Abstract
BACKGROUND: Neuroblastoma is the most common extracranial solid tumor in children. Peptide receptor radionuclide therapy (PRRT) is a treatment modality with great potential, however, the predictive indicators for its efficacy remain unclear. The aim of the study is to evaluate the prognostic utility of quantitative metrics obtained from (18)F-AlF-NOTATATE PET/CT at baseline and post-treatment for predicting response in PRRT in pediatric neuroblastoma. METHODS: Patients with high-risk neuroblastoma that was either recurrent or resistant to treatment were prospectively enrolled for one or two cycles of (177)Lu-PRRT. (18)F-AlF-NOTATATE PET/CT was performed 1 month before and after PRRT; some patients underwent mid-treatment scans (7 weeks post-cycle). Treatment response was evaluated using a modified approach combining principles from European Organization for Research and Treatment of Cancer (EORTC) criteria and Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) criteria. Lesions were delineated semiautomatically to obtain maximum standardized uptake value (SUV(max)), mean standardized uptake value (SUV(mean)), ratio of tumor SUV(max) to liver SUV(max) (SUV(T/L)), ratio of tumor SUV(max) to spleen SUV(max) (SUV(T/S)), tumor volume, total lesion activity, and heterogeneity values. Data were analyzed using independent t-tests or Mann-Whitney U tests. Receiver operating characteristic curves were used to determine the optimal cut-offs for PET parameters. RESULTS: Twenty-two patients (13 boys, 9 girls) were included. Baseline PET revealed significantly lower SUV(T/S), tumor volume, and total lesion activity in non-progressive lesions (p < 0.05); SUV(T/S) predicted efficacy (area under the curve [AUC], 0.588). Interim PET showed significantly lower SUV(max), SUV(mean), SUV(T/L), and SUV(T/S) in non-progressive lesions (p < 0.05); SUV(T/L) predicted efficacy (AUC, 0.740). The SUV(max) ratio (interim/baseline) had the highest predictive accuracy, with a cut-off of 1.25 (AUC, 0.796; sensitivity, 73.03%; specificity, 76.92%). CONCLUSION: Quantitative baseline and mid-treatment (18)F-AlF-NOTATATE PET/CT-derived parameters possess value in predicting PRRT response. An interim-to-baseline PET-derived lesion SUV(max) ratio of ≤1.25 can effectively predict neuroblastoma response to PRRT.