The diagnostic roles of fused <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography and bone scintigraphy in children and young adults with bone sarcomas: a systematic review and meta-analysis

Osteosarcoma and Ewing sarcoma are the most common primary malignant bone diseases in children. An accurate diagnosis and staging of these tumors play a pivotal role in choosing the optimal treatment and predicting outcomes. In recent years, fused 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) has been increasingly used in the diagnosis of bone sarcomas. It is frequently applied in conjunction with, or as a replacement for bone scintigraphy (BS), in order to determine the extent of the disease. However, the questions on the diagnostic significance of these methods and the choice of the most effective approach to the management of children with bone sarcomas still remain unanswered. We conducted a systematic review and meta-analysis to compare the diagnostic roles of 18 F-FDG PET/CT and BS in staging and restaging of bone sarcomas in children and young adults. The study was carried out in accordance with the Cochrane PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two independent researchers looked for prospective and retrospective studies evaluating the sensitivity and specificity of 18 F-FDG PET/CT and BS in staging and restaging of bone sarcomas in children and young adults, published over the last 15 years. The quality of the included studies was assessed using the QUADAS-2 tool. Summary Receiver Operating Characteristic curves were calculated using STATA 17 software packages and the RevMan 5.3 tool to evaluate the overall diagnostic value of PET/CT and BS. The certainty of evidence was evaluated using the GRADE system. This systematic review and meta-analysis included 8 studies (530 patients with bone sarcomas). These studies used 11 patient cohorts (osteosarcoma: 5 cohorts, 305 patients; Ewing sarcoma: 6 cohorts, 225 patients). We discovered that 18 F-FDG PET/CT had high sensitivity in staging and restaging of bone sarcomas (94% (95% confidence interval (CI) 89–97)). On the other hand, BS demonstrated lower sensitivity (69% (95% CI 58–79), the mean difference being 25% (95% CI 18.89–31.00), p < 0.001). At the same time, the specificity of 18 F-FDG PET/CT and the specificity of BS were found to be comparable (96% (95% CI 83–99) and 92% (95% CI 82–97) respectively, p = 0.15). All the results were confirmed in a subgroup analysis of patients with osteosarcoma and Ewing sarcoma. The results of our systematic review and meta-analysis lead us to conclude that 18 F-FDG PET/CT is a more sensitive method for staging and restaging of bone sarcomas in children and young adults, compared to BS. However, both methods have high specificity. Considering our findings, future clinical research in children with bone sarcomas should be aimed at further data collection to clarify the diagnostic roles of 18 F-FDG PET/CT and BS both in children with osteosarcoma and in children with Ewing sarcoma, in order to identify clear indications and choose the best imaging method for detecting metastatic bone lesions, with the aim of developing an optimal diagnostic strategy.