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      Prophylactic cranial irradiation for patients with small-cell lung cancer: a systematic review of the literature with meta-analysis

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          Abstract

          Background

          Small cell lung cancer (SCLC) accounts for about 13% of all lung cancer cases. Small cell lung cancer (SCLC) accounts for about 13% of all lung cancer cases. The purpose of the present article is to assess the role of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) by performing a systematic review of the randomized trials published in the literature.

          Methods

          Randomized controlled trials were identified that compared brain metastases incidence and overall survival between PCI and No PCI in patients with SCLC. Search strategies were limited to the English language and to articles published since 1997, and included: databases searched from 1997 to March 2013 –CINAHL, Embase, Medline, Web of Science, and CENTRAL. Methodological quality was assessed with the Jadad scale. The main end points were brain metastasis and survival.

          Results

          The review identified 5 trials, although few were of high quality. Two trials reported the one-year incidence of brain metastasis. PCI reduced the incidence of brain metastasis in one year, with a pooled relative risk of 0.45 (95% CI, 0.35 to 0.58; P < 0.00001). Four trials described the one year survival rate. The combined result revealed a significant (P = 0.01) survival benefit in the group assigned to PCI as compared with the control group, with a pooled relative risk of 0.87 (95% CI, 0.79 to 0.97). Three trials reported the three-year survival rate. The combined result revealed a great significant (P < 0.00001) survival benefit in the PCI group as compared with the No PCI group, with a pooled relative risk of 0.87 (95% CI, 0.83 to 0.91). the Five-year survival rate was compared in four trials Compared with the No PCI group, the PCI group had a significant (P < 0.00001) survival benefit with a pooled relative risk of 0.92 (95% CI, 0.88 to 0.95).

          Conclusions

          The present systematic review indicates that PCI decreases brain metastases incidence and that PCI improves survival in SCLC patients. Prophylactic cranial irradiation should be part of standard care for all patients with small-cell lung cancer who have a response to initial chemotherapy, and it should be part of the standard treatment in future studies involving these patients.

          Electronic supplementary material

          The online version of this article (doi:10.1186/1471-2407-14-793) contains supplementary material, which is available to authorized users.

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          Most cited references31

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          Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group.

          Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival. We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival. The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P= 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P<0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P<0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy. Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.
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            Prophylactic cranial irradiation in extensive small-cell lung cancer.

            We conducted a randomized trial of prophylactic cranial irradiation in patients with extensive small-cell lung cancer who had had a response to chemotherapy. Patients between the ages of 18 and 75 years with extensive small-cell lung cancer were randomly assigned to undergo prophylactic cranial irradiation (irradiation group) or receive no further therapy (control group). The primary end point was the time to symptomatic brain metastases. Computed tomography or magnetic resonance imaging of the brain was performed when any predefined key symptom suggestive of brain metastases was present. The two groups (each with 143 patients) were well balanced regarding baseline characteristics. Patients in the irradiation group had a lower risk of symptomatic brain metastases (hazard ratio, 0.27; 95% confidence interval [CI], 0.16 to 0.44; P<0.001). The cumulative risk of brain metastases within 1 year was 14.6% in the irradiation group (95% CI, 8.3 to 20.9) and 40.4% in the control group (95% CI, 32.1 to 48.6). Irradiation was associated with an increase in median disease-free survival from 12.0 weeks to 14.7 weeks and in median overall survival from 5.4 months to 6.7 months after randomization. The 1-year survival rate was 27.1% (95% CI, 19.4 to 35.5) in the irradiation group and 13.3% (95% CI, 8.1 to 19.9) in the control group. Irradiation had side effects but did not have a clinically significant effect on global health status. Prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival. (ClinicalTrials.gov number, NCT00016211 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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              Small-cell lung cancer.

              Small-cell lung carcinoma is an aggressive form of lung cancer that is strongly associated with cigarette smoking and has a tendency for early dissemination. Increasing evidence has implicated autocrine growth loops, proto-oncogenes, and tumour-suppressor genes in its development. At presentation, the vast majority of patients are symptomatic, and imaging typically reveals a hilar mass. Pathology, in most cases of samples obtained by bronchoscopic biopsy, should be undertaken by pathologists with pulmonary expertise, with the provision of additional tissue for immunohistochemical stains as needed. Staging should aim to identify any evidence of distant disease, by imaging of the chest, upper abdomen, head, and bones as appropriate. Limited-stage disease should be treated with etoposide and cisplatin and concurrent early chest irradiation. All patients who achieve complete remission should be considered for treatment with prophylactic cranial irradiation, owing to the high frequency of brain metastases in this disease. Extensive-stage disease should be managed by combination chemotherapy, with a regimen such as etoposide and cisplatin administered for four to six cycles. Thereafter, patients with progressive or recurrent disease should be treated with additional chemotherapy. For patients who survive long term, careful monitoring for development of a second primary tumour is necessary, with further investigation and treatment as appropriate.
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                Author and article information

                Contributors
                happy_wanda@163.com
                kate435@163.com
                gas19@163.com
                wanglilixiaomao@163.com
                zhengxiangrong@163.com
                wanggongchao@126.com
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                31 October 2014
                31 October 2014
                2014
                : 14
                : 1
                : 793
                Affiliations
                [ ]School of Nursing, Shandong University, Jinan, 250012 China
                [ ]School of Medicine, Shandong University, Jinan, 250012 China
                Article
                4984
                10.1186/1471-2407-14-793
                4232715
                25361811
                e251e228-c2aa-401f-8aa9-edc35f9b6dfe
                © Zhang et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
                : 8 April 2013
                : 17 October 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Oncology & Radiotherapy
                prophylactic cranial irradiation,small-cell lung cancer,meta-analysis

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