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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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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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Douglas Kondziolka, Ricky Madhok, L. Dade Lunsford, David Mathieu, Juan J. Martin, Ajay Niranjan, and John C. Flickinger

Object

Meningiomas of the cerebral convexity are often surgically curable because both the mass and involved dura mater can be removed. Stereotactic radiosurgery has become an important primary or adjuvant treatment for patients with intracranial meningiomas. The authors evaluated clinical and imaging outcomes in patients with convexity meningiomas after radiosurgery.

Methods

The patient cohort consisted of 125 patients with convexity meningiomas managed using radiosurgery at some point during an 18-year period. The patient series included 76 women, 55 patients who had undergone prior resection, and 6 patients with neurofibromatosis Type 2. Tumors were located in frontal (80 patients), parietal (24 patients), temporal (12 patients), and occipital (9 patients) areas. The WHO tumor grades in patients with prior resections were Grade I in 34 patients, Grade II in 15 patients, and Grade III in 6 patients. Seventy patients underwent primary radiosurgery and therefore had no prior histological tumor diagnosis. The mean tumor volume was 7.6 ml. Radiosurgery was performed using the Leksell Gamma Knife with a mean tumor margin dose of 14.2 Gy.

Results

Serial imaging was evaluated in 115 patients (92%). After primary radiosurgery, the tumor control rate was 92%. After adjuvant radiosurgery, the control rate was 97% for Grade I tumors. The actuarial tumor control rates at 3 and 5 years for the entire series were 86.1 ± 3.8% and 71.6 ± 8.6%, respectively. For patients with benign tumors (Grade I) and those without prior surgery, the actuarial tumor control rate was 95.3 ± 2.3% and 85.8 ± 9.3%, respectively. Delayed resection after radiosurgery was performed in 9 patients (7%) at an average of 35 months. No patient developed a subsequent radiation-induced tumor. The overall morbidity rate was 9.6%. Symptomatic peritumoral imaging changes compatible with edema or adverse radiation effects developed in 5%, at a mean of 8 months.

Conclusions

Stereotactic radiosurgery provides satisfactory control rates either after resection or as an alternate to resection, particularly for histologically benign meningiomas. Its role is most valuable for patients whose tumors affect critical neurological regions and who are poor candidates for resection. Both temporary and permanent morbidity are related to brain location and tumor volume.

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Akiyoshi Ogino, L. Dade Lunsford, Hao Long, Stephen Johnson, Andrew Faramand, Ajay Niranjan, John C. Flickinger, and Hideyuki Kano

OBJECTIVE

This report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs).

METHODS

Between 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22–85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015–0.63 cm3). The median margin dose was 12.5 Gy (range 11.0–25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7–50.0 Gy).

RESULTS

The progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569–5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059–4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS.

CONCLUSIONS

SRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

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Anand V. Germanwala, Jeffrey C. Mai, Nestor D. Tomycz, Ajay Niranjan, John C. Flickinger, Douglas Kondziolka, and L. Dade Lunsford

Object

The aim of this paper was to determine prognostic factors for adult medulloblastoma treated with boost Gamma Knife surgery (GKS) following resection and craniospinal irradiation.

Methods

The authors performed a retrospective analysis of 12 adult patients with histologically proven medulloblastoma or supratentorial primitive neuroectodermal tumor who between February 1991 and December 2004 underwent ≥ 1 sessions of GKS for posttreatment residual or recurrent tumors (6 tumors in each group). Before GKS, all patients had undergone a maximal feasible resection followed by craniospinal irradiation. Nine patients also received systemic chemotherapy. Stereotactic radiosurgery was applied to residual and recurrent posterior fossa tumor as well as to foci of intracranial medulloblastoma metastases. The median time interval from initial diagnosis and resection to the first GKS treatment was 24 months (range 2–37 months). The mean GKS-treated tumor volume was 9.4 cm3 (range 0.5–39 cm3).

Results

Following adjunctive radiosurgery, 5 patients had no evidence of tumor on magnetic resonance (MR) imaging, 3 patients had stable tumor burden on MR imaging, and 4 patients had evidence of tumor progression locally with or without intracranial metastases. All patients with tumor progression died. Eight patients survive with a mean cumulative follow-up of 72.4 months (range 21– 152 months). No acute radiation toxicity or delayed radiation necrosis was observed among any of the 12 patients. The majority of patients who achieved tumor eradication (80%) and tumor stabilization (67%) after GKS had residual tumor as the reason for their referral for GKS. The best outcomes were attained in patients with residual disease who were younger, had smaller tumor volumes, had no evidence of metastatic disease, and had received higher cumulative GKS doses.

Conclusions

Single or multiple GKS sessions were a well-tolerated, feasible, and effective adjunctive treatment for posterior fossa residual or recurrent medulloblastoma as well as intracranial metastatic medulloblastoma in adult patients.

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Kyung-Jae Park, Douglas Kondziolka, Hideyuki Kano, Oren Berkowitz, Safee Faraz Ahmed, Xiaomin Liu, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

Object

Vertebrobasilar ectasia (VBE) is an unusual cause of trigeminal neuralgia (TN). The surgical options for patients with medically refractory pain include percutaneous or microsurgical rhizotomy and microvascular decompression (MVD). All such procedures can be technically challenging. This report evaluates the response to a minimally invasive procedure, Gamma Knife surgery (GKS), in patients with TN associated with severe vascular compression caused by VBE.

Methods

Twenty patients underwent GKS for medically refractory TN associated with VBE. The median patient age was 74 years (range 48–95 years). Prior surgical procedures had failed in 11 patients (55%). In 9 patients (45%), GKS was the first procedure they had undergone. The median target dose for GKS was 80 Gy (range 75–85 Gy). The median follow-up was 29 months (range 8–123 months) after GKS. The treatment outcomes were compared with 80 case-matched controls who underwent GKS for TN not associated with VBE.

Results

Intraoperative MR imaging or CT scanning revealed VBE that deformed the brainstem in 50% of patients. The trigeminal nerve was displaced in cephalad or lateral planes in 60%. In 4 patients (20%), the authors could identify only the distal cisternal component of the trigeminal nerve as it entered into the Meckel cave.

After GKS, 15 patients (75%) achieved initial pain relief that was adequate or better, with or without medication (Barrow Neurological Institute [BNI] pain scale, Grades I–IIIb). The median time until pain relief was 5 weeks (range 1 day–6 months). Twelve patients (60%) with initial pain relief reported recurrent pain between 3 and 43 months after GKS (median 12 months). Pain relief was maintained in 53% at 1 year, 38% at 2 years, and 10% at 5 years. Some degree of facial sensory dysfunction occurred in 10% of patients. Eventually, 14 (70%) of the 20 patients underwent an additional surgical procedure including repeat GKS, percutaneous procedure, or MVD at a median of 14 months (range 5–50 months) after the initial GKS. At the last follow-up, 15 patients (75%) had satisfactory pain control (BNI Grades I–IIIb), but 5 patients (25%) continued to have unsatisfactory pain control (BNI Grade IV or V). Compared with patients without VBE, patients with VBE were much less likely to have initial (p = 0.025) or lasting (p = 0.006) pain relief.

Conclusions

Pain control rates of GKS in patients with TN associated with VBE were inferior to those of patients without VBE. Multimodality surgical or medical management strategies were required in most patients with VBE.

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Hideyuki Kano, John C. Flickinger, Aya Nakamura, Rachel C. Jacobs, Daniel A. Tonetti, Craig Lehocky, Kyung-Jae Park, Huai-che Yang, Ajay Niranjan, and L. Dade Lunsford

OBJECTIVE

The management of large-volume arteriovenous malformations (AVMs) with stereotactic radiosurgery (SRS) remains challenging. The authors retrospectively tested the hypothesis that AVM obliteration rates can be improved by increasing the percentage volume of an AVM that receives a minimal threshold dose of radiation.

METHODS

In 1992, the authors prospectively began to stage anatomical components in order to deliver higher single doses to AVMs > 15 cm3 in volume. Since that time 60 patients with large AVMs have undergone volume-staged SRS (VS-SRS). The median interval between the first stage and the second stage was 4.5 months (2.8–13.8 months). The median target volume was 11.6 cm3 (range 4.3–26 cm3) in the first-stage SRS and 10.6 cm3 (range 2.8–33.7 cm3) in the second-stage SRS. The median margin dose was 16 Gy (range 13–18 Gy) for both SRS stages.

RESULTS

AVM obliteration after the initial two staged volumetric SRS treatments was confirmed by MRI alone in 4 patients and by angiography in 11 patients at a median follow-up of 82 months (range 0.4–206 months) after VS-SRS. The post–VS-SRS obliteration rates on angiography were 4% at 3 years, 13% at 4 years, 23% at 5 years, and 27% at 10 years. In multivariate analysis, only ≥ 20-Gy volume coverage was significantly associated with higher total obliteration rates confirmed by angiography. When the margin dose is ≥ 17 Gy and the 20-Gy SRS volume included ≥ 63% of the total target volume, the angiographically confirmed obliteration rates increased to 61% at 5 years and 70% at 10 years.

CONCLUSIONS

The outcomes of prospective VS-SRS for large AVMs can be improved by prescribing an AVM margin dose of ≥ 17 Gy and adding additional isocenters so that ≥ 63% of the internal AVM dose receives more than 20 Gy.

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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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Thomas J. Flannery, Hideyuki Kano, L. Dade Lunsford, Sait Sirin, Matthew Tormenti, Ajay Niranjan, John C. Flickinger, and Douglas Kondziolka

Object

Because of their critical location adjacent to brain, cranial nerve, and vascular structures, petroclival meningiomas remain a clinical challenge. The authors evaluated outcomes in 168 patients with petroclival meningiomas who underwent Gamma Knife surgery (GKS) during a 21-year interval.

Methods

Gamma Knife surgery was used as either primary or adjuvant treatment of 168 petroclival meningiomas involving the region between the petrous apex and the upper two-thirds of the clivus. The most common presenting symptoms were trigeminal nerve dysfunction, balance problems, diplopia, and hearing loss. The median tumor volume was 6.1 cm3 (range 0.3–32.5 cm3), and the median radiation dose to the tumor margin was 13 Gy (range 9–18 Gy).

Results

During a median follow-up of 72 months, neurological status improved in 44 patients (26%), remained stable in 98 (58%), and worsened in 26 (15%). Tumor volume decreased in 78 patients (46%), remained stable in 74 (44%), and increased in 16 (10%), all of whom were subjected to additional management strategies. Overall 5- and 10-year progression-free survival rates were 91 and 86%, respectively. Patients followed up for at least 10 years (31 patients) had tumor and symptom control rates of 97 and 94%, respectively. Eight patients had repeat radiosurgery, 4 underwent delayed resection, and 4 had fractionated radiation therapy. Cerebrospinal fluid diversion was performed in 7 patients (4%). Significant risk factors for tumor progression were a tumor volume ≥ 8 cm3 (p = 0.001) and male sex (p = 0.02).

Conclusions

In this 21-year experience, GKS for petroclival meningiomas obviated initial or further resection in 98% of patients and was associated with a low risk of adverse radiation effects. The authors believe that radiosurgery should be considered as an initial option for patients with smaller-volume, symptomatic petroclival meningiomas.

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Daniel A. Tonetti, Bradley A. Gross, Kyle M. Atcheson, Brian T. Jankowitz, Hideyuki Kano, Edward A. Monaco III, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

The authors of this study found that, given the latency period required for arteriovenous malformation (AVM) obliteration after stereotactic radiosurgery (SRS), a study with limited follow-up cannot assess the benefit of SRS for unruptured AVMs.

METHODS

The authors reviewed their institutional experience with “ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)–eligible” AVMs treated with SRS between 1987 and 2016, with the primary outcome defined as stroke (ischemic or hemorrhagic) or death (AVM related or AVM unrelated). Patients with at least 3 years of follow-up in addition to those who experienced stroke or died during the latency period were included. Secondary outcome measures included obliteration rates, patients with new seizure disorders, and those with new focal deficits without stroke.

RESULTS

Of 233 patients included in this study, 32 had a stroke or died after SRS over the mean 8.4-year follow-up (14%). Utilizing the 10% stroke or death rate at a mean 2.8-year follow-up for untreated AVMs in ARUBA, the rate in the authors’ study is significantly lower than that anticipated at the 8.4-year follow-up for an untreated cohort (14% vs 30%, p = 0.0003). Notwithstanding obliteration, in this study, annualized rates of hemorrhage and stroke or death after 3 years following SRS were 0.4% and 0.8%, respectively. The overall obliteration rate was 72%; new seizure disorders, temporary new focal deficits without stroke, and permanent new focal deficits without stroke occurred in 2% of patients each.

CONCLUSIONS

After a sensible follow-up period exceeding the latency period, there is a lower rate of stroke/death for patients with treated, unruptured AVMs with SRS than for patients with untreated AVMs.