Abstract
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Objectives: Despite advances in delivering dose-intensive and myeloablative therapy with hematopoietic stem cell support, the survival for patients presenting with metastatic neuroblastoma remains poor, with a 3-year event free survival (EFS) of about 60%. Modern treatment protocols are based on risk stratification which incorporates age of diagnosis, tumor stage, tumor histology, and molecular and cytogenetics including MYCN amplification. 18F-FDG PET/CT plays a role in disease staging and follow up in patients with meta-iodobenzylguanidine (MIBG) negative disease. The role of 18F-FDG PET/CT in patients with MIBG-avid disease continues to be explored. The objective of this study was to report FDG PET findings in a cohort of children with neuroblastoma and assess for predictive associations with survival.
Methods: A single institution retrospective review was performed to identify all patients with newly diagnosed neuroblastoma for whom a pre-therapy 18F-FDG PET/CT was obtained between July 2006 and July 2019. All FDG-PET examinations had been performed utilizing 0.1-0.14 mCi/kg of FDG with imaging performed approximately 1 hour after radiopharmaceutical administration. Using the PET-edge tool in MIM (MIM Software; Cleveland, OH), a single observer drew regions of interest around the primary tumor to measure SUVmax, SUVmean, tumor volume (TV), and total lesional glycolysis (TLG, SUVmean x tumor volume). Event free survival (EFS) was defined as the time from diagnosis to tumor recurrence or death. Overall survival (OS) was defined as the time from diagnosis to death. Univariate and multivariate (age-adjusted) analysis using a Cox proportional hazards regression test was used to assess the predictive performance of PET indices for EFS and OS. Optimal thresholds for the PET indices were determined using receiver operating characteristics (ROC) curve analysis, and the survival significance of these thresholds were determined using a log-rank test.
Results: A total of 55 patients were identified. The median age at diagnosis was 2.92 years (range 0.011-10.4 years). Nine patients (16%) experienced disease recurrence, and eleven patients (20%) expired during the study period. Average follow-up was 1654 days (range 27-4433 days). SUVmax ranged from 1.1 to 11.2 (mean 4.38 ± 2.23). SUVmean ranged from 0.78 to 4.67 (mean 2.05 ± 0.84). Tumor volume ranged from 0.80 to 1039 mL (mean 179 ± 232 mL). TLG ranged from 0.77 to 2681 (mean 418 ± 601 mL). SUVmax (p = 0.028) and SUVmean (p = 0.045) were significantly associated with overall survival, with age-adjusted hazard ratios of 1.30 and 2.04, respectively. An SUVmax threshold of 4.77 (p = 0.028) best predicted OS with a median OS of 2604 days for patients with SUVmax above this threshold versus >2957 days (median survival not met during study period) for patients with SUVmax below this threshold.
Conclusions: Higher pretreatment SUVmax and SUVmean on 18F-FDG PET/CT are associated with lower overall survival in newly diagnosed neuroblastoma.