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Marshall J. Huang, Hideyuki Kano, Seyed H. Mousavi, Ajay Niranjan, Edward A. Monaco III, Yoshio Arai, John C. Flickinger and L. Dade Lunsford

OBJECTIVE

The goal of this retrospective cohort study was to assess long-term outcomes in patients with vestibular schwannoma (VS) who underwent stereotactic radiosurgery (SRS) after initial microsurgical resection.

METHODS

From the authors' database of 1770 patients with VS, the authors retrospectively analyzed data from 173 Gamma Knife SRS procedures for VS after 1 (128 procedures) or multiple (45 procedures) microsurgical resections. The median length of the interval between the last resection and SRS was 42 months (range 2–329 months). The median length of clinical follow-up was 74 months (range 6–285 months). Progression-free survival after SRS was determined with Kaplan-Meier analysis.

RESULTS

At the time of SRS, the hearing of 161 patients (93%) was Gardner-Robertson Class V, and 81 patients (47%) had facial neuropathy (i.e., facial function with House-Brackmann [HB] grades of III–VI), 87 (50%) had trigeminal neuropathy, and 71 (41%) reported imbalance or disequilibrium disorders. The median tumor volume was 2.7 cm3 (range 0.2–21.6 cm3), and the median dose to the tumor margin was 13 Gy (range 11–20 Gy). Radiosurgery controlled growth of 163 (94%) tumors. Progression-free survival after SRS was 97% at 3 years, 95% at 5 years, and 90% at 10 years. Four patients with delayed tumor progression underwent repeat SRS at a median of 35 months (range 23–64 months) after the first SRS. Four patients (2.3%) with tumor progression underwent repeat resection at a median of 25 months (range 19–33 months). Among the patients with any facial dysfunction (indicated by HB grades of II–VI), 19% had improvement in this condition after SRS, and 5.5% with some facial function (indicated by HB grades of I–V) developed more facial weakness. Among patients with trigeminal neuropathy, 20% had improvement in this condition, and 5.8% developed or had worsened trigeminal neuropathy after SRS.

CONCLUSIONS

Stereotactic radiosurgery offered a safe and effective long-term management strategy for VS patients whose tumors remained or recurred after initial microsurgery.

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Greg Bowden, Hideyuki Kano, Ellen Caparosa, Daniel Tonetti, Ajay Niranjan, Edward A. Monaco III, John Flickinger, Yoshio Arai and L. Dade Lunsford

OBJECT

A visual field deficit resulting from the management of an arteriovenous malformation (AVM) significantly impacts a patient's quality of life. The present study was designed to investigate the clinical and radiological outcomes of stereotactic radiosurgery (SRS) performed for AVMs involving the postgeniculate visual pathway.

METHODS

In this retrospective single-institution analysis, the authors reviewed their experience with Gamma Knife surgery for postgeniculate visual pathway AVMs performed during the period between 1987 and 2009.

RESULTS

During the study interval, 171 patients underwent SRS for AVMs in this region. Forty-one patients (24%) had a visual deficit prior to SRS. The median target volume was 6.0 cm3 (range 0.4–22 cm3), and 19 Gy (range 14–25 Gy) was the median margin dose. Obliteration of the AVM was confirmed in 80 patients after a single SRS procedure at a median follow-up of 74 months (range 5–297 months). The actuarial rate of total obliteration was 67% at 4 years. Arteriovenous malformations with a volume < 5 cm3 had obliteration rates of 60% at 3 years and 79% at 4 years. The delivered margin dose proved significant given that 82% of patients receiving ≥ 22 Gy had complete obliteration. The AVM was completely obliterated in an additional 18 patients after they underwent repeat SRS. At a median of 25 months (range 11–107 months) after SRS, 9 patients developed new or worsened visual field deficits. One patient developed a complete homonymous hemianopia, and 8 patients developed quadrantanopias. The actuarial risk of sustaining a new visual deficit was 3% at 3 years, 5% at 5 years, and 8% at 10 years. Fifteen patients had hemorrhage during the latency period, resulting in death in 9 of the patients. The annual hemorrhage rate during the latency interval was 2%, and no hemorrhages occurred after confirmed obliteration.

CONCLUSIONS

Despite an overall treatment mortality of 5%, related to latency interval hemorrhage, SRS was associated with only a 5.6% risk of new visual deficit and a final obliteration rate close to 80% in patients with AVMs of the postgeniculate visual pathway.

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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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Douglas Kondziolka, Phillip V. Parry, L. Dade Lunsford, Hideyuki Kano, John C. Flickinger, Susan Rakfal, Yoshio Arai, Jay S. Loeffler, Stephen Rush, Jonathan P. S. Knisely, Jason Sheehan, William Friedman, Ahmad A. Tarhini, Lanie Francis, Frank Lieberman, Manmeet S. Ahluwalia, Mark E. Linskey, Michael McDermott, Paul Sperduto and Roger Stupp

Object

Estimating survival time in cancer patients is crucial for clinicians, patients, families, and payers. To provide appropriate and cost-effective care, various data sources are used to provide rational, reliable, and reproducible estimates. The accuracy of such estimates is unknown.

Methods

The authors prospectively estimated survival in 150 consecutive cancer patients (median age 62 years) with brain metastases undergoing radiosurgery. They recorded cancer type, number of brain metastases, neurological presentation, extracranial disease status, Karnofsky Performance Scale score, Recursive Partitioning Analysis class, prior whole-brain radiotherapy, and synchronous or metachronous presentation. Finally, the authors asked 18 medical, radiation, or surgical oncologists to predict survival from the time of treatment.

Results

The actual median patient survival was 10.3 months (95% CI 6.4–14). The median physician-predicted survival was 9.7 months (neurosurgeons = 11.8 months, radiation oncologists = 11.0 months, and medical oncologist = 7.2 months). For patients who died before 10 months, both neurosurgeons and radiation oncologists generally predicted survivals that were more optimistic and medical oncologists that were less so, although no group could accurately predict survivors alive at 14 months. All physicians had individual patient survival predictions that were incorrect by as much as 12–18 months, and 14 of 18 physicians had individual predictions that were in error by more than 18 months. Of the 2700 predictions, 1226 (45%) were off by more than 6 months and 488 (18%) were off by more than 12 months.

Conclusions

Although crucial, predicting the survival of cancer patients is difficult. In this study all physicians were unable to accurately predict longer-term survivors. Despite valuable clinical data and predictive scoring techniques, brain and systemic management often led to patient survivals well beyond estimated survivals.

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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, 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.