The prognostic value of baseline EARL standardized FDG PET indices in pediatric and adolescent high-grade osteosarcoma

Objective: To investigate the prognostic value of baseline European Association of Nuclear Medicine Research Ltd. (EARL) standardized [¹⁸F]fluorodeoxyglucose positron emission tomography-computed tomography ([¹⁸F]FDG PET-CT) quantitative values for survival and to evaluate cutoff values identified in other studies. Materials and methods: Pediatric and adolescent patients with high-grade osteosarcoma were included. Baseline [¹⁸F]FDG PET-CT, with EARL-accredited reconstructions, was the standard diagnostic staging procedure. Cox proportional hazard analysis for event-free survival (EFS) and overall survival (OS) was performed with clinical prognostic factors. Kaplan–Meier analysis and log-rank tests were applied to investigate the prognostic performance of the [¹⁸F]FDG PET indices. Results: In total, 66 patients were included in this study. In the univariable Cox regression analysis, peak lean-body mass corrected SUV (SUL_peak) (hazard ratio (HR): 1.04), total lesion glycolysis (TLG) (HR: 1.0), and metabolic tumor volume (MTV) (HR: 1.0) were not associated with EFS or OS. Log-rank analysis showed a significant difference in EFS for all SUL_max and SUL_peak cutoffs. For MTV_total the maximum Youden, and for TLG_total, the maximum Youden and maximally selected rank cutoff resulted in a significant EFS difference. No cutoff for any measure showed a significant difference in OS between the groups. ROC curves for event status had an AUC of 0.67, 0.66, 0.64, and 0.64 for SUL_max, SUL_peak, MTV_total, and TLG_total, respectively. Conclusion: In this study, the baseline EARL-standardized [¹⁸F]FDG PET indices of children and adolescents with osteosarcoma were not prognostic of EFS or OS. The proposed prognostic cutoffs from earlier studies suffer from important technical and statistical issues. Key Points: Question Prognostic value of baseline [¹⁸F]FDG PET-CT imaging markers have been reported for histologic response and survival in high-grade osteosarcoma but have not been validated for clinical practice. Findings Baseline SUV_peak, TLG_total, and MTV_totalmeasured on EARL-accredited reconstructions were not prognostic factors for survival in pediatric and adolescent patients with high-grade osteosarcoma. Clinical relevance A wide range of values for SUV_peakand SUV_maxcutoffs with similar prognostic value were identified, questioning the value of a single proposed cutoff. Lack of validation, with important technical and statistical issues of proposed prognostic cutoffs, limits clinical implementation.