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As the present study was explorative, we did not perform power analysis prior to study initiation. To minimize sparse data bias, we chose to dichotomize the following data: (1) ASA score into groups with score 1 + 2 and 3 + 4; (2) Karnofsky score into groups with ≥70 (determined by the patient being self-supportive or not) and <70 and (3) anatomical location in upper and lower extremity.

Since no previous studies have defined a reference interval for plasma IL-6 and YKL-40 in patients with MBD, we decided to dichotomize using the median for IL-6 (11.8 ng/L) and the age-corrected 50% percentile (180 ug/L) for YKL-40 in univariate analysis.

As we expected >20 primary causes for the metastatic lesion to be included into the study, we chose to categorize the variable by prognostic group as proposed by Sørensen et al. [2].

Continuous variables are reported as median and IQR as we did not expect normal distribution, and in order to eliminate the expected right screwed values for biochemical variables, these were reported as log2-transformed variables in multivariate analysis.

OS was estimated by the Kaplan–Meier estimator. Correlation between IL-6 and YKL-40 was investigated using the Spearman Rank test. Cox regression models were fitted to identify prognostic factors for OS, and the assumption of proportionality was tested with scaled Schoenfeld residuals.

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