Cheng-Ying Shiau

Radiosurgery for brain metastases: Relationship of dose and pattern of enhancement to local control

PURPOSEnThis study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS).nnnMETHODS AND MATERIALSnAll brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model.nnnRESULTSnOf 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving > or = 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55).nnnCONCLUSIONnA minimum prescribed radiosurgical dose > or = 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a new finding in this retrospective analysis, needs to be confirmed.

Gamma knife radiosurgery as a single treatment modality for large cerebral arteriovenous malformations.

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.

Gamma knife surgery for vestibular schwannoma: 10-year experience of 195 cases

OBJECTnThe authors conducted a study to determine the optimal radiation dose for vestibular schwannoma (VS) and to examine the histopathology in cases of treatment failure for better understanding of the effects of irradiation.nnnMETHODSnA retrospective study was performed of 195 patients with VS; there were 113 female and 82 male patients whose mean age was 51 years (range 11-82 years). Seventy-two patients (37%) had undergone partial or total excision of their tumor prior to gamma knife surgery (GKS). The mean tumor volume was 4.1 cm3 (range 0.04-23.1 cm3). Multiisocenter dose planning placed a prescription dose of 11 to 18.2 Gy on the 50 to 94% isodose located at the tumor margin. Clinical and magnetic resonance (MR) imaging follow-up evaluations were performed every 6 months. A loss of central enhancement was demonstrated on MR imaging in 69.5% of the patients. At the latest MR imaging assessment decreased or stable tumor volume was demonstrated in 93.6% of the patients. During a median follow-up period of 31 months resection was avoided in 96.8% of cases. Uncontrolled tumor swelling was noted in five patients at 3.5, 17, 24, 33, and 62 months after GKS, respectively. Twelve of 20 patients retained serviceable hearing. Two patients experienced a temporary facial palsy. Two patients developed a new trigeminal neuralgia. There was no treatment-related death. Histopathological examination of specimens in three cases (one at 62 months after GKS) revealed a long-lasting radiation effect on vessels inside the tumor.nnnCONCLUSIONSnRadiosurgery had a long-term radiation effect on VSs for up to 5 years. A margin 12-Gy dose with homogeneous distribution is effective in preventing tumor progression, while posing no serious threat to normal cranial nerve function.

Gamma knife surgery for cavernous hemangiomas: an analysis of 125 patients

OBJECTnThe authors sought to determine the value of gamma knife surgery (GKS) in the treatment of cavernous hemangiomas (CHs).nnnMETHODSnBetween 1993 and 2002, a total of 125 patients with symptomatic CHs were treated with GKS. Ninety-seven patients presented with bleeding and 45 of these had at least two bleeding episodes. Thirteen patients presented with seizures combined with hemorrhage, and 15 patients presented with seizures alone. The mean margin dose of radiation was 12.1 Gy and the mean follow-up time was 5.4 years. In the 112 patients who had bled the number of rebleeds after GKS was 32. These rebleeds were defined both clinically and based on magnetic resonance imaging for an annual rebleeding rate of 32 episodes/492 patient-years or 6.5%. Twenty-three of the 32 rebleeding episodes occurred within 2 years after GKS. Nine episodes occurred after 2 years; thus, the annual rebleeding rate after GKS was 10.3% for the first 2 years and 3.3% thereafter (p = 0.0038). In the 45 patients with at least two bleeding episodes before GKS, the rebleeding rate dropped from 29.2% (55 episodes/188 patient-years) before treatment to 5% (10 episodes/197 patient-years) after treatment (p < 0.0001). Among the 28 patients who presented with seizures, 15 (53%) had good outcomes (Engel Grades I and II). In this study of 125 patients, symptomatic radiation-induced complications developed in only three patients.nnnCONCLUSIONSnGamma knife surgery can effectively reduce the rebleeding rate after the first symptomatic hemorrhage in patients with CH. In addition, GKS may be useful in reducing the severity of seizures in patients with CH.

Relationship between pattern of enhancement and local control of brain metastases after radiosurgery

PURPOSEnA desired goal in the radiosurgery (RS) of brain metastases is improved local control. Our earlier retrospective review identified pattern of enhancement on day-of-treatment imaging as a prognostic indicator for freedom from progression (FFP) after RS in 219 brain metastases. The current study was performed to corroborate this preliminary finding.nnnMETHODS AND MATERIALSnRecords and imaging studies of patients treated with RS from 1991 to 1997 were reviewed. Each metastasis was categorized as homogeneously-, heterogeneously-, or ring-enhancing. Kaplan-Meier FFP was calculated from the date of RS to the first imaging showing tumor progression. Univariate and multivariate analyses were performed using Cox proportional hazard models stratified by primary site and type of RS (alone, as a boost, or for recurrence).nnnRESULTSnOf 682 lesions in 258 patients, 518 lesions in 193 patients were evaluable. Pattern of enhancement was homogeneous in 59%, heterogeneous in 32%, and ring-like in 8% of lesions. One-year FFP probabilities for homogeneously-, heterogeneously-, and ring-enhancing lesions were 90% (95% confidence interval, 84-93%), 76% (64-84%), and 57% (35-74%), respectively. The p-value for pattern of enhancement from the stratified multivariate analysis was 0.019 adjusting for RS dose and treatment period (1991-1994 vs. 1995-1997). Similar results were achieved adjusting for tumor volume instead of RS dose.nnnCONCLUSIONnPattern of enhancement is confirmed as a significant prognostic factor for FFP of brain metastases treated with RS, independent of dose and volume. A possible explanation is radioresistance of hypoxic tumor cells associated with necrotic regions, suggesting future investigations with radiosensitizers, hypoxic cell sensitizers, or strategies to improve tumor oxygenation.

Staged radiosurgery for extra-large cerebral arteriovenous malformations : method, implementation, and results

OBJECTnThe effectiveness and safety of radiosurgery for small- to medium-sized cerebral arteriovenous malformations (AVMs) have been well established. However, the management for large cerebral AVMs remains a great challenge to neurosurgeons. In the past 5 years the authors performed preplanned staged radiosurgery to treat extra-large cerebral AVMs.nnnMETHODSnAn extra-large cerebral AVM is defined as one with nidus volume > 40 ml. The nidus volume of cerebral AVM is measured from the dose plan-that is, as being the volume contained within the best-fit prescription isodose. From January 2003 to December 2007, the authors treated 6 patients with extra-large AVMs by preplanned staged GKS. Staged radiosurgery is implemented by rigid transformation with translation and rotation of coordinates between 2 stages. The average radiation-targeted volume was 60 ml (range 47-72 ml). The presenting symptoms were seizure in 4 patients and a bleeding episode in 2. One patient had undergone a previous craniotomy and evacuation of hematoma. The mean interval between the 2 radiosurgical sessions was 6.9 months (range 4.5-9.1 months). The prescribed marginal dose given to the nidus volume in each stage ranged from 16 to 18.6 Gy. The expected marginal dose of total nidus was 17-19 Gy. Regular follow-up MR imaging was performed every 6 months. The mean follow-up period was 28 months (range 12-54 months).nnnRESULTSnMost of the patients exhibited clinical improvement: relief of headache and reduced frequency of seizure attack. All patients had significant regression of nidus observed on MR imaging follow-up. Two patients had angiogram-confirmed complete obliteration of the nidus 45 and 60 months after the second-stage radiosurgical session. One patient experienced minor bleeding 8 months after the second-stage radiosurgery with mild headache. She had satisfactory recovery without clinical neurological deficit after conservative treatment.nnnCONCLUSIONSnThese preliminary results indicate that staged radiosurgery is a practical strategy to treat patients with extra-large cerebral AVMs. It takes longer to obliterate the AVMs. The observed high signal T2 changes after the radiosurgery appeared clinically insignificant in 6 patients followed up for an average of 28 months. Longer follow-up is necessary to confirm its long-term safety.

Large vestibular schwannomas treated by Gamma Knife surgery: long-term outcomes

OBJECTnAlthough radiosurgery has been well accepted as a treatment for small- to medium-sized vestibular schwannomas (VSs), its application in the treatment of large VSs remains controversial because of unfavorable effects such as tumor swelling and potential compression of the brainstem. The authors present a retrospective study spanning 17 years, during which 21 patients underwent Gamma Knife surgery (GKS) for large VSs. Long-term outcomes are reported, and possible factors affecting tumor responses to GKS are analyzed.nnnMETHODSnFive hundred thirteen patients harboring VSs underwent GKS between March 1993 and October 2009. A large VS was defined as a tumor whose diameter was > 3 cm. This paper focuses on 21 patients who harbored large VSs ranging in volume from 12.7 to 25.2 cm(3) (mean 17.3 cm(3)) and were treated by GKS. Fourteen of these patients had undergone 1 or more craniotomies previously to remove the tumor. Seven patients underwent GKS alone because of patient preference or a poor clinical condition that precluded microsurgery with general anesthesia. The mean radiation dose directed to the tumor ranged from 15 to 17.5 Gy. The mean radiation dose prescribed to the tumor margin was 11.9 Gy (range 11-14 Gy). The mean follow-up period was 66 months (range 12-155 months), and the median follow-up period was 53 months.nnnRESULTSnThe tumor control rate was 90.5% (19 of 21 lesions). No deterioration in facial nerve or trigeminal nerve function was noted. Disturbances in balance (some temporary) occurred in 5 patients. Three of the 21 patients developed initial tumor swelling, which required minor surgical interventions, including aspiration using an Ommaya reservoir or placement of a ventriculoperitoneal shunt. All 3 patients recovered satisfactorily after aspiration of an enlarging cyst or ventriculoperitoneal shunt placement. There was no significant correlation between tumor control and the following factors: patient age or sex, tumor volume, radiation dose, previous operation, presence of brainstem compression, petrous bone invasion, T2 signal ratio between tumor and brainstem, and presence of a cyst. However, there was a significant correlation between the T2 signal ratio between tumor and brainstem and the duration of tumor swelling (p = 0.003).nnnCONCLUSIONSnTreatment of large VSs remains a challenge to neurosurgeons regardless of whether they perform microsurgery or radiosurgery. Control of tumor growth and preservation of neurological function are the main goals of treatment. Although delayed microsurgery was required in 2 patients (9.5%), the satisfactory tumor control rate and excellent preservation of facial and trigeminal nerve function are the great advantages of radiosurgery. Radiosurgery is not only a practical treatment for patients with small- to medium-sized VSs, but it is also an excellent tool for treating larger tumors up to 25 cm(3). In selected cases, radiosurgery plays an important role in treating large VSs with satisfactory results.

Gamma Knife surgery for craniopharyngioma: report on a 20-year experience

OBJECTnAlthough craniopharyngiomas are benign intracranial tumors, their high recurrence rates and intimate associations with surrounding neurovascular structures make gross tumor resection challenging. Stereotactic radiosurgery has been introduced as a valuable adjuvant therapy for recurrent or residual craniopharyngiomas. However, studies with large patient populations documenting long-term survival and progression-free survival rates are rare in the literature. The current study aims to report the long-term radiosurgical results and to define the prognostic factors in a large cohort of patients with a craniopharyngioma.nnnMETHODSnA total of 137 consecutive patients who underwent 162 sessions of Gamma Knife surgery (GKS) treatments at the Taipei Veterans General Hospital between 1993 and 2012 were analyzed. The patients median age was 30.1 years (range 1.5-84.9 years), and the median tumor volume was 5.5 ml (range 0.2-28.4 ml). There were 23 solid (16.8%), 23 cystic (16.8%), and 91 mixed solid and cystic (66.4%) craniopharyngiomas. GKS was indicated for residual or recurrent craniopharyngiomas. The median radiation dose was 12 Gy (range 9.5-16.0 Gy) at a median isodose line of 55% (range 50%-78%).nnnRESULTSnAt a median imaging follow-up of 45.7 months after GKS, the rates of tumor control were 72.7%, 73.9%, and 66.3% for the solid, cystic, and mixed tumors, respectively. The actuarial progression-free survival rates plotted by the Kaplan-Meier method were 70.0% and 43.8% at 5 and 10 years after radiosurgery, respectively. After repeated GKS, the actuarial progression-free survival rates were increased to 77.3% and 61.2% at 5 and 10 years, respectively. The overall survival rates were 91.5% and 83.9% at the 5- and 10-year follow-ups, respectively. Successful GKS treatment can be predicted by tumor volume (p = 0.011). Among the 137 patients who had clinical follow-up, new-onset or worsened pituitary deficiencies were detected in 11 patients (8.0%). Two patients without tumor growth had a worsened visual field, and 1 patient had a new onset of third cranial nerve palsy.nnnCONCLUSIONSnThe current study suggests that GKS is a relatively safe modality for the treatment of recurrent or residual craniopharyngiomas, and it is associated with improved tumor control and reduced in-field recurrence rates. Acceptable rates of complications occurred.

AVM Radiosurgery: Where is the Volume Limit?

To evaluate the role of radiosurgery for large AVM (nidus volume > 8 ml). 200 cerebral AVM patients treated by Gamma Knife radiosurgery constituted the study database. Of them, 90 had a nidus volume > 8 ml. 38 of the 90 patients who fulfilled the following criteria were enrolled in result analysis. They were either treated more than 24 months ago or proved cured at any time earlier than 24 months. Grades of the AVM were II/2, III/11, IV/20, V/5 (Spetzler-Martin grading system). Integrated stereotaxic MR and stereotaxic x-ray angiography were used for treatment guidance. Volumes of the AVM nidi of the 38 patients were 8∼26 ml, median 11 ml. The prescribed mean maximum and minimum irradiation doses to the delineated AVM nidi were 36 Gy and 18 Gy, respectively. 21 patients were cured of AVM at 18∼36, mean 23 months, after radiosurgery. Almost complete obliteration occurred in 6 patients at 24∼46, mean 37 months, and subtotal obliteration occurred in 11 patients at 27∼60, mean 38 months, after radiosurgery. Nidus volume, not AVM grading, had an impact on the cure rate of AVM radiosurgery. T2-weighted high signals in the vicinity of the AVM were observed in 32 of 38 patients. Minor neurological deficits occurred in 3 patients. Re-bleeding occurred in 3 patients during the follow-up periods. Gamma Knife radiosurgery is currently an effective treatment alternative for large AVM, up to a nidus volume of 21 ml. The waiting time for complete obliteration of large AVM appears to be longer than for small ones. Nidus volume is the most decisive factor in radiosurgery of large AVM. Application of MR improves the conformity of treatment volume in AVM radiosurgery. The improvement minimizes the irradiation volumes and makes radiosurgery for large AVM safer.

Gamma Knife surgery for clival epidural-osseous dural arteriovenous fistulas

OBJECTIVE Clival epidural-osseous dural arteriovenous fistula (DAVF) is often associated with a large nidus, multiple arterial feeders, and complex venous drainage. In this study the authors report the outcomes of clival epidural-osseous DAVFs treated using Gamma Knife surgery (GKS). METHODS Thirteen patients with 13 clival epidural-osseous DAVFs were treated with GKS at the authors institution between 1993 and 2015. Patient age at the time of GKS ranged from 38 to 76 years (median 55 years). Eight DAVFs were classified as Cognard Type I, 4 as Type IIa, and 1 as Type IIa+b. The median treatment volume was 17.6 cm3 (range 6.2-40.3 cm3). The median prescribed margin dose was 16.5 Gy (range 15-18 Gy). Clinical and radiological follow-ups were performed at 6-month intervals. Patient outcomes after GKS were categorized as 1) complete improvement, 2) partial improvement, 3) stationary, and 4) progression. RESULTS All 13 patients demonstrated symptomatic improvement, and on catheter angiography 12 of the 13 patients had complete obliteration and 1 patient had partial obliteration. The median follow-up period was 26 months (range 14-186 months). The median latency period from GKS to obliteration was 21 months (range 8-186 months). There was no intracranial hemorrhage during the follow-up period, and no deaths occurred. Two adverse events were observed following treatment, and 2 patients required repeat GKS treatment with eventual complete obliteration. CONCLUSIONS Gamma Knife surgery offers a safe and effective primary or adjuvant treatment modality for complex clival epidural-osseous DAVFs. All patients in this case series demonstrated symptomatic improvement, and almost all patients attained complete obliteration.