Lesion Analysis of F-Metafluorobenzylguanidine PET Imaging in Neuroblastoma.

A PET analog of metaiodobenzylguanidine (MIBG)-F-metafluorobenzylguanidine (F-MFBG)-allows for rapid same-day imaging. We previously reported on the safety and feasibility of F-MFBG PET imaging in patients with neuroendocrine tumors. We now report a comprehensive analysis of lesion detection with F-MFBG imaging in patients with neuroblastoma compared with I-MIBG imaging.

A Single Institutional Experience Using Romiplostim to Treat Therapy-Related Thrombocytopenia in Pediatric Solid Tumor Patients.

Chemotherapy-induced thrombocytopenia (CIT) is a common toxicity in patients with cancer, leading to chemotherapy dose reductions and increased platelet transfusions. Although there are well-documented data using thrombopoietin receptor agonists (TPO-RA) in both adult CIT and pediatric immune thrombocytopenia, there is a paucity of data in pediatric CIT. This is a single institutional, retrospective study evaluating the use and safety of romiplostim in pediatric patients with solid tumors undergoing cancer treatment.

Rapid COJEC without myeloablative therapy for high-risk neuroblastoma.

Myeloablative therapy (MAT) is included in high-risk neuroblastoma (HR-NB) treatment programs of the Children's Oncology Group (COG) and the Societe Internationale d'Oncologie Pediatrique Europe Neuroblastoma (SIOPEN), but not at Memorial Sloan Kettering Cancer Center (MSK). COG and SIOPEN programs achieved 3-5-year event-free survival rates of ~50%-60%, similar to the MSK experience without MAT which involved patients treated with COG or MSK induction and anti-G mAb murine-3F8 + granulocyte-macrophage colony-stimulating factor (GM-CSF). We now present the first report on rapid COJEC without MAT.

Clinical Significance of Promoter Mutations in Neuroblastoma.

Purpose: Telomere maintenance mechanisms including amplification (A) (via upregulated telomerase reverse transcriptase [] expression), rearrangements (-RA), and mutations confer neoplastic immortality in neuroblastoma (NB) cells. Clinical characterization of patients with NB harboring activating somatic promoter point mutations (-PM) in NB may improve stratification.

Methods: To identify -PM and -RA, tumors were profiled by the Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets targeted next-generation sequencing platform and whole-genome sequencing, respectively.

Pulmonary Toxicity Associated With Concurrent Lorlatinib and Anti-GD2 Monoclonal Antibody Therapy in Patients With Neuroblastoma.

Background: The anaplastic lymphoma kinase (ALK) inhibitor lorlatinib demonstrated safety without pulmonary toxicity in early-phase trials in patients with neuroblastoma. Lorlatinib is being tested with chemotherapy and immunotherapy in the Children's Oncology Group study ANBL1531. However, pulmonary toxicity was noted in patients receiving lorlatinib concurrently with anti-disialoganglioside 2 (GD2) monoclonal antibody (mAb) dinutuximab on the trial.

Accelerating Drug Development for Neuroblastoma: Consensus Statement From the Third Neuroblastoma Drug Development Strategy Forum.

High-risk neuroblastoma is a poor prognosis cancer of the sympathetic nervous system that accounts for a disproportionate number of childhood cancer deaths. Many viable biological targets have been identified, and the number of potential combinations is even larger. Several products have attained marketing authorization for treatment of patients with neuroblastoma.

A Phase II Trial of Naxitamab plus Stepped-up Dosing of GM-CSF for Patients with High-Risk Neuroblastoma in First Complete Remission.

Purpose: Naxitamab is a humanized form of the murine anti-GD2 mAb 3F8. In an international trial, naxitamab + GM-CSF was effective against chemoresistant high-risk neuroblastoma (HR-NB), leading to approval by the FDA. We now report results with patients in first complete remission (CR).

Safety observations in neuroblastoma patients undergoing 18 F- m FBG PET.

Objective: Limited safety data have been published on fluorine-18 ( 18 F) meta-fluorobenzylguanidine ( m FBG), a new PET radiopharmaceutical for imaging neural crest and neuroendocrine tumors. As part of a prospective clinical trial, safety data in patients with neuroblastoma were collected and analyzed.

Methods: Between April 2015 and January 2022, 27 patients with neuroblastoma underwent 18 F- m FBG PET imaging as part of an ongoing single-center phase 1/2 trial (NCT02348749).

Omalizumab for Treatment of Anti-GD2 Antibody-related Urticaria.

Outcomes for high-risk neuroblastoma have improved with the addition of antidisialoganglioside (GD2) antibody-mediated immunotherapy to multimodality therapy. Urticaria is an expected side effect of anti-GD2 immunotherapy. Rarely, despite maximal use of antihistamines and H2 receptor antagonists, refractory urticaria can result in impaired quality of life, and delays or discontinuation of immunotherapy.

Ovarian function in female survivors of high-risk neuroblastoma.

Introduction: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy.

Methods: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center.

Long Prime-Boost Interval and Heightened Anti-GD2 Antibody Response to Carbohydrate Cancer Vaccine.

The carbohydrate ganglioside GD2/GD3 cancer vaccine adjuvanted by β-glucan stimulates anti-GD2 IgG1 antibodies that strongly correlate with improved progression-free survival (PFS) and overall survival (OS) among patients with high-risk neuroblastoma. Thirty-two patients who relapsed on the vaccine (first enrollment) were re-treated on the same vaccine protocol (re-enrollment). Titers during the first enrollment peaked by week 32 at 751 ± 270 ng/mL, which plateaued despite vaccine boosts at 1.

Evolutionary Strategies AI Addresses Multiple Technical Challenges in Deep Learning Deployment: Proof-of-Principle Demonstration for Neuroblastoma Brain Metastasis Detection.

Two significant obstacles hinder the advancement of Radiology AI. The first is the challenge of overfitting, where small training data sets can result in unreliable outcomes. The second challenge is the need for more generalizability, the lack of which creates difficulties in implementing the technology across various institutions and practices.

Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells.

Background: The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.

Methods: The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1).

Intraoperative Radiation Therapy for Relapsed or Refractory High-Risk Neuroblastoma: A 27-Year Experience.

Purpose: To evaluate outcomes after intraoperative radiation therapy (IORT) in high-risk neuroblastoma (NB), including local control, overall survival, and toxicity.

Methods And Materials: This was a single institution retrospective study of 92 pediatric patients with NB treated with IORT from 1995 to 2022. Each IORT application was considered a separate event for a total of 110 sites treated.

GM-CSF, G-CSF or no cytokine therapy with anti-GD2 immunotherapy for high-risk neuroblastoma.

Colony-stimulating factors have been shown to improve anti-disialoganglioside 2 (anti-GD2) monoclonal antibody response in high-risk neuroblastoma by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). A substantial amount of research has focused on recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant to anti-GD2 monoclonal antibodies. There may be a disparity in care among patients as access to GM-CSF therapy and anti-GD2 monoclonal antibodies is not uniform.

Targeting GD2-positive Refractory/Resistant Neuroblastoma and Osteosarcoma with Anti- CD3 x Anti-GD2 Bispecific Antibody Armed T cells.

Background: Since treatment of neuroblastoma (NB) with anti-GD2 monoclonal antibodies provides a survival benefit in children with minimal residual disease and our preclinical study shows that anti-CD3 x anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs) were highly cytotoxic to GD2+ cell lines, we conducted a phase I/II study in recurrent/refractory patients to establish safety and explore the clinical benefit of GD2BATs.

Methods: The 3+3 dose escalation study (NCT02173093) phase I involved 9 evaluable patients with NB (n=5), osteosarcoma (OST) (n=3), and desmoplastic small round cell tumors (DSRCT) (n=1) with twice weekly infusions of GD2BATs at 40, 80, or 160 x 10 GD2BATs/kg/infusion with daily interleukin 2 (300,000 IU/m) and twice weekly granulocyte-macrophage colony stimulating factor (250 μg/m). Phase II portion of the trial was conducted in patients with NB at the dose 3 level of 160 x 10 GD2BATs/kg/infusion but failed to enroll the planned number of patients.

Stage 4N neuroblastoma before and during the era of anti-G immunotherapy.

Patients with stage 4N neuroblastoma (distant metastases limited to lymph nodes) stand out as virtually the only survivors of high-risk neuroblastoma (HR-NB) before myeloablative therapy (MAT) and immunotherapy with anti-G monoclonal antibodies (mAbs) became standard. Because no report presents more recent results with 4N, we analyzed our large 4N experience. All 51 pediatric 4N patients (<18 years old) diagnosed 1985 to 2021 were reviewed.

Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults.

Purpose: Adult-onset neuroblastoma (AON) differs significantly in biology and clinical behavior from childhood-onset disease. AON poses therapeutic challenges since tolerance of intensive multimodality therapies that are standard of care for pediatric neuroblastoma (NB) is poor. AON is enriched for somatic mutations including anaplastic lymphoma kinase (), deemed to be an oncogenic driver in NB.

Ganglioneuroblastoma intermixed: Clinicopathological implications of diagnosis at presentation and genomic correlations.

Background: Ganglioneuroblastoma intermixed (GNBI) is classified as "favorable" histology by International Neuroblastoma Pathology Classification system. However, the International Neuroblastoma Risk Group (INRG) stratifies patients using wider clinicopathological and cytogenetic/molecular parameters. While the diagnosis of GNBI is typically made on resected tumor, it may sometimes be rendered on initial biopsy.

Clonal evolution during metastatic spread in high-risk neuroblastoma.

Patients with high-risk neuroblastoma generally present with widely metastatic disease and often relapse despite intensive therapy. As most studies to date focused on diagnosis-relapse pairs, our understanding of the genetic and clonal dynamics of metastatic spread and disease progression remain limited. Here, using genomic profiling of 470 sequential and spatially separated samples from 283 patients, we characterize subtype-specific genetic evolutionary trajectories from diagnosis through progression and end-stage metastatic disease.

Radioimmunoscintigraphy and Pretreatment Dosimetry of I-Omburtamab for Planning Treatment of Leptomeningeal Disease.

Radiolabeled antibody treatment with I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pretreatment I-omburtamab imaging and dosimetric analysis in patients before therapy.

Skeletal muscle metastases in neuroblastoma share common progenitors with primary tumor and biologically resemble stage MS disease.

Introduction: While subcutaneous metastases are often observed with stage MS neuroblastoma, an entity that usually resolves spontaneously, skeletal muscle metastases (SMM) have been rarely described. The purpose of this retrospective study was to investigate the significance of SMM in neuroblastoma.

Patients And Methods: Seventeen patients with neuroblastoma SMM were diagnosed at a median age of 4.

Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma: A Phase 2 Randomized Clinical Trial.

Importance: Among patients with high-risk relapsed metastatic neuroblastoma, oral β-glucan adjuvant during GD2/GD3 ganglioside vaccine boost has stimulated IgG antibody response, which was associated with improved survival; however, the effectiveness of oral β-glucan during the vaccine priming phase remains unproven.

Objective: To isolate the adjuvant effect of oral β-glucan on antibody response to GD2/GD3 ganglioside vaccine in patients with high-risk neuroblastoma.

Design, Setting, And Participants: In this phase 2 randomized clinical trial, enrolled patients with high-risk neuroblastoma were randomized to 2 groups to receive the GD2/GD3 vaccine at a large cancer center in a major metropolitan area from October 2018 to September 2020.

Phase 1 study of intraventricular I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies.

Background: The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal, and the need for newer therapeutic targets and modalities is critical. The cell surface glycoprotein B7H3 is expressed on a range of solid tumors with a restricted expression on normal tissues. We hypothesized that compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab injected intraventricularly could safely target CNS malignancies.