Individualized risk assessment in neuroblastoma: Prediction of outcome based on metabolic activity in I-123-MIBG-SPECT

Objectives: Risk-adapted treatment in children with neuroblastoma (NB) follows clinical and genetic factors. This study evaluated the metabolic tumor volume (MTV) and its asphericity (ASP) in pre-therapeutic I-123-MIBG-SPECT (IMS) for individualized image-based prediction of outcome.

Methods: Retrospective analysis of 22 consecutive children with newly diagnosed NB (f:10; m:12; median age, 1.7 [0.3-6.8] years) undergoing pretherapeutic IMS. MTV and asphericity as the relative deviation of the MTV surface from an isovolumetric sphere were defined for each primary tumor using semi-automatic, background-adapted thresholds. Cox regression, ROC analysis (cut-off determination) and Kaplan-Meier analyses with log-rank test were performed regarding event-free survival (EFS) and overall survival (OS). Analyzed parameters included ASP, MTV, laboratory parameters (such as urinary homovanillic acid-to-creatinine ratio [HVA/C] or serum lactate dehydrogenase [LDH]), age, tumor stage and genetic factors. The predictive accuracy of the optimal multifactorial models was determined by Harrell’s C and the χ2.

Results: Median follow-up was 37 [6-102] months (disease progression / relapse, n=8; death, n=4). Only ASP (p=0.034; hazard ratio [HR], 1.03 for one-unit increase) and MTV (p=0.031; HR, 1.012) were significant predictors of EFS in univariate Cox, only ASP was predictive in multivariate analysis (p=0.024; HR, 1.041). Mean EFS for high (>31.6%) vs. low ASP was 20 vs. 82 months (p=0.022), EFS for high (>46.7 ml) vs. low MTV was 18 vs. 83 months (p=0.008). A combined risk model of high ASP and high HVA/C predicted EFS with the highest accuracy. In Kaplan-Meier analysis, shorter OS was predicted by high ASP (p=0.003), MTV (p<0.001; cut-off, >82.5 ml), HVA/C (>215 µmol/g; p=0.021), LDH (p<0.001) and MYCN amplification (p=0.001). A combination of high MTV and high HVA/C predicted OS with the highest accuracy.

Conclusion: In this explorative study, pre-therapeutic markers of tumor metabolic activity in neuroblastoma (ASP, MTV, urinary HVA-to-creatinine ratio) allowed to separate children with high and low risk for progression / relapse or shorter OS under current therapy regimens. Research Support: No external funding. Figure:Kaplan-Meier curves with log-rank test are displayed for patients with 0, 1 or 2 risk factors according to the predictive model regarding EFS (ASP, HVA/C) or OS (MTV, HVA/C), respectively. Log-rank test was performed for the overall model.