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      The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases

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          Translated abstract

          Background

          The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort.

          Methods

          From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated.

          Results

          In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer ( n = 213 pts.; 300 lesions) and breast cancer ( n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control.

          Conclusion

          After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

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          Most cited references19

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          Phase I study of individualized stereotactic body radiotherapy of liver metastases.

          To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases. Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks. Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months). Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.
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            Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure.

            The authors report data concerning the safety, effectiveness, and patterns of failure obtained in a Phase I/II study of stereotactic body radiotherapy (SBRT) for spinal metastatic tumors. Sixty-three cancer patients underwent near-simultaneous computed tomography-guided SBRT. Spinal magnetic resonance imaging was conducted at baseline and at each follow-up visit. The National Cancer Institute Common Toxicity Criteria 2.0 assessments were used to evaluate toxicity. The median tumor volume of 74 spinal metastatic lesions was 37.4 cm3 (range 1.6-358 cm3). No neuropathy or myelopathy was observed during a median follow-up period of 21.3 months (range 0.9-49.6 months). The actuarial 1-year tumor progression-free incidence was 84% for all tumors. Pattern-of-failure analysis showed two primary mechanisms of failure: 1) recurrence in the bone adjacent to the site of previous treatment, and 2) recurrence in the epidural space adjacent to the spinal cord. Grade 3 or 4 toxicities were limited to acute Grade 3 nausea, vomiting, and diarrhea (one case); Grade 3 dysphagia and trismus (one case); and Grade 3 noncardiac chest pain (one case). There was no subacute or late Grade 3 or 4 toxicity. Analysis of the data obtained in the present study supports the safety and effectiveness of SBRT in cases of spinal metastatic cancer. The authors consider it prudent to routinely treat the pedicles and posterior elements using a wide bone margin posterior to the diseased vertebrae because of the possible direct extension into these structures. For patients without a history of radiotherapy, more liberal spinal cord dose constraints than those used in this study could be applied to help reduce failures in the epidural space.
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              Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial.

              To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver tumors. Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm(3) (range, 1 to 132 cm(3)). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity.
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                Author and article information

                Contributors
                +41 44 255 90 87 , nicolaus.andratschke@usz.ch
                Kontakt@strahlentherapie-distler.de
                Michael.Allgaeuer@barmherzige-regensburg.de
                Becker@radiochirurgicum.de
                Oliver@Blanck.de
                Judit.Boda-Heggemann@medma.uni-heidelberg.de
                Thomas.Brunner@uniklinik-freiburg.de
                Marciana.Duma@mri.tum.de
                Sabine.Gerum@med.uni-muenchen.de
                Matthias.Guckenberger@usz.ch
                Guido.Hildebrandt@uni-rostock.de
                Rainer_Klement@gmx.de
                Lewitzki_V@ukw.de
                Chrisian.Ostheimer@uk-halle.de
                Alexandros.Papachristofilou@usb.ch
                Cor.Petersen@uke.de
                Info@szhh.info
                Robert.Semrau@uk-koeln.de
                Stefan.Wachter@klinikum-passau.de
                Daniel.Habermehl@tum.de
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                13 March 2018
                13 March 2018
                2018
                : 18
                : 283
                Affiliations
                [1 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, University Hospital Zürich, Department of Radiation Oncology, , University of Zurich, ; Rämistrasse 100, 8091 Zurich, Switzerland
                [2 ]Department of Radiation Oncology, Strahlentherapie Bautzen, Bautzen, Germany
                [3 ]ISNI 0000 0000 9321 0488, GRID grid.469954.3, Department of Radiation Oncology, , Krankenhaus Barmherzige Brüder, ; Regensburg, Germany
                [4 ]RadioChirurgicum CyberKnife Südwest, Radiation Oncology, Göppingen, Germany
                [5 ]ISNI 0000 0004 0646 2097, GRID grid.412468.d, Department of Radiation Oncology, , Universitätsklinikum Schleswig-Holstein, ; /Lübeck, Kiel, Germany
                [6 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, University Hospital Mannheim, Department of Radiation Oncology, , University of Heidelberg, ; Mannheim, Germany
                [7 ]ISNI 0000 0000 9428 7911, GRID grid.7708.8, Department of Radiation Oncology, , University Hospital Freiburg, ; Freiburg, Germany
                [8 ]ISNI 0000 0004 0477 2438, GRID grid.15474.33, Department of Radiation Oncology, , Klinikum rechts der Isar- Technische Universität München, ; Munich, Germany
                [9 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Department of Radiation Oncology, , University of Munich – LMU Munich, ; Munich, Germany
                [10 ]ISNI 0000 0000 9737 0454, GRID grid.413108.f, Department of Radiation Oncology, , University Hospital Rostock, ; Rostock, Germany
                [11 ]ISNI 0000 0004 0493 3473, GRID grid.415896.7, Department of Radiation Oncology, , Leopoldina Hospital Schweinfurt, ; Schweinfurt, Germany
                [12 ]ISNI 0000 0001 1378 7891, GRID grid.411760.5, Department of Radiation Oncology, , University Hospital Würzburg, ; Würzburg, Germany
                [13 ]ISNI 0000 0004 0390 1701, GRID grid.461820.9, Department of Radiation Oncology, , University Hospital Halle, ; Halle, Germany
                [14 ]GRID grid.410567.1, Department of Radiation Oncology, , University Hospital Basel, ; Basel, Switzerland
                [15 ]ISNI 0000 0001 2180 3484, GRID grid.13648.38, Department of Radiation Oncology, , University Medical Center Hamburg-Eppendorf, ; Hamburg, Germany
                [16 ]Department of Radiation Oncology, Strahlenzentrum Hamburg, Hamburg, Germany
                [17 ]ISNI 0000 0000 8852 305X, GRID grid.411097.a, Department of Radiation Oncology, , University Hospital of Cologne, ; Cologne, Germany
                [18 ]Klinikum Passau, Radiation Oncology, Passau, Germany
                [19 ]ISNI 0000 0001 0328 4908, GRID grid.5253.1, Department of Radiation Oncology, , University Hospital Heidelberg, ; Heidelberg, Germany
                Author information
                http://orcid.org/0000-0003-3647-5916
                Article
                4191
                10.1186/s12885-018-4191-2
                5851117
                29534687
                7e1d8eb9-96d5-499e-8b43-cba8bfd02a38
                © The Author(s). 2018

                Open AccessThis 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
                : 24 October 2017
                : 6 March 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                stereotactic body radiotherapy,liver oligometastases,outcome,treated metastases control,oligometastases,oligo-recurrence,sync-oligometastases

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