Publications by authors named "Jason Sheehan"

516 Publications

An International Multicenter Matched Cohort Analysis of Incidental Meningioma Progression During Active Surveillance or After Stereotactic Radiosurgery: The IMPASSE Study.

Neuro Oncol 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurosurgery, University of Liverpool & The Walton Centre NHS Trust, Lower Lane, Liverpool, UK.

Background: The optimal management of patients with an incidental meningiomas remains unclear. The aim of this study was to characterize the radiologic and neurological outcomes of expectant and SRS management of asymptomatic meningioma patients.

Methods: Using data from 14 centers across 10 countries, the study compares SRS outcomes to active surveillance of asymptomatic meningiomas. Local tumor control of asymptomatic meningiomas and development of new neurological deficits attributable to the tumor were evaluated in the SRS and conservatively managed groups.

Results: In unmatched cohorts, 727 meningioma patients underwent SRS and were followed for a mean of 57.2 months. In the conservatively managed cohort, 388 patients were followed for a mean of 43.5 months. Tumor control was 99.0% of SRS and 64.2% of conservatively managed patients (p<0.001; OR 56.860 (95%CI 26.253-123.150))). New neurological deficits were 2.5% in the SRS and 2.8% of conservatively managed patients (p=0.764; OR 0.890 (95% CI 0.416-1.904)). After 1:1 propensity matching for patient age, tumor volume, location, and imaging follow-up, tumor control in the SRS and conservatively managed cohorts was 99.4% and 62.1%, respectively (p<0.001; OR 94.461 (95% CI 23.082-386.568)). In matched cohorts, new neurological deficits were noted in 2.3% of SRS treated and 3.2% of conservatively managed patients (p=0.475; OR 0.700 (95% CI 0.263-1.863)).

Conclusions: SRS affords superior radiologic tumor control compared to active surveillance without increasing the risk of neurological deficits in asymptomatic meningioma patients. While SRS and active surveillance are reasonable options, SRS appears to alter the natural history of asymptomatic meningiomas including tumor progression in the majority of patients treated.
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http://dx.doi.org/10.1093/neuonc/noab132DOI Listing
June 2021

In Regard to Tibbs et al.

Int J Radiat Oncol Biol Phys 2021 Jun;110(2):611-612

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia.

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http://dx.doi.org/10.1016/j.ijrobp.2020.12.059DOI Listing
June 2021

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.

Thyroid 2021 May 11. Epub 2021 May 11.

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA.

Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm (range: 0.003-38.18 cm), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452,  = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904;  = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945;  = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.
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http://dx.doi.org/10.1089/thy.2020.0947DOI Listing
May 2021

Sonodynamic therapy for metastatic melanoma to the brain.

J Neurooncol 2021 Jun 10;153(2):373-374. Epub 2021 May 10.

Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.

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http://dx.doi.org/10.1007/s11060-021-03768-wDOI Listing
June 2021

8+ Year Performance of the Gamma Knife Perfexion/Icon Patient Positioning System and Possibilities for Preemptive Fault Detection Using Statistical Process Control.

Med Phys 2021 May 7. Epub 2021 May 7.

Departments of Radiation Oncology, University of Virginia, Charlottesville, VA, USA.

Background: The large fractional doses, steep dose gradients, and small targets found in intracranial radiosurgery require extremely low beam delivery uncertainty. In the case of Gamma Knife radiosurgery (GKRS), this includes minimizing patient positioning system (PPS) positioning uncertainty. Existing QA techniques are recipe based, and feature point in time pass/fail tolerances. However, modern treatment machines, including the Gamma Knife Perfexion/Icon systems, record extensive internal data in treatment logs. These data can be analyzed through statistical process control (SPC) methods which are designed to detect changes in process behavior. The purpose of this study was to characterize the long-term (8+ year) performance of a Perfexion/Icon unit and use SPC methods to determine if performance changes could be detected at levels lower than existing QA and internal manufacturer performance tolerances.

Methods: In-house software was developed to parse Perfexion/Icon log-files and store relevant information on shot delivery in a relational database. A last-in, first-out (LIFO) queuing algorithm was created to heuristically match messages associated with a given delivered shot. Filtering criteria were developed to filter QA and uncompleted shots. The resulting matched shots were extracted. Achieved versus planned PPS position was determined for each PPS motor as well as for the vector magnitude difference in PPS position. Exponentially weighted moving average (EWMA) control charts were plotted to determine when process behavior changed over time.

Results: 53833 shots were delivered over an 8+ year span in the study. The mean vector magnitude PPS difference was 32.7 µm, with 97.5% of all shots within 70.1 µm. Several changes in PPS positioning behavior were observed over time, corresponding with control system faults on several occasions requiring PPS recalibration. EWMA control charts clearly demonstrate that these faults could be identified and possibly predicted as many as 3 years before there were faults beyond control system tolerance.

Conclusion: The PPS of Gamma Knife Perfexion/Icon systems has extremely low positioning uncertainties. EWMA control chart method can be utilized to track PPS performance over time and can potentially detect changes in performance that may indicate a component requiring maintenance. This would allow planned service visits to mitigate problems and prevent unplanned downtime.
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http://dx.doi.org/10.1002/mp.14924DOI Listing
May 2021

Stereotactic Radiosurgery for Post-Operative Metastatic Surgical Cavities: A Critical Review and International Society of Stereotactic Radiosurgery (ISRS) Practice Guidelines.

Int J Radiat Oncol Biol Phys 2021 Apr 20. Epub 2021 Apr 20.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Canada.

Purpose: The purpose of this critical review is to summarize the literature specific to single fraction stereotactic radiosurgery (SRS) and multiple fraction stereotactic radiotherapy (SRT) for post-operative brain metastases resection cavities and present practice recommendations on behalf of the ISRS.

Methods And Materials: Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) approach to search for manuscripts reporting SRS/SRT outcomes for post-operative brain metastases tumor bed resection cavities with a search end date of July 20, 2018.  Prospective studies, consensus guidelines, and retrospective series that included exclusively post-operative brain metastases and had at minimum 100 patients were considered eligible.

Results: The Embase and Pubmed search revealed a total of 157 manuscripts of which 77 were selected, and 55 manuscripts of which 23 were selected, for full text screening, respectively. Eight retrospective series, 1 phase II prospective study, 3 randomized controlled trials, and 1 consensus contouring paper were deemed appropriate for inclusion.  The data suggest that SRS/SRT to surgical cavities with prescription doses 30-50 Gy EQD2, 50-70 Gy EQD2, and 70-90 EQD2 are associated with rates of local control ranging from 60.5% to 91% (median 80.5%).  Randomized data suggests improved local control with single fraction SRS compared to observation and improved cognitive outcomes as compared to WBRT.  Toxicity of SRS/SRT in the post-operative setting were limited and reviewed herein.

Conclusions: Although randomized data raise concern for poorer local control following resection cavity SRS than WBRT, these findings may be driven by factors such as conservative prescription doses utilized in the SRS arm. Retrospective studies suggest high rates of local control following single fraction SRS and hypofractionated SRT for post-operative brain metastases. With a superior neurocognitive profile and no survival disadvantage to withholding WBRT, the ISRS recommends SRS as first-line treatment for eligible post-operative patients. Emerging data suggests that fractionated SRT may provide superior local control compared to single fraction SRS, in particular, for large tumor cavity volumes/diameters and potentially for patients with a pre-operative diameter greater than 2.5 cm.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.016DOI Listing
April 2021

Dual Regeneration of Muscle and Nerve by Intramuscular Infusion of Mitochondria in a Nerve Crush Injury Model.

Neurosurgery 2021 Jun;89(1):E49-E59

Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan.

Background: Peripheral nerve injuries result in muscle denervation and apoptosis of the involved muscle, which subsequently reduces mitochondrial content and causes muscle atrophy. The local injection of mitochondria has been suggested as a useful tool for restoring the function of injured nerves or the brain.

Objective: To determine outcomes following the administration of isolated mitochondria into denervated muscle after nerve injury that have not been investigated.

Methods: Muscle denervation was conducted in a sciatic nerve crushed by a vessel clamp and the denervated gastrocnemius muscle was subjected to 195 μg hamster green fluorescent protein (GFP)-mitochondria intramuscular infusion for 10 min.

Results: The mitochondria were homogeneously distributed throughout the denervated muscle after intramuscular infusion. The increases in caspase 3, 8-oxo-dG, Bad, Bax, and ratio of Bax/Bcl-2 levels in the denervated muscle were attenuated by mitochondrial infusion, and the downregulation of Bcl-2 expression was prevented by mitochondrial infusion. In addition, the decrease in the expression of desmin and the acetylcholine receptor was counteracted by mitochondrial infusion; this effect paralleled the amount of distributed mitochondria. The restoration of the morphology of injured muscles and nerves was augmented by the local infusion of mitochondria. Mitochondrial infusion also led to improvements in sciatic functional indexes, compound muscle action potential amplitudes, and conduction latencies as well as the parameters of CatWalk (Noldus) gait analysis.

Conclusion: The local infusion of mitochondria can successfully prevent denervated muscle atrophy and augment nerve regeneration by reducing oxidative stress in denervated muscle.
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http://dx.doi.org/10.1093/neuros/nyab105DOI Listing
June 2021

Stereotactic radiosurgery before bilateral adrenalectomy is associated with lowered risk of Nelson's syndrome in refractory Cushing's disease patients.

Acta Neurochir (Wien) 2021 Jul 24;163(7):1949-1956. Epub 2021 Mar 24.

Department of Neurosurgery, University of Virginia, Charlottesville, VA, 22908, USA.

Background: Nelson's syndrome is a rare but challenging sequelae of Cushing's disease (CD) after bilateral adrenalectomy (BLA). We sought to determine if stereotactic radiosurgery (SRS) of residual pituitary adenoma performed before BLA can decrease the risk of Nelson's syndrome.

Methods: Consecutive patients with CD who underwent BLA after non-curative resection of ACTH secreting pituitary adenoma and had at least one follow-up visit after BLA were studied. Nelson's syndrome was diagnosed based on the combination of rising ACTH levels, increasing volume of the pituitary adenoma and/or hyperpigmentation.

Results: Fifty patients underwent BLA for refractory CD, and 43 patients (7 men and 36 women) had at least one follow-up visit after BAL. Median endocrine, imaging, and clinical follow-up were 66 months, 69 months, and 80 months, respectively. Nine patients (22%) were diagnosed with the Nelson's syndrome at median time after BLA at 24 months (range: 0.6-119.4 months). SRS before BLA was associated with reduced risk of the Nelson's syndrome (HR = 0.126; 95%CI [0.022-0.714], p=0.019), while elevated ACTH level within 6 months after BLA was associated with increased risk for the Nelson's syndrome (HR = 9.053; 95%CI [2.076-39.472], p=0.003).

Conclusions: SRS before BLA can reduce the risk for the Nelson's syndrome in refractory CD patients requiring BLA and should be considered before proceeding to BLA. Elevated ACTH concentration within 6 months after BLA is associated with greater risk of the Nelsons' syndrome. When no prior SRS is administered, those with a high ACTH level shortly after BLA may benefit from early SRS.
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http://dx.doi.org/10.1007/s00701-021-04823-1DOI Listing
July 2021

Role of Stereotactic Radiosurgery in Intracranial Histiocytosis: a Systematic Review of Literature of an Emerging Modality for Localized Disease.

World Neurosurg 2021 Jun 17;150:64-70. Epub 2021 Mar 17.

Department of Radiation Therapy, Postgraduate Institute of Medical Education and Research, Chandigarh. Electronic address:

Background: A histiocytosis is a group of immunoproliferative disorders of clonal cells. The management protocols are still evolving, with chemotherapy as the mainstay of treatment.

Objective: This study aims to evaluate the feasibility, safety, efficacy, and complication profile of stereotactic radiosurgery for intracranial histiocytosis.

Methodology: The authors reviewed PubMed, Scopus, Web of Science, and Embase for "radiosurgery" and "histiocytosis" in the English/Japanese language following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The patient profile, radiosurgical parameters (dose and isodose), target volume, and mode of radiosurgery (Gamma knife, LINAC radiosurgery, etc.) were collected. Its use as primary or adjuvant therapy, clinical and radiological outcome was also evaluated.

Results: We identified 7 studies (9 patients); mean age: 41.9 years (24-57 years). Six patients received Gamma-knife radiosurgery, whereas 3 received CyberKnife radiosurgery. The Langerhans cell histiocytosis variants were eosinophilic granuloma in 3, whereas 4 were not defined. Two cases had Rosai-Dorfman disease, and 2 different yet pathogenetically related histiocytic disorders. Four patients harbored lesions in the pituitary stalk and posterior pituitary, 2 patients in the petrous region, 1 patient had a pontine lesion, and 2 patients had multiple lesions. The dose delivered ranged from 8 to 28 Gy. A total of 18 lesions (9 patients) were followed for 81.67 patient-years: 7 (39%) disappeared, 8 (44.4%) showed radiological reduction, and 2 (11%) remained stable. One lesion (5%) showed an increase in size needed surgical excision. There were no adverse effects.

Conclusion: The role of stereotactic radiosurgery needs to be further evaluated as the current cohort with only 9 cases (2 are Rosai-Dorfman disease) is insufficient to make conclusions. It may be a viable alternative in localized disease, along with chemotherapy and targeted surgery.
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http://dx.doi.org/10.1016/j.wneu.2021.03.047DOI Listing
June 2021

Spontaneous pneumocephalus associated with a melanoma brain metastasis: a Case Report.

J Neurooncol 2021 May 9;152(3):617-619. Epub 2021 Mar 9.

Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA, USA.

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http://dx.doi.org/10.1007/s11060-021-03728-4DOI Listing
May 2021

Onyx embolization for dural arteriovenous fistulas: a multi-institutional study.

J Neurointerv Surg 2021 Feb 25. Epub 2021 Feb 25.

Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA.

Background: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance.

Objective: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs.

Methods: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models.

Results: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes.

Conclusions: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.
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http://dx.doi.org/10.1136/neurintsurg-2020-017109DOI Listing
February 2021

The evolution of stereotactic radiosurgery in neurosurgical practice.

J Neurooncol 2021 Feb 21;151(3):451-459. Epub 2021 Feb 21.

Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.

Introduction: Stereotactic radiosurgery (SRS) was born in an attempt to treat complex intracranial pathologies in a fashion whereby open surgery would create unnecessary or excessive risk. To create this innovation, it was necessary to harness advances in other fields such as engineering, physics, radiology, and computer science.

Methods: We review the history of SRS to provide context to today's current state, as well as guide future advancement in the field.

Results: Since time of Lars Leksell, the young Swedish neurosurgeon who pioneered the development of the SRS, the collegial and essential partnership between neurosurgeons, radiation oncologists and physicists has given rise to radiosurgery as a prominent and successful tool in neurosurgical practice.

Conclusion: We examine how neurosurgeons have helped foster the SRS evolution and how this evolution has impacted neurosurgical practice as well as that of radiation oncology and neuro-oncology.
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http://dx.doi.org/10.1007/s11060-020-03392-0DOI Listing
February 2021

Beyond guidelines: analysis of current practice patterns of AANS/CNS tumor neurosurgeons.

J Neurooncol 2021 Feb 21;151(3):361-366. Epub 2021 Feb 21.

Department of Neurological Surgery, Weill Medical College of Cornell University, 525 E. 68th St, Box 99, New York, NY, 10065, USA.

Introduction: Evidence-based medicine guidelines are increasingly published and sanctioned by organized neurosurgery. However, implementation, interpretation, and use of clinical guidelines may vary substantially on a regional, national and international basis. Survey research can help bridge the gap by providing a snapshot of neurosurgeon attitudes, knowledge, and practices. The American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Section on Tumors formed a Survey Committee to formalize the process by which surveys are submitted and reviewed before distribution to our membership. The goal of this committee is to provide peer-review so that collected information will be scientifically robust and useful to the neurosurgical community.

Methods: Surveys submitted to the AANS/CNS tumor section between 2015 and 2019 were reviewed and metrics such as response rate and publication status assessed.

Results: Six surveys were submitted to the Survey Committee of the AANS/CNS section on tumors between 2015 and 2019. Four have been circulated to section members, of which three have been published. Response rate has averaged 19% (range 16-23%), a majority of respondents (mean 70%) practice in academic settings.

Conclusions: The AANS/CNS Section on Tumors Survey Committee has and continues to help promote and improve the practice of surveying our community to answer important questions that can advance future training, research, and practice. There remains significant room for improvement in response rates, but ongoing tumor section efforts to increase member engagement will likely improve these numbers.
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http://dx.doi.org/10.1007/s11060-020-03389-9DOI Listing
February 2021

Internal carotid artery stenosis and risk of cerebrovascular ischemia following stereotactic radiosurgery for recurrent or residual pituitary adenomas.

Pituitary 2021 Feb 20. Epub 2021 Feb 20.

Department of Neurosurgery, University of Virginia Health System, Charlottesville, VA, 22908, USA.

Purpose: To evaluate the incidence of internal carotid artery (ICA) stenosis and cerebrovascular accident in a series of patients treated with stereotactic radiosurgery (SRS) for recurrent or residual pituitary adenoma.

Methods: All patients treated with single fraction SRS in our institution for recurrent or residual non-functioning-, growth hormone- and ACTH-secreting pituitary adenomas were retrospectively identified and reviewed. A comprehensive literature review to identify studies reporting on ICA steno-occlusive disease following SRS for pituitary adenomas and compare the risks of carotid stenosis and ischemic stroke in the SRS treated group to the general population figures.

Results: 528 patients [312 women and 216 men; median age at SRS 46 years old (range 12-80 years)] treated with SRS at our institution met study inclusion criteria. Mean clinical and radiologic follow-ups were 68.87 (SD ± 43.29) and 55.99 months (SD ± 38.03), respectively, and there were no clinically evident cerebral ischemic events noted. Asymptomatic, post-SRS, ICA stenosis occurred in two patients. A total of eight patients with ICA steno-occlusive disease following pituitary adenoma radiosurgery have been reported. Two of them suffered from ischemic stroke with however excellent recovery.

Conclusion: As compared to the general population, SRS for pituitary adenomas does not seem to confer appreciable increased risk for ICA steno-occlusive disease and ischemic stroke. However, post-SRS radiation vessel injuries do occur and physicians should be aware about this rare event. Prompt identification and management according to current guidelines are essential to prevent ischemic strokes.
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http://dx.doi.org/10.1007/s11102-021-01134-7DOI Listing
February 2021

Observation Versus Intervention for Low-Grade Intracranial Dural Arteriovenous Fistulas.

Neurosurgery 2021 May;88(6):1111-1120

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial.

Objective: To compare the outcomes of observation versus intervention for low-grade dAVFs.

Methods: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up.

Results: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively.

Conclusion: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs.
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http://dx.doi.org/10.1093/neuros/nyab024DOI Listing
May 2021

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

Int J Radiat Oncol Biol Phys 2021 Jul 3;110(3):804-814. Epub 2021 Feb 3.

Department of Neurologic Surgery, University of Virginia Health System, Charlottesville, Virginia.

Purpose: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial.

Methods And Materials: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis.

Results: Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%).

Conclusions: SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.048DOI Listing
July 2021

Working Toward Consensus on Sporadic Vestibular Schwannoma Care: A Modified Delphi Study.

Otol Neurotol 2020 Dec;41(10):e1360-e1371

Hong Kong Neurosurgical Associates, Hong Kong SAR, People's Republic of China.

Objective: To address variance in clinical care surrounding sporadic vestibular schwannoma, a modified Delphi study was performed to establish a general framework to approach vestibular schwannoma care. A multidisciplinary panel of experts was established with deliberate representation from key stakeholder societies. External validity of the final statements was assessed through an online survey of registered attendees of the 8th Quadrennial International Conference on Vestibular Schwannoma.

Study Design: Modified Delphi method.

Methods: The panel consisted of 16 vestibular schwannoma experts (8 neurotology and 8 neurosurgery) and included delegates representing the AAOHNSF, AANS/CNS tumor section, ISRS, and NASBS. The modified Delphi method encompassed a four-step process, comprised of one prevoting round to establish a list of focus areas and three subsequent voting rounds to successively refine individual statements and establish levels of consensus. Thresholds for achieving moderate consensus, at ≥67% agreement, and strong consensus, at ≥80% agreement, were determined a priori. All voting was performed anonymously via the Qualtrics online survey tool and full participation from all panel members was required before procession to the next voting round.

Results: Through the Delphi process, 103 items were developed encompassing hearing preservation (N = 49), tumor control and imaging surveillance (N = 20), preferred treatment (N = 24), operative considerations (N = 4), and complications (N = 6). As a result of item refinement, moderate (4%) or strong (96%) consensus was achieved in all 103 final statements. Seventy-nine conference registrants participated in the online survey to assess external validity. Among these survey respondents, moderate (N = 21, 20%) or strong (N = 73, 71%) consensus was achieved in 94 of 103 (91%) statements, and no consensus was reached in 9 (9%). Of the four items with moderate consensus by the expert panel, one had moderate consensus by the conference participants and three had no consensus.

Conclusion: This modified Delphi study on sporadic vestibular schwannoma codifies 100% consensus within a multidisciplinary expert panel and is further supported by 91% consensus among an external group of clinicians who regularly provide care for patients with vestibular schwannoma. These final 103 statements address clinically pragmatic items that have direct application to everyday patient care. This document is not intended to define standard of care or drive insurance reimbursement, but rather to provide a general framework to approach vestibular schwannoma care for providers and patients.
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http://dx.doi.org/10.1097/MAO.0000000000002917DOI Listing
December 2020

Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.

J Neurosurg 2021 Jan 22:1-7. Epub 2021 Jan 22.

1Division of Neurosurgery, Department of Surgery, Université de Sherbrooke, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Québec, Canada.

Objective: Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations.

Methods: The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed.

Results: Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression.

Conclusions: SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.
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http://dx.doi.org/10.3171/2020.8.JNS20887DOI Listing
January 2021

Local failure after stereotactic radiosurgery (SRS) for intracranial metastasis: analysis from a cooperative, prospective national registry.

J Neurooncol 2021 Apr 22;152(2):299-311. Epub 2021 Jan 22.

Department of Neurological Surgery, University of Virginia Health System, 1300 Jefferson Park Ave, Charlottesville, VA, 22908, USA.

Introduction: Stereotactic radiosurgery (SRS) has been increasingly employed to treat patients with intracranial metastasis, both as a salvage treatment after failed whole brain radiation therapy (WBRT) and as an initial treatment. "Several studies have shown that SRS may be as effective as WBRT with the added benefit of preserving neuro-cognition". However, some patients may have local failure following SRS for intracranial metastasis, defined as increase in total lesion volume by 25% after at least 3 months of follow up.

Methods: The SRS registry, established by the Neuro point alliance (NPA) under the auspices of the American Association of Neurological Surgeons (AANS), was queried for patients with intracranial metastasis receiving SRS at the participating sites. Demographic, clinical symptoms, tumor, and treatment characteristics as well as follow up status were summarized for the cohort. A multivariable explanatory cox- regression was performed to evaluate the impact of each of the factors on time to local failure.at last follow-up.

Results: A total of 441 patients with 1255 intracranial metastatic lesions undergoing SRS were identified. The most common primary cancer histology was non-small cell lung cancer (43.8%, n = 193). More than half of the cohort had more than 1 metastatic lesion (2-3 lesions: 29.5%, n = 130; more than 3 lesions: 25.2% (n = 111). The average duration of follow-up for the cohort was found to be 8.4 months (SD = 7.61). The mean clinical treatment volume (CTV), after adding together the volume of each lesion for each patient was 5.39 cc (SD = 7.6) at baseline. A total of 20.2% (n = 89) had local failure (increase in volume by  > 25%) with a mean time to progression of 7.719 months (SD = 6.09). The progression free survival (PFS) for the cohort at 3, 6 and 12 months were found to be 94.9%, 84.3%, and 69.4%, respectively. On multivariable cox regression analysis, factors associated with increased hazard of local failure included male gender (HR 1.65, 95% CI 1.03-2.66, p = 0.037), chemotherapy at or before SRS (HR = 2.39, 95% CI 1.41-4.05, p = 0.001), WBRT at or before SRS (HR = 2.21, 95% CI 1.16- 4.22, p = 0.017), while surgical resection (HR 0.45, 95% CI 0.21-0. 97, p = 0.04) and immunotherapy (0.34, 95% CI 0.16-0.50, p = 0.014) were associated with lower hazard of local failure.

Conclusion: Factors found to be predictive of local failure included higher RPA score and those receiving chemotherapy, while patients undergoing surgical resection and those with occipital lobe lesions were less likely to experience local failure. Our analyses not only corroborate those previously reported but also demonstrate the utility of a multi-institutional registry to advance real-world SRS research for patients with intracranial metastatic lesions.
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http://dx.doi.org/10.1007/s11060-021-03698-7DOI Listing
April 2021

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

Neurosurgery 2021 03;88(4):828-837

Department of Radiation Oncology, University of Colorado, Denver, Colorado.

Background: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas.

Objective: To study the safety and effectiveness of SRS for perioptic meningiomas.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus.

Results: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline.

Conclusion: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.
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http://dx.doi.org/10.1093/neuros/nyaa544DOI Listing
March 2021

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study.

Neurosurgery 2021 04;88(5):980-988

Department of Neurologic Surgery, Mayfield Clinic, Cincinnati, Ohio.

Background: Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described.

Objective: To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs.

Methods: An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model.

Results: A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively.

Conclusion: AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.
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http://dx.doi.org/10.1093/neuros/nyaa553DOI Listing
April 2021

Time from stereotactic radiosurgery to immunotherapy in patients with melanoma brain metastases and impact on outcome.

J Neurooncol 2021 Mar 11;152(1):79-87. Epub 2021 Jan 11.

Department of Neurosurgery, University of Virginia School of Medicine, Charlottesville, USA.

Background: The role of immunotherapy for metastatic melanoma has expanded over the past decade triggering questions regarding the combination and timing of immunotherapy and radiation for brain metastases. We used the National Cancer Database (NCDB) to see if the time from radiation to immunotherapy in patients with melanoma brain metastases had an impact on survival.

Methods: We queried the NCDB from 2010 to 2015 for patients with melanoma brain metastases treated with immunotherapy and stereotactic radiosurgery (SRS). Receiver operator characteristic (ROC) curve analysis was done to determine a timepoint associated with outcome. Cox regression was used to identify predictors of survival. Propensity matching was done to account for indication bias.

Results: We identified 247 patients meeting the above criteria. The median patient age was 62 years (27-90) and the vast majority were Caucasian (99%). The median SRS dose was 22 Gy (18-24 Gy).The median time to SRS was 39 days (0-344) and the median time to immunotherapy was 56 days (6-454). The ROC analysis revealed 8 days from SRS to immunotherapy as associated with outcome. Fifty-six patients had immunotherapy prior to SRS, 30 patients had immunotherapy within 0-7 days of SRS, and the remaining 161 had immunotherapy greater than 7 days from SRS. Three year survival rates were 21%, 55%, and 35% for those timeframes, respectively (p = 0.0153). Propensity matching of the 0-7 day and > 7 day groups yielded 28 pairs and Kaplan Meier analysis showed 3 year overall survival of 55% and 35%, in favor of immunotherapy within 7 days of SRS (p = 0.0357). Multivariable Cox regression identified lack of extracranial disease, more recent year of treatment, and time from SRS to immunotherapy of 0-7 days as predictors of improved survival.

Conclusions: Immunotherapy within 7 days of SRS shows a possible association with improve outcomes in patients with brain metastases from melanoma.
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http://dx.doi.org/10.1007/s11060-020-03663-wDOI Listing
March 2021

Editorial: Radiosurgical induced malignancy associated with stereotactic radiosurgery.

Acta Neurochir (Wien) 2021 04 6;163(4):969-970. Epub 2021 Jan 6.

Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.

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http://dx.doi.org/10.1007/s00701-020-04667-1DOI Listing
April 2021

Proton and Heavy Particle Intracranial Radiosurgery.

Biomedicines 2021 Jan 3;9(1). Epub 2021 Jan 3.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA.

Stereotactic radiosurgery (SRS) involves the delivery of a highly conformal ablative dose of radiation to both benign and malignant targets. This has traditionally been accomplished in a single fraction; however, fractionated approaches involving five or fewer treatments have been delivered for larger lesions, as well as lesions in close proximity to radiosensitive structures. The clinical utilization of SRS has overwhelmingly involved photon-based sources via dedicated radiosurgery platforms (e.g., Gamma Knife and Cyberknife) or specialized linear accelerators. While photon-based methods have been shown to be highly effective, advancements are sought for improved dose precision, treatment duration, and radiobiologic effect, among others, particularly in the setting of repeat irradiation. Particle-based techniques (e.g., protons and carbon ions) may improve many of these shortcomings. Specifically, the presence of a Bragg Peak with particle therapy at target depth allows for marked minimization of distal dose delivery, thus mitigating the risk of toxicity to organs at risk. Carbon ions also exhibit a higher linear energy transfer than photons and protons, allowing for greater relative biological effectiveness. While the data are limited, utilization of proton radiosurgery in the setting of brain metastases has been shown to demonstrate 1-year local control rates >90%, which are comparable to that of photon-based radiosurgery. Prospective studies are needed to further validate the safety and efficacy of this treatment modality. We aim to provide a comprehensive overview of clinical evidence in the use of particle therapy-based radiosurgery.
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http://dx.doi.org/10.3390/biomedicines9010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823941PMC
January 2021

Stereotactic radiosurgery training patterns across neurosurgical programs: a multi-national survey.

J Neurooncol 2021 Jan 4;151(2):325-330. Epub 2021 Jan 4.

Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA, 22908, USA.

Introduction: The field of neurosurgery has witnessed a dramatic increase in the use of stereotactic radiosurgery (SRS) as a modality to treat various cranial and spinal pathologies. However, studies have consistently demonstrated disparities in SRS training. Accordingly, the present study represents a cross-sectional analysis of current SRS training and practice patterns.

Methods: An online survey was utilized to collect data from participants. Two-sided t-tests were used in order to compare frequency tables for statistically significant differences between groups. Qualitative analyses were performed by modified thematic analyses, employing open and axial coding.

Results: A total of 67 participants completed the online survey (16.4% response rate). The majority of participants were neurosurgery attendings (58.2%), followed by neurosurgery residents (25.4%). The majority of participants reported that resident exposure to SRS was gained primarily through non-SRS focused rotations (52.2%). The survey found that exposure to tumor cases was most frequent, followed by functional, vascular, and spine indications. The majority of participants (49.3%) indicate that residents are not competent or exhibit a low level of competency in SRS at the completion of neurosurgical residency. Qualitative analyses demonstrated that respondents believe SRS is a critical modality in current cranial neurosurgical care and that increased training is needed.

Conclusions: This study provides a multi-national analysis of SRS residency training and practice patterns, and aims to stimulate improvement in SRS in training worldwide. Enhanced resident training in SRS must include wider exposure to vascular, neoplastic, functional and pediatric indications for SRS.
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http://dx.doi.org/10.1007/s11060-020-03670-xDOI Listing
January 2021

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

J Neurosurg 2021 Jan 1:1-9. Epub 2021 Jan 1.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS.

Results: Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS.

Conclusions: SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.
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http://dx.doi.org/10.3171/2020.7.JNS202064DOI Listing
January 2021

Stereotactic Radiosurgery for Vestibular Schwannomas: Tumor Control Probability Analyses and Recommended Reporting Standards.

Int J Radiat Oncol Biol Phys 2021 May 26;110(1):100-111. Epub 2020 Dec 26.

Machine Learning Department, Moffitt Cancer Center, Tampa, Florida.

Purpose: We sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS).

Methods And Materials: Studies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions.

Results: Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented.

Conclusions: With current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.019DOI Listing
May 2021

Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation.

Neurosurgery 2021 03;88(4):791-796

Department of Neurological Surgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible.

Objective: To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project.

Methods: A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively.

Results: Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure.

Conclusion: GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.
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http://dx.doi.org/10.1093/neuros/nyaa538DOI Listing
March 2021

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations.

J Neurosurg 2020 Dec 11:1-9. Epub 2020 Dec 11.

14Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus.

Methods: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death.

Results: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively.

Conclusions: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.
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http://dx.doi.org/10.3171/2020.7.JNS201731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192588PMC
December 2020

A comparison of stereotactic body radiation therapy for metastases to the sacral spine and treatment of the thoracolumbar spine.

J Radiosurg SBRT 2020 ;7(2):95-103

University of Virginia/Riverside, Radiosurgery Center, 500 J Clyde Morris Blvd, Newport News, VA 23601, USA.

This study compares the outcomes of stereotactic body radiation therapy (SBRT) for sacral and thoracolumbar spine metastases. This analysis considered each sacral spine SBRT treatment at a single institution and a cohort of consecutive thoracolumbar treatments. 28 patients with 35 sacral treatments and 41 patients with 49 thoracolumbar treatments were included. Local control was 63% and 90%, respectively. The sacral cohort contained more lesions with ≥2 vertebrae and epidural and paraspinal involvement. Sacral patients had larger treatment volumes, increased rates of subsequent SBRT, decreased propensity for pain improvement, and decreased local control (p=0.02 on Kaplan-Meier analysis). Multivariate analysis demonstrated that PTV > 50 cc and epidural involvement were correlated with decreased local control. No cases had grade ≥3 toxicity. SBRT for sacral spine metastases is a distinct disease process than metastases to the thoracolumbar spine, resulting in lower rates of local control and pain improvement.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717089PMC
January 2020