Purpose: Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing RT. No further clinical benefit has been achieved using alternative radiation strategies. Here, we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiationinduced DNA damage, making it a potential radiosensitizer in the treatment of DIPG. Experimental Design: We evaluated the effects of GSK-J4 on genes associated with DNA double-strand break (DSB) repair in DIPG cells by RNA sequence, ATAC sequence, and quantitative real-time PCR. Radiation-induced DNA DSB repair was analyzed by immunocytochemistry of DSB markers gH2AX and 53BP1, DNA-repair assay, and cell-cycle distribution. Clonogenic survival assay was used to determine the effect of GSK-J4 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and GSK-J4 was evaluated in patient-derived DIPG xenografts. Results: GSK-J4 significantly reduced the expression of DNA DSB repair genes and DNA accessibility in DIPG cells. GSK-J4 sustained high levels of gH2AX and 53BP1 in irradiated DIPG cells, thereby inhibiting DNA DSB repair through homologous recombination pathway. GSK-J4 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and GSK-J4 compared with either monotherapy. Conclusions: Together, these results highlight GSK-J4 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.

Background Most people can think of important attributes they believe physicians should have. The CanMEDS framework defines domains of attributes in medical training (leader, medical expert, scholar, communicator, advocate, collaborator and professional). Whether some are more valued by different stakeholders is unknown. Previous research has shown that patients can receive sub-optimal care if physician and patient expectations of a healthcare encounter differ. This study sought to identify what different stakeholders identified as the single most important attribute for a physician to possess.   Methods A simple survey asked the question ‘what is the single most important attribute a physician should have?’ at a single academic teaching hospital and affiliated medical school. The survey was administered to medical students, doctors, nurses, patients and caregivers. Age and gender were also collected. Responses were placed into domains of response and analyzed to identify trends. The primary outcome is a descriptive analysis of the findings.   Results From 362 individuals who responded, 109 different responses were given. The single most common answer was ‘compassion’ (n=86). Responses were categorized to 5 domains: caring (n=209); professional/collaborator (n=58); medical expert (n=54); communicator (n=32); and other (n=9). Women chose attributes in the caring domain more frequently than men (64% v 49%), though this domain was the most popular for both genders. Medical students were less likely to highly value communication attributes.   Conclusions All stakeholder group identified attributes in the caring domain as being most important. This result acts as a reminder to the healthcare profession.

Background The 1993 International Neuroblastoma Response Criteria (INRC) were revised in 2017 to include modern functional imaging studies and methods for quantifying disease in bone marrow. We hypothesized the 2017 INRC would enable more precise assessment of response to treatment and provide superior prognostic information compared with the 1993 criteria. Methods High‐risk (HR) neuroblastoma patients from two institutions in Chicago diagnosed between 2006 and 2016 were identified. Patients were assessed post induction chemotherapy via the 1993 and 2017 INRC and classified as responder (≥ mixed response [MXR] or ≥ minor response [MR], respectively) or nonresponder (< MXR or < MR). Event‐free survival (EFS) and overall survival (OS) for responders versus nonresponders were determined from end induction and stratified by Cox regression. Patients with progressive disease at end induction were eliminated from the EFS analyses but included in the OS analysis. Results The 1993 criteria classified 52 of the 60 HR patients as responders, whereas 54 responders were identified using the 2017 criteria (Spearman correlation r = 0.82, P < 0.001). No statistically significant difference in EFS was observed for responders versus nonresponders using either criteria (P = 0.48 and P = 0.08). However, superior OS was observed for responders (P = 0.01) using either criteria. Both criteria were sensitive in identifying responders among those with good outcomes. The specificity to identify nonresponders among those with poor outcomes was poor. Conclusions In HR neuroblastoma, end‐induction response defined by the 1993 or 2017 INRC is associated with survival. Larger cohorts are needed to determine if the 2017 INRC provides more precise prognostication.

Objective: To compare outcomes of obese and nonobese pediatric patients with acute promyelocytic leukemia (APL) from the Cancer and Leukemia Group B trial (CALGB) 9710 and the Children's Oncology Group trial AAML0631. Methods: Data including demographics, adverse events, overall and event-free survival (EFS) were analyzed. Results:The prevalence of obesity was 34% on C9710 and 35% on AAML0631. There was significantly lower overall and EFS in the obese population on multivariable analysis on AAML0631 but not on CALGB 9710. Eleven patients died during therapy or in follow-up. Conclusion:The prevalence of obesity is higher in pediatric patients with APL compared to the general population. The decreased EFS and OS in obese patients on AAML0631 suggest that the presence of obesity can influence outcomes using the most current treatment. These findings support the need for further research on the potential role of obesity in pediatric APL leukemogenesis.