This review evaluated radiotherapy alone or in combination with other treatments in adult patients with single or multiple brain metastases of cancer. The authors concluded that surgical excision followed by radiotherapy should be considered for selected patients with single metastases and whole brain radiotherapy be considered for those with multiple metastases. Overall, the authors' conclusions appear reliable.

To determine the role of radiotherapy alone or in combination with other treatments in adult patients with single or multiple brain metastases of cancer.

The authors searched MEDLINE, Cancerlit, CINAHL, EMBASE (from inception to 2002 or 2003) and The Cochrane Library (2002, issue 4). Search terms were reported. They also searched the Physicians Data Query clinical trials database and the proceedings of scientific meetings (listed), and screened reference lists of relevant articles. Only English-language reports were included.

Randomised controlled trials (RCTs) and quasi-randomised controlled studies of external beam radiotherapy or radiosurgery in adult patients with single or multiple brain metastases from cancer of any histology were eligible for the review. Studies that used prophylactic radiotherapy were excluded. Outcomes of interest were survival, intracranial progression-free duration, response of metastases to therapy, quality of life, symptom control, neurological function and toxicity. Included studies involved a variety of different comparisons, mostly in patients with multiple metastases. The most common control regimen was 3000cGY (centigray) in 10 fractions.

Two reviewers selected studies for the review.

Validity was assessed using the Jadad scale and given a score between 0 and 5. The authors did not state explicitly how many reviewers performed the validity assessment

Data on numbers of events and participants in each treatment group were used to derive relative risks and 95% confidence intervals for dichotomous outcomes. Where possible, data were extracted on an intention-to-treat basis. Mortality at six months after randomisation was estimated from Kaplan-Meier curves. Tumour response was defined as the sum of complete and partial response and required a 50% or greater decrease in lesion size and a stable or decreasing dose of corticosteroids. Data were extracted in duplicate.

Studies were synthesised narratively by type of metastasis (single or multiple) and comparison. Where possible, pooled relative risks were calculated by meta-analysis using random-effects models. Differences between studies were discussed in the text and were evident from tables. Statistical heterogeneity in meta-analyses was assessed by the ² test.

Twenty-seven trials were included in the review (total number of participants unclear). Jadad scores ranged from 1 to 4. Four of the 27 trials involved patients with single brain metastases, one involved patients with one to three metastases and the rest involved patients with multiple metastases.

For patients with single brain metastasis, surgical excision combined with whole brain radiotherapy did not improve survival compared with whole brain radiotherapy alone (three trials). Postoperative whole brain radiotherapy reduced intracranial recurrence, but did not improve survival compared with surgery alone (one trial). For patients with multiple metastases, altered dose fractionation schedules of whole brain radiotherapy did not improve survival compared with a standard schedule (nine trials) and addition of radiosensitizers did not improve survival or response (five trials). Whole brain radiotherapy and radiosurgery boost did not improve survival over whole brain radiotherapy alone in patients with multiple metastases (three trials), but a benefit was reported in one trial for patients with a single metastasis. In one trial, whole brain radiotherapy plus supportive care increased median survival compared with supportive care alone (14 versus 10 weeks), but the statistical significance of the result was uncertain. Results for other outcomes (including toxicity) and comparisons were reported.

For patients with single brain metastases, surgical excision should be considered for those with good performance status and minimal evidence of extra-cranial disease; post-operative whole brain radiotherapy should be considered to reduce recurrence. Whole brain radiotherapy was recommended for multiple metastases; supportive care with or without whole brain radiotherapy was an option for patients with poor performance status. Additional conclusions were listed in the report.

The inclusion criteria were clear. The authors searched a number of relevant sources, although restriction of the review to English-language studies meant that some studies may have been missed. Validity was assessed using a standard method, although clearer reporting of whether trials were randomised or quasi-randomised would have aided interpretation of the results. Review methods were not reported in detail, but it appeared that measures were taken to reduce errors and bias in study selection and data extraction. Relevant details of included studies were presented. Studies were synthesised narratively with meta-analysis where several studies covered the same comparison and outcome. Heterogeneity was assessed statistically, but not explored; in some cases studies were pooled where this may not have been appropriate. Overall, the authors' recommendations reflected the evidence presented and appear reliable

Practice: See Authors' Conclusions.

Research: The authors did not state any implications for further research.

Cancer Care Ontario; Ontario Ministry of Health and Long-term Care.

Tsao MN, Lloyd NS, Wong RKS et al. Radiotherapeutic management of brain metastases: a systematic review and meta-analysis. Cancer Treatment Reviews 2005;31:256-273.

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.