Heterogeneity and irregularity of FDG uptake as a prognostic marker for outcome in patients with Ewing sarcoma

Objectives: To determine the prognostic value of FDG-PET for progression-free survival (PFS) and overall survival (OAS) in patients with Ewing sarcoma, we evaluated two novel parameters for tumor heterogeneity and irregularity.

Methods: Twenty-two pts ( age 14.9±8.5) with Ewing Sarcoma (EWS) received FDG-PET for primary staging prior to treatment. Tumor segmentation was performed with ROVER using semi-automatic background detection. Shape irregularity (IRREG) was defined as the deviation of the tumor's shape from sphere symmetry, quantified by the ratio of the third power of the tumor's surface to the second power of its volume. Scale heterogeneity (HETER) was determined using a multiscale variance technique (MSVT) calculating the AUC ratio of heterogeneity-curves based on spatial scales of 8, 16 and 32 mm and varying binarization thresholds. Association of OAS and PFS with heterogeneity parameters (IRREG, HETER) as well as SUVmax was analyzed using Kaplan-Meier (KM) curves. Groups were separated by the best discrimination threshold according to ROC analysis and compared by log-rank test.

Results: Seventeen pts survived with a mean OAS of 58.5 months (min, 18.8 m; max, 97.8 m). Fifteen pts were progression free with a mean PFS of 50.1 month ranging from 2.7 to 91.0 months. KM analysis revealed a 5-year OAS rate of 92% for pts with SUVmax >7 and of 42% in pts with SUVmax ≤ 7 (p=0.012). Pts with HETER >37.5% showed a 5-year OAS rate of 38% compared with 92% in pts with HETER ≤ 37.5% (p=0.004). Higher IRREG> 2.2 was associated with higher 5-year OAS (98% vs. 56%; p=0,049). Higher SUVmax (>7.8) was also associated with higher 5-year PFS rates (91% vs. 62%; p=0.019) whereas neither IRREG nor HETER were predictive for PFS.

Conclusions: Surprisingly, in EWS higher initial SUVmax was significantly correlated with a higher OAS and PFS. Scale heterogeneity seems to be a new promising parameter for prediction of outcome based on FDG-PET in EWS.