Citations

1535 Background: Ambulatory management of select patients with febrile neutropenia (FN) may substantially decrease patients’ burden of illness and improve their quality of life, and is recommended by American Society of Clinical Oncology (ASCO) guidelines. However, in the United States, inpatient management remains the universal standard. We hereby report the health care utilization associated with the DEFeNDR remote patient monitoring (RPM) program, which leverages technology and virtual centralized nurse monitoring to facilitate ambulatory management of FN as an alternative to hospital-based care. Methods: Adult patients with cancer hospitalized with FN were assessed daily for eligibility to participate in the DEFeNDR program. Eligibility criteria included MASCC score >21 (per ASCO guidelines), and clinical judgment of the attending provider. Patients receiving cellular therapy (CAR-T, BMT) in the prior 100 days were excluded. Eligible patients agreeing to participate in the 30-day program were provided a kit containing cellular-enabled, pre-connected devices to facilitate monitoring, including twice-daily vital signs and electronic symptom questionnaires. Data were EHR-integrated in real-time and embedded decision trees facilitated alerts for adverse trends. RPM nurses responded to alerts and escalated care as indicated by pre-specified care pathways. Program assessment was performed at 20 weeks after full implementation. The primary outcome was the mean proportion of evaluable days spent inpatient (mPEDI) within 30 days of eligibility compared between those who participated in the program vs. those who declined. Results: 35 patients were offered participation in the DEFeNDR program. Of these, 17 participated and 18 declined. Baseline characteristics are provided. Participating patients experienced mPEDI of 6.9% (Standard Error [SE], 3.7%), compared with 17.7% (SE, 3.6%) for patients who declined participation. Due to small sample size, this difference (10.8%) did not reach statistical significance (Wilcoxon Rank Sums p-value, 0.15). 30-day mortality did not differ between groups. Mean inpatient days were also lower for patients participating in the program. Additionally, when readmitted, patients participating in RPM experienced a trend toward shorter length of stay and lower rates of intensive care unit utilization. Conclusions: A trend towards decreased burden of inpatient care is evident among patients participating in the DEFeNDR program. Further studies are warranted to assess comparative effectiveness of this model vs usual care.[Table: see text]

11535 Background: Twenty-five percent of patients with Ewing Sarcoma (EWS) have metastatic disease at diagnosis, most commonly in the lungs. Our objectives were to compare overall (OS) and pulmonary disease-free survival (PDFS) between patients with metastatic EWS at diagnosis who achieve rapid complete response (RCR), defined as radiographic resolution of all pulmonary nodules at the end of induction chemotherapy, and those with residual pulmonary nodules after induction chemotherapy (non-RCR). Methods: This multi-center, retrospective cohort study included children under 20 years of age with metastatic EWS treated from 2007-2020 at 19 institutions participating in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups, and p < 0.05 was considered significant. Kaplan-Meier curves were generated for OS and PDFS. Cox regression was performed for OS, controlling for whole lung irradiation (WLI), extrapulmonary metastases, and age. Results: Among 153 patients with metastatic EWS at diagnosis, 61 (40%) achieved RCR, and 87 (57%) did not (5 unknown). The median number of pulmonary nodules was 3.5 in the RCR vs 5 in the non-RCR groups (p = 0.02), while bilateral disease was present in 44 (72%) RCR vs 75 (86%) non-RCR patients (p = 0.03). Pulmonary relapse occurred in 58 (38%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = 0.14). Factors associated with pulmonary relapse in the univariate analysis include median age [15 years (IQR: 12-17) with pulmonary relapse vs 12 years (IQR: 9-16) without (p = 0.03)] and extrapulmonary metastases at diagnosis [24 (41%) patients with pulmonary relapse vs 26 (27%) patients without pulmonary relapse (p = 0.05)]. WLI was performed in 100 patients and was not associated with a reduction in pulmonary relapse (p = 0.93). Complete surgical clearance of pulmonary disease was attempted in 29 (19%) patients, including 17 of the patients who met the criteria for RCR. On Kaplan-Meier analyses, 5-year PDFS did not significantly differ based on RCR (67%) vs. non-RCR (53%, p = 0.13), or WLI (61%) vs. no WLI (54%, p = 0.32). However, 5-year OS did vary significantly between patients with RCR and WLI (85%), RCR without WLI (55%), non-RCR with WLI (60%), and non-RCR without WLI (25%; p < 0.01). In Cox regression analysis, RCR was associated with improved OS after controlling for WLI, extrapulmonary metastases, and patient age (HR 0.51, p = 0.03). Conclusions: Patients with EWS who had pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse. Further research is needed to determine whether clearance of pulmonary disease achieved through surgical metastasectomy provides a comparable survival benefit and if any subsets of patients have a reduced risk of pulmonary relapse after resection.

Objective: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. Background: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. Methods: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. Results: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P=0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P=0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P=0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. Conclusions: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

AbstractCardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Anticipating and understanding cancers’ need for specific gene activities is key for novel therapeutic development. Here we utilized DepMap, a cancer gene dependency screen, to demonstrate that machine learning combined with network biology can produce robust algorithms that both predict what genes a cancer is dependent on and what network features coordinate such gene dependencies. Using network topology and biological annotations, we constructed four groups of novel engineered machine learning features that produced high accuracies when predicting binary gene dependencies. We found that in all examined cancer types, F1 scores were greater than 0.90, and model accuracy remained robust under multiple hyperparameter tests. We then deconstructed these models to identify tumor type-specific coordinators of gene dependency and identified that in certain cancers, such as thyroid and kidney, tumors’ dependencies are highly predicted by gene connectivity. In contrast, other histologies relied on pathway-based features such as lung, where gene dependencies were highly predictive by associations with cell death pathway genes. In sum, we show that biologically informed network features can be a valuable and robust addition to predictive pharmacology models while simultaneously providing mechanistic insights.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.

Objectives:Patients with Trisomy 21 (T21) commonly have gastrointestinal symptoms and diseases that prompt evaluation with esophagogastroduodenoscopy (EGD). Our objective is to characterize duodenal histological abnormalities in these patients when undergoing EGD. A secondary aim is to explore associations of histologic findings with different therapies.Methods:Patients 30 years old or younger with T21 who underwent EGD from 2000 to 2020 at 6 hospitals were included in this retrospective cohort study. Duodenal biopsies were categorized based on reported histopathology findings as normal or abnormal. Abnormal pathology reports were reviewed and categorized into villous atrophy (VA) and duodenitis without VA. The VA group was further categorized based on the presence or absence of celiac disease (CD).Results:We identified 836 patients with T21 who underwent EGD, 419 (50.1%) of whom had duodenal histologic abnormalities. At the time of the first (index) abnormal duodenal biopsy, 290 of 419 had VA and of those, 172 of 290 met CD diagnostic criteria, while 118 of 290 did not meet CD criteria (nonspecific VA). Among the patients with an abnormal biopsy, acid suppression at the time of the index biopsy was less common in patients with VA‐CD compared to patients without VA or patients with nonspecific VA (12.2% vs 45.7% vs 44.9%).Conclusions:Half of the T21 patients in this cohort had abnormal duodenal biopsies including a subgroup with nonspecific VA. In this cohort, acid suppression use was more prevalent in patients with abnormalities other than CD.