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Hideyuki Kano, Ajay Niranjan, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

Object

To evaluate outcome predictors after stereotactic radiosurgery (SRS) in patients with trigeminal schwannomas, the authors compared tumor control, functional preservation, and complications with tumor grade, tumor volume, patient age, and tumor imaging characteristics.

Methods

The records of 33 consecutive patients with trigeminal schwannoma treated via Gamma Knife surgery were retrospectively reviewed. The median patient age was 49.5 years (range 15.1–82.5 years). Eleven patients had undergone prior tumor resection. Two patients had neurofibromatosis Type 2. Lesions were classified as root type (6 tumors), ganglion type (17 tumors), and dumbbell type (10 tumors) based on their location. The median radiosurgery target volume was 4.2 cm3 (range 0.5–18.0 cm3), and the median dose to the tumor margin was 15.0 Gy (range 12–20 Gy).

Results

At an average of 6 years (range 7.2–147.9 months), the rate of progression-free survival (PFS) at 1, 5, and 10 years after SRS was 97.0, 82.0, and 82.0%, respectively. Factors associated with improved PFS included female sex, smaller tumor volume, and a root or ganglion tumor type. Neurological symptoms or signs improved in 11 (33.3%) of 33 patients and were unchanged in 19 (57.6%). Three patients (9.1%) had symptomatic disease progression. Patients who had not undergone a prior tumor resection were significantly more likely to show improvement in neurological symptoms or signs.

Conclusions

Stereotactic radiosurgery is an effective and minimally invasive management option in patients with residual or newly diagnosed trigeminal schwannomas. Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment.

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Seong-Hyun Park, Hideyuki Kano, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

Object

To assess the long-term outcomes of stereotactic radiosurgery (SRS) for cerebellopontine angle (CPA) meningiomas, the authors retrospectively reviewed data from a 20-year experience. They evaluated progression-free survival as well as improvement, stabilization, or deterioration in clinical symptoms.

Methods

Seventy-four patients with CPA meningiomas underwent SRS involving various Gamma Knife technologies between 1990 and 2010. The most common presenting symptoms were dizziness or disequilibrium, hearing loss, facial sensory dysfunction, and headache. The median tumor volume was 3.0 cm3 (range 0.3–17.1 cm3), and the median radiation dose to the tumor margin was 13 Gy (range 11–16 Gy). The median follow-up period was 40 months (range 4–147 months).

Results

At last imaging follow-up, the tumor volume had decreased in 46 patients (62%), remained stable in 26 patients (35%), and increased in 2 patients (3%). The progression-free survival after SRS was 98% at 1 year, 98% at 3 years, and 95% at 5 years. At the last clinical follow-up, 23 patients (31%) showed neurological improvement, 43 patients (58%) showed no change in symptoms or signs, and 8 patients (11%) had worsening symptoms or signs. The neurological improvement rate after SRS was 16% at 1 year, 31% at 3 years, and 40% at 5 years. The post-SRS deterioration rate was 5% at 1 year, 10% at 3 years, and 16% at 5 years. A multivariate analysis demonstrated that trigeminal neuralgia was the symptom most likely to worsen after SRS (HR 0.08, 95% CI 0.02–0.31; p = 0.001). Asymptomatic peritumoral edema occurred in 4 patients (5%) after SRS, and symptomatic adverse radiation effects developed in 7 patients (9%).

Conclusions

Stereotactic radiosurgery for CPA meningiomas provided a high tumor control rate and relatively low risk of ARE. Tumor compression of the trigeminal nerve by a CPA meningioma resulted in an increased rate of facial pain worsening in this patient experience.

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Hideyuki Kano, Ajay Niranjan, Aftab Khan, John C. Flickinger, Douglas Kondziolka, Frank Lieberman, and L. Dade Lunsford

Object

In this study the authors evaluated the role of stereotactic radiosurgery (SRS) in the management of progressive or newly diagnosed small-volume oligodendrogliomas. Tumor control, survival, and complications were assessed in patients with oligodendroglioma who underwent Gamma Knife radiosurgery as a primary or adjuvant procedure.

Methods

The authors retrospectively reviewed 30 patients with oligodendroglioma (12 Grade II and 18 Grade III) who underwent SRS between 1992 and June 2006 at the University of Pittsburgh. The median patient age was 43.2 years (range 10.8–75.4 years). Twenty-four patients had previously undergone resection of the tumor, whereas tumors in 6 were diagnosed based on biopsy findings. The SRS was performed in 25 patients who had imaging-defined tumor progression despite prior fractionated radiation (22 patients) and/or chemotherapy (20 patients). The median target volume was 15.4 cm3 (range 0.07–48.7 cm3) and the median margin dose was 14.5 Gy (range 11–20 Gy).

Results

At an average of 39.2 months of follow-up (range 12–133 months), 17 patients were dead and 13 were living. The overall survival rates from diagnosis to 5 and 10 years were 90.9 and 68.2%, respectively, for Grade II and 52.1% at 5 years and 26.1% at 10 years for Grade III. Factors associated with an improved progression-free survival included lower tumor grade and smaller tumor volume. In 13 patients who had loss of heterozygosity testing, patients with 1p19q loss of heterozygosity had a significantly improved survival after diagnosis (p = 0.04).

Conclusions

The SRS modality is a minimally invasive additional option for patients with residual or recurrent oligodendrogliomas. It may also be considered as an alternative to initial resection in small-volume tumors located in the cortical brain region.

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L. Dade Lunsford, Aftab A. Khan, Ajay Niranjan, Hideyuki Kano, John C. Flickinger, and Douglas Kondziolka

Object

A retrospective study was conducted to reassess the benefit and safety of stereotactic radiosurgery (SRS) in patients with solitary cerebral cavernous malformations (CCMs) that bleed repeatedly and are poor candidates for surgical removal.

Methods

Between 1988 and 2005 at the University of Pittsburgh, the authors performed SRS in 103 evaluable patients (57 males and 46 females) with solitary symptomatic CCMs. The mean patient age was 39.3 years. Ninety-eight percent of these patients had experienced 2 or more hemorrhages associated with new neurological deficits. Seventeen patients (16.5%) had undergone attempted resection before radiosurgery. Ninety-three CCMs were located in deep brain structures and 10 were in subcortical lobar areas of functional brain importance. The median malformation volume was 1.31 ml, and the median tumor margin dose was 16 Gy.

Results

The follow-up ranged from 2 to 20 years. The annual hemorrhage rate—that is, a new neurological deficit associated with imaging evidence of a new hemorrhage—before SRS was 32.5%. After SRS 22 hemorrhages were observed within 2 years (10.8% annual hemorrhage rate) and 4 hemorrhages were observed after 2 years (1.06% annual hemorrhage rate). The risk of hemorrhage from a CCM was significantly reduced after radiosurgery (p < 0.0001). Overall, new neurological deficits due to adverse radiation effects following SRS developed in 14 patients (13.5%), with most occurring early in our experience. Modifications in technique (treatment volume within the T2-weighted MR imaging–defined margin, use of MR imaging, and dose reduction for CCM in critical brainstem locations) further reduced risks after SRS.

Conclusions

Data in this study provide further evidence that SRS is a relatively safe procedure that reduces the rebleeding rate for CCMs located in high-surgical-risk areas of the brain.

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Ajay Niranjan, Hideyuki Kano, Aditya Iyer, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

OBJECT

After initial standard of care management of glioblastoma multiforme (GBM), relatively few proven options remain for patients with unresected progressive tumor. Numerous reports describe the value of radiosurgery, yet this modality appears to remain underutilized. The authors analyzed the outcomes of early adjuvant stereotactic radiosurgery (SRS) for unresected tumor or later salvage SRS for progressive GBM. Radiosurgery was performed as part of the multimodality management and was combined with other therapies. Patients continued to receive additional chemotherapy after SRS and prior to progression being documented. In this retrospective analysis, the authors evaluated factors that affected patient overall survival (OS) and progression-free survival.

METHODS

Between 1987 and 2008 the authors performed Gamma Knife SRS in 297 patients with histologically proven GBMs. All patients had received prior fractionated radiation therapy, and 66% had undergone one or more chemotherapy regimens. Ninety-six patients with deep-seated unresectable GBMs underwent biopsy only. Of those in whom excision had been possible, resection was considered to be gross total in 68 and subtotal in 133. The median patient age was 58 years (range 23–89 years) and the median tumor volume was 14 cm3 (range 0.26–84.2 cm3). The median prescription dose delivered to the imaging-defined tumor margin was 15 Gy (range 9–25 Gy). The median follow-up duration was 8.6 months (range 1.1–173 months). Cox regression models were used to analyze survival outcomes. Variables examined included age, residual versus recurrent tumor, prior chemotherapy, time to first recurrence, SRS dose, and gross tumor volume.

RESULTS

The median survival times after radiosurgery and after diagnosis were 9.03 and 18.1 months, respectively. The 1-year and 2-year OS after SRS were 37.9% and 16.7%, respectively. The 1-year and 2-year OS after diagnosis were 76.2% and 30.8%, respectively. Using multivariate analysis, factors associated with improved OS after diagnosis were younger age (< 60 years) at diagnosis (p < 0.0001), tumor volume < 14 cm3 (p < 0.001), use of prior chemotherapy (p = 0.001), and radiosurgery at the time of recurrence (p < 0.0001). Multivariate analysis showed that younger age (p < 0.0001) and smaller tumor volume (< 14 cm3) (p = 0.001) were significantly associated with increased OS after SRS. Adverse radiation effects were seen in 69 patients (23%). Fifty-eight patients (19.5%) underwent additional resection after SRS. The median survivals after diagnosis for recursive partitioning analysis Classes III, IV and V+VI were 31.6, 20.8, and 16.7 months, respectively.

CONCLUSIONS

In this analysis 30% of a heterogeneous cohort of GBM patients eligible for SRS had an OS of 2 years. Radiosurgery at the time of tumor progression was associated with a median survival of 21.8 months. The role of radiosurgery for GBMs remains controversial. The findings in this study support the need for a funded and appropriately designed clinical trial that will provide a higher level of evidence regarding the future role of SRS for glioblastoma patients in whom disease has progressed despite standard management.

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Greg Bowden, Hideyuki Kano, Daniel Tonetti, Ajay Niranjan, John Flickinger, Yoshio Arai, and L. Dade Lunsford

Object

Sylvian fissure arteriovenous malformations (AVMs) present substantial management challenges because of the critical adjacent blood vessels and functional brain. The authors investigated the outcomes, especially hemorrhage and seizure activity, after stereotactic radiosurgery (SRS) of AVMs within or adjacent to the sylvian fissure.

Methods

This retrospective single-institution analysis examined the authors' experiences with Gamma Knife surgery for AVMs of the sylvian fissure in cases treated from 1987 through 2009. During this time, 87 patients underwent SRS for AVMs in the region of the sylvian fissure. Before undergoing SRS, 40 (46%) of these patients had experienced hemorrhage and 36 (41%) had had seizures. The median target volume of the AVM was 3.85 cm3 (range 0.1–17.7 cm3), and the median marginal dose of radiation was 20 Gy (range 13–25 Gy).

Results

Over a median follow-up period of 64 months (range 3–275 months), AVM obliteration was confirmed by MRI or angiography for 43 patients. The actuarial rates of confirmation of total obliteration were 35% at 3 years, 60% at 4 and 5 years, and 76% at 10 years. Of the 36 patients who had experienced seizures before SRS, 19 (53%) achieved outcomes of Engel class I after treatment. The rate of seizure improvement was 29% at 3 years, 36% at 5 years, 50% at 10 years, and 60% at 15 years. No seizures developed after SRS in patients who had been seizure free before treatment. The actuarial rate of AVM hemorrhage after SRS was 5% at 1, 5, and 10 years. This rate equated to an annual hemorrhage rate during the latency interval of 1%; no hemorrhages occurred after confirmed obliteration. No permanent neurological deficits developed as an adverse effect of radiation; however, delayed cyst formation occurred in 3 patients.

Conclusions

Stereotactic radiosurgery was an effective treatment for AVMs within the region of the sylvian fissure, particularly for smaller-volume AVMs. After SRS, a low rate of hemorrhage and improved seizure control were also evident.

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Greg Bowden, Hideyuki Kano, Daniel Tonetti, Ajay Niranjan, John Flickinger, and L. Dade Lunsford

Object

Arteriovenous malformations (AVMs) of the posterior fossa have an aggressive natural history and propensity for hemorrhage. Although the cerebellum accounts for the majority of the posterior fossa volume, there is a paucity of stereotactic radiosurgery (SRS) outcome data for AVMs of this region. The authors sought to evaluate the long-term outcomes and risks of cerebellar AVM radiosurgery.

Methods

This single-institution retrospective analysis reviewed the authors' experience with Gamma Knife surgery during the period 1987–2007. During this time 64 patients (median age 47 years, range 8–75 years) underwent SRS for a cerebellar AVM. Forty-seven patients (73%) presented with an intracranial hemorrhage. The median target volume was 3.85 cm3 (range 0.2–12.5 cm3), and the median marginal dose was 21 Gy (range 15–25 Gy).

Results

Arteriovenous malformation obliteration was confirmed by MRI or angiography in 40 patients at a median follow-up of 73 months (range 4–255 months). The actuarial rates of total obliteration were 53% at 3 years, 69% at 4 years, and 76% at 5 and 10 years. Elevated obliteration rates were statistically higher in patients who underwent AVM SRS without prior embolization (p = 0.005). A smaller AVM volume was also associated with a higher rate of obliteration (p = 0.03). Four patients (6%) sustained a hemorrhage during the latency period and 3 died. The cumulative rates of AVM hemorrhage after SRS were 6% at 1, 5, and 10 years. This correlated with an overall annual hemorrhage rate of 2.0% during the latency interval. One patient experienced a hemorrhage 9 years after confirmed MRI and angiographic obliteration. A permanent neurological deficit due to adverse radiation effects developed in 1 patient (1.6%) and temporary complications were seen in 2 additional patients (3.1%).

Conclusions

Stereotactic radiosurgery proved to be most effective for patients with smaller and previously nonembolized cerebellar malformations. Hemorrhage during the latency period occurred at a rate of 2.0% per year until obliteration occurred.

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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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Hideyuki Kano, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Daniel Tonetti, Ajay Niranjan, and L. Dade Lunsford

Object

The purpose of this study was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs).

Methods

Between 1987 and 2009, SRS was performed in 474 patients with SM Grade III AVMs. The AVMs were categorized by scoring the size (S), drainage (D), and location (L): IIIa was a small AVM (S1D1L1, N = 282); IIIb was a medium/deep AVM (S2D1L0, N = 44); and IIIc was a medium/eloquent AVM (S2D0L1, N = 148). The median target volume was 3.8 ml (range 0.1–26.3 ml) and the margin dose was 20 Gy (range 13–25 Gy). Eighty-one patients (17%) underwent prior embolization, and 58 (12%) underwent prior resection.

Results

At a mean follow-up of 89 months, the total obliteration rates documented by angiography or MRI for all SM Grade III AVMs increased from 48% at 3 years to 69% at 4 years, 72% at 5 years, and 77% at 10 years. The SM Grade IIIa AVMs were more likely to obliterate than other subgroups. The cumulative rate of hemorrhage was 2.3% at 1 year, 4.4% at 2 years, 5.5% at 3 years, 6.4% at 5 years, and 9% at 10 years. The SM Grade IIIb AVMs had a significantly higher cumulative rate of hemorrhage. Symptomatic adverse radiation effects were detected in 6%.

Conclusions

Treatment with SRS was an effective and relatively safe management option for SM Grade III AVMs. Although patients with residual AVMs remained at risk for hemorrhage during the latency interval, the cumulative 10-year 9% hemorrhage risk in this series may represent a significant reduction compared with the expected natural history.

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Greg Bowden, Hideyuki Kano, Ellen Caparosa, Seong-Hyun Park, Ajay Niranjan, John Flickinger, and L. Dade Lunsford

OBJECT

Non–small cell lung cancer (NSCLC) is the most frequent cancer that metastasizes to brain. Stereotactic radiosurgery (SRS) has become the management of choice for most patients with such metastatic tumors. Therefore, the authors endeavored to elucidate the survival and SRS outcomes for patients with NSCLC metastasis at their center.

METHODS

In this single-institution retrospective analysis, the authors reviewed their experience with NSCLC metastasis during a 10-year period from 2001 to 2010. Seven hundred twenty patients underwent Gamma Knife radiosurgery. A total of 1004 SRS procedures were performed, and 3143 tumors were treated. The NSCLC subtype was adenocarcinoma in 386 patients, squamous cell carcinoma in 111 patients, and large cell carcinoma in 34 patients. The median aggregate tumor volume was 4.5 cm3 (range 0.1–88 cm3).

RESULTS

The median survival time after diagnosis of brain metastasis from NSCLC was 12.6 months, and the median survival after SRS was 8.5 months. The 1-, 2-, and 5-year survival rates after SRS were 39%, 21%, and 10%, respectively. Postradiosurgery survival was decreased in patients treated with prior whole-brain radiation therapy compared with SRS alone (p = 0.003). Aggregate tumor volume was inversely related to survival after SRS (p < 0.001), and the histological subgroups demonstrated significant survival differences (p = 0.023). The overall local tumor control rate in the entire group was 92.8%. One hundred seventy-four patients (24%) underwent repeat SRS for new or resistant metastatic deposits.

CONCLUSIONS

Stereotactic radiosurgery is an effective means of providing local control for NSCLC metastases. Neurological function and survival benefit from serial patient monitoring and repeat SRS for new tumors.