Phase I Study of I-Metaiodobenzylguanidine With Dinutuximab ± Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy Trial.

Purpose: We conducted a phase I trial to determine the safety, tolerability, and preliminary antitumor activity of I-metaiodobenzylguanidine (MIBG) combined with the anti-GD2 antibody dinutuximab with or without the histone deacetylase inhibitor vorinostat in patients with relapsed/refractory neuroblastoma (rNBL).

Methods: In part A, patients with MIBG-avid rNBL received MIBG intravenously (IV) on day 1 at 12, 15, or 18 mCi/kg per the rolling six design and dinutuximab (17.5 mg/m once daily) IV on days 8-11 and 29-32 and granulocyte-macrophage colony-stimulating factor (250 mcg/m once daily) subcutaneously on days 8-17 and 29-38.

Racial and Ethnic Survival Disparities Among Children With High-Risk Neuroblastoma: A Children's Oncology Group Report.

Importance: Whether population-based racial and ethnic survival disparities for children with high-risk neuroblastoma persist in the clinical trial setting is unknown.

Objective: To investigate racial and ethnic survival disparities among children with high-risk neuroblastoma treated on frontline clinical trials.

Design, Setting, And Participants: This retrospective cohort study used data from Children's Oncology Group (COG) high-risk neuroblastoma trials from January 1, 2007, to December 31, 2016, with a data freeze on June 30, 2021.

A phase 1 dose-escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma.

Background: This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.

Methods: Patients aged 2-21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28-day cycles.

Gadolinium-based contrast media does not improve the staging of neuroblastoma image-defined risk factors at diagnosis.

Background: Neuroblastoma risk stratification relies on prognostic risk factors and image-defined risk factors (IDRFs). Evaluating neuroblastoma typically involves magnetic resonance imaging (MRI) with gadolinium-based contrast media (GBCM, "contrast"). However, there are concerns regarding adverse effects and cost of GBCM.

Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results.

Vα24-invariant natural killer T cells (NKTs) have anti-tumor properties that can be enhanced by chimeric antigen receptors (CARs). Here we report updated interim results from the first-in-human phase 1 evaluation of autologous NKTs co-expressing a GD2-specific CAR with interleukin 15 (IL15) (GD2-CAR.15) in 12 children with neuroblastoma (NB).

Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas.

Background: Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies.

Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor.

Purpose: Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy.

Patients And Methods: Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded.

MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere.

Management of neurofibromatosis type 1-associated plexiform neurofibromas.

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management.

Selumetinib in children with neurofibromatosis type 1 and asymptomatic inoperable plexiform neurofibroma at risk for developing tumor-related morbidity.

Background: Selumetinib was recently approved for the treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). This parallel phase II study determined the response rate to selumetinib in children with NF1 PN without clinically significant morbidity.

Methods: Children with NF1 and inoperable PNs, which were not yet causing clinically significant morbidity but had the potential to cause symptoms, received selumetinib at 25 mg/m2 orally twice daily (1 cycle = 28 days).

Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG).

Background: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non-small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors.

Methods: STARTRK-NG (NCT02650401) is a phase 1/2 trial.

Examining Violence Against Women at a Regional Level 1 Trauma Center During the COVID-19 Pandemic.

Introduction: There is a growing concern that certain public health restrictions imposed to prevent the spread of coronavirus disease 2019 (COVID-19) could result in more violence against women (VAW). We sought to determine if the rates and types of VAW changed during the COVID-19 pandemic at our level 1 trauma center (L1TC).

Methods: We performed a retrospective review of female patients who presented to our L1TC because of violence from 2019 through 2020.

A safety and feasibility trial of I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study.

Introduction: I-meta-iodobenzylguanidine ( I-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by I MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma.

Methods: Patients with MIBG-avid high-risk neuroblastoma were eligible.

Myeloablative Busulfan/Melphalan Consolidation following Induction Chemotherapy for Patients with Newly Diagnosed High-Risk Neuroblastoma: Children's Oncology Group Trial ANBL12P1.

Consolidation using high-dose chemotherapy with autologous stem cell transplantation (ASCT) is an important component of frontline therapy for children with high-risk neuroblastoma. The optimal preparative regimen is uncertain, although recent data support a role for busulfan/melphalan (BuMel). The Children's Oncology Group (COG) conducted a trial (ANBL12P1) to assess the tolerability and feasibility of BuMel ASCT following a COG induction.

Prognostic significance of pretreatment F-FDG positron emission tomography/computed tomography in pediatric neuroblastoma.

Background: F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) shows tumor activity in most neuroblastomas, but the role of F-FDG PET/CT in neuroblastoma remains to be defined.

Objective: This study explored the prognostic significance of F-FDG PET in newly diagnosed neuroblastic tumors.

Materials And Methods: This retrospective study reviewed all F-FDG PET/CT examinations performed for a new diagnosis of suspected neuroblastoma.

NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas.

Purpose: Patients with neurofibromatosis type 1 (NF1) frequently develop plexiform neurofibromas (PNs), which can cause significant morbidity. We performed a phase II trial of the MAPK/ERK kinase inhibitor, mirdametinib (PD-0325901), in patients with NF1 and inoperable PNs. The primary objective was response rate based on volumetric magnetic resonance imaging analysis.

Tolerance of dinutuximab therapy for treatment of high-risk neuroblastoma in two patients with end-stage renal disease on dialysis.

Autologous hematopoietic cell transplant (aHCT) has a significant survival advantage in patients with high-risk (HR) neuroblastoma. Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication and may result in chronic renal disease leading to delay in subsequent posttransplant therapy and limitations of treatment options. Dinutuximab represents an important therapeutic advance in the treatment of pediatric HR neuroblastoma, but historically has not been administered in patients with GFR < 60 mL/m /min.

Sentinel lymph node biopsy in head and neck rhabdomyosarcoma.

Head and neck rhabdomyosarcoma lymph node staging is challenging due to varied patterns of lymphatic drainage and the suboptimal predictive value of available imaging modalities. Furthermore, regional relapse rates are unacceptably high, and the toxicity of empiric radiation is undesirable in the pediatric and young adult population. In an attempt to improve locoregional control without excess morbidity, we have adopted routine sentinel lymph node biopsy in head and neck rhabdomyosarcoma, which is safe and feasible in pediatric patients.

Change in liver, spleen and bone marrow magnetic resonance imaging signal intensity over time in children with solid abdominal tumors.

Background: Reticuloendothelial system MRI signal hypointensity is common in pediatric oncology patients with solid abdominal tumors.

Objective: To assess changes in liver, spleen and bone marrow T2-weighted MRI signal intensity over time and their relationship to blood transfusion history in children with solid abdominal tumors.

Materials And Methods: In this retrospective study we measured liver, spleen and bone marrow signal intensity on axial T2-weighted MR images obtained December 2009 through February 2016 in children with hepatoblastoma, neuroblastoma, ganglioneuroblastoma and Wilms tumor.

Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ, for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined.

Significant and Sustained Reduction in Chemotherapy Errors Through Improvement Science.

Purpose: A majority of children with cancer are now cured with highly complex chemotherapy regimens incorporating multiple drugs and demanding monitoring schedules. The risk for error is high, and errors can occur at any stage in the process, from order generation to pharmacy formulation to bedside drug administration. Our objective was to describe a program to eliminate errors in chemotherapy use among children.