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Huai-che Yang, Hideyuki Kano, Nasir Raza Awan, L. Dade Lunsford, Ajay Niranjan, John C. Flickinger, Josef Novotny Jr., Jagdish P. Bhatnagar and Douglas Kondziolka

Object

Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium-sized vestibular schwannomas. To assess the potential role of SRS in larger tumors, the authors reviewed their recent experience.

Methods

Between 1994 and 2008, 65 patients with vestibular schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had previously undergone resection.

Results

The median follow-up duration was 36 months (range 1–146 months). At the first planned imaging follow-up at 6 months, 5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%) were smaller. Two patients (3%) underwent resection within 6 months due to progressive symptoms. Two years later, with 63 tumors overall after the 2 post-SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%) tumors had a volume reduction of 10–50%, 18 (29%) were stable in volume (volume change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients with serviceable hearing before SRS still had serviceable hearing after SRS more than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%) trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis, patients who had a previous resection (p = 0.010), those with a tumor volume exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had less likelihood of tumor control after SRS.

Conclusions

Although microsurgical resection remains the primary management choice in patients with low comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm and without significant mass effect can be managed satisfactorily with Gamma Knife radiosurgery.

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Kyung-Jae Park, Hideyuki Kano, Douglas Kondziolka, Ajay Niranjan, John C. Flickinger and L. Dade Lunsford

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 cm3 (range 0.7–5.9 cm3). 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 cm3) 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.

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Donald N. Liew, Hideyuki Kano, Douglas Kondziolka, David Mathieu, Ajay Niranjan, John C. Flickinger, John M. Kirkwood, Ahmad Tarhini, Stergios Moschos and L. Dade Lunsford

Object

To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from melanoma, the authors assessed clinical outcomes and prognostic factors for survival and tumor control.

Methods

The authors reviewed 333 consecutive patients with melanoma who underwent SRS for 1570 brain metastases from cutaneous and mucosal/acral melanoma. The patient population consisted of 109 female and 224 male patients with a median age of 53 years. Two hundred eleven patients (63%) had multiple metastases. One hundred eighteen patients (35%) underwent whole-brain radiation therapy (WBRT). The target volume ranged from 0.1 cm3 to 37.2 cm3. The median marginal dose was 18 Gy.

Results

Actuarial survival rates were 70% at 3 months, 47% at 6 months, 25% at 12 months, and 10% at 24 months after radiosurgery. Factors associated with longer survival included controlled extracranial disease, better Karnofsky Performance Scale score, fewer brain metastases, no prior WBRT, no prior chemotherapy, administration of immunotherapy, and no intratumoral hemorrhage before radiosurgery. The median survival for patients with a solitary brain metastasis, controlled extracranial disease, and administration of immunotherapy after radiosurgery was 22 months. Sustained local tumor control was achieved in 73% of the patients. Sixty-four (25%) of 259 patients who had follow-up imaging after SRS had evidence of delayed intratumoral hemorrhage. Sixteen patients underwent a craniotomy due to intratumoral hemorrhage. Seventeen patients (6%) had asymptomatic and 21 patients (7%) had symptomatic radiation effects. Patients with ≤ 8 brain metastases, no prior WBRT, and the recursive partitioning analysis Class I had extended survivals (median 54.3 months).

Conclusions

Stereotactic radiosurgery is an especially valuable option for patients with controlled systemic disease even if they have multiple metastatic brain tumors.

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Douglas Kondziolka, Hideyuki Kano, Gillian L. Harrison, Huai-che Yang, Donald N. Liew, Ajay Niranjan, Adam M. Brufsky, John C. Flickinger and L. Dade Lunsford

Object

To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from breast cancer, the authors assessed clinical outcomes and prognostic factors for survival.

Methods

The records from 350 consecutive female patients who underwent SRS for 1535 brain metastases from breast cancer were reviewed. The median patient age was 54 years (range 19–84 years), and the median number of tumors per patient was 2 (range 1–18 lesions). One hundred seventeen patients (33%) had a single metastasis to the brain, and 233 patients (67%) had multiple brain metastases. The median tumor volume was 0.7 cm3 (range 0.01–48.9 cm3), and the median total tumor volume for each patient was 4.9 cm3 (range 0.09–74.1 cm3).

Results

Overall survival after SRS was 69%, 49%, and 26% at 6, 12, and 24 months, respectively, with a median survival of 11.2 months. Factors associated with a longer survival included controlled extracranial disease, a lower recursive partitioning analysis (RPA) class, a higher Karnofsky Performance Scale score, a smaller number of brain metastases, a smaller total tumor volume per patient, the presence of deep cerebral or brainstem metastases, and HER2/neu overexpression. Sustained local tumor control was achieved in 90% of the patients. Factors associated with longer progression-free survival included a better RPA class, fewer brain metastases, a smaller total tumor volume per patient, and a higher tumor margin dose. Symptomatic adverse radiation effects occurred in 6% of patients. Overall, the condition of 82% of patients improved or remained neurologically stable.

Conclusions

Stereotactic radiosurgery was safe and effective in patients with brain metastases from breast cancer and should be considered for initial treatment.

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Yoshio Arai, Hideyuki Kano, L. Dade Lunsford, Josef Novotny Jr., Ajay Niranjan, John C. Flickinger and Douglas Kondziolka

Object

The object of this study was to determine whether the radiation dose rate affects clinical outcomes in patients who undergo stereotactic Gamma Knife surgery (GKS) to manage typical trigeminal neuralgia (TN).

Methods

The authors retrospectively studied pain relief in 165 patients with medically intractable TN, who underwent 80-Gy GKS using a single 4-mm collimator between 1994 and 2005. No patient had received prior radiation treatment. The measured relative helmet output factor of the Gamma Knife was 0.8 throughout this interval, and the dose rate varied from 1.21 Gy/minute to 3.74 Gy/minute (median 2.06 Gy/minute). Irradiation time varied from 26.73 to 95.11 minutes. The authors divided patients into a low-dose-rate (LDR) group, in which the dose rate varied from 1.21 to 2.05 Gy/minute, and a high-dose-rate (HDR) group, in which the dose rate varied from 2.06 to 3.74 Gy/minute. Post-GKS, the patients' pain control was determined using the Barrow Neurological Institute (BNI) pain scale.

There was no statistically significant difference between groups with respect to history of prior microvascular decompression (p = 0.410) or peripheral neuroablative procedures (p = 0.583). The length of symptoms in patients varied from 3 to 414 months with a median of 84 months (p = 0.698). Median follow-up was 26 months with a maximum of 139 months.

Results

Initial pain relief was obtained in 71% of patients in the LDR group and 78% in the HDR group (p = 0.547). Patients who initially obtained improved pain relief (BNI Scores I–IIIa) after GKS maintained pain control for median durations of 52 months (LDR group) and 54 months (HDR group) (p = 0.403). New or increased facial sensory dysfunction was found in 14.5% of patients in the LDR group and in 19.3% of patients in the HDR group (p = 0.479).

Conclusions

The authors found that the GKS dose rate did not affect pain control or morbidity within the range of 1.21–3.74 Gy/minute. Cobalt 60 source decay did not affect outcomes of GKS for TN pain management, even for dose rates approximating a 2-half-life decay of the isotope.

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Editorial

Arteriovenous malformations

Douglas Kondziolka

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Editorial

The value of a postoperative computed tomography scan

Douglas Kondziolka

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Hideyuki Kano, Huai-che Yang, Douglas Kondziolka, Ajay Niranjan, Yoshio Arai, John C. Flickinger and L. Dade Lunsford

Object

To evaluate the role of stereotactic radiosurgery (SRS) in patients with recurrent or residual intracranial ependymomas after resection and fractionated radiation therapy (RT), the authors assessed overall survival, distant tumor relapse, progression-free survival (PFS), and complications.

Methods

The authors retrospectively reviewed the records of 21 children with ependymomas who underwent SRS for 32 tumors. There were 17 boys and 4 girls with a median age of 6.9 years (range 2.9–17.2 years) in the patient population. All patients underwent resection of an ependymoma followed by cranial or neuraxis (if spinal metastases was confirmed) RT. Eleven patients had adjuvant chemotherapy. Twelve patients had low-grade ependymomas (17 tumors), and 9 patients had anaplastic ependymomas (15 tumors). The median radiosurgical target volume was 2.2 cm3 (range 0.1–21.4 cm3), and the median dose to the tumor margin was 15 Gy (range 9–22 Gy).

Results

Follow-up imaging demonstrated therapeutic control in 23 (72%) of 32 tumors at a mean follow-up period of 27.6 months (range 6.1–72.8 months). Progression-free survival after the initial SRS was 78.4%, 55.5%, and 41.6% at 1, 2, and 3 years, respectively. Factors associated with a longer PFS included patients without spinal metastases (p = 0.033) and tumor volumes < 2.2 cm3 (median tumor volume 2.2 cm3, p = 0.029). An interval ≥18 months between RT and SRS was also associated with longer survival (p = 0.035). The distant tumor relapse rate despite RT and SRS was 33.6%, 41.0%, and 80.3% at 1, 2, and 3 years, respectively. Factors associated with a higher rate of distant tumor relapse included patients who had spinal metastases before RT (p = 0.037), a fourth ventricle tumor location (p = 0.002), and an RT to SRS interval < 18 months (p = 0.015). The median survival after SRS was 27.6 months (95% CI 19.33–35.87 months). Overall survival after SRS was 85.2%, 53.2%, and 23.0% at 1, 2, and 3 years, respectively. Adverse radiation effects developed in 2 patients (9.5%).

Conclusions

Stereotactic radiosurgery offers an additional option beyond repeat surgery or RT in pediatric patients with residual or recurrent ependymomas after initial management. Patients with smaller-volume tumors and a later recurrence responded best to radiosurgery.

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Glenn T. Gobbel, Douglas Kondziolka, Wendy Fellows-Mayle and Martin Uram

Object

Cell transplantation has shown promise for the treatment of various neurological disorders, but the factors that influence cell survival and integration following transplantation are poorly understood. In fact, little is known regarding how simple but potentially critical variables, including the method of cellular preparation and administration, might affect transplant success. The goal of the present study was to determine the impact of time between tissue preparation and implantation on cellular viability. Time can vary with cell preparation, delivery to the operating room, and surgical technique. This study was also designed to evaluate the sensitivity of various methods of assessing implant viability.

Methods

Cell lines of neural progenitor cells and bone marrow stromal cells were generated from healthy adult mice. On the day of experimentation, the cells were collected, suspended in a balanced salt solution, and sequentially assessed for viability for up to 3.5 hours based on their appearance under phase-contrast microscopy, their ability to retain a fluorescent dye, and their attachment to a cultivation surface for 24 hours.

Results

When viability was measured based on the ability of cells to retain a fluorescent dye, there was a decrease in viability of 10–15% each hour. Based on the ability of the cells to attach to a culture surface and grow for 24 hours, viability decreased more rapidly at approximately 20% per hour. In addition, only about one-third of the cells judged viable based on phase-contrast microscopy or acute dye retention were found to be viable based on plating, and only 10% of the cells initially judged as viable were still capable of survival after 3 hours in suspension.

Conclusions

The authors' results indicate that that there can be significant losses in viability between preparation and implantation and that more sophisticated methods of evaluation, such as the ability of cells to attach to a substrate and grow, may be required to detect decreases in viability. The time between preparation and implantation will be an important factor in clinical trial design.

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Edward A. Monaco III, Aftab A. Khan, Ajay Niranjan, Hideyuki Kano, Ramesh Grandhi, Douglas Kondziolka, John C. Flickinger and L. Dade Lunsford

Object

The authors performed a retrospective review of prospectively collected data to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) for the treatment of patients harboring symptomatic solitary cavernous malformations (CMs) of the brainstem that bleed repeatedly and are high risk for resection.

Methods

Between 1988 and 2005, 68 patients (34 males and 34 females) with solitary, symptomatic CMs of the brainstem underwent Gamma Knife surgery. The mean patient age was 41.2 years, and all patients had suffered at least 2 symptomatic hemorrhages (range 2–12 events) before radiosurgery. Prior to SRS, 15 patients (22.1%) had undergone attempted resection. The mean volume of the malformation treated was 1.19 ml, and the mean prescribed marginal radiation dose was 16 Gy.

Results

The mean follow-up period was 5.2 years (range 0.6–12.4 years). The pre-SRS annual hemorrhage rate was 32.38%, or 125 hemorrhages, excluding the first hemorrhage, over a total of 386 patient-years. Following SRS, 11 hemorrhages were observed within the first 2 years of follow-up (8.22% annual hemorrhage rate) and 3 hemorrhages were observed in the period after the first 2 years of follow-up (1.37% annual hemorrhage rate). A significant reduction (p < 0.0001) in the risk of brainstem CM hemorrhages was observed following radiosurgical treatment, as well as in latency period of 2 years after SRS (p < 0.0447). Eight patients (11.8%) experienced new neurological deficits as a result of adverse radiation effects following SRS.

Conclusions

The results of this study support a role for the use of SRS for symptomatic CMs of the brainstem, as it is relatively safe and appears to reduce rebleeding rates in this high-surgical-risk location.