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Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis |
Meert A P, Paesmans M, Berghmans T, Martin B, Mascaux C, Vallot F, Verdebout J M, Lafitte J J, Sculier J P |
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Authors' objectives To determine the role of prophylactic cranial irradiation (PCI) in small-cell lung cancer (SCLC).
Searching MEDLINE was searched using the keywords 'small cell lung carcinoma' and 'prophylactic cranial irradiation'. Additional studies were identified from the personal bibliography of one of the authors, and references reported in the selected studies. Studies had to be published as a full paper in either French or English, and before January 2000, to be included in the review.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs) were included.
Specific interventions included in the reviewStudies in which patients did or did not receive PCI were included in the review. The dose ranged from 8 to 40 Gy.
Participants included in the reviewStudies had to deal with SCLC exclusively to be included in the review.
Outcomes assessed in the reviewNo inclusion criteria relating to the outcomes were specified. The outcomes reported were time to relapse in the brain (brain metastases incidence) and survival.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the reviewers performed the selection.
Assessment of study quality Studies were scored on two quality scales, the score proposed by Chalmers et al. (see Other Publications of Related Interest) and the score proposed by the European Lung Cancer Working Party (details presented in an appendix). Nine investigators read each publication to guarantee the critical reading of the selected articles. The score of each item was determined by consensus, at meetings where at least two thirds of the investigators needed to be present. The final score was expressed in a percentage ranging from 0 to 100%, where higher values reflected a larger application of methodological standards.
Data extraction The authors do not state how the data were extracted for the review, or how many of the reviewers performed the data extraction.
Data were extracted on the following: the authors; dates; stage; cerebral work-up; PCI (Gray); timing of PCI administration; dose; and the number of patients. If hazard ratios (HRs) were not presented, they were approximated using the total number of events and the log rank statistic, its p-value or the 0-E statistic (difference between the numbers of observed and expected events). If this data were unavailable but the data were presented graphically, then these were used to estimate the survival rates at specified times in order to reconstruct the HR.
Methods of synthesis How were the studies combined?The studies were classified as positive if the statistical test comparing the survival distributions between the arms was significant at the 5% level in favour of the experimental arm. All other studies were classified as negative. The correlation between quality scores was measured by the Spearman rank correlation coefficient.
Non-parametric Mann-Whitney or Kruskal-Wallis tests were performed to compare the quality score distributions according to the values of the considered discrete variable. HRs were estimated for each study, where a HR of less than 1 indicated a survival benefit for the intervention arm. HRs for the incidence of brain metastases and survival were pooled, but no details of the methods used were presented.
How were differences between studies investigated?Heterogeneity was not formally investigated. However, subgroup analyses were performed for patients in complete remission only, and for subgroups of patients with initial PCI, limited disease, any stage disease, or who had a computed tomography (CT) brain scan at initial staging or just before randomisation for PCI.
Results of the review Twelve RCTs (n=1,547) were included.
Brain metastases incidence (10 RCTs).
The HR was 0.48 (95% confidence interval, CI: 0.39, 0.60) for all patients, and 0.49 (95% CI: 0.39, 0.62) for patients in complete remission only.
No measures of heterogeneity were presented. Subgroup analyses: the decrease in brain metastases was also present in the subgroup analyses performed.
Survival (11 RCTs).
The HR was 0.94 (95% CI: 0.87, 1.02) for all patients, and 0.82 (95% CI: 0.71, 0.96) for patients in complete remission only.
No measures of heterogeneity were presented.
Subgroup analyses: there was no significant effect of PCI on survival for those with initial PCI, limited disease, and those with no CT scan before randomisation. PCI increased survival in those with all stages disease, those with a brain CT scan for staging, and those with a brain CT scan before randomisation.
Toxicity was rarely adequately described.
Authors' conclusions PCI decreased the incidence of brain metastases, and improved survival in SCLC patients in complete remission. However, these effects were obtained in patients who had no systematic neuropsychological and brain imagery assessments. The long-term toxicity has not been evaluated prospectively. While PCI can be recommended in patients with SCLC, and complete remission documented by a work-up including a brain CT scan, data are lacking to generalise its use to any complete remission situations.
CRD commentary This was an average review of the area. The literature search was limited to one database, and only studies published in English or French were included. It is therefore possible that important studies have been missed, and that the results may be subject to publication bias. The inclusion criteria were clearly stated. Extensive details of the complicated, methodological assessments performed were presented. However, the authors failed to provide any details of how the studies were assessed for relevance, or how the data were extracted from the included studies. The tables of results were limited and further study details would have been beneficial; for example, the tables and text provided no details of the comparator interventions. The methods used to pool the studies were not described, and heterogeneity does not appear to have been assessed. Thus, it is not possible to say whether it was appropriate to pool the studies.
The authors' conclusions appear to be supported by the results, but should be interpreted with some degree of caution due to the limitations highlighted.
Implications of the review for practice and research Practice: The authors did not state any implications for practice.
Research: The authors state that new trials adapted to more modern imagery techniques, such as magnetic resonance imaging, are necessary.
Funding Funded in part by FNRS-Televie (Belgium), grant number 7.4512.98.
Bibliographic details Meert A P, Paesmans M, Berghmans T, Martin B, Mascaux C, Vallot F, Verdebout J M, Lafitte J J, Sculier J P. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer 2001; 1:5 Other publications of related interest Chalmers TC, Smith H, Blackburn B, Silverman B, Schroeder B, Reitman D, et al. A method for assessing the quality of a randomiszed control trial. Control Clin Trials 1981;2:31-49.
Indexing Status Subject indexing assigned by NLM MeSH Brain Neoplasms /prevention & Carcinoma, Small Cell /drug therapy /prevention & Cranial Irradiation /methods; Humans; Lung Neoplasms /drug therapy /pathology /radiotherapy; Neoplasm Recurrence, Local /prevention & Randomized Controlled Trials as Topic; Remission Induction; control; control /radiotherapy /secondary; control /secondary AccessionNumber 12001008285 Date bibliographic record published 31/10/2002 Date abstract record published 31/10/2002 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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