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      Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases—Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept

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          Abstract

          Background: Pre-operative radiosurgery (SRS) preceding the resection of brain metastases promises to circumvent limitations of post-operative cavity SRS. It minimizes uncertainties regarding delineation and safety margins and could reduce dose exposure of the healthy brain (HB). Methods: We performed a systematic treatment plan comparison on 24 patients who received post-operative radiosurgery of the resection cavity at our institution. Comparative treatment plans were calculated for hypofractionated stereotactic radiotherapy (7 × 5 Gray (Gy)) in a hypothetical pre-operative (pre-op) and two post-operative scenarios, either with (extended field, post-op-E) or without the surgical tract (involved field, post-op-I). Detailed volumetric comparison of the resulting target volumes was performed, as well as dosimetric comparison focusing on targets and the HB. Results: The resection cavity was significantly smaller and different in morphology from the pre-operative lesion, yielding a low Dice Similarity Coefficient (DSC) of 53% ( p = 0.019). Post-op-I and post-op-E targets showed high similarity (DSC = 93%), and including the surgical tract moderately enlarged resulting median target size (18.58 ccm vs. 22.89 ccm, p < 0.001). Dosimetric analysis favored the pre-operative treatment setting since it significantly decreased relevant dose exposure of the HB (Median volume receiving 28 Gy: 6.79 vs. 10.79 for pre-op vs. post-op-E, p < 0.001). Dosimetrically, pre-operative SRS is a promising alternative to post-operative cavity irradiation that could furthermore offer practical benefits regarding delineation and treatment planning. Comparative trials are required to evaluate potential clinical advantages of this approach.

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          Tolerance of normal tissue to therapeutic irradiation

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            Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.

            Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.
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              Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial.

              For the treatment of a single metastasis to the brain, surgical resection combined with postoperative radiotherapy is more effective than treatment with radiotherapy alone. However, the efficacy of postoperative radiotherapy after complete surgical resection has not been established. To determine if postoperative radiotherapy resulted in improved neurologic control of disease and increased survival. Multicenter, randomized, parallel group trial. University-affiliated cancer treatment facilities. Ninety-five patients who had single metastases to the brain that were treated with complete surgical resections (as verified by postoperative magnetic resonance imaging) between September 1989 and November 1997 were entered into the study. Patients were randomly assigned to treatment with postoperative whole-brain radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation group, 46 patients) for the brain metastasis, with median follow-up of 48 weeks and 43 weeks, respectively. The primary end point was recurrence of tumor in the brain; secondary end points were length of survival, cause of death, and preservation of ability to function independently. Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%] of 46; P<.001) and at other sites in the brain (7 [14%] of 49 vs 17 [37%] of 46; P<.01). Patients in the radiotherapy group were less likely to die of neurologic causes than patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P=.003). There was no significant difference between the 2 groups in overall length of survival or the length of time that patients remained functionally independent. Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated with surgical resection alone.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                01 March 2019
                March 2019
                : 11
                : 3
                : 294
                Affiliations
                [1 ]Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; eric.tonndorf-martini@ 123456med.uni-heidelberg.de (E.T.-M.); daniela.schmitt@ 123456med.uni-heidelberg.de (D.S.); aylin_ck@ 123456hotmail.de (A.C.); dreselthorsten@ 123456web.de (T.D.); denise.bernhardt@ 123456med.uni-heidelberg.de (D.B.); kristin.lang@ 123456med.uni-heidelberg.de (K.L.); philipp.hoegen@ 123456med.uni-heidelberg.de (P.H.); sebastian.adeberg@ 123456med.uni-heidelberg.de (S.A.); angela.paul@ 123456med.uni-heidelberg.de (A.P.); juergen.debus@ 123456med.uni-heidelberg.de (J.D.); stefan.rieken@ 123456med.uni-heidelberg.de (S.R.)
                [2 ]National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
                [3 ]Institute of Medical Biometry and Informatics (IMBI), University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany; weber@ 123456imbi.uni-heidelberg.de
                [4 ]Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Im Neuenheimer Feld 450, 69120 Heidelberg, Germany
                [5 ]Clinical Cooperation Unit Radiation Oncology (E050), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
                Author notes
                [* ]Correspondence: rami.elshafie@ 123456med.uni-heidelberg.de ; Tel.: +49-6221-56-8201
                Author information
                https://orcid.org/0000-0002-1355-7882
                https://orcid.org/0000-0003-4850-9116
                https://orcid.org/0000-0001-8463-514X
                Article
                cancers-11-00294
                10.3390/cancers11030294
                6468393
                30832257
                b529c6d7-2a1f-4b76-978c-72bbb371fa72
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 January 2019
                : 25 February 2019
                Categories
                Article

                tumor,radiosurgery,neurosurgery,metastases,radiotherapy,radiation therapy,stereotactic

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