Pediatric Intracranial Arteriovenous Malformation: Long-Term Outcomes with Linear Accelerator (LINAC)-Based Radiosurgery.

PURPOSE: To analyze and report the long-term outcomes of intracranial arteriovenous malformations (AVM) treated with linear accelerator (LINAC)-based radiosurgery (LBRS) in the pediatric population. METHODS AND MATERIALS: A series of 34 pediatric patients (≤18 years old) who were treated between 2002 and 2016 were analyzed. All patients were treated with LBRS in a single fraction, with a median dose of 16.8 Gy to the 80% isodose line. Median age at treatment was 14.4 years (range 5.5-18.9). Median AVM volume was 2.91 mL (range 0.228-27.313). Median modified radiosurgery-based AVM score was 0.83 (range 0.18-2.96). The most common presenting symptom was intracranial hemorrhage (ICH) (n = 22, 64.7%). Nine patients underwent intervention before LBRS, which included prior embolization or resection. Seven lesions were in eloquent locations, defined as basal ganglia, thalamus, or brainstem. Cerebral angiography was done to confirm obliteration. RESULTS: Median follow-up time was 98 months (range 36-200 months). Twenty-two of the 34 lesions were obliterated (64.7%) with median time to obliteration of 37 months (range 14-79). No deaths occurred during the follow up period; however, two patients experienced ICH after treatment. Three other patients were treated for symptomatic radiation necrosis. CONCLUSIONS: Treatment of intracranial AVM with LBRS in the pediatric population is demonstrated to be safe and effective with long-term follow up.

A comparative outcomes analysis of patients treated for arteriovenous malformation with LINAC-based stereotactic radiosurgery by a standard frame-based technique or a frameless technique utilizing 3-dimensional rotational angiography.

Previous work at our institution treating arteriovenous malformation (AVM) with radiosurgery (RS) demonstrated superior nidus visualization and geometric accuracy with use of 3-dimensional rotational angiography (3DRA) compared to biplanar digital subtraction angiography. We have since adopted a unique radiosurgical protocol that utilizes 3DRA in the planning of linear accelerator (LINAC)-based RS delivered in a frameless manner. This study seeks to compare clinical outcomes between patients treated by this novel approach and those treated by our historic frame-based protocol. Clinical data were queried for all patients treated for AVM by single-fraction RS from 2003 to 2017. RICs were identified and classified as radiologic, symptomatic, or permanent. Excellent outcome was defined as nidus obliteration without intracranial hemorrhage (ICH) or symptomatic RIC. Clinical predictors of study outcomes were identified through univariate and multivariate logistic regression using backwards elimination to optimize a predictive model. 131 AVMs in 124 patients were included with a median follow-up of 88 months. 59 AVMs received frame-based RS and 72 AVMs received frameless RS. Rate of obliteration was 64% for frame-based RS and 61% for frameless RS (p = 0.70). Radiologic, symptomatic, and permanent RICs rates were 68%, 17%, and 8%, respectively, for frame-based cases, versus 40% (p < 0.01), 8% (p = 0.13), and 3% (p = 0.15), respectively, for frameless cases. Excellent outcome was achieved in 49% of frame-based cases and 53% of frameless cases (p = 0.68). These results illustrate the safety and effectiveness of frameless LINAC-based AVM RS utilizing 3DRA.

De novo superior cerebellar artery aneurysm following radiosurgery for trigeminal neuralgia.

Stereotactic radiosurgery is a commonly used method for treatment of trigeminal neuralgia. Radiation has been known to be a factor in the later development of aneurysms. Aneurysms have been reported to occur after radiation delivered in a variety of methods including both externally delivered radiation radiosurgery and brachytherapy. We report here an incidence of a de novo aneurysm presenting following radiosurgery treatment for trigeminal neuralgia. The patient was treated using frame-based LINAC radiosurgery receiving 90Gy to the mid cisternal extent of the nerve via a 4mm conical collimator. The patient presented with progressive hypoesthesia 11years after treatment. Imaging evaluation demonstrated the presence of an aneurysm abutting the treated trigeminal nerve. The aneurysm was successfully coil embolized. The patient's facial hypoesthesia, however, did not improve following embolization. We believe that this is the first report of such an aneurysm occurring after radiosurgery for trigeminal neuralgia. De novo aneurysms are a recognized long term complication of radiotherapy and radiosurgery treatment. This report shows such aneurysms can occur with very small treatment volumes. Late sensory changes following radiosurgery for trigeminal neuralgia should prompt workup for de novo aneurysms as well as other late adverse radiation effects.

Hypofractionated stereotactic radiosurgery for treatment of cerebral arteriovenous malformations: outcome analysis with use of the modified arteriovenous malformation scoring system.

Radiosurgery has long been an accepted modality for definitive treatment of cerebral arteriovenous malformations (AVM). Efforts to improve the therapeutic ratio for this indication include use of staged volume procedures and hypofractionation. This study reviews our experience with a cohort of patients treated with hypofractionated radiosurgery. Over a 3year period, 38 patients harboring 39 cerebral AVM were treated with hypofractionated stereotactic radiotherapy. Seventeen of these patients presented due to hemorrhage, four were asymptomatic unruptured lesions and the remainder were symptomatic unruptured lesions. The median AVM volume was 11.43 cc and median modified Radiosurgery-Based Arteriovenous Malformation Score (mRBAS) was 2.02. The median follow-up was 7.32years. Four patients harboring four AVM were lost to follow-up before a result could be ascertained leaving 35 AVM for analysis. Excellent outcomes (AVM obliteration without new deficits) occurred in 17 of 34 (50%) patients and in 18 of 35 (51%) AVM treated. AVM obliteration was seen in 26 of 35 (74%) lesions treated. Two patients died during the follow-up period (6%). A poor result (major deficit without obliteration) was seen in one patient. Of 19 patients harboring AVM with mRBAS >2.0, an excellent outcome was achieved in eight (42%). Hypofractionation for cerebral AVM can result in satisfactory obliteration rates, but with risk of significant complications commensurate with mRBAS. Further study of this technique will be needed to ascertain the degree of incremental improvement, if any, over other radiosurgery treatment methods.

A comparative study of stereotactic radiosurgery, hypofractionated, and fractionated stereotactic radiotherapy in the treatment of skull base meningioma.

OBJECTIVES: To compare the outcomes of skull base meningiomas treated with stereotactic radiosurgery (SRS), hypofractionated stereotactic radiotherapy (hFSRT), and fractionated stereotactic radiotherapy (FSRT). METHODS: A total of 220 basal meningiomas in 213 patients were treated using SRS (N=55), hFSRT (N=22), and FSRT (N=143). The median age was 59 years (28 to 84 y). Prior surgery was performed in 74 cases; 39 patients received adjuvant radiotherapy after incomplete resection and 35 patients received salvage radiotherapy after tumor progression. In 146 cases, radiation was the primary therapy. Ten patients had World Health Organization II or III meningiomas. RESULTS: The median follow-up was 32 months (7 to 97 mo). Median tumor volume was 2.8 cm (0.10 to 16.94 cm), 4.8 cm (0.88 to 20.38 cm), and 11.1 cm (0.43 to 214.00 cm) and the median dose was 1250 cGy in 1 fraction to the 80% isodose line (IDL), 2500 cGy in 5 fractions to the 90% IDL, and 5040 cGy in 28 fractions to the 90% IDL for the SRS, hFSRT, and FSRT groups, respectively. Radiographic control was achieved in 91%, 94%, and 95% (P=0.25), whereas clinical response was seen in 89%, 100%, and 91% (P=0.16) in the SRS, hFSRT, and FSRT groups, respectively. CONCLUSIONS: There is no significant difference in the radiographic and clinical response in patients with skull base meningioma treated with SRS, hFSRT, or FSRT and thus gives the clinician the impetus to tailor treatment techniques to the location and size of the tumor at presentation.

Photon-based fractionated stereotactic radiotherapy for postoperative treatment of skull base chordomas.

OBJECTIVES: We report our series of skull base chordoma patients who underwent surgical resection followed by high-dose fractionated stereotactic radiotherapy (FSRT) as an alternative to proton radiotherapy (RT). METHODS: Between 2002 and 2009, 12 patients with skull base chordomas without prior radiation history were treated with adjuvant or salvage RT. FSRT with dynamic conformal arcs and intensity-modulated radiation therapy boost was used until 2006 when image-guided intensity-modulated FSRT was instituted. Median dose of 66.6 Gy (range, 48.6 to 68.4 Gy) was delivered in 180 cGy fractions prescribed to the 90% isodose line that covered the target volume to achieve a median isocenter dose of 74 Gy (range, 54 to 76 Gy). RESULTS: Median follow-up was 42 months. Median time from surgery to initiation of RT was 3.6 months. Overall survival was 76.4% at 5 years, and 46.9% and 37.5% of patients were free of progression at 24 and 60 months, respectively. Six patients had disease progression after radiation with a median time to progression of 17.3 months. One patient was salvaged with radiosurgery and surgical resection, with stable disease almost 7 years since diagnosis. Two patients were salvaged with molecular targeted therapy with stable disease at 20 and 23 months. At last follow-up, 9 patients had stable or reduced disease. CONCLUSIONS: FSRT as postoperative treatment of skull base chordomas resulted in promising overall survival results comparable with the published literature of particle therapy without significant complications. Our technique for treating skull base chordomas can be considered a safe and less costly alternative to proton RT.

Microvascular decompression for trigeminal neuralgia in patients with and without prior stereotactic radiosurgery.

BACKGROUND: Radiosurgery has emerged as an important primary treatment means of typical trigeminal neuralgia. Despite its high safety and efficacy, the likelihood of recurrence is significant, potentially requiring salvage treatment. Posterior fossa exploration and microvascular decompression is an option for salvage treatment. Results are presented regarding a single-surgeon experience, and a grading scale is proposed for postirradiation surgical findings. METHODS: A retrospective analysis of the author's experience with 109 consecutive posterior fossa explorations for typical trigeminal neuralgia performed over a period of 8 years is included in this analysis. There were 42 patients undergoing microvascular decompression following recurrence of pain after radiosurgery, and 67 patients underwent microvascular decompression without prior radiosurgery. Operative findings were reviewed and categorized. A 4-category typing system is proposed. The Barrow Neurological Institute Pain Scale Score was used to categorize post-microvascular decompression outcomes. RESULTS: Within the postradiosurgery group, 41 of 42 patients had initial treatment success (Barrow Neurological Institute score 1 to 3), comparing favorably with the nonirradiated group, in which 59 of 67 patients had initial successful treatment (P=0.15, Fisher exact test, 2-tailed). Findings of conflicting vessel atherosclerosis and adhesions between conflicting vessel and nerve were only seen in the postradiosurgery group, whereas arachnoid thickening requiring sharp dissection was seen in both postradiosurgery and nonirradiated groups. Increased difficulty of dissection in either the radiosurgery or the nonirradiated groups did not appear to affect the likelihood of satisfactory outcome. CONCLUSIONS: Microvascular decompression can be performed in the postradiosurgery setting safely with high efficacy. Dissection typically was not significantly more difficult in comparison to procedures performed without prior history of radiosurgery intervention.

Frameless image-guided radiosurgery for initial treatment of typical trigeminal neuralgia.

OBJECTIVE: To review retrospectively initial experience at a single institution using frameless image-guided radiosurgery (IGRS) for trigeminal neuralgia employing the Novalis linear accelerator (LINAC) with ExacTrac robotic patient positioning device. METHODS: Over an 18-month period, 44 patients (27 women and 17 men; median age 65 years) were treated with frameless IGRS for typical trigeminal neuralgia (14 cases involved left-sided pain and 30 cases involved right-sided pain), responsive to anticonvulsant medications, with Barrow Neurological Institute Pain Scale (BNI-PS) scores of 4 or 5. All cases were initial radiosurgery treatments with an isocenter dose of 90 Gy delivered via a 4-mm circular collimator forming a spheroid dose envelope. Intrafraction positioning data were collected for all patients. The median follow-up was 15 months. RESULTS: Overall intrafraction positioning error was 0.49 mm ± 0.44. After treatment, 40 patients achieved a BNI-PS score of IIIb or better; 19 patients achieved a BNI-PS score of I. The median time to pain relief was 4 weeks. Overall, new hypoesthesia was seen in five patients. No other complications were seen. CONCLUSIONS: Use of frameless IGRS methods for treatment of trigeminal neuralgia showed results similar to the authors' prior experience with frame-based treatment methods. IGRS using frameless methods is a suitable treatment method for patients with trigeminal neuralgia and may be applicable to other functional indications.

Control of brain metastases using frameless image-guided radiosurgery.

OBJECT: Radiosurgery is an important and well-accepted method in the management of brain metastases. Using conventional frame-based techniques, high lesional control rates are expected. The introduction of image-guided techniques allows for improved patient comfort and workflow. Some controversy exists as to the accuracy of imageguided techniques and consequently the impact they might have on control of brain metastases (as opposed to the level of control achieved with frame-based methods). The authors describe their initial 15-month experience with image-guided radiosurgery (IGRS) using Novalis with ExacTrac for management of brain metastases. METHODS: The authors reviewed the cases of brain metastasis treated by means of IGRS in their tertiary regional radiation oncology service over a 15-month period. During the study period 54 patients (median age 57.9 years) harboring 108 metastases were treated with IGRS. The median time from cancer diagnosis to development of brain metastasis was 12 months (range 0-144 months). The median tumor volume was 0.98 cm(3) (range 0.03-19.07 cm(3)). The median prescribed dose was 18 Gy to the 80% isodose line (range 14-20 Gy). Lesions were followed with postradiosurgery MR imaging every 2-3 months following treatment. RESULTS: The median follow-up period was 9 months (range 0-20 months). Median actuarial survival was 8.6 months following IGRS. Eight patients with 18 lesions died within the first 2 months after the procedure, before scheduled follow-up imaging. Thus 90 lesions (in 46 patients) were followed up with imaging studies. Lesions that were unchanged or reduced in size were considered to be under control. The 6-month actuarial lesion control rate was 88%. Smaller lesions (< 1 cm(3)) had a statistically improved likelihood of complete imaging response (loss of all contrast-enhancement p = 0.01). CONCLUSIONS: Image-guided radiosurgical treatment of brain metastases resulted in high rates of tumor control comparable to control rates reported for frame-based methods. High control rates were seen for small lesions in which spatial precision in dose delivery is critical. These data suggests that in regard to lesion control, IGRS using Novalis with ExacTrac is equivalent to frame-based radiosurgery methods.

Comparison of early complications for patients with convexity and parasagittal meningiomas treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy.

OBJECTIVE: Patients with convexity and parasagittal (CPS) meningiomas treated with stereotactic radiosurgery (SRS) have been shown to be at risk for posttreatment symptomatic peritumoral edema (SPTE). We sought to analyze the pattern of this complication and compare it with the SPTE experienced in our patients treated with fractionated stereotactic radiotherapy. METHODS: From January 2003 to October 2005, 32 patients with CPS meningiomas were treated. Thirty patients with a total of 38 lesions had sufficient follow-up for analysis. Group A (n = 14) patients were treated with single fraction SRS, and Group B (n = 16) patients were treated with fractionated stereotactic radiotherapy. The lesion volume was different between the two groups with the Group B median volume (7.46 cm) being larger than that for Group A (2.84 cm) (P = 0.0008). Conversely age, follow-up, sex, prior surgical events, number of lesions, tumor location, and atypical histology did not differ between these groups. The median marginal dose for patients in Group A was 14 Gy (range, 12.5-18 Gy). For Group B, six patients received a median marginal dose of 50.4 Gy in 28 fractions, and 10 patients received a marginal dose of 25 Gy in five fractions. RESULTS: Seven of the 30 patients treated in this series developed posttreatment SPTE. The incidence of SPTE in Group A (six of 14 patients) was significantly higher than that in Group B (one of 16 patients) (P = 0.031). The median time to onset of SPTE in the six patients in Group A was 4 months. In Group B, one patient had onset of SPTE in 3 months. On univariate analysis, larger tumor volume (P = 0.0014) and tumor margin dose >14 Gy in patients undergoing SRS (P = 0.031) was associated with onset of SPTE. Age, previous surgery, and tumor location were not associated with onset of SPTE. CONCLUSION: Despite larger lesion volumes, fractionated stereotactic radiotherapy is associated with less risk of posttreatment SPTE than SRS for patients with CPS meningiomas in our series. For patients treated with SRS, smaller volume and dose <14 Gy seems to be safe. Longer follow-up will be required to compare late complications and tumor control rates in these patients.

Prognostic factors for radiosurgery treatment of trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia treatment results are thought to be highly dependent upon selection criteria. We retrospectively analyzed a series of patients to determine the likelihood of treatment success for patients treated with radiosurgery. METHODS: A retrospective analysis of 82 patients treated with linear accelerator radiosurgery was undertaken with a median follow-up period of 18 months. Patients were evaluated with a standard inventory using the Barrow Neurological Institute pain scale as the primary means of outcome measurement. Patients were treated with a linear accelerator using a single isocenter plan delivered via a 4-mm collimator, typically with seven noncoplanar arcs to a peak dose of 85 or 90 Gy in primary treatments and 60 Gy in retreatments. The primary target was the cisternal component of the trigeminal nerve. Posttreatment outcomes were analyzed in light of pretreatment patient characteristics, including age, sex, anticonvulsant responsiveness, quality and pattern of pain, length of disease, number of previous procedures, and radiation dose exposure to the root entry zone. Univariate analysis and multivariate logistic regression analysis were used to determine the prognostic significance of various pretreatment variables. RESULTS: Good results as defined by a Barrow Neurological Institute outcome score of IIIb or better were seen in 85.3% of patients. Excellent results as defined by a Barrow Neurological Institute outcome score of I were seen in 49% of patients. The median time to satisfactory improvement of pain was 4 weeks. Only one variable, sensitivity to anticonvulsant medication, was found to be statistically significant in both univariate (P = 0.003) and multivariate analysis (P = 0.025). All other variables analyzed failed to reach statistical significance. Complications were not common, with seven patients (8.5%) developing new-onset hypoesthesia and two patients (2%) developing dry eye symptoms. CONCLUSION: Anticonvulsant responsiveness is the single most important prognostic indicator of treatment success for patients presenting with facial pain. Other predictive factors generally failed to reach statistical significance. Linear accelerator radiosurgery for trigeminal neuralgia is a safe and effective treatment for well-selected patients, with results similar to those obtained with gamma unit radiosurgery.

Chained lightning: part III--Emerging technology, novel therapeutic strategies, and new energy modalities for radiosurgery.

Radiosurgery is fundamentally the harnessing of energy and delivering it to a focal target for a therapeutic effect. The evolution of radiosurgical technology and practice has served toward refining methodologies for better conformal energy delivery. In the past, this has resulted in developing strategies for improved beam generation and delivery. Ultimately, however, our current instrumentation and treatment modalities may be approaching a practical limit with regard to further optimizing energy containment. In looking forward, several strategies are emerging to circumvent these limitations and improve conformal radiosurgery. Refinement of imaging techniques through functional imaging and nanoprobes for cancer detection may benefit lesion localization and targeting. Methods for enhancing the biological effect while reducing radiation-induced changes are being examined through dose fractionation schedules. Radiosensitizers and photosensitizers are being investigated as agents for modulating the biological response of tissues to radiation and alternative energy forms. Discovery of new energy modalities is being pursued through development of microplanar beams, free electron lasers, and high-intensity focused ultrasound. The exploration of these future possibilities will provide the tools for radiosurgical treatment of a broader spectrum of diseases for the next generation.

Contemporary methods of radiosurgery treatment with the Novalis linear accelerator system.

Radiosurgery has emerged as an indispensable component of the multidisciplinary approach to neoplastic, functional, and vascular diseases of the central nervous system. In recent years, a number of newly developed integrated systems have been introduced for radiosurgery and fractionated stereotactic radiotherapy treatments. These modern systems extend the flexibility of radiosurgical treatment in allowing the use of frameless image-guided radiation delivery as well as high-precision fractionated treatments. The Novalis linear accelerator system demonstrates adequate precision and reliability for cranial and extracranial radiosurgery, including functional treatments utilizing either frame-based or frameless image-guided methods.

Chained lightning, part II: neurosurgical principles, radiosurgical technology, and the manipulation of energy beam delivery.

The fundamental principle in the radiosurgical treatment of neurological conditions is the delivery of energy to a lesion with minimal injury to surrounding structures. The development of radiosurgical techniques from Leksell's original design has focused on the refinement of various methodologies to achieve energy containment within a target. This article is the second in a series reviewing the evolution of radiosurgical instruments with respect to issues of energy beam generation and delivery for improved conformal therapy. Continuing with concepts introduced in an earlier article, this article examines specific aspects of beam delivery and the emergence of stereotactic radiosurgery as a measure for focusing energy beams within a target volume. The application of stereotactic principles and devices to gamma ray and linear accelerator-based energy sources provides the methodology by which energy beams are generated and targeted precisely in a focal lesion. Advanced technological systems are reviewed, including fixed beams, dynamic radiosurgery, multileaf collimation, beam shaping, and robotics as various approaches for manipulating beam delivery. Radiosurgical instruments are also compared with regard to mechanics, geometry, and dosimetry. Finally, new radiosurgical designs currently on the horizon are introduced. In exploring the complex history of radiosurgery, it is evident that the discovery and rediscovery of ideas invariably leads to the development of innovative technology for the next generation.

Stereotactic radiosurgery: indications and results - part 2.

Stereotactic radiosurgery and fractionated stereotactic radiotherapy represent an increasingly important option in the treatment of central nervous system disease. In this article, we discuss indications for stereotactic radiosurgery and review results reported in the medical literature.

Stereotactic radiosurgery: instrumentation and theoretical aspects-part 1.

In the five decades since its introduction as a concept, radiosurgery has been technically refined to the point where it has revolutionized many aspects of treating central nervous system disease.This article reviews the technical basis of stereotactic radiosurgery as well as the radiobiologic principles underlying its use.

Treatment of trigeminal neuralgia with linear accelerator radiosurgery: initial results.

OBJECT: Radiosurgery has emerged as an important treatment of trigeminal neuralgia. Substantial advantages have been demonstrated in safety and comfort over other modalities. Radiosurgical treatment of trigeminal neuralgia has been well investigated with gamma knife devices involving fixed cobalt sources. Few reports exist concerning trigeminal neuralgia treated using linear accelerator (LINAC)-based devices. In recent years these devices have reached the level of mechanical precision that is required for such functional treatments. The authors describe their initial experience with radiosurgical treatment of trigeminal neuralgia when using a BrainLAB Novalis LINAC device equipped with the commercially available 4-mm collimator. METHODS: A total of 32 patients were treated in a 12-month period between November 2002 and November 2003. The median patient age was 67 years (range 38-84 years). Facial pain was graded using the Barrow Neurological Institute (BNI) scoring system. All patients' pain was BNI Grade IV or V prior to treatment. Of these patients, 22 were undergoing initial treatment, and 10 were undergoing retreatment for recurrent pain following various treatments including percutaneous procedures, gamma knife surgery (GKS), or microvascular decompression. Two patients had multiple sclerosis. In patients undergoing initial radiosurgery, the most proximal segment of the cisternal portion of the trigeminal nerve received 85 to 90 Gy administered in a 5- or 7-noncoplanar arc single-isocenter plan with a 4-mm circular collimator. In patients undergoing repeated radiosurgery, the target received 60 Gy. Overall good and excellent results (BNI Grade I, II, or III) were achieved in 25 (78%) of 32 patients. The median time to pain relief was 6 weeks. Fair results (improvement in pain with BNI Grade IV) were achieved in three patients (9%), and poor results (no improvement in pain and BNI Grade IV or V) were seen in four (13%). Two patients demonstrated new trigeminal dysfunction following treatment. No other complications occurred. CONCLUSIONS: High-precision imaging and LINAC instrumentation have allowed for treatment of trigeminal neuralgia with results and safety comparable to those achieved using GKS. Linear accelerator-based radiosurgery with the Novalis device is a safe and effective method of managing trigeminal neuralgia and may become the preferred means at centers where the technology is available.

Gamma knife radiosurgery for benign cavernous sinus tumors: quantitative analysis of treatment outcomes.

OBJECTIVE: We review our 8-year experience with gamma knife radiosurgery (GKRS) for the treatment of patients with benign cavernous sinus tumors and present a quantitative analysis of factors relevant to treatment outcomes. METHODS: From 1994 to 2002, a total of 139 patients with benign cavernous sinus tumors were treated in 145 sessions. Their median age was 53 years, and the median follow-up was 3.5 years. The tumors included 57 meningiomas, 76 pituitary tumors (49 nonfunctional adenomas, 15 prolactinomas, 5 adrenocorticotropic hormone-secreting tumors, 6 growth hormone-secreting tumors, and 1 plurihormone-secreting tumor), 4 schwannomas, 1 hemangioma, and 1 paraganglioma. Sekhar tumor grades were as follows: I, n = 28 (20%); II, n = 42 (30%); III, n = 42 (30%); IV, n = 19 (14%); and V, n = 8 (6%). The median tumor volume was 3.4 cm(3), and the median prescribed dose was 15 Gy defined to the 50% isodose line. RESULTS: A total of 136 treated tumors (97.8%) were well controlled by GKRS, with low morbidity. For meningiomas, 29 tumors (51%) were unchanged and 26 (46%) were smaller at a median of 15.2 months. For pituitary tumors, 50 (66%) were unchanged and 25 (33%) were smaller at a median of 20.6 months. Improvement in cranial nerve (CN) function was seen in 19 (36.5%) of 52 patients with pre-GKRS deficits, and 3 patients (2.2%) developed new stable CN deficits after GKRS: 1 patient developed IVth CN palsy at 9 months, and 2 developed persistent VIth CN palsies at 43 and 45 months, respectively, that required surgical correction. Two patients developed transient VIth CN palsies at 48 months that self-resolved after another year. Endocrine function normalized for all 6 treated patients with a growth hormone-secreting tumor at a median of 18 months. One of the 5 adrenocorticotropic hormone-secreting tumors required retreatment after 17 months because of continued cortisol elevation. Thirteen (87%) of 15 prolactinoma patients had normalized prolactin levels within 2 years of the procedure; 2 patients relapsed by endocrine criteria at 18 and 22 months after GKRS. Two patients with normalized prolactin levels completed three normal pregnancies within 3 years of treatment. Six patients (4.3%) with a median tumor volume of 8 cm(3) developed radiation-induced injury at a median of 36 months after GKRS. Five of these patients also underwent external beam radiotherapy and received a median dose of 52.2 Gy in 30 fractions. Quantitative analysis revealed that the radiation dose to critical structures (optic apparatus and pons) is correlated with their distance from tumor margins. Underdosed tumor volume, tumor volume, and total treated volume are correlated with treatment outcomes. CONCLUSION: GKRS is a safe and effective treatment for selected patients with benign cavernous sinus tumors and is an important adjunct for treating postoperative tumor residual and/or recurrent tumor. Continued analysis of treated patients over an extended time is needed to evaluate long-term disease control and potential late GKRS complications.

Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test.

OBJECT: Transsphenoidal adenomectomy with resection of a defined pituitary adenoma has been the treatment of choice for CD for the last 30 years. Surgical resection, however, may not always result in long-term remission of CD. This is particularly important in light of the high risk of morbidity and mortality in patients in the unsuccessfully treated cushingoid state. As such, it is interesting to identify prognostic factors that may predict the likelihood of long-term remission. METHODS: The authors review their series of 174 patients who have undergone transsphenoidal procedures for CD over a period of 20 years with minimum follow-up periods of 5 years. Selection of these patients was based on clinical, imaging, and laboratory criteria that included serum cortisol levels, loss of diurnal variation in serum cortisol levels, urinary free cortisol concentration, and results of a dexamethasone suppression test, petrosal sinus sampling, and corticotroph-releasing hormone stimulation tests as indicated. All patients who met the biochemical criteria underwent transsphenoidal microsurgery. The authors found an overall rate of remission of 74% at 5 years postoperatively. Patients in whom morning serum cortisol concentrations were lower than 3 microg/dl (83 nmol/L) on postoperative Day 3, following an overnight dexamethasone suppression test, had a 93% chance of remission at the 5-year follow-up examination. Patients with cortisol concentrations higher than this level uniformly failed to achieve long-term remission. CONCLUSIONS: Transsphenoidal microsurgery is an effective means of control for patients with adrenocorticotrophic hormone-producing microadenomas. Clinical outcome correlated well with the size of the tumor, as measured on preoperative imaging studies, and with postoperative morning cortisol levels following an overnight dexamethasone suppression test. Postoperative cortisol levels can be used as a useful prognostic indicator of the likelihood of future recurrence following transsphenoidal adenomectomy in CD.