Gamma Knife

A Team Approach to Treating Patients

George Bovis, MD Patrick Sweeney, MD Jagan Venkatesan, MS Matt White, MS

Illinois Gamma Knife Center Elk Grove Village, IL Disclosures

 Shareholders in IGKC Purpose

 Define Stereotactic Radiosurgery  Discuss specifics of Gamma Knife radiosurgery- 4c/Perfexion  Review clinical indications and our experience at the Illinois Gamma Knife Center  Discuss ‘competing’ indications for GKRS (Proton Beam Therapy) Stereotactic Radiosurgery  SINGLE FRACTION  High dose  Small volume  High conformality  Excludes sensitive structures  Exclusively CRANIAL  Exclusively FRAME- BASED OLD SCHOOL DEFINITION Stereotactic Radiation: 2014

 SABR (stereotactic ablative body RT)  SBRT (stereotactic body radiotherapy  SRT (stereotactic radiotherapy)  SRS (stereotactic radiosurgery) 1980s 1990s 2000s 2010s

Radiation 2-d 3-d CRT IMRT IGRT Therapy

Stereotactic Frame based Frame based Radiosurgery Relocatable frames

Gamma U series

Exclusively CRANIAL Frameless

CRANIAL, SPINE, LUNG, PROSTATE, LIVER, PANCREAS

Linac based We are all radiosurgeons now!

Varian True Beam Gamma Knife

 Lars Leksell Swedish Neurosurgeon  First developed Gamma Knife in 1968  Was a neurosurgical device that used radiation Stereotaxy

 Implies defining a point in space relative to a Cartesian coordinate system: FRAME  There are surgical instruments that use stereotaxis to locate targets in the body  In radiation therapy simulation and treatment we also use stereotaxis but it is relative to a CT-generated image: PATIENT Gamma Knife Radiosurgery

Only exclusively frame-based intracranial system that is still used today

All other radiosurgery systems are capable of frameless and extracranial indications The Leksell Patient frame

vs The Leksell Frame placement and Coordinate System History

 1951 Lars Leksell  Large Number of Converging Beams of Ionizing Radiation  Creating Small Volumes of Necrosis at Stereotactically Targeted Region of Brain History

 LINAC  Gamma Radiation  Protons  Stereotaxis  Target Visualization ◦ X-Ray ◦ Pneuomoencephalography ◦ History

 Cobalt-60 Unit  1967 Gamma Knife ◦ 179 Co-60 Sources ◦ Sophiahemmet Hospital  1974 Gamma Knife U – Unit ◦ 201 Co-60 Sources ◦ Karolinska Hospital History

 1970-1987  CT  MRI  Improved Stereotaxis with Computers  Better Understanding of Radiobiology History

 1968 – 1982  Treated 762 patients  Trigeminal Neuralgia  Acoustic Neuroma  AVM 

 Metastasis  Functional History

 1987 - First Gamma Knife installed in U.S., at the University of Pittsburgh ◦ Lunsford  1989 Mayo Clinic ◦ Coffey  Formalized And Methodical Study of GK SRS  Publication of Huge Body of Scientific Work Evolution

 Cobalt-60  201 Sources  Leksell Frame  Trunnion Mode  Collimator Size ◦ 4 mm, 8 mm, 14 mm, 18 mm ◦ Manually Mounted Evolution

 Computer Based Workstations  Planning Software  3D Dosimetry and Anatomical Imaging  Improved Conformality and Selectivity  Robotic Automatic Positioning System (APS) Evolution Evolution

 2002 – Elekta ◦ Next Generation of GK  2 Principles Would Not Change ◦ Converging Beams ◦ Frame  Goals For New Machine ◦ Best Dosimetry ◦ Best Radiation Protection ◦ Unlimited Cranial Reach ◦ Fully Robotic and Automated ◦ Outstanding Patient Comfort ◦ Ease of Treatment For Pt and Staff ◦ Maintain Relevance of Cumulative Worldwide Literature

The Anatomy of the Gamma Knife 4C

1 - Couch Support 4 - Shielding Door 7 - Shielding 2 - Patient Couch 5 - Beam Channel 8 - Helmet In Treatment 3 - Helmet 6 - Cobalt-60 Sources Position 9 - Sliding Cradle The Perfexion The Perfexion System

The Perfexion Couch

PerfeXion Shielding

Not Good Protection or Shielding

PerfeXion Jean Regis, et al “Radiosurgery With The World’s First Fully Robotized Leksell Gamma Knife PerfeXion in Clinical Use: A 200- Patient Prospective, Randomized, Controlled Comparison With The GK 4C”. 64 (2), Feb 2009

 33 % Reduction in Tx Time  30 % Reduction in Shots Used  Nearly All Cases Single Run  No Collisions  8.2 X Less XRT To Vertex  13 X Less XRT To Sternum  15 X Less XRT To Gonads PerfeXion STILL A Growth Area in Neurosurgery

 WBRT vs SRS/GK for Multiple Mets (# ?) ◦ Kalkanis, S, et al. Evidence-based clinical practice parameter guidelines for the treatment of patiens with metastatic brain tumors. J Neurooncology (2010) 96: 7-10. ◦ Robinson, P, et al. Methodology used to develop the AANS/CNS management of brain metastases evidence- based clinical practice parameter guidelines. J Neurooncology (2010) 96: 11-16. ◦ Gaspar, L, et al. The whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncology (2010) 96: 17-32. ◦ Kalkanis, S, et al. The role of surgical resection in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncology (2010) 96: 33-43.  Epilepsy (MTLE) ◦ NIH Study – Radiosurgery or Open for Epilepsy (ROSE), PI Nicholas Barbaro  Cluster Headache ◦ Kano, K, et al. Stereotactic radiosurgery for intractable cluster headache: an initial report from the North American Gamma Knife Consortium. J Neurosurgery. April 30, 2010  DBS vs SRS/GK for OCD, Depression PerfeXion

 “Gamma Knife Comes With Patients”  Direct Patient Requests  “Gold Standard”  Exercise In Efficiency  More Options For Your Patients  “Complete Brain

“A Pinpoint Beam Strays Invisibly, Harming Instead of Healing”

By Walt Bogdanich and Kristina Rebelo

December 28, 2010  http://www.nytimes.com/2010/12/29/he alth/29radiation.html?_r=1 PerfeXion Illinois Gamma Knife Center

 2005 ◦ 2 Neurosurgeons ◦ 2 Radiation Oncologists  2014 ◦ 8 Neurosurgeons ◦ 4 Radiation Oncologists Gamma Knife: Dosimetry

 SHOTS: spheres of dose  ‘Pack’ shots into irregular shaped targets  MRI/CT/Angio  Rarely contour  Never add a margin  Prescribe to 50% isodose line  Not concerned about inhomogeneity in the target ◦ MD/PD: maximum dose/Rx dose  Very concerned about Cleveland Clinic conformality: ◦ CI: volume of Rx isodose/ volume of target volume at Rx isodose level Linac-based SRS

 Circular collimators  mMLC  Dynamic arcs  IMRT

� Contour � Small margin � Homogenous dose distribution Gamma Knife Radiosurgery

Target

Isodose lines Gamma: Knife: A Team Approach Gamma Knife Process

 Outpatient  One day Imaging Planning Treatment  Treat to 7 pts/day  Stand-alone clinic: plan and treat patients/ consults/follow-ups The four basic steps on Tx Day

1. Head Frame Placement 2. Imagin g

3. Treatment 4. The planning Treatment Gamma Knife Advantages A Neurosurgeon’s perspective

Lower Risks Compared to Open Surgery Better Tolerared than Open Surgery Outpatient No Recovery Time Return to work in 1 day Very Accurate and Precise Treatment for previously inoperable brain tumors. Simple Procedure (when performed correctly) “A Fool With A Tool, Is Still a Fool” Pain-Free Gamma Knife treatment usually more cost-effective than Open Surgery. Clinical Indications

 Brain Metastasis   Vestibular Schwannomas  Trigeminal Neuralgia  Arteriovenous Malformations  Gliomas  Skull-Base Tumors  Pituitary Tumors  Other functional disorders ◦ OCD, Epilepsy, Tremors Our Experience…

Brain Metastasis  Most Common Indication  Ideal targets ◦ Round ◦ Non-infiltrating ◦ Easily Defined  Most common Tumor Types ◦ Breast ◦ Lung ◦ Melanoma ◦ Renal ◦ Colon Brain Metastasis

 Whole Brain RT becoming more controversial ◦ Especially in solitary metastasis  What is the maximum number of metastasis to treat? 5…10…15….. 53 yo female with multiple brain metastasis. Refused WBRT

Mets Plan 1 (6 Months) Mets Plan 2 (3 & 6 Months) Arteriovenous Malformations (AVM)  Abnormal collection of blood vessels bypassing the capillary system  Can occur in any part of the body  Symptoms are headache/seizures Arteriovenous Malformations (AVM)   New Data: Lancet, 383: 614- Natural History 621, 2014 ◦ 2-4 % Rate of Rupture per Year ◦ 10-20 % Mortality per Rupture ARUBA TRIAL (A randomised trial ◦ 30-50 % Major Neurological of unruptured brain AVM) ◦ Randomized patients with Morbidity per Rupture unruptured AVMs to medical mgmt alone versus some  Likelihood of rupture in intervention (surgery, lifetime embolization, SRS, combinations) ◦ Medical management alone is 105 – Age in Years superior to interventional therapy in the prevention of death or stroke ◦ 10% in medical mgmt had death or stroke vs. 30.7% in the intervention arm AVM visualized on MRI AVM with Angio & MRI 3D Model of the AVM AVM Case 1

Presentation @ Initial Consult

2 Years Post Gamma Knife AVM Case 2

Presentation 4 Years Post GK AVM Case 3

Presentation 1 Year Post GK Meningioma  Tumors that arise from the meninges  90-95% are benign  Many are asymptomatic and require no intervention  Surgery is primary treatment  SRS is reasonable for small, unresectable meningiomas

Meningioma Plan (1.5 Years) Trigeminal Neuralgia (TN)  Lancinating Pain in distribution of CN V  Unilateral  Relieved by medication  Normal exam ‘triggers’ Treatments: MVD, PSR, GKRS TN Plan Vestibular Schwannoma  Acoustic neuroma  Benign tumor of the vestibulochochlear nerve (CN 8)  3000 per year in US  Treatment options: ◦ observation ◦ Surgery ◦ SRS (GKRS) ◦ fSRT ◦ conventional RT  SRS has become prime treatment for these tumors Microsurgery Results

 Best Current Results Published By High Volume (Tumors < 3 cm) ◦ High Rate of Complete Rsxn ◦ Low Recurrence Rate ◦ High Rate of Normal / Near Normal CN 7 Function 85% ◦ Hearing Preservation ??? Depends on approach and Pre-Operative Hearing 12 - 80% Chance of Deafness / Hearing Loss Kaylie DM, Horgan MJ, Delashaw JB, McMenomey SO: A Meta-Analysis comparing outcomes of microsurgery and gamma knife radiosurgery. Laryngoscope 110:1850-1856, 2000. Pollock BE, Lunsford LD, Noren G: Vestibular-schwannoma management in the next century: a radiosurgical perspective. Neurosurgery 43:475-483 Sekhar LN, Gormley WB, Wright DC: The best treatment for vestibular schwannoma (acoustic neuroma): Microsurgery or radiosurgery? A J Otol 17:676-682, 1996 Gamma Knife Radiosurgery

 Frame Application  MRI with Gad  Planning  Treatment Gamma Knife Radiosurgery Advantages  Single Morning Session, Outpatient Treatment  No Recovery  No Post-Treatment Restrictions  Very Well Tolerated  “Highly Successful” ◦ Tumor Control 98% ◦ Facial Nerve Function Preserving 99% ◦ Hearing Preservation 60 - 80% Gamma Knife Radiosurgery Disadvantages / Risks

 “Tumor is still there!”  Adverse Radiation Effects ◦ 2%  Malignant Transformation ◦ 1 / 1,000  Infection ◦ 1 / 4,000  2 % Failure Rate Requiring Further Treatment  6 month – 3 years Latency of Response Gamma Knife Radiosurgery

 12 - 13 Gy to 50% Isodose  Maximal Dose 24 - 26 Gy  Keeping Median Cochlear Dose < 4 Gy Increases Chance of Hearing Preservation  Average: 12-15 Isocenters, Using 4mm, 8mm Collimators Gamma Knife Radiosurgery RESULTS Pollock BE, Driscoll CLW, Foote RL, Link MJ. Patient Outcomes After Vestibular Schwannoma Management: A Prospective Comparison of Microsurgical Resection and Stereotactic Radiosurgery. Neurosurgery 59 (1) July 2006: 77-85.

 Prospective Cohort Study of 82 Pts  All Tumors < 3 cm  82 Patients ◦ 46 GK SRS ◦ 36 Microsurgery Gamma Knife Radiosurgery RESULTS Pollock BE, Driscoll CLW, Foote RL, Link MJ. Patient Outcomes After Vestibular Schwannoma Management: A Prospective Comparison of Microsurgical Resection and Stereotactic Radiosurgery. Neurosurgery 59 (1) July 2006: 77-85.

CN 7 CN 7 CN 7 CN 8 CN 8 CN 8 Fx Fx Fx Fx Fx Fx

3 mo 1 yr Last 3 mo 1 yr Last GK 100 100 96 77 63 63 SRS Micro- 61 69 75 5 5 5 Surgery Gamma Knife Radiosurgery RESULTS

Presentation 12 Months Post GK Gamma Knife Radiosurgery RESULTS

Presentation 6 Months post GK 2 Years post GK Gamma Knife Radiosurgery RESULTS

GK 6mo 9mo 12mo 24mo Acoustic Neuromas A Radiosurgical Perspective of the Future

Microsurgery GK Radiosurgery

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0 1987 1990 1993 1996 1999 2002 2005 2010 2020 Vestibular Schwannomas

 GK SRS is very safe and effective treatment for Acoustic Neuromas  GK SRS compares favorably to Microsurgery for Preservation CN 7 and CN 8 Functions  GK SRS is Best for Tumors < 3 cm

GK for OCD…?!?

• 90 Gy to 50% isodose line (180 Gy) • Target is anterior limb of internal capsule • 4 shots in both right and left hemisphere • EXPERIMENTAL Obsessive Compulsive Disorder (OCD) 3D Model of an OCD Tx Pituitary tumors

 Keep the optic apparatus dose below 8 Gy with single fraction  If the tumor is abutting or too close to the optic apparatus- not a candidate for Gamma Knife  Small/ functional tumors > 5 mm from optic apparatus are excellent candidates for Gamma Knife  Macroadenomas/ Non- functional pituitary tumors: PBT or GK Pituitary Plan Protons vs. GKRS First Principles:

 Gamma Knife  PBT ◦ Intracranial ◦ Adherent to or close ◦ Above the foremen to critical structures magnum ◦ Large (> 3cm) ◦ < 3 cm ◦ Ill-defined ◦ Clearly imaged ◦ ‘lower skull base’ ◦ Away from critical structures (optic apparatus) Cavernous sinus meningioma Glomus vagale tumor

What about protons?  Brain metastasis NO  AVMs NO  Vestibular schwannoma NO (probably)  Trigeminal neuralgia NO  Pituitary tumors YES  Meningioma ◦ Large/involving optic apparatus YES ◦ Small/peripheral NO