192 results on '"Sneed PK"'
Search Results
2. Surgical Cavity Constriction and Local Progression Between Resection and Adjuvant Radiosurgery for Brain Metastases.
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Aghi, Manish, Shah, JK, Potts, MB, Sneed, PK, Aghi, MK, and McDermott, MW
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Stereotactic radiosurgery (SRS) to a surgical cavity after brain metastasis resection is a promising treatment for improving local control. The optimal timing of adjuvant SRS, however, has yet to be determined. Changes in resection cavity volume and local more...
- Published
- 2016
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3. Whole-procedural radiological accuracy for delivering multi-session gamma knife radiosurgery with a relocatable frame system
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Ma, Lijun, Sneed, Patricia, Pinnaduwage, Dilini, McDermott, Michael, and Sneed, PK
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A newly developed Gamma Knife relocatable eXtend frame system has enabled the delivery of multi-session Gamma Knife radiosurgery without the use of skull pin fixation frame system. In this study, we investigate and report for the first time the whole proce more...
- Published
- 2014
4. Deep arteriovenous malformations in the basal ganglia, thalamus, and insula: Multimodality management, patient selection, and results
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Potts, MB, Jahangiri, A, Jen, M, Sneed, PK, McDermott, MW, Gupta, N, Hetts, SW, Young, WL, and Lawton, MT
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Clinical Sciences ,Neurosciences - Abstract
OBJECTIVE: This study sought to describe a single institutions experience treating arteriovenous malformations (AVMs) of the basal ganglia, thalamus, and insula in a multimodal fashion.
- Published
- 2014
5. High-precision volume-staged Gamma Knife surgery and equivalent hypofractionation dose schedules for treating large arteriovenous malformations
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Fogh, S, Ma, L, Gupta, N, Sahgal, A, Nakamura, JL, Barani, I, Sneed, PK, McDermott, M, and Larson, DA
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Intracranial Arteriovenous Malformations ,Radiation ,Neurology & Neurosurgery ,hypofractionation ,stereotactic radiosurgery ,Clinical Sciences ,arteriovenous malformation ,Neurosciences ,Brain ,Radiosurgery ,Magnetic Resonance Imaging ,Treatment Outcome ,Gamma Knife surgery ,Clinical Research ,Humans ,Dose Fractionation, Radiation ,volume staging ,Child ,Dose Fractionation - Abstract
ObjectThe goal of this study was to develop a technique for performing submillimeter high-precision volume-staged Gamma Knife surgery and investigate its potential benefits in comparison with hypofractionated stereotactic radiotherapy (SRT) for treating large arteriovenous malformations (AVMs).MethodsThe authors analyzed 7 pediatric AVM cases treated with volume-staged stereotactic radiosurgery (SRS) using the Gamma Knife Perfexion at the University of California, San Francisco. The target and normal tissue contours from each case were exported for hypofractionated treatment planning based on the Gamma Knife Extend system or the CyberKnife SRT. Both the Gamma Knife Extend and CyberKnife treatment plans were matched to yield the same level of target coverage (95%-98%) and conformity indices (1.24-1.46). Finally, hypofractionated treatment plans were compared with volume-staged treatment plans for sparing normal brain by using biologically equivalent 12-Gy normal brain volumes.ResultsHypofractionated Gamma Knife Extend and CyberKnife treatment plans exhibited practically identical sparing of normal brain for the studied cases. However, when matching such values with volume-staged treatments for the biological effective dose, only conservative dose fractionation schemes, such as 27.3 Gy in 5 fractions and 25 Gy in 4 fractions, were found to be comparable to the volume-staged treatments. On average, this represents a mean 18.7% ± 7.3% reduction in the single-fraction biologically equivalent dose for hypofractionated treatments versus the reference volume-staged treatments (p < 0.001).ConclusionsVolume staging remains advantageous over hypofractionation in delivering a higher dose to the target and for better sparing of normal brain tissue in the treatment of large AVMs. More clinical data are needed, however, to justify the clinical superiority of this increased dose when compared with a hypofractionated treatment regimen. more...
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- 2012
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6. Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma.
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Prados MD, Chang SM, Butowski N, DeBoer R, Parvataneni R, Carliner H, Kabuubi P, Ayers-Ringler J, Rabbitt J, Page M, Fedoroff A, Sneed PK, Berger MS, McDermott MW, Parsa AT, Vandenberg S, James CD, Lamborn KR, Stokoe D, and Haas-Kogan DA more...
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- 2009
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7. Radiosurgery for brain metastases from primary lung carcinoma.
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Hoffman R, Sneed PK, McDermott MW, Chang S, Lamborn KR, Park E, Wara WM, and Larson DA
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PURPOSE: Brain metastases are a common problem in patients with lung cancer. This retrospective review was performed to describe the efficacy and toxicity of stereotactic radiosurgery for brain metastases from lung carcinoma and to evaluate prognostic factors for survival. PATIENTS AND METHODS: A retrospective review was performed of 113 patients with the diagnosis of lung carcinoma who underwent radiosurgery with or without whole-brain radiotherapy for management of newly diagnosed or recurrent, single, or multiple brain metastases from 1991 through 1998 at the University of California, San Francisco. Freedom from progression and survival were measured from the date of radiosurgery and estimated using the Kaplan-Meier method. Prognostic factors were evaluated with the log-rank test and Cox proportional hazards models. RESULTS: The median patient age at the time of radiosurgery was 59 years (range, 37-82 years), and the median Karnofsky performance score was 90 (range, 50-100). The median survival time from radiosurgery was 12.0 months overall, 13.9 months for 41 patients treated with radiosurgery alone initially, 14.5 months for 19 patients treated with radiosurgery and whole-brain radiotherapy initially, and 10.0 months for 53 patients with recurrent brain metastases. Among newly diagnosed patients, multivariate analysis showed that improved survival was associated with absence of extracranial metastases and fewer brain metastases. Among patients with recurrent brain metastases, improved survival was associated with higher Karnofsky performance score, control of the primary tumor, and fewer metastases. Measured by lesion, 1-year local freedom from progression probabilities were 81% for radiosurgery alone, 86% for radiosurgery and whole-brain radiotherapy, and 65% for radiosurgery performed after recurrence. In patients with newly diagnosed brain metastases, there was a significantly greater risk of developing subsequent brain metastases and of worse overall brain freedom from progression after radiosurgery alone versus radiosurgery and whole-brain radiotherapy. One-year brain freedom from progression probabilities were 13% without salvage therapy and 62% with salvage therapy in the 41 patients treated initially with radiosurgery alone, versus 67% without salvage therapy and 89% with salvage therapy in the 19 patients treated initially with radiosurgery plus whole-brain radiotherapy. DISCUSSION: Radiosurgery is an effective therapy for selected patients with newly diagnosed or recurrent brain metastases from lung carcinoma. Initial whole-brain radiotherapy with radiosurgery appears to improve brain control but not survival. Prospective, randomized trials are needed to further investigate the role of radiosurgery with and without whole-brain radiotherapy for brain metastases. [ABSTRACT FROM AUTHOR] more...
- Published
- 2001
8. Gamma knife radiosurgery for malignant melanoma brain metastases.
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Seung SK, Sneed PK, Mcdermott MW, Shu HG, Leong SP, Chang S, Petti PL, Smith V, Verhey LJ, Wara WM, Phillips TL, and Larson DA
- Abstract
PURPOSE: To evaluate the efficacy and toxicity of gamma knife radiosurgery in the treatment of melanoma metastases to the brain. PATIENTS AND METHODS: We retrospectively reviewed 55 patients with single or multiple intracranial melanoma metastases treated at the University of California, San Francisco, with gamma knife radiosurgery from 1991 through 1995. Sixteen patients were treated with gamma knife radiosurgery for recurrence following previous radiation therapy, 11 received radiosurgery as a boost to whole-brain radiation therapy, and 28 had radiosurgery alone for initial management of brain metastases. The median minimum radiosurgery tumor dose for 140 treated lesions was 19 Gy (range, 10-22 Gy) prescribed at the 35% to 90% isodose contour (median, 50%). The median total target volume per patient was 6.1 cc (range, 0.25-28.3 cc). RESULTS: With a median follow-up of 75 weeks in living patients, the median survival times were 35 weeks overall: 35 weeks for patients with solitary metastases versus 33 weeks for those with multiple metastases. A factor that was significant in univariate analysis of survival was total target volume treated. This parameter remained significant on multivariate analysis. The actuarial median freedom from progression analyzed by lesion for 113 lesions in 46 patients with imaging follow-up was 89 weeks with 6-month and 1-year actuarial freedom from progression rates of 89% (95% confidence interval, 80%-95%) and 77% (95% confidence interval, 62%-87%). In univariate analysis, improved freedom from progression was associated with smaller target volume treated, smaller maximum diameter, or higher prescribed dose. Four patients (7%) developed acute Radiation Therapy Oncology Group grade > or = 2 morbidity, and five patients (9%) developed late grade > or = 2 morbidity. DISCUSSION: Median survival and freedom from progression in patients treated with radiosurgery for melanoma metastatic to the brain are comparable to results in published radiosurgery series of grouped histologies. For melanoma patients, total intracranial tumor volume appears to be of greater prognostic significance than the absolute number of metastases treated. We conclude that gamma knife radiosurgery is effective and should be considered among various management strategies. [ABSTRACT FROM AUTHOR] more...
- Published
- 1998
9. Adverse radiation effect versus tumor progression following stereotactic radiosurgery for brain metastases: Implications of radiologic uncertainty.
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Salans M, Ni L, Morin O, Ziemer B, Capaldi DPI, Raleigh DR, Vasudevan HN, Chew J, Nakamura J, Sneed PK, Boreta L, Villanueva-Meyer JE, Theodosopoulos P, and Braunstein S
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- Humans, Treatment Outcome, Retrospective Studies, Uncertainty, Radiosurgery adverse effects, Radiosurgery methods, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Brain Neoplasms pathology, Radiation Injuries diagnostic imaging, Radiation Injuries etiology, Radiation Injuries surgery
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Background: Adverse radiation effect (ARE) following stereotactic radiosurgery (SRS) for brain metastases is challenging to distinguish from tumor progression. This study characterizes the clinical implications of radiologic uncertainty (RU)., Methods: Cases reviewed retrospectively at a single-institutional, multi-disciplinary SRS Tumor Board between 2015-2022 for RU following SRS were identified. Treatment history, diagnostic or therapeutic interventions performed upon RU resolution, and development of neurologic deficits surrounding intervention were obtained from the medical record. Differences in lesion volume and maximum diameter at RU onset versus resolution were compared with paired t-tests. Median time from RU onset to resolution was estimated using the Kaplan-Meier method. Univariate and multivariate associations between clinical characteristics and time to RU resolution were assessed with Cox proportional-hazards regression., Results: Among 128 lesions with RU, 23.5% had undergone ≥ 2 courses of radiation. Median maximum diameter (20 vs. 16 mm, p < 0.001) and volume (2.7 vs. 1.5 cc, p < 0.001) were larger upon RU resolution versus onset. RU resolution took > 6 and > 12 months in 25% and 7% of cases, respectively. Higher total EQD2 prior to RU onset (HR = 0.45, p = 0.03) and use of MR perfusion (HR = 0.56, p = 0.001) correlated with shorter time to resolution; larger volume (HR = 1.05, p = 0.006) portended longer time to resolution. Most lesions (57%) were diagnosed as ARE. Most patients (58%) underwent an intervention upon RU resolution; of these, 38% developed a neurologic deficit surrounding intervention., Conclusions: RU resolution took > 6 months in > 25% of cases. RU may lead to suboptimal outcomes and symptom burden. Improved characterization of post-SRS RU is needed., (© 2024. The Author(s).) more...
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- 2024
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10. Epigenetic reprogramming shapes the cellular landscape of schwannoma.
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Liu SJ, Casey-Clyde T, Cho NW, Swinderman J, Pekmezci M, Dougherty MC, Foster K, Chen WC, Villanueva-Meyer JE, Swaney DL, Vasudevan HN, Choudhury A, Pak J, Breshears JD, Lang UE, Eaton CD, Hiam-Galvez KJ, Stevenson E, Chen KH, Lien BV, Wu D, Braunstein SE, Sneed PK, Magill ST, Lim D, McDermott MW, Berger MS, Perry A, Krogan NJ, Hansen MR, Spitzer MH, Gilbert L, Theodosopoulos PV, and Raleigh DR more...
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- Humans, Epigenesis, Genetic, Cellular Reprogramming genetics, Tumor Microenvironment genetics, Neurilemmoma genetics, Neurilemmoma pathology
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Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy., (© 2023. The Author(s).) more...
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- 2024
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11. Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.
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Chen WC, Choudhury A, Youngblood MW, Polley MC, Lucas CG, Mirchia K, Maas SLN, Suwala AK, Won M, Bayley JC, Harmanci AS, Harmanci AO, Klisch TJ, Nguyen MP, Vasudevan HN, McCortney K, Yu TJ, Bhave V, Lam TC, Pu JK, Li LF, Leung GK, Chan JW, Perlow HK, Palmer JD, Haberler C, Berghoff AS, Preusser M, Nicolaides TP, Mawrin C, Agnihotri S, Resnick A, Rood BR, Chew J, Young JS, Boreta L, Braunstein SE, Schulte J, Butowski N, Santagata S, Spetzler D, Bush NAO, Villanueva-Meyer JE, Chandler JP, Solomon DA, Rogers CL, Pugh SL, Mehta MP, Sneed PK, Berger MS, Horbinski CM, McDermott MW, Perry A, Bi WL, Patel AJ, Sahm F, Magill ST, and Raleigh DR more...
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- Humans, Biomarkers, Gene Expression Profiling, Neoplasm Recurrence, Local pathology, Prospective Studies, Meningeal Neoplasms genetics, Meningeal Neoplasms radiotherapy, Meningeal Neoplasms pathology, Meningioma genetics, Meningioma radiotherapy, Meningioma pathology
- Abstract
Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.) more...
- Published
- 2023
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12. Analysis of upfront resection or stereotactic radiosurgery for local control of solid and cystic cerebellar hemangioblastomas.
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Carrete LR, Morshed RA, Young JS, Avalos LN, Sneed PK, Aghi MK, McDermott MW, and Theodosopoulos PV
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- Humans, Treatment Outcome, Retrospective Studies, Neoplasm Recurrence, Local surgery, Follow-Up Studies, Radiosurgery, Hemangioblastoma surgery, Cerebellar Neoplasms radiotherapy, Cerebellar Neoplasms surgery
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Objective: The purpose of this study was to identify rates of and risk factors for local tumor progression in patients who had undergone surgery or radiosurgery for the management of cerebellar hemangioblastoma and to describe treatments pursued following tumor progression., Methods: The authors conducted a retrospective single-center review of patients who had undergone treatment of a cerebellar hemangioblastoma with either surgery or stereotactic radiosurgery (SRS) between 1996 and 2019. Univariate and multivariate regression analyses were performed to examine factors associated with local tumor control., Results: One hundred nine patients met the study inclusion criteria. Overall, these patients had a total of 577 hemangioblastomas, 229 of which were located in the cerebellum. The surgical and SRS cohorts consisted of 106 and 123 cerebellar hemangioblastomas, respectively. For patients undergoing surgery, tumors were treated with subtotal resection and gross-total resection in 5.7% and 94.3% of cases, respectively. For patients receiving SRS, the mean target volume was 0.71 cm3 and the mean margin dose was 18.0 Gy. Five-year freedom from lesion progression for the surgical and SRS groups was 99% and 82%, respectively. The surgical and SRS cohorts contained 32% versus 97% von Hippel-Lindau tumors, 78% versus 7% cystic hemangioblastomas, and 12.8- versus 0.56-cm3 mean tumor volumes, respectively. On multivariate analysis, factors associated with local tumor progression in the SRS group included older patient age (HR 1.06, 95% CI 1.03-1.09, p < 0.001) and a cystic component (HR 9.0, 95% CI 2.03-32.0, p = 0.001). Repeat SRS as salvage therapy was used more often for smaller tumor recurrences, and no tumor recurrences of < 1.0 cm3 required additional salvage surgery following repeat SRS., Conclusions: Both surgery and SRS achieve high rates of local control of hemangioblastomas. Age and cystic features are associated with local progression after SRS treatment for cerebellar hemangioblastomas. In cases of local tumor recurrence, salvage surgery and repeat SRS are valid forms of treatment to achieve local tumor control, although resection may be preferable for larger recurrences. more...
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- 2023
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13. Stereotactic Radiosurgery for Primary Central Nervous System Lymphoma.
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Wu SY, Braunstein SE, Rubenstein JL, and Sneed PK
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Background Primary central nervous system lymphoma (PCNSL) is rare, with a treatment backbone that typically includes high-dose methotrexate-based chemotherapy, with radiation often reserved for persistent or progressive disease. In this study, we report the outcomes of stereotactic radiosurgery (SRS) in patients with PCNSL to potentially defer whole brain radiotherapy (WBRT) or as salvage after WBRT. Methodology We performed a single-institution, retrospective review of 20 patients with PCNSL who received single-fraction or fractionated SRS to 32 lesions between September 1992 and July 2019. Results The median age at SRS was 67 years (interquartile range (IQR) = 56-74 years). The median Karnofsky Performance Status (KPS) at SRS was 80 (IQR = 50-80). In total, 18 (90%) patients received methotrexate-based chemotherapy prior to SRS, with a median of eight cycles (IQR = 5-10). A total of 10 patients received SRS for recurrent disease after chemotherapy and/or WBRT, nine patients received SRS for the persistent disease after chemotherapy alone, and one patient received up-front SRS. Overall, five patients received SRS following WBRT. The median SRS dose was 16 Gy (IQR = 14-22.5 Gy) in one fraction (IQR = 1-5 fractions). Eight patients (40%) were treated with consolidative pomalidomide or lenalidomide following SRS. The local control rate was 100% (32/32 lesions at a median follow-up of 15 months). In total, 13 of 16 (81%) patients with available follow-up experienced distant brain recurrence. The median time to distant failure following SRS was 10 months (IQR = 1-16 months). Three patients received salvage SRS, and three patients received salvage WBRT. The median overall survival from diagnosis was 39 months (95% confidence interval = 24-54 months). KPS at the time of SRS was significantly correlated with time to progression (p = 0.002). The use of lenalidomide or pomalidomide after SRS was associated with improved overall survival after SRS (three vs. 14 months, p = 0.035). Consolidative etoposide and cytarabine after initial methotrexate-based chemotherapy was also associated with improved survival following SRS (eight vs. 47 months, p = 0.028). Conclusions SRS offers effective local tumor control for patients with PCNSL; however, the majority of patients experience distant progression. SRS may have a role in the salvage setting for patients with recurrence after WBRT, or allow deferral of WBRT in select patients, although systemic therapy appears to strongly influence outcomes in this cohort., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Wu et al.) more...
- Published
- 2023
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14. Mutational Status and Clinical Outcomes Following Systemic Therapy with or without Focal Radiation for Resected Melanoma Brain Metastases.
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Vasudevan HN, Susko MS, Ma L, Nakamura JL, Raleigh DR, Boreta L, Fogh S, Theodosopoulos PV, McDermott MW, Tsai KK, Sneed PK, and Braunstein SE
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- Humans, Proto-Oncogene Proteins B-raf genetics, Protein Kinase Inhibitors, Mutation, Retrospective Studies, Radiosurgery methods, Brain Neoplasms genetics, Brain Neoplasms therapy, Brain Neoplasms pathology, Melanoma therapy, Melanoma drug therapy
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Background: Brain metastases occur frequently in advanced melanoma and traditionally require surgery and radiation therapy. New evidence demonstrates that systemic therapies are effective for controlling metastatic melanoma brain metastases. This study evaluated outcomes after resection of melanoma brain metastases treated with systemic therapy, with or without focal radiotherapy., Methods: All patients received immunotherapy or BRAF/MEK inhibitors preoperatively or in the immediate 3 months postoperatively. Resection cavity failure, distant central nervous system progression, and adverse radiation effects were reported in the presence and absence of focal radiotherapy using the Kaplan-Meier method., Results: Between 2011 and 2020, 37 resection cavities in 29 patients met criteria for analysis. Of lesions, 22 (59%) were treated with focal radiotherapy, and 15 (41%) were treated with targeted therapy or immunotherapy alone. The 12- and 24-month freedom from local recurrence was 64.8% (95% confidence interval [CI] 42.1%-99.8%) and 46.3% (95% CI 24.5%-87.5%), respectively, for systemic therapy alone and 93.3% (95% CI 81.5%-100%) at both time points for focal radiotherapy (P = 0.01). On univariate analysis, focal radiotherapy was the only significant factor associated with reduction of local recurrence risk (hazard ratio 0.10, 95% CI 0.01-0.85; P = 0.04). There were no significant differences in central nervous system progression-free survival or overall survival between patients who received systemic therapy plus focal radiotherapy compared with systemic therapy alone. BRAF mutation status was reviewed for either the brain metastasis (n = 9 patients, 31%) or the primary site (n = 20 patients, 69%), and patients harboring BRAF
V600E mutations had worse progression-free survival (P = 0.043)., Conclusions: Focal radiotherapy with systemic therapy for resected melanoma brain metastases significantly decreased resection cavity recurrence compared with systemic therapy alone. BRAF mutation status correlated with poorer outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.) more...- Published
- 2023
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15. Adverse radiation effect and freedom from progression following repeat stereotactic radiosurgery for brain metastases.
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Sneed PK, Chan JW, Ma L, Braunstein SE, Theodosopoulos PV, Fogh SE, Nakamura JL, Boreta L, Raleigh DR, Ziemer BP, Morin O, Hervey-Jumper SL, and McDermott MW
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- Humans, Retrospective Studies, Treatment Outcome, Radiosurgery adverse effects, Radiosurgery methods, Radiation Injuries diagnostic imaging, Radiation Injuries etiology, Radiation Injuries surgery, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Brain Neoplasms pathology, Melanoma secondary
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Objective: The authors previously evaluated risk and time course of adverse radiation effects (AREs) following stereotactic radiosurgery (SRS) for brain metastases, excluding lesions treated after prior SRS. In the present analysis they focus specifically on single-fraction salvage SRS to brain metastases previously treated with SRS or hypofractionated SRS (HFSRS), evaluating freedom from progression (FFP) and the risk and time course of AREs., Methods: Brain metastases treated from September 1998 to May 2019 with single-fraction SRS after prior SRS or HFSRS were analyzed. Serial follow-up magnetic resonance imaging (MRI) and surgical pathology reports were reviewed to score local treatment failure and AREs. The Kaplan-Meier method was used to estimate FFP and risk of ARE measured from the date of repeat SRS with censoring at the last brain MRI., Results: A total of 229 retreated brain metastases in 124 patients were evaluable. The most common primary cancers were breast, lung, and melanoma. The median interval from prior SRS/HFSRS to repeat SRS was 15.4 months, the median prescription dose was 18 Gy, and the median duration of follow-up imaging was 14.5 months. At 1 year after repeat SRS, FFP was 80% and the risk of symptomatic ARE was 11%. The 1-year risk of imaging changes, including asymptomatic RE and symptomatic ARE, was 30%. Among lesions that demonstrated RE, the median time to onset was 6.7 months (IQR 4.7-9.9 months) and the median time to peak imaging changes was 10.1 months (IQR 5.6-13.6 months). Lesion size by quadratic mean diameter (QMD) showed similar results for QMDs ranging from 0.75 to 2.0 cm (1-year FFP 82%, 1-year risk of symptomatic ARE 11%). For QMD < 0.75 cm, the 1-year FFP was 86% and the 1-year risk of symptomatic ARE was only 2%. Outcomes were worse for QMDs 2.01-3.0 cm (1-year FFP 65%, 1-year risk of symptomatic ARE 24%). The risk of symptomatic ARE was not increased with tyrosine kinase inhibitors or immunotherapy before or after repeat SRS., Conclusions: RE on imaging was common after repeat SRS (30% at 1 year), but the risk of a symptomatic ARE was much less (11% at 1 year). The results of repeat single-fraction SRS were good for brain metastases ≤ 2 cm. The authors recommend an interval ≥ 6 months from prior SRS and a prescription dose ≥ 18 Gy. Alternatives such as HFSRS, laser interstitial thermal therapy, or resection with adjuvant radiation should be considered for recurrent brain metastases > 2 cm. more...
- Published
- 2022
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16. Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.
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Choudhury A, Magill ST, Eaton CD, Prager BC, Chen WC, Cady MA, Seo K, Lucas CG, Casey-Clyde TJ, Vasudevan HN, Liu SJ, Villanueva-Meyer JE, Lam TC, Pu JK, Li LF, Leung GK, Swaney DL, Zhang MY, Chan JW, Qiu Z, Martin MV, Susko MS, Braunstein SE, Bush NAO, Schulte JD, Butowski N, Sneed PK, Berger MS, Krogan NJ, Perry A, Phillips JJ, Solomon DA, Costello JF, McDermott MW, Rich JN, and Raleigh DR more...
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- DNA Methylation genetics, Humans, Neurofibromin 2 genetics, Proteomics, Meningeal Neoplasms genetics, Meningioma genetics
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Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.) more...
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- 2022
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17. Recurrent Radiation-Induced Cavernous Malformation After Gamma Knife Stereotactic Radiosurgery for Brain Metastasis.
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Chew JJ, Sneed PK, and Chang EF
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Cavernous malformations are a rare complication of radiation therapy reported most commonly as a late complication after cranial irradiation for pediatric malignancies. However, cavernous malformations after stereotactic radiosurgery in adult patients are not well characterized. We present a case of a 67-year-old female with metastatic breast cancer who received Gamma Knife stereotactic radiosurgery for brain metastases and developed a cavernous malformation at the site of a treated metastasis 30 months after treatment. She underwent resection and did well until 55 months later, when she developed symptomatic recurrence of cavernous malformation without evidence of tumor recurrence, requiring repeat resection. This represents the first reported case of radiation-induced cavernous malformation treated with stereotactic radiosurgery for brain metastases, who later developed a recurrence of the cavernous malformation. As patients with brain metastases are living longer and are increasingly treated with stereotactic radiosurgery, awareness of cavernous malformation as a potential complication and the risk of recurrence is critical to ensure appropriate diagnosis and management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Chew et al.) more...
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- 2022
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18. Resection with intraoperative cesium-131 brachytherapy as salvage therapy for recurrent brain tumors.
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Chen WC, Lafreniere M, Phuong C, Liu SJ, Baal JD, Lometti M, Morin O, Ziemer B, Vasudevan HN, Lucas CG, Hervey-Jumper SL, Theodosopoulos PV, Magill ST, Fogh S, Nakamura JL, Boreta L, Sneed PK, McDermott MW, Raleigh DR, and Braunstein SE more...
- Abstract
Objective: The authors' objective was to examine the safety and efficacy of salvage intracranial cesium-131 brachytherapy in combination with resection of recurrent brain tumors., Methods: The authors conducted a retrospective chart review of consecutive patients treated with intraoperative intracranial cesium-131 brachytherapy at a single institution. Permanent suture-stranded cesium-131 seeds were implanted in the resection cavity after maximal safe tumor resection. The primary outcomes of interest were local, locoregional (within 1 cm), and intracranial control, as well as rates of overall survival (OS), neurological death, symptomatic adverse radiation effects (AREs), and surgical complication rate graded according to Common Terminology Criteria for Adverse Events version 5.0., Results: Between 2016 and 2020, 36 patients received 40 consecutive cesium-131 implants for 42 recurrent brain tumors and received imaging follow-up for a median (interquartile range [IQR]) of 17.0 (12.7-25.9) months. Twenty patients (55.6%) with 22 implants were treated for recurrent brain metastasis, 12 patients (33.3%) with 16 implants were treated for recurrent atypical (n = 7) or anaplastic (n = 5) meningioma, and 4 patients (11.1%) were treated for other recurrent primary brain neoplasms. All except 1 tumor (97.6%) had received prior radiotherapy, including 20 (47.6%) that underwent 2 or more prior radiotherapy treatments and 23 (54.8%) that underwent prior resection. The median (IQR) tumor size was 3.0 (2.3-3.7) cm, and 17 lesions (40.5%) had radiographic evidence of ARE prior to salvage therapy. Actuarial 1-year local/locoregional/intracranial control rates for the whole cohort and patients with metastases and meningiomas were 91.6%/83.4%/47.9%, 88.8%/84.4%/45.4%, and 100%/83.9%/46.4%, respectively. No cases of local recurrence of any histology (0 of 27) occurred after gross-total resection (p = 0.012, log-rank test). The 1-year OS rates for the whole cohort and patients with metastases and meningiomas were 82.7%, 79.1%, and 91.7%, respectively, and the median (IQR) survival of all patients was 26.7 (15.6-36.4) months. Seven patients (19.4%) experienced neurological death from progressive intracranial disease (7 of 14 total deaths [50%]), 5 (13.9%) of whom died of leptomeningeal disease. Symptomatic AREs were observed in 9.5% of resection cavities (n = 4), of which 1 (2.4%) was grade 3 in severity. The surgical complication rate was 16.7% (n = 7); 4 (9.5%) of these patients had grade 3 or higher complications, including 1 patient (2.4%) who died perioperatively., Conclusions: Cesium-131 brachytherapy resulted in good local control and acceptable rates of symptomatic AREs and surgical complications in this heavily pretreated cohort, and it may be a reasonable salvage adjuvant treatment for this patient population. more...
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- 2022
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19. Long-Term Report of a Comprehensive Molecular and Genomic Analysis in NRG Oncology/RTOG 0424: A Phase II Study of Radiation and Temozolomide in High-Risk Grade II Glioma.
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Fleming JL, Pugh SL, Fisher BJ, Lesser GJ, Macdonald DR, Bell EH, McElroy JP, Becker AP, Timmers CD, Aldape KD, Rogers CL, Doyle TJ, Werner-Wasik M, Bahary JP, Yu HM, D'Souza DP, Laack NN, Sneed PK, Kwok Y, Won M, Mehta MP, and Chakravarti A more...
- Subjects
- DNA Methylation genetics, DNA Modification Methylases genetics, DNA Repair Enzymes genetics, DNA-Binding Proteins genetics, Genomics, Humans, RNA-Binding Proteins genetics, Temozolomide therapeutic use, Tumor Suppressor Proteins genetics, Brain Neoplasms drug therapy, Glioma drug therapy
- Abstract
Purpose: This study sought to determine the prognostic significance of the WHO-defined glioma molecular subgroups along with additional alterations, including MGMT promoter methylation and mutations in ATRX , CIC , FUBP1 , TERT , and TP53 , in NRG/RTOG 0424 using long-term follow-up data., Methods: Mutations were determined using an Ion Torrent sequencing panel. 1p/19q co-deletion and MGMT promoter methylation were determined by Affymetrix OncoScan and Illumina 450K arrays. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios were calculated using the Cox proportional hazard model. Multivariable analyses (MVAs) included patient pretreatment characteristics., Results: We obtained complete molecular data to categorize 80/129 eligible patients within the WHO subgroups. Of these, 26 (32.5%) were IDH mutant/co-deleted, 28 (35%) were IDH mutant/non-co-deleted, and 26 (32.5%) were IDH wild-type. Upon single-marker MVA, both IDH mutant subgroups were associated with significantly better OS and PFS ( P values < .001), compared with the IDH wild-type subgroup. MGMT promoter methylation was obtained on 76 patients, where 58 (76%) were methylated and 18 (24%) were unmethylated. Single-marker MVAs demonstrated that MGMT promoter methylation was statistically significant for OS ( P value < .001) and PFS ( P value = .003). In a multimarker MVA, one WHO subgroup comparison ( IDH mutant/co-deleted v IDH wild-type) was significant for OS ( P value = .045), whereas MGMT methylation did not retain significance., Conclusion: This study reports the long-term prognostic effect of the WHO molecular subgroups, MGMT promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and MGMT both serve as strong prognostic indicators, but that MGMT does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond IDH and 1p/19q status., Competing Interests: Stephanie L. Pugh Research Funding: Pfizer, Millennium Glenn J. Lesser Honoraria: SDP Oncology Consulting or Advisory Role: Cancer Expert Now, Agios, Incysus Research Funding: Novocure, Oblato, Denovo Biopharma, Global Coalition for Adaptive Research Other Relationship: NCI, ASCO David R. Macdonald Research Funding: Celgene, Servier Erica H. Bell Patents, Royalties, Other Intellectual Property: US20180002762A1 Joseph P. McElroy Employment: Pfizer Cynthia D. Timmers Employment: Incyte Stock and Other Ownership Interests: Array BioPharma, Seattle Genetics, Exact Sciences, Incyte, Arbutus Biopharma, PDS Biotechnology Consulting or Advisory Role: Ventana Medical Systems C. Leland Rogers Employment: Barrow Neurological Institute, GammaWest Cancer Services Stock and Other Ownership Interests: GT Technologies Maria Werner-Wasik Stock and Other Ownership Interests: Illumina Honoraria: AstraZeneca Patents, Royalties, Other Intellectual Property: Signal transduction inhibitor in lymphoma Hsiang-Hsuan Michael Yu Honoraria: UpToDate, Elsevier, Sermo, Guidepoint Global Consulting or Advisory Role: Novocure Speakers' Bureau: BrainLAB Research Funding: Bristol Myers Squibb/Sanofi, Merck Travel, Accommodations, Expenses: BrainLAB David P. D'Souza Consulting or Advisory Role: AbbVie Nadia N. Laack Research Funding: Bristol Myers Squibb Minesh P. Mehta Leadership: Oncoceutics Stock and Other Ownership Interests: Chimerix Consulting or Advisory Role: Tocagen, Karyopharm Therapeutics, Mevion Medical Systems, ZappRx, Sapience Therapeutics Patents, Royalties, Other Intellectual Property: WARF patent 14/934,27, Topical Vasoconstritor Preparations and Methods for Protecting Cells During Cancer Chemotherapy and Radiotherapy Uncompensated Relationships: Xcision Medical Systems, ViewRay Arnab Chakravarti Research Funding: Varian Medical Systems No other potential conflicts of interest were reported. Stephanie L. Pugh Research Funding: Pfizer, Millennium Glenn J. Lesser Honoraria: SDP Oncology Consulting or Advisory Role: Cancer Expert Now, Agios, Incysus Research Funding: Novocure, Oblato, Denovo Biopharma, Global Coalition for Adaptive Research Other Relationship: NCI, ASCO David R. Macdonald Research Funding: Celgene, Servier Erica H. Bell Patents, Royalties, Other Intellectual Property: US20180002762A1 Joseph P. McElroy Employment: Pfizer Cynthia D. Timmers Employment: Incyte Stock and Other Ownership Interests: Array BioPharma, Seattle Genetics, Exact Sciences, Incyte, Arbutus Biopharma, PDS Biotechnology Consulting or Advisory Role: Ventana Medical Systems C. Leland Rogers Employment: Barrow Neurological Institute, GammaWest Cancer Services Stock and Other Ownership Interests: GT Technologies Maria Werner-Wasik Stock and Other Ownership Interests: Illumina Honoraria: AstraZeneca Patents, Royalties, Other Intellectual Property: Signal transduction inhibitor in lymphoma Hsiang-Hsuan Michael Yu Honoraria: UpToDate, Elsevier, Sermo, Guidepoint Global Consulting or Advisory Role: Novocure Speakers' Bureau: BrainLAB Research Funding: Bristol Myers Squibb/Sanofi, Merck Travel, Accommodations, Expenses: BrainLAB David P. D'Souza Consulting or Advisory Role: AbbVie Nadia N. Laack Research Funding: Bristol Myers Squibb Minesh P. Mehta Leadership: Oncoceutics Stock and Other Ownership Interests: Chimerix Consulting or Advisory Role: Tocagen, Karyopharm Therapeutics, Mevion Medical Systems, ZappRx, Sapience Therapeutics Patents, Royalties, Other Intellectual Property: WARF patent 14/934,27, Topical Vasoconstritor Preparations and Methods for Protecting Cells During Cancer Chemotherapy and Radiotherapy Uncompensated Relationships: Xcision Medical Systems, ViewRay Arnab Chakravarti Research Funding: Varian Medical Systems No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.) more...
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- 2021
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20. Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.
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Seymour ZA, Chan JW, McDermott MW, Grills I, Ye H, Kano H, Lehocky CA, Jacobs RC, Lunsford LD, Chytka T, Liščák R, Lee CC, Yang HC, Ding D, Sheehan JP, Feliciano CE, Rodriguez-Mercado R, Chiang VL, Hess JA, Sommaruga S, McShane B, Lee JYK, Vasas LT, Kaufmann AM, and Sneed PK more...
- Subjects
- Adult, Follow-Up Studies, Humans, Prospective Studies, Retrospective Studies, Treatment Outcome, Intracranial Arteriovenous Malformations diagnostic imaging, Intracranial Arteriovenous Malformations radiotherapy, Intracranial Arteriovenous Malformations surgery, Radiosurgery adverse effects, Radiosurgery methods
- Abstract
Objective: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs)., Methods: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic., Results: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE., Conclusions: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes. more...
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- 2021
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21. Letter: Patterns of Intermediate- and High-Risk Meningioma Recurrence After Treatment With Postoperative External Beam Radiotherapy.
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Susko MS, Chen WC, Vasudevan HN, Magill ST, Lucas CG, Oberheim Bush NA, Solomon DA, Theodosopoulos PV, McDermott MW, Villanueva-Meyer JE, Boreta L, Nakamura JL, Sneed PK, Braunstein SE, and Raleigh DR more...
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- 2021
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22. Damage to the Superior Retinae After 30 Gy Whole-Brain Radiation.
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Chan L, Sneed PK, and Horton JC
- Abstract
Purpose: The most common treatment protocol for whole-brain radiation therapy (WBRT) is 30 Gy in 10 fractions. This regimen entails a low risk of radiation retinopathy, with fewer than a dozen reported cases. We describe a case of radiation retinopathy that was confined to the superior retinae. These regions were the only portions of the eyes that were included in the treatment field., Methods and Materials: Observational case report consisting of clinical examination, review of radiation treatment planning and implementation, computerized visual field testing, and fundus photography., Results: A 36-year-old man with metastatic lung adenocarcinoma developed radiation retinopathy 16 months after WBRT to 30 Gy in 10 fractions. The retinopathy was largely confined to the superior halves of the retinae. There was corresponding geographic inferior visual field loss in both eyes. Review of the patient's treatment protocol revealed that the superior retinae received a substantial radiation dose, approaching 30 Gy, whereas the inferior retinae were essentially outside the treatment field., Conclusions: In this patient, the correlation between the treatment field and the resulting local development of radiation retinopathy demonstrated unequivocally that the relatively low dose used in routine WBRT (ie, 30 Gy in 10 fractions) can induce radiation retinopathy., (© 2021 The Authors.) more...
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- 2021
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23. Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation.
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Muster R, Ko N, Smith W, Su H, Dickey MA, Nelson J, McCulloch CE, Sneed PK, Clarke JL, Saloner DA, Eisenmenger L, Kim H, and Cooke DL
- Abstract
Brain arteriovenous malformations (bAVMs) are relatively rare, although their potential for secondary intracranial haemorrhage (ICH) makes their diagnosis and management essential to the community. Currently, invasive therapies (surgical resection, stereotactic radiosurgery and endovascular embolisation) are the only interventions that offer a reduction in ICH risk. There is no designated medical therapy for bAVM, although there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs. In this single-arm pilot study, two patients with large bAVMs (deemed unresectable by an interdisciplinary team) received bevacizumab 5 mg/kg every 2 weeks for 12 weeks. Due to limitations of external funding, the intended sample size of 10 participants was not reached. Primary outcome measure was change in bAVM volume from baseline at 26 and 52 weeks. No change in bAVM volume was observed 26 or 52 weeks after bevacizumab treatment. No clinically important adverse events were observed during the 52-week study period. There were no observed instances of ICH. Sera vascular endothelial growth factor levels were reduced at 26 weeks and returned to baseline at 52 weeks. This pilot study is the first to test bevacizumab for patients with bAVMs. Bevacizumab therapy was well tolerated in both subjects. No radiographic changes were observed over the 52-week study period. Subsequent larger clinical trials are in order to assess for dose-dependent efficacy and rarer adverse drug effects. Trial registration number: NCT02314377., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...
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- 2021
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24. Redistributing Central Target Dose Hot Spots for Hypofractionated Radiosurgery of Large Brain Tumors: A Proof-of-Principle Study.
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Ma L, Braunstein SE, Golden E, Fogh S, Nakamura J, McDermott MW, and Sneed PK
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- Humans, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Radiosurgery
- Abstract
Objective: The present proof-of-principle study investigated radiobiological effects of redistributing central target dose hot spots across different treatment fractions during hypofractionated stereotactic radiosurgery (HSRS) of large intracranial tumors., Methods: Redistribution of central target dose hot spots during HSRS was simulated, and its effects were evaluated in eight cases of brain metastases. To assess dose variations in the target across N number of treatment fractions, a generalized biologically effective dose (gBED) was formulated. The gBED enhancement ratio was defined as the ratio of gBED in the tested treatment plan (with central target dose hot spot redistributions across fractions) to gBED in the conventional treatment plan (without central target dose hot spot redistributions)., Results: At a median α value of 0.3/Gy, the tested treatment plans resulted in average gBED increases of 15.6 ± 3.5% and 8.3 ± 1.8% for α/β ratios of 2 and 10 Gy, respectively. In comparison with conventional treatment plans, the differences in the Paddick conformity index and gradient index did not exceed 2%., Conclusion: Redistributing central target dose hot spots across different treatment fractions during HSRS may be considered promising for enhancing gBED in the target. It may be beneficial for management of large intracranial neoplasms; thus, it warrants further clinical testing. more...
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- 2021
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25. Impact of the Skull Size on the Normal Brain Radiation Dose During Gamma Knife Radiosurgery: Results of a Pilot Study.
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Ma L, Fogh S, Braunstein SE, Auguste K, Theodosopoulos PV, McDermott MW, and Sneed PK
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- Brain surgery, Child, Humans, Pilot Projects, Radiation Dosage, Radiotherapy Dosage, Skull surgery, Radiosurgery
- Abstract
Objective: The objective of the present study was evaluation of the interrelationships between changes in the skull size and variations in the normal brain radiation dose during Gamma Knife surgery (GKS)., Methods: With use of systematic modeling within Leksell GammaPlan
® (Elekta AB; Stockholm, Sweden) in each of 15 analyzed cases, the skull was "expanded" and "contracted" by variation of its measurement values from 0 to ±3 cm. The mean normal brain radiation dose was then computed for each variant of the adjusted skull size and compared with the original treatment plan. Variations in the maximum point dose delivered to selected critical anatomical structures were also investigated., Results: With changes in the skull radius within ±3 cm, the maximum absolute deviation in the mean normal brain radiation dose was 0.8%. As the skull radius increased, the mean normal brain radiation dose also increased linearly (confidence level >99%) with a positive slope of 0.2% per centimeter of radius length change. The maximum point dose deviations in all evaluated critical anatomical structures did not exceed 0.5%, with an overall trend toward a dose increase in parallel with an increase in the skull radius., Conclusion: The small skull size of pediatric patients may be associated with dosimetric advantages in terms of normal brain sparing during GKS. more...- Published
- 2021
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26. Feasibility and Significance of Dose Adaptation via Linear Couch Translations to Correct for Rotational Shifts During Frameless Brain Radiosurgery with the Gamma Knife Icon™.
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Cheung JP, Morin O, Braunstein SE, Sneed PK, Theodosopoulos PV, McDermott MW, and Ma L
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- Brain, Cone-Beam Computed Tomography, Feasibility Studies, Humans, Brain Neoplasms surgery, Radiosurgery
- Abstract
Objective: The present study aimed to examine the technical feasibility and effectiveness of adapting the radiation dose distributions with three-dimensional (3D) linear couch translations in contrast to full six-dimensional couch maneuvers to correct for rotational shifts during frameless radiosurgical treatment with the Gamma Knife Icon™ (Elekta AB; Stockholm, Sweden)., Methods: The original magnetic resonance images used for radiosurgery treatment planning (15 targets) were digitally processed to simulate rotational shifts of ±1, ±2, ±3, ±5, and ±10 degrees in the transverse plane and imported back into Leksell GammaPlan
® (Elekta AB), creating "uncorrected" treatment plans. In addition, geometrically optimized 3D translation shifts were consequently applied to each isocenter in all "uncorrected" treatment plans to account for systematically introduced rotational shifts and to produce "corrected" treatment plans. The differences in the dose distribution between the original treatment plans and the "uncorrected" and "corrected" treatment plans were calculated and compared at each rotational shift position., Results: The "uncorrected" treatment plans resulted in a significant deterioration in target coverage (by 8-72%) and selectivity (by 2-42%), with some targets being missed completely with rotations of ±3 or more degrees. In contrast, in all "corrected" treatment plans, the average decreases in target coverage and selectivity were only 1% (maximum values 4-5%)., Conclusion: Applications of 3D linear couch translations successfully overcome gross uncertainties in dose distributions caused by up to ±10 degrees of rotational shifts in a target. As a result, rapid dose adaptation with 3D couch translations is unique and effective for frameless radiosurgery with the Gamma Knife Icon™. more...- Published
- 2021
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27. A Prognostic Gene-Expression Signature and Risk Score for Meningioma Recurrence After Resection.
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Chen WC, Vasudevan HN, Choudhury A, Pekmezci M, Lucas CG, Phillips J, Magill ST, Susko MS, Braunstein SE, Oberheim Bush NA, Boreta L, Nakamura JL, Villanueva-Meyer JE, Sneed PK, Perry A, McDermott MW, Solomon DA, Theodosopoulos PV, and Raleigh DR more...
- Subjects
- Adult, Aged, Cohort Studies, Female, Humans, Male, Meningeal Neoplasms pathology, Meningeal Neoplasms surgery, Meningioma pathology, Meningioma surgery, Middle Aged, Multivariate Analysis, Neurosurgical Procedures, Prognosis, Retrospective Studies, Risk Factors, Meningeal Neoplasms genetics, Meningioma genetics, Neoplasm Recurrence, Local genetics, Transcriptome
- Abstract
Background: Prognostic markers for meningioma are needed to risk-stratify patients and guide postoperative surveillance and adjuvant therapy., Objective: To identify a prognostic gene signature for meningioma recurrence and mortality after resection using targeted gene-expression analysis., Methods: Targeted gene-expression analysis was used to interrogate a discovery cohort of 96 meningiomas and an independent validation cohort of 56 meningiomas with comprehensive clinical follow-up data from separate institutions. Bioinformatic analysis was used to identify prognostic genes and generate a gene-signature risk score between 0 and 1 for local recurrence., Results: We identified a 36-gene signature of meningioma recurrence after resection that achieved an area under the curve of 0.86 in identifying tumors at risk for adverse clinical outcomes. The gene-signature risk score compared favorably to World Health Organization (WHO) grade in stratifying cases by local freedom from recurrence (LFFR, P < .001 vs .09, log-rank test), shorter time to failure (TTF, F-test, P < .0001), and overall survival (OS, P < .0001 vs .07) and was independently associated with worse LFFR (relative risk [RR] 1.56, 95% CI 1.30-1.90) and OS (RR 1.32, 95% CI 1.07-1.64), after adjusting for clinical covariates. When tested on an independent validation cohort, the gene-signature risk score remained associated with shorter TTF (F-test, P = .002), compared favorably to WHO grade in stratifying cases by OS (P = .003 vs P = .10), and was significantly associated with worse OS (RR 1.86, 95% CI 1.19-2.88) on multivariate analysis., Conclusion: The prognostic meningioma gene-expression signature and risk score presented may be useful for identifying patients at risk for recurrence., (Copyright © 2020 by the Congress of Neurological Surgeons.) more...
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- 2020
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28. Germline MUTYH Mutation in a Pediatric Cancer Survivor Developing a Secondary Malignancy.
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Lavergne V, Sabnis A, Tupule A, Davidson PR, Kline C, Matthay K, Nicolaides T, Goldsby R, Braunstein S, Fogh SE, Sneed PK, Menzel P, Nakamura A, DuBois SG, Haas-Kogan DA, and Nakamura JL
- Subjects
- Adolescent, Adult, Cancer Survivors, Child, Combined Modality Therapy, Female, Humans, Male, Neoplasms genetics, Neoplasms pathology, Neoplasms, Second Primary etiology, Neoplasms, Second Primary genetics, Phenotype, Prognosis, Young Adult, Biomarkers, Tumor genetics, DNA Glycosylases genetics, Germ-Line Mutation, Neoplasms therapy, Neoplasms, Second Primary pathology
- Abstract
Radiotherapy-induced second malignant neoplasms (SMNs) are a severe late complication in pediatric cancer survivors. Germline mutations in tumor suppressor genes contribute to SMNs; however, the most relevant germline variants mediating susceptibility are not fully defined. The authors performed matched whole-exome sequencing analyses of germline and tumor DNA from 4 pediatric solid tumor survivors who subsequently developed radiation-associated SMNs. Pathogenic and predicted deleterious germline variants were identified for each patient and validated with Sanger sequencing. These germline variants were compared with germline variants in a cohort of 59 pediatric patients diagnosed with primary sarcomas. Pathway analysis was performed to test for similarities in the germline variant profiles between individuals diagnosed with SMNs or primary sarcomas. One index patient was found to have a pathogenic germline monoallelic mutation in the MUTYH gene, which encodes the base excision repair enzyme adenine DNA glycosylase. This specific germline mutation is associated with a form of familial adenomatous polyposis, a new diagnosis in the patient. Germline-level genetic similarity exists between SMN-developing patients and patients developing primary sarcomas, with relevant genes involved in signal transduction and DNA repair mechanisms. The authors identify a germline MUTYH mutation in a pediatric cancer survivor developing an SMN. Germline mutations involving specific pathways such as base excision repair may identify individuals at risk for developing SMNs. The composition of germline variants in individual patients may enable estimates of patient-specific risk for developing SMNs. The authors anticipate that further analyses of germline genomes and epigenomes will reveal diverse genes and mechanisms influencing cancer risk. more...
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- 2020
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29. Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma.
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Magill ST, Vasudevan HN, Seo K, Villanueva-Meyer JE, Choudhury A, John Liu S, Pekmezci M, Findakly S, Hilz S, Lastella S, Demaree B, Braunstein SE, Bush NAO, Aghi MK, Theodosopoulos PV, Sneed PK, Abate AR, Berger MS, McDermott MW, Lim DA, Ullian EM, Costello JF, and Raleigh DR more...
- Subjects
- Aged, Antigens, CD genetics, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology, Cadherins genetics, Diffusion Magnetic Resonance Imaging methods, Epigenomics, Female, Genetic Markers, Genomics, Humans, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms pathology, Receptor-Like Protein Tyrosine Phosphatases, Class 5 genetics, Transcriptome, Brain Neoplasms genetics, Brain Neoplasms metabolism, Gene Expression Profiling methods, Genetic Heterogeneity, Magnetic Resonance Imaging methods, Meningeal Neoplasms genetics, Meningeal Neoplasms metabolism
- Abstract
Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas. Our data reveal that regional alterations in chromosome structure underlie clonal transcriptomic, epigenomic, and histopathologic signatures in meningioma. Stereotactic co-registration of sample coordinates to preoperative magnetic resonance images further suggest that high apparent diffusion coefficient (ADC) distinguishes meningioma regions with proliferating cells enriched for developmental gene expression programs. To understand the function of these genes in meningioma, we develop a human cerebral organoid model of meningioma and validate the high ADC marker genes CDH2 and PTPRZ1 as potential targets for meningioma therapy using live imaging, single cell RNA sequencing, CRISPR interference, and pharmacology. more...
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- 2020
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30. Letter: Treatment Outcomes and Dose Rate Effects Following Gamma Knife Stereotactic Radiosurgery for Vestibular Schwannomas.
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Paddick I, Hopewell JW, Klinge T, Graffeo CS, Pollock BE, and Sneed PK
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- Clinical Protocols, Hearing, Humans, Treatment Outcome, Neuroma, Acoustic surgery, Radiosurgery
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- 2020
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31. Dose response and architecture in volume staged radiosurgery for large arteriovenous malformations: A multi-institutional study.
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Seymour ZA, Chan JW, Sneed PK, Kano H, Lehocky CA, Jacobs RC, Ye H, Chytka T, Liscak R, Lee CC, Yang HC, Ding D, Sheehan J, Feliciano CE, Rodriguez-Mercado R, Chiang VL, Hess JA, Sommaruga S, McShane B, Lee J, Vasas LT, Kaufmann AM, Grills I, and McDermott MW more...
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- Adult, Follow-Up Studies, Humans, Prospective Studies, Retrospective Studies, Treatment Outcome, Intracranial Arteriovenous Malformations radiotherapy, Intracranial Arteriovenous Malformations surgery, Radiosurgery
- Abstract
Background: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult., Methods: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival., Results: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy., Conclusion: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure., (Copyright © 2019 Elsevier B.V. All rights reserved.) more...
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- 2020
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32. Stereotactic Radiosurgery to More Than 10 Brain Metastases: Evidence to Support the Role of Radiosurgery for Ideal Hippocampal Sparing in the Treatment of Multiple Brain Metastases.
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Susko MS, Garcia MA, Ma L, Nakamura JL, Raleigh DR, Fogh S, Theodosopoulos P, McDermott M, Sneed PK, and Braunstein SE
- Subjects
- Aged, Brain Neoplasms secondary, Female, Hippocampus surgery, Humans, Male, Middle Aged, Retrospective Studies, Salvage Therapy methods, Treatment Outcome, Brain Neoplasms surgery, Cranial Irradiation mortality, Neoplasm Recurrence, Local surgery, Radiosurgery methods
- Abstract
Background: Brain metastases are a common occurrence, with literature supporting the treatment of a limited number of brain metastases with stereotactic radiosurgery (SRS), as opposed to whole brain radiotherapy (WBRT). Less well understood is the role of SRS in patients with ≥10 brain metastases., Methods: Patients treated with SRS to ≥10 brain metastases without concurrent WBRT between March 1999 and December 2016 were reviewed. Analysis was performed for overall survival, treated lesion freedom from progression (FFP), freedom from new metastases (FFNMs), and adverse radiation effect. Hippocampal volumes were retrospectively generated in patients treated with up-front SRS for evaluation of dose volume metrics., Results: A total of 143 patients were identified with 75 patients having up-front SRS and 68 patients being treated as salvage therapy after prior WBRT. The median number of lesions per patient was 13 (interquartile range [IQR], 11-17). Median total volume of treatment was 4.1 cm
3 (IQR, 2.0-9.9 cm3 ). The median 12-month FFP for up-front and salvage treatment was 96.8% (95% confidence interval [CI], 95.5-98.1) and 83.6% (95% CI, 79.9-87.5), respectively (P < 0.001). Twelve-month FFNMs for up-front and salvage SRS was 18.8% (95% CI, 10.9-32.3) versus 19.2% (95% CI, 9.7-37.8), respectively (P = 0.90). The mean hippocampal dose was 150 cGy (IQR, 100-202 cGy)., Conclusions: Excellent rates of local control can be achieved when treating patients with >10 intracranial metastases either in the up-front or salvage setting. Hippocampal sparing is readily achievable with expected high rates of new metastatic lesions in treated patients., (Copyright © 2019 Elsevier Inc. All rights reserved.) more...- Published
- 2020
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33. Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival.
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Chapman CH, Hara JH, Molinaro AM, Clarke JL, Oberheim Bush NA, Taylor JW, Butowski NA, Chang SM, Fogh SE, Sneed PK, Nakamura JL, Raleigh DR, and Braunstein SE
- Abstract
Background: Optimal techniques and patient selection for salvage reirradiation of high-grade glioma (HGG) are unclear. In this study, we identify prognostic factors for freedom from progression (FFP) and overall survival (OS) after reirradiation, risk factors for high-grade toxicity, and validate clinical prognostic scores., Methods: A total of 116 patients evaluated between 2000 and 2018 received reirradiation for HGG (99 WHO grade IV, 17 WHO grade III). Median time to first progression after initial therapy was 10.6 months. Salvage therapies before reirradiation included surgery (31%) and systemic therapy (41%). Sixty-five patients (56%) received single-fraction stereotactic radiosurgery (SRS) as reirradiation. The median biologically effective dose (BED) was 47.25 Gy, and the median planning target volume (PTV) was 4.8 cc for SRS and 95.0 cc for non-SRS treatments. Systemic therapy was given concurrently to 52% and adjuvantly to 74% of patients., Results: Median FFP was 4.9 months, and median OS was 11.0 months. Significant multivariable prognostic factors for FFP were performance status, time to initial progression, and BED; for OS they were age, time to initial progression, and PTV volume at recurrence. High-grade toxicity was correlated to PTV size at recurrence. Three-level prognostic scores were generated for FFP and OS, with cross-validated receiver operating characteristic area under the curve (AUC) of 0.640 and 0.687, respectively., Conclusions: Clinical variables at the time of reirradiation for HGG can be used to prognosticate FFP and OS. more...
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- 2019
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34. Radiotherapy for recurrent intracranial epidermoid cysts without malignant transformation: a single-institution case series.
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Morshed RA, Wu SY, Sneed PK, and McDermott MW
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- Adult, Brain Diseases pathology, Epidermal Cyst pathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Prognosis, Young Adult, Brain Diseases radiotherapy, Epidermal Cyst radiotherapy, Neoplasm Recurrence, Local radiotherapy, Radiotherapy, Adjuvant
- Abstract
Introduction: Recurrent intracranial epidermoid cysts may be difficult to address surgically given their proximity to critical neurovascular structures of the skull base. There are emerging reports of using radiotherapy (RT) for the treatment of recurrent epidermoid cysts. Here, we report a case series of adjuvant fractionated external beam RT for recurrent intracranial epidermoid cysts., Methods: A single-institution review of all recurrent epidermoid cysts treated with adjuvant therapy between 2000 and 2017 was performed., Results: Eight patients with recurrent epidermoid cysts who underwent adjuvant external beam RT were identified. Average age at initial diagnosis was 42.2 years, and median clinical follow-up after initial diagnosis and RT was 16.4 and 2.9 years, respectively. The median number of surgical resections prior to RT was 3 (range 2-5). Rationale for RT included multiple recurrent disease, rapid recurrence following prior resection, increased risk of further surgical morbidity, and patient preference. Median dose was 50.4 delivered in 1.8 Gy fractions (median 28 fractions). By the date of last follow-up, no patient has demonstrated progression, and there have been no cases of malignant degeneration., Conclusion: Adjuvant RT should be considered in the context of recurrent epidermoid cysts to decrease the likelihood of further recurrences. more...
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- 2019
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35. Direct and indirect costs associated with stereotactic radiosurgery or open surgery for medial temporal lobe epilepsy: Results from the ROSE trial.
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Langfitt JT, Quigg M, Yan G, Yu W, Ward MM, Barbaro NM, Chang EF, Broshek DK, Laxer KD, Cole AJ, Sneed PK, Hess C, Tripathi M, Heck CN, Miller JW, Garcia PA, McEvoy A, Fountain NB, Salanova V, Knowlton RC, Bagić A, Henry T, Kapoor S, McKhann G, Palade AE, Reuber M, and Tecoma E more...
- Subjects
- Adult, Costs and Cost Analysis, Epilepsy, Temporal Lobe economics, Female, Humans, Male, Middle Aged, Patient Acceptance of Health Care statistics & numerical data, Epilepsy, Temporal Lobe surgery, Health Care Costs statistics & numerical data, Radiosurgery economics
- Abstract
Objective: To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery., Methods: We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing., Results: Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95% confidence interval [CI] = 50.7-115.6) and ATL (n = 18, mean = $79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up., Significance: Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.) more...
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- 2019
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36. Integrated models incorporating radiologic and radiomic features predict meningioma grade, local failure, and overall survival.
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Morin O, Chen WC, Nassiri F, Susko M, Magill ST, Vasudevan HN, Wu A, Vallières M, Gennatas ED, Valdes G, Pekmezci M, Alcaide-Leon P, Choudhury A, Interian Y, Mortezavi S, Turgutlu K, Bush NAO, Solberg TD, Braunstein SE, Sneed PK, Perry A, Zadeh G, McDermott MW, Villanueva-Meyer JE, and Raleigh DR more...
- Abstract
Background: We investigated prognostic models based on clinical, radiologic, and radiomic feature to preoperatively identify meningiomas at risk for poor outcomes., Methods: Retrospective review was performed for 303 patients who underwent resection of 314 meningiomas (57% World Health Organization grade I, 35% grade II, and 8% grade III) at two independent institutions, which comprised primary and external datasets. For each patient in the primary dataset, 16 radiologic and 172 radiomic features were extracted from preoperative magnetic resonance images, and prognostic features for grade, local failure (LF) or overall survival (OS) were identified using the Kaplan-Meier method, log-rank tests and recursive partitioning analysis. Regressions and random forests were used to generate and test prognostic models, which were validated using the external dataset., Results: Multivariate analysis revealed that apparent diffusion coefficient hypointensity (HR 5.56, 95% CI 2.01-16.7, P = .002) was associated with high grade meningioma, and low sphericity was associated both with increased LF (HR 2.0, 95% CI 1.1-3.5, P = .02) and worse OS (HR 2.94, 95% CI 1.47-5.56, P = .002). Both radiologic and radiomic predictors of adverse meningioma outcomes were significantly associated with molecular markers of aggressive meningioma biology, such as somatic mutation burden, DNA methylation status, and FOXM1 expression. Integrated prognostic models combining clinical, radiologic, and radiomic features demonstrated improved accuracy for meningioma grade, LF, and OS (area under the curve 0.78, 0.75, and 0.78, respectively) compared to models based on clinical features alone., Conclusions: Preoperative radiologic and radiomic features such as apparent diffusion coefficient and sphericity can predict tumor grade, LF, and OS in patients with meningioma., (© The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.) more...
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- 2019
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37. Preoperative Dural Contact and Recurrence Risk After Surgical Cavity Stereotactic Radiosurgery for Brain Metastases: New Evidence in Support of Consensus Guidelines.
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Susko M, Yu Y, Ma L, Nakamura J, Fogh S, Raleigh DR, Golden E, Theodosopoulos PV, McDermott MW, Sneed PK, and Braunstein SE
- Abstract
Purpose: The incidence of brain metastases is increasing as a result of more routine diagnostic imaging and improved extracranial systemic treatment strategies. As noted in recent consensus guidelines, postoperative stereotactic radiosurgery (SRS) to the resection cavity has lower rates of local control than whole brain radiation therapy but improved cognitive outcomes. Further analyses are needed to improve local control and minimize toxicity., Methods and Materials: Patients receiving SRS to a resection cavity between 2006 and 2016 were retrospectively analyzed. Presurgical variables, including tumor location, diameter, dural/meningeal contact, and histology, were collected, as were SRS treatment parameters. Patients had routine follow-up with magnetic resonance imaging, and those noted to have local failure were further assessed for the recurrence location, distance from the target volume, and dosimetric characteristics., Results: Overall, 82 patients and 85 resection cavities underwent postoperative SRS during the study period. Of these, 58 patients with 60 resection cavities with available follow-up magnetic resonance imaging scans were included in this analysis. With a median follow-up of 19.8 months, local recurrence occurred in 12 of the resection cavities for a 15% 1-year and 18% 2-year local recurrence rate. Pretreatment tumor volume contacted the dura/meninges in 100% of cavities with recurrence versus 67% of controlled cavities ( P = .025). A total of 5 infield, 5 marginal, and 4 out-of-field recurrences were found, with a median distance to the centroid from the target volume of 3 mm. The addition of a 10-mm dural margin increased the target volume overlap with the recurrence contours for 10 of the 14 recurrences., Conclusions: Dural contact was associated with an increased rate of recurrence for patients who received SRS to a surgical cavity, and the median distance of marginal recurrences from the target volume was 3 mm. These results provide evidence in support of recent consensus guidelines suggesting that additional dural margin on SRS volumes may benefit local control. more...
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- 2019
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38. Impact of pretreatment growth on Tumor control for vestibular schwannomas following gamma knife.
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Chang J, Breshears JD, Molinaro AM, Sneed PK, McDermott MW, Theodosopoulos PV, and Tward AD
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- Cohort Studies, Female, Humans, Male, Middle Aged, Preoperative Period, Prognosis, Retrospective Studies, Time Factors, Neuroma, Acoustic pathology, Neuroma, Acoustic surgery, Radiosurgery, Tumor Burden
- Abstract
Objectives/hypothesis: To determine if volumetric growth prior to gamma knife (GK) radiosurgery predicts long-term tumor control., Study Design: Retrospective cohort study., Methods: Sporadic vestibular schwannomas (VS) treated with GK between 2002 and 2014 at a single tertiary care center were identified. Patients were included if they had over 6 months of pretreatment observation and over 1.5 years of posttreatment follow-up. Volumetric tumor analysis was performed on T1 postcontrast imaging. Pretreatment and posttreatment volume change was calculated. Tumors with over 20% volume increase were classified as growing., Results: There were 62 patients included in this study; 48 had pretreatment growth and 14 had no pretreatment growth. Median tumor volume was 0.58 ± 1.8 cm
3 and median follow-up was 3.3 ± 2.0 years. For tumors with and without pretreatment growth, salvage treatment rates were 2% and 7% (P = .35), and posttreatment radiologic stability rates were 73% and 86%, respectively (P = .33). Median pretreatment growth was 27 ± 33% per year for tumors with posttreatment radiographic growth and 18 ± 26% per year for tumors without posttreatment radiographic growth (P = .99)., Conclusions: Pretreatment growth was not associated with increased salvage treatment or posttreatment radiographic progression rates in VS following GK., Level of Evidence: 4 Laryngoscope, 129:743-747, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.) more...- Published
- 2019
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39. Temporal Dynamics of Pseudoprogression After Gamma Knife Radiosurgery for Vestibular Schwannomas-A Retrospective Volumetric Study.
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Breshears JD, Chang J, Molinaro AM, Sneed PK, McDermott MW, Tward A, and Theodosopoulos PV
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- Disease Progression, Humans, Magnetic Resonance Imaging, Retrospective Studies, Neuroma, Acoustic diagnostic imaging, Neuroma, Acoustic epidemiology, Neuroma, Acoustic pathology, Neuroma, Acoustic surgery, Radiosurgery
- Abstract
Background: The optimal observation interval after the radiosurgical treatment of a sporadic vestibular schwannoma, prior to salvage intervention, is unknown., Objective: To determine an optimal postradiosurgical treatment interval for differentiating between pseudoprogression and true tumor growth by analyzing serial volumetric data., Methods: This single-institution retrospective study included all sporadic vestibular schwannomas treated with Gamma Knife radiosurgery (Eketa AB, Stockholm, Sweden; 12-13 Gy) from 2002 to 2014. Volumetric analysis was performed on all available pre- and posttreatment magnetic resonance imaging scans. Tumors were classified as "stable/decreasing," "transient enlargement", or "persistent growth" after treatment, based on incrementally increasing follow-up durations., Results: A total of 118 patients included in the study had a median treatment tumor volume of 0.74 cm3 (interquartile range [IQR] = 0.34-1.77 cm3) and a median follow-up of 4.1 yr (IQR = 2.6-6.0 yr). Transient tumor enlargement was observed in 44% of patients, beginning at a median of 1 yr (IQR = 0.6-1.4 yr) posttreatment, with 90% reaching peak volume within 3.5 yr, posttreatment. Volumetric enlargement resolved at a median of 2.4 yr (IQR 1.9-3.6 yr), with 90% of cases resolved at 6.9 yr. Increasing follow-up revealed that many of the tumors initially enlarging 1 to 3 yr after stereotactic radiosurgery ultimately begin to shrink on longer follow-up (45% by 4 yr, 77% by 6 yr)., Conclusion: Tumor enlargement within ∼3.5 yr of treatment should not be used as a sole criterion for salvage treatment. Patient symptoms and tumor size must be considered, and giving tumors a chance to regress before opting for salvage treatment may be worthwhile. more...
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- 2019
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40. Visual field defects after radiosurgery versus temporal lobectomy for mesial temporal lobe epilepsy: Findings of the ROSE trial.
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Quigg M, Barbaro NM, Ward MM, Chang EF, Broshek DK, Langfitt JT, Yan G, Laxer KD, Cole AJ, Sneed PK, Hess CP, Yu W, Newman SA, Mueller S, Tripathi M, Heck CN, Miller JW, Garcia PA, McEvoy A, Fountain NB, Salanova V, Knowlton RC, Bagić A, Henry T, Kapoor S, McKhann G, Palade AE, Reuber M, and Tecoma E more...
- Subjects
- Adult, Epilepsy, Temporal Lobe epidemiology, Female, Humans, Incidence, Male, Sclerosis epidemiology, Sclerosis radiotherapy, Sclerosis surgery, Treatment Outcome, Vision Disorders epidemiology, Visual Field Tests, Visual Fields, Anterior Temporal Lobectomy adverse effects, Epilepsy, Temporal Lobe radiotherapy, Epilepsy, Temporal Lobe surgery, Postoperative Complications epidemiology, Radiosurgery adverse effects, Vision Disorders etiology
- Abstract
Purpose: Stereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9-100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ., Methods: This prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated., Results: No patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status., Conclusion: The nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.) more...
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- 2018
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41. Brain metastasis growth on preradiosurgical magnetic resonance imaging.
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Garcia MA, Anwar M, Yu Y, Duriseti S, Merritt B, Nakamura J, Hess C, Theodosopoulos PV, McDermott M, Sneed PK, and Braunstein SE
- Subjects
- Adult, Aged, Aged, 80 and over, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasms surgery, Prognosis, Radiotherapy Dosage, Radiotherapy, Intensity-Modulated methods, Brain Neoplasms secondary, Magnetic Resonance Imaging methods, Neoplasms pathology, Radiosurgery
- Abstract
Purpose: A previous analysis showed that brain metastases that are treated with frameless stereotactic radiation surgery (SRS) and planned with magnetic resonance imaging (MRI) >14 days before SRS had worse local control (LC). To evaluate if worse LC may be due to unaccounted interval metastasis growth and radiosurgical marginal miss, we quantified growth before SRS on preradiosurgical imaging., Methods and Materials: We reviewed data from patients who were treated with fixed-frame SRS for brain metastases at our institution between 2010 and 2013 and had pretreatment diagnostic brain MRI and SRS-planning MRI scans available. Metastases were contoured on the pretreatment MRI scan and the day-of-treatment planning MRI scan for volumetric comparison. Growth rates were calculated. Serial volumetric contour expansions on the pretreatment MRI scans were used to determine the minimum margin necessary to encompass the entire metastasis on day of the SRS. LC was estimated by Kaplan-Meier method., Results: Among 411 brain metastases in 165 patients, the time between pretreatment and treatment MRI was associated with metastasis growth (P < .001) with a mean growth rate of 0.02 ml/day (95% confidence interval, 0.01-0.03) and a 1.35-fold volume increase at 14 days. Time between MRI scans was associated with the amount of margin that was needed to target the entire brain metastasis volume on the day of the SRS (P < .001), as were volume of metastasis on the pre-treatment MRI (P < .001) and melanoma histology (P < .001). LC was not associated with growth rate among patients who underwent fixed-frame SRS., Conclusions: Time between pretreatment MRI and SRS is associated with brain metastasis growth, but LC is not compromised when patients receive fixed-frame SRS with same-day MRI planning. Margins may be needed for metastases that are treated with frameless SRS to account for growth between the planning MRI and SRS delivery., Summary: In this study, we quantify brain metastasis growth over time by taking advantage of the availability of 2 pretreatment magnetic resonance imaging scans taken at 2 time points among patients treated with frame-fixed radiation surgery. We found that metastasis growth is associated with time, initial metastasis size, melanoma histology, and concurrent chemotherapy. Performing serial margin expansions demonstrated factors that are associated with the amount of margin that is needed to target the entire metastasis on the day of radiation surgery., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2018
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42. Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma.
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Rubenstein JL, Geng H, Fraser EJ, Formaker P, Chen L, Sharma J, Killea P, Choi K, Ventura J, Kurhanewicz J, Lowell C, Hwang J, Treseler P, Sneed PK, Li J, Wang X, Chen N, Gangoiti J, Munster PN, and Damato B more...
- Subjects
- Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Recurrence, Survival Rate, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms mortality, Lenalidomide administration & dosage, Lymphoma drug therapy, Lymphoma mortality, Maintenance Chemotherapy, Rituximab administration & dosage
- Abstract
There is an unmet need for effective biological therapies for relapsed central nervous system (CNS) lymphoma. Lenalidomide is active in activated B-cell type diffuse large B-cell lymphoma and rituximab is effective in CNS lymphoma. These observations are the basis for this first trial of an immunomodulatory drug as monotherapy in CNS lymphoma, and, in patients with inadequate responses to lenalidomide, with rituximab. In an independent cohort, we evaluated lenalidomide maintenance after salvage with high-dose methotrexate or focal irradiation in relapsed primary CNS lymphoma (PCNSL). We determined safety, efficacy, and cerebrospinal fluid (CSF) penetration of lenalidomide at 10-, 15-, and 20-mg dose levels in 14 patients with refractory CD20
+ CNS lymphoma. Nine subjects with relapsed, refractory CNS lymphoma achieved better than partial response with lenalidomide monotherapy, 6 maintained response ≥9 months, and 4 maintained response ≥18 months. Median progression-free survival for lenalidomide/rituximab was 6 months. In the independent cohort, response duration with lenalidomide maintenance after complete responses 2 through 5 were significantly longer than response durations after standard therapy. The CSF/plasma partition coefficient of lenalidomide was ≥20% at 15- and 20-mg dose levels. Change in CSF interleukin-10 at 1 month correlated with clinical response and response duration to lenalidomide. Metabolomic profiling of CSF identified novel biomarkers, including lactate, and implicated indoleamine-2,3 dioxygenase activity with CNS lymphoma progression on lenalidomide. We conclude that lenalidomide penetrates ventricular CSF and is active as monotherapy in relapsed CNS lymphomas. We provide evidence that maintenance lenalidomide potentiates response duration after salvage in relapsed PCNSL and delays whole brain radiotherapy (WBRT). This trial was registered at www.clinicaltrials.gov as #NCT01542918., (© 2018 by The American Society of Hematology.) more...- Published
- 2018
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43. Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial.
- Author
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Barbaro NM, Quigg M, Ward MM, Chang EF, Broshek DK, Langfitt JT, Yan G, Laxer KD, Cole AJ, Sneed PK, Hess CP, Yu W, Tripathi M, Heck CN, Miller JW, Garcia PA, McEvoy A, Fountain NB, Salanova V, Knowlton RC, Bagić A, Henry T, Kapoor S, McKhann G, Palade AE, Reuber M, and Tecoma E more...
- Subjects
- Adult, Dose-Response Relationship, Radiation, Drug Resistant Epilepsy radiotherapy, Drug Resistant Epilepsy surgery, Epilepsy, Temporal Lobe complications, Epilepsy, Temporal Lobe psychology, Female, Functional Laterality, Humans, Longitudinal Studies, Male, Memory Disorders diagnosis, Memory Disorders etiology, Middle Aged, Postoperative Complications diagnosis, Quality of Life, Single-Blind Method, Treatment Outcome, Vision Disorders diagnosis, Vision Disorders etiology, Anterior Temporal Lobectomy methods, Epilepsy, Temporal Lobe radiotherapy, Epilepsy, Temporal Lobe surgery, Radiosurgery methods
- Abstract
Objective: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE)., Methods: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up., Results: A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients., Significance: These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.) more...
- Published
- 2018
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44. Salvage therapy outcomes for atypical meningioma.
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Chen WC, Hara J, Magill ST, Wu A, Aghi MK, Theodosopoulos PV, Perry A, McDermott MW, Sneed PK, Raleigh DR, and Braunstein SE
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Meningeal Neoplasms diagnostic imaging, Meningioma diagnostic imaging, Middle Aged, Neoplasm Recurrence, Local, Radiosurgery adverse effects, Retrospective Studies, Survival Analysis, Treatment Outcome, Meningeal Neoplasms therapy, Meningioma therapy, Salvage Therapy adverse effects
- Abstract
Atypical menginomas demonstrate increased clinical aggressiveness characterized by recurrence and diminished survival. The optimal management of atypical meningioma in the recurrent setting is especially not well defined. To characterize outcomes following salvage treatment of recurrent atypical meningioma and to identify risk factors for further recurrence. Retrospective chart review was performed on 65 patients who underwent salvage treatment of atypical meningioma at a single institution. Data were analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. Sixty-five patients with recurrent atypical meningioma and median imaging follow-up of 4.0 years (range 1.9-6.6 years) underwent 62 surgeries and 114 radiation treatments (RT) for salvage therapy. Salvage modality was surgery (21%), surgery/RT (25%), or RT alone (54%), associated with 2 year local freedom from recurrence (LFFR) of 36, 59, and 73%, respectively (P = 0.01). Twenty percent of patients experienced CTCAE grade ≥ 3 toxicity with salvage therapy. Thirty-nine percent of patients experienced ≥ 3 recurrences. The median disease-free survival intervals after first and second salvage treatments were 2.9 and 1.3 years, respectively. On univariate Cox analysis, prior subtotal resection, prior RT, tumor diameter > 2.5 cm, and multifocal local recurrence were associated with recurrence after salvage therapy. On multivariate logistic regression, only multifocal local recurrence was associated with further recurrence. Recurrent atypical meningioma is clinically and pathologically more aggressive than primary atypical meningioma, and the likelihood of durable local control with salvage therapy is lower. Future efforts should identify patients at risk of recurrence, and aggressive upfront treatment should be employed. more...
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- 2018
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45. Histopathological features predictive of local control of atypical meningioma after surgery and adjuvant radiotherapy.
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Chen WC, Magill ST, Wu A, Vasudevan HN, Morin O, Aghi MK, Theodosopoulos PV, Perry A, McDermott MW, Sneed PK, Braunstein SE, and Raleigh DR
- Subjects
- Aged, Brain Neoplasms surgery, Cohort Studies, Female, Humans, Kaplan-Meier Estimate, Karnofsky Performance Status, Male, Meningioma surgery, Middle Aged, Neoplasm Recurrence, Local, Patient Selection, Predictive Value of Tests, Prognosis, Progression-Free Survival, Retrospective Studies, Risk Assessment, Salvage Therapy, Survival Analysis, Brain Neoplasms pathology, Brain Neoplasms therapy, Meningioma pathology, Meningioma therapy, Neurosurgical Procedures methods, Radiotherapy, Adjuvant methods
- Abstract
Obejective: The goal of this study was to investigate the impact of adjuvant radiotherapy (RT) on local recurrence and overall survival in patients undergoing primary resection of atypical meningioma, and to identify predictive factors to inform patient selection for adjuvant RT., Methods: One hundred eighty-two patients who underwent primary resection of atypical meningioma at a single institution between 1993 and 2014 were retrospectively identified. Patient, meningioma, and treatment data were extracted from the medical record and compared using the Kaplan-Meier method, log-rank tests, multivariate analysis (MVA) Cox proportional hazards models with relative risk (RR), and recursive partitioning analysis., Results: The median patient age and imaging follow-up were 57 years (interquartile range [IQR] 45–67 years) and 4.4 years (IQR 1.8–7.5 years), respectively. Gross-total resection (GTR) was achieved in 114 cases (63%), and 42 patients (23%) received adjuvant RT. On MVA, prognostic factors for death from any cause included GTR (RR 0.4, 95% CI 0.1–0.9, p = 0.02) and MIB1 labeling index (LI) ≤ 7% (RR 0.4, 95% CI 0.1–0.9, p = 0.04). Prognostic factors on MVA for local progression included GTR (RR 0.2, 95% CI 0.1–0.5, p = 0.002), adjuvant RT (RR 0.2, 95% CI 0.1–0.4, p < 0.001), MIB1 LI ≤ 7% (RR 0.2, 95% CI 0.1–0.5, p < 0.001), and a remote history of prior cranial RT (RR 5.7, 95% CI 1.3–18.8, p = 0.03). After GTR, adjuvant RT (0 of 10 meningiomas recurred, p = 0.01) and MIB1 LI ≤ 7% (RR 0.1, 95% CI 0.003–0.3, p < 0.001) were predictive for local progression on MVA. After GTR, 2.2% of meningiomas with MIB1 LI ≤ 7% recurred (1 of 45), compared with 38% with MIB1 LI > 7% (13 of 34; p < 0.001). Recursive partitioning analysis confirmed the existence of a cohort of patients at high risk of local progression after GTR without adjuvant RT, with MIB1 LI > 7%, and evidence of brain or bone invasion. After subtotal resection, adjuvant RT (RR 0.2, 95% CI 0.04–0.7, p = 0.009) and ≤ 5 mitoses per 10 hpf (RR 0.1, 95% CI 0.03–0.4, p = 0.002) were predictive on MVA for local progression., Conclusions: Adjuvant RT improves local control of atypical meningioma irrespective of extent of resection. Although independent validation is required, the authors’ results suggest that MIB1 LI, the number of mitoses per 10 hpf, and brain or bone invasion may be useful guides to the selection of patients who are most likely to benefit from adjuvant RT after resection of atypical meningioma. more...
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- 2018
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46. Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation.
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Vasudevan HN, Braunstein SE, Phillips JJ, Pekmezci M, Tomlin BA, Wu A, Reis GF, Magill ST, Zhang J, Feng FY, Nicholaides T, Chang SM, Sneed PK, McDermott MW, Berger MS, Perry A, and Raleigh DR
- Subjects
- Cell Proliferation genetics, DNA Methylation, Female, Forkhead Box Protein M1 biosynthesis, Forkhead Box Protein M1 metabolism, Gene Expression, Humans, Male, Meningioma metabolism, Meningioma pathology, Transfection, Tumor Cells, Cultured, Wnt Signaling Pathway, Forkhead Box Protein M1 genetics, Meningioma genetics
- Abstract
Meningioma is the most common primary intracranial tumor, but the molecular drivers of aggressive meningioma are incompletely understood. Using 280 human meningioma samples and RNA sequencing, immunohistochemistry, whole-exome sequencing, DNA methylation arrays, and targeted gene expression profiling, we comprehensively define the molecular profile of aggressive meningioma. Transcriptomic analyses identify FOXM1 as a key transcription factor for meningioma proliferation and a marker of poor clinical outcomes. Consistently, we discover genomic and epigenomic factors associated with FOXM1 activation in aggressive meningiomas. Finally, we define a FOXM1/Wnt signaling axis in meningioma that is associated with a mitotic gene expression program, poor clinical outcomes, and proliferation of primary meningioma cells. In summary, we find that multiple molecular mechanisms converge on a FOXM1/Wnt signaling axis in aggressive meningioma., (Published by Elsevier Inc.) more...
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- 2018
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47. Radiation-induced Cavernous Malformation as a Late Sequelae of Stereotactic Radiosurgery for Epilepsy.
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Winkler EA, Rutledge C, Ward M, Tihan T, Sneed PK, Barbaro N, Garcia P, McDermott M, and Chang EF
- Abstract
Stereotactic radiosurgery (SRS) is a promising treatment for medically intractable mesial temporal lobe epilepsy. SRS for epilepsy has had an acceptable safety profile with reports of radiation-induced vascular malformations confined to central nervous system pathologies with prominent angiogenesis - namely, primary brain tumors, metastases, and arteriovenous malformations. Theoretical risks for radiation-induced lesions following radiosurgery for epilepsy have yet to be established. Of 13 patients treated in a pilot trial for medial temporal lobe epilepsy, one developed multiple delayed radiation-induced cavernous malformations following radiosurgery. This patient received a prescription dose of 20 Gy delivered to the amygdala, anterior hippocampus, and parahippocampal gyrus. Eight years following treatment, computed tomography imaging demonstrated an evolving hyperdensity in the mesial temporal lobe. Magnetic resonance imaging confirmed multiple T2 hypointense lesions with a mixed-signal intensity core in the left parahippocampal gyrus and anterior temporal lobe. The patient was initially managed conservatively. However, recurrent hemorrhage ultimately caused an acute deterioration in mental status, aphasia, and hemiparesis, necessitating surgical resection. Pathology confirmed radiation-induced cavernous malformations. This represents the first case of a radiation-induced vascular lesion as a long-term sequela of radiosurgery for epilepsy and illustrates the potential for this complication even when low doses are used in patients without angiogenic lesions. Optimal timing and indications for surgical resection of radiation-induced cavernous malformations prior to the development of neurologic symptoms warrant further refinement. Long-term vigilance and clinical monitoring are required., Competing Interests: The authors have declared that no competing interests exist. more...
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- 2018
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48. Resection Cavity Contraction Effects in the Use of Radioactive Sources (1-25 versus Cs-131) for Intra-Operative Brain Implants.
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Han DY, Ma L, Braunstein S, Raleigh D, Sneed PK, and McDermott M
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Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity. Dose distribution estimated via TG-43 calculations and biological effective dose (BED) calculations were compared for both I-125 and Cs-131, accounting for resection cavity contractions. Results Resection cavity volumes were found to contract with an effective half-life of approximately 3.4 months (time to reach 50% of maximum volume contraction). As a result, significant differences in dose distributions were noted between I-125 and Cs-131 radioactive sources. For example, when comparing with static volume, assuming no contraction effect, I-125 exhibited a 31.8% and 30.5% increase in D90 and D10 values (i.e., the minimal dose to 90% and 10% of the volume respectively) in the peripheral target areas over the follow-up period of 20.5 months. In contrast, Cs-131 seeds only exhibited a 1.44% and 0.64% increase in D90 and D10 values respectively. Such discrepancy is likewise similar for BED calculations. Conclusion Resection cavity contractions affects Cs-131 dose distribution significantly less than that of I-125 for permanent brain implants. Care must be taken to account for cavity contractions when prescribing accumulative doses of a radioactive source in performing the brain implant procedures., Competing Interests: The authors have declared that no competing interests exist. more...
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- 2018
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49. Patient-Specific Fetal Dose Determination for Multi-Target Gamma Knife Radiosurgery: Computational Model and Case Report.
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Paulsson AK, Braunstein S, Phillips J, Theodosopoulos PV, McDermott M, Sneed PK, and Ma L
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A 42-year-old woman at 29 weeks gestation via in vitro fertilization who presented with eight metastatic brain lesions received Gamma Knife stereotactic radiosurgery (GKSRS) at our institution. ;In this study, we report our clinical experience and a general procedure of determining the fetal dose from patient-specific treatment plans and we describe quality assurance measurements to guide the safe practice of multi-target GKSRS of pregnant patients. To estimate fetal dose pre-treatment, peripheral dose-to-focal dose ratios (PFRs) were measured in a phantom at the distance approximating the fundus of uterus. Post-treatment, fetal dose was calculated from the actual patient treatment plan. Quality assurance measurements were carried out via the extrapolation dosimetry method in a head phantom at increasing distances along the longitudinal axis. The measurements were then empirically fitted and the fetal dose was extracted from the curve. The computed and measured fetal dose values were compared with each other and associated radiation risk was estimated. Based on low estimated fetal dose from preliminary phantom measurements, the patient was accepted for GKSRS. Eight brain metastases were treated with prescription doses of 15-19 Gy over 143 min involving all collimator sizes as well as composite sector mixed shots. Direct fetal dose computation based on the actual patient's treatment plan estimated a maximum fetal dose of 0.253 cGy, which was in agreement with surface dose measurements at the level of the patient's uterine fundus during the actual treatment. Later phantom measurements also estimated fetal dose to be in the range of 0.21-0.28 cGy (dose extrapolation curve R
2 = 0.998). Using the National Council on Radiation Protection and Measurements (NCRP) population-based model, we estimate the fetal risk of secondary malignancy, which is the primary toxicity after 25 weeks gestation, to be less than 0.01%. Of note, the patient delivered the baby via scheduled cesarean section at 36 weeks without complications attributable to the GKSRS procedure. GKSRS of multiple brain metastases was demonstrated to be safe and feasible during pregnancy. The applicability of a general patient-specific fetal dose determination method was also demonstrated for the first time for such a treatment., Competing Interests: The authors have declared financial relationships, which are detailed in the next section. more...- Published
- 2017
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50. Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis.
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Raleigh DR, Seymour ZA, Tomlin B, Theodosopoulos PV, Berger MS, Aghi MK, Geneser SE, Krishnamurthy D, Fogh SE, Sneed PK, and McDermott MW
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- Adult, Aged, Aged, 80 and over, Brain surgery, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Brain Neoplasms surgery, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Brachytherapy methods, Brain pathology, Brain Neoplasms therapy, Iodine Radioisotopes therapeutic use, Radiosurgery methods
- Abstract
OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (
125 I) brachytherapy for brain metastases. METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of125 I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models. RESULTS The median age at surgery was 59 years (range 29.9-81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21-76.2 cm3 ). Gross-total resection was achieved in 81% of the cases. The median number of125 I sources implanted per cavity was 28 (range 4-93), and the median activity was 0.73 mCi (range 0.34-1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0-22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02-13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05). CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent125 I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients. ▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV. more...- Published
- 2017
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