Serial Profiling of Circulating Tumor DNA Identifies Dynamic Evolution of Clinically Actionable Genomic Alterations in High-Risk Neuroblastoma.

Neuroblastoma evolution, heterogeneity, and resistance remain inadequately defined, suggesting a role for circulating tumor DNA (ctDNA) sequencing. To define the utility of ctDNA profiling in neuroblastoma, 167 blood samples from 48 high-risk patients were evaluated for ctDNA using comprehensive genomic profiling. At least one pathogenic genomic alteration was identified in 56% of samples and 73% of evaluable patients, including clinically actionable ALK and RAS-MAPK pathway variants. Fifteen patients received ALK inhibition (ALKi), and ctDNA data revealed dynamic genomic evolution under ALKi therapeutic pressure. Serial ctDNA profiling detected disease evolution in 15 of 16 patients with a recurrently identified variant-in some cases confirming disease progression prior to standard surveillance methods. Finally, ctDNA-defined ERRFI1 loss-of-function variants were validated in neuroblastoma cellular models, with the mutant proteins exhibiting loss of wild-type ERRFI1's tumor-suppressive functions. Taken together, ctDNA is prevalent in children with high-risk neuroblastoma and should be followed throughout neuroblastoma treatment. SIGNIFICANCE: ctDNA is prevalent in children with neuroblastoma. Serial ctDNA profiling in patients with neuroblastoma improves the detection of potentially clinically actionable and functionally relevant variants in cancer driver genes and delineates dynamic tumor evolution and disease progression beyond that of standard tumor sequencing and clinical surveillance practices. See related commentary by Deubzer et al., p. 2727. This article is highlighted in the In This Issue feature, p. 2711.

Network comparison and the within-ensemble graph distance.

Quantifying the differences between networks is a challenging and ever-present problem in network science. In recent years, a multitude of diverse, ad hoc solutions to this problem have been introduced. Here, we propose that simple and well-understood ensembles of random networks-such as Erdos-Rényi graphs, random geometric graphs, Watts-Strogatz graphs, the configuration model and preferential attachment networks-are natural benchmarks for network comparison methods. Moreover, we show that the expected distance between two networks independently sampled from a generative model is a useful property that encapsulates many key features of that model. To illustrate our results, we calculate this within-ensemble graph distance and related quantities for classic network models (and several parameterizations thereof) using 20 distance measures commonly used to compare graphs. The within-ensemble graph distance provides a new framework for developers of graph distances to better understand their creations and for practitioners to better choose an appropriate tool for their particular task.

Child Life Specialists' Experiences Addressing Social Determinants of Health: A Web-Based Survey.

We used Google Forms to survey 110 child life specialists on their experiences addressing family psychosocial issues. Most respondents were female (99%) and white (95%), with mean age 34 ± 10 years. Ninety-five percent reported addressing family psychosocial issues during the previous 3 months, including parental separation/divorce (71%), poverty/financial needs (64%), parental mental illness (59%), substance abuse at home (54%), homelessness/housing problems (54%), bullying (49%), physical neglect (46%), physical abuse (46%), unemployment (46%), emotional neglect (45%), and hunger/food insecurity (42%). Eighty-five percent of respondents reported addressing family psychosocial issues once per month or more often, with 80% providing coping strategies, 76% providing family support, 66% providing therapeutic play, and 66% providing psychological preparation. These findings indicate that child life specialists frequently address a range of family psychosocial issues. Further research is needed to clarify the role and impact of child life services on social determinants of health.