors were treated between October 2000 and June 2003. There were three patients (23.1%) with chordomas and 10 (76.9%) with chondrosarcomas. There were nine men and four women who ranged in age between 19 and 69 years. All patients first underwent maximal tumor resection. Within 2 to 10 months after surgery they were treated with GKS. The mean postoperative tumor volume treated with GKS was 9.7 cm3 (range 1.4-20.3 cm3). Follow-up computerized tomography and magnetic resonance imaging examinations with volumetric tumor analysis were performed every 6 months after GKS. The mean treatment dose was 17 Gy and the mean isodose was 52%. The mean follow-up duration was 17 months during which there was only one tumor recurrence at the margin of the radiation field. The mean volume reduction was 35.4%. CONCLUSIONS: Results of this treatment strategy are encouraging but the efficacy of this multimodal treatment combining surgery and early GKS requires a longer follow up.

Volume reduction in meningiomas after gamma knife surgery.

OBJECT: The purpose of this study was to evaluate the volume-reducing effects of gamma knife surgery (GKS) of meningiomas with and without previous surgical treatment. METHODS: A group of 127 patients with a mean age of 57.1 years (range 9-81 years) with 142 meningiomas (128 World Health Organization Grade I and 14 Grade II) were included in this study. The management strategy reduces tumor volume with surgery when necessary (81 patients). Stereotactic GKS with a Gamma Knife model C was performed in all tumors of suitable size. Magnetic resonance imaging follow-up examinations with volumetric tumor analysis was performed 6 months after treatment and annually thereafter. The mean tumor volume was 5.9 cm3 (range < 5 to > 40 cm3). The mean follow-up time after GKS was 29.3 months (range 11-61 months). The mean prescription dose was 13.8 Gy (range 10-18 Gy). A reduction in volume occurred in 117 (82.4%) of all tumors, and in 20 tumors (14.1%) growth ceased. The overall tumor control rate of 96.4%. The mean volume reduction achieved with GKS was more than 46.1%. Only five tumors (3.5%) stowed a volume increase. CONCLUSIONS: Gamma knife surgery was effective in reducing meningioma volume at short-term follow up. Further studies are needed to examine the development of these findings over a longer period.

Increased preservation of functional hearing after gamma knife surgery for vestibular schwannoma.

OBJECT: Gamma knife surgery (GKS) for vestibular schwannoma is still associated with an additional hearing loss of approximately 30%. The purpose of this study was to record the effect on hearing preservation of maintaining a margin dose of 13 Gy while reducing the maximum dose to 20 Gy. METHODS: Seventy-eight of 95 patients who entered a prospective protocol with a follow up of at least 12 months (mean 22 months) were evaluated. The mean tumor volume was 2.28 cm3. After a mean follow-up duration of 22 months, the magnetic resonance imaging-based tumor control rate was 87%. In two cases a second procedure (surgery) was necessary. Thus, the clinical control rate was 97.5%. In two cases there was an increase in trigeminal dysesthesia. One patient suffered transient facial nerve impairment. Functional hearing was preserved in 83.4% of the patients with functional hearing preoperatively. CONCLUSIONS: Reducing the maximum dose to 20 Gy seems to be an effective treatment, which probably increases preservation of functional hearing without sacrificing the high tumor control rates achieved in radiosurgery. Postradiosurgery tumor swelling occurred in 25% of the cases and was not correlated with hearing deterioration.

Gamma knife model C with the automatic positioning system and its impact on the treatment of vestibular schwannomas.

OBJECT: The aim of this study was to assess the effects of the gamma knife automatic positioning system (APS) on the treatment of patients, particularly effects of this system on the treatment of patients with vestibular schwannomas (VSs), with a view to reducing loss of hearing. METHODS: The dose delivery with an increased number of shots was checked with GAFChromic Film for various numbers of shots (one to 129). The results in the first 549 patients were recorded. In addition a series of 59 patients with VSs treated with 13 Gy to the 65% isodose is presented. The authors have termed this the "13 on 65" concept. The film dosimetry showed that a large number of small shots did not materially affect the dose and dose distribution produced by gamma knife treatment. The APS was used alone in 72% of arteriovenous malformations, 71% of meningiomas, 94% of VSs, and 84% of pituitary adenomas. Metastatic tumors were accessible in a pure APS mode in 59% of all cases, glioma in 58%, and uveal melanoma in 10% of the cases. Thus two thirds of patients could be treated using APS alone. It was possible to use the APS and manual systems together for complex or very eccentrically placed targets. The APS resulted in the use of a larger number of isocenters. After a mean follow-up period of 15 months, the results in patients with the VSs in whom 13 Gy was delivered to the 65% isodose were similar to those in patients treated with the more conventional 50% margin isodose. There was no change in the incidence of hearing loss within the study period, and the incidence of trigeminal and facial neuropathies remained unchanged after treatment as well. CONCLUSIONS: The APS encourages the design of more conformal dose plans. The greater use of smaller collimators results in a steeper dose gradient with a smaller amount of radiation outside the target volume. Because the APS is able to apply a large number of smaller isocenters in an acceptable time, the number of isocenters used is increased. An increased number of isocenters can also be used to reduce the maximum radiation dose and increase the homogeneity in a given dose plan.