Stereotactic radiosurgery (SRS) uses precisely targeted beams of radiation from multiple angles to treat brain tumors with minimal damage to surrounding tissue. It can be delivered via linear accelerator, Gamma Knife, or Cyberknife. SRS provides high tumor control rates for both benign and malignant brain tumors with relatively low risk of side effects. While SRS alone may be sufficient to treat a limited number of brain metastases, whole brain radiation is often added to improve control of additional metastases. Neurosurgeons play an important role in patient selection and treatment planning for SRS.

1. Update: Stereotactic Radiosurgery (SRS)
for Brain Tumors
Herb Engelhard, M.D., Ph.D. The University of Illinois at Chicago
October, 2018
Includes images freely available on the Internet.

2. SRS – Brain tumors
• Important knowledge for your clinical practice!
• Types: Linear accelerator – based (LINAC) vs. Gamma Knife vs. Cyberknife
• All use stereotaxis and beams from multiple vantage points to deliver a precise and high dose of
radiation to a chosen target volume, with minimal damage to adjacent tissue.
• All in widespread use – but few head to head studies*.
• Made its debut in the late 1960s; widespread use in the 1990s with coupling to CT then MRI.
Resulted in a “paradigm shift” in the management of brain tumor patients.
• Proton Beam therapy (e.g. Mass General) is also a type of external beam radiation therapy,
which can be precisely targeted – not covered in this lecture.
• Unfortunately, precision alone is not the key for defeating glioblastoma, due to its
infiltrating nature.
J Neurosurg. 2016 Dec;125(Suppl 1):97-103.
Dosimetric characterization of hypofractionated Gamma Knife radiosurgery of large or complex
brain tumors versus linear accelerator-based treatments.
Dong P, Pérez-Andújar A, Pinnaduwage D, Braunstein S, Theodosopoulos P, McDermott M, Sneed P, Ma L.
*

3. Radiosurgery was
invented by the Swedish
neurosurgeon Lars
Leksell. For history, see
Wikipedia / references.
VARIAN
TrueBeam
(LINAC)
Gamma
Knife
Cyberknife
Devices for delivery

4. SRS for brain tumors: A multidisciplinary team
• Radiation oncologist, neurosurgeon,
radiation physicist, radiologist.
• With modern imaging, tissue diagnosis is
rarely required.
• Neurosurgeon’s role:
• Provide patients (patient selection),
• Educate patients about their options and the
advantages / disadvantages to each treatment
approach,
• Approve treatment plan,
• Apply frame if needed,
• Be present for the critical portion of treatment,
• Follow-up after the procedure, and long term.
 Patients (& families) are entitled to
information
 “Wow, we never knew …”
 Options and choices are important
 Often, there is not just one right answer
 Doctors should allow second opinions
 The bottom line: Follow the Golden Rule
Our philosophy ...
UNIVERSITY OF ILLINOIS - CHICAGO

5. SRS: Some fundamental principles
• Tumors that are resistant to fractionated
radiotherapy (e.g. melanoma) may respond well to
radiosurgery.
• In addition to tumors, SRS is effective for
functional disorders / pain (e.g. trigeminal
neuralgia) and AVMs. 75% of AVM vessels are
obliterated within 2-3 years.
• 3 cm diameter is a typical cut-off size for SRS.
• Beginning in 2003, SRS was performed more
frequently than craniotomy for brain tumors
other than meningioma (Lundsford et al., 2012).
Barnett GH, Linskey ME, Adler JR, et al.
Stereotactic radiosurgery—an organized
neurosurgery-sanctioned definition. J
Neurosurg 2007;106:1–5.

6. Very short wavelength
Very high energy
SRS:
Proton beam uses high-energy particles

7. • Fundamental principle: selective ionization of tissue, by means of high-
energy beams of radiation. In SRS, this destructive effect is precise.
• Ionization is the production of ions and free radicals which are extremely
damaging to cells.
• These produce irreparable damage to DNA, proteins, and lipids, resulting in
cell death (tissue necrosis).
• SRS with doses > 10 Gy per fraction, in addition to directly killing cells, also
cause vascular damage (proliferative vasculopathy) resulting in decreased
perfusion and indirect tumor cell death.
• The radiation dose is usually measured in gray - one gray (Gy) is the
absorption of one joule of energy per kilogram of mass.
• A unit that attempts to take into account both the different organs that are
irradiated and the type of radiation is the sievert (Sv), a unit that describes
both the amount of energy deposited and the biological effectiveness.
SRS: Mechanism of action / dose definition
Rat C6 glioma
1. Cytotoxic
2.Vascular

8. LINAC vs. Gamma Knife vs. Cyberknife
Gamma Knife
• Has traditionally required
placement of a frame.
• MRI scan is obtained after the frame is placed.
• Targeting is calculated using the placement of
“shots”, i.e. spheres of various sizes.
• Targeted area of patient is placed into the center of
the helmet (isocenter of 201 Cobalt-60 sources).
Patient may require repositioning.
• Probably has the most accuracy.
Cyberknife (Dr. John Adler)
• Imaging (with CT) and then treatment delivery is
performed in real time. Co-registration of CT and
MRI data prior to treatment.
• Minimal patient immobilization – no frame.
• Collimated small-diameter beams are delivered
using a linear accelerator attached to a highly
mobile robotic arm.
LINAC
• May be used with or without a head frame.
• Greatest flexibility – also may be used for standard
external beam radiation.
All: Outpatient procedure 
Initial accuracy in
1986 was < 0.5 mm,
making it comparable
to GK
#1: Sweden
1968

9. SRS in the pediatric age group
May require more sedation /
general anesthesia
craniopharyngioma
ependymoma
glioma
medulloblastoma
See Erin
Murphy et al
for review.
“Toxicities are not
insignificant …”

10. Beam collimation and targeting
Gamma Knife: Helmet
LINAC: Multileaf collimator (or cones)
UIC: leaflets are 0.5 cm
Classically in Gamma Knife, the target is brought to the center
of the 201 radioactive cobalt sources, while with LINAC, the
source of the beam is moved in arcs to focus the radiation dose.

11. Gamma Knife frame placement,
imaging, positioning

12. GK planning with “shots”
Involvement of neurosurgeon: entire process
– all day. Frame placement through frame
removal and instruction.
• GK by 2005: 350,000 treatments
• Has an 18,000 kg shield
Neurosurgeons can bill for their
SRS work – even if they don’t
place a frame.

13. UIC has LINAC
For our LINAC-based unit,
a head CT is obtained in the
radiation therapy suite with
the mask or frame in place,
then the MRI images are
co-registered with the CT
slices for dose planning.
See typical treatment plan
(distribute)
Representative unit

14. Normal Workflow
1. Neurosurgery consultation
2. Radiation oncology consultation
3. Planning MRI or PET
4. Simulation (CT) with mask (more convenient)
or frame (has to all be done one day but more
accurate)
5. Image fusion
6. Treatment planning
7. Plan approval
8. QA on plan – ensure no “collisions”
9. Treatment delivery
CT / MRI co-registration i.e. fusion

15. SRS: Treatment plan (LINAC)
Software: BrainLab
• Target volume(s)
• Dose
• Number of fractions (1, 3, 5) – if >5,
neurosurgery’s not involved!
• Fields, with gantry angle and collimator
• Structures, and relative doses
• Coordinates
• Isodose contours
• Dose – volume histograms
Includes:
Cyberknife planning is similar to LINAC, with
neurosurgeon confirming structures and target volume.
More and more, neurosurgeons are left out of this
process altogether, especially for brain metastases.
Utilizes multiple arcs
Avoid critical structures, e.g. brainstem, optic
apparatus, cochlea

16. Select the right treatment modality to fit each patient’s disease
Intensity Modulated SRS/SRT Composite SRSIntensity Modulated Arcs
Circular Arc Conformal Shaped BeamsCircular Arc multiple isocenter Dynamic Shaped Arcs
Thank you to Dr. Matthew
Koshy for providing
illustrations used in this
Powerpoint!

17. Safety – LINAC
Collision detection systems
Live view monitoring system / audio monitoring
Pre-treatment dry run
SRS – Risks
Vary according to tumor type / size / location, prior
radiation, and radiation dose given.
Acute (0-7 days), subacute (one week – 6 months),
and chronic (longer than 6 months).
SRS COMPLICATIONS
Acute: Rare. Nausea (2-11%), edema (2-
6%), seizures (2-6%). Rx: anti-emetics;
preop steroids; anti-convulsants.
Subacute: Alopecia (6%), “flare”
phenomenon (increase in apparent
tumor size from tumor necrosis).
Chronic: Radiation necrosis (dependent
on tumor diameter), secondary
neoplasm (extremely rare).

18. NO!
• Too big
• Symptoms /
IICP
• Dural tail
• (Need for
histology)

19. SRS – tumor indications and results
Dependent on referral patterns …
Most patients
can immediately
return to all
normal
activities.
Incidence of all pediatric cancers

20. SRS – Benign brain tumors
• SRS is performed frequently on benign brain tumors, and extensive
data is available for almost every tumor type.
• Generally considered to be safe and effective.
• The majority of the data in the literature pertains to Gamma Knife.
• Meningioma: SRS is highly effective, with reports of tumor control
rates at 10 years ranging from 67-100%, with minimal morbidity in
appropriately-selected patients. Overall toxicity: 8%
• Repeat radiosurgery may be possible for recurrent tumors.
• Pituitary adenoma series: 83-100% control. Acoustic schwannoma: 90
– 97% control. Hearing preservation: 80%. Yet controversy over
surgery vs. SRS continues.
UNIVERSITY OF ILLINOIS - CHICAGO
Meningioma
Schwannoma
Pituitary adenoma

21. Hiroyuki Nakamura, Hidefumi Jokura, Kou Takahashi, Nagatoshi
Boku, Atsuya Akabane and Takashi Yoshimoto
American Journal of Neuroradiology . September 2000, 21 (8) 1540-1546.
SRS: treatment response; dosage
Stopping growth is the victory –
often there will eventually be some regression.
“Marginal dose”
Meningioma: 12-15 Gy
Schwannoma: 12-13 Gy
Pituitary adenoma: 12-16 Gy
(Secretory: acromegaly, Cushing’s –
20-25 Gy.)
Cranial nerves usually tolerate 16-18 Gy
Need 2 mm from chiasm – tolerates <8 Gy
Brainstem: < 12 Gy
IF CLOSE: FRACTIONATE!
For fractionated SRS: Biologically equivalent dose equation
Five treatments of 6 Gy = 18 Gy in one dose
Three treatments of 7-9 Gy = 18 Gy in one dose
These are general
guidelines – please
see specific studies!

22. SRS – Malignant brain tumors
• SRS is performed frequently on malignant brain tumors, and extensive data is available for almost
every tumor histology.
• #1 brain tumor = brain met. > 200,000 patients per year in U.S. While locally invasive, mets
displace brain tissue – not as infiltrative as glioma.
• Mets: #1 diagnosis of patients receiving radiosurgery. High rate of local control and low risk of side
effects. Used alone or in conjunction with whole brain RT and/or surgery.
• Multiple studies since 1990 have evaluated WBRT vs. SRS vs. WBRT+SRS.
• “For patients with a limited number of brain metastases, there is no survival benefit for WBRT+SRS
compared with SRS alone”.
• “While the addition of WBRT to SRS improves local and distant control of metastases, patients
treated with SRS alone have better cognitive outcomes and a lower risk of late adverse effects.”
• Initial use of SRS alone may require salvage treatment such as repeat SRS, WBRT or surgery.
Lung
Breast
Kidney
GI
Melanoma
Many others

23. Grandhi R, Kondziolka D, Panczykowski D, Monaco EA 3rd, Kano H,
Niranjan A, Flickinger JC, Lunsford LD: Stereotactic radiosurgery using
the Leksell Gamma Knife Perfexion unit in the management of patients
with 10 or more brain metastases. J Neurosurg. 2012, 117:237–
45. 10.3171/2012.4.JNS11870
Case report: 47 mets (2015)
Too many to treat?
How many mets is too many? One!
More lesions =
more likely to
develop
additional lesions

24. SRS is an option for selected
patients with GBM.
2018
• Occurrence of new neoplasia (GBM) in
the SRS dose field has been reported.
Recurrence vs. radionecrosis
• Biopsy for enlarging lesions after SRS for brain mets
frequently reveals radiation necrosis (one study: 68% -
Narloch et al., 2017).
Citation: Moreau J, Khalil T, Dupic G, Chautard E, Lemaire J-J, Magnier F, et al. (2018) Second course
of stereotactic radiosurgery for locally recurrent brain metastases: Safety and efficacy. PLoS ONE 13(4):
e0195608. https://doi.org/10.1371/journal.pone.0195608

25. Final thoughts
Every neurosurgeon should be trained / familiar with SRS.
If we don’t keep involved, we will lose access to this important
treatment modality.
Excellent courses are available.
SRS indications are likely to continue to expand.
Sometimes, no option
is really that great ..