Lecture by Dr. Mary Jane Lymphat on Molecular Markers in Glioma Management

Jul 16, 2024

Lecture by Dr. Mary Jane Lymphat on Molecular Markers in Glioma Management

Introduction

  • Dr. Mary Jane Lymphat: Neuro-oncologist at Odette Cancer Center and Sunnybrook Health Sciences, Clinical Investigator at the University of Toronto.
  • Clinical Interests:
    • Treating CNS tumors and neurological complications of cancer.
    • Treating young adult patients with gliomas.
  • Educational Background: Recent graduate of the Neuro-Oncology fellowship program at Massachusetts General Hospital, Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School.
  • Research Interest: Using large patient cohort data sets to study relationships between imaging, genetic biomarkers, and clinical outcomes in gliomas.
  • Recipient of a research grant from BTFC in 2021.

Presentation Overview

  • Focus on current use and impact of molecular and genomic markers in glioma clinical care.
  • Discussion on potential benefits and limitations of these markers.
  • Influence on management decisions for gliomas, particularly in young adults.
  • Emphasis on clinical applications and relevance in patient care.

Background on Brain Tumors

  • Primary Brain Tumors: Originate from cells within the brain.
  • Secondary Brain Tumors (Metastases): Originate from cancers elsewhere in the body.
  • Gliomas: Type of primary brain tumor, with Glioblastoma (GBM) being the most common and aggressive form.
  • GBM Incidence and Survival: Approximately 4.1 per 100,000 cases/year with poor overall survival.

Diagnostic Techniques and Challenges

  • Pre-2016 Diagnosis: Biopsy and microscopic examination were primary methods to diagnose and grade tumors (Grade 1-4 based on cell aggressiveness).
  • Limitations: Small tissue samples could lead to incorrect diagnosis; variability between pathologists.

Molecular Biomarkers

  • Revised Classification (2016): Incorporation of molecular or genetic markers to improve accuracy.
  • Advantages:
    • Confirm Diagnosis: Knowing the exact type of tumor.
    • Convey Prognosis: Indicating aggressiveness based on genetic changes.
    • Match Therapy: Aligning specific mutations with targeted treatments.
  • Common Molecular Techniques: Staining, chromosomal analysis, next-generation sequencing, methylation profiling.
  • Cost Considerations: Tests like Foundation One can cost $1,000-$2,000s per panel.

Key Glioma Biomarkers

  1. IDH Mutation:
    • IDH-Mutant Tumors: More indolent behavior.
    • IDH-Wild Type Tumors: More aggressive (e.g., Glioblastoma).
  2. 1p/19q Co-Deletion:
    • Identifies Oligodendroglioma, associated with better prognosis.
  3. MGMT Promoter Methylation:
    • Predicts response to treatments like Temozolomide and radiation.

Treatment and Advances

  • Impact of IDH Mutations and MGMT Status on treatment decisions.
  • IDH Inhibitors: Targeting IDH-mutant tumors, ongoing trials (e.g., Indigo Trial).
  • Challenges in Treatment:
    • Radiation/Chemotherapy: Side effects especially in young adults.
    • Targeted Therapy: Better tolerated, but requires more research and validation.

Molecular Markers in Glioblastoma (IDH Wild-Type)

  • GBM Characteristics: Larger and more aggressive on MRI, different treatment approach compared to other gliomas.
  • Revised Definition of GBM:
    • IDH-Wild Type: True Glioblastoma.
    • IDH-Mutant: Now called Grade 4 IDH Mutant Astrocytomas.
  • Advanced Treatment Protocols:
    • Radiation and Chemotherapy (Temozolomide).
    • MGMT status to guide treatment efficiency.

Challenges and Future Directions

  • Barriers: Blood-brain barrier, developing resistance to therapy, cost, and availability of molecular testing in Canada.
  • Innovative Approaches:
    • Focused Ultrasound: Opening blood-brain barrier for treatment delivery.
    • Adaptive Clinical Trials: Like GBM AGILE, aimed at rapid and efficient testing of new treatments.

Special Considerations for Young Adults

  • Biological Differences: Tumors in younger individuals behave differently than in older adults.
  • Clinical Trials and Specialized Support: Multidisciplinary approach, need for better representation in research.
  • Adolescent and Young Adult (AYA) CNS Oncology Consortium: Collaboration for case discussion and exploration of treatment options.

Conclusion

  • Molecular Testing: Crucial for accurate diagnosis and personalized treatment plans.
  • Patient Role: Participation in research can improve understanding and treatment of gliomas.
  • Advocacy: Importance of groups like BTFC in improving access to molecular testing and addressing disparities.

Questions and Answers

  • Temozolomide vs. PCB Chemotherapy: Variations due to lack of comparative clinical trials, provider preferences.
  • Impact of Chemotherapy: Monitoring necessary, benefit weighed against quality of life.
  • Molecular Testing Costs and Access: Challenges in the Canadian healthcare system.
  • Focus Ultrasound and Drug Delivery: Emerging technology, still under investigation.

Acknowledgments

  • BTFC for grant and support.
  • Patients and caregivers for their contributions to research.
  • CNS Oncology groups and collaborators for their ongoing efforts.