Radiation oncology Stereotactic Radiosurgery, Stereotactic Radiotherapy of Central Nervous System Tumours

1. SRS, SRT, SBRT for CNS
tumours
Moderator
Prof. Rakesh Kapoor
Dr. Namrata Das
4th semester, Junior Resident
Department of Radiotherapy

2. Definition
Stereotaxis:
Greek word stereo (3-D approach)+taxis (tactile -
touch), i.e. ordered in 3-dimensions
Concept:
Stereotaxy is a minimally-invasive form of surgical
intervention which makes use of three-dimensional
coordinate system to:
• locate small targets inside the body
• to perform on them some action such as ablation
(removal), biopsy, injection, stimulation,
implantation, radiosurgery etc.

3. Stereotactic Biopsy/
injection/stimulation
Stereotactic Radiosurgery/
Radiotherapy

4. Stereotactic irradiation
Stereotactic irradiation refers to irradiation technique that:
• uses computer calculated 3-dimensional coordinates
• to deliver a prescribed dose of ionizing radiation, using multiple non-
coplanar photon radiation beams (LINAC) or radiation from multiple
Co-60 source (Gamma knife) with extreme precision
• To stereotactically localized lesions, primarily in the brain
Stereotactic techniques were initially attempted in the CNS
but now are used for other sites in the body

5. Stereotactic radiosurgery (SRS) and stereotactic radiotherapy
(SRT) are techniques to administer precisely directed, high-
dose radiation that tightly conforms to an intracranial target
to create a desired radiobiological response while minimizing
dose to the normal tissue.
Stereotactic body radiotherapy (SBRT) is a radiation
technique that utilizes precisely targeted radiation to a
tumour in a single or limited sessions in extracranial sites
while minimizing dose to normal tissue.
Definition

6. Stereotactic radiosurgery (SRS)
• intracranial lesion is stereotactically defined using a rigid frame (type of
EBRT, not a surgery)
• high dose per fraction is delivered (type of usually more than 10 Gy)
• usually treated in a single session (single day discharge)
• can be up to 4 fractions but fractionated SRS (fSRS) a more accurate term
• 4 Rs of radiobiology do not apply
Stereotactic radiotherapy (SRT)
Delivering dose in multiple fractions (more than or equal to 5) to
sterotactically localized target using relocatable frames
Stereotactic Radiosurgery (SRS)
Stereotactic Radiotherapy (SRT)
Stereotactic Body Radiotherapy (SBRT)
CRANIAL SITE
SPINE, EXTRA-CRANIAL
SITE

7. Radiobiological basis of SRS/SRT
• Vascular mediated mechanism for SRS/SBRT
• Radio-immunology of ablative radiation
• Opposite of traditional radiotherapy by conventional fractionation which
treats broad areas of normal and diseased tissue to uniform doses
• Ablative doses to only the diseased tissue in a single (or limited)
treatment sparing the normal healthy tissue

8. Low dose, fractionated radiotherapy:
• Cell death from radiation induced DNA
damage
• Radiosensitive, oxygenated cells
preferentially killed, allowing reperfusion
and reoxygenation of hypoxic cells
High dose radiotherapy:
• Tumour cell death secondary to
ischemia
• Endothelial cell death leads to
tumour starvation
Vascular mediated mechanism for SRS/SBRT

9. HIGH DOSE PER
FRACTION
Endothelial cell ASM (Acid
sphingomyelinase)
translocated to outer leaflet
of cell membrane
Sphingomyelin
hydrolysed to ceramide
Window of radiation doses for ceramide mediated
death starts at 8-10 Gy and peaks at 10-25 Gy

10. • Intact immune system necessary for efficient tumour control
• Multiple retrospective studies have shown poor clinical outcome in
immunocompromised patients after radiation
Radio-immunology of ablative radiation
Proposed mechanism of
immunological response following
high dose per fraction radiation
Studies suggest that RT can generate
an autologous in situ tumour vaccine
and induce anti-tumoral immunity
that contributes to higher local control
rates when ablative RT doses given
Basis for newer studies combining
SABR/SRS with immunotherapy

11. Radio-immunology of ablative radiation

12. Rationale for Fractionated SRS and single SRS approaches
Orange: Target lesion
Red: 100% isodose
Light blue: 80% isodose
impinging on brainstem
• BED2 for single fraction (15
Gy/#) plan is higher (84Gy)
versus fractionated (5 Gy/5#)
• Treating in 5 fractions yields
similar tumour control (BED10
= 37.5 in both)
• Treating in a single session
with 12 Gy yields same
normal tissue toxicity but with
lower tumour control
BRAINSTEM

13. SRS SRT
Target ≤ 3cm lesions lesions >3cm
Safety margins Treatment volume same as
target volume
Treatment volume larger
than target volume
No. of fractions 1-5 (usually single) More than or equal to 6
(fractionated)
Immobilization device Uses a rigid stereotactic
head or body frame
Uses a repositionable
stereotactic mask or body
mold
Optimal dose Very high dose delivered
during one treatment session
Moderate “fractions” of
the complete high dose
delivered over multiple
treatment sessions
Differences between SRS and SRT

14. Rationale of SRS/SRT in CNS tumours
• CNS tumour treatment pose unique problems:
• chemo/ immuno therapy → blood brain barrier
• invasive brain surgery → high Risk
• non-invasive radiotherapy → too non-specific
• Stereotactic irradiation was introduced in 1952 by a neurosurgeon using
pre-existing stereotactic neurosurgery frames to decrease the morbidity
of open procedures
“The tools used by the surgeon must be adapted to the task – and where the human brain is concerned they
cannot be too refined.”
-Professor Lars Leksell (1907-1986)

15. Tumour volume: As size increases, normal tissue radiation increases
RTOG dose escalation study of cerebral metastasis, recommended marginal
doses were:
• 24 Gy: <2Gy
• 18 Gy: 2 to 3 cm
• 15 Gy: 3 to 4 cm
• Not recommended for lesions more than 4 cm
Proximity to cranial nerves: Cranial nerves II and VIII most sensitive and SRS
avoided if dose > 10 Gy delivered
Rationale of SRS/SRT in CNS tumours

16. Location of lesion: Fractionated RT preferred for treatment of lesions in
deep gray matter or brainstem
Neurocognitive function:
• SRS preferred over whole brain RT for focal intracranial lesions – less
NCF decline
• There is inevitable spillage of radiation in SRS too. Therefore for larger
lesions or patients who undergo multiple rounds of SRS, higher risk of
NCF decline
Rationale of SRS/SRT in CNS tumours

17. Key Requirements for optimal stereotactic
irradiation
Requirement Rationale
Small target/treatment volume Reducing the volume of normal and target tissue
improves tolerance
Sharply defined target Sharply defined targets can be treated with little or no
extra margin of surrounding normal tissue and/or
without unintentional underdosage of the target
(marginal miss)
Accurate radiation delivery No margin of normal tissue needed for set up error
and/or reduced chance of underdosing target
High conformality Reduces the treatment volume to match the target
volume
Sensitive structures excluded from target Dose-limiting structures )optic chiasm, spinal cord etc.)
should be able to be defined and excluded from the
target volume to limit the risk of radiation injury

18. History
Discovery of X Rays (1895), Radioactivity
(1896)
- Clinical use of ionizing radiation to cure
cancer
Advances in neurosurgery and the
invention of stereotactic frames
Lars Leskell and the invention of
Radiosurgery

19. (a) Elekta gamma knife with
converging beams in original U
model helmet
(b) Original Leskell Gamma unit
First Linear Accelerator based SRS

20. Physics of Radiosurgery
“SRS is a single fraction radiation therapy procedure for treating
intracranial lesions using a combination of a stereotactic apparatus and
narrow multiple beams delivered through noncoplanar isocentric arcs.”
-Faiz M Khan, The Physics of Radiation Therapy
Principle:
• Precisely locate the target stereo tactically using special frames
• Hold the target still
• Accurately aim the radiation beam
• Shape the radiation beam to the target
• Deliver a radiation dose that damages abnormal cells yet sparing
normal cells

21. Major advances in stereotactic
localization, noninvasive
neuroimaging, and radiation physics
made it possible to selectively
irradiate a sharply defined target,
largely sparing the surrounding
normal tissue. This approach, called
stereotactic radiosurgery (SRS), is
achieved by focusing multiple
radiation beams on the tumor tissue
from different directions

22. Characteristics
Characteristics of stereotactic irradiation are as follows :
• High doses of the order of 10-15 Gy are delivered to target volume to achieve better tumor
control
• High degree of dose conformity
• PTVs are small & range from 1-35cm3 so that
• Less irradiation of normal tissue
• Less morbidity
• With requirement for
• positional accuracy +/- 1mm
• dose delivery accuracy +/- 5%

23. Different machines for delivering SRS/SRT
1. Gamma knife, Rotating
Gamma Systen (RGS): Co-60
gamma rays
2. Cyberknife

24. 3. Modified Linear Accelerator/
Tomotherapy
4. Charged particles
Different machines for delivering SRS/SRT

25. SRS Techniques
Leskell Gamma Knife Radiosurgery
• 1st Gamma unit was developed
in 1968 by Leksell at Karolinska
institute, Stockholm.
• Gamma radiation from Cobalt-60
Source
• Targeting precision of within 0.2
mm
• Multiple targets can be easily
treated in one session

26. COMPONENTS:
• A radiation unit with an upper
hemispherical shield (central
body)
• Lower half of hemisphere has a
shielding door
• An operating table & sliding
cradle
• A control unit
• Planning system
Leskell Gamma Knife Radiosurgery

27. • Source:
Perfexion model: 192 Cobalt 60
sources distributed in 8 sectors
• Dimension: 2 cm height, 1 mm
diameter
• Housed in hemisphere called
Central body
• Shield: 18000 kgs surrounding the
hemispherical array of Co60
sources
Leskell Gamma Knife Radiosurgery

28. Leskell Gamma Knife Radiosurgery
• Collimation helmets: 4, 8, 16
mm diameter
• Depth helmet: Confirms the
position of head ring on
patients head

29. Treatment components
• Position stabilization (attachment of a frame or frameless)
• Imaging for localization (CT, MRI, angiography, PET etc.)
• Computer assisted tumour localization (i.e., “image guidance”)
• Treatment planning – number of isocentres, number, placement and
length of arcs or angles, number of beams, beam size and weight etc.
• Isodose distributions, dosage prescription and calculation
• Simulation of prescribed arcs or fixed portals
• Radiation treatment delivery

31. SRS/SRT team
•Radiation Oncologist
•Neurosurgeon
•Medical Physicist
•Neuro-Radiologist
•Neuro-Anesthesiologist
•Neuro-Oncology Nurse
•Radiation Therapy Technologist

32. Frame Fixation
SRS frames
Leksell frame in Gamma Knife
BRW (Brown-Roberts-Wells) & CRW (Cosman-Roberts-Wells) in
X-Knife
Relocatable frames for fractionated stereotactic irradiation (SRT)
GTC (Gill-Thomas-Cosman)
• helps us in defining the images in a coordinate
• system - fiducial points: accurate positioning of the patient at the time of
• treatment

33. Frame Fixation
To check whether
frame will cover area of
interest
60 year old F, pituitary adenoma

34. Diagnostic Imaging
• CT or MRI can be used
MRI (preferred)
• Requires MRI compatible localization
box.
• scans directly in axial, saggital, coronal
or oblique planes
• Better imaging of soft tissue tumors.
• Can assess neural invasion
Angiography for AVM

35. Image Transfer
Networking
- Local area networking (LAN)
PACS
- to Gamma plan
- to X-plan
• Magneto Optical disc
• DAC tape
• Film scanner
• CT, MR film

36. Depth Helmet
• The Depth Helmet provides quantitative
quality assurance for relocatable head rings
(GTC).
• Checks that head ring has not moved b/w CT
scanning & treatment delivery.
• confirms that head rings have been
accurately repositioned on patient prior to
each SRT treatment.
• A Depth Probe with millimeter scale passed
into the guide tubes on the helmet to
measure distance from the hole to the
patient's head with millimeter accuracy.
• This measurement data provides a
permanent and precise record of positional
accuracy for every treatment

37. Depth Helmet

38. Treatment Planning
• Defining isocenter
• Dose prescription
• Plan Evaluation
• QA & Set up

39. Treatment Planning
Target vol. is encompassed by
70% to 90% isodose while using
single isocenter.
Entire treatment volume
encompassed by 50% isodose
curve while using multiple
isocenters
• For better dose conformity
• For reduced dose to normal
tissue

40. Treatment Planning
• Delineation of target and critical
structures
• Prescription of dose: 12 Gy at 50
% isodose
Safety Limits
Cochlea 7.4 Gy
Brainstem 12 Gy
Optic Pathway 8 Gy
CN VII < 14 Gy
CN VIII < 12 Gy

41. Treatment Planning
Techniques of plan evaluation
• Display of isodose lines over target volume
• Display of 3-D dose shells
• Display of DVHs
Radiation oncologists approve the plan

42. Set up and Treatment

45. Linear Accelerator Based
Radiosurgery
4 or 6MV LINACS with tight mechanical and electrical
tolerances, are modified for radio surgery
• A remotely controlled motorized couch
• Tertiary collimation that brings collimator closer to the
surface
• to reduce geometric penumbra ( inversely proportional
to SDD)
Tertiary collimation is either :
• Cone based
• Micro MLC based

46. CONE BASED
Highly collimated narrow
beams defined by
• 15 cm long circular cones
made of Cerrobend Lead,
encased in stainless steel.
• The cones are mounted
below X-ray jaws
• A range of cones with dia.
from 5mm to 40mm in steps
of 2.5mm are used for SRS
lesions

47. MICRO MLC BASED
Used for small irregular field
SRS/SRT
- for greater conformity & efficiency
than circular collimators
• Computer controlled motorized
leaves
• Number of Leaves : 52 (26 pair)
• Field Size (max): 10 cm x 10 cm
• Leaf Width at Isocenter: 2.5 mm at
isocenter

48. Cyber Knife
Three key components:
• Advanced light weight LINAC
(High energy 6 MV beam)
• Robotic arm pointing LINAC
beam from wide variety of
angles
• Several X-ray cameras
combined with powerful
software to track patient
position

49. • Uses complex system of cameras, motion tracking softwares,
fibreoptic sensing technology & Infra red emitters
• Records breathing movement with sequential X-ray images of
implanted radio-opaque markers 3-4 mm long

50. Robot precisely follows moving tumour to deliver radiation to desired
target

51. Advantages
• Procedure painless, no anaesthesia,
completed in 30-90 min, immediate
recovery
• Appropriate for many patients
otherwise diagnosed as inoperable
• No invasive head frame or other
rigid immobilization device is
required
• The ability to perform radiosurgery
(1-5 fractions) on targets
throughout the body, not just the
brain
Disadvantages
• More time consuming
• Requires placement of fiducials

52. Clinical uses of SRS and SRT
Arteriovenous
malformations (AVM)
Benign brain tumors
• Acoustic neuromas
• Meningiomas
• Pineal & pituitary
tumors
Malignant brain tumors including
Gliomas
Astrocytomas
Metastatic brain tumors
Functional disorders
Intractable Pain
Trigeminal Neuralgia
Psychiatric Diseases
Parkinson’s Disease and Epilepsy

53. PGI Experience
YEAR Meningio
ma
Schwanno
ma
AVM Pituitary
adenoma
Trigeminal
Neuralgia
Cavernous
Lesion
Glomus
Lesion
Jugular
SOL
Total
2016 67 65 52 38 15 12 8 2 271
2015 62 44 44 34 22 7 6 - 223

54. Site Dose
Trigeminal neuralgia 80 – 90 Gy single shot at 7-8 mm anterior to emergence
of nerve. Repeat GK if good response to first GK with at
least 3 years
Pituitary adenoma Non secretory: 12 – 17 Gy
Secretory: 20 – 28 Gy
Meningioma 10- 20 Gy
Schwannoma Virgin Lesion: 11- 13 Gy
Recurrent after 3 years if GK/EBRT: 10 – 12 Gy
AVM 23 – 25 Gy at margins, assess response at 2 years
Retreatment for residual lesion, <1cc: 22-24 Gy
3.5 – 8 cc: 19 – 32 Gy
8 – 13 cc: 18 – 20 Gy
Metastasis > 20 mm: 22 – 25 Gy
< 20 mm: 25 – 30 Gy
Prior EBRT> 16 – 20 Gy
Glial tumour Low grade: 15 – 17 Gy
High grade: < 3 cm, unifocal: 7 – 10 Gy
PGI Experience

55. SRS for brain metastasis
Brain metastasis are the most common intracranial malignancy
Indications:
1. Single brain metastasis:
Accessible site: Surgery followed by WBRT/SRS
Inaccessible site: SRS is an alternative but all studies are comparisons of
WBRT followed by SRS boost versus surgery

56. SRS for brain metastasis
2. Multiple brain metastasis:
1) Limited number of tumours, all < 3 cm
2) High tumour burden or multiple large tumours

57. 2. Dose:
• < 2 cm: 22-25 Gy
• > 2 cm: 25-30 Gy
• Prior EBRT: 16-20 Gy
3. Local Control: 1 yr LC: 70-80%
4. Side effects:
• Acute: nausea, dizziness, vomiting
• Late: radiation necrosis, optic neuropathy
SRS for brain metastasis

58. SRS for Pituitary adenoma
Multiple treatment options available: medical therapy, microscopic or
endoscopic trans-sphenoidal surgery, radiosurgery, radiation therapy, or
observation.
1. Indication:
Stereotactic radiosurgery (SRS) is usually indicated for:
(1) incomplete surgical resections that leave residual tumor
(2) tumor recurrence
(3) cases in which medical therapy provides inadequate hormone
control.

59. SRS for Pituitary adenoma
Study Mean
Dose
Tumour
control
Hormonal
control
Visual
field
defects
Induced
hypopituitaris
m
Zhang et al
n=79
31.3
Gy
92% 96% One None
Izawa et al
n=56
23.8
Gy
93.6% 30.3%
cure
80.3%
imp.
One None
2. Dose:
- functioning: 12 – 17 Gy
- non-functioning: 13 - 15 Gy
3. Results:

60. 4. Side effects:
- hypothalamic, hypopituitarism
- Cranial neuropathy

61. SRS for glial tumours
1. Indications:
• unresectable LGG such as pilocytic astrocytoma, selected
oligodendrogliomas
• salvage therapy in patients with recurrent or residual glial tumors.
2. Dose:
Due to the possibility of adverse radiation effects (ARE) after repeated
fractionated radiation therapy, SRS is often used to boost the tumor
radiobiological effect for smaller-volume recurrent or progressive tumors.

62. SRS for vestibular schwannoma
Vestibular schwannomas (more commonly referred to as acoustic neuromas) are
tumors arising from the Schwann cells of the eighth cranial nerve. These tumors are
commonly slow-growing, but growth can be variable.
1. Dose (PGI):
• Virgin lesion: 11-13 Gy
• Recurrence after 3 years of GK/EBRT: 10-12 Gy
2. Results: Kondziolka D et al (2003) treated 157 patients (40 undergone previous surgery):
Median follow up : 9.1 years
Decrease in tumor size : 114 (73%)
No change : 40 (25.5%)
Increase in size : 3 (1.9%)
Normal facial nerve function : 95%

63. 3. Side effects:
- Hearing loss
- Facial, trigeminal neuropathy
SRS for vestibular schwannoma

64. SRS for AVM
1. Indications:
• small- to medium-sized
AVMs less than 3–3.5 cm in
diameter
• AVMs located in deep or
eloquent brain regions
2. Dose:
16 to 25 Gy and obliteration
rates tend to improve at
doses greater than 17 Gy

65. SRS for AVM
3. Results:
Obliteration rates depend on a multitude of factors relating to AVM
characteristics and treatment parameters, and they vary widely from
50% to 90% in reported studies
4. Side effects:
hemiparesis (48.9% of all symptomatic patients), headache (16.3%),
seizures (12.1%), sensory dysfunction (7.1%), and ataxia (3.5%)

66. SRS for Trigeminal Neuralgia
1. Indication:
Microvascular decompression was the gold standard but since the
1970s, SRS has gained popularity
2. Dose:60 to 90 Gy to 4 mm isocenter
3. Results: 58% were free of pain at a median follow-up of 18 months,
and another 36% had significant improvement (>50%) in their pain
HISTORY: (1951) First time SRS was used by Dr. Leksell for treating two
patients with trigeminal neuralgia using 280 kV X rays

67. SRS for Trigeminal Neuralgia
It is postulated that TN results
from a combination of central
demyelination of the nerve
root entry zone (REZ) and the
subsequent, reinforced
electrical excitability of the
nerve

68. SBRT for Spinal Tumours
1. Indication:
The most common and ideal
indications for spine SBRT are in
patients with no prior history of
radiation, oligometastatic
disease, limited or no epidural
disease and no spinal instability.

69. 2. Dose
- not standardized
- 24 Gy in 3 fractions
SBRT for Spinal Tumours

70. SBRT for Spinal Tumours
3.Results: De novo metastasis,
Guckenberger et al (2014) treated
387 spinal metastases across 8
institutions with a median dose of 24
Gy in 3 fxs. Median overall survival
was noted to be 19.5 months, and 1-
yr and 2-yr local control rates were
89.9% and 83.9%
4. Side effects:
Vertebral Compression fracture
Radial plexopathy

72. SRS Complications
ACUTE:
Severe acute reaction:
Rare: 835 consecutive patients: 18 had a neurological event within 7
days of treatment (e.g. new focal deficit or seizure), three died
Immediate side effects: Two weeks after SRS, approximately one third
patients had mild dizziness, nausea headache

73. SRS Complications
LATE:
1. Radiation Necrosis:
With greater use of SRS, the incidence of
radiation necrosis is increasing. Radiation
necrosis develops in 7–24% of patients
undergoing SRS.
Bevacizumab has emerged as the best
supported agent in the management of
radiation necrosis.

74. SRS Complications and Management
LATE:
2. Optic neuropathy
RON can develop as early as 3 months post radiation, but can take
years to develop. The peak incidence is 1–1.5 years.

75. Role of re-irradiation with SRS
• Re-irradiation of brain metastasis in NSCLC with SRS in currently being
tried on a case to case basis.
• Balermpas et al. reported on 31 patients with 32 recurrent brain
metastases:
- Median interval was 12 months
- Sequence was WBRT + SRS + SRS
- One year survival and local control was 62% and 80%

76. Conclusion
• With the advancement in equipment and better understanding of
radiobiology of high dose per fraction radiation, the role of SRS and
SRT is increasing
• Both the techniques require meticulous treatment planning and
execution
• Local control in oligometastatic patients have increased by it
• Recent interest has been shown in ultra-fast dose rate radiotherapy
(excess of 40 Gy/s) – FLASH radiotherapy

77. Thank you