Presidential Lecture Series Regis College, Weston, MA October 25, 2017 THE BRIGHAM AND WOMEN’S DEPARTMENT OF NEUROSURGERY (1913 -2017) Brain Cancer E. A. Chiocca, MD Ph. D Dept. of Neurological Surgery Institute for the Neurosciences Brigham and Women’s Hospital Surgical Neuro-oncology Dana Farber Cancer Institute Harvard Medical School Skull Base and Pituitary Center ED LAWS, MD TIM SMITH, MD Ph. D OSSAMA AL-MEFTY, MD IAN DUNN, MD Ph. D HASAN ZAIDI Research Faculty JAKUB GODLEWSKI, Ph. D AGNIESZKA BRONISZ, Ph. D Neurosurgical ICU BILL GORMLEY, SEAN LAWLER, Ph. D MD KHALID SHAH, Ph. D NATHALIE AGAR, Ph. D Cerebrovascular Center XIN WANG, Ph. D KAI FRERICHS, MD Ph. D FENG BEI, Ph. D ROSE DU, MD Ph. D ALI AZIZ-SULTAN, MD NIRAV PATEL, MD RAM CHAVALI, MD Spine Center MICHAEL GROFF, MD JOHN CHI, MD Ph. D Yi LU, MD Ph. D KURTUS DAFFORD, MD STEVEN SARIS, MD Functional NS REES COSGROVE, MD Neuro-oncological Surgery ALEXANDRA GOLBY, MD PHD ELIZABETH CLAUS, MD MPH PIERPAOLO PERUZZI, MD PHD TRACY ANSAY, MD
Cerebral Metastases and Primary Brain Tumor Incidence Proportion Expected Cases Expected Cerebral Mets Lung 20% 213, 380 42, 676 Melanoma 7% 59, 940 4, 196 Breast 5% 178, 480 8, 924 Renal 6. 5% 51, 190 3, 327 Colorectal 2% 153, 760 3, 075 62, 198 Primary Brain Tumor 20, 500
Glioblastoma
Behavioral and cognitive changes occupational disability and loss of independence Vision changes resulting in motor vehicle accident and riving restrictions Language Impairment with loss of ability to communicate All from the same tumor - Glioblastoma Let sided weakness resulting in increased independence and loss of ambulation
Glioblastoma Treatment • Gross Total Resection of Contrast-Enhancing area , if possible Stupp Regimen (External Limited Field Radiation and Concurrent Temozolomide followed by TMZ alone) • Gliadel, Avastin, Optune (TT Fields)- FDA approved
GROSS TOTAL RESECTION (GTR)
MOVIES?
Limited external field radiation (tumor cavity and 2 cm around it) + Temozolomide x 6 weeks Followed by Temozolomide for 6 months+
Glioblastoma always recurs December 2010 March 2011
GBM Recurrence • - More surgery Gliadel Avastin Laser Interstitial thermotherapy (LITT) Clinical Trial
Where do we go from here?
Ongoing/Planned Immunotherapy Strategies • • • Improved vaccines – Tetanus toxoid – Neovax, IMA 950 (Immatics) Hypofractionated RT + checkpoint inhibitors Checkpoint inhibitors with hypermutated tumors Combination of vaccines and checkpoint inhibitors – Neovax with pembrolizumab Combination of complementary immunotherapies – Ipilimumab (CTLA 4 Ab) + nivolumab (PD 1 Ab) – Anti-LAG and anti-CD 137 with nivolumab – IDO inhibitors + checkpoint inhibitors? – Gene/OV therapies + checkpoint inhibitors • • • Combination of checkpoint inhibitors and viral therapies – Multiple preclinical studies suggests antitumor effect of viral therapies augmented by combination with PD 1 antibodies, etc Combination of checkpoint inhibitors and antiangiogenic therapies – VEGF immunosuppressive – Anti-VEGF therapy may affect balance of M 1 and M 2 macrophages Combination of immunotherapies and targeted therapies – BRAF inhibitors with checkpoint inhibitors in melanoma – Two therapies not mutually exclusive
Gene- vs. Viral oncolytic-based therapy TK ADENOVIRAL VECTOR Ganciclovir GENETICALLY ENGINEERED VIRUS TK TK ICP 6 - Cell death GCV-P DNA damage No viral replication ICP 6 -
Clinical. Trials for Newly diagnosed GBM 1 - in situ injection of Adenoviral vector-TK (Ad-TK, GMCI) + valacyclovir (completed phase 2) for adults 2 - in situ injection of Adenoviral vector-TK (Ad-TK, GMCI) + valacyclovir + nivolumab (multi-institutional, starting) Clinical Trials for recurrent GBM 1 - in situ injection of Adenoviral vector- IL 12 (Ziopharm sponsor) (completed phase 1) 2 - in situ injection of oncolytic HSV 1 (Chiocca inventor/sponsor/PI) (accruing)
Prolonged Immune Surveillance! Patient Alive 8+ Years Post Surgery Small Anterior Temporal Lobectomy, Most Tumor Remained and Injected Increased Inflammation Pre-Op Continued Tumor Reduction Note ventricle increase Reduced Edema Tumor necrosis Complete Image Response Immediate Post-Op 3 months 6 months 12 months 24 months 36 months 60 months
THANK YOU!
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