Multiparametric MRI biomarkers in pediatric osteosarcoma: associations of ADC, necrosis, and tumor volume with histologic and clinical outcomes in a retrospective cohort study.
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BACKGROUND: Assessment of response to neoadjuvant chemotherapy in pediatric osteosarcoma is challenging, as histologic evaluation of tumor necrosis is only available after surgical resection. Quantitative MRI parameters, including diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC) values, tumor volume, and radiologic necrosis, may provide noninvasive information related to treatment response and outcomes. OBJECTIVE: To evaluate quantitative MRI features before and after neoadjuvant chemotherapy in pediatric osteosarcoma and to investigate their associations with histologic response and clinical outcomes. MATERIALS AND METHODS: This retrospective single-center cohort study included 50 pediatric patients with histologically confirmed osteosarcoma (2014-2023) who underwent MRI with DWI at diagnosis and after neoadjuvant chemotherapy. Tumor volume, radiologic necrosis, and ADC parameters (minimum, mean, and maximum) were independently assessed by two musculoskeletal radiologists. Histologic response was graded using the Huvos system. Associations between imaging parameters and histologic response, survival outcomes, and relapse were evaluated using nonparametric and exploratory time-to-event analyses. RESULTS: Fifty pediatric patients were included (mean age 13.2 years; 62% male), of whom 21% had metastatic disease at diagnosis. Pre-treatment ADC minimum differed between good and poor histologic responders (median 661.75 vs 851.0×10⁻⁶ mm2/s; P=0.047). Tumor volume variation showed evidence of association with Huvos grade (Spearman ρ=-0.402, P=0.004). Post-treatment tumor volume was associated with clinical outcome (P=0.005), and larger pre- and post-treatment volumes were observed in patients who relapsed. All ADC parameters increased after chemotherapy (P<0.01). Pre-treatment ADC minimum showed evidence of association with overall survival (ρ=-0.300, P=0.038), while post-treatment ADC minimum was associated with disease-free survival (ρ=-0.458, P=0.028). ROC analysis of pre-treatment ADC minimum yielded an AUC of 0.68 for histologic response. CONCLUSION: Quantitative MRI parameters demonstrate exploratory associations with histologic response and clinical outcomes in pediatric osteosarcoma, providing additional information when interpreted alongside conventional MRI features and clinical data.