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Gregory Neil Bowden, Jong Oh Kim, Andrew Faramand, Kevin Fallon, John Flickinger, and L. Dade Lunsford

OBJECTIVE

The use of Gamma Knife stereotactic radiosurgery (GKSRS) for the treatment of extensive intracranial metastases has been expanding due to its superior dosimetry and efficacy. However, there remains a dearth of data regarding the dose parameters in actual clinical scenarios. The authors endeavored to calculate the radiation dose to the brain when treating ≥ 15 brain metastases with GKSRS.

METHODS

This retrospective analysis reviewed dosage characteristics for patients requiring single-session GKSRS for the treatment of ≥ 15 brain metastases. Forty-two patients met the inclusion criteria between 2008 and 2017. The median number of tumors at the initial GKSRS procedure was 20 (range 15–39 tumors), accounting for 865 tumors in this study. The median aggregate tumor volume was 3.1 cm3 (range 0.13–13.26 cm3), and the median marginal dose was 16 Gy (range 14–19 Gy).

RESULTS

The median of the mean brain dose was 2.58 Gy (range 0.95–3.67 Gy), and 79% of patients had a dose < 3 Gy. The 12-Gy dose volume was a median of 12.45 cm3, which was equivalent to 0.9% of the brain volume. The median percentages of brain receiving 5 Gy and 3 Gy were 6.7% and 20.4%, respectively. There was no correlation between the number of metastases and the mean dose to the brain (p = 0.8). A greater tumor volume was significantly associated with an increased mean brain dose (p < 0.001). The median of the mean dose to the bilateral hippocampi was 2.3 Gy. Sixteen patients had supplementary GKSRS, resulting in an additional mean dose of 1.4 Gy (range 0.2–3.8 Gy) to the brain.

CONCLUSIONS

GKSRS is a viable means of managing extensive brain metastases. This procedure provides a relatively low dose of radiation to the brain, especially when compared with traditional whole-brain radiation protocols.

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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.

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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, Huai-che Yang, Ajay Niranjan, John Flickinger, and L. Dade Lunsford

Object

The outcomes of stereotactic radiosurgery for arteriovenous malformations (AVMs) within or adjacent to the ventricular system are largely unknown. This study assessed the long-term outcomes and hemorrhage risks for patients with AVMs within this region who underwent Gamma Knife surgery (GKS) at the University of Pittsburgh.

Methods

The authors retrospectively identified 188 patients with ventricular-region AVMs who underwent a single-stage GKS procedure during a 22-year interval. The median patient age was 32 years (range 3–80 years), the median target volume was 4.6 cm3 (range 0.1–22 cm3), and the median marginal dose was 20 Gy (range 13–27 Gy).

Results

Arteriovenous malformation obliteration was confirmed by MRI or angiography in 89 patients during a median follow-up of 65 months (range 2–265 months). The actuarial rates of total obliteration were 32% at 3 years, 55% at 4 years, 60% at 5 years, and 64% at 10 years. Higher rates of AVM obliteration were obtained in the 26 patients with intraventricular AVMs. Twenty-five patients (13%) sustained a hemorrhage during the initial latency interval after GKS, indicating an annual hemorrhage rate of 3.4% prior to AVM obliteration. No patient experienced a hemorrhage after AVM obliteration was confirmed by imaging. Permanent neurological deficits due to adverse radiation effects developed in 7 patients (4%).

Conclusions

Although patients in this study demonstrated an elevated hemorrhage risk that remained until complete obliteration, GKS still proved to be a generally safe and effective treatment for patients with these high-risk intraventricular and periventriclar AVMs.

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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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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010

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Jason P. Sheehan, Ajay Niranjan, Jonas M. Sheehan, John A. Jane Jr., Edward R. Laws, Douglas Kondziolka, John Flickinger, Alex M. Landolt, Jay S. Loeffler, and L. Dade Lunsford

Object. Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas.

Methods. Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas.

A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low.

Conclusions. Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes.