Stereotactic Radiosurgery for Intracranial Metastases Michelle Alonso-Basanta, MD PhD Helene Blum Assistant Professor Chief, Central Nervous System Section Associate Chief of Clinical Operations Department of Radiation Oncology University of Pennsylvania May 13, 2016
Stereotactic Radiosurgery Brain: To deliver safe, high doses of radiation to a target with little to no normal tissue exposure Stereotactic Body Radiation Therapy Any treatment delivered to the body delivered in one to five fractions with image guidance Concept of precision, accuracy, imaging into the practice of radiotherapy in the body 2
General Principles of Radiation Biology Risk of long term side effects: Dose per fraction Location, location, location Size impact dose per fraction Histology plays a role in treatment response to dose per fraction 3
Indications Varied histologies and have evolved over years: Functional: essential tremors, OCD, trigeminal neuralgia Vascular: AVMs, AV fistulas Benign: Schwannoma, Meningiomas, Pituitary Adenomas Malignant Brain metastases Gliomas Meningiomas 4
History 1950s: Swedish professors: Lars Leksell, professor of neurosurgery at the Karolinska Institute in Stockholm Borje Larsson, radiation biologist of the Gustaf Werner Institute, Uppsala University Combining radiation beams with stereotactic (guiding) devices capable of pinpointing targets within the brain. 5
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Gamma Knife (GK) Specific for brain (and upper cervical spine as per company) Requires placement of frame (neurosurgery) Usually limited to one fraction 7
History 1975: potential of stereotactic radiosurgery for eliminating brain tumors, a second Gamma Knife installed at the Karolinska Institute 1987: Introduced in the United States at UPMC Presbyterian; 5 th in the world. 2007: Newest generation Gamma Knife unit, Perfexion, entered service at UPMC Presbyterian. 8
Perfexion 9
Courtesy of V. Wilson 10
Perfexion No helmet Rods of various sizes: 4mm, 8mm, 16mm Can block individual areas (sectors) without plugging 11
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Brain Metastases Post-WBRT Recurrence Boost Upfront Newly diagnosed Breast cancer Surgical Bed 14
So, what s the number. Overall survival for a number of studies - NO DIFFERENCE Volume?? Other factors? 15
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No difference in OS Median Survival (p > 0.05): 6.4 months after up-front GKS 6.5 months after GKS with WBRT 6.8 months after salvage GKS 20
Multi-variate Analysis for OS Presumed radiation necrosis: 5% No GKS-related mortality 21
What about upfront UPenn Data 38 cases of patients with no prior surgery or radiation 90% believed to have 1-3 metastases At time of procedure 4 or more metastases found SRS was done using Gamma Knife (Elekta) 22
Overall Survival OS: 6.8 months 23
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Salvage Median time to WBRT 10.3 months 27
Leptomeningeal disease: 13% Radiation Necrosis: 2% 28
Surgical Bed Radiation Whole Brain SRS alone 29
Current Open Trial 30
Penn Data 31
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18% Local Failure 33
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DIF: Median 7.3 months from GK 35
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Cyberknife (CK) For anywhere in the body (although originally designed for spine by a neurosurgeon) Undergone a number of evolutions as well Current model has robot couch, allows lung tracking as well as spine tracking Does not require placement of frame although for the majority of cases, fiducials are needed (exceptions spine, some lung) Limited to one to five fractions 40
X-ray Sources IMAGING SYSTEM Linear Accelerator ROBOTIC DELIVERY SYSTEM TARGETING SOFTWARE Manipulator Image Detectors Courtesy of J. Kolker 41
Indications Brain metastases Large cavities Meningiomas Larger grade I meningiomas Recurrent gliomas Prior radiation 42
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July 2013 September 2013 January 2014 April 2014 44
Brain Metastases: Surgical bed 3 other lesions 45
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Penn Data 49
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Freedom from Local Failure 24% 51
Freedom from Distant Failure 62% 52
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Brain Metastases: Breast 49 year old physician No evidence of disease Headaches 55
September 2011 56
October 2011 57
Brain Metastases: Breast Biopsy Breast adenocarcinoma Options? 58
November 2011 59
CK 60
CK 61
CK EOT 12/15/2011 62
August 2012 63
December 2015 64
Summary - Why is this important? Future direction: looking at Proton SRS comparisons Pros and Cons PENN has every possible modality of radiation to individualize treatment Choice is dependent on histology, location (like real estate!) and size We are not in a vacuum it requires a multi-disciplinary approach 65
Collaborators 2016 Radiation Oncology Physics/Dosimetry James Metz Robert A. Lustig Goldie Kurtz Jay F. Dorsey Alexander Lin Peter Ahn J. Nicholas Lukens James Kolker Suneel Nagda Geoffrey Geiger Neurosurgery M. Sean Grady John Y.K. Lee Donald O Rourke Steven Brem Timothy Lucas Eric Zager Neil Malhotra James Schuster Paul Marcotte 66
Collaborators 2016 NeuroRadiology Laurie Loevner Kim Learned Ron Wolf John Woo Suyash Mohan Linda Bagley Harish Poptani (London) Ragini Verma Christos Davatzikos NeuroInterventional Bryan Pukenas Robert W. Hurst NeuroOncology Arati Desai Otorhinolaryngology Bert O Malley James Palmer Jason Newman Nithin Adappa Christopher Rassekh David Kennedy Douglas Bigelow Michael Ruckenstein 67
Collaborators 2016 Neuro-Ophthalmology Grant Liu Madhura Tamhankar Neuropathology Maria Martinez-Lage Zissimos Mourelatos Neurology Amy Pruitt Raymond Price John Pollard Danielle Becker Neuropsychiatry Carol Armstrong Cardiology Douglas Jacoby Endocrinology Julia Kharlip Peter Snyder 68
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Thank You 70