New techniques in radiation therapy such as intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) have led to increased accuracy and conformality in radiation treatment planning and delivery. Precise patient immobilization and volumetric imaging are essential for conformal radiation therapy. Target volumes must be carefully delineated on imaging to guide radiation treatment. Advanced imaging such as PET and MRI can provide biological and functional information to aid target definition. Treatment planning systems then facilitate virtual simulation, dose calculation and evaluation to design conformal radiation plans.
4. Solutions ?
Electrons
Protons
Neutrons
Use alternative radiation
Develop technologies to circumvent limitations
modalities
π- Mesons
Heavy Charged Nuclei
Antiprotons
5. Development Timeline
Takahashi discusses conformal RT
1950
1st MLCs invented (1959)
Proimos develops gravity oriented
1960
blocking and conformal field shaping
Tracking Cobalt unit invented
1970
at Royal Free Hospital
1st inverse planning algorithm Brahame conceptualized inverse planning
1980
developed by Webb (1989) & gives prototype algorithm for (1982-88)
Boyer and Webb develop Carol demonstrates NOMOS MiMIC (1992)
principle of static IMRT (1991) Tomotherapy developed in Wisconsin
(1993)
1990
Stein develops optimal dMLC equations
First discussion of Robotic (1994)
IMRT (1999)
6. Modulation: Examples
Block: Wedge:
Binary Modulation Uniform Modulation
Coarse spatial and Fine spatial
Coarse intensity coarse intensity
Fine Spatial and Fine
Intensity modulation
7. Conformal Radiotherapy
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
8. 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.
9. 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)
10. 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)
11. 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)
14. Step & Shoot IMRT
Since beam is interrupted between
movements leakage radiation is
less.
Easier to deliver and plan.
More time consuming
Intesntiy
Distance
15. 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
16. 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)
18. How to Plan CFRT
Patient positioning Volumetric Data Image Transfer
and Immobilization acqusition to the TPS
Target Volume
Delineation
Treatment QA Treatment Delivery
Forward
Planning
Inverse
Planning
Dose distribution 3D Model
Analysis generation
19. 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
Holds the Target in place while the beam is turned on
20. Types of Immobilization
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”
21. Cranial Immobilization
BrainLab System
TLC System
Leksell Frame
Gill Thomas Cosman System
23. Accuracy of systems
System Techniqe Setup Accuracy
Noninvasive Non invasive,
0.7– 0.8 mm (± 0.5–0.6 mm)
Stereotactic frame mouthpiece
Non invasive, x = 1.0 mm ± 0.7; y= 0.8 mm ± 0.8; z = 1.7
Latinen Frame
nasion, earplugs mm ± 1.0
Non invasive, X = 0.35 mm ± 0.06; Y = 0.52 mm ± 0.09;
GTC Frame
mouthpiece Z= 0.34 mm ± 0.09
Stereotactic Body Non invasive,
X = 5 – 7 mm ,Y = 1 cm Z = 1.0 cm (mean)
Frame vacccum based
Non invasive,
Heidelberg frame X = 5 mm,Y = 5 mm, Z = 10 mm (mean)
vaccum based
Non invasive, X = 0.4 ± 3.9 mm , Y = 0.1 ± 1.6 mm Z = 0.3
Body Fix Frame Vacccum based ± 3.6 mm. Rotation accuracy of 1.8 ± 1.6
with plastic foil degrees.
With the precision of the body fix frame the
target volume will be underdosed (< 90% of
prescribed dose) 14% of the time!!!
24. CT simulator
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
25. 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
26. 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
27. 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%
28. Markers for PET Scans
Metabolic marker
2- 18
Fluoro 2- Deoxy Glucose
Proliferation markers
Radiolabelled thymidine: 18
F
Fluorothymidine
Radiolabelled amino acids: 11
C Methyl
methionine, 11C Tyrosine
Hypoxia markers
Cu-diacetyl-bis(N-4-
60
methylthiosemicarbazone) (60Cu-
ATSM)
Apoptosis markers
99
m
Technicium Annexin V
PET Fiducials
29. 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
31. 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.
33. 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
34. 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.
36. 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.
38. 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)
39. 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
40. 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.
41. 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
42. Planning workflow
Total Dose
Total Time of delivery of dose
Define a dose objective
Total number of fractions
Choose Number of Beams Organ at risk dose levels
Choose beam angles and couch angles
Choose Planning Technique
Forward Planning Inverse Planning
43. “Forward” Planning
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.
45. “Inverse” Planning
Inverse Planning
1. Dose distribution specified
Forward Planning
3. Beam Fluence
modulated to recreate
2. Intensity map created
intensity map
46. 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
48. 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.
52. Why 4D Planning?
Organ motion types:
Types of movement:
Interfraction motion
Translations:
Intrafraction motion
Craniocaudal
Lateral
Even intracranial structures
can move – 1.5 mm shift
Vertical
when patient goes from
Rotations:
sitting to supine!!
Roll
Pitch
Yaw
Shape:
Flattening
Balloning
Pulsation
53. Interfraction Motion
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
54. 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
Normal breathing: 11 -18
2° to Cardiac motion: 9 ± 6
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
55. IGRT: Solutions
Imaging techniques
USG based Video based Planar X-ray CT MRI
●BAT ●AlignRT
●Sonoarray ●Photogrammetry
●I-Beam ●Real Time Video guided Fan Beam Cone Beam
●Resitu
IMRT
●Video substraction
●Tomotherapy
●In room CT
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)
56. IGRT: Solution Comparision
DOF = degrees of freedom – directions in which motion can be
corrected – 3 translations and 3 rotations
57. EPI
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.
58. Types of EPID
Liquid Matrix Ion Chamber*
Camera based devices
Amorphous silicon flat panel detectors
Amorphous selenium flat panel detectors
Electrode High voltage applied
connected to
high voltage
“Output” Output read out
Liquid 2,2,4 - ionized liquid
electrode by the lower
trimethylpentane
electrodes
60. 4 D CT acqusition
Axial scans are acquired
with the use of a RPM
camera attached to couch.
The “cine” mode of the scanner is used to
acquire multiple axial scans at
predetermined phases of respiratory cycle
for each couch position
61. RPM System
Patient imaged with the RPM system to
ascertain baseline motion profile
A periodicity filter algorithm
checks the breathing periodicity
Breathing comes to a rythm
Breathing cycle is recorded
63. 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
64. 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.
65. 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
66. 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
68. Automated Contouring
Individaul
Pixels
+
=
Day 1 Image Day 2 Image
Due to the changes in shape
of the object the same pixel
occupies a different
coordinate in the 2nd image
Deformable Image registration circumvents this problems
69. 4D Treatment Planning
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.
70. 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
71. 4D Treatment delivery
Options for 4D delivery
Ignore motion Freeze the motion Follow the motion (Tracking)
Patient breaths normally Breathing is controlled
Respiratory Gating Breath holding (DIBH)
Jet Ventilation
Active Breathing control
72. Minimizing Organ Motion
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)
73. 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
74. 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)
77. Adaptive Radiotherapy (ART)
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
78. ART: Concept
1. 2. 3.
●Offline ART
●Conventional Rx ➢ Individual patient based
●Online ART
➢ Individual patient based
➢ Sample Population based
margins
margins ➢ Frequent imaging of margins
➢ Daily imaging of patients
➢ Accomadates variations of
patients
➢ Daily error corrected
setup for the populations ➢ Estimated systemic error
➢ No or infrequent imaging
corrected based on prior to the treatment
➢ Smallest margin
➢ Largest margin
repeated measurements
➢ A small margin kept for required
➢ Plans adapted to the
random error
➢ Plans adapted to average changing anatomy daily!
changes
79. ART: Why ?
Due to a change in the contours (e.g. Weight Loss) the
actual dose received by the organ can vary significantly
from the planned dose despite accurate setup and lack of
motion.
80. ART: Problem
Real time adaptive RT is not possible “today”
84. Helical Tomotherapy
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
85. 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.
86. 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
87. 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
92. Prostate Cancer
Rectal Toxicity:
Grade 2: 7 patients (1.5%); Grade 3: 3 patients (less than
1%)
The 8-year actuarial likelihood of late grade 2 or greater rectal
toxicity 1.6%.
Urinary Toxicity:
Grade 2 chronic urethritis in 50 patients (9%); Urethral
stricture requiring dilation (grade 3) developed in 18 patients
(3%).
The 8-year actuarial likelihood of late grade 2 or greater
urinary toxicities was 15%.
47% patient developed ED (43% IMRT alone; 57% ADT)
No 2nd cancers!
93. Prostate Cancer
Arcangeli et al (2007) WP-IMRT
91% with Prostate boost
71%
N = 55; All had NAADT, Risk of
63%
nodal mets > 15%
Dose:
55 – 59 Gy (Pelvis)
66 – 80 Gy (Prostate)
33 – 40 fractions
No Gr III toxicity
Late Gr II toxicity:
Rectum: 2 yr actuarial probablity
8%
94. Head and Neck Cancers
Author Year N CCT Dose Result
Huang 2003 41 (I) Yes 70/60/50 (2.18 68% Stage IV; 31% Gr III mucositis;
(P,NR) Gy per #) 7% Gr IV mucositis; Gr II xerostomia
58.5%; 2 yr Locoregional control
89% ; 2 yr OS 89%
Wendt 2006 39 (I) Yes 60-70 Gy / 48 Gr III mucositis 11%; 12% Gr III
(P,NR) -54 Gy (I) xerostomia at 6 months; 2yr Crude
LC 70%; 50 % recurrences outside
high dose region
Yao (P,NR) 2007 90 (I) Yes 70/60/54 Gy All N2/N3 disease; 71% Oropharynx;
(SIB) 3 yr LC 96%; OS 67.5%; PET useful
in patient selection for ND (10)
Arruda 2006 50 (I) Yes 70 / 59.4 -54 Gy All oropharynx; 92% ≥ St III; 33%
(P,NR) (76% - SIB) Gr II xerostomia (1 yr); Gr III
mucositis 38%; 2 yr LRC 88%; OS
98%
Table showing Results of IMRT in H&N Ca
95. Head and Neck Cancers
Author Year N CCT Dose Result
Chao 2003 126 Yes 72 -68/ 64 -60 Gy 59% Post op IMRT; 67% St IV; 2 yr
(P,NR) (I) (30%) (SIB) LRC 85% ; 89% (Post ND)
Thorstad 2005 356 Yes 70/56 Gy – Def.; 63% Post op; 90% ≥ St III; 5 Yr LRC
(P,NR) (I) (40%) 64/54 Gy – 76%; 14% of the failures were
Postop marginal. All marginal failures in post
op patients.
Wolden 2005 79 (I) Yes 70 Gy (59 – All Npx; 80% ≥ Stage III; 3 yr
(P,NR) Hyperfractionated actuarial LC 91%; OS 83%; Gr III
; 15 - SIB) hearing loss 15%; 32% Gr II
xerostomia at 1 yr; distant mets
dominant form of therapy
Daly 2007 69 (I) Yes 66 Gy -Def (2.2 33% Post op; 2 yr LC and OS 92% and
(P,NR) Gy per #); 60.2 – 74%(Def); 87% and 87% (Post op);
Post op (2.15 per Mean xerstomia significantly improved
#) than CRT
Schwartz 2007 49 (I) Yes 60 / 50 Gy (25#) All Stage III/IV; Gr III mucositis 55%,
(P,NR) - SIB Gr III dermatitis 8%; 2 yr LC 83% ;
OS 80%
Table showing results of IMRT in H& N Ca
96. Head and Neck Cancers
Author Year N CCT Dose Result
Huang 2003 41 (I) Yes 70/60/50 68% Stage IV; 31% Gr III mucositis; 7%
(P,NR) (2.18 Gy per Gr IV mucositis; Gr II xerostomia 58.5%;
#) 2 yr Locoregional control 89% ; 2 yr OS
89%
Jabbari 2004 30 (I), No 60-78 Gy (I); At 12 months, median XQ and HNQOL
(P,NR) 10 (C) 63 -76.8 (C) scores were lower (better) in the IMRT
compared with the standard RT patients
by 19 and 20 points, respectively
Pow (P,R) 2006 24 No 68-70 / 66- All Stage II Npx; At 1 yr 83% had
(I),21 68(I); 68 / 66 recovered 25% of the pre RT parotid flow
(C) (C) in IMRT (9.5% in Conv RT arm). Subscale
scores for role-physical, bodily pain, and
physical function were significantly higher
in the IMRT group
Braam 2006 30 (I), No I – 69/66/54 83% in I arm treated definitively (23% in
(P,NR) 26 (C) (30#), C – 50 C arm);mean parotid flow ratio was 18%
-70/46-50(25 (C) and 64% (I); parotid gland
– 35#) complication rate was 81% (C) and 56%
(I) (p = 0.04).
Table showing Salivary sparing and QOL improvement with IMRT
97. Breast Cancer
Largest randomized trial
Donovan et al (2007)
305 patients – 156(standard)
and 150 (IMRT)
1997 – 2000
Aim:Impact of improved
radiation dosimetry with IMRT in
terms of external assessments
of change in breast appearance
and patient self-assessments of
breast discomfort, breast
hardness and quality of life.
Dose: 50 Gy / 25# with 10 Gy
boost
98. Breast Cancer
➢ The control arm had 1.7 times (95% CI 1.2–2.5) more likely to have had some
change than the IMRT arm, p = 0.008.
➢ Areas with dose > 105% have 1.9 times higher risk of any change in cosmesis
99. 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.
100. Lung Cancer
Author Year N CCT Dose Result
Yom et al 2005 37 (I) Yes 63 Gy (median) 7% incidence of Gr III
(R, NR) pneumonitis
Yorke et al 2005 78 No Dose escalation 22% incidence of Gr III
(P, NR) (3D) (50.7 – 90 Gy); pneumonitis above doses of 70
Gy.
Videtec (R, 2006 28 (I) No 50 Gy in 5 fraction 64% T1; 2.6% Gr II pneumonitis,
NR) (SBRT) no Gr III reactions; LC and OS at
1 yr 96.4% and 93% respectively
Scarbrough 2006 17 (I) Yes 71.2 Gy (69–73.5 Mean age 70; 73% IIIB, FU 1 yr,
(R, NR) Gy) No Gr III tox, 2 yr OS 66%
Jensen (P, 2007 17 (I) Yes 66 Gy Patients no suited for CCRT. 1 Gr
NR (citux) III esophagitis; 79% response (6
mo)
Yom et al 2007 68 (I), Yes 63 Gy (median); 60% stage IIIB, FU = 8 mo
(R, NR) 222 Dose > 60 Gy (median); Gr III pneumonitis 8%
(3D) 84% (I), 63% (32% for 3D CRT); V20 35% (I) vs
(3D) 38%(3D) (p = 0.001)
Table showing results of IMRT in Lung Cancer
101. Brain Tumors
Author Year N Dose Result
Sultanem 2004 25 60 Gy (GTV); 40 All GBM,Post op volume < 110 cc;
Gy (CTV); 20 # Majority RPA class 4/5; The 1-year
overall survival rate is 40%, Median
survial 9 mo. No late toxicity.
Luchi 2006 25 48 – 68 Gy 2 AA patients; Median KPS 70; 2 yr PFS
(GTV); 40 Gy 53.6%; 2 yr survival 55.6%; Pattern of
(CTV1); 32 Gy death – CSF dissemination most
(CTV2); 8 # common cause of death!
Narayana 2006 58 60 Gy (PTV); 70% GBM; 1 yr OS 30% (2 yr 0%) for
30# GBM; No Gr III late toxicity; Pattern of
failure – local
Table showing results of IMRT in brain tumors
102. Cervical Cancer
Author Year N CCT Dose Result
Mundt 2003 36 Y 45 Gy (1.8 80% stage I-II; PTV S3 to L4/5
(P,NR) (53%) Gy/#) interspace; Chronic GI toxicity 15% (n=
3; 1 Gr II, 2 Gr I); 50% incidence in
Conventional
Mundt 2002 40 Y 45 Gy (1.8 60% Acute Gr II toxicity (90% Gr II in
(P,NR) Gy/#) Conv.); Less GU toxicity (10% vs 20%);
Patients not requiring antidiarrheal
halved!
Chen 2007 33 Y 50.4 Gy / All Stage I -II; All Post Hysterectomy; 1
(P,NR) 28# yr LRC 93%; Acute GI toxicity 36% (Gr I-
II); Acute Gu toxicity 30% (Gr I-II)
Beriwal 2007 36 Y 45 Gy 2 Yr LC 80%; 2 yr OS 65%; 11 had
(P,NR) (EFRT) + recurrences – 9 distant; Gr III toxicity –
10-15 Gy 10%
boost
Kochanski 2005 62 Y 45 Gy (1.8 29% Post op; 20 Stage IIB-IIIB; 3 yr DFS
(64%) Gy /#) 72.7%; 3 yr pelvic control 87.5%; 5% Gr
II or higher late toxicity
103. Anal Canal
Author Year N CCT Dose Result
Salama et 2006 40 (I) Yes 45 Gy WP + 9 Gy 12.5% Gr III GI toxicity, 0 Gr III
al (R, NR) boost skin toxicity, 2 year colostomy-
free, disease free, and overall
survival 81%, 73%, and 86%
Milano et al 2005 17 (I) Yes 45 Gy WP + 9 Gy 53% Gr II GI toxicity, No Gr III
(P, NR) boost acute or late complications. 82%
CR rate, the 2-year CFS, PFS,
and overall survial are: 82%,
65%, and 91%
Devisetty 2006 34 (I) Yes 45 Gy WP + 9 Gy 17% Acute GI toxicity; volume of
(P,NR) boost bowel receiving 22 Gy (V22) was
correlated with toxicity (31.8%
acute GI toxicity for V22 > 563 cc
vs. 0% for V22 ≤ 563 cc)
Hwang 2006 12 (I) Yes 30.6 Gy WP + 42% Gr III dermal toxicity, 8% Gr
(P,NR) 14.4 Gy Low III GI toxicity, 83% CR rate
Pelvic + 9 Gy
boost
105. Stereotaxy
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
106. 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 Treatment radiation is possible in one
planning
system – cyberknife
Postioning of patinet with the
Sites used:
frame after verification
Cranial
Extracranial
QA of treatment and delivery of
therapy
107. Sterotactic Radiation
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
108. 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
109. LINAC Radiosurgery
Conventional LINAC aperture modified
by a tertiary collimator.
Two commercial machines
Varian Trilogy
Novalis
110. Cyberknife
Roof mounted KV X-ray
Robotic arm with
6 degrees of
6 MV LINAC freedon
Circular Collimator
attached to head
Frameless patient Floor mounted Amorphous
immobilization couch silicon detectors
111. Advantages of Cyberknife
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.
112. 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
113. Results
Tumor Year N Result
Brain mets 2004 333 (164 Survival advantage for patients with single
(Andrews et al) SRT / 164 brain mets (Median survival 6.5 – 4.9 mo);
C) Better functional status at follow up – SRT with
WBRT Rx in single brain mets (RTOG 9508)
Benign brain 2003 285 95% tumor control (media F/U 10 yr); actuarial
tumors tumor control rate at 15 years was 93.7%.
( Kondziolka et al) Normal facial nerve function was maintained in
95% with aucostic neuromas
Malignant Glioma UP 203 SRT + EBRT + BCNU did not result in significant
(Souhami et al) survial advantage – 13.6 vs 13.5 mo (RTOG
9305)
Malignant Glioma 2002 203 SRT + EBRT + BCNU did not result in significant
(Souhami et al) improvement in Quality adjusted survival
(RTOG 9305)
The only randomized trial comparing stereotactic radiation therapy boost
has failed to reveal a significant survival benefit for patients with malignant
gliomas. (RTOG 9305). However 18% of the patients in the stereotactic
radiotherapy arm had significant protocol deviations.
115. Brachytherpy
An inherently conformal
method of radiation delivery
Relies on the inverse square
law for the conformity
Unlike traditional EBRT
brachytherapy is both :
Physically conformal
Biologically conformal
Rapid dose fall off
from the radio-isotope
Recent advances have
Dose
focused on better method of
target identification and
radio-isotope placement.
Distance
116. Brachytherapy: What's New
Image Based Brachytherapy Image Assisted
Image Guided Brachytherapy Brachytherapy
Robotic Brachytherapy‡
Electronic Brachytherapy*
Image Based Brachytherapy: Technique where advanced
imaging modalites are used to gain information about the
volumetric dose delivery by brachytherapy
Image Guided Brachytherapy: Technique where imaging
is used to guide brachytherapy source placement as well
give information regarding the volumetric dose distribution
117. Image Assisted Brachytherapy
Principle: Cross sectional imaging utilized to plan and
analyze a brachytherapy procedure
Steps:
Image assisted provisional treatment planning
Image guided application
Image assisted definitive treatment planning
Image assisted quality control of dose delivery
Provisional planning refers to the planning of the implant
prior to the placement of the applicator in situ – important to
realize the significant anatomical distrortions 2° to the
applicator placement.
Definitive planning refers to the definitve treatment
planning with the applicator in situ.
119. Equipment: Imaging
Site 1st Choice 2nd Choice
Mobile Tongue MRI CT
Floor of mouth MRI CT, US
Oropharynx MRI, ES CT
Nasopharynx ES, MRI CT
Cervix MRI CT, US (Endo)
Endometrium MRI, ES CT, US (Endo)
Vagina US (endo), MRI CT
Breast Mammography, MRI CT, US
Bladder ES, MRI, CT US
Prostate MRI US (endo), CT
Anorectal ES, MRI, US (endo) CT
Oesophagus ES, Oesophagogram (Barium) CT, MRI, US (endo)
Bile duct Cholangiogram, ES CT, US, MRI
Soft tissue sarcoma MRI CT
Bronchus ES, CT, Chest X Ray MRI
Brain MRI CT
Table showing Imaging modality of choice in different anatomical areas
121. Image Acqusition
Images should be acquired in 3 dimensions parallel and
perpendicular to the axis of the applicator
This minimizes reconstruction related artifacts
The best modality in this respect is the MRI
CE MRI can provide excellent soft tissue contrast too
Para Sagittal Para Coronal Para Axial
122. Tumor Delineation
Tumor delineation requires a good
clinical examination in
brachytherapy:
Mucosal infiltration is usually
picked up on visual inspection only.
The ideal imaging modality for soft
tissue resolution : MRI
Tumors are usually contoured in
the T2 weighted image
T1 images are better for detection
of lymphadenopathy
123. Target Volumes
The target volumes as defined by ICRU 58 are similiar to the
ICRU 62 recommendations
Modifications specific to brachytherapy:
PTV generally “approximates” CTV as applicators are
considered to maintain positional accuracy.
If the patient is treated with EBRT / Sx prior to brachy the CTV
is the initial tumor volume (GTV) prior to treatment.
The GTV for brachytherapy should be recorded seperately in
such cases.
Due to high dose gradient organ delineation is meaningful if
done in the vicinity of the applicator
For luminal structures wall delineation can give a better idea
about the dose received as compared to the whole volume
124. Image based brachytherapy
Dose Distribution at level of 3 D view of the
ovoids and tandem applicator geometry
Bladder
Rectum
3 D Dose
distribution
125. Provisional Planning
B Mode USG with stepper
Pubic
Template arch
Prostate
Urethra
Rectum
Saggital Image with template overlay
Acquired sagittal image
demonstrating bladder prostate
interface
126. Provisional Planning
Beaulieu et al reported on 35 cases (IJROBP 2002)
Prostate contours were created in a preplan setting as well
as in the operating room (OR).
In 63% of patients the volume of the prostate drawn had
changed.
These changes in volume and shape resulted in a mean dose
coverage loss of 5.7%.
In extreme cases, the V100 coverage loss was 20.9%.
At present applied clinically for prostate cancer only.
For both intraluminal and intracavitary significant changes of
the anatomy on application preclude provisional planning.
127. Image Guided Brachytherapy
Radiation Oncologist Contouring and dose
acquiring sectional planning being done The finalized plan with
USG images on the TPS the superimposed grid
on the template
indicated the point of
placement of each
needle
128. Image Guided Brachytherapy
“Seed afterloader” with
the needle containing
the in postion.
Needles being
inserted into the
prostate under
direct USG
A machine called the guidance
seed loader can
receive instructions
from the TPS directly
129. Image Guide Brachytherapy
Final Seed placement
View of the B Mode Stepped USG device
with the template for insertion of the
needles. Some needles have been
placed already
131. Results
Keasten et al (IJROBP 2006)
564 patients of prostate CA – IGRT or IGBRT (5 yr FU)
5-year BC rates were similar in both groups (78–82% for IGRT vs
80–84% for IGBRT)
IGRT higher chronic grade≥2 GI toxicity (22% vs 12% for
EBRT+HDR)
EBRT+HDR higher chronic grade≥2 GU toxicity (30% vs 17% for
IGRT)
Nandalur et al (IJROBP 2006)
479 Prostate cancer patients IGRT vs IGBT
5 yr biochemical control rates > 90% (GR III toxicity ~ 4-6%!!)
C-IGBT patients experienced significantly less chronic grade 2 GI
toxicity and sexual dysfunction.
132. Electronic Brachytherapy
AXXENT Customized Ballon
Applicator
X ray Source Assembly
KV Xray Tube
133. Conclusions
Conformal radiation therapy requires a good imaging guidance and
better machines for delivery – development expensive and time
consuming
Dosimetric results invariably show superiorty of conformal
avoidance
IMRT the best conformal EBRT technique can allow new methods
of radiotherapy – bringing hypofractionation back into fashion
Several unresolved questions – sparse but emerging clinical data
Cancers of developing nations – stand maximum to gain from
Conformal radiation therapy
Approach – Cautious Embrace?
134. Thank You
Radiotherapy can treat 30% cancers while Chemo/Biotherapy 2% -
But considered as the “sticking plaster” of oncology”
S. Webb
Editor's Notes
Effecient delivery requires fast beam cycling – dark current in tube can cause unwanted radiation during movement.
A third system (BodyFIX, Medical Intelligence) has been evaluated by Fuss et al. (2004). It consists of a base plate with variable sizes of a vacuum cushions and a clear plastic foil covering the patient’s body. The cushion is modeled using an additional vacuum between the patient’s front and a plastic foil. An arch-like attachment can be affixed to the base plate providing CT-, MR-, and PET-visible fiducials.
Radiolabelled Thymidine based markers are based on the principle that they can be used to detect proliferation of cells as onlu actively divinding cells take up thymidine.The use of these markers can thus allow the oncologist to obtain a rough idea of the proliferation markers. The use of cell proliferation markers namely amino acids provides us with the advantage that the inflammatory cells take up less of the substance and so it is possible to image the tumor bearing tissues seperately. Hypoxia markers are substances that contain a nitroimidazole entity which is reduced and subsequently the entire molecule is taken up by the concerned cell. It acts as a hypoxia marker in such circumstances. Among all the hypoxic cell markers the Cu-ASTM i s the best as: The images are produced within 10 min of contrast injection. Images have high contrast with moderate doses. The substance is taken up by cells with active mitochondria and thus it is possible to distinguish alive cells from necrotic ones. Apoptosis markers are based on certain molecules that avidly bind to domains of membrane lipids that are exposed on apoptotic cells, Annexin V is an example of such a molecule and it binds to the membrane bound phosphatidyl serine which is exposed on the outer leaflet of cell membrane on cell death.
The registration metrics used are of two broad types: Geometry based metrics : This metric type finds the difference between two images based on several points or surface of a structure(s) in question Intensity based metrics : This type of metric attempts to evaluate the difference in the two images by using numerical grey scale differences. The geometry based metrics are limited by the ability to precisely determine the location of identical points or delineate the surface of the organ in question in two image sets. This is allright in certain structures like the brain. However the different levels of imaging contrast provided by different studies makes the use of this process difficult in practice in other areas The intensity based metrics on the other hand determine the differnce in the intensity distribution of voxels and calculate the degree of transformations required. Various types of intensity based metrices exist: Sum of squared differences Cross correlation metric Mutual information metric The mutual information technique is most commonly used to estimate the differnce in the intensity of voxel values. The technique's strength lies in the fact that it can overcome differences due to areas of different contrasts in the two images and in addition it can overcome the problem due to missing data.
This diagram illustrates the three senarios faced by the oncologist in choosing a PTV Senario A : Here the OAR are far away and the PTV can be derived by simple addition of the internal margin and setup margin. Also note that the IM is constant and definable. Here the TCP is highest but if there are critical OARs nearby they can be seriuosly damaged. Senario B : Here the IM is not well defined and hence the PTV margins are not simple addition of the IM and SM. This is a typical senario in areas where the target volume has significant interfraction and intrafraction movement. The PTV margins are derived mainly from clinical experience. Senario C : This includes a series of senarios where the OARs are closer and closer to the gross tumor (as represented by the inward pointed arrow\\. Alsot the IM varies with time. Due to closeness of the margin, a single margin is defined to include the SM and IM depending on the distance to the OAR. Note that in all these senarios the margin doesnot impinge upon the GTV – if id did the treatment aim would be palliation instead of cure.
Organs can be classified into 4 broad types based on the arrangement of the FSUs: Serial : Where the FSUs are arranged in serial and damage to one can result in the total impairment of function of the organ. Example: Spinal cord Parallel : Here the FSU are arranged in parallel so that damage to a certain proportion of the FSUs are required befor e functional deterioration becomes apparent. Example Parotid Gland, Lung and Kidney Serial in parallel : These organs have serially arranged FSU so that damage to a single FSU can impair the function significantly but damage to a certain proportion is still required before the damage becomes apparent. Example: Heart. Combination of serial and parallel organs : Here the damage to the serial component can result in the stoppage of function of the organ concerned. Example is the nephron The concept of the organization of the FSUs has lead to a new classification of organs for purposes of calculation of the equivalent dose. Organs are now classified into 3 categories: Critical Element(CE) : Example Spinal Cord Critical Volume (CV) : Example Lung Graded Response (GR) : Example oral mucosa
BEV Display : The observer’s viewing point is at the source of radiation looking out along the axis of the radiation beam. Allows planner to visualize target volumes and critcal organ volumes facilitating planning of the aperture. REV Display : The planner can simulate any arbitrary viewing location within the treatment room. Allows planner to appreciate the composite beam arrangement and geometry Digitally Composite Radiograph is a type of DRR that allows different ranges of CT numbers that relate to a certain tissue type to be selectively suppressed or enhanced in the image. Analogous to a transmission radiograph through a virtual patient where certain tissue types have been removed , leaving only the organs of interest to be displayed. Allow better visualization of the organ of interest
Spatial dose distribution in the 3 dimensional volume is first defined. Defination of dose coverage for the PTV(s) Defination of sparing for the organ at risk Establishment of a hierarchy of targets and organs at risk Beam intensity distribution required to achieve this dose distribution goal would be calculated. Photon Fluence required to deliver this intensity distribution is then generated.
Normally optimization as done today is a repetative process which requires plan generation, calculatio, evaluation and repeat iteration by changing the priorities or penalties. As such the process of designing priorities and penalties is not intuitive and optimization solution will not arrive at the biologically optimal solution in all cases. Multicriteria optimization is a process where a set of inverse plans are generated with variety of dose solutions. These solutions form a continuum from one extreme of the dose spectrum to the other. These plans together form a set of pareto optimal solutions and one solution among them is the pareto optimal. The pareto optimal is that solution where an improvement in one criteria will not occur without a deterioration in the other. The planner then has to choose the pareto optimal instead of choosing the criteria or the penalty. A software allows an interactive visualization of the possible solutions and based on the EUD concept one can determine the TCP and NTCP that is acceptable. For this the sliders in the triangular area are moved back and forth for each organ so that the solution for that TCP and NTCP is taken from the database and presented to the individual.
Langen, K. M., & Jones, D. T. (2001). Organ motion and its management. International journal of radiation oncology, biology, physics, 50(1), 265-78.
Room mounted OBI systems are present in two modern day systems: Cyberknife (Accuray) BrainLAB (Exectrac system) RTRT system installed at the Hokkoido university The advantages of the room mounted OBI are: Advantageous for real time tracking of implanted radiological markers High degree of mechanical precision As the intensifiers or the As-Si panels are far away from the treatment head so image is not deteriorated by the simultaneous scatter from the MV beam. In addition the mechanical precision is very high as the parts are not moving The disadvantages of the room mounted OBI are: Small field of view Poor imaging effeciency – so high doses of radiation have to be used unconventional imaging angles are another downside The gantry mounted systems have the advantages that: They have a large field of view Can image tumors from conventional angles Cone beam CT scans can be obtained Direct tumor tracking like in lung is also possible Gantry mounted systems are available commercially by Varian as well as Elekta IRIS (Intgrated Radiotherapy Imaging System) developed at Japan uses two orthogonally mounted gantry based OBI system and can potentially give more accurate tumor localization
During the simulation process the CT scans are acquired with the tracking system in situ so that the motion can be recorded. The system can acquire the CT scan in two modes: In one mode the scans are acquired in only the specified phase of respiration – a single set of CT scans is acquired (prospective trigerring). In the other mode CT images are continously acquired at all phases of the respiratory cycle for each position and subsequntly the images are correlated with the respiratory cycle phase to generate imaging data for each phase (retrospective triggering - 4-D CT) The treatment process is analogous with the beam being turned on at the particular phase of treatment only. The limitations of the system include: The patient should be cooperative and hold breath regularly in a taught pattern The patient should be taught regarding the process The imaging and treatment are time consuming Treatment time is increased by 10 -15 min The period of gating can be choosen according to: Phase of respiration : usually the end expiration is more reproducible Amplitude of respiration: The beam turns on at predetermined degrees of excursion of the chest.
This is an example of a 4 D CT scan acquired for a patient with implanted hepatic markers. The first CT scan represents the image of the patient in a normal helical CT. Note that due to the nature of respiratory motion the implanted fiducial appears twice in the normal image. The motion artifacts are present in the CT image and the outline of the abdominal skin is also jagged because of the motion. These defects are absent in the 3D CT data sets as they were taken for the same respiratory phase.
Various image matching algorithms are available. All of them work on the principle of creation of deformation vector maps from the 4 D CT data and then image is manipulated for voxel matching. Each algorithm has a similiarty metric or end point which is to be acheived e.g. matching contour of a designated organ and an interpolation method. Various methods in development have errors ranging from 1 -3 mm and are not foolproof yet.
Maximum experience with this modality is in the William Beaumont Hospital mDIBH technique has the advantage of moving the lung away from the treatment fields 2 sets of CT scans are taken – one free breathing for setup and the other with ABC for treatment Patients are setup according to coordinates provided by the setup CT The ABC apparatus is used to deliver the treatment synchronized to the mDIBH phase. Segments of fields for IMRT are subdivided to coincide with the breath hold sessions Mean Setup variation of 2.5 mm in sueproinferior direction Mean setup variation of 1.6 mm in the transverse direction Treatment time usually 15 min Other studies: Hepatic Tumors (University of Michigan) Setup error reduced with mean error of 6.7 mm to 3.5 mm in superoinferior direction Reduced margins allowed increase in tumor dose by 5 Gy In Lung tumors movements in lung tumors can be as low as 2 mm
The treatment to an imaged tumor position can only be delivered after a certain period of time in which the image is processed. The time for image processing and the signal processing for MLC / machine movement is unavoidable. Thus actual real time Adaptive radiotherapy is not possible.
The 5-year and 7 year bRFS rate for 2991 localized prostate cancer patients: Radical Prostatectomy : 81% , 76% EBRT <72, 51%, 48% EBRT ≥72, 81% , 81% Permanent Implant: 83%, 75% (Kupelian, P. A., Potters, L., Khuntia, D., Ciezki, J. P., Reddy, C. A., Reuther, A. M., et al. (2004). Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy >=72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. International Journal of Radiation Oncology*Biology*Physics, 58(1), 25-33.)
The use of 3DCRT, particularly with only 3–4 beam angles, can reduce toxicity but has limited potential for dose escalation beyond the current standard in node (+) patients. IMRT is of minimal value in node (-) cases, but is beneficial in node (+) cases or those with target volumes close to the esophagus. In node positive (+) cases, however, IMRT reduced the lung V20 and mean dose by 15% and lung NTCP by 30% compared to 3DCRT. When meeting all normal tissue constraints in node (+) patients, IMRT can deliver RT doses 25–30% greater than 3DCRT and 130–140% greater than ENI. While the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.
In Brain Tumors especially high grade leisons IMRT is being evaluated as a method to deliver hypofractionated radiation to the gross tumor volume without excessive neurotoxicity. However the approach is not validated yet. Small series have also looked at IMRT in situations like clival chordomas, optic nerve gliomas and pituitary tumors.
In Carcinoma Cervix IMRT can be used in the following senarios: As a replacement for 4 field box technique to deliver WPRT As a replacement for conventional RT for EFRT As an alternative to Brachytherapy when ICBT is not possible. Along with brachytherapy for boosting the pelvic nodes as an alternative to parametrial EBRT boost or Interstital brachytherapy As a method to reduce bone marrow radiation dose to ensure better chemotolerance for concomitant Chemoradiation.
The IMRT plans improved the dose conformality around the PTV and pelvic lymph nodes, keeping Dmax within the PTV. Particularly helpful for inguinal lymph nodes coverage with a >25% improvement. IMRT plans greatly improved tissue sparing for critical normal structures including the bladder, femoral heads and bowel. Mean bladder dose decreased 59–65%, femoral head dose by 3–22%, and bowel dose by 27–38%. The low dose to bone marrow was similar for the different plans. PTV coverage and tissue sparing appeared to be equivalent between standard and integrated boost plans.
LINAC based stereotactic radiotherapy offers several advantages which include: Treatemnt of wide range of leisons possible Treatment can be given for extracranial target The machine can be used for IMRT/IMAT etc On board imaging including stereoscopic Xrays and On board KC CT scanners are intergrated. RPM system based motion gating possible. Patient postion can be maintained with non invasive frame based systems Both MLC based and circular collimator based aperture designing possible. Output is higher so the entire treatment is completed quickly Collimators used in radiosurgery are of two types: Conical Collimators: Used in the NOVALIS BrainLAB system Circular Collimators Used in the Trilogy system Collimators come in diameters of 1 -35 mm – However use is cumbersome MicorMLCs circimvent the problem of a fixed collimator opening by allowing a dynamic field shaping.
It consists of a robotic system with 6 MV LINAC. The robotic arms are computer controlled and have
Applicators used for IGBRT should be such that the applicator doesnot produce an artifact on the cross sectional imaging technique being used. For this purpose special CT/MRI Compatible apllicators should be used. The applicators are usually made up of a titanium alloy which has other advantages like: Corrosion resistance High tensile stength Easy to clean Precisely machined to minimize tissue trauma Long service life Capable of repeated use The principle disadvantage of using Titanium in these applicators is the cost. Now a days carbon fibre based brachytherapy applicators are also available.
Patient is first placed in lithotomy position and 150 cc of contrast is introduced into the bladder. The urethra may be delineated with air filled gel which gives good contrast on USG A B mode USG is taken from the base of the prostate to the apex and the prostate is contoured at 5 mm intervals. The dose distribution is planned and needles are inserted using the template. Indications for prostate brachythearpy are : Patients should have a life expectancy of at least five years. The disease should be localised within the prostate capsule, ie stage T1 and T2. GS < 7 ; PSA < 10 ng/mL (if treated with implant only) IPSS score < 15 There should be no evidence of metastases in bones or pelvic lymph nodes. The prostate volume should be less than 50 – 60 cm³ in order to avoid interference with the pubic arch. Patients with T2 tumors with GS > 7 and PSA > 20 are best served with a boost implant
Beaulieu L, Aubin S, Tascherean R, et al. Dosimetric impact of the variation of the prostate volume and shape between pretreatment planning and treatment procedure. Int J Radiat Oncol Biol Phys. 2002;53(1):215–221.
Goes by the name of AXXENT Uses a 30 - 50 KV Miniature Xray tube which is actively water cooled The Xray tube is attached to a High Voltage Cable and the assembly is flexible and retractable like a HDR source assembly. Output 10 cGy at 1 cm in water. Air Kerma Rates are comparable to 10 Ci Ir 192 HDR Source Source is 2 mm in diameter Has a different anisotropy profile than HDR Sources Radiobiology is still under investigation – preclinical trials in animals have indicated need for a further dose rate correction.