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      Normofractionated stereotactic radiotherapy versus CyberKnife-based hypofractionation in skull base meningioma: a German and Italian pooled cohort analysis

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          Abstract

          Background

          This retrospective German and Italian multicenter analysis aimed to compare the role of normofractionated stereotactic radiotherapy (nFSRT) to CyberKnife-based hypofractionated stereotactic radiotherapy (CK-hFSRT) for skull base meningiomas.

          Methods

          Overall, 341 patients across three centers were treated with either nFSRT or CK-hFSRT for skull base meningioma. Treatment planning was based on computed tomography (CT) and magnetic resonance imaging (MRI) following institutional guidelines. Most nFSRT patients received 33 × 1.8 Gy, and most CK-hFSRT patients received 5 × 5 Gy. The median follow-up time was 36 months (range: 1–232 months).

          Results

          In the CK-hFSRT group, the 1-, 3-, and 10-year local control (LC) rates were 99.4, 96.8, and 80.3%, respectively. In the nFSRT group, the 1-, 3-, and 10-year LC rates were 100, 99, and 79.1%, respectively. There were no significant differences in LC rates between the nFSRT and CK-hFSRT groups ( p = 0.56, hazard ratio = 0.76, 95% confidence interval, 0.3–1.9). In the CK-hFSRT group, only one case (0.49%) of severe toxicity (CTCAE 4.0   3) was observed. In the nFSRT group, three cases (2.1%) of grade III toxicity were observed.

          Conclusion

          This analysis of pooled data from three centers showed excellent LC and low side effect rates for patients treated with CK-hFSRT or nFSRT. The efficacy, safety, and convenience of a shortened treatment period provide a compelling case for the use of CK-hFSRT in patients with moderate size skull base meningioma and provided that OAR constraints are met.

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          Most cited references52

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          Use of normal tissue complication probability models in the clinic.

          The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included. Copyright 2010 Elsevier Inc. All rights reserved.
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            Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET.

            To evaluate the influence of 68-Ga-labeled DOTA (0)-D-Phe (1)-Tyr (3)-Octreotide positron emission tomography ([68Ga]-DOTATOC-PET) for target definition for fractionated stereotactic radiotherapy (FSRT) as a complementary modality to computed tomography (CT) and magnetic resonance imaging (MRI). Because meningiomas show a high expression of somatostatin receptor subtype 2, somatostatin analogs such as DOTATOC offer the possibility of receptor-targeted imaging. Twenty-six patients received stereotactic CT, MRI, and [68Ga]-DOTATOC-PET as part of their treatment planning. Histology was: World Health Organization (WHO) Grade 1 61.5%, WHO Grade 2 7.7%, WHO Grade 3 3.9%, and undetermined 26.9%. Six patients received radiotherapy as primary treatment, 2 after subtotal resection; 17 patients were treated for recurrent disease. Dynamic PET scans were acquired before radiotherapy over 60 min after intravenous injection of 156 +/- 29 MBq [68Ga]-DOTATOC. These PET images were imported in the planning software for FSRT. Planning target volume (PTV)-I outlined on CT and contrast-enhanced MRI was compared with PTV-II outlined on PET. PTV-III was defined with CT, MRI, and PET and was actually used for radiotherapy treatment. PTV-III was smaller than PTV-I in 9 patients, the same size in 7 patients, and larger in 10 patients. Median PTV-I was 49.6 cc, median PTV-III was 57.2 cc. In all patients [68Ga]-DOTATOC-PET delivered additional information concerning tumor extension. PTV-III was significantly modified based on DOTATOC-PET data in 19 patients. In 1 patient no tumor was exactly identified on CT/MRI but was visible on PET. These data demonstrate that [68Ga]-DOTATOC-PET improves target definition for FSRT in patients with intracranial meningiomas. Radiation targeting with fused DOTATOC-PET, CT, and MRI resulted in significant alterations in target definition in 73%.
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              Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients.

              To determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. One hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20-90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1-5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm(3) (range, 0.5-50.5 cm(3)), and the median tumor margin dose was 16 Gy (range, 12-36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. Overall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. Radiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.
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                Author and article information

                Contributors
                alfredo.conti@charite.de
                carolin.senger@charite.de
                gueliz.acker@charite.de
                anne.kluge@charite.de
                apontoriero@unime.it
                alberto.cacciola0@gmail.com
                stpergolizzi@unime.it
                germano@unime.it
                harun.badakhshi@klinikum.evb.de
                markus.kufeld@cyber-knife.net
                franziska.meinert@charite.de
                phuong.nguyen@charite.de
                franziska.loebel@charite.de
                peter.vajkoczy@charite.de
                volker.budach@charite.de
                030-450527152 , david.kaul@charite.de
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                12 November 2019
                12 November 2019
                2019
                : 14
                : 201
                Affiliations
                [1 ]ISNI 0000 0004 1757 1758, GRID grid.6292.f, Department of Neurosurgery, , University of Bologna, ; Bologna, Italy
                [2 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Department of Neurosurgery, , Charité Universitätsmedizin Berlin, ; Berlin, Germany
                [3 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, CyberKnife Center, , Charité Universitätsmedizin Berlin, ; Berlin, Germany
                [4 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Department of Radiation Oncology, , Charité Universitätsmedizin Berlin, ; Berlin, Germany
                [5 ]GRID grid.484013.a, Berlin Institute of Health (BIH), ; 10178 Berlin, Germany
                [6 ]ISNI 0000 0001 2178 8421, GRID grid.10438.3e, Department of Radiation Oncology, , University of Messina, ; Messina, Italy
                [7 ]Ernst von Bergmann Medical Center, Department of Radiation Oncology, Potsdam, Germany
                Author information
                https://orcid.org/0000-0002-7906-5629
                Article
                1397
                10.1186/s13014-019-1397-7
                6852939
                31718650
                a8398ccf-e622-41a2-b200-8c56719c8810
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 July 2019
                : 14 October 2019
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                meningioma,skull base,radiosurgery,fractionated stereotactic radiotherapy,hypofractionated stereotactic radiotherapy,cyberknife

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