Concurrent Hepatoblastoma and Wilms Tumor Leading to Diagnosis of Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4.

COVID-19 has changed the way we think about training future pediatric hematologists/oncologists.

COVID-19 has upended medical practice and education, but has also catalyzed enhancements in the field. Early on, a local group of researchers united to investigate the impact of the pandemic on pediatric hematology oncology (PHO). From this group, a regional educational series was established, "virtual-Symposium of Pediatric Hematology/Oncology of New York" (v-SYMPHONY).

Clinical Utilization, Utility, and Reimbursement for Expanded Genomic Panel Testing in Adult Oncology.

Purpose: The routine use of large next-generation sequencing (NGS) pan-cancer panels is required to identify the increasing number of, but often uncommon, actionable alterations to guide therapy. Inconsistent coverage and variable payment is hindering NGS adoption into clinical practice. A review of test utilization, clinical utility, coverage, and reimbursement was conducted in a cohort of patients diagnosed with high-risk cancer who received pan-cancer panel testing as part of their clinical care.

Being Precise About Precision Medicine: What Should Value Frameworks Incorporate to Address Precision Medicine? A Report of the Personalized Precision Medicine Special Interest Group.

Precision medicine is a dynamic area embracing a diverse and increasing type of approaches that allow the targeting of new medicines, screening programs or preventive healthcare strategies, which include the use of biologic markers or complex tests driven by algorithms also potentially taking account of patient preferences. The International Society for Pharmacoeconomics and Outcome Research expanded its current work around precision medicine to (1) describe the evolving paradigm of precision medicine with examples of current and evolving applications, (2) describe key stakeholders perspectives on the value of precision medicine in their respective domains, and (3) define the core factors that should be considered in a value assessment framework for precision medicine. With the ultimate goal of improving health of well-defined patient groups, precision medicine will affect all stakeholders in the healthcare system at multiple levels spanning the individual perspective to the societal perspective.

Whole-Genome and Whole-Exome Sequencing in Pediatric Oncology: An Assessment of Parent and Young Adult Patient Knowledge, Attitudes, and Expectations.

Purpose: The complexity of results generated from whole-genome sequencing (WGS) and whole-exome sequencing (WES) adds challenges to obtaining informed consent in pediatric oncology. Little is known about knowledge of WGS and WES in this population, and no validated tools exist in pediatric oncology.

Methods: We developed and psychometrically evaluated a novel WGS and WES knowledge questionnaire, the Precision in Pediatric Sequencing Knowledge Questionnaire (PIPseqKQ), to identify levels of understanding among parents and young adult cancer survivors (≥ 18 years old), off therapy for at least 1 year from a single-institution pediatric oncology outpatient clinic.

Precision Medicine in Children and Young Adults with Hematologic Malignancies and Blood Disorders: The Columbia University Experience.

Background: The advent of comprehensive genomic profiling has markedly advanced the understanding of the biology of pediatric hematological malignancies, however, its application to clinical care is still unclear. We present our experience integrating genomic data into the clinical management of children with high-risk hematologic malignancies and blood disorders and describe the broad impact that genomic profiling has in multiple aspects of patient care.

Methods: The Precision in Pediatric Sequencing Program at Columbia University Medical Center instituted prospective clinical next-generation sequencing (NGS) for high-risk malignancies and blood disorders.

Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations.

Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated.

Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure.

Neurocognitive functioning and quality of life in patients with recurrent malignant gliomas treated on a phase Ib trial evaluating topotecan by convection-enhanced delivery.

Background: Malignant gliomas are highly proliferative, invasive tumors that are resistant to conventional treatment, and disease progression is often accompanied by physical and mental debilitation. Neurocognitive functioning (NCF) and quality of life (QoL) were evaluated as part of a prospective phase Ib dose-escalation study of topotecan by convection-enhanced delivery (CED) for adult patients with recurrent malignant gliomas.

Methods: Sixteen patients were enrolled, and NCF and QoL were evaluated using the Cognitive Stability Index and SF-36 at baseline and monthly for 4 months post treatment.

Overcoming challenges to meaningful informed consent for whole genome sequencing in pediatric cancer research.

Background: Introducing whole genome sequencing (WGS) into pediatric cancer research at diagnosis poses unique challenges related to informed consent. WGS requires tissue obtained prior to initiating treatment, when families may be overwhelmed with uncertainty and fear. Motivation to participate may be high without fully understanding the range of possible results, including secondary findings.

Deregulation of Rab5 and Rab4 proteins in p85R274A-expressing cells alters PDGFR trafficking.

Activated receptor tyrosine kinases recruit many signaling proteins to activate downstream cell proliferation and survival pathways, including phosphatidylinositol 3-kinase (PI3K) consisting of a p85 regulatory protein and a p110 catalytic protein. We have recently shown the p85alpha protein also has in vitro GTPase activating protein (GAP) activity towards Rab5 and Rab4, small GTPases that regulate vesicle trafficking events for activated receptors. Expression of a GAP-defective mutant, p85R274A, resulted in sustained levels of activated platelet-derived growth factor receptors (PDGFRs) and enhanced downstream signaling.

Neuropsychological functioning of children treated with intensive chemotherapy followed by myeloablative consolidation chemotherapy and autologous hematopoietic cell rescue for newly diagnosed CNS tumors: an analysis of the Head Start II survivors.

Background: To evaluate the neuropsychological late effects amongst survivors treated on the Head Start II protocol between 1997 and 2003.

Procedures: Forty-nine patients (mean age 2.9 years) diagnosed with a malignant brain tumor underwent baseline neuropsychological assessment prior to autologous hematopoietic cell transplantation (AuHCT).

Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation.

Rab proteins regulate vesicle fusion events during the endocytosis, recycling, and degradation of activated receptor tyrosine kinases. The p85alpha subunit of phosphatidylinositol 3-kinase has GTPase-activating protein activity toward Rab5 and Rab4, an activity severely reduced by a single point mutation (p85-R274A). Expression of p85-R274A resulted in increased platelet-derived growth factor receptor (PDGFR) activation and downstream signaling (Akt and MAPK) and in decreased PDGFR degradation.