Professional Documents
Culture Documents
Radiation therapy
Moderator:
Dr S C Sharma
Department of Radiotherapy
PGIMER
Chandigarh
Trends
1750
1500
1250
1000
750
500
250
0
1990 1995 2000 2005
3 DCRT IMRT
Gamma Knife
Radiation
Stereotactic radiotherapy LINAC based
Therapy
Cyberknife
Electrons
Protons
Neutrons
Use alternative radiation
Develop technologies to circumvent limitations
modalities
π- Mesons
Antiprotons
Development Timeline
1950
1st MLCs invented (1959)
1960
Proimos develops gravity oriented
blocking and conformal field shaping
1970
at Royal Free Hospital
1980
Brahame conceptualized inverse planning
developed by Webb (1989) & gives prototype algorithm for (1982-88)
Block: Wedge:
Binary Modulation Uniform Modulation
Conformal radiotherapy
(CFRT) is a technique that
aims to exploit the
potential biological
improvements consequent
on better spatial
localization of the high-
dose irradiation volume
- S. Webb
in Intensity Modulated Radiotherapy
IOP
Problems in conformation
Nature of the photon beam
is the biggest impediment
Has an entrance
dose.
Has an exit dose.
Follows the inverse
square law.
Types of CFRT
Two broad subtypes :
Techniques aiming to
employ geometric
fieldshaping alone
Techniques to modulate
the intensity of fluence
across the geometrically-
shaped field (IMRT)
Modulation : Intensity or Fluence
?
Intensity Modulation is a misnomer – The actual term is
Fluence
Fluence referes to the number of “particles” incident on an
unit area (m-2)
How to modulate intensity
Cast metal compensator
Jaw defined static fields
Multiple-static MLC-shaped fields
Dynamic MLC techniques (DMLC)
including modulated arc therapy (IMAT)
Binary MLCs - NOMOS MIMiC and in
tomotherapy
Robot delivered IMRT
Scanning attenuating bar
Swept pencils of radiation (Race Track
Microtron - Scanditronix)
Comparision
MLC based IMRT
√
Step & Shoot IMRT
Since beam is interrupted between
movements leakage radiation is
less.
Easier to deliver and plan.
More time consuming
Intesntiy
Distance
Dynamic IMRT
Faster than Static IMRT
Smooth intensity modulation
acheived
Beam remains on throughout –
leakage radiation increased
More susceptible to tumor
motion related errors.
Additional QA required for MLC
motion accuracy.
Intesntiy
Distance
Caveats: Conformal Therapy
Significantly increased expenditure:
Machine with treatment capability
Imaging equipment: Planning and Verification
Software and Computer hardware
Extensive physics manpower and time required.
Conformal nature – highly susceptible to motion and setup related
errors – Achilles heel of CFRT
Target delineation remains problematic.
Treatment and Planning time both significantly increased
Radiobiological disadvantage:
Decreased “dose-rate” to the tumor
Increased integral dose (Cyberknife > Tomotherapy > IMRT)
3D Conformal
Radiation Planning
How to Plan CFRT
Target Volume
Delineation
Treatment Treatment Delivery
QA
Forward
Planning
Inverse
Planning
Dose distribution 3D Model
Analysis generation
Positioning and Immobilization
Two of the most important aspects of conformal radiation
therapy.
Basis for the precision in conformal RT
Needs to be:
Comfortable
Reproducible
Minimal beam attenuating
Affordable
Invasive
Frame based
Noninvasive
Immoblization
devices
Frameless
Usually based on a combination of heat deformable
“casts” of the part to be immobilized attached to a
baseplate that can be reproducibly attached with the
treatment couch.
The elegant term is “Indexing”
Cranial Immobilization
BrainLab System
TLC System
Leksell Frame
70 – 85 cm bore
Scanning Field of View (SFOV) 48 cm –
60 cm – Allows wider separation to be
imaged.
Multi slice capacity:
Speed up acquistion times
Reduce motion and breathing artifacts
Allow thinner slices to be taken – better
DRR and CT resolution
Allows gating capabilities
Flat couch top – simulate treatment
table
MRI
Superior soft tissue resolution
Ability to assess neural and marrow infiltration
Ability to obtain images in any plane - coronal/saggital/axial
Imaging of metabolic activity through MR Spectroscopy
Imaging of tumor vasculature and blood supply using a new
technique – dynamic contrast enhanced MRI
No radiation exposure to patient or personnel
PET: Principle
Unlike other imaging can
biologically characterize a leison
Relies on detection of photons
liberated by annhilation reaction
of positron with electron
Photons are liberated at 180° angle
and simultaneously – detection of
this pair and subsequent mapping
of the event of origin allows spatial
localization
The detectors are arranged in an
circular array around the patient
PET- CT scanners integrate both
imaging modalities
PET-CT scanner
PET scanner
Flat couch top insert
CT Scanner
60 cm
Allows hardware based registration as the patient is scanned in the
treatment position
CT images can be used to provide attenuation correction factors for the
PET scan image reducing scanning time by upto 40%
Markers for PET Scans
Metabolic marker
2- 18
Fluoro 2- Deoxy Glucose
Proliferation markers
Radiolabelled thymidine: 18
F
Fluorothymidine
Radiolabelled amino acids: 11C Methyl
methionine, 11C Tyrosine
Hypoxia markers
Cu-diacetyl-bis(N-4-
60
methylthiosemicarbazone) (60Cu-
ATSM)
Apoptosis markers
99
Technicium Annexin V
m
PET Fiducials
Image Registration
Technique by which the coordinates of identical points in
two imaging data sets are determined and a set of
transformations determined to map the coordinates of one
image to another
Uses of Image registration:
Study Organ Motion (4 D CT)
Assess Tumor extent (PET / MRI fusion)
Assess Changes in organ and tumor volumes over time
(Adaptive RT)
Types of Transformations:
Rigid – Translations and Rotations
Deformable – For motion studies
Concept
Process: Image Registration
The algorithm first measures the degree of mismatch between
identical points in two images (metric).
The algorithm then determines a set of transformations that
minimize this metric.
Optimization of this transformations with multiple iterations take
place
After the transformation the images are “fused” - a display which
contains relevant information from both images.
Image Registration
Target Volume delineation
The most important and most error prone step in
radiotherapy.
Also called Image Segmentation
The target volume is of following types:
GTV (Gross Target Volume)
CTV (Clinical Target Volume)
ITV (Internal Target Volume)
PTV (Planning Target Volume)
Other volumes:
Targeted Volume
Irradiated Volume
Biological Volume
Target Volumes
GTV: Macroscopic extent of the tumor as defined by
radiological and clinical investigations.
CTV: The GTV together with the surrounding microscopic
extension of the tumor constitutes the CTV. The CTV also
includes the tumor bed of a R0 resection (no residual).
ITV (ICRU 62): The ITV encompasses the GTV/CTV with an
additional margin to account for physiological movement of
the tumor or organs. It is defined with respect to a internal
reference – most commonly rigid bony skeleton.
PTV: A margin given to above to account for uncertainities
in patient setup and beam adjustment.
Target Volumes
Definitions: ICRU 50/62
GTV
CTV
Treated Volume: Volume of the
tumor and surrounding normal
ITV
tissue that is included in the isodose
surface representing the irradiation
TV
dose proposed for the treatment
(V95)
Irradiated Volume: Volume
included in an isodose surface with
PTV
IV a possible biological impact on the
normal tissue encompassed in this
volume. Choice of isodose depends
on the biological end point in mind.
Example
PTV
CTV
GTV
Organ at Risk (ICRU 62)
Normal critical structures whose
radiation sensitivity may
significantly influence treatment
planning and/or prescribed dose.
A planning organ at risk volume
(PORV) is added to the contoured
organs at risk to account for the
same uncertainities in patient
setup and treatment as well as
organ motion that are used in the
delineation of the PTV.
Each organ is made up of a
functional subunit (FSU)
Biological Target Volume
A target volume that
incorporated data from
molecular imaging techniques
Target volume drawn
incorporates information
regarding:
Cellular burden
Cellular metabolism
Tumor hypoxia
Tumor proliferation
Intrinsic Radioresistance or
sensitivity
Biological Target Volumes
Lung Cancer:
30 -60% of all GTVs and PTVs are changed with PET.
Increase in the volume can be seen in 20 -40%.
Decrease in the volume in 20 – 30%.
Several studies show significant improvement in nodal
delineation.
Head and Neck Cancer:
PET fused images lead to a change in GTV volume in 79%.
Can improve parotid sparing in 70% patients.
3 D TPS
Treatment planning systems are complex computer systems
that help design radiation treatments and facilitate the
calculation of patient doses.
Several vendors with varying characteristics
Provide tools for:
Image registration
Image segmentation: Manual and automated
Virtual Simualtion
Dose calculation
Plan Evaluation
Data Storage and transmission to console
Treatment verification
Planning workflow
Total Dose
A technique where the planner will try a variety of
combinations of beam angles, couch angles, beam weights
and beam modifying devices (e.g. wedges) to find a
optimum dose distribution.
Iterations are done manually till the optimum solution is
reached.
Choice for some situations:
Small number of fields: 4 or less.
Convex dose distribution required.
Conventional dose distribution desired.
Conformity of high dose region is a less important concern.
Planning Beams
Digital Composite
Beams Eye View Radiograph
Display
Room's Eye
View
“Inverse” Planning
Inverse Planning
Forward Planning
3. Beam Fluence
modulated to recreate
2. Intensity map created
intensity map
Optimization
Refers to the technique of finding the best physical and
technically possible treatment plan to fulfill the specified
physical and clinical criteria.
A mathematical technique that aims to maximize (or
minimize) a score under certain constraints.
It is one of the most commonly used techniques for inverse
planning.
Variables that may be optimized:
Intensity maps
Number of beams
Number of intensity levels
Beam angles
Beam energy
Optimization
Optimization Criteria
Refers to the constraints that need to be fulfilled during the
planning process
Types:
Physical Optimization Criteria: Based on physical dose coverage
Biological Optimization Criteria: Based on TCP and NTCP
calculation
A total objective function (score) is then derived from these
criteria.
Priorities are defined to tell the algorithm the relative
importance of the different planning objectives (penalties)
The algorithm attempts to maximize the score based on the
criteria and penalties.
Multicriteria Optimization
Intestine
Sliders for
adjusting EUD
PTV GTV
Plan Evaluation
Differential DVH
Cumulative DVH
Organ motion types:
Types of movement:
Interfraction motion
Translations:
Intrafraction motion
Craniocaudal
Lateral
Even intracranial structures
Prostate:
Rectum:
Motion max in SI and AP
Diameter: 3 – 46 mm
SI 1.7 - 4.5 mm
Volumes: 20 – 40%
AP 1.5 – 4.1 mm
In many studies decrease
in volume found
Lateral 0.7 – 1.9 mm
SV motion > Prostate
Bladder:
Uterus:
Max transverse diameter
mean 15 mm variation
SI: 7 mm
SI displacement 15 mm
AP : 4 mm
Volume variation 20% -
Cervix: 50%
SI: 4 mm
Intrafraction Motion
Liver:
Lung:
Normal Breathing: 10 – 25
Quiet breathing
mm
AP 2.4 ± 1.3 mm
Deep breathing: 37 – 55 mm
Lateral 2.4 ± 1.4 mm
Kidney:
SI 3.9 ± 2.6 mm
2° to Cardiac motion: 9 ± 6
Normal breathing: 11 -18
mm mm lateral motion
Deep Breathing: 14 -40 mm
Tumors located close to the
chest wall and in upper lobe
Pancreas: show reduced interfraction
motion.
Average 10 -30 mm
Maximum motion is in
tumors close to mediastinum
IGRT: Solutions
Imaging techniques
MV CT KV CT
Siemens
Mobile C arm
KV X-ray OBI
Varian OBI
Elekta
Siemens Inline
Gantry Mounted Room Mounted MV X-ray
Varian OBI
Cyberknife
EPI
Elekta Synergy
RTRT (Mitsubishi)
IRIS
BrainLAB
(Exectrac)
IGRT: Solution Comparision
Uses of EPI:
Correction of individual interfraction errors
Estimation of poulation based setup errors
Verification of dose distribution (QA)
Problems with EPI:
Poor image quality (MV xray)
Increased radiation dose to patient
Planar Xray – 3 dimensional body movement is not seen
Tumor is not tracked – surrogates like bony anatomy or
implanted fiducials are tracked.
Types of EPID
Liquid Matrix Ion Chamber*
Camera based devices
Amorphous silicon flat panel detectors
Amorphous selenium flat panel detectors
Intensifier
KV Xray
Normal
Problems with 4 D CT
The image quality depends on the reproducibility of the
respiratory motion.
The volume of images produced is increased by a factor of
10.
Specialized software needed to sort and visualize the 4D
data.
Dose delivered during the scans can increase 3-4 times.
Image fusion with other modalities remains an unsolved
problem
4D Target delineation
Target delineation can be done on all images acquired.
Methods of contouring:
Manual
Automatic (Deformable Image Registration)
Why automatic contouring?
Logistic Constraints: Time requirement for a single
contouring can be increased by a factor of ~ 10.
Fundamental Constraints:
To calculate the cumulative dose delivered to the tumor during
the treatment.
However the dose for each moving voxel needs to be integrated
together for this to occur.
So an estimate of the individual voxel motion is needed.
4D Manual Contouring
The tumor is manually contoured in end expiration and end
inspiration
The two volumes are fused to generate at MIV – Maximum
Intensity Volume
The projection of this to a DRR is called MIP (Maximum
Intensity Projection)
End Inspiration
MIV
End Expiration
Automated Contouring
Technique by which a single moving voxel is matched on CT
slices that are taken in different phases of respiration
The treatment is planned on a reference CT – usually the
end expiration (for Lung)
Matching the voxels allows the dose to be visualized at each
phase of respiration
Several algorithms under evaluation:
Finite element method
Optical flow technique
Large deformation diffeomorphic image registration
Splines thin plate and b
Automated Contouring
Movement
vectors
Automated Contouring
Individaul
Pixels
+
=
A treatment plan is usually
generated for a single phase of
CT.
The automatic planning
software then changes the field
apertures to match for the PTV
at each respiratory phase.
MLCs used should be aligned
parallel to the long axis of the
largest motion.
Limitations of 4D Planning
Computing resource intensive – Parallel calculations require
computer clusters at present
No commercial TPS allows 4 D dose calculation
Respiratory motion is unpredictable – calculated dose good
for a certain pattern only
Incorporating respiratory motion in dynamic IMRT means
MLC motion parameters become important constraints
Tumor tracking is needed for delivery if true potential is to
be realized
The time delay for dMLC response to a detected motion
means that even with tracking gating is important
4D Treatment delivery
Abdominal Compression(Hof
Breath Hold technique:
et al. 2003 – Lung tumors):
Patients instructed to hold
Cranio-caudal movement of breath in one phase
tumor 5.1±2.4 mm.
Usually 10 -13 breath holding
Lateral movement 2.6±1.4 sessions tolerated (each 12 -16
sec)
Anterior-posterior
movement 3.1±1.5 mm
Reduced lung density in
irradiated area – reduced
volume of lung exposed to high
dose
Tumor motion restricted to 2-3
mm (Onishi et al 2003 – Lung
tumors)
Minimizing Organ Motion
Active Breathing Control
Consists of a spirometer to “actively” suspend the patients
breathing at a predetermined postion in the respiratory cycle
A valve holds the respiratory cycle at a particular phase of
respiration
Breath hold duration : 15 -30 sec
Usually immobilized at moderate DIBH (Deep Inspiration Breath
Hold) – 75% of the max inspiratory capacity
Max experience: Breast
Intrafractional lung motion reduced
Mean reproducibility 1.6 mm
Tracking Target motion
Also known as Real-time Postion Management respiratory
tracking system (RPM)
Various systems:
Video camera based tracking (external)
Radiological tracking:
Implanted fiducials
Direct tracking of tumor mass
Non radiographic tracking:
Implanted radiofrequncy coils (tracked magnetically)
Implanted wireless transponders (tracked using wireless signals)
3-D USG based tracking (earlier BAT system)
Results
Adaptive radiotherapy is a technique by which a conformal
radiation dose plan is modified to conform to a mobile and
deformable target.
Two components:
Adapt to tumor motion (IGRT)
Adapt to tumor / organ deformation and volume change.
4 ways to adapt radiation beam to tracked tumor motion:
Move couch electronically to adapt to the moving tumor
Move a charged particle beam electromagnetically
Move a robotic lightweight linear accelerator
Move aperture shaped by a dynamic MLC
ART: Concept
1. 2. 3.
Offline ART
Conventional Rx
Individual patient based
Online ART
Sample Population based margins
Individual patient based
margins
Frequent imaging of margins
Accomadates variations of patients
Daily imaging of patients
setup for the populations
Estimated systemic error
Daily error corrected
No or infrequent imaging corrected based on prior to the treatment
Largest margin repeated measurements
Smallest margin required
A small margin kept for
Plans adapted to the
random error changing anatomy daily!
Plans adapted to average
changes
ART: Why ?
Gantry dia 85 cm
Integrated S Band LINAC
6 MV photon beam
No flattening filter – output
increased to 8 Gy/min at
center of bore
Independant Y - Jaws are
provided (95% Tungsten)
Fan beam from the jaws can
have thickness of 1 -5 cm
along the Y axis
Helical Tomotherapy
LINAC
Binary MLCs are provided – 2
positions – open or closed
Cone Beam
Pneumatically driven 64 leaves
Y jaw
Open close time of 20 ms
Binary MLC
Width 6.25 mm at isocenter
10 cm thick
Y jaw
Interleaf transmission – 0.5% in
field and 0.25% out field
Maximum FOV = 40 cm
Fan Beam
However Targets of 60 cm dia
meter can be treated.
Helical Tomotherapy
Flat Couch provided allows
automatic translations during
treatment
Target Length long as 160 cm
can be treated
“Cobra action” of the couch
limits the length treatable
Manual lateral couch translations
possible
Automatic longitudinal and
vertical motions possible
Helical Tomotherapy
Integrated MV CT obtained by an
integrated CT detector array.
MV beam produced with 3.5 MV photons
Allows accurate setup and image guidance
Allows higher image resolution than cone
beam MV CT (3 cm dia with 3% contrast
difference)
Tissue heterogenity calculations can be
done reliably on the CT images as scatter is
less (HU more reliable per pixel)
Not affected by High Z materials (implant)
Dose 0.3 – 3 Gy depending on slice
thickness
Dose verification possible
Breat Cancer
Leonard et al 2007 – APBI
55 patients , Non randomized
All patients stage I
Dose: 34 Gy (n=7) / 38.5 (n = 48) BID over 5 days
Median F/U – 1 yr
Good to excellent cosmesis:
Patient assessed: 98% (54)
Physician assessed: 98% (54)
Considered a reasonable option for patients who have large
target volumes and/or target volumes that are in anatomic
locations that are very difficult to cover.
Lung Cancer
Derived from the greek words Stereo = 3 dimensional space
and Taxis = to arrange.
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.
Stereotactic radiotherapy uses this technique to position a
target reference point, defined in the tumor, in the isocenter
of the radiation machine (LINAC, gamma knife, etc.).
Units used:
Gamma Knife
LINAC with special collimators or mico MLC
Cyberknife
Neutron beams
Stereotactic Radiation
Rigid application of a
Two braod groups:
stereotactic frame to the patient
Radiosurgery: Single
treatment fraction
3 D Volumetric imaging with the
Radiotherapy: Multiple
frame attached
fractions
Frameless stereotactic
Target delineation and radiation is possible in one
Treatment planning
system – cyberknife
The first machine used by Leksell in 1951 was a 250 KV Xray
tube.
In 1968 the Gamma knife was available
LINAC based stereotactic radiation appeared in 1980
Other machines using protons (1958) and heavy ions – He
(1978) were also used for stereotactic postioning of the
Bragg's Peak
Gamma Knife
Designed to provide an
overall treatment accuracy
of 0.3 mm
3 basic components
Spherical source housing
4 types of collimator
helmets
Couch with electronic
controls
201 Co60 sources (30 Ci)
Unit Center Point 40 cm
Dose Rate 300 cGy/min
LINAC Radiosurgery
Conventional LINAC aperture modified
by a tertiary collimator.
Two commercial machines
Varian Trilogy
Novalis
Cyberknife
Circular Collimator
attached to head
An image-guided, frameless radiosurgery system.
Non-isocentric treatment allows for simultaneous
irradiation of multiple lesions.
The lack of a requirement for the use of a head-frame allows
for staged treatment.
Real time organ position and movement correction facility
Potentially superior inverse optimization solutions
available.
Cyberknife
185 published articles till date; 5000 patients treated.
73 worldwide installations
Areas where clinically evaluated:
Intracranial tumors
Trigeminal neuralgia and AVMs
Paraspinal tumors – 1° and 2°
Juvenile Nasopharyngeal Angiofibroma
Perioptic tumors
Localized prostate cancer
However till date maximum expirence with Intracranial or
Peri-spinal Stereotactic RT
Results