Kyung Jae Park

Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: A multicenter study

OBJECT Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. METHODS Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). RESULTS Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. CONCLUSIONS Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations

OBJECT The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery. METHODS In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm(3). Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8-13.8 months). The median target volume was 11.5 cm(3) (range 4.0-26 cm(3)) in the first-stage SRS and 9.5 cm(3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both stages. RESULTS In 17 patients, AVM obliteration was confirmed after 2-4 SRS procedures at a median follow-up of 87 months (range 0.4-209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33-113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0-1, 1-5, and 5-10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS. CONCLUSIONS Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.

Long-term outcomes after gamma knife stereotactic radiosurgery for nonfunctional pituitary adenomas.

BACKGROUND Nonfunctional pituitary adenomas (NFPAs) represent approximately 50% of all pituitary tumors. OBJECTIVE To evaluate the long-term outcomes of stereotactic radiosurgery for NFPAs. METHODS We evaluated the management outcomes of Gamma Knife radiosurgery in 125 patients with NFPAs over an interval of 22 years. The median patient age was 54 years (range, 16-88 years). One hundred ten patients (88%) had residual or recurrent tumors after ≥ 1 surgical procedures, and 17 (14%) had undergone prior fractionated radiation therapy. The median target volume was 3.5 cm3 (range, 0.4-28.1 cm3), and the median tumor margin dose was 13.0 Gy (range, 10-25 Gy). RESULTS Tumor volume decreased in 66 patients (53%), remained stable in 46 (37%), and increased in 13 (10.4%) during a median of 62 months (maximum, 19 years) of imaging follow-up. The actuarial tumor control rates at 1, 5, and 10 years were 99%, 94%, and 76%, respectively. Factors associated with a reduced progression-free survival included larger tumor volume (≥ 4.5 cm3) and ≥ 2 prior recurrences. Of 88 patients with residual pituitary function, 21 (24%) suffered new hormonal deficits at a median of 24 months (range, 3-114 months). Prior radiation therapy increased the risk of developing new pituitary hormonal deficits. One patient (0.8%) had a decline in visual function, and 2 (1.6%) developed new cranial neuropathies without tumor progression. CONCLUSION Stereotactic radiosurgery can provide effective management for patients with newly diagnosed NFPAs and for those after prior resection and/or radiation therapy.

Aneurysms Increase the Risk of Rebleeding After Stereotactic Radiosurgery for Hemorrhagic Arteriovenous Malformations

Background and Purpose— The purpose of this study was to define the risk of rebleeding after stereotactic radiosurgery (SRS) for hemorrhagic arteriovenous malformations with or without associated intracranial aneurysms. Methods— Between 1987 and 2006, we performed Gamma Knife SRS on 996 patients with brain arteriovenous malformations; 407 patients had sustained an arteriovenous malformation hemorrhage. Sixty-four patients (16%) underwent prior embolization and 84 (21%) underwent prior surgical resection. The median target volume was 2.3 mL (range, 0.1–20.7 mL). The median margin dose was 20 Gy (range, 13.5–27 Gy). Results— The overall rate of total obliteration defined by angiography or MRI was 56%, 77%, 80%, and 82% at 3, 4, 5, and 10 years, respectively. Before obliteration, 33 patients (8%) sustained an additional hemorrhage after SRS. The overall annual hemorrhage rate until obliteration after SRS was 1.3%. The presence of a patent aneurysm was significantly associated with an increased rehemorrhage risk after SRS (annual hemorrhage rate, 6.4%) compared with patients with a clipped or embolized aneurysm (annual hemorrhage rate, 0.8%; P=0.033). Conclusions— When an aneurysm is identified in patients with arteriovenous malformations selected for SRS, additional endovascular or surgical strategies should be considered to reduce the risk of bleeding during the latency interval.

Gamma Knife surgery for subependymal giant cell astrocytomas: Clinical article

OBJECT The authors report their experience of using Gamma Knife surgery (GKS) in patients with subependymal giant cell astrocytoma (SEGA). METHODS Over a 20-year period, the authors identified 6 patients with SEGAs who were eligible for GKS. The median patient age was 16.5 years (range 7-55 years). In 4 patients, GKS was used as a primary management therapy. One patient underwent radiosurgery for recurrent tumors after prior resection, and in 1 patient GKS was used as an adjunct after subtotal resection. The median tumor volume at GKS was 2.75 cm(3) (range 0.7-5.9 cm(3)). A median radiation dose of 14 Gy (range 11-20 Gy) was delivered to the tumor margin. RESULTS The median follow-up duration was 73 months (range 42-90 months). Overall local tumor control was achieved in 4 tumors (67%) with progression-free periods of 24, 42, 57, and 66 months. Three tumors regressed and one remained unchanged. In 2 patients the tumors progressed, and in 1 of these patients the lesion was managed by repeated GKS with subsequent tumor regression. The other relatively large tumor (5.9 cm(3)) was excised 9 months after GKS. The progression-free period for all GKS-managed tumors varied from 9 to 66 months. There were no cases of hydrocephalus or GKS-related morbidity. CONCLUSIONS Gamma Knife surgery may be an additional minimally invasive management option for SEGA in a patient who harbors a small but progressively enlarging tumor when complete resection is not safely achievable. It may also benefit patients with a residual or recurrent tumor that has progressed after surgery.

Repeat gamma knife radiosurgery for trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) may recur after treatment by gamma knife stereotactic radiosurgery (GKSR). OBJECTIVE: To evaluate management outcomes in patients who underwent repeat GKSR for TN. METHODS: The authors reviewed their experience with repeat GKSR in 119 patients with recurrent TN. The median patient age was 74 years (range, 34-96 years). The median interval between procedures was 26 months. The median target dose for repeat GKSR was 70 Gy (range, 50-90 Gy) and the median cumulative dose was 145 Gy (range, 120-170 Gy). The median follow-up was 48 months (range, 6-187 months) after repeat GKSR. RESULTS: After repeat GKSR, 87% of patients achieved initial pain relief (Barrow Neurological Institute pain score I–IIIb). Pain relief was maintained in 87.8% at 1 year, 69.8% at 3 years, and 44.2% at 5 years. Facial sensory dysfunction occurred in 21% of patients within 18 months after GKSR. Longer pain relief was observed in patients who had recurrent pain in a reduced pain distribution of the face compared with the pain distribution at the time of their initial GKSR, and in those who developed additional trigeminal sensory loss after a repeat procedure. A cumulative edge of brainstem dose ≥ 44 Gy was more likely to be associated with the development of sensory loss. CONCLUSION: Repeat GKSR provides a similar rate of pain relief as the first procedure. The best responses were observed in patients who had good pain control after the first procedure and those who developed new sensory dysfunction in the affected trigeminal distribution.

Stereotactic radiosurgery after embolization for arteriovenous malformations

We sought to define the long-term benefits and risks of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) patients who underwent prior embolization. Between 1987 and 2006, we performed Gamma Knife® SRS on 120 patients with AVM who underwent embolization followed by SRS. Sixty-four patients (53%) had at least 1 prior hemorrhage. The median number of embolizations varied from 1 to 5. The median target volume was 6.6 cm3 (range, 0.2-26.3 cm3). The median margin dose was 18 Gy (range, 13.5-25 Gy). After embolization, 25 patients (21%) developed symptomatic neurological deficits. The overall rates of total obliteration documented by either angiography or magnetic resonance imaging were 35, 53, 55 and 59% at 3, 4, 5 and 10 years, respectively. Nine patients (8%) had a hemorrhage during the latency interval and 7 patients died due to hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8, 3.5, 5.4, 7.7 and 7.7% at 1, 2, 3, 5 and 10 years, respectively. Permanent neurological deficits due to adverse radiation effects developed in 3 patients (2.5%) after SRS. Using a case-match control technique, we found that embolization prior to SRS was associated with a lower rate of total obliteration (p=0.028) in comparison to radiosurgery alone. In this 20-year experience, we found that prior embolization reduced the rate of total obliteration after SRS and latency interval hemorrhage risks were not affected by prior embolization. In the future, the role of embolization after SRS should be explored.

Supratentorial Arachnoid Cyst Located in the Brain Parenchyma: Case Report

BACKGROUND AND IMPORTANCE:Arachnoid cysts have not been reported to be located within the brain parenchyma. We present a case of an arachnoid cyst that was contained entirely within the right frontal lobe devoid of communication with the subarachnoid space and ventricle. CLINICAL PRESENTATION:A 65-year-old woman presented with a 1-year history of progressive headache and nausea. Computed tomographic and magnetic resonance imagining scans showed a well-defined, nonenhancing mass measuring 5 × 5 × 3.5 cm in the right frontal lobe. The mass appeared to be contained entirely within the brain parenchyma. The patient underwent a right frontal craniotomy, at which time the cystic mass was identified in the brain parenchyma without any communication with the arachnoid space. The cyst contained a clear fluid, and its wall was excised. The fluid contents demonstrated a composition similar to that of normal cerebrospinal fluid. Histological and immunohistochemical examinations of the cyst wall were compatible with the diagnosis of an arachnoid cyst. Postoperatively, the symptoms of the patient resolved, and no recurrence was observed up to 6 months after removal. CONCLUSION:The present case showed an intraparenchymal arachnoid cyst arising in the frontal lobe. Although the etiology is not known, an arachnoid cyst should be included in the differential diagnosis of primary intracerebral cysts.

Multistaged volumetric management of large arteriovenous malformations.

We sought to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume AVMs unsuitable for surgery. Two decades ago, we prospectively began to stage anatomical components in order to deliver higher single doses to AVMs>10 cm3 in volume. Forty-seven patients with large AVMs underwent volume-staged SRS. The median interval between the two SRS procedures was 4.9 months (range, 3-14 months). The median nidus volume was 11.5 cm3 (range, 4.0-26 cm3) in the first stage of SRS and 9.5 cm3 in the second. The median margin dose was 16 Gy (range, 13-18 Gy) for both SRS stages. The actuarial rates of total obliteration after 2-staged SRS were 7, 20, 28 and 36% at 3, 4, 5 and 10 years, respectively. Sixteen patients needed additional SRS at a median interval of 61 months (range, 33-113 months) after the 2-staged SRS. After repeat procedure(s), the eventual obliteration rate was 66% at 10 years. The cumulative rates of AVM hemorrhage after SRS were 4.3, 8.6, 13.5 and 36.0% at 1, 2, 5 and 10 years, respectively. Symptomatic adverse radiation effects were detected in 13% of patients. Successful prospective volume-staged SRS for large AVMs unsuitable for surgery requires 2 or more procedures to complete the obliteration process. Patients remain at risk for hemorrhage if the AVM persists.

Combining Brain Diagnosis and Therapy in a Single Strategy: The Safety, Reliability, and Cost Implications Using Same-Day versus Separate-Day Stereotactic Procedures

Background: A therapeutic radiosurgery procedure usually follows a separate diagnostic stereotactic procedure after days or weeks. Objectives: To define the clinical reliability, safety, and cost implications of same-day diagnostic stereotactic biopsy and therapeutic radiosurgery. Methods: During an 8-year interval, 26 patients underwent stereotactic brain biopsy followed by immediate therapeutic stereotactic radiosurgery in a single-day combined procedure. The intraoperative diagnosis was determined using standard histopathological techniques. Diagnostic accuracy, hospital costs, and contribution margins associated with this treatment strategy were compared to those of 26 case-matched patients (controls) who underwent a stereotactic diagnostic procedure followed by a separate-day outpatient SRS procedure within 6 weeks during the same time interval. Results: The intraoperative diagnosis correlated with the final histopathological diagnosis in 96% of the patients. Biopsy-related morbidity did not occur in this series. The mean total costs of same-day patients was significantly lower than the costs of patients who had two-stage procedures (USD 9,077 ± 2,366 vs. 11,284 ± 3,025; p = 0.008). The net contribution to the hospital margin of USD 13,736 was not significantly different between the two management strategies. Conclusions: The advantages of the same-day approach included a single stereotactic head frame application, reduced total admission time, consecutive histopathological diagnosis and therapy in a single hospital admission, and reduced total hospital costs. For patients who are highly suspected to have a brain tumor for which SRS is likely to be an effective therapeutic strategy, same-day diagnostic stereotactic biopsy followed by therapeutic SRS proved to be a safe, reliable, and cost-effective management strategy.