The review concluded that, compared with whole brain radiotherapy alone, whole brain radiotherapy with radiosensitizer did not significantly improve overall survival, local control and tumour response in patients with brain metastases. Without further details on study quality and given other methodological concerns in the review methods, it is difficult to judge the reliability of the authors' conclusions.

To compare the efficacy and safety of whole brain radiotherapy with radiosensitizer versus whole brain radiotherapy alone in the treatment of brain metastases.

MEDLINE was searched without language restriction from 1966 to 2008. EMBASE, CANCERLIT, LILACS and The Cochrane Library were searched without language restriction from January 1998 and July 2007. Search terms were reported. Conference proceedings from Annual Meetings of the American Society of Clinical Oncology were searched. Reference lists of relevant publications were screened.

Randomised controlled trials (RCTs) and quasi-randomised controlled trials that compared whole brain radiotherapy with radiosensitizer versus whole brain radiotherapy alone in adult patients with Computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated brain metastases from histologically proven solid tumours (excluding small-cell lung cancer, germ cell tumours and lymphomas) were eligible for inclusion. Studies that evaluated use of surgery and/or whole brain radiotherapy for single brain metastases were excluded. Review outcomes included overall survival, local brain tumour response, central nervous system progression, quality of life and adverse events.

Total dose of whole brain radiotherapy in included studies ranged from 30Gy to 37.5Gy in 10-15 fractions. Included studies used the radiosensitizers: lonidamide, metronidazole, misonidazole, bromodeoxyuridine, motexafin gadolinium, efaproxiral and thalidomide.

Two reviewers independently selected studies for inclusion.

Study quality was assessed with the Jadad scale, a five-point scale of randomisation, blinding and withdrawals.

Two reviewers independently performed the validity assessment. Any disagreements were resolved by consensus.

Event rates were extracted to enable calculation of odds ratios (ORs) with 95% confidence intervals (CIs). The proportion of survivors at six months was estimated from Kaplan-Meier probability survival curves.

Two reviewers independently performed data extraction. Any disagreements were resolved by consensus.

Where appropriate, studies were combined in a meta-analysis. Pooled odds ratios with 95% CIs were calculated. Statistical heterogeneity was assessed (the authors did not state which statistic was used to derive the p value). Where appropriate, outcomes (which included adverse events and quality of life) were synthesised narratively.

Eight RCTs (n=2,317 reported in the text, n=2,753 based on Table 1) were included in meta-analyses. Sample size ranged from 58 to 554. Study quality was not reported.

Compared with whole brain radiotherapy alone, whole brain radiotherapy with radiosensitizer was not significantly associated with an improvement in overall survival at six months (OR 1.03, 95% CI 0.84 to 1.25; seven RCTs), local brain tumour response (OR 0.8, 95% CI 0.5 to 1.03; four RCTs) and central nervous system progression (OR 1.1, 95% CI 0.9 to 1.3; four RCTs)

No significant heterogeneity was observed in the outcomes of overall survival and central nervous system progression; the result of statistical heterogeneity assessment for the outcome of local brain tumour response was not presented.

Seven RCTs reported treatment-related serious adverse events. One RCT reported that 11% of efaproxiral-treated patients had grade three adverse event of hypoxemia. One RCT reported that the rate of patients who experienced Grade three to four adverse events in the group of whole brain radiotherapy with thalidomide was significantly higher than the group of whole brain radiotherapy alone (p<0.0001). One RCT reported three fatal toxicities in 34 patients who received whole brain radiotherapy with bromodeoxyuridine.

Results of quality of life and neurocognitive progression were reported.

Compared with whole brain radiotherapy alone, whole brain radiotherapy with radiosensitizer did not significantly improve overall survival, local control and tumour response in patients with brain metastases.

This review's inclusion criteria were clear. Relevant sources were searched. Efforts were made to find both published and unpublished studies without language restriction, which minimised potential for publication and language biases. Sufficient attempts were taken to minimise errors and biases in the review process. Relevant criteria were used to examine study quality, but the quality of included studies was not presented. Clinical heterogeneity was investigated and a narrative synthesis was appropriate for some secondary outcomes given the high level of clinical heterogeneity identified. Statistical heterogeneity was assessed for pooling the results of main efficacy outcomes, but there was limited reporting of the results of the assessment. The authors did not state which statistical model was used in meta-analyses, which made it difficult to assess whether an appropriate approach was employed to pool the results. The conclusions reflected the evidence presented. However, without further details on study quality and given other methodological concerns outlined above, it is difficult to judge the reliability of the authors' conclusions.

Practice: The authors stated that efforts should be made to use multimodality approaches that included surgery and radiosurgery to improve survival outcomes for patients with brain metastases.

The authors did not state any implications for research.

Not stated.

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.