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and Number or location of SBM were also combined irrespective of any differences in cut-off points used. Two review authors (O.H and L.B.) extracted the data on standardized forms. When consensus could not be reached a third review author (P.D.S.D.) was consulted.
Statistical analysis
II
SYSTEMATIC REVIEW
Statistical pooling of the results was not possible; therefore a level of evidence synthesis was performed for each prognostic factor. The levels of evidence were defined as follows:18,19
• Strong evidence: consistent findings (≥75%) in multiple high-quality cohorts.
• Moderate evidence: consistent findings (≥75%) in multiple cohorts, of which only one cohort was of high quality.
• Limited evidence: findings of one high-quality cohort, or consistent (≥75%) findings in one or more low-quality cohorts.
• Inconclusive: inconsistent findings (<75%) irrespective of study quality.
Inter-observer agreement for the risk of bias assessment was determined by the kappa-statistic20. All analyses were performed using SPSS 20.0, Armonk NY, IBM Corp.
RESULTS
Study selection
The initial search yielded 4676 results (Medline n=1996; Embase n=1389; Web of Science n=1092; Cochrance n=145; Cinahl n=54). A total of 1687 duplicates were removed, leaving 2989 studies. After screening, 142 full-text articles were obtained, of which 120 did not meet the eligibility criteria: 33 studies were based on duplicate cohorts, 49 studies focused on a single primary tumor, 23 studies had less than 100 participants, 13 studies did not perform a multivariate analysis and two studies were excluded based on language. In total, 22 studies were included (figure 1).3,4,5,6,8,21-37 During the selection process, the reviewers disagreed on seven inclusions. Consensus was reached for all studies.
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