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      The role of surgical resection in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

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          Abstract

          Question

          Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings?

          Target population

          These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection.

          Recommendations

          Surgical resection plus WBRT versus surgical resection alone

          Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone.

          Surgical resection plus WBRT versus SRS ± WBRT

          Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift).

          Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible.

          Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below.

          Question

          Does surgical resection in addition to WBRT improve outcomes when compared with WBRT alone?

          Target population

          This recommendation applies to adults with a newly diagnosed single brain metastasis amenable to surgical resection; however, the recommendation does not apply to relatively radiosensitive tumors histologies (i.e., small cell lung cancer, leukemia, lymphoma, germ cell tumors and multiple myeloma).

          Recommendation

          Surgical resection plus WBRT versus WBRT alone

          Level 1 Class I evidence supports the use of surgical resection plus post-operative WBRT, as compared to WBRT alone, in patients with good performance status (functionally independent and spending less than 50% of time in bed) and limited extra-cranial disease. There is insufficient evidence to make a recommendation for patients with poor performance scores, advanced systemic disease, or multiple brain metastases.

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          Most cited references20

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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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            Brain metastases: epidemiology and pathophysiology.

            Metastases are the most common tumors of the central nervous system (CNS), but cancer databases are often incomplete leading to underestimation of the incidence of even symptomatic brain metastases. Brain imaging studies are not routinely performed on neurologically asymptomatic cancer patients and autopsy studies are outdated. Furthermore, while incidence rates for cancers are stable and mortality is decreasing due to earlier detection and better therapy, the incidence of brain metastases appears to be increasing. The pathophysiology of brain metastases is a complex multistage process, mediated by molecular mechanisms; from the primary organ, cancer cells must transform, grow and be transported to the CNS where they can lay dormant for various lengths of time before invading and growing further. Understanding the pathophysiology of brain metastases is of great importance, because it may lead to the development of more efficient therapies to combat brain tumor growth or to possibly make the CNS an undesirable environment for tumor progression.
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              • Article: not found

              A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis.

              Cerebral metastasis is a common oncologic problem that occurs in 15-30% of cancer patients; approximately half such metastases are single. Previous retrospective studies and two randomized trials reported that the addition of surgical extirpation prior to radiation therapy increased survival, neurologic function, and quality of life compared with radiation alone in patients with a single brain metastasis. A randomized controlled trial was conducted in which patients with a single brain metastasis were allocated to undergo radiation alone or surgery plus radiation. Radiation consisted of 3000 centigray to the whole brain in 10 fractions. Forty-three patients received radiation alone and 41 patients surgery plus radiation. All but two of the study patients died. No difference in survival was detected between the groups; the median survival for the radiation group was 6.3 months (95% confidence interval, 3-11.4) compared with 5.6 months for the surgery plus radiation group (95% confidence interval, 3.9-7.2) (P = 0.24). Most patients died within the first year (69.8% in the radiation arm vs. 87.8% in the surgery plus radiation arm). There were no significant differences in the 30-day mortality, morbidity, or causes of death. Extracranial metastases was an important predictor of mortality (relative risk, 2.3). The mean proportion of days that the Karnofsky performance status was > or = 70% did not differ between the 2 groups. This trial failed to demonstrate that the addition of surgery to radiation therapy improved outcome of patients with a single brain metastasis. Thus, the efficacy of surgery plus radiation compared with radiation alone needs to be addressed by further clinical trials and/or a meta-analysis.
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                Author and article information

                Contributors
                kalkanis@neuro.hfh.edu , skalkan1@hfhs.org
                Journal
                J Neurooncol
                Journal of Neuro-Oncology
                Springer US (Boston )
                0167-594X
                1573-7373
                4 December 2009
                4 December 2009
                January 2010
                : 96
                : 1
                : 33-43
                Affiliations
                [1 ]Department of Neurosurgery, Henry Ford Health System, 2799 West Grand Blvd, K-11, Detroit, MI 48202 USA
                [2 ]Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA USA
                [3 ]Department of Radiation Oncology, University of Colorado-Denver, Denver, CO USA
                [4 ]Department of Radiation Oncology, Carolinas Medical Center, Charlotte, NC USA
                [5 ]Department of Neurosurgery, Carolina Neurosurgery and Spine Associates, Charlotte, NC USA
                [6 ]Department of Neurosciences, California Pacific Medical Center, San Francisco, CA USA
                [7 ]Department of Neurosurgery, Ohio State University Medical Center, Columbus, OH USA
                [8 ]McMaster University Evidence-based Practice Center, Hamilton, ON Canada
                [9 ]Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA USA
                [10 ]Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA USA
                [11 ]Department of Neurosurgery, University of California San Francisco, San Francisco, CA USA
                [12 ]Department of Human Oncology, University of Wisconsin School of Public Health and Medicine, Madison, WI USA
                [13 ]Department of Neurology, Henry Ford Health System, Detroit, MI USA
                [14 ]Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA USA
                [15 ]Department of Neurology, Northshore University Health System, Evanson, IL USA
                [16 ]Department of Neurology, Barrow Neurological Institute, Phoenix, AZ USA
                [17 ]Department of Neurosurgery, Iowa Spine and Brain Institute, Iowa City, IA USA
                [18 ]Department of Neurosurgery, University of California-Irvine Medical Center, Orange, CA USA
                Article
                61
                10.1007/s11060-009-0061-8
                2808516
                19960230
                f302b1b0-9561-4fb9-b0a4-bef6c0131d81
                © The Author(s) 2009
                History
                : 7 September 2009
                : 8 November 2009
                Categories
                Invited Manuscript
                Custom metadata
                © Springer Science+Business Media, LLC. 2010

                Oncology & Radiotherapy
                stereotactic radiosurgery,practice guideline,brain metastases,surgical resection,radiotherapy,systematic review

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