BackgroundThe chemosensitivity of osteosarcoma patients to MTX is closely related to prognosis. There is currently a lack of advance prediction methods for MTX sensitivity.ObjectiveWe proposed novel peri-osteosarcoma fat parameters based on computed tomography (CT) to evaluate the chemotherapy response preoperatively and calculate the correlation between image characteristics and methotrexate (MTX) blood concentration and systemic inflammation.Materials and methodsPediatric patients with osteosarcoma (OS) who were treated with high-dose MTX were retrospectively studied and grouped according to postoperative Huvos classification. Clinical data were collected and reviewed. Image characteristics including peri-osteosarcoma fat volume and fat attenuation index were measured using the threshold method based on CT images. Statistical significance, correlation and prediction performance were performed.ResultsEighteen patients (good response (GR) group/poor response (PR) group: 10/8) was enrolled. MTX peak value at 6 h differed significantly between the two groups which was significantly higher in GR group (745.1 μmol/L vs 529.0 μmol/Lp= 0.001). Peri-osteosarcoma fat attenuation index was significantly lower in GR group compared with that in PR group (− 104.90 vs. − 97.19,p< 0.0001). MTX blood concentration at 6 h negatively correlated with peri-osteosarcoma fat attenuation index (R= − 0.519,p= 0.027). In addition, 6 h MTX blood concentration (OR 0.974; 95% CI 0.951–0.998,p= 0.037) and FAI (OR 2.108; 95% CI 1.047–4.243,p= 0.037) were, respectively, independently related to good response to chemotherapy. The prediction performance on chemotherapy response of peri-osteosarcoma fat attenuation index and 6 h MTX blood concentration were both good with the comparable area under the ROC curve (0.950, 95% CI 0.856–1.000 and 0.963, 95% CI 0.878–1.00).ConclusionsPeri-osteosarcoma fat parameters based on CT were associated with the chemotherapy response and the MTX blood concentration, but not with the systemic inflammation. Combined with the requirement of current clinical practice, peri-osteosarcoma fat parameters may have the potential to be valuable image characteristics for monitoring chemotherapy response in OS pediatric patients.