Accreditation/Credit Designation

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from ThermoFisher Scientific.

Community Practice Connections™: Precision Medicine in Oncology: Current Role and Future Potential of In-House NGS Technologies

Release Date: January 6, 2020
Expiration Date: January 6, 2021
Media: Internet - based

Activity Overview

Next-generation sequencing (NGS) is a widely used instrument in the field of adult hematology/oncology. However, key differences between pediatric and adult cancers at the genetic level limit the utility of the most well-established NGS panels for pediatric cancer testing. With the emergence of pediatric-tumor–specific testing assays, it is important for clinicians to remain up to date on the latest technologies to ensure that their patients with childhood cancers receive the best possible care. This activity will provide you with an overview of the history of NGS in cancer care and its developing role in pediatric hematology/oncology; the rationales for the different testing platforms, along with their utility, strengths, and limitations; and a critical evaluation of data supporting clinical application of established biomarkers in a variety of pediatric cancers.

Click to view slides from the live conference Precision Medicine in Oncology: Current Role and Future Potential of In-House NGS Technologies

Benefits of Participating

  • Learn the latest information regarding the optimal use of NGS in pediatric cancer, including the specific ways it can contribute to diagnosis and treatment
  • Compare and contrast current and emerging NGS technologies
  • Learn from case studies how the use of NGS can be applied in a variety of different malignancies
  • Hear expert perspectives on where this field is headed and how it may benefit patients now and in the future

Acknowledgement of Commercial Support

This activity is supported by an educational grant from ThermoFisher Scientific.

Instructions for This Activity and Receiving Credit

  • You will need to log in to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “Educational Content/Videos” will be available for your reference.
  • To receive a CME Certificate, you must complete the activity.
  • Complete the Posttest and pass with a score of 70% or higher, complete the Evaluation, and then click on “Request for Credit.” You may immediately download a CME Certificate upon completion of these steps.

Target Audience

This educational activity is directed toward medical oncologists and fellows who treat patients with cancer. Surgical oncologists, radiation oncologists, nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of cancer are invited to participate.

Learning Objectives

Upon successful completion of this educational activity, you should be better prepared to:

  • Outline the clinical implications of next-generation sequencing (NGS) for pediatric and young adult patients with cancer.
  • Develop evidence-based strategies to individualize treatment of pediatric and young adult patients with cancer based on assessment of tumor profile and patient characteristics.
  • Identify the role of multidisciplinary teams to facilitate, interpret, and implement novel in-house NGS technologies in clinical practice.
  • Assess methods to overcome barriers to facilitate the use of NGS strategies for pediatric and young adult patients in community settings.

Faculty, Staff, and Planners’ Disclosures

Chair

Timothy Triche
Timothy Triche, MD, PhD
Professor of Pathology and Pediatrics
Keck School of Medicine of the University of Southern California
Co-Director, Center for Personalized Medicine
Children’s Hospital Los Angeles
Los Angeles, CA

Disclosures: no relevant financial relationships with commercial interests.

Faculty

Jaclyn Biegel
Jaclyn Biegel, PhD
Director and Division Chief of Genomic Medicine
Center for Personalized Medicine
Children’s Hospital Los Angeles
Professor of Pathology (Clinical Scholar)
Keck School of Medicine of the University of Southern California
Los Angeles, CA

Disclosures: no relevant financial relationships with commercial interests.

Leo Mascarenhas
Leo Mascarenhas, MD, MS
Deputy Director, Cancer and Blood Disease Institute
Section Head, Oncology
Children’s Hospital Los Angeles
Associate Professor of Clinical Pediatrics
Keck School of Medicine of the University of Southern California
Los Angeles, CA

Disclosures: Grant Research Support: AstraZeneca; Consultant: Bayer, Eli Lilly, AstraZeneca; Speakers Bureau: Bayer; Other: AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Incyte Corporation, Jazz Pharmaceuticals, Pfizer.

The staff of Physicians' Education Resource®, LLC (PER®) have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, PER® makes it a policy to ensure fair balance, independence, objectivity, and scientific rigor in all its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that create a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for CME purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or the company that provided commercial support.

PER Pulse™ Recaps

1 of 3

Community Practice Connection™: Precision Medicine in Oncology: Current Role and Future Potential of Next-Generation Sequencing is a continuing medical education¬–certified activity in which Timothy Triche, MD, PhD; Jaclyn Biegel, PhD; and Leo Mascarenhas, MD, MS, discuss the latest developments in the use of next-generation sequencing in the assessment of pediatric malignancies.

This first of 3 PER Pulse™ Recaps focuses on the evolving role of next-generation sequencing (NGS) in the evaluation of pediatric cancer, specifically in the context of precision medicine. Below are some highlights:

  • Advances in molecular testing, particularly the use of NGS, have significantly improved the understanding of cancer as a genomic disease and have led to the expanding role of precision medicine in pediatric oncology and hematology.1-3
  • NGS has shed light on genomic alterations, such as single-nucleotide variants, copy number alterations, and structural changes, that characterize different types of malignancies.4,5
  • This results in more accurate diagnosis and classification and the opportunity to use targeted therapies.
    • Example: The detection of somatic mutations, fusions, and other genomic abnormalities led to the use of targeted therapies in Philadelphia (Ph) chromosome–positive and Ph-like acute lymphoblastic leukemia and ALK-mutated neuroblastoma.6,7
  • Results of studies of precision medicine in pediatric cancers suggest that at least 30% to 50% of patients have actionable mutations.8,9
    • Example of a prognostic genetic defect: MYCN amplification in a patient with neuroblastoma, associated with a poor prognosis
    • Example of an actionable genetic defect: NTRK fusion, which can be targeted by a TRK inhibitor10
  • Increased use of targeted therapies has improved survival in children with leukemia and solid tumors.1,10-13
  • Incorporating NGS into clinical practice has been limited by lack of comprehensive genetic profiling in pediatric patients with cancer.
  • Pediatric cancer is significantly different from adult cancer and requires a different approach to molecular profiling.9,13,14 Compared with malignancies in adults, pediatric malignancies:
    • Are characterized by a lower mutational burden at diagnosis
    • Usually harbor fewer somatic DNA single nucleotide variants, multinucleotide variants, and insertions/deletions
    • Are more likely to be driven by gene fusions and copy number alterations9,13,14
  • Most NGS panels are designed for adult cancers and do not cover the common genetic alterations found in pediatric tumors.15
  • A custom NGS panel, OncoKids, has been developed to meet the unmet need in pediatric oncology.15

“About 50% of pediatric patients will have an actionable mutation. So this is not a trivial undertaking. It has significant clinical impact.”

—Timothy Triche, MD, PhD

References

  1. Ahmed AA, Vundamati DS, Farooqi MS, Guest E. Precision medicine in pediatric cancer: current applications and future prospects. High Throughput. 2018;7(4):pii:E39. doi: 10.3390/ht7040039.
  2. Kalia M. Personalized oncology: recent advances and future challenges. Metabolism. 2013;62(suppl 1):S11-S14. doi: 10.1016/j.metabol.2012.08.016.
  3. Garraway LA, Verweij J, Ballman KV. Precision oncology: an overview. J Clin Oncol. 2013;31(15):1803-1805. doi: 10.1200/JCO.2013.49.4799.
  4. Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010;11(10):685-696. doi: 10.1038/nrg2841.
  5. Ding L, Wendl MC, Koboldt DC, Mardis ER. Analysis of next-generation genomic data in cancer: accomplishments and challenges. Hum Mol Genet. 2010;19(R2):R188-R196. doi: 10.1093/hmg/ddq391.
  6. Bresler SC, Weiser DA, Huwe PJ, et al. ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma. Cancer Cell. 2014;26(5):682-694. doi: 10.1016/j.ccell.2014.09.019.
  7. Maese L, Tasian SK, Raetz EA. How is the Ph-like signature being incorporated into ALL therapies? Best Pract Res Clin Haematol. 2017;30(3):222-228. doi: 10.1016/j.beha.2017.06.001.
  8. Rahal Z, Abdulhai F, Kadara H, Saab R. Genomics of adult and pediatric tumors. Am J Cancer Res. 2018;8(8):1356-1386.
  9. Gröbner SN, Worst BC, Weischenfeldt J, et al. The landscape of genomic alterations across childhood cancers [erratum in Nature. 2018;559(7714):E10. doi: 10.1038/s41586-018-0167-2]. Nature. 2018;555(7696):321-327. doi: 10.1038/nature25480.
  10. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378(8):731-739. doi: 10.1038/nature25480.
  11. Caporalini C, Moscardi S, Tamburini A, Pierossi N, Di Maurizio M, Buccoliero AM. Inflammatory myofibroblastic tumor of the tongue. Report of a pediatric case and review of the literature. Fetal Pediatr Pathol. 2018;37(2):117-125. doi: 10.1080/15513815.2017.1385667.
  12. Tsui PC, Lee YF, Liu ZWY, et al. An update on genomic-guided therapies for pediatric solid tumors. Future Oncol. 2017;13(15):1345-1358. doi: 10.2217/fon-2017-0003.
  13. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science 2013;339(6127):1546-1558. doi: 10.1126/science.1235122.
  14. Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214-218. doi: 10.1038/nature12213.
  15. Hiemenz MC, Ostrow DG, Busse TM, et al. OncoKids: a comprehensive next-generation sequencing panel for pediatric malignancies. J Mol Diagn. 2018;20(6):765-776. doi: 10.1016/j.jmoldx.2018.06.009.

2 of 3

Community Practice Connection™: Precision Medicine in Oncology: Current Role and Future Potential of Next-Generation Sequencing is a continuing medical education¬–certified activity in which Timothy Triche, MD, PhD; Jaclyn Biegel, PhD; and Leo Mascarenhas, MD, MS, discuss the latest developments in the use of next-generation sequencing in the assessment of pediatric malignancies.

This second of 3 PER Pulse™ Recaps compares the different methods of next-generation sequencing (NGS) in the assessment of pediatric cancer and describes the features of the OncoKids NGS panel.

  • NGS methods include single-gene testing, multigene panels, whole genome sequencing, whole exome sequencing, and RNA sequencing.1
  • OncoKids: a custom amplification-based NGS assay designed to detect the important diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, including leukemias, brain tumors, sarcomas, and embryonal tumors (neuroblastoma, retinoblastoma, Wilms tumor, and liver tumors)2
  • NGS
    • Involves a combined DNA and RNA sequencing assay
    • Uses low-input amounts of DNA (20 ng) and RNA (20 ng)
    • Interrogates DNA and RNA from formalin-fixed, paraffin-embedded, and frozen tissue, bone marrow, and peripheral blood
  • OncoKids can be used to:
    • Identify diagnostic mutations or gene fusions that will help determine prognosis and guide therapy
    • Monitor disease remission and recurrence
    • Distinguish relapse or metastasis from a second tumor
    • Identify novel therapeutics based on molecular features
  • A study of OncoKids found2:
    • Strong performance characteristics such as analytic sensitivity, detection sensitivity, and reproducibility
    • In most cases of malignancy, the test found at least 1 variant that had strong clinical significance
    • Demonstrated advantages over FISH and RT-PCR testing for gene fusions
    • Detected several driver mutations in B-cell ALL not detected by cytogenetics

References

  1. Ahmed AA, Vundamati DS, Farooqi MS, Guest E. Precision medicine in pediatric cancer: current applications and future prospects. High Throughput. 2018;7(4):pii:E39. doi: 10.3390/ht7040039.
  2. Hiemenz MC, Ostrow DG, Busse TM, et al. OncoKids: a comprehensive next-generation sequencing panel for pediatric malignancies. J Mol Diagn. 2018;20(6):765-776. doi: 10.1016/j.jmoldx.2018.06.009.

3 of 3

Community Practice Connection™: Precision Medicine in Oncology: Current Role and Future Potential of Next-Generation Sequencing is a continuing medical education¬–certified activity in which Timothy Triche, MD, PhD; Jaclyn Biegel, PhD; and Leo Mascarenhas, MD, MS, discuss the latest developments in the use of next-generation sequencing in the assessment of pediatric malignancies.

This third of 3 PER Pulse™ Recaps reviews what to consider when choosing among the different tests and the rationale for in-house NGS testing. It also provides several case studies that illustrate the clinical value of NGS in pediatric cancer.

  • When choosing among the different NGS tests, consider1:
    • The patient’s phenotype
    • Number of genes that need to be analyzed
    • Sequencing coverage of the exons
    • Copy number alterations involving the genes of interest
    • Turnaround time
    • Insurance issues
  • NGS has several benefits i the assessment of pediatric cancer.2
    • Leads to a more specific diagnosis:
      • Example: An 11-year-old girl with sarcoma had a localized recurrence. OncoKids NGS assay identified an SS18-SSX2 gene fusion, allowing for more specific therapy.
    • Corrects an incorrect diagnosis:
      • Example: A 13-year-old girl with chest wall mass diagnosed as Ewing sarcoma. NGS identified MYOD1 and PIK3CA mutations. Diagnosis was changed to rhabdomyosarcoma, spindle cell variant.
    • Refines a diagnosis, with implications for treatment
    • Uncovers an underlying condition
      • Example: In a 9-year-old boy with localized high-grade osteosarcoma of the left distal femur, NGS led to the diagnosis of Li-Fraumeni cancer syndrome.
  • Reasons to consider in-house use of NGS:
    • There is no other way to reliably, inexpensively, and accurately identify the relevant gene targets.
    • Although panels are available from commercial vendors, it is better to have local availability and expertise to ensure rapid turnaround time and appropriate assay use.
    • Availability of in-house or local testing enables an oncology practice to use current and emerging targeted therapies, often without need to refer the patient to another medical center.

References

  1. Ahmed AA, Vundamati DS, Farooqi MS, Guest E. Precision medicine in pediatric cancer: current applications and future prospects. High Throughput. 2018;7(4):pii:E39. doi: 10.3390/ht7040039.
  2. Hiemenz MC, Ostrow DG, Busse TM, et al. OncoKids: A comprehensive next-generation sequencing panel for pediatric malignancies. J Mol Diagn. 2018;20(6):765-776. doi: 10.1016/j.jmoldx.2018.06.009.

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