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      Saturday, December 9, 2023
      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
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      CME / ABIM MOC / CE

      Neuro-Oncology Updates: Insights on the Diagnosis and Management of Low-Grade Glioma, Glioblastoma, and NF1

      • Authors: Katherine Peters, MD, PhD; Maciej Mrugala, MD, PhD, MPH; Cynthia Campen, MD, MSCE
      • CME / ABIM MOC / CE Released: 3/10/2023
      • Valid for credit through: 3/10/2024, 11:59 PM EST
      Start Activity

      • Credits Available

        Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

        ABIM Diplomates - maximum of 1.00 ABIM MOC points

        Nurses - 1.00 ANCC Contact Hour(s) (0.75 contact hours are in the area of pharmacology)

        IPCE - 1.0 Interprofessional Continuing Education (IPCE) credit

        You Are Eligible For

        • Letter of Completion
        • ABIM MOC points

      Target Audience and Goal Statement

      This activity is intended for oncologists (including pediatric oncologists), neurologists, neurosurgeons, neuropathologists, nurses, and other healthcare professionals (HCPs) involved in the care of patients with neuro-oncologic disorders.

      The goal of this activity is for learners to be better able to recognize and care for patients with low-grade gliomas, glioblastoma (GBM), and neurofibromatosis type 1 (NF1)-associated tumors.

      Upon completion of this activity, participants will:

      • Have increased knowledge regarding the
        • Defining characteristics of certain neuro-oncologic diseases
        • Clinical trial data evaluating therapies for patients with certain neuro-oncologic diseases
      • Have greater competence related to
        • Making an accurate diagnosis for patients with certain neuro-oncologic diseases
        • Individualizing care for patients with certain neuro-oncologic diseases
      • Demonstrate greater confidence in their ability to
        • Care for patients with certain neuro-oncologic diseases throughout their care journey

      Disclosures

      Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

      All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.

      Disclosures for additional planners can be found here.

      Faculty

      • Katherine Peters, MD, PhD

        Associate Professor of Neurology and Neurosurgery
        Duke University School of Medicine
        Durham, North Carolina

        Disclosures

        Katherine Peters, MD, PhD, has the following relevant financial relationships:
        Consultant or advisor for: Ono Pharmaceutical Co., Ltd.; NuVox, Sapience; SERVIER
        Research funding from: AbbVie, Inc.; Biomimetix; Sapience; SERVIER; Varian

      • Maciej Mrugala, MD, PhD, MPH

        Professor of Medicine and Neurology
        Director
        Neuro-Oncology Program
        Director
        Neuro-Oncology Fellowship Program
        Mayo Clinic
        Phoenix, Arizona

        Disclosures

        Maciej Mrugala, MD, PhD, MPH, has the following relevant financial relationships:
        Consultant or advisor for: Alexion Pharmaceuticals, Inc.; Biocept; Ensoma; Merck & Co., Inc.
        Research funding from: Arbor Pharmaceuticals, Inc.

      • Cynthia Campen, MD, MSCE

        Clinical Associate Professor of Medicine
        Stanford University School of Medicine
        Stanford, California

        Disclosures

        Cynthia Campen, MD, MSCE, has the following relevant financial relationships:
        Consultant or advisor for: Alexion Advisory Board (former)

      Editors

      • Charlotte Warren

        Senior Director, Content Development, Medscape, LLC

        Disclosures

        Charlotte Warren has no relevant financial relationships.

      • Tristin Abair, PhD

        Senior Medical Writer, Medscape, LLC

        Disclosures

        Tristin Abair, PhD, has no relevant financial relationships.

      Compliance Reviewer/Nurse Planner

      • Leigh Schmidt, MSN, RN, CNE, CHCP

        Associate Director, Accreditation and Compliance, Medscape, LLC

        Disclosures

        Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

      Peer Reviewer

      This activity has been peer reviewed and the reviewer has no relevant financial relationships.

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      Medscape

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      In support of improving patient care, Medscape, LLC is jointly accredited with commendation by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

      IPCE

      This activity was planned by and for the healthcare team, and learners will receive 1.00 Interprofessional Continuing Education (IPCE) credit for learning and change.

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      • Medscape, LLC designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

        Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Aggregate participant data will be shared with commercial supporters of this activity.

        The European Union of Medical Specialists (UEMS)-European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

        College of Family Physicians of Canada Mainpro+® participants may claim certified credits for any AMA PRA Category 1 credit(s)™, up to a maximum of 50 credits per five-year cycle. Any additional credits are eligible as non-certified credits. College of Family Physicians of Canada (CFPC) members must log into Mainpro+® to claim this activity.

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      • Awarded 1.0 contact hour(s) of continuing nursing education for RNs and APNs; 0.75 contact hours are in the area of pharmacology.

        Contact This Provider

      For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

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      There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

      This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.

      Follow these steps to earn CME/CE credit*:

      1. Read about the target audience, learning objectives, and author disclosures.
      2. Study the educational content online or print it out.
      3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming.

      You may now view or print the certificate from your CME/CE Tracker. You may print the certificate, but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period, you can print out the tally as well as the certificates from the CME/CE Tracker.

      *The credit that you receive is based on your user profile.

      < PATHWAYS IN RARE DISEASE Being Rare Together
      From Medscape Education Oncology
      CME / ABIM MOC / CE

      Neuro-Oncology Updates: Insights on the Diagnosis and Management of Low-Grade Glioma, Glioblastoma, and NF1

      Authors: Katherine Peters, MD, PhD; Maciej Mrugala, MD, PhD, MPH; Cynthia Campen, MD, MSCEFaculty and Disclosures

      CME / ABIM MOC / CE Released: 3/10/2023

      Valid for credit through: 3/10/2024, 11:59 PM EST

      processing....

      References

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      2. Affronti ML, et al. Pilot study to describe the trajectory of symptoms and adaptive strategies of adults living with low-grade glioma. Semin Oncol Nurs. 2018;34:472-485.
      3. Louis DN, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131:803-820. 
      4. National Comprehensive Cancer Network (NCCN). Central Nervous System Cancers (Version 2.2022). 2022. Accessed February 15, 2023. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf
      5. Aghi MK, et al. The role of surgery in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2015;125:503-530.
      6. van den Bent MJ, et al. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet. 2005;366:985-990. 
      7. Thurin E, et al. Proton therapy for low-grade gliomas in adults: a systematic review. Clin Neurol Neurosurg. 2018;174:233-238.
      8. Shih HA, et al. Proton therapy for low-grade gliomas: results from a prospective trial. Cancer. 2015;121:1712-1719.
      9. Buckner JC, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med. 2016;374:1344-1355.
      10. Bell EH, et al. Comprehensive genomic analysis in NRG Oncology/RTOG 9802: a phase III trial of radiation versus radiation plus procarbazine, lomustine (CCNU), and vincristine in high-risk low-grade glioma. J Clin Oncol. 2020;38:3407-3417.
      11. Baumert BG, et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016;17:1521-1532.
      12. Schreck KC, et al. BRAF mutations and the utility of RAF and MEK inhibitors in primary brain tumors. Cancers (Basel). 2019;11:1262. 
      13. Andrews LJ, et al. Prevalence of BRAFV600 in glioma and use of BRAF inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review. Neuro Oncol. 2022;24:528-540.
      14. Wen PY, et al. Dabrafenib plus trametinib in patients with BRAF V600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol. 2022;23:53-64.
      15. Kaley T, et al. BRAF inhibition in BRAF V600-mutant gliomas: results from the VE-BASKET study. J Clin Oncol. 2018;36:3477-3484.
      16. Yau WH, et al. Combination of BRAF and MEK inhibition in BRAF V600E mutant low-grade ganglioglioma. J Clin Pharm Ther. 2020;45:1172-1174.
      17. Touat M, et al. Vemurafenib and cobimetinib overcome resistance to vemurafenib in BRAF-mutant ganglioglioma. Neurology. 2018;91:523-525.
      18. Mellinghoff IK, et al. Ivosidenib in isocitrate dehydrogenase 1-mutated advanced glioma. J Clin Oncol. 2020;38:3398-3406.
      19. Mellinghoff IK, et al. Vorasidenib, a dual inhibitor of mutant IDH1/2, in recurrent or progressive glioma; results of a first-in-human phase I trial. Clin Cancer Res. 2021;27:4491-4499.
      20. Mellinghoff IK, et al. A phase 1, open-label, perioperative study of ivosidenib (AG-120) and vorasidenib (AG-881) in recurrent, IDH1-mutant, low-grade glioma: updated results. Neuro Oncol. 2019;21(suppl 6):ACTR-66.
      21. Mellinghoff IK, et al. INDIGO: a global, randomized, double-blind, phase III study of vorasidenib (VOR; AG-881) vs placebo in patients with residual or recurrent grade II glioma with an isocitrate dehydrogenase 1/2 (IDH1/2) mutation. J Clin Oncol. 2020;38(15 suppl):TPS2574.
      22. Peters K, et al. Safety of tumor-specific peptide vaccine targeting isocitrate dehydrogenase 1 mutation in recurrent resectable low grade glioma patients. Neuro Oncol. 2019;21(suppl 6):ATIM-31.
      23. Platten M, et al. A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature. 2021;592:463-468.
      24. Torre M, et al. Molecular and clinicopathologic features of gliomas harboring NTRK fusions. Acta Neuropathol Commun. 2020;8:107.
      25. Rong L, et al. Emerging therapies for glioblastoma: current state and future directions. J Exp Clin Cancer Res. 2022;41:142.
      26. Tan AC, et al. Management of glioblastoma: state of the art and future directions. CA Cancer J Clin. 2020;70:299-312.
      27. Louis DN, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23:1231-1251.
      28. Chowdhary SA, et al. Survival outcomes and safety of carmustine wafers in the treatment of high-grade gliomas: a meta-analysis. J Neurooncol. 2015;122:367-382.
      29. Molina E, et al. Maximizing safe resections: the roles of 5-aminolevulinic acid and intraoperative MR imaging in glioma surgery-review of the literature. Neurosurg Rev. 2019;42:197-208.
      30. Stummer W, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7:392-401.
      31. Perry JR, et al. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017;376:1027-1037.
      32. Stupp R, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459-466.
      33. Stupp R, et al. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012;48:2192-2202.
      34. Stupp R, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318:2306-2316.
      35. Taphoorn MJB, et al. Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: a secondary analysis of a randomized clinical trial. JAMA Oncol. 2018;4:495-504.
      36. Kreisl TN, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740-745.
      37. Friedman HS, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733-4740.
      38. Wick W, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017;377:1954-1963.
      39. Lombardi G, et al. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019;20:110-119.
      40. Bevacizumab [prescribing information]. Approved 2004. Revised May 2009.
      41. Goff KM, et al. Proton radiotherapy for glioma and glioblastoma. Chin Clin Oncol. 2022;11:46. 
      42. Miller R, et al. Scalp-sparing radiation with concurrent temozolomide and tumor treating fields (SPARE) for patients with newly diagnosed glioblastoma. Front Oncol. 2022;12:896246.
      43. Szklener K, et al. New directions in the therapy of glioblastoma. Cancers (Basel). 2022;14:5377.
      44. Desjardins A, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med. 2018;379:150-161.
      45. Reardon DA, et al. Rindopepimut with bevacizumab for patients with relapsed EGFRvIII-expressing glioblastoma (ReACT): results of a double-blind randomized phase II trial. Clin Cancer Res. 2020;26:1586-1594. 
      46. Liau LM, et al. First results on survival from a large phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018;16:142.
      47. Liau LM, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial. JAMA Oncol. 2023;9:112-121.
      48. Fisher MJ, et al. Management of neurofibromatosis type 1-associated plexiform neurofibromas. Neuro Oncol. 2022;24:1827-1844.
      49. Miller DT, et al. Health supervision for children with neurofibromatosis type 1. Pediatrics. 2019;143:e20190660. 
      50. Legius E, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med. 2021;23:1506-1513.
      51. McCaughan JA, et al. Further evidence of the increased risk for malignant peripheral nerve sheath tumour from a Scottish cohort of patients with neurofibromatosis type 1. J Med Genet. 2007;44:463-466.
      52. Dombi E, et al. NF1 plexiform neurofibroma growth rate by volumetric MRI: relationship to age and body weight. Neurology. 2007;68:643-647.
      53. Selumetinib [prescribing information]. Approved 2020. Revised December 2021.
      54. de Blank PMK, et al. MEK inhibitors for neurofibromatosis type 1 manifestations: clinical evidence and consensus. Neuro Oncol. 2022;24:1845-1856. 
      55. Gross AM, et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med. 2020;382:1430-1442.
      56. Gross AM, et al. Selumetinib in children with neurofibromatosis type 1 and asymptomatic inoperable plexiform neurofibroma at risk for developing tumor-related morbidity. Neuro Oncol. 2022;24:1978-1988.
      57. O’Sullivan Coyne G, et al. Phase II trial of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886 hydrogen sulfate) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN). J Clin Oncol. 2020;38(15 suppl):3612.
      58. Weiss BD, et al. NF106: a neurofibromatosis clinical trials consortium phase II trial of the MEK inhibitor mirdametinib (PD-0325901) in adolescents and adults with NF1-related plexiform neurofibromas. J Clin Oncol. 2021;39:797-806.
      59. Mueller S, et al. MEK inhibitor binimetinib shows clinical activity in children with neurofibromatosis type 1- associated plexiform neurofibromas: a report from PNOC and the NF Clinical Trials Consortium. Neuro Oncol. 2020;22(suppl 3):NFB-17.
      60. McCowage GB, et al. Trametinib in pediatric patients with neurofibromatosis type 1 (NF-1)-associated plexiform neurofibroma: a phase I/IIa study. J Clin Oncol. 2018;36(15 suppl):10504.
      61. Fisher MJ, et al. Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial. Nat Med. 2021;27:165-173.
      « Return to: Neuro-Oncology Updates: Insights on the Diagnosis and Management of Low-Grade Glioma, Glioblastoma, and NF1
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