Stereotactic radiotherapy and its applications

1. Stereotactic Radiosurgery and
Radiotherapy
Dr Umesh V
Department of Radiotherapy and Oncology
Kasturbha Medical College, Manipal

2. Introduction
• Stereotactic radiotherapy dates back more than 50 years; however, this form of
treatment has entered the domain of radiation oncology only in the past 10–15 years
• Stereotaxy (stereo + taxis – Greek, orientation in space) is a method which defines a
point in the patient’s body by using an external three-dimensional coordinate system
which is rigidly attached to the patient.
• This results in a highly precise delivery of the radiation dose to an exactly defined
target (tumor) volume.

3. Radiobiology

4. Radiobiology beyond 5 Rs in SRT/SRS/SBRT
• Endothelial cell damage may enhance the cytotoxic effect of irradiation on tumor
cells- Zvi Fuks and Richard Kolesnick proposed that the radiation sensitivity of tumors
to dose fractions of 10 Gy or more was governed by the sensitivity of the tumor
endothelial cells to apoptosis
• Vascular damage at high doses produces secondary cell killing-Song and colleagues,
suggests that radiation doses higher than about 10 Gy induce vascular damage
leading to indirect tumor cell death.
• Enhanced antitumor immunity after tumor irradiation

5. Indications
• Brain- Metastases, Pituatory Adenoma, Schwanoma, Meningioma, Trigeminal
neuralgia, AVM & small Gliomas and boosts
• Spinal metastasis
• Lung Cancer and lung metastasis
• Early stage Prostate cancer
• Liver metastases
• Hepatocellular carcinoma and portal vein thrombosis

6. Immobilization
• Brain- frame and frameless
• Thermoplastic masks
• Other sites- VAC LOC

7. Pre Treatment Evaluation
• Consent
• Look for signs of hemorrhage in brain
• Any allergies for Intravenous contrast
• Renal function tests
• Ophthalmic evaluation
• Pure tone audiometry
• Hormonal analysis in children
• In Young females rule out pregnancy
• Patients with lobar AVMs were placed prophylactically on anticonvulsants for a period
of 2 to 4 weeks around the time of the procedure.

8. Techniques
• Immobilisation
• CT simulation
• Image acquisition and registration
• Contouring
• Beam Placement
• Plan evaluation
• Set up verification
• Treatment

9. Immobilisation
•Frame immobilization
•Frameless immobilisation

10. Frame
• Stereotactic radiotherapy is based on the rigid connection of the stereotactic frame
to the patient during CT, MRI, and angiography imaging
• The stereotactic frame is the base for the fixation of the other stereotactic
elements (localizer and positioner) and for the definition of the origin (point 0) of
the stereotactic coordinates.
• During the whole treatment procedure, from the performance of the stereotactic
imaging to the delivery of the irradiation treatment, the stereotactic frame must not
be removed from the patient.
• In case of relocatable frames it must be assured that the position of the patient is
exactly the same relative to the frame after reapplication of the relocatable frame

11. Different types of Frame systems
• There are different stereotactic frame systems described in detail in the literature:
 the BRW system
 the CRW system
the Leksell system
the BrainLAB system
Each system is different with regard to material of the stereotactic frame, design, and
connection with the localizer and positioner and accuracy of repositioning

18. Simulation
• Patient will be immobilized with either a frame based or frameless stereotactic
method
• CT scanning was done in spiral mode using a pitch of 0.75, 512 × 512 pixel size, and
slices in thickness and spacing of 1.2 mm acquired throughout the entire cranium.
Tube voltage and tube potential were set at 130 kV and 300 mA to obtain high quality
reconstructed slices
• Assessment of images after acquiring is a must.
• If the site of the lesion is supratentorial and close to pituatory flexing of the neck is
recommended
• If infratentorial neutral spine positioning is advised.

19. • In addition, a mouth bite positioned against the upper dentition attached to the
stereotactic frame was applied to prevent any head tilt movement
• If any head tilt the imaging must be repeated
• If there are head tilts in more than 3 times the procedure is abandoned and
remoulding or re fixation of the frame is advised
• A localizer is mounted over the frame in order to provide a three dimensional (3D)
stereotactic coordinate array for target localization.

21. Image registration
• The Ct Angiography , MRI and planning CT datasets
were imported into the planning system and
stereotactic coordinates localization were
performed by the software by identifying the
location of six localizer rods on the outside surfaces
of the right, left, and anterior walls of the localizer
box.
• Localization establishes the 3D stereotactic
coordinate system for treatment planning and
delivery

22. Pituatory adenoma
• Pituitary adenomas (PAs) are the third most common intracranial tumors in surgical
practice, accounting for approximately 10 to 25% of all intracranial neoplasms
• Historically, surgery has been established as the standard for pituitary treatment(
recurrence rate 3-18%)
• Patients usually warrant radiotherapy after surgery
• The mean treatment dose ranges from 15 to 21 Gy for SRS and from 45 to 52 Gy for
SRT, typically split up in fractions of 1.8 Gy.
• The achieved mean local control for both SRS and SRT treatments is 96% with an
average hormonal response rate of 80%.

28. Trigeminal Neuralgia
• Trigeminal neuralgia (TN), also known as tic douloureux, is a pain syndrome
recognizable by patient history alone.
• The condition is characterized by intermittent unilateral facial pain.
• The pain follows the unilateral (>95%) sensory distribution of trigeminal nerve (V),
typically radiating to the maxillary (V2) or mandibular (V3) area.
• Ophthalmic division (V1) pain alone occurs in <5% patients.
• Physical examination findings are typically normal, although mild light touch or pin
perception loss has been described in the central area of the face.
• Significant sensory loss suggests that the pain syndrome is secondary to another
process, and requires high-resolution neuroimaging to exclude other causes of facial
pain.

29. Pathophysiology
• Peripheral injury or disease of the trigeminal nerve increases afferent firing in the
nerve by ephaptic transmission between afferent unmyelinated axons and partially
damaged myelinated axons
• Pain is perceived when nociceptive neurons in a trigeminal nucleus involve thalamic
relay neurons.
• Blood vessel-nerve cross compression, aneurysms, chronic meningeal inflammation,
tumors or other lesions may irritate trigeminal nerve roots along the pons.
• Development of trigeminal neuralgia in a young person (<45 years) raises the
possibility of multiple sclerosis, which should be investigated.

30. Management
• Medical- Carbamazepine, Oxcarbazapine, baclofen, gabapentin (Neurontin), and
Klonazepin
• Surgery- peripheral nerve blocks or ablation, gasserian ganglion and retrogasserian
ablative procedures, microvascular decompression (MVD)
• Radiosurgery-Radiosurgery is a good alternative for most patients with medically
refractory trigeminal neuralgia, especially those who do not want to accept the
greater risk of an MVD for a greater chance of pain relief.

33. Procedure
• The MRI was co-registered with the planning CT image set
• The target was localized to the base of the trigeminal nerve at the junction of nerve
entry into Meckel’s Cave and exit from the brainstem.
• The treatment plans were optimized in order to minimize brainstem dose as well as
avoided beam entry through the eyes.

39. AVM
• Arteriovenous malformations (AVMs) are congenital vascular anomalies comprised of an
abnormal number of blood vessels that are abnormally constructed.
• The blood vessels directly shunt blood from arterial input to the venous system without an
intervening capillary network to dampen pressure.
• Both abnormal blood vessel construction and abnormal blood flow lead to a risk of rupture
and intracranial hemorrhage.
• In addition, patients with lobar vascular malformations may suffer from intractable vascular
headaches or develop seizure disorders.

40. Patient characteristics & Epidemiology
• Patient’s age – even though it is congenital in origin they usually present in young
adults
• Brain AVMs occur in about 0.1 percent of the population, one-tenth the incidence of
intracranial aneurysms.
• Supratentorial lesions account for 90 percent of brain AVMs; the remainder are in
the posterior fossa. They usually occur as single lesions, but as many as 9 percent are
multiple.
• Brain AVMs underlie 1 to 2 percent of all strokes, 3 percent of strokes in young
adults, and 9 percent of subarachnoid hemorrhages

41. Pathophysiology
• AVMs are congenital lesions composed of a complex tangle of arteries and veins
connected by one or more fistulae.
• The vascular conglomerate is called the nidus.
• The nidus has no capillary bed, and the feeding arteries drain directly to the draining
veins.
• The arteries have a deficient muscularis layer.
• The draining veins often are dilated owing to the high velocity of blood flow through
the fistulae.
• Deranged production of vasoactive proteins is under investigation as the angiogenetic
link to pathophysiology.

42. Presentation
• Brain AVMs usually present between the ages of 10 and 40 years
• AVMs produce neurological dysfunction through 3 main mechanisms.
 Hemorrhage may occur in the subarachnoid space, the intraventricular space or,
most commonly, the brain parenchyma.
 In the absence of hemorrhage, seizures may occur as a consequence of AVM:
approximately 15-40% of patients present with seizure disorder.
 Progressive neurological deficit may occur in 6-12% of patients over a few months to
several years. These slowly progressive neurological deficits are thought to relate to
siphoning of blood flow away from adjacent brain tissue (the "steal phenomenon”).

43. Diagnosis
• Computed Tomography- Flow voids may be identified on CT with contrast
administration in and around the region of the nidus of the brain AVM. CT
characteristically demonstrates intraparenchymal hemorrhage without significant
edema in patients who present with hemorrhage.
• Magnetic resonance imaging- MRI is very sensitive for delineating the location of the
brain AVM nidus and often an associated draining vein. It also has unique sensitivity in
demonstrating remote bleeding related to these lesions. Dark flow voids are
appreciated on T1 and T2-weighted studies
• Angiography

45. Angiography
• Angiography — Angiography is the gold standard for the diagnosis, treatment
planning, and follow-up after treatment of brain AVMs.
• ●Anatomical and physiological information such as the nidus configuration, its
relationship to surrounding vessels, and localization of the draining or efferent
portion of the brain AVM are readily obtained with this technique.
• ●The presence of associated aneurysm suggests a lesion at higher risk for subsequent
hemorrhage.
• ●Contrast transit times provide additional useful information regarding the flow state
of the lesion which is critical for endovascular treatment planning.

47. Management

48. Surgery
• Open microsurgical excision offers the best chance
immediate cure in patients considered to be at high
risk of hemorrhage.
• An important factor in recommending therapy is an
assessment of surgical risk.
• Multiple or large lesions, those in eloquent brain
areas, and those with deep venous drainage are
more difficult to safely resect.
• Many surgeons use a classification system (Spetzler-
Martin grading scale) that assesses the surgical risk .

50. Interpretation of Spletzer Martin Grade
• Microsurgery is an effective and relatively safe option for patients with SM Grade I or
II AVMs.
• In contrast, Grade IV and V AVMs are associated with higher risks and less success
regardless of the option selected.
• The SM Grade III AVMs are a heterogeneous group that includes different subtypes of
AVMs according to their size, location in critical brain regions, and venous drainage
• Stereotactic radiosurgery (SRS) has been widely used to manage SM Grade III AVMs.

51. Target Delineation
• Organ at risk( OAR ) need to be contoured first in T1 weighted MRI – CT fused images
• OARS which need to be contoured are
Whole Brain
Bilateral Optic nerve
Optic Chiasma and a 5 mm PRV
Brain stem and PRV
Bilateral Cochlea
Hippocampus
3 mm of skin needs to be contoured

52. Contouring of the AVM
• On Planning CT- Following contrast administration, and especially with CTA with
feeding arteries, draining veins, and intervening nidus visible in the so-called "bag of
worms" appearance.
• DSA-Remains the gold standard to exquisitely delineate the location and number of
feeding vessels and the pattern of drainage.
• On angiography, an AVM appears as a tightly packed mass of enlarged feeding arteries
that supply a central nidus.
• Fusion of Planning CT , CT angiography , MRI and DSA correlation are required for
accurate delineation of a AVM by radiotherapy.

54. Dose Prescription
• The K index—calculated as the prescribed minimum dose of radiation delivered x
(AVM volume)1/3—has been proposed to guide the dose of radiation delivered.
• However, its use may be limited to SRS for small AVMs, with obliteration rates
increasing linearly up to a value of 27
• Various studies have prescribed various doses based on the volume of AVM
• Conventionally Volumes of AVM 12-14cc can be prescribed a SRS doe of 20-24 Gy
single fraction
• Volumes of 14 to 20cc can be prescribed a dose of 15-18 Gy
• Volumes above 20cc it is better to go with Staged Radiosurgery

58. Isodose prescription
• Dose prescribed to an isodose line (shell) that conforms to the periphery of the
target
• Typically 80% line (sharper dose fall-off outside the target)for LINEAR ACCELERATOR
based SRS with single isocentre
• Multiple isocentres 70% isodose line
• 50% isodose lines for Gamma Knife based SRS systems

60. Adverse effects
• Neurological deficits- 0-17%
• Seizures- 0-9%
• Radiation Induced imaging changes- In MRI upto 30%
• Rebleed or hemorrhage- 60-70%
• Cyst formation- 1.5-3.4%
• Radiation induced neoplasms- 0.64% at 10 years
• Very Rarely cognitive changes

61. Vestibular Schwanomas( VS)
• Management - Observation may be appropriate in selecting NF-2 and some elderly
patients, but early intervention appears to be the best strategy for long-term hearing
preservation in most patients .
• Surgery appears to be the best initial treatment in patients with tumors sufficiently
large enough to cause symptomatic brainstem compression with obstructive
hydrocephalus.
• SRS and SRT should be considered the best management strategy for the majority of
small to medium sized tumor VS patients
• Patients who had small tumors (≤3 cm) and non-serviceable hearing were usually
selected for SRS treatment.
• Patients who did not have the aforementioned criteria or were not suitable for SRS
were selected for HSRT or CSRT treatment

65. Liver
• SBRT is a noninvasive, safe and effective modality for the treatment of HCC> 6 cm
• Strongly considered for first-line definitive therapy when transplant is not an option
with one to three lesions up to 6 cm
• At the time of simulation, the excursion of the right dome of the diaphragm (superior
portion of the liver) should be observed under fluoroscopy or 4D CT to estimate liver
motion and determine the required expansion when delineating the Planning Target
Volume (PTV) from the Gross Tumor Volume (GTV).

66. • Ideally, patients should be assessed for suitability for Active Breathing Control (ABC)
or diaphragmatic control device.
• Patients with severe lung disease and patients who cannot tolerate diaphragmatic or
breathing control devices can be treated without them
• It is very important to obtain a triphasic CT scan with the patient in the treatment
position since HCC is better visualized in the arterial phase of the study.
• The CT scan should extend through the whole liver and down below the kidneys.
• Therefore scan from the carina down to the iliac crests.
• Oral GI contrast to opacify the stomach and duodenum should be used for patients
with peripheral-medial liver lesions or lesions of the caudate lobe

67. Planning
• When treating HCC with SBRT, the CTV should be equivalent to the GTV.
• Internal target volume (ITV) takes into account the internal movement of the target
lesion, primarily related to patient’s breathing which can be minimized with
respiratory gating, breath hold or compression devices.
• The PTV takes into account treatment setup uncertainty and as well as patient’s
breathing motion (ITV).
• Achievable accuracies for the liver range from 1.8 to 5 mm (Benedict et al. 2010;
Fuss et al. 2004; Herfarth et al. 2001; Wulf et al. 2000).
• Therefore, most common PTV values often range from 2 to 5 mm around the ITV
(Benedict et al. 2010; Choi et al. 2008; Seo et al. 2010)
• If breathing control is not feasible for whatever reason, the margins will need to be
expanded to take this into account.

68. Dose prescription
• Doses are often prescribed to a lower isodose line (usually80%) encompassing the
surface of the PTV, with very little margin for beam penumbra at the target edge and
a rapid dose falloff, thereby sparing nearby organs at risk (Benedict et al. 2010).
• When planning liver SBRT use multiple (5–10) highly conformal beams, with
noncoplanar arrangements that avoid opposition of fields, and intensity modulation
to create a parabolic beam entrance profile; this approach will aid in achieving a
sharp dose falloff outside the PTV.
• The parabolic entrance profile can be accomplished with field-in-field technique or
electronic compensation (Papiez et al. 2003).

69. OARS
• Patients with CTP-A liver cirrhosis, the dose to one-third of the uninvolved liver is
restricted to <10 Gy, (3.3 Gy/fxn) and <500 cc of uninvolved liver should receive <7
Gy (2.3 Gy/fxn).
• For patients with CTP-B cirrhosis, dose to one-third of the uninvolved liver is
restricted to <18 Gy (3.6 Gy/fxn), and <500 cc of uninvolved liver should receive < 12
Gy (2.4 Gy/fxn) (Andolino et al. 2011; Cárdenes et al. 2010).
• SBRT may not be safe for patients with CTP score of 8 or greater unless they are
already listed for transplant

70. • To minimize rib/chest wall toxicity including pain or fracture, the maximal dose
should remain <50 Gy and the dose received by 5 cc of chest wall should be <40 Gy.
• Other constraints include: maximal cord dose to be kept lower than 6 Gy per
fraction, for a total of 18 Gy in three fractions;[2/3 of the right kidney to receive
no<15 Gy total dose, and[1/3 of the left kidney to receive no <15 Gy total dose
(Cárdenes et al. 2010).

71. Toxicity
• Expected toxicity includes fatigue, nausea and vomiting which should gradually
subside over several months to days.
• The most significant toxicity derived from this therapy is RILD.
• Herfarth reaction

72. Studies No of pts Dose GTV(CC)
Median
Median
FU(m)
LC(%) Toxicity (%) OS
Blomgren et
al
11 30Gy/3# 22 12 100 10 Crude 65%
Herfarth et
al
1 26Gy/1#(80
% iso)
10 6 0 17.8M
Choi et al 20 50Gy/5-10# 3.8 23 80 0 1y-75%
2y-40%
Mendez
Romero et
al
8 25Gy/5 #
30gy/10#
22.2 12.9 75 18 1y-75%
Tse et al 31 24-54Gy/6# 173 17.6 65 16 1y-48%
K won et al 42 36Gy/3# 15.4 28.7 72 30-34% 1y-75%
Seo et
al(salvage)
38 60Gy/3#
44Gy/ 4#
40.5 15 63 0 1y-68%
Andolino et
al
60 44Gy/3# 29 27 90 0 2y-67%

74. Spinal SBRT
• Most of the available trials on bone metastases have been conducted on spinal bone
metastases and have shown good results with the use of SBRT.
• SBRT may have a role in treating selected patients with painful bone metastases.
• One of the benefits from SBRT would be in treating the tumor with a certain margin
instead of treating all or a big part of the bone, thus reducing the risk of adverse
effects.
• This option is especially beneficial for radioresistant tumors such as renal cell
carcinoma, melanoma or sarcoma where the higher dose per fraction may add some
benefit and provide a radiobiological advantage.

76. Non eligible patients
• Histologies of myeloma or lymphoma
• Non-ambulatory patients
• Spine instability due to a compression fracture
• > 50% loss of vertebral body height
• Frank spinal cord compression or displacement or epidural compression within 3 mm
of the spinal cord
• Patients with rapid neurologic decline
• Bony retropulsion causing neurologic abnormality
• Prior radiation to the index spine
• Patients for whom an MRI of the spine is medically contraindicated
• Patients allergic to contrast dye used in MRIs or CT scans or who cannot be
premedicated for the use of contrast dye.

77. SBRT
• No premedications required
• Patients must be positioned in a stable supine position capable for reproducibility of
positioning and immobilization from simulation to treatment, allowing the patient to
feel as comfortable as possible
• Vac Loc or thermoplastic masks can be used for immobilization.
• 3mm slice thickness CT scan is done if associated with soft tissue contrast may be
required.

78. Target Delineation

79. • An epidural lesion is included in the target volume provided that there is a ≥ 3 mm
gap between the spinal cord and the edge of the epidural lesion.
• A paraspinal mass ≤ 5 cm in the greatest dimension contiguous with spine metastasis
is included in the target volume
• The target as defined above will not be enlarged (i.e., no “margin” for presumed
microscopic extension)

80. Spinal cord
• Two spinal cord volumes are contoured- conventional and partial spinal cord
• The conventional spinal cord should be contoured starting at least 10 cm above the
superior extent of the target volume and continuing on every CT slice to at least 10
cm below the inferior extent of the target volume
• The partial spinal cord should be contoured starting from 5-6 mm above the superior
extent of the target volume to 5-6 mm below the inferior extent of the target
volume
• Three cord dose constraints are given
the dose constraints for the partial spinal cord is 10 Gy to no more than 10% of the
partial spinal cord volume
the dose constraint for the conventional spinal cord is 10 Gy to the spinal cord
volume less than 0.35cc
the maximum cord dose is 14 Gy for less than 0.03cc

81. TOXICITY
• Vertebral compression fracture
• Radiation Myelopathy
• Esophageal toxicity
• Flare pain