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      Systemic Therapy after Radiotherapy Significantly Reduces the Risk of Mortality of Patients with 1–3 Brain Metastases: A Retrospective Study of 250 Patients

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          Abstract

          Background:

          For patients with a brain metastasis (BM), systemic therapy is usually administered after the completion of radiotherapy, especially in cases of multiple BMs. However, the role of systemic therapy in patients with a limited number of BMs is not clear. Therefore, we conducted a retrospective study to explore this question.

          Methods:

          Consecutive patients with a pathologically confirmed malignancy and 1–3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China.

          Results:

          A total of 250 patients were enrolled; of them, 135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy. In patients receiving whole-brain radiation therapy (WBRT) as radiotherapy, 28 received WBRT alone and 35 patients received WBRT plus systemic therapy. Of the patients treated with stereotactic radiosurgery (SRS), 107 received SRS alone and 80 received SRS plus systemic therapy. Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone (hazard ratio [ HR] = 0.294, 95% confidence interval [ CI] = 0.158–0.548). Further, when the analysis was conducted in subgroups of WBRT ( HR = 0.230, 95% CI = 0.081–0.653) or SRS ( HR = 0.305, 95% CI = 0.127–0.731), systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs.

          Conclusion:

          Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1–3 BMs.

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          Most cited references23

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          Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.

          Promising results from new approaches such as radiosurgery or stereotactic surgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous Radiation Therapy Oncology Group (RTOG) brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions. The database included 1200 patients from three consecutive RTOG trials conducted between 1979 and 1993, which tested several different dose fractionation schemes and radiation sensitizers. Using recursive partitioning analysis (RPA), a statistical methodology which creates a regression tree according to prognostic significance, eighteen pretreatment characteristics and three treatment-related variables were analyzed. According to the RPA tree the best survival (median: 7.1 months) was observed in patients or = 70, < 65 years of age with controlled primary and no extracranial metastases; Class 3: KPS < 70; Class 2- all others. Using these classes or stages, new treatment techniques can be tested on homogeneous patient groups.
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            A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database.

            The purpose of this study is to introduce a new prognostic index for patients with brain metastases and compare it with three published indices. Treatment for brain metastases varies widely. A sound prognostic index is thus important to guide both clinical decision making and outcomes research. A new index was developed because of limitations in the three existing indices and new data (Radiation Therapy Oncology Group 9508) are available since the others were developed. All four indices were compared using the Radiation Therapy Oncology Group database of 1,960 patients with brain metastases from five randomized trials. The ability of the four indices to distinguish its separate classes was determined statistically. Advantages and disadvantages of each index are discussed. Recursive partitioning analysis (RPA) and the new Graded Prognostic Assessment (GPA) had the most statistically significant differences between classes (p < 0.001 for all classes). The new index, the GPA, is as prognostic as the RPA and more prognostic than the other indices. The GPA is the least subjective, most quantitative and easiest to use of the four indices. Future clinical trials should compare the GPA with the RPA to prospectively validate these findings.
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              Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer.

              Brain metastasis (BM) is a leading cause of death from non-small-cell lung cancer (NSCLC). Reasoning that activation of the epidermal growth factor receptor (EGFR) contributes to radiation resistance, we undertook a phase II trial of the EGFR inhibitor erlotinib with whole-brain radiation therapy (WBRT) in an attempt to extend survival time for patients with BM from NSCLC. Additional end points were radiologic response and safety. Eligible patients had BM from NSCLC, regardless of EGFR status. Erlotinib was given at 150 mg orally once per day for 1 week, then concurrently with WBRT (2.5 Gy per day 5 days per week, to 35 Gy), followed by maintenance. EGFR mutation status was tested by DNA sequencing at an accredited core facility. Forty patients were enrolled and completed erlotinib plus WBRT (median age, 59 years; median diagnosis-specific graded prognostic assessment score, 1.5). The overall response rate was 86% (n = 36). No increase in neurotoxicity was detected, and no patient experienced grade ≥ 4 toxicity, but three patients required dose reduction for grade 3 rash. At a median follow-up of 28.5 months (for living patients), median survival time was 11.8 months (95% CI, 7.4 to 19.1 months). Of 17 patients with known EGFR status, median survival time was 9.3 months for those with wild-type EGFR and 19.1 months for those with EGFR mutations. Erlotinib was well tolerated in combination with WBRT, with a favorable objective response rate. The higher-than-expected rate of EGFR mutations in these unselected patients raises the possibility that EGFR-mutated tumors are prone to brain dissemination.
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                Author and article information

                Journal
                Chin Med J (Engl)
                Chin. Med. J
                CMJ
                Chinese Medical Journal
                Medknow Publications & Media Pvt Ltd (India )
                0366-6999
                20 December 2017
                : 130
                : 24
                : 2916-2921
                Affiliations
                [1 ]Department of Radiation Oncology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China
                [2 ]Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, China
                [3 ]Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
                Author notes
                Address for correspondence: Prof. Bo Li, Department of Radiation Oncology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China E-Mail: linghberg@ 123456163.com
                Article
                CMJ-130-2916
                10.4103/0366-6999.220296
                5742918
                29237923
                29f0de4a-7d2a-4306-a88d-81e586281d43
                Copyright: © 2017 Chinese Medical Journal

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 16 July 2017
                Categories
                Original Article

                brain metastasis,stereotactic radiosurgery,systemic therapy,whole-brain radiation therapy

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