Assessment of Treatment Responses in Children and Adolescents with Ewing Sarcoma with Metabolic Tumor Parameters Derived from 18F-FDG-PET/CT and Circulating Tumor DNA

Zielsetzung To perform a prospective integrated analysis of 18F-FDG-PET/CT and circulating tumor DNA (ctDNA) to assess responses to multimodal chemotherapy in children and adolescents suffering from Ewing Sarcoma (EwS).

Material und Methoden A total of 20 patients with histologically confirmed EwS underwent multiple PET/CT examinations, performed at the time of each patient’s initial diagnosis and after the second and fifth induction chemotherapy block (EWING2008, NCT00987636). All 263 positive lesions were assessed quantitatively to calculate PET-derived parameters, including whole-body metabolic tumor volume and whole-body total lesion glycolysis. Tumor-specific ctDNA in patient plasma samples was quantified using digital droplet PCR, and the correlations between ctDNA levels and PET-parameters were analyzed. Radiographical responses to multimodal chemotherapy as assessed with PET were compared to biochemical responses as assessed with changes in ctDNA levels.

Ergebnisse Twenty patients underwent a total of 87 PET/CT scans. Significant correlations between and ctDNA levels were observed (all p<0.0001). The combination of a positive PET/CT examination and a positive corresponding ctDNA sample before therapy initiation had a positive predictive value of 100% for the presence of EwS. Evaluation of treatment response after the fifth block of induction chemotherapy showed an agreement between the radiographical response and biochemical response of 89%, (p<0.05). Non-detectable ctDNA after the second block of induction chemotherapy was associated with complete biochemical and radiographical responses after the fifth block of induction chemotherapy in 16/17 patients. During a median follow-up period of 36 months, 4 patients had tumor relapses, which, were accompanied by an increase in plasma ctDNA levels and a positive PET/CT.

Schlußfolgerungen The combination of PET/CT and ctDNA quantification is promising for assessing treatment responses and detecting tumor relapses in children and young adolescents suffering from EwS.