Histogram Analysis of Apparent Diffusion Coefficient Maps Provides Genotypic and Pretreatment Phenotypic Information in Pediatric and Young Adult Rhabdomyosarcoma

Introduction: We evaluate the role of apparent diffusion coefficient (ADC) histogram metrics in stratifying pediatric and young adult Methods: We retrospectively evaluated baseline diffusion-weighted imaging (DWI) from 38 patients with rhabdomyosarcomas (Not otherwise specified: 2; Embryonal: 21; Spindle Cell: 2; Alveolar: 13, mean +/- std dev age: 8.1 +/- 7.76 years). The diffusion images were obtained on a wide range of 1.5 T and 3 T scanners at multiple sites. FOXO1 fusion status was available for 35 patients, nine of whom harbored the fusion. 13 patients were TNM stage 1, eight had stage 2 disease, nine were stage 3, and eight had stage 4 disease. 23 patients belonged to Clinical Group III and seven to Group IV, while two and five were CG I and II, respectively. Nine patients were classified as low risk, while 21 and five were classified as intermediate and high risk respectively. Histogram parameters of the apparent diffusion coefficient (ADC) map from the entire tumor were obtained based on manual tumor contouring. A two-tailed Mann-Whitney U test was used for all two-group, and the Kruskal-Wallis's test was used for multiple-group comparisons. Bootstrapped receiver operating characteristic (ROC) curves and areas under the curve (AUC) were generated for the statistically significant histogram parameters to differentiate genotypic and phenotypic parameters. Results: Alveolar rhabdomyosarcomas had a statistically significant lower 10th Percentile (586.54 +/- 164.52, mean +/- std dev, values are in x 10-6 mm(2)/s) than embryonal rhabdomyosarcomas (966.51 +/- 481.33) with an AUC of 0.85 (95%CI. 0.73-0.95) for differentiating the two. The 10th percentile was also significantly different between FOXO1 fusion-positive (553.87 +/- 187.64) and negative (898.07 +/- 449.38) rhabdomyosarcomas with an AUC of 0.83 (95% CI 0.71-0.94). Alveolar rhabdomyosarcomas also had statistically significant lower Mean, Median, and Root Mean Squared ADC histogram values than embryonal rhabdomyosarcomas. Four, five, and seven of the 18 histogram parameters evaluated demonstrated a statistically significant increase with higher TNM stage, clinical group, assignment, and pretreatment risk stratification, respectively. For example, Entropy had an AUC of 0.8 (95% CI. 0.67-0.92) for differentiating TNM stage 1 from >= stage 2 and 0.9 (95% CI. 0.8-0.98) for differentiating low from intermediate or high-risk stratification. Conclusion: Our findings demonstrate the potential of ADC histogram metrics to predict clinically relevant variables for rhabdomyosarcoma, including FOXO1 fusion status, histopathology, Clinical Group, TNM staging, and risk stratification.