Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging.

2022

2022 Mar 01

1536-3678

<p>Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population.</p>

10.1097/MPH.0000000000002430

J Pediatr Hematol Oncol

35235547

Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma.

2020

2020 Nov 24

1460-2105

<p><strong>BACKGROUND: </strong>Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials.</p>

<p><strong>METHODS: </strong>We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided.</p>

<p><strong>RESULTS: </strong>In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P &lt; .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P &lt; .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P &lt; .001) compared with the unexposed group.</p>

<p><strong>CONCLUSIONS: </strong>Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.</p>

10.1093/jnci/djaa107

J Natl Cancer Inst

33227816

Development and Clinical Validation of a Large Fusion Gene Panel for Pediatric Cancers.

2019

2019 Jun 27

1943-7811

<p>Gene fusions are one of the most common genomic alterations in pediatric cancer. Many fusions encode oncogenic drivers and play important roles in cancer diagnosis, risk stratification, and treatment selection. We report the development and clinical validation of a large custom-designed RNA sequencing panel, CHOP Fusion panel, using anchored multiplex PCR technology. The panel interrogates 106 cancer genes known to be involved in nearly 600 different fusions reported in hematological malignancies and solid tumors. The panel works well with different types of samples including formalin-fixed, paraffin-embedded samples. The panel demonstrated excellent analytic accuracy with 100% sensitivity and specificity on 60 pediatric tumor validation samples. In addition to identifying all known fusions in the validation samples, three unrecognized yet clinically significant fusions were also detected. Two-hundred and sevety-six clinical cases were analyzed after the validation and 51 different fusions were identified in 104 cases. Of these, 16 fusions were not previously reported at the time of discovery. These fusions provided genomic information useful for clinical management. Our experience demonstrates that CHOP Fusion panel can detect the vast majority of known and certain novel clinically relevant fusion genes in pediatric cancers accurately, efficiently, and cost effectively, and provides an excellent tool for new fusion gene discovery.</p>

10.1016/j.jmoldx.2019.05.006

J Mol Diagn

31255796

Clinical utility of custom-designed NGS panel testing in pediatric tumors.

2019

32

2019 May 28

1756-994X

<p><strong>BACKGROUND: </strong>Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, the standard approach was single-gene or focused multigene testing, but many centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report the laboratory validation and clinical utility of a large cohort of clinical NGS somatic sequencing results in diagnosis, prognosis, and treatment of a wide range of pediatric cancers.</p>

<p><strong>METHODS: </strong>Subjects were accrued retrospectively at a single pediatric quaternary-care hospital. Sequence analyses were performed on 367 pediatric cancer samples using custom-designed NGS panels over a 15-month period. Cases were profiled for mutations, copy number variations, and fusions identified through sequencing, and their clinical impact on diagnosis, prognosis, and therapy was assessed.</p>

<p><strong>RESULTS: </strong>NGS panel testing was incorporated meaningfully into clinical care in 88.7% of leukemia/lymphomas, 90.6% of central nervous system (CNS) tumors, and 62.6% of non-CNS solid tumors included in this cohort. A change in diagnosis as a result of testing occurred in 3.3% of cases. Additionally, 19.4% of all patients had variants requiring further evaluation for potential germline alteration.</p>

<p><strong>CONCLUSIONS: </strong>Use of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients.</p>

10.1186/s13073-019-0644-8

Genome Med

31133068

Unintended consequences of evolution of the Common Terminology Criteria for Adverse Events.

2019

e27747

2019 Apr 09

1545-5017

<p><strong>BACKGROUND: </strong>Adverse events (AEs) on Children's Oncology Group (COG) trials are reported manually by clinical research assistants (CRAs). The Common Terminology Criteria for Adverse Events (CTCAE) was developed to provide standardized definitions for identifying and grading AEs. The CTCAE has expanded significantly over its five versions, but the impact of CTCAE definitional changes has not been examined.</p>

<p><strong>PROCEDURE: </strong>This study compared AE number and ascertainment among the first four CTCAE versions using a case vignette. Each CTCAE version was used to create a list of AEs and grades by two separate CRAs.</p>

<p><strong>RESULTS: </strong>The CTCAE expanded from 9 categories and 49 AEs in v1.0 to 26 categories and 790 AEs in v4.0. CRAs independently selected different approaches to AE ascertainment-comprehensive and parsimonious. The number of AEs identified in the parsimonious approach was stable with 10-14 in each CTC version. The comprehensive approach identified 9, 20, 29, and 37 AEs in CTC versions 1.0, 2.0, 3.0, and 4.0, respectively. Only approximately 65% of AEs were conclusively graded in versions 2.0 to 4.0 using the comprehensive approach.</p>

<p><strong>CONCLUSIONS: </strong>CTCAE has increased in complexity. Although this increased complexity allows for more granular AE reporting, these data demonstrate potential unintended negative consequences of increasing CTC AE complexity, including the risk of varying approaches to AE capture. A comprehensive evaluation of CTC AE definitions and CRA reporting practices across COG institutions and AEs are needed to improve the accuracy and efficiency of AE reporting.</p>

10.1002/pbc.27747

Pediatr Blood Cancer

30968531

Resource utilization and toxicities after single versus tandem autologous stem cell rescue in high-risk neuroblastoma using a national administrative database.

2018

e27372

2018 Aug 01

1545-5017

<p><strong>BACKGROUND: </strong>High-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) has improved event-free survival for children with high-risk neuroblastoma. Common regimens include carboplatin/etoposide/melphalan (CEM), busulfan/melphalan (BuMel), and tandem HDC-ASCR [thiotepa/cyclophosphamide (TC) followed by CEM]. To complement clinical trial data and to evaluate the clinical burden associated with these regimens, resource ultilization (RU) was evaluated. An administrative database was used to evaluate RU in a previously developed high-risk neuroblastoma cohort. Single CEM and BuMel patients were followed for 60&nbsp;days from the first day of the HDC-ASCR preparative regimen or until death, whichever came first. Tandem patients were followed from the first day of the first HDC-ASCR preparative regimen through day 60 from the first day of the second HDC-ASCR. Resources compared included inpatient days, ICU-level care, and medications administered.</p>

<p><strong>RESULTS: </strong>A cohort of 578 patients was evaluated; 422 patients underwent single HDC-ASCR with CEM, 67 received BuMel, 72 underwent TC/CEM, and 17 received only the first portion of tandem HDC-ASCR. The median number of inpatient days and days of exposure to antibiotics, opioids, and total parenteral nutrition were higher in the tandem group than in the CEM and BuMel groups. However, the rate of use of several ICU-level resources per 1000 hospital days was lower for the tandem group.</p>

<p><strong>CONCLUSIONS: </strong>These data suggest that while patients undergoing tandem HDC-ASCR were hospitalized longer, the severity of illness during hospitalization was not greater in tandem patients.</p>

10.1002/pbc.27372

Pediatr Blood Cancer

30070014

Hospital Variation in Intensive Care Resource Utilization and Mortality in Newly Diagnosed Pediatric Leukemia.

2018

e312-20

2018 Jun

1529-7535

<p><strong>OBJECTIVES: </strong>To evaluate hospital-level variability in resource utilization and mortality in children with new leukemia who require ICU support, and identify factors associated with variation.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study.</p>

<p><strong>SETTING: </strong>Children's hospitals contributing to the Pediatric Health Information Systems administrative database from 1999 to 2011.</p>

<p><strong>PATIENTS: </strong>Inpatients less than 25 years old with newly diagnosed acute lymphocytic leukemia or acute myeloid leukemia requiring ICU support (n = 1,754).</p>

<p><strong>INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: </strong>Evaluated exposures included leukemia type, year of diagnosis, and hospital-wide proportion of patients with public insurance. The main outcome was hospital mortality. Wide variability existed in the ICU resources used across hospitals. Combined acute lymphocytic leukemia and acute myeloid leukemia mortality varied by hospital from 0% (95% CI, 0-14.8%) to 42.9% (95% CI, 17.7-71.1%). A mixed-effects model with a hospital-level random effect suggests significant variation across hospitals in mortality (p = 0.007). When including patient and hospital factors as fixed effects into the model, younger age, acute myeloid leukemia versus acute lymphocytic leukemia diagnosis, leukemia diagnosis prior to 2005, hospital-wide proportion of public insurance patients, and hospital-level proportion of leukemia patients receiving ICU care are significantly associated with mortality. The variation across hospitals remains significant with all patient factors included (p = 0.021) but is no longer significant after adjusting for the hospital-level factors proportion of public insurance and proportion receiving ICU care (p = 0.48).</p>

<p><strong>CONCLUSIONS: </strong>Wide hospital-level variability in ICU resource utilization and mortality exists in the care of children with leukemia requiring ICU support. Hospital payer mix is associated with some mortality variability. Additional study into how ICU support could be standardized through clinical practice guidelines, impact of payer mix on hospital resources allocation to the ICU, and subsequent impact on patient outcomes is warranted.</p>

10.1097/PCC.0000000000001525

Pediatr Crit Care Med

29528977

Center-level variation in accuracy of adverse event reporting in a clinical trial for pediatric acute myeloid leukemia: A report from the Children's Oncology Group.

2017

2017 Jun 22

1592-8721

10.3324/haematol.2017.168815

Haematologica

28642300

Using electronic medical record data to report laboratory adverse events.

2017

2017 Feb 01

1365-2141

<p>Despite the importance of adverse event (AE) reporting, AEs are under-reported on clinical trials. We hypothesized that electronic medical record (EMR) data can ascertain laboratory-based AEs more accurately than those ascertained manually. EMR data on 12 AEs for patients enrolled on two Children's Oncology Group (COG) trials at one institution were extracted, processed and graded. When compared to gold standard chart data, COG AE report sensitivity and positive predictive values (PPV) were 0-21·1% and 20-100%, respectively. EMR sensitivity and PPV were &gt;98·2% for all AEs. These results demonstrate that EMR-based AE ascertainment and grading substantially improves laboratory AE reporting accuracy.</p>

10.1111/bjh.14538

Br. J. Haematol.

28146330

The Role of Acuity of Illness at Presentation in Early Mortality in Black Children with Acute Myeloid Leukemia.

2016

2016 Nov 10

1096-8652

<p>Black patients with acute myeloid leukemia (AML) experience higher mortality than White patients. We compared induction mortality, acuity of illness prior to chemotherapy, and insurance type between Black and White patients to assess whether acuity of presentation mediates the disparity. Within a retrospective cohort of 1,122 children with AML treated with two courses of standard induction chemotherapy between 2004 to 2014 in the Pediatric Health Information System (PHIS) database, the association between race (Black versus White) and inpatient mortality during induction was examined. Intensive Care Unit (ICU)-level resource utilization during the first 72 hours following admission for initial AML chemotherapy was evaluated as a potential mediator. The total effect of race on mortality during Induction I revealed a strong association (unadjusted HR 2.75, CI: 1.18, 6.41). Black patients had a significantly higher unadjusted risk of requiring ICU-level resources within the first 72 hours after initial presentation (17% versus 11%; RR 1.52, CI: 1.04, 2.24). Mediation analyses revealed the indirect effect of race through acuity accounted for 61% of the relative excess mortality during Induction I. Publicly insured patients experienced greater induction mortality than privately insured patients regardless of race. Black patients with AML have significantly greater risk of induction mortality and are at increased risk for requiring ICU-level resources soon after presentation. Higher acuity amongst Black patients accounts for a substantial portion of the relative excess mortality during Induction I. Targeting factors affecting acuity of illness at presentation may lessen racial disparities in AML induction mortality. This article is protected by copyright. All rights reserved.</p>

10.1002/ajh.24605

Am. J. Hematol.

27862214