Precision Medicine in Pediatric Oncology

Precision Medicine in Pediatric Oncology

Publication date: Feb 14, 2020

The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition.

The Precision Medicine Initiative has defined it as an emerging approach for the prevention and treatment of disease that considers individual variability in environment, lifestyle, and genes. 1 Molecular diagnostics techniques that can analyze the individual genetic variability of tumors have provided greater understanding and additional strategies to treat cancers. 2-4 For example, MYCN amplification in a patient with neuroblastoma is associated with a poor prognosis, so identification of this defect may indicate that treatment should be changed (as when standard chemotherapy and surgery are likely to be of no value).

The use of next-generation sequencing (NGS) has greatly facilitated the understanding of pediatric cancer and identified additional therapeutic opportunities. 2 These advances have been particularly striking in the assessment and treatment of pediatric cancers that have a different genetic makeup, with a fewer number of actionable targets, than adult tumors. 5 The use of NGS has led to the increased use of targeted therapies and improved survival in children with leukemia and solid tumors. 2,6-8 For example, the detection of somatic mutations, fusions, and other genomic abnormalities has resulted in the use of targeted therapies in Philadelphia (Ph) chromosome-positive and Ph-like acute lymphoblastic leukemia (ALL) and ALK-mutated neuroblastoma. 9,10 Somatic genomic testing has become the standard of care in a variety of pediatric cancers.

Genomic profiling has become particularly important in the evaluation of central nervous system (CNS) tumors, and the use of genetic profiling has been included in the World Health Organization classification of CNS malignancy. 11 In the section that follows, Theodore Laetsch, MD, discusses the current status of pediatric precision oncology and different clinical scenarios in which it can be effectively applied.

Dr Laetsch: At the most basic level, precision medicine means refining the treatment based on the individual patient and tumor characteristics, and this has been going on for a long period of time using biomarkers to define therapy.

I think some of the earliest examples of this are using the patient’s age or their white blood cell count when they initially presented to define the treatment for pediatric leukemia and pediatric ALL, but more recently, it has focused on the use of genetic markers.

This example reflects how the era of precision medicine is evolving to use not just molecular characterization of the tumor but actually a targeted agent to improve outcomes, and the same is now going on in leukemia, where they’re studying a variety of BCR-ABL-like leukemias, the Philadelphia-like leukemias, to see if a similar philosophy works with targeting of these fusions that are identified.

As I’ve discussed, for some cancers, molecular testing is absolutely standard of care at the time of diagnosis, for example, in patients with neuroblastoma and leukemia.

Dr Laetsch: I’ve discussed a number of these potential molecular alterations, including MYCN amplification for neuroblastoma, and more recently, a discovery of ALK-activating mutations in neuroblastoma, which are now being targeted, as well as the Philadelphia chromosome and Philadelphia-like mutation in pediatric ALL.

Q: Could you describe the incidence and presentation of NTRK fusion-positive solid tumors and hematologic malignancies in pediatric patients?

I think also, given the number of patients who have been sequenced and the variability of the techniques for sequencing, you can’t completely exclude the presence of NTRK fusions and other tumors.

Concepts Keywords
ABL Oncology
Acute Lymphoblastic Leukemia Chemotherapy
ALK Neuroblastoma
AMA Larotrectinib
Assay Chemical compounds
Biomarker Clinical medicine
Biomarkers Entrectinib
Blood ROS1
Cancer Anaplastic lymphoma kinase
Central Nervous System Tyrosine kinase receptors
Chemotherapy Chemotherapy surgery
Clinical Trials System CNS tumors
Colon Individual patient tumor
Congenital Repairdeficient tumors
Congestive Heart Failure Infantile fibrosarcoma
Continuing Education Leukemias
Cross Outcomes leukemia
Cytopenias Papillary thyroid melanoma
Dallas Pan cancer
Dizziness Frequency tumors
DNA MYCN amplification neuroblastoma
Fatigue Mutations neuroblastoma
FDA Soft tissue sarcomas
Fetal Relevant pediatric tumor
Fibrosarcoma Pediatric cancer Q
Frequency Molecular characterization tumor
Gastrointestinal Lymphoma
Genetic Common cancer
Genetic Defect Pediatric cancer
Genetic Profiling Fatigue dizziness
Genetic Variability Specific cancers leukemia
Gliomas
Hematologic Malignancies
Hematologist
Hematology
Hepatotoxicity
Histologic
Histology
Hyperuricemia
Incidence
Jim Smith
Kinase Inhibitor
Leukemia
Leukemias
Liver
Lung
Lymphoma
Malignancies
Malignancy
Melanoma
Molecular Genetic
Mutation
NCI
Neuroblastoma
Norma
NTRK
Oncological
Oncologist
Oncology
Pathognomonic
Pediatric
Pediatric Cancer
Pediatric Oncology
Pediatrics
PER
Philadelphia
Philadelphia Chromosome
Philosophy
Physician
Prognosis
Relapse
Remission
RNA
Sarcoma
Sequencing
Soft Tissue Sarcomas
Somatic
Substitute
Targeted Therapies
Targeted Therapy
Texas
Thyroid
Toxicity
TRK
Tumor

Semantics

Type Source Name
disease MESH Cancer
drug DRUGBANK Etoperidone
drug DRUGBANK Tropicamide
disease MESH lifestyle
disease MESH neuroblastoma
disease MESH leukemia
disease MESH abnormalities
disease MESH acute lymphoblastic leukemia
disease MESH genetic markers
drug DRUGBANK Lauric Acid
disease MESH Philadelphia chromosome
disease MESH diagnosis
disease MESH soft tissue sarcomas
disease MESH relapses
disease MESH microsatellite instability
drug DRUGBANK Pembrolizumab
drug DRUGBANK Larotrectinib
drug DRUGBANK Entrectinib
disease MESH hematologic malignancies
disease MESH fibrosarcoma
disease MESH congenital
disease MESH lymphoma
disease MESH papillary thyroid cancer
disease MESH melanoma
pathway KEGG Melanoma
disease MESH gliomas
disease MESH lung cancer
disease MESH colon cancer
disease MESH vision disorders
disease MESH congestive heart failure
disease MESH hyperuricemia
disease MESH community

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