PET-CT-based host metabolic (PETMet) features are associated with pathologic response in gastroesophageal adenocarcinoma.

Background: F-FDG PET-CT-based host metabolic (PETMet) profiling of non-tumor tissue is a novel approach to incorporate the patient-specific response to cancer into clinical algorithms.

Materials And Methods: A prospectively maintained institutional database of gastroesophageal cancer patients was queried for pretreatment PET-CTs, demographics, and clinicopathologic variables. F-FDG PET avidity was measured in 9 non-tumor tissue types (liver, spleen, 4 muscles, 3 fat locations).

Non-RB1 germline cancer predisposing variants found in retinoblastoma patients.

Purpose: It is well known that individuals with hereditary retinoblastoma are at lifelong high risk for developing subsequent malignant neoplasms (SMN). However, the role that non- germline variants play in tumorigenesis and SMN risk has not yet been studied. The purpose of this study is to report the frequency and spectrum of non- germline cancer predisposing variants in individuals with retinoblastoma (RB).

Development of F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance.

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with F-fluoromisonidazole (F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret F-FMISO hypoxia PET.

ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer.

Importance: There are insufficient data comparing 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence.

Objective: To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence.

Design, Setting, And Participants: This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023.

Imaging with [Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumours of the lung and prostate: a phase 1/2, first-in-human trial.

Background: Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and feasibility of the DLL3-targeted imaging tracer [Zr]Zr-DFO-SC16.56 (composed of the anti-DLL3 antibody SC16.

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.

Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.

ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.

Conventional and novel [F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma.

Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T F-fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes.

Persistent or New Cytopenias Predict Relapse Better than Routine Bone Marrow Aspirate Evaluations After Hematopoietic Cell Transplantation for Acute Leukemia or Myelodysplastic Syndrome in Children and Young Adult Patients.

The clinical value of serial routine bone marrow aspirates (rBMAs) in the first year after allogeneic hematopoietic cell transplantation (alloHCT) to detect or predict relapse of acute leukemia (AL) and myelodysplastic syndrome (MDS) in pediatric and young adult patients is unclear. The purpose of this analysis was to determine if assessment of minimal residual disease (MRD) by multiparameter flow cytometry (MFC, MFC-MRD) or donor chimerism (DC) in rBMAs or serial complete blood counts (CBCs) done in the year after alloHCT predicted relapse of AL or MDS in pediatric and young adult patients. We completed a retrospective analysis of patients with AL or MDS who had rBMAs performed after alloHCT between January 2012 and June 2018.

Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell-depleted hematopoietic cell transplantation in pediatric and young adult patients.

Background Aims: Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving various types of EX-VIVO T-cell-depleted (EX-VIVO-TCD) HCT.

First-in-Human Evaluation of Site-Specifically Labeled Zr-Pertuzumab in Patients with HER2-Positive Breast Cancer.

Radioimmunoconjugates targeting human epidermal growth factor receptor 2 (HER2) have shown potential to noninvasively visualize HER2-positive tumors. However, the stochastic approach that has been traditionally used to radiolabel these antibodies yields poorly defined and heterogeneous products with suboptimal in vivo performance. Here, we describe a first-in-human PET study on patients with HER2-positive breast cancer evaluating the safety, biodistribution, and dosimetry of Zr-site-specific (ss)-pertuzumab PET, a site-specifically labeled radioimmunoconjugate designed to circumvent the limitations of random stochastic lysine labeling.

Safety and tolerability of intravenous aprepitant and fosaprepitant in children with cancer: A retrospective, single-center review.

NK-1 receptor antagonists (NK1-RA) are key agents for chemotherapy-induced nausea and vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy. Current pediatric practice guidelines recommend the use of intravenous fosaprepitant or oral aprepitant. However, there are reports of hypersensitivity reactions with fosaprepitant due to polysorbate 80.

First-in-human imaging with [Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumors of the lung and prostate.

Background: Delta-like ligand 3 (DLL3) is aberrantly expressed on the cell surface in many neuroendocrine cancers including small cell lung cancer (SCLC) and neuroendocrine prostate cancer (NEPC). Several therapeutic agents targeting DLL3 are in active clinical development. Molecular imaging of DLL3 would enable non-invasive diagnostic assessment to inform the use of DLL3-targeting therapeutics or to assess disease treatment response.

Retrospective Evaluation of Cystatin C as a Measure of Renal Function in Pediatric Hematopoietic Stem Cell Transplant Patients Receiving Foscarnet for Cytomegalovirus Reactivation.

Background: Cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation has considerable morbidity and mortality, and foscarnet is a treatment option that requires renal dose adjustment. Serum creatinine (SCr)-based estimated glomerular filtration rate (eGFR) equations are used to estimate renal function for patients receiving foscarnet, but cystatin C (cysC) has been shown as a possible alternative. Data examining cysC-based eGFR in this population is sparse.

T-cell depleted allogeneic hematopoietic stem cell transplant for the treatment of Fanconi anemia and MDS/AML.

The only curative approach for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) arising in patients with Fanconi anemia (FA) is allogeneic hematopoietic stem cell transplantation (HCT); however, HCT approaches are inconsistent and limited data on outcomes exist. We retrospectively evaluated outcomes of thirty patients with FA and MDS/AML who underwent first allogeneic HCT with a T-cell depleted (TCD) graft at our institution. Patients were transplanted on successive protocols with stepwise changes in cytoreduction and GVHD prophylaxis.

Bleeding in Critically Ill Children With Malignancy or Hematopoietic Cell Transplant: A Single-Center Prospective Cohort Study.

Objectives: To determine the incidence of bleeding in critically ill children with malignancy and to describe associated patient characteristics, interventions, and clinical outcomes.

Design: Prospective cohort study.

Setting: PICU in a specialized cancer hospital.

A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.

Unlabelled: Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions.

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents.

Purpose: There is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders.

Clinical Targeted Next-Generation Panel Sequencing Reveals Amplification Is a Poor Prognostic Factor in Osteosarcoma.

Purpose: Osteosarcoma risk stratification, on the basis of the presence of metastatic disease at diagnosis and histologic response to chemotherapy, has remained unchanged for four decades, does not include genomic features, and has not facilitated treatment advances. We report on the genomic features of advanced osteosarcoma and provide evidence that genomic alterations can be used for risk stratification.

Materials And Methods: In a primary analytic patient cohort, 113 tumor and 69 normal samples from 92 patients with high-grade osteosarcoma were sequenced with OncoPanel, a targeted next-generation sequencing assay.

Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant.

BackgroundRefractory CMV viremia and disease are associated with significant morbidity and mortality in recipients of hematopoietic stem cell transplant (HCT).MethodsIn phase I/II trials, we treated 67 subjects for CMV viremia or disease arising after HCT with adoptive transfer of banked, third-party, CMVpp65-sensitized T cells (CMVpp65-VSTs). All were evaluable for toxicity and 59 for response.

The safety and efficacy of methylnaltrexone in pediatric oncology patients: A single center experience.

Introduction: Peripherally acting -opioid receptor antagonists (PAMORAs) are used in the treatment of opioid induced constipation without impacting the actions of opioid analgesics. Subcutaneous methylnaltrexone was one of the first PAMORAs approved in April 2008 for the treatment of opioid induced constipation in adult patients. The safety and effectiveness of methylnaltrexone has not been established in pediatric patients.