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Neal Luther, Douglas Kondziolka, Hideyuki Kano, Seyed H. Mousavi, John C. Flickinger and L. Dade Lunsford

Object

The authors sought to better define the clinical response of patients who underwent stereotactic radiosurgery (SRS) for brain metastases located in the region of the motor cortex.

Methods

A retrospective analysis was performed in 2026 patients with brain metastasis who underwent SRS with the Gamma Knife between 2002 and 2012, and multiple factors that affect motor function before and after SRS were evaluated. Ninety-four patients with tumors ≥ 1.5 cm in diameter located in or adjacent to the motor strip were identified, including 2 patients with bilateral motor strip metastases.

Results

Motor function improved after SRS in 30 (31%) of 96 cases, remained stable in 48 (50%), and worsened over time in 18 (19%) instances. Forty-seven patients had no motor weakness prior to radiosurgery; 10 (22%) developed new Grade 3/5–4/5 weakness. Thirty (68%) of 44 patients with ≥ 3/5 pre-SRS weakness improved, 6 (14%) remained stable, and 8 (18%) worsened. Three of 5 patients with < 3/5 pre-SRS motor function improved. Motor deficits prior to SRS did not correlate with a worse outcome; however, worse outcomes were associated with larger tumor volumes. The median tumor volume in patients whose function improved or remained stable was 5.3 cm3, but it was 9.2 cm3 in patients who worsened (p < 0.05). Tumor volumes > 9 cm3 were associated with a higher risk of worsening motor function. Adverse radiation effects occurred in 5 patients.

Conclusions

Most intact patients with brain metastases in or adjacent to motor cortex maintained neurological function after SRS, and most patients with symptomatic motor weakness remained stable or improved. Larger tumor volumes were associated with less satisfactory outcomes.

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Douglas Kondziolka, Seyed H. Mousavi, Hideyuki Kano, John C. Flickinger and L. Dade Lunsford

Object

Management recommendations for patients with smaller-volume or newly diagnosed vestibular schwannomas (< 4 cm3) need to be based on an understanding of the anticipated natural history of the tumor and the side effects it produces. The natural history can then be compared with the risks and benefits of therapeutic intervention using a minimally invasive strategy such as stereotactic radiosurgery (SRS).

Methods

The authors reviewed the emerging literature stemming from recent recommendations to “wait and scan” (observation) and compared this strategy with published outcomes after early intervention using SRS or results from matched cohort studies of resection and SRS.

Results

Various retrospective studies indicate that vestibular schwannomas grow at a rate of 0–3.9 mm per year and double in volume between 1.65 and 4.4 years. Stereotactic radiosurgery arrests growth in up to 98% of patients when studied at intervals of 10–15 years. Most patients who select “wait and scan” note gradually decreasing hearing function leading to the loss of useful hearing by 5 years. In contrast, current studies indicate that 3–5 years after Gamma Knife surgery, 61%–80% of patients maintain useful hearing (speech discrimination score > 50%, pure tone average < 50).

Conclusions

Based on published data on both volume and hearing preservation for both strategies, the authors devised a management recommendation for patients with small vestibular schwannomas. When resection is not chosen by the patient, the authors believe that early SRS intervention, in contrast to observation, results in long-term tumor control and improved rates of hearing preservation.

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Seyed H. Mousavi, Berkcan Akpinar, Ajay Niranjan, Vikas Agarwal, Jonathan Cohen, John C. Flickinger, Douglas Kondziolka and L. Dade Lunsford

OBJECTIVE

Contrast enhancement of the retrogasserian trigeminal nerve on MRI scans frequently develops after radiosurgical ablation for the management of medically refractory trigeminal neuralgia (TN). The authors sought to evaluate the clinical significance of this imaging finding in patients who underwent a second radiosurgical procedure for recurrent TN.

METHODS

During a 22-year period, 360 patients underwent Gamma Knife stereotactic radiosurgery (SRS) as their first surgical procedure for TN at the authors' center. The authors retrospectively analyzed the data from 59 patients (mean age 72 years, range 33–89 years) who underwent repeat SRS for recurrent pain at a median of 30 months (range 6–146 months) after the first SRS. The isocenter was 4 mm, and the median maximum doses for the first and second procedures were 80 Gy and 70 Gy, respectively. A neuroradiologist and a neurosurgeon blinded to the treated side evaluated the presence of nerve contrast enhancement on MRI series at the time of the repeat procedure. The authors correlated the presence of this imaging change with clinical outcomes. Pain outcomes and development of trigeminal sensory dysfunction were evaluated with the Barrow Neurological Institute (BNI) Pain Scale and BNI Numbness Scale, respectively. The mean length of follow-up after the second SRS was 58 months (95% CI 49–68 months).

RESULTS

At the time of the repeat SRS, contrast enhancement of the trigeminal nerve on MRI scans was observed in 31 patients (53%). Five years after the SRS, patients with this enhancement had lower actuarial rates of complete pain relief after the repeat SRS (27% [95% CI 7%–47%]) than patients without the enhancement (76% [95% CI 58%–94%]) (p < 0.001). At the 5-year follow-up, patients with the contrast enhancement also had a higher risk for trigeminal sensory loss after repeat SRS (75% [95% CI 59%–91%]) than patients without contrast enhancement (26% [95% CI 10%–42%]) (p = 0.001). Dysesthetic pain after repeat SRS was observed for 8 patients with and for 2 patients without contrast enhancement.

CONCLUSIONS

Trigeminal nerve contrast enhancement on MRI scans observed at the time of a repeat SRS for TN was associated with less satisfactory pain control and more frequently detected facial sensory loss. Residual contrast enhancement at the time of a repeat SRS may warrant consideration of dose reduction or further separation of the radiosurgical targets.

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Seyed H. Mousavi, Ajay Niranjan, Berkcan Akpinar, Marshall Huang, Hideyuki Kano, Daniel Tonetti, John C. Flickinger and L. Dade Lunsford

OBJECTIVE

In the era of MRI, vestibular schwannomas are often recognized when patients still have excellent hearing. Besides success in tumor control rate, hearing preservation is a main goal in any procedure for management of this population. The authors evaluated whether modified auditory subclassification prior to radiosurgery could predict long-term hearing outcome in this population.

METHODS

The authors reviewed a quality assessment registry that included the records of 1134 vestibular schwannoma patients who had undergone stereotactic radiosurgery during a 15-year period (1997–2011). The authors identified 166 patients who had Gardner-Robertson Class I hearing prior to stereotactic radiosurgery. Fifty-three patients were classified as having Class I-A (no subjective hearing loss) and 113 patients as Class I-B (subjective hearing loss). Class I-B patients were further stratified into Class I-B1 (pure tone average ≤ 10 dB in comparison with the contralateral ear; 56 patients), and I-B2 (> 10 dB compared with the normal ear; 57 patients). At a median follow-up of 65 months, the authors evaluated patients' hearing outcomes and tumor control.

RESULTS

The median pure tone average elevations after stereotactic radiosurgery were 5 dB, 13.5 dB, and 28 dB in Classes I-A, I-B1, and I-B2, respectively. The median declines in speech discrimination scores after stereotactic radiosurgery were 0% for Class I-A (p = 0.33), 8% for Class I-B1 (p < 0.0001), and 40% for Class I-B2 (p < 0.0001). Serviceable hearing preservation rates were 98%, 73%, and 33% for Classes I-A, I-B1, and I-B2, respectively. Gardner-Robertson Class I hearing was preserved in 87%, 43%, and 5% of patients in Classes I-A, I-B1, and I-B2, respectively.

CONCLUSIONS

Long-term hearing preservation was significantly better if radiosurgery was performed prior to subjective hearing loss. In patients with subjective hearing loss, the difference in pure tone average between the affected ear and the unaffected ear was an important factor in long-term hearing preservation.

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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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Seyed H. Mousavi, Ajay Niranjan, Berkcan Akpinar, Edward A. Monaco III, Jonathan Cohen, Jagdish Bhatnagar, Yue-Fang Chang, Hideyuki Kano, Sakibul Huq, John C. Flickinger and L. Dade Lunsford

OBJECTIVE

During the last 25 years, more than 100,000 patients worldwide with trigeminal neuralgia (TN) have undergone stereotactic radiosurgery (SRS) with a standard dose of radiation. However, the radiobiological effect of radiation is determined by the amount of energy delivered to the tissue (integral dose [ID] = mean dose × target volume) and is directly associated with the nerve volume. Although the trigeminal nerve volume varies among patients with TN, the clinical impact of this variation in delivered energy is unknown. The objective of this study was to evaluate the effect of delivered ID on the outcome of TN radiosurgery.

METHODS

The authors evaluated 155 patients with unilateral TN who had undergone SRS as their initial surgical management over a 13-year period. The authors measured the postganglionic ID within the SRS target and retrospectively stratified patients into 3 groups: low (< 1.4 mJ), medium (1.4–2.7 mJ), and high (> 2.7 mJ) ID. Clinical outcomes, which included pain status (scored using the Barrow Neurological Institute Pain Scale) and sensory dysfunction (scored using the Barrow Neurological Institute Numbness Scale), were evaluated at a median follow-up of 71 months.

RESULTS

Patients who were treated with a medium ID had superior pain relief either with or without medications (p = 0.006). In the medium ID group, the rates of complete pain relief without medications at 1, 3, and 6 years after SRS were 67%, 54%, and 33%, respectively, while the rates in the rest of the cohort were 55%, 36%, and 19%, respectively. Patients given a high ID had a higher rate of post-SRS trigeminal sensory deterioration (p < 0.0001). At 1, 3, and 6 years after SRS, the high ID group had an estimated rate for developing sensory dysfunction of 35%, 45%, and 50%, respectively, while the rates in patients receiving low and medium IDs were 3%, 4%, and 9%, respectively. The optimal clinical outcome (maximum pain relief and minimal trigeminal sensory dysfunction) was obtained in patients who had received a medium ID.

CONCLUSIONS

With current dose selection methods, nerve volume affects long-term clinical outcomes in patients with TN who have undergone SRS. This study suggests that the prescribed SRS dose should be customized for each TN patient based on the nerve volume.

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Hideyuki Kano, Alejandro Morales-Restrepo, Aditya Iyer, Gregory M. Weiner, Seyed H. Mousavi, John M. Kirkwood, Ahmad A. Tarhini, John C. Flickinger and L. Dade Lunsford

OBJECTIVE

The goal of this study was to use 4 prognostic indices to compare survival times of patients who underwent Gamma Knife stereotactic radiosurgery (SRS) to treat melanoma brain metastases.

METHODS

The authors analyzed 422 consecutive patients (1440 brain metastases) who underwent Gamma Knife SRS. The median total brain tumor volume was 4.7 cm3 (range 0.3–69.3 cm3), and the median number of metastases was 2 (range 1–32). One hundred thirty-two patients underwent whole-brain radiation therapy. Survival times were compared using recursive partitioning analysis (RPA), the Score Index for Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), and the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA).

RESULTS

The overall survival times after SRS were compared. With the RPA index, survival times were 2.6 months (Class III, n = 27), 5.5 months (Class II, n = 348), and 13.0 months (Class I, n = 47). With the DS-GPA index, survival times were 2.8 months (Scores 0–1, n = 67), 4.2 months (Scores 1.5–2.0, n = 143), 6.6 months (Scores 2.5–3.0, n = 111), and 9.4 months (Scores 3.5–4.0, n = 101). With the SIR, survival times were 3.2 months (Scores 0–3, n = 56), 5.8 months (Scores 4–7, n = 319), and 12.7 months (Scores 8–10, n = 47). With the BSBM index, survival times were 2.6 months (BSBM0, n = 47), 5.4 months (BSBM1, n = 282), 11.0 months (BSBM2, n = 86), and 8.8 months (BSBM3, n = 7). The DS-GPA index was the most balanced by case numbers in each class and provided the overall best prognostic index for overall survival.

CONCLUSIONS

The DS-GPA index proved most balanced and predictive of survival for patients with melanoma who underwent SRS as part of management for brain metastases. Patients whose DS-GPA score was ≥ 2.5 had predictably improved survival times after SRS.

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Or Cohen-Inbar, Cheng-Chia Lee, Seyed H. Mousavi, Hideyuki Kano, David Mathieu, Antonio Meola, Peter Nakaji, Norissa Honea, Matthew Johnson, Mahmoud Abbassy, Alireza M. Mohammadi, Danilo Silva, Huai-Che Yang, Inga Grills, Douglas Kondziolka, Gene H. Barnett, L. Dade Lunsford and Jason Sheehan

OBJECTIVE

Hemangiopericytomas (HPCs) are rare tumors widely recognized for their aggressive clinical behavior, high recurrence rates, and distant and extracranial metastases even after a gross-total resection. The authors report a large multicenter study, through the International Gamma Knife Research Foundation (IGKRF), reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly discovered HPCs.

METHODS

Eight centers participating in the IGKRF participated in this study. A total of 90 patients harboring 133 tumors were identified. Patients were included if they had a histologically diagnosed HPC managed with SRS during the period 1988–2014 and had a minimum of 6 months' clinical and radiological follow-up. A de-identified database was created. The patients' median age was 48.5 years (range 13–80 years). Prior treatments included embolization (n = 8), chemotherapy (n = 2), and fractionated radiotherapy (n = 34). The median tumor volume at the time of SRS was 4.9 cm3 (range 0.2–42.4 cm3). WHO Grade II (typical) HPCs formed 78.9% of the cohort (n = 71). The median margin and maximum doses delivered were 15 Gy (range 2.8–24 Gy) and 32 Gy (range 8–51 Gy), respectively. The median clinical and radiographic follow-up periods were 59 months (range 6–190 months) and 59 months (range 6–183 months), respectively. Prognostic variables associated with local tumor control and post-SRS survival were evaluated using Cox univariate and multivariate analysis. Actuarial survival after SRS was analyzed using the Kaplan-Meier method.

RESULTS

Imaging studies performed at last follow-up demonstrated local tumor control in 55% of tumors and 62.2% of patients. New remote intracranial tumors were found in 27.8% of patients, and 24.4% of patients developed extracranial metastases. Adverse radiation effects were noted in 6.7% of patients. During the study period, 32.2% of the patients (n = 29) died. The actuarial overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression–free survival (PFS) was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Review of these 76 treated tumors showed that 17 presented as an in-field recurrence and 59 were defined as an out-of-field recurrence. Margin dose greater than 16 Gy (p = 0.037) and tumor grade (p = 0.006) were shown to influence PFS. The development of extracranial metastases was shown to influence overall survival (p = 0.029) in terms of PFS; repeat (multiple) SRS showed additional benefit.

CONCLUSIONS

SRS provides a reasonable rate of local tumor control and a low risk of adverse effects. It also leads to neurological stability or improvement in the majority of patients. Long-term close clinical and imaging follow-up is necessary due to the high probability of local recurrence and distant metastases. Repeat SRS is often effective for treating new or recurrent HPCs.