Background The use of next‐generation sequencing for fusion identification is being increasingly applied and aids our understanding of tumor biology. Some fusions are responsive to approved targeted agents, while others have future potential for therapeutic targeting. Although some pediatric central nervous system tumors may be cured with surgery alone, many require adjuvant therapy associated with acute and long‐term toxicities. Identification of targetable fusions can shift the treatment paradigm toward earlier integration of molecularly targeted agents. Methods Patients diagnosed with glial, glioneuronal, and ependymal tumors between 2002 and 2019 were retrospectively reviewed for fusion testing. Testing was done primarily using the ArcherDx FusionPlex Solid Tumor panel, which assesses fusions in 53 genes. In contrast to many previously published series chronicling fusions in pediatric patients, we compared histological features and the tumor classification subtype with the specific fusion identified. Results We report 24 cases of glial, glioneuronal, or ependymal tumors from pediatric patients with identified fusions. With the exception of BRAF:KIAA1549 and pilocytic/pilomyxoid astrocytoma morphology, and possibly QKI‐MYB and angiocentric glioma, there was not a strong correlation between histological features/tumor subtype and the specific fusion. We report the unusual fusions of PPP1CB‐ALK, CIC‐LEUTX, FGFR2‐KIAA159, and MN1‐CXXC5 and detail their morphological features. Conclusions Fusion testing proved to be informative in a high percentage of cases. A large majority of fusion events in pediatric glial, glioneuronal, and ependymal tumors can be identified by relatively small gene panels.

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Background Patient-physician communication is critical for helping patients understand and complete the complex steps needed to diagnose stage and treat lung cancer. We assessed which domains of patient-physician communication about lung cancer and its treatment are associated with receipt of disease-directed, stage-appropriate treatment. Methods Patients with recently-diagnosed lung cancer were recruited from four medical centers in New York City from 2008 to 2011. Participants were surveyed about discussions with physicians regarding treatment, symptoms and needs. Multiple regression analysis and structural equation modeling were used to assess which communication factors were associated with disease treatment. Results Of the 352 participants, 191 (54%) received disease-directed, stage-appropriate treatment. Unadjusted associations between communication items and treatment found that participants who felt that their physicians explained the risks and disadvantages of lung cancer treatment (P<0.01), discussed their chances of cure (P=0.02), discussed goals of treatment (P<0.01) or who were warm and friendly (P=0.04) were more likely to undergo treatment. Three communication domains were identified: treatment information, physician support, and patient symptoms/needs. After adjusting for known determinants of lung cancer treatment, increased treatment information was associated with higher probability of cancer-directed treatment (P=0.003). Other communication domains (physician support or patient symptoms/needs) were not independent predictors of treatment (P>0.05 for both comparisons). Conclusions These data suggest that treatment information is particularly important for increasing the probability of cancer-directed therapy among lung cancer patients. Clinicians should ensure that they clearly discuss treatment goals and options with patients while maintaining empathy, supporting patient needs, and addressing symptoms.

Innate lymphoid cells (ILCs) develop from common lymphoid progenitors (CLPs), which further differentiate into the common ILC progenitor (CILP) that can give rise to both ILCs and natural killer (NK) cells. Murine ILC intermediates have recently been characterized, but the human counterparts and their developmental trajectories have not yet been identified, largely due to the lack of homologous surface receptors in both organisms. Here, we show that human CILPs (CD34+CD117+α4β7+Lin−) acquire CD48 and CD52, which define NK progenitors (NKPs) and ILC precursors (ILCPs). Two distinct NK cell subsets were generated in vitro from CD34+CD117+α4β7+Lin−CD48−CD52+ and CD34+CD117+α4β7+Lin−CD48+CD52+ NKPs, respectively. Independent of NKPs, ILCPs exist in the CD34+CD117+α4β7+Lin−CD48+CD52+ subset and give rise to ILC1s, ILC2s, and NCR+ ILC3s, whereas CD34+CD117+α4β7+Lin−CD48+CD52− ILCPs give rise to a distinct subset of ILC3s that have lymphoid tissue inducer (LTi)–like properties. In addition, CD48-expressing CD34+CD117+α4β7+Lin− precursors give rise to tissue-associated ILCs in vivo. We also observed that the interaction of 2B4 with CD48 induced differentiation of ILC2s, and together, these findings show that expression of CD48 by human ILCPs modulates ILC differentiation.

Background: The National Lung Screening Trial demonstrated that screening for lung cancer improved overall survival (OS) and reduced lung cancer mortality in the 55- to 74-year-old age group by increasing the proportion of cancers detected at an early stage. Because of the increasing life expectancy of the American population, we investigated whether screening for lung cancer might benefit men and women aged 75–84 years.Materials/Methods: Rates of non-small cell lung cancer (NSCLC) from 2000 to 2009 were calculated in both younger and older age groups using the surveillance epidemiology and end reporting database. OS and lung cancer-specific survival (LCSS) in patients with Stage I NSCLC diagnosed from 2004 to 2009 were analyzed to determine the effects of age and treatment.Results: The per capita incidence of NSCLC decreased in the 55–74 cohort, but increased in the 75–84 cohort over the study period. Crude lung cancer death rates in the two age groups who had no specific treatment were 39.5 and 44.9%, respectively. These rates fell in both age groups when increasingly aggressive treatment was used. Rates of OS and LCSS improved significantly with increasingly aggressive treatment in the 75–84 age group. The survival benefits of increasingly aggressive treatment in 75- to 84-year-old females did not differ from their counterparts in the younger cohort.Conclusion: Screening for lung cancer might be of benefit to individuals at increased risk of lung cancer in the 75–84 age group. The survival benefits of aggressive therapy are similar in females between 55–74 and 75–84 years old.

Purpose: Many US academic centers have acquired community practices to expand their clinical care and research footprint. The objective of this assessment was to determine whether the acquisition and integration of community oncology practices by Yale/Smilow Cancer Hospital improved outcomes in quality of care, disease team integration, clinical trial accrual, and patient satisfaction at network practice sites. Methods: We evaluated quality of care by testing the hypothesis that core Quality Oncology Practice Initiative measures at network sites that were acquired in 2012 were significantly different after their 2016 integration into the network. Clinical and research integration were measured using the number of tumor board case presentations and total accruals in clinical trials. We used Press-Ganey scores to measure patient satisfaction pre- and postintegration. Results: Mean Quality Oncology Practice Initiative scores at Smilow Care Centers were significantly higher in 2016 than in 2012 for core measures related to improvement in tumor staging ( z = 1.33; P < .05), signed consent and documentation plans for antineoplastic treatment ( z = 2.69; P < .01; and z = 2.36; P < .05, respectively), and appropriately quantifying and addressing pain during office visits ( z = 2.95; P < .05; and z = 3.1; P < .01, respectively). A total of 493 cases were presented by care center physicians at the tumor board in 2017 compared with 45 presented in 2013. Compared with 2012, Smilow Care Center clinical trial accrual increased from 25 to 170 patients in 2017. Last, patient satisfaction has remained at greater than the 90th percentile pre- and postintegration. Conclusion: The process of integration facilitates the ability to standardize cancer practice and provides a platform for quality improvement.

Helper Innate lymphoid cells (ILCs) are tissue resident lymphocytes that play a critical role in a number of biological processes. Several transcription factors are required for the differentiation of hematopoietic stem cells (HSCs) into ILCs. Recent studies demonstrate GATA3 as a transcriptional regulator that plays an essential role in ILC development. We aimed to modulate the differentiation of human cord blood-derived CD34 + cells into ILCs by transient and ectopic expression of mRNA encoding transcription factors known to be important for ILC lineage differentiation, including GATA3, TOX, NFIL3, ID2, and RORγt. Using this experimental protocol, only GATA3 significantly modulated HSCs to differentiate into helper ILCs. Transient overexpression of GATA3 drove the emergence of CD34 + α4β7 + early ILC progenitors during the first few days of culture. These ILC progenitors further acquired IL-7Rα and CD117 to give rise to immediate ILC precursors. In support of these findings, analysis of the genes induced by GATA3 in HSCs showed an upregulation of those associated with ILC development. Moreover, we show GATA3 also acts on more committed progenitors and significantly shifts the differentiation of progenitors away from the ILC1/NK lineage to the ILC2 and ILC3 lineage. In summary, transient overexpression of GATA3 mRNA in CD34 + HSCs enhances the differentiation of HSCs into the helper ILC lineages, at the expense of NK cell development.

Diphtheria is a rare cause of infection in highly vaccinated populations and may not be recognized by modern clinicians. Infections by nontoxigenic Corynebacterium diphtheriae are emerging. We report the first case of necrotizing epiglottitis secondary to nontoxigenic C diphtheriae. A fully vaccinated child developed fever, poor oral intake, and sore throat and was found to have necrotizing epiglottitis. Necrotizing epiglottitis predominantly occurs in the immunocompromised host. Laboratory evaluation revealed pancytopenia, and bone marrow biopsy was diagnostic for acute lymphoblastic leukemia. Clinicians should be aware of aggressive infections that identify immunocompromised patients. This case highlights the features of a reemerging pathogen, C diphtheriae.