First Edition

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CyberKnife Radiosurgery at St. Johns

• First Edition
• Release Date 7/8/2005
• Expiration Date 7/8/2008
• Sponsored by St. Johns Health System,
  Springfield, Missouri

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CyberKnife Radiosurgery at St. Johns
Continuing Medical Education (CME) Information

• Overview
• CyberKnife radiosurgery is a new and promising
  treatment for patients with a variety of tumors,
  pain syndromes or functional disorders. This
  presentation discusses the development of the
  CyberKnife, how it works, several of the
  important applications of its technology and
  clinical data to support its use.
• Description
• This CME activity includes
• PowerPoint Presentation
• CME Credit Registration Form with post-test
  examination evaluation
• The estimated time for completion is 35 minutes.
• Intended Audience
• This CME activity is intended for primary care
  physicians.

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CyberKnife Radiosurgery at St. Johns
Continuing Medical Education (CME) Information

• Learning Objectives
• After completing this CME activity, participants
  should be able to
• Review general principles of radiation treatment
  and radiosurgery.
• Describe CyberKnife technology and its resulting
  accuracy.
• List indications for using stereotactic
  radiosurgery in the brain and spine with outcomes
  data for treated patients.
• Recognize the limitations of stereotactic
  radiosurgery.
• Educational Need
• This CME program was developed to educate
  physicians on state of the art radiosurgical care
  of patients with neurosurgical diseases.

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CyberKnife Radiosurgery at St. Johns CME
Information

• Faculty Advisory Committee
• Alan M. Scarrow, MD, JD Bill
  Hennessey Teresa Shull
• St. Johns Clinic Neurosurgery
  Terry Nigh Alan Scarrow
• Co-Director, St. Johns Radiosurgery Center
  Eddie Spain
• Disclosure Policy
• It is the policy of the St. Johns CME Program
  to insure balance, independence, objectivity and
  scientific rigor in all its CME activities.
  Consistent with this policy, CME participants
  should be informed before the program begins
  when 1) the CME activity is receiving commercial
  support from a proprietary entity 2) potential
  conflict(s)-of-interest exist between the faculty
  and program content and/or with the proprietary
  entity providing commercial support to the CME
  activity 3) faculty intend to discuss
  information regarding unapproved/unlabeled
  commercial products during their presentation.
• The intent of this policy is to provide CME
  participants with information on which they can
  make their own judgments to determine whether a
  presentation has been influenced with regard to
  exposition or conclusion.

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CyberKnife Radiosurgery at St. Johns CME
Information

• Disclosures
• Dr. Scarrow and Advisory Committee members
  disclosed no significant relationship with
• the manufacturer or provider of any commercial
  product or service discussed in this
• presentation.
• Dr. Scarrow will not be presenting information
  regarding commercial products that are not
• FDA-approved (unlabeled) for the use under
  discussion or that are still investigational.
• This CME activity is funded by St. Johns Health
  System and is receiving no commercial
• support.
• Educational Disclaimer
• The primary purpose of this CME activity is
  education. The views and opinions expressed
• in this presentation are those of the
  participating faculty and do not constitute the
  opinion
• or endorsement of, or promotion by St. Johns
  Health System or its affiliates.
• It is intended to inform you about the knowledge,
  techniques and experiences of
• professionals who are willing to share such
  information with colleagues. Participants
• should use their personal and professional
  judgment when considering further application
• of this information, particularly as it may
  relate to patient diagnosis or treatment
  decisions

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CyberKnife Radiosurgery at St. Johns CME
Information

• Accreditation and CME Credit Designation
• ?St. Johns Health System is accredited by the
  Missouri State Medical Association to provide
  continuing medical education for physicians.
• This enduring CME activity has been planned and
  produced in accordance with the Accreditation
  Council for Continuing Medical Education
  Essentials.
• ?St. Johns Health System designates this
  educational activity for a maximum of 0.5
  Category 1 credit toward the AMA Physicians
  Recognition Award. Each physician should claim
  the amount of credit actually spent in the CME
  activity.
• For questions regarding program content or
  post-test questions contact
• Dr. Alan Scarrow [phone]

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CyberKnife Radiosurgery at St. Johns CME
Information

• Obtaining CME credit
• On the last slide of this presentation, click on
  the link to the CME Credit Registration
• Form Post Test and print the document.
• Print your full name and address.
• Complete the Post-test Examination placing
  your answers on the Post-Test
• Answers Section.
• Address the evaluation questions.
• Document the amount of time spent to
  complete this CME activity.
• Send the form to the St. Johns CME
  Office before the posted expiration
• date.
• If you have any questions regarding this process,
  please contact Teresa Shull at
• [phone] or e-mail at tshull_at_sprg.mercy.net
  .
• Grading of post-tests and processing of CME
  credit will be completed within
• 60 days upon receipt. A score of at least 70 is
  required to receive CME credit.

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CyberKnife Radiosurgery at St. Johns

• Alan Scarrow, M.D., J.D.
• Neurosurgery
• Co-Director, St. Johns Radiosurgery Center

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CyberKnife Radiosurgery

• CyberKnife
• What is a CyberKnife?
• How does it work?
• How is it different from other radiation devices?
  
• Is there evidence that it works?

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CyberKnife
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CyberKnife How is it different?

• Evolution of radiosurgery
• Stereotactic radiosurgery invented by Swedish
  neurosurgeon Dr. Lars Leksell in 1968

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CyberKnife How is it different?

• GammaKnife radiosurgery commercialized and
  utilized throughout the world during 70s, 80s,
  90s
• Butonly applicable for intracranial tumors since
  the brain is the only organ that can be
  immobilized
• Question How to apply similar principles of
  radiosurgery to the rest of the body?

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CyberKnife How is it different?

• Next step in evolution linear accelerator with
  intensity modulation useful both intracranial
  (with a head frame) and extracranial
• Better butprecision, accuracy and immobilization
  still a challenge outside the brain

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CyberKnife How is it different?

• Next step in evolution CyberKnife
• First and only radiosurgery device with patented
  real-time imaging coupled to radiation delivery
• CyberKnife winner of 2005 Most Promising New
  Product Award (Phoenix Medical Device
  Diagnostic Conference)

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CyberKnife How is it different?

• CyberKnife has linear accelerator mounted on
  robotic arm w/ infinite angles of radiation
  delivery vs. IMRT w/ only single plane delivery
  (a.k.a. isocenter delivery)
• vs.
• sphere disc

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CyberKnife How is it different?

• CyberKnife precision and accuracy
• Most accurate image guided radiosurgery system in
  the world total end to end clinical accuracy
  0.95 mm
• No need for frame to immobilize head

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CyberKnife How is it different?

• Attempts to replicate CyberKnife precision and
  accuracy (e.g. Novalis BrainLab)
• Do not monitor tumor movement (only chest
  movement)
• Internal tracking (CK) v. external tracking (NBL)
• Cannot make real-time adjustments in radiation
  delivery (CyberKnife patent)
• Must use head frame to deliver sufficient
  precision and accuracy intracranially

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CyberKnife Radiosurgery

• Radiosurgery
• What is radiosurgery?
• Misnomer? Oxymoron? Term of art?
• Traditional single session, precise delivery of
  a therapeutically effective radiation dose to an
  image defined target
• Expanded spatially accurate and highly conformal
  doses of radiation targeted at well defined
  structures with ablative intent
• Comparison to radiation therapy less concerned
  with targeting accuracy and anatomic precision
  normal tissues protected by dividing doses into
  multiple fractions separated by time to allow for
  recovery of normal tissues
• Shotgun vs. laser guided rifle
• Primum non nocere

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CyberKnife Process

• Patient selected for CyberKnife treatment
• ? pt brought in for history, physical, review of
  images
• ? fiducials placed close to tumor (except in
  brain where no fiducials are needed)
• ? CT or MRI of tumor and fiducials downloaded
  into CyberKnife
• ? treatment planning with tumor and critical
  structures outlined, dose determined
• ? treatment initiated w/tracking of fiducials
  during radiation delivery

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Clinical Evidence for Radiosurgery

• Most studies based on either GammaKnife or
  platform-based linear accelerator data
• Assumption that CyberKnife outcome data will be
  similar given the more precise and accurate means
  of delivering radiation to the tumor

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Types of Clinical Evidence

• Class I Prospective, randomized, controlled
  trials
• Class II Prospective studies (data collected
  prospectively) with retrospective analysis e.g.
  observational, cohort, case control studies
• Class III Retrospective studies (data collected
  retrospectively) e.g. clinical series,
  registries, case reviews, expert opinion

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CyberKnife Radiosurgery

• Which neurological diseases or conditions are
  responsive to CyberKnife radiosurgery?
• Tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Tremors
• Seizures
• Intractable pain
• Glaucoma

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Tumors

• Primary/metastatic
• Brain/spine
• Malignant/benign
• Primary therapy/adjunctive therapy
• Single treatment/staged treatment
• Therapeutic/palliative

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Adult Primary Brain Tumors

• Malignant
• Gliomas account for 30-40 of all supratentorial
  tumors
• Grade I and II well-differentiated astrocytomas
• Grade III anaplastic astrocytomas
• Grade IV glioblastoma multiforme (GBM) account
  for 50 of all gliomas
• Benign
• Meningiomas (16 of all supratentorial tumors)
• Acoustic neuromas
• Pituitary adenomas
• Jugular schwannomas

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Adult Malignant Brain Tumors

• GBM and Stereotactic Radiosurgery (SRS)
• 1 study w/ Class I evidence
• Entry criteria no prior rad or chemo, Karnofsky
  gt 60, life expect gt 3 mo, adequate BM reserves,
  acceptable renal and hepatic fxn, NL CXR, tumor
  diameter lt 40 mm
• Group 1 EBRT carmustine (BCNU) (80 pts)
• Group 2 SRS EBRT BCNU (80 pts)
• med. survival 13.6 mo no difference in survival,
  quality of life, cognitive function
• 4 cases of late radiation toxicity in Group 2

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Adult Malignant Brain Tumors

• GBM and SRS
• 1 study w/ Class III evidence
• Failed EBRT and/or chemo, Karnofsky gt 50, used
  with paclitaxel (Taxol)
• 88 pts
• Smaller tumor volumes with better survival

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Adult Malignant Brain Tumors

• GBM and SRS Summary
• Useful in selected cases
• Does not cure GBM
• Why is SRS not very effective for GBM?

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Adult Benign Brain Tumors

• Meningiomas
• Location, location, location, size
• Treatments observation, surgery, SRS

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Adult Benign Brain Tumors

• Meningiomas and SRS
• 2 studies w/ Class III evidence
• Study 1
• Entry criteria tumors lt3 cm diameter (untreated
  or residual following surgery) with exceptions
  for larger tumors in the elderly (100 pts)
• 5 yr follow up for tumors lt 3 cm 97 pts with
  controlled tumor growth tumors gt 3 cm with
  increased risk of radiation induced edema
• 4 of 23 pts with tumors gt 3 cm required repeat
  surgery to relieve persistent mass effect of
  radiation induced edema

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Adult Benign Brain Tumors

• Meningioma Study 2
• Entry criteria tumor volume lt 20 cm3 high
  surgical risk or advanced age or patient
  preference (50 pts)
• 14 mo follow up neuro exam improved, normal or
  unchanged in 43/50 pts tumor growth controlled
  in all but 1

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Adult Benign Brain Tumors

• Meningiomas and SRS Summary
• Some evidence to support controlled growth
• Useful for patients with
• Tumors adjacent or enmeshed with critical
  structures
• Significant medical morbidities
• Advanced age
• Aversion to surgery

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Adult Benign Brain Tumors

• Acoustic neuromas (AN)
• One of the original uses for SRS
• Well defined, circumscribed
• Fairly high operative morbidity

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Adult Benign Brain Tumors

• AN and SRS
• 1 Class II study (207 pts)
• Entry criteria acoustic neuroma
• Pts chose microsurgery (110 pts) v. SRS (97 pts)
• 4 yr follow up

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Adult Benign Brain Tumors

• Significantly lower morbidity w/ SRS
• Complaint s/p microsurgery s/p radiosurgery
• Facial palsy 47 0
• Loss of fnct. hear. 63 30
• Hemifacial spasm 27 3
• Tinnitus 40 50
• Hypesthesia 29 4
• No return to work 34 1

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Adult Benign Brain Tumors

• Class III data
• Some variation in upper limit of size (3-4 cm in
  diameter)
• Some variation in single shot v. staged SRS
• Tumor control rate gt90
• Low morbidity comparable to Class II data

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Adult Benign Brain Tumors

• AN and SRS Summary
• SRS preferable to microsurgery in many if not
  most cases due to lower morbidity
• Size is most common limiting factor for SRS (lt4
  cm diameter)
• Tumor control rates very good

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Adult Benign Brain Tumors

• Pituitary adenomas
• First line treatment usually medical or
  microsurgical
• SRS generally reserved for residual or recurrent
  tumor
• GH, ACTH, null cell, resistant PRL tumors

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Adult Benign Brain Tumors

• Pituitary adenomas and SRS
• 2 Class II trials abundant Class III data w/
  similar results
• Class II trial 1
• Entry criteria GH secreting tumors w/
  post-operative GH level gt 3 ng/mL and elevated
  IGF-1 or evidence of growing sellar mass (17 pts)
• Follow up 24 mo 14/17 with resolution of high GH
  levels, no tumor growth

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Adult Benign Brain Tumors

• Class II Trial 2
• Entry criteria hormone excess or local invasion
  s/p surgery and EBRT (21 pts 13 GH, 4 ACTH, 1
  PRL, 3 null cell)
• Median follow up 33 mo GH 12/13 w/ ? in disease
  activity 4/4 ACTH better clinically but w/
  continued ? ACTH PRL pt progressed despite SRS
  2/3 null cell tumors controlled
• No visual deficits

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Adult Benign Brain Tumors

• Pituitary adenoma and SRS summary
• SRS typically used as adjunct to microsurgical or
  medical treatment
• Particularly helpful in more difficult tumors
  such as GH and ACTH
• Low incidence of optic nerve injury

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Adult Benign Brain Tumors

• Jugular Foramen Tumors
• Paragangliomas (glomus tumors), schwannomas,
  meningiomas
• May present with pulsatile tinnitus, hearing
  loss, pain, or lower cranial nerve dysfunction
• 1 Class III study
• Entry criteria residual or newly diagnosed tumor
  (25 pts)

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Adult Benign Brain Tumors

• Jugular Foramen Tumors and SRS
• Median follow up 38.7 mo 11 pts w/ tumor
  shrinkage, 13 unchanged, 1 w/ slight increase
• 16 w/ improvement in neurological exam, 9 w/
  unchanged exam

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Adult Metastatic Tumors

• Brain Metastases
• Account for 20-30 of all supratentorial brain
  tumors most common brain tumor overall
• Most common metastatic tumors
• Sources lung 45, breast 10, renal 7, GI 6,
  melanoma 3
• Incidence testes 46, melanoma 40, lung 21,
  breast 9
• When imaged w/ MRI, the majority of pts present
  with gt 1 metastasis

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Adult Metastatic Tumors

• Brain metastases and SRS
• 2 studies with Class I evidence
• 3 studies with Class II evidence
• Many with Class III evidence

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Adult Metastatic Tumors

• Class I Study 1
• Entry criteria histologic confirmation of tumor
  type, all mets lt 25 mm diameter, pts w/ 2-4 mets
  on contrast MRI, Karnofsky score gt 70 (no
  surgery)
• Group 1 whole brain radiation therapy (WBRT) (14
  pts) Group 2 WBRT SRS (13 pts)
• Trial stopped at 27 mo follow up due to
  significant benefit in Group 2
• median survival Group 1-7.5 mo v. Group 2 -11 mo
• median time to local failure in Group 2-36 mo

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Adult Metastatic Tumors

• Class I study 2
• Entry criteria contrast MRI w/ 1-3 mets, max
  tumor diameter 4 cm with no other met gt 3 cm,
  Karnofsky gt 70, NL coagulation and blood count,
  no brain stem mets, no tumor within 1 cm of optic
  chiasm, no treatment of systemic cancer within 1
  mo of proposed SRS
• Group 1 WBRT (167 pts) Group 2 WBRT SRS (164
  pts)
• No significant survival difference for pts w/
  multiple mets
• Significant survival advantage in Group 2 for pts
  w/ single met, improved Karnofsky scores, ?
  steroid use
• 43 greater chance of developing recurrence in
  Group 1

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Adult Metastatic Tumors

• Class II and III studies
• Demonstrate shift in cause of death from brain
  mets to systemic disease
• Establish SRS dosing based on size of tumor
• Local control rate gt 90 at 1 yr follow up
• Smaller tumors with better control rate
• Improved functional outcome (KPS) and neurologic
  exam in pts treated with SRS
• Single met with better survival than multiple
• SRS effective with relatively radioresistant
  tumors such as melanoma, colon ca

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Adult Metastatic Tumors

• Brain metastases and SRS summary
• SRS important primary or adjunct treatment for
  pts w/ brain metastases
• SRS WBRT shown to have improved overall
  survival and functional capacity over WBRT alone
• Smaller and fewer mets associated with improved
  survival
• SRS shifts cause of death from brain mets to
  systemic disease

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Adult Metastatic Tumors

• Uveal melanoma
• SRS as alternative to enucleation
• 1 Class III study w/ 81 pts
• Median follow up 15 mo local control rate 87,
  tumor regression in 60, stabilization in 24,
  progression in 16
• Visual improvement in 15
• 10/12 pts with tumor progression underwent
  enucleation
• 10 pts w/ optic nerve damage, 11 w/ iris damage,
  4 w/ vitreous hemorrhage

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Adult Spine Tumors

• SRS and spine CyberKnife only territory
• Do not attempt this at home
• Useful for primary and metastatic, malignant and
  benign disease
• Question Will extracranial tumors respond to
  CyberKnife radiosurgery in a similar manner to
  intracranial tumors treated with traditional
  radiosurgical devices?

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Adult Spine Tumors

• Spine tumors and SRS
• 3 Class II studies (2 studies same pt group)
• 1 Class III study
• Class II studies 1 and 2
• Entry criteria pain or progressive neurological
  deficit, may have SRS as primary therapy or
  adjunct to EBRT or surgery, malignant or benign
  disease, Karnofsky gt 50, no overt spine
  instability, no neurologic deficit from bony
  compression (may have had compression from
  tumor), prior radiation treatments not exceeding
  maximum dose tolerance of spinal cord (125 pts)
• All pts treated with single dose radiosurgery

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Adult Spine Tumors

• Class II studies 1 and 2
• Median follow up 18 mo
• 74/79 pts w/ pain prior to treatment with
  significant relief
• 16/18 pts w/ myelopathy from tumor compression
  had improvement in symptoms
• 2/18 w/ myelopathy progressed to complete
  paraplegia
• No radiation myelopathy at 27 mo follow up

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Adult Spine Tumors

• Class II study 3
• benign spine lesions only (neurofibroma,
  paraganglioma, schwannoma, meningioma, spinal
  chordoma, hemangioma
• Entry criteria no overt instability or
  neurologic deficit from bony compression, prior
  radiation did not exceed tolerance of spinal cord
  (15 pts)
• All pts w/ single treatment
• All pts w/ pain prior to treatment pain free at 1
  mo follow up

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Adult Spine Tumors

• Class III study
• 10 tumors (5 mets, 2 schwannomas, 1
  hemangioblastoma, 1 meningioma, 1 chordoma), 6
  vascular malformations
• Treated in 1-5 staged radiosurgical treatments
• Follow up 3-48 mo local tumor control in 6/10

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Adult Spine Tumors

• Spine tumors and SRS summary
• CyberKnife has gained acceptance as a primary or
  adjunct treatment for all types of spine tumors
• May be used in malignant and benign disease
• Excellent treatment for pain due to bony or
  neural compression
• Neurologic symptoms due to tumor compression no
  bar to treatment
• Thus fartumors outside of the brain seem to
  respond to CyberKnife SRS in a manner similar to
  those in the brain

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Intractable Cancer Pain

• Often due to bony metastases
• We respect and value the dignity of each human
  life at all stages of development and conditions.
  We seek to promote good health and well-being
  while at the same time strive to relieve
  suffering and address its causes. We believe this
  service is an opportunity for all involved to
  come to a deeper understanding of the true
  meaning and gift of life.
• Primum non nocere

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Intractable Cancer Pain

• 1 Class II study
• Entry criteria pain related to bony metastases,
  Karnofsky gt 40, all prior pain treatments
  inadequate except morphine, no prior brain
  radiation (9 pts)
• Some Class III evidence

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Intractable Cancer Pain

• SRS treatment of entire pituitary w/160 Gy
• Follow up 1-24 mo all pts pain free within first
  few days following treatment
• No hormonal dysfunction
• Mechanism? Possible release of endorphins
  mimicking action of morphine

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Summary SRS for Brain and Spine Tumors

• CyberKnife SRS useful in both brain and spine
  tumors
• Malignant and benign disease including
  radioresistant tumors
• Increases mean survival in many cases and halts
  tumor progression in others
• Excellent at relieving pain from bone metastases
  or neural compression
• Useful as primary therapy or as adjunct to
  chemotherapy, EBRT or surgery

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Accessing the CyberKnife

• Physician referral to St. Johns Radiosurgery
  Center
• CK intake form with short pt vignette and most
  recent radiographic images (XR, CT, MRI, or PET)
• Review of each case by team of radiation
  oncologist and surgeon
• Notification to referring MD

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CyberKnife Patient Care Package

• Total pt care package
• Outpatient treatments
• Branson shows, golf, fish, fine dining

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CyberKnife Radiosurgery at St. Johns CME
Credit Documents

• In order to receive CME credit, please use your
  mouse pointer and left click on the link below.
  When the document is opened, print the document,
  complete the information and return it to the
  address listed on the form. Thank you for
  participating.
• Link CME Form Post Test - CyberKnife
  Radiosurgery at St. John's