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.