Glioma Breakout Session. Chris McPherson, MD Neurosurgeon Dale Greene, RN Nurse ee Connie Wagenknecht Advanced Oncology Certified Nurse Practitioner

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1 Glioma Breakout Session Chris McPherson, MD Neurosurgeon Dale Greene, RN Nurse ee Connie Wagenknecht Advanced Oncology Certified Nurse Practitioner

2 WHAT IS A GLIOMA?

3 Glial Cells Glia = Glue (Greek) Glia = Support cells

4 Astrocyte - transport nutrients and hold neurons in place Glial Cell Types Oligodendrocyte - provide insulation (myelin) to neurons

5 WHAT DOES GLIOMA GRADE MEAN?

6 WHO Grade (World Health Organization) Grades tumors on a scale based on degree of malignancy Grade 1 = Pilocytic astrocytoma, Ganglioglioma, DNET Most Benign, slow growing Grade 2 = Low grade glioma, Astrocytoma and Oligodendroglioma Slow growing Potential for malignant transformation Grade 3 = Malignant Glioma, Anaplastic Astrocytoma and Anaplastic Oligodendroglioma Actively growing cells Invasive Grade 4 = Glioblastoma Rapidly growing cells Invasive

7 WHO Grade 2 Glioma - Astrocytoma WHO Grade 4 Glioma Glioblastoma

8 WHAT SYMPTOMS DO GLIOMAS CAUSE?

9 Seizures Seizures common for all glioma patients 50-90% low grade gliomas, 20-50% of GBM patients When to use anti-seizure medicine? Anyone having seizures Around the time of surgery Patients felt at higher risk for seizures Medications Certain medications affect chemotherapy Dilantin, not Keppra Weigh side effect risk vs. benefit Coming off seizure medicine For patients without seizures or without seizure for a period of time, can be considered Need to taper off and avoid driving during that time

10 Headache Headache common for glioma patients Steroids can be beneficial, but side effects are important consideration Pain medications as needed Relaxation techniques, alternative therapies can play a role

11 Other symptoms Based on specific location of tumor Frontal lobe difficulty with speech, concentration, memory, weakness Temporal lobe difficulty with speech, memory Parietal lobe weakness/numbness Occipital lobe vision Cerebellum balance, coordination, walking

12 WHAT CAUSES GLIOMAS?

13 Radiation increases risk Rare syndromes increase risk Lei Fraumani syndrome Neurofibromatosis Bottom line is, in most cases: We don t know! Ohio Brain Tumor Study Consortium of 4 major centers in Ohio University of Cincinnati Case Western Reserve Cleveland, Ohio Cleveland Clinic Cleveland, Ohio James Cancer Center Columbus, Ohio

14 ARE FAMILY MEMBERS WITH GLIOMA AT INCREASED RISK?

15 In the majority of cases No British Journal of Cancer 2001 Familial analysis of 432 patients with astrocytoma from Sweden 24 pts (5%) had 2 or more members of family with glioma, felt to be a familial tendency Compare to 10% of breast cancer and 20% of colon cancer are familial

16 A few familial syndromes known to increase risk Neurofibromatosis Lei Fraumeni syndrome In most cases, not familial

17 HOW LONG HAS MY TUMOR BEEN THERE?

18 Low Grade Gliomas Slow growth rate Can sit quietly for years before causing symptoms Malignant Gliomas (GBM) Primary GBM arises spontaneously and can grow quickly, weeks to months Secondary GBM arises from a low grade glioma and can be present for years Bottom line no way to know how long the tumor has been present

19 WHAT IS STANDARD TREATMENT FOR GLIOMAS?

20 Background: Treatment Options Surgery Radiation Chemotherapy

21 Low Grade Glioma Standard treatment Observation is an option for some tumors Surgery if possible, Functional preservation most important Biopsy for diagnosis if able Goal of total resection Role of radiation is controversial Delays time to progression Long term side effects, cognition and memory, development of other tumors Role of chemotherapy is controversial Long term side effects, development of other cancers, leukemia

22 Malignant Glioma / GBM Standard Treatment Stupp protocol Maximal surgical resection Radiation, 6 weeks of fractionated radiation Chemotherapy

23 Chemotherapy Options TEMODAR (2005) Damages DNA to kill tumor cells Newly diagnosed and recurrent AVASTIN (2009) Prevents blood vessels to starve the tumor Recurrent tumors only

24 Treatment of Recurrence All options are available Surgery with/without implants (wafers, seeds) Radiation / Radiosurgery Chemotherapy Temodar Avastin Clinical Trials

25 WHAT S NEW IN GLIOMA TREATMENT?

26 Tumor Markers Markers 1p/19q IDH-1 MGMT EGFRvIII Help guide treatment decisions

27 Tumor Genetics Utilize tumor s genes For treatment For diagnosis For follow-up

28 Genetics of Malignant Gliomas EGFRvIII Mutation Present in 30% GBM Mellinghoff et al. NEJM 2005; 353:

29 Genetics of Malignant Gliomas Dr. Bhassi s lab at UC developed a way to measure amount of circulating EGFRvIII mutations in the blood

30 Follow-up monitoring of treatment TUMOR RECURRENCE?

31 Vaccines Utilize the Human Immune System

32 Utilize the Human Immune System Vaccine Trials: 1) DC-Vax - Phase III trial for newly diagnosed glioblastoma 2) Celldex (ACT Study) - Phase III trial for newly diagnosed EGRFvIII mutated glioblastoma 3) Celldex (RE-ACT Study) - Phase II trial for recurrent EGFRvIII mutated glioblastoma

33 NovoCure Tumor Treating Fields Approved for Recurrent GBM Recently approved for newly diagnosed GBM

34 Individualized Approach to Treatment We analyze each patient s tumor and devise a treatment plan that is personalized: Patient A Patient B Patient C Genetic Target Vaccine Antibody Target

35 QUESTIONS?