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P A C I F I C N E U R O . O R G
Surgical Clinical Trials for High Grade Gliomas
Achal Singh Achrol, M.D.
Chief, Glioma Surgery Program, John Wayne Cancer InstituteDirector, Neurovascular Surgery, Pacific Neuroscience Institute
Providence Saint John’s Health Center
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
OutlineHigh grade glioma and glioblastoma overview, standard therapies
Extent of surgical resection and fluorescence-guided surgery
Overview of neurosurgical trials in high grade glioma and glioblastoma
Current experience with intratumoral convection enhanced deliverytherapies at PNI and JWCI
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
IntroductionGlioblastoma is the most common primary brain tumor
Incidence highest in patients 45-55 years old – “prime of life”
Median survival 15 months with best current therapy involving surgery and chemoradiation (1-5% survive three years after diagnosis)
Hallmarks of tumor:Aggressive, infiltrative growth and vasogenic edemaNecrosisMicrovascular proliferation
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
Benefit of Complete Microsurgical Resection
1 - Stupp et al Lancet Oncology 2009 2 - Stummer et al Neurosurgery 2008
Consensus that maximal safe resection is goal even when full resection not possible is reflected across guidelines
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
Fluorescence-Guided Surgery (FGS)
Improved intraoperative visualization in real-time
Permits more extensive resection of malignant brain tumors with infiltrative biology
Permits safer resection of eloquent malignant brain tumors in combination with intraoperative motor and language mapping
Impacts overall survival and has potential to reduce neurologic deficits
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
GBM MGMT Methylation and Chemoradiation Response
Stupp et al Median OS MGMT-M 23.4 mos vs. MGMT-UM 12.6 mos
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
Summary of Current GBM TherapiesMicrosurgical resection is beneficial
Goal is maximum safe cytoreductionMolecular profiling of tissue for targeted therapy selection
Radiotherapy with concurrent and adjuvant Temozolomide is the standrd of care Maintenance Temozolomide x 6-12 months after RT
Bevacizumab can be used at 1st FailureNovo-TTF is approved for recurrent GBMConsider rechallenge with Temozolomide and Re-Irradiation (ERRT, SRS)Clinical Trials: Targeted Therapies, Immunotherapies, Intratumoral Therapies
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
Neurosurgical Trials in HGG and GBMBiological
Gene TherapyViral VectorsSynthetic Vectors
ImmunomodulationImmunotoxinsImmunostimulationCell-Based Immune Therapies
NonbiologicalChemotherapy
ImplantDevice-Assisted Infusion
ThermalNanoparticle-BasedStereotactic Laser
RadiationBrachytherapyNanoparticle Augmentation Photodynamic Therapy
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
Convection-Enhanced Delivery Experience at JWCI and PNI
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P A C I F I C N E U R O . O R G
Patient #1: Segmented Tumor and Clinical Target
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P A C I F I C N E U R O . O R G
Patient #1: Catheter Placement Plan
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P A C I F I C N E U R O . O R G
Patient #1: Pre‐Op IV Contrast vs. Intra‐op CED Distribution
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P A C I F I C N E U R O . O R G
Patient #2: Segmented Tumor and Clinical Target
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P A C I F I C N E U R O . O R G
Patient #2: Catheter Placement Plan
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P A C I F I C N E U R O . O R G
Patient #2: Pre‐Op IV Contrast vs. Intra‐op CED Distribution
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P A C I F I C N E U R O . O R G
Patient #3: Segmented Tumor and Clinical Target
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P A C I F I C N E U R O . O R G
Patient #3: Catheter Placement Plan
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P A C I F I C N E U R O . O R G
Patient #3: Catheter Placement Plan (CT hardware avoidance)
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P A C I F I C N E U R O . O R G
Patient #3: Pre‐Op IV Contrast vs. Intra‐op CED Distribution
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P A C I F I C N E U R O . O R G
Achal Singh Achrol M.D. [email protected]
SummaryNew treatment approaches are required for GBM involving maximizing surgical resection and targeting remaining infiltrative cancer cells due to high local recurrence
Use of adjuvant therapies will remain essential for providing tumor control and prevention of relapse
Other novel therapies such as immunotherapy and intratumoral convection-enhanced delivery will also play an important role in GBM management
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