Application of pretreatment 18F-FDG PET metabolic parameters in children with Langerhans cell histiocytosis

To evaluate whether pre-treatment ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) metabolic parameters can predict cfBRAF V600E mutation status and prognosis in pediatric Langerhans cell histiocytosis (LCH). We retrospectively analyzed 64 newly diagnosed pediatric LCH patients who underwent pre-treatment ¹⁸F-FDG PET/CT between September 2020 and March 2024. Metabolic parameters were measured, including maximum standardized uptake value (SUVmax), tumor-to-liver standardized uptake value ratio (SUVR_liver), tumor-to-bone marrow standardized uptake value ratio (SUVR_BM), total metabolic tumor volume (tMTV), and total lesion glycolysis (tTLG). Associations between metabolic parameters and cfBRAF V600E mutation status were assessed using ROC curve analysis. PFS was evaluated using Kaplan-Meier analysis and Cox proportional hazards regression. The cfBRAF V600E mutation was detected in 22 patients (34%). All metabolic parameters were significantly higher in mutation-positive patients (all P < 0.05). SUVR_liver demonstrated the highest diagnostic performance (AUC 0.806, optimal cut-off 6.9), followed by tMTV (AUC 0.792, optimal cut-off 6.2 cm³). Multivariate logistic regression identified three independent predictors of mutation status: younger age (odds ratio [OR] = 0.595, P = 0.001), higher tMTV (OR = 26.760, P = 0.001), and advanced clinical stage (OR = 7.199, P = 0.005). During a median follow-up of 25.2 months, tMTV was the strongest independent predictor of PFS in multivariate Cox regression analysis. Patients with tMTV ≥ 14.66 cm³ had significantly worse outcomes than those with lower values (log-rank P < 0.001). Pre-treatment ¹⁸F-FDG PET/CT metabolic parameters can predict both cfBRAF V600E mutation status and clinical outcomes in pediatric LCH patients. SUVR_liver and tMTV show excellent diagnostic performance for mutation prediction, while tMTV independently predicts prognosis. These non-invasive biomarkers can aid in risk stratification and treatment planning.