2.2. Eligibility criteria
Clinical trials (phase I, II and III), prospective and retrospective
cohort studies, cross-sectional studies, and case series of patients
with ES were all considered for inclusion in this review. Case reports,
reviews, viewpoints or conference reports were excluded. Studies in
non-English language were excluded. Results from 1970-2020 were
included, though studies incorporating data both after and before 1970
were excluded if it was unclear which data/patients met inclusion
criteria for dates. If data were identified to be reported in
>1 study, the study with the higher ‘n’ was selected.
Data extraction
The data collected for each study in the systematic review included:
authors; journal; year of publication; country of origin; study design;
study population; and study sample size. For references providing only
aggregate data, the following were collected: percentage of patients
with BM metastasis; percentage of patients with isolated BM metastasis;
clinical predictors of BM metastasis; sensitivity of FDG-PET scans to
detect BM metastasis; specificity of FDG-PET scans to exclude BM
metastasis; PPV of positive FDG-PET scans for “true” BM metastasis by
biopsy; NPV of negative FDG-PET scans for no BM metastasis by biopsy;
and any other imaging features associated with BM metastasis. For
references providing patient level data, the following was also
collected when available: age of each ES patient; primary tumor site of
each ES patient; BM metastasis status (if present, subcategorized as
either isolated BM metastasis vs BM + additional areas of metastasis);
results of FDG-PET scan if completed at diagnosis; and results of
unilateral or bilateral BMBA at diagnosis (if yes, was BM disease
identified).
2.4. Data synthesis
To determine the incidence of BM metastasis in newly diagnosed ES
patients, studies reporting newly diagnosed BM metastatic disease in a
homogenous background population of all newly diagnosed ES patients were
included. Studies reporting the incidence of BM metastatic disease in
patients with metastatic disease were used for a separate calculation.
The number of patients from each study was totaled to provide each
patient with uniform weight in calculations of descriptive statistics.
To determine the sensitivity, specificity, PPV and NPV of FDG-PET scans
in comparison to BMBA for the presence of BM metastasis in newly
diagnosed ES patients, studies were included if results of FDG-PET scans
and BMBA for diagnosis of BM metastasis were provided. A study was
considered to sufficiently report on the status of BM metastasis via
FDG-PET scan if it reported FDG-PET BM results separately from primary
tumor or metastatic bone lesions. Studies were excluded if they reported
the incidence of bone metastasis but not BM metastasis by FDG-PET scans.