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      Feasibility of a simultaneously integrated boost concept for hypofractionated stereotactic radiotherapy of unresected brain metastases

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          Abstract

          Background

          In stereotactic radiotherapy, dose is prescribed to an isodose surrounding the planning target volume (PTV). However, the desired dose inhomogeneity inside the PTV leaves the specific dose distribution to the gross tumor volume (GTV) unspecified. A simultaneously integrated boost (SIB) to the GTV could solve this shortcoming. In a retrospective planning study with 20 unresected brain metastases, a SIB approach was tested against the classical prescription.

          Methods

          For all metastases, the GTV was isotropically enlarged by 3 mm to a PTV. Two plans were generated, one according to the classical 80% concept with 5 times 7 Gy prescribed (on D 2%) to the 80% PTV surrounding isodose (with D 98%(PTV) ≥ 35 Gy), and the other one following a SIB concept with 5 times 8.5 Gy average GTV dose and with D 98%(PTV) ≥ 35 Gy as additional requirement. Plan pairs were compared in terms of homogeneity inside GTV, high dose in PTV rim around GTV, and dose conformity and gradients around PTV using Wilcoxon matched pairs signed rank test.

          Results

          The SIB concept was superior to the classical 80% concept concerning dose homogeneity inside GTV: Heterogeneity index of GTV was in the SIB concept (median 0.0513, range 0.0397–0.0757) significantly (p = 0.001) lower than in the 80% concept (median 0.0894, range 0.0447–0.1872). Dose gradients around PTV were not inferior. The other examined measures were comparable.

          Conclusion

          Our stereotactic SIB concept better defines the dose distribution inside PTV and can be considered for clinical use.

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          Most cited references21

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          Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

          We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. Japan Brain Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05.

            To determine the maximum tolerated dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors and brain metastases. Adults with cerebral or cerebellar solitary non-brainstem tumors
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              Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis

              Purpose to investigate the factors affecting survival and toxicity in patients treated with stereotactic radiosurgery (SRS), with special attention to volumes of brain receiving a specific dose (V10 - V16 Gy) as predictors for brain radionecrosis. Patients and Methods Two hundred six consecutive patients with 310 cerebral metastases less than 3.5 cm were treated with SRS as primary treatment and followed prospectively at University of Rome La Sapienza Sant'Andrea Hospital. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. Univariate and multivariate analysis using a Cox proportional hazards regression model were performed to determine the predictive value of prognostic factors for treatment outcome and SRS-related complications. Results Median overall survival and brain control were 14.1 months and 10 months, respectively. The 1-year and 2-year survival rates were 58% and 24%, and respective brain control were 43% and 22%. Sixteen patients recurred locally after SRS, with 1-year and 2-year local control rates of 92% and 84%, respectively. On multivariate analysis, stable extracranial disease and KPS >70 were associated with the most significant survival benefit. Neurological complications were recorded in 27 (13%) patients. Severe neurological complications (RTOG Grade 3 and 4) occurred in 5.8% of patients. Brain radionecrosis occurred in 24% of treated lesions, being symptomatic in 10% and asymptomatic in 14%. On multivariate analysis, V10 through V16 Gy were independent risk factors for radionecrosis, with V10 Gy and V12 Gy being the most predictive (p = 0.0001). For V10 Gy >12.6 cm3 and V12 Gy >10.9 cm3 the risk of radionecrosis was 47%. Conclusions SRS alone represents a feasible option as initial treatment for patients with brain metastases, however a significant subset of patients may develop neurological complications. Lesions with V12 Gy >8.5 cm3 carries a risk of radionecrosis >10% and should be considered for hypofractionated stereotactic radiotherapy especially when located in/near eloquent areas.
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                Author and article information

                Contributors
                Christine.Kornhuber@uk-halle.de
                Stephan.Ensminger@uk-halle.de
                Patrick.Huebsch@uk-halle.de
                Martin.Janich@uk-halle.de
                Chris.Leucht@uk-halle.de
                Dirk.Vordermark@uk-halle.de
                Christian.Dietzel@uk-halle.de
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                22 May 2023
                22 May 2023
                2023
                : 18
                : 88
                Affiliations
                GRID grid.9018.0, ISNI 0000 0001 0679 2801, Department of Radiation Oncology, , Martin Luther University Halle-Wittenberg, ; Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany
                Article
                2266
                10.1186/s13014-023-02266-9
                10204235
                37217934
                488eba3b-17ca-400b-b7de-2779bef7a8cf
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 7 January 2023
                : 17 April 2023
                Funding
                Funded by: Martin-Luther-Universität Halle-Wittenberg (1043)
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2023

                Oncology & Radiotherapy
                brain metastases,hypofractionated stereotactic radiotherapy,simultaneously integrated boost

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