Brief Report: Comprehensive Clinicogenomic Profiling of Small Cell Transformation From EGFR-Mutant NSCLC Informs Potential Therapeutic Targets.

Introduction: NSCLC transformation to SCLC has been best characterized with EGFR-mutant NSCLC, with emerging case reports seen in ALK, RET, and KRAS-altered NSCLC. Previous reports revealed transformed SCLC from EGFR-mutant NSCLC portends very poor prognosis and lack effective treatment. Genomic analyses revealed TP53 and RB1 loss of function increase the risk of SCLC transformation. Little has been reported on the detailed clinicogenomic characteristics and potential therapeutic targets for this patient population. Methods: In this study, we conducted a single-center retrospective analysis of clinical and genomic characteristics of patients with EGFR-mutant NSCLC transformed to SCLC. Demographic data, treatment course, and clinical molecular testing reports were extracted from electronic medical records. Kaplan-Meier analyses were used to estimate survival outcomes. Next generation sequencing-based assays was used to identify EGFR and co-occurring genetic alterations in tissue or plasma before and after SCLC transformation. Single-cell RNA sequencing (scRNA-seq) was performed on a patient-derived-xenograft model generated from a patient with EGFR-NSCLC transformed SCLC tumor. Results: A total of 34 patients were identified in our study. Median age at initial diagnosis was 58, and median time to SCLC transformation was 24.2 months. 68% were female and 82% were never smokers. 79% of patients were diagnosed as stage IV disease, and over half had brain metastases at baseline. Median overall survival of the entire cohort was 38.3 months from initial diagnoses and 12.4 months from time of SCLC transformation. Most patients harbored EGFR exon19 deletions as opposed to exon21 L858R alteration. Continuing EGFR tyrosine kinase inhibitor post-transformation did not improve overall survival compared with those patients where tyrosine kinase inhibitor was stopped in our cohort. In the 20 paired pretransformed and post-transformed patient samples, statistically significant enrichment was seen with PIK3CA alterations (p = 0.04) post-transformation. Profiling of longitudinal liquid biopsy samples suggest emergence of SCLC genetic alterations before biopsy-proven SCLC, as shown by increasing variant allele frequency of TP53, RB1, PIK3CA alterations. ScRNA-seq revealed potential therapeutic targets including DLL3, CD276 (B7-H3) and PTK7 were widely expressed in transformed SCLC. Conclusions: SCLC transformation is a potential treatment resistance mechanism in driver-mutant NSCLC. In our cohort of 34 EGFR-mutant NSCLC, poor prognosis was observed after SCLC transformation. Clinicogenomic analyses of paired and longitudinal samples identified genomic alterations emerging post-transformation and scRNA-seq reveal potential therapeutic targets in this population. Further studies are needed to rigorously validate biomarkers and therapeutic targets for this patient population.

Disparities in mortality among acute myeloid leukemia-related hospitalizations.

Racial and socioeconomic disparities have become apparent in acute myeloid leukemia (AML) outcomes. We conducted a retrospective cohort study of hospitalizations for adults with a diagnosis of AML from 2009 to 2018 in the Nationwide Inpatient Sample (NIS). We categorized patients' ages in groups of <60 years and ≥60 years and stratified them by reported race/ethnicity. Exposures of interest were patient sociodemographics, hospital characteristics, and Elixhauser-comorbidity Index. Outcome of interest was in-hospital death. Statistical analyses included survey logistic regression to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to quantify the independent associations between patient characteristics and mortality. Of 622,417 AML-related hospitalizations, 57.6% were in patients ≥60 years. The overall rate of in-hospital death was 9.4%. Compared to patients <60, older patients experienced a higher rate of in-hospital death. In both age groups and in all ethnicities, mortality decreased over time. Differences in mortality were observed based on gender, payer, hospital location, and teaching status. For hospitalizations in patients ≥60, NH-Black race was associated with inferior in-hospital death outcomes (OR 1.17; CI 1.08-1.28). Urban teaching hospitals were associated with a 38% increase (OR 1.38; CI 1.06-1.80) in inpatient mortality in patients <60 and a 15% decrease (OR 0.85; CI 0.77-0.95) in inpatient mortality in patients ≥60. Our results highlight the increased need to recognize the role of race/ethnicity and socioeconomic factors and their contribution to disparate outcomes in AML.

Hospital Use and Mortality in Transition-Aged Patients With Sickle Cell Disease.

OBJECTIVES: Childhood mortality in sickle cell disease (SCD) has decreased, but the transition period is associated with poor outcomes and higher mortality rates. We analyzed recent US hospitalizations and mortality trends in the transition-aged population and evaluated for differences between patients with and without SCD. METHODS: Nationwide Inpatient Sample database was used to analyze hospitalizations among individuals aged 16 to 24 years from 2003 to 2017. Diagnoses were coded by using International Classification of Diseases, Ninth Revision, Clinical Modification and International Classification of Diseases, 10th Revision, Clinical Modification. We performed bivariate analyses to assess associations between sociodemographic characteristics and SCD hospitalizations, joinpoint regression analysis to describe mortality rate trends in SCD hospitalizations, and adjusted survey logistic regression to assess associations between patient characteristics and in-hospital mortality among transition-aged SCD and non-SCD-related hospitalizations. RESULTS: There were 37 344 532 hospital encounters of patients aged 16 to 24 years during 2003-2017; both SCD and non-SCD hospitalizations increased with age. Female patients accounted for 78% of non-SCD and 54.9% of SCD hospitalizations. Although there was a +3.2% average annual percent change in SCD hospitalizations, total SCD in-hospital mortality rates did not have a statistically significant increase in average annual percent change over the study period. Patients with SCD aged 19 to 21 and 22 to 24 were more likely to suffer in-hospital mortality than those aged 16 to 18 (odds ratio = 2.09 and 2.71, respectively); the increased odds in mortality by age were not seen in our non-SCD population. CONCLUSIONS: Transition-aged hospitalizations increase with age, but SCD hospitalizations have disparate age-related mortality rates. Hospital-based comprehensive care models are vital to address the persistent burden of early adulthood mortality in SCD.

Community-Academic Partnerships to Promote Health Literacy and Address Social Needs Among Low-Income Families During COVID-19.

Brighter Bites is a school-based health promotion program that delivers fresh produce and nutrition education to low-income children and their families across 6 locations in the US. This article provides a perspective on how, despite coronavirus disease 2019-related school closures, Brighter Bites pivoted rapidly to collaborate with medical and public health institutions to improve health and food literacy among their families. Through these partnerships, Brighter Bites was able to rapidly provide accurate, evidence-based information related to coronavirus disease 2019 and other social needs, including food, housing, transportation, and access to health care, to help fill a needed gap in vulnerable communities.

Clinical outcomes of a novel combination of lenalidomide and rituximab followed by stem cell transplantation for relapsed/refractory aggressive B-cell non-hodgkin lymphoma.

We retrospectively compared outcomes of patients with relapsed/refractory non-Hodgkin lymphoma (NHL) who underwent stem cell transplantation (SCT) with stable disease or better following a novel combination of lenalidomide and rituximab (LR) treatment and did not undergo SCT in a phase I/II clinical trial. We retrospectively compared outcomes of patients who underwent SCT with that of patients who had stable disease or better following LR treatment and did not undergo SCT. Twenty-two patients enrolled in LR clinical trial and undergone SCT were identified, 13 with mantle cell lymphoma (MCL) and nine with large B-cell lymphoma (LBCL). All patients who underwent SCT achieved complete response. In the MCL subset, there were no significant differences between SCT and non-SCT groups except that non-SCT patients were older and had a higher mantle-cell international prognostic index score. There was no difference between SCT-group and non-SCT-group in response duration (P=0.3), progression-free survival (PFS) (P=0.304) and overall survival (OS) (P=0.87). In LBCL subgroup, there were no significant differences between two groups except that non-SCT group had a higher international prognostic index score. Patients with LBCL who underwent SCT had significantly longer response duration (P=0.001), PFS (P=0.000), and OS (P=0.003) than the non-SCT group. The novel therapeutic combination offers a bridge to SCT in patients with relapsed/refractory aggressive B-cell NHL.