De Preter et al. Page 7684

Improving risk classification of children with neuroblastoma is an important challenge in pediatric oncology. Through one of the largest microRNA (miRNA) expression studies on cancer biopsies, De Preter and colleagues developed a 25-miRNA signature that identifies neuroblastoma patients with increased risk for adverse outcome. This classifier is independent of currently used risk factors and enables further patient stratification within the current highrisk subgroup. Importantly, the 25-miRNA signature performs equally well in archived formalin-fixed, paraffin-embedded material as it does in fresh frozen samples. Results were confirmed in 2 independent patient cohorts and indicate that use of the miRNA signature can substantially improve risk stratification of patients with neuroblastoma.

Fleuren et al. Page 7693

The insulin-like growth factor 1 receptor (IGF-1R) is a potential new therapeutic target. Unfortunately, a suitable biomarker predictive for anti-IGF-1R therapy response is not available. Fleuren and colleagues investigated whether indium-111-labeled R1507 (111In-R1507) immuno-SPECT, a novel noninvasive, in vivo screening method to visualize membranous IGF-1R expression and accessibility, can be used to predict IGF-1R treatment response in Ewing sarcoma and osteosarcoma. This novel imaging technique could clearly distinguish among high, modest, and nonresponsive xenografts, whereas conventional techniques could not. This new technique may therefore enable the selection of patients susceptible to IGF-1R targeted therapy and monitor treatment response.

Eigentler et al. Page 7732

Ever since its approval in 1976, dacarbazine has represented the standard of care for the treatment of patients with metastatic melanoma; however, only a minority of melanoma patients responds to dacarbazine treatment. This article presents clinical evidence that the combination of dacarbazine with the tumor-targeting immunocytokine L19-IL2 (a biopharmaceutical agent consisting of the human recombinant antibody L19, specific to the alternatively-spliced EDB domain of fibronectin, fused to human interleukin-2) is well tolerated in patients with metastatic melanoma and can induce long-lasting objective responses in a subset of patients.

Taniguchi et al. Page 7808

Examination of epidermal growth factor (EGFR) mutations is a diagnostic routine for treatment of lung cancer that involves the use of EGFR tyrosine kinase inhibitors. Because it is difficult to obtain primary lesions, especially in patients with progressive disease, a noninvasive procedure is desirable. Taniguchi and colleagues used BEAMing (beads, emulsion, amplification, and magnetics) to detect EGFR mutations in circulating tumor DNA. In addition to its high sensitivity, BEAMing can estimate the extent to which the activating mutation alleles have been converted into resistant alleles. Because BEAMing and next-generation sequencers are based on the same technologic principle, we can predict how next-generation sequencers will detect mutations in circulating tumor DNA based on the findings from this study.