New Techniques In Radiation Therapy
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New Techniques in Radiation therapy Moderator: Dr S C Sharma Department of Radiotherapy PGIMER Chandigarh
Trends Number of Publications in Google Scholar 2000 1750 1500 1250 1000 750 500 250 0
1990
1995 3 DCRT
2000 IMRT
IGRT
2005
Overview 3 DCRT
Teletherapy
IGRT
IMRT
DART
Tomotherapy
Gamma Knife
Radiation Therapy
Stereotactic radiotherapy
LINAC based Cyberknife
Image Assisted Brachytherpy
Brachytherapy Electronic Brachytherapy
Solutions ?
Electrons Protons Neutrons Use alternative radiation Develop technologies to circumvent limitations modalities π- Mesons Heavy Charged Nuclei Antiprotons
Takahashi discusses conformal RT
Tracking Cobalt unit invented at Royal Free Hospital
1970
1st inverse planning algorithm developed by Webb (1989)
1980
1960
1st MLCs invented (1959)
1950
Development Timeline
1990
Boyer and Webb develop principle of static IMRT (1991)
First discussion of Robotic IMRT (1999)
Proimos develops gravity oriented blocking and conformal field shaping
Brahame conceptualized inverse planning & gives prototype algorithm for (1982-88) Carol demonstrates NOMOS MiMIC (1992) Tomotherapy developed in Wisconsin (1993) Stein develops optimal dMLC equations (1994)
Modulation: Examples
Block: Binary Modulation
Coarse spatial and Coarse intensity
Wedge: Uniform Modulation
Fine spatial coarse intensity
Fine Spatial and Fine Intensity modulation
Conformal Radiotherapy Conformal radiotherapy (CFRT) is a technique that aims to exploit the potential biological improvements consequent on better spatial localization of the highdose 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 geometricallyshaped 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
Intesntiy
Distance
Since beam is interrupted between movements leakage radiation is less.
Easier to deliver and plan.
More time consuming
Dynamic IMRT
Intesntiy
Distance
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.
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
Patient positioning and Immobilization
Treatment QA
Volumetric Data acqusition
Image Transfer to the TPS
Target Volume Delineation
Treatment Delivery Forward Planning Inverse Planning Dose distribution Analysis
3D Model 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
Holds the Target in place while the beam is turned on
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”
Cranial Immobilization
BrainLab System
TLC System Leksell Frame
Gill Thomas Cosman System
Extracranial Immobilization
Body Fix system Elekta Body Frame
Accuracy of systems System
Techniqe
Noninvasive Stereotactic frame
Non invasive, mouthpiece
Latinen Frame GTC Frame Stereotactic Body Frame Heidelberg frame Body Fix Frame
Setup Accuracy 0.7– 0.8 mm (± 0.5–0.6 mm)
Non invasive, x = 1.0 mm ± 0.7; y= 0.8 mm ± 0.8; z = 1.7 nasion, earplugs mm ± 1.0 Non invasive, mouthpiece Non invasive, vacccum based Non invasive, vaccum based Non invasive, Vacccum based with plastic foil
X = 0.35 mm ± 0.06; Y = 0.52 mm ± 0.09; Z= 0.34 mm ± 0.09 X = 5 – 7 mm ,Y = 1 cm Z = 1.0 cm (mean) X = 5 mm,Y = 5 mm, Z = 10 mm (mean) X = 0.4 ± 3.9 mm , Y = 0.1 ± 1.6 mm Z = 0.3 ± 3.6 mm. Rotation accuracy of 1.8 ± 1.6 degrees.
With the precision of the body fix frame the target volume will be underdosed (< 90% of prescribed dose) 14% of the time!!!
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
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
Radiolabelled thymidine: Fluorothymidine
18
F
Radiolabelled amino acids: 11C Methyl methionine, 11C Tyrosine
Cu-diacetyl-bis(N-4methylthiosemicarbazone) (60CuATSM) 60
Apoptosis markers
PET Fiducials
Fluoro 2- Deoxy Glucose
Hypoxia markers
18
Proliferation markers
2-
99
Technicium Annexin V
m
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
ITV
TV
IV
PTV
Treated Volume: Volume of the tumor and surrounding normal tissue that is included in the isodose surface representing the irradiation dose proposed for the treatment (V95) Irradiated Volume: Volume included in an isodose surface with 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 Total Time of delivery of dose Define a dose objective
Choose Number of Beams
Choose beam angles and couch angles
Choose Planning Technique
Forward Planning
Inverse Planning
Total number of fractions Organ at risk dose levels
“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.
Planning Beams
Digital Composite Radiograph
Beams Eye View Display Room's Eye View
“Inverse” Planning Inverse Planning
1. Dose distribution specified
Forward Planning
2. Intensity map created
3. Beam Fluence modulated to recreate 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
Bladder
DVH display Rectum
PTV
GTV
Plan Evaluation
Differential DVH
Cumulative DVH Colour Wash Display
Image Guided Radiotherapy and 4D planning
Why 4D Planning?
Organ motion types:
Interfraction motion
Intrafraction motion
Even intracranial structures can move – 1.5 mm shift when patient goes from sitting to supine!!
Types of movement:
Translations:
Craniocaudal
Lateral
Vertical
Rotations:
Roll
Pitch
Yaw
Shape:
Flattening
Balloning
Pulsation
Interfraction Motion
Prostate: 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
Lateral 0.7 – 1.9 mm SV motion > Prostate
Uterus:
Rectum:
SI: 7 mm AP : 4 mm
Cervix:
SI: 4 mm
In many studies decrease in volume found
Bladder:
Max transverse diameter mean 15 mm variation SI displacement 15 mm Volume variation 20% 50%
Intrafraction Motion
Liver:
Lung:
Deep breathing: 37 – 55 mm
Kidney:
Normal Breathing: 10 – 25 mm
Normal breathing: 11 -18 mm
Deep Breathing: 14 -40 mm
Pancreas:
Average 10 -30 mm
Quiet breathing
AP 2.4 ± 1.3 mm
Lateral 2.4 ± 1.4 mm
SI 3.9 ± 2.6 mm
2° to Cardiac motion: 9 ± 6 mm lateral motion Tumors located close to the chest wall and in upper lobe show reduced interfraction motion. Maximum motion is in tumors close to mediastinum
IGRT: Solutions Imaging techniques
USG based
Video based
BAT Sonoarray I-Beam Resitu
Planar X-ray
AlignRT Photogrammetry Real Time Video guided IMRT Video substraction
CT
MRI
Fan Beam
Cone Beam
Tomotherapy In room CT
MV CT Siemens
KV X-ray OBI Gantry Mounted Varian OBI Elekta Synergy IRIS
Room Mounted Cyberknife RTRT (Mitsubishi) BrainLAB (Exectrac)
MV X-ray EPI
KV CT Mobile C arm Varian OBI Elekta Siemens Inline
IGRT: Solution Comparision
DOF = degrees of freedom – directions in which motion can be corrected – 3 translations and 3 rotations
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.
Types of EPID
Liquid Matrix Ion Chamber*
Camera based devices
Amorphous silicon flat panel detectors
Amorphous selenium flat panel detectors
Electrode connected to high voltage “Output” Liquid 2,2,4 electrode trimethylpentane
High voltage applied
ionized liquid
Output read out by the lower electrodes
On board imaging
Intensifier
Gantry mounted OBI
KV Xray Room Mounted OBI
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
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
4D CT Data set
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
+
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
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.
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 Options for 4D delivery
Ignore motion
Freeze the motion
Patient breaths normally
Respiratory Gating
Follow the motion (Tracking)
Breathing is controlled
Breath holding (DIBH) Jet Ventilation Active Breathing control
Minimizing Organ Motion
Abdominal Compression(Hof et al. 2003 – Lung tumors):
Cranio-caudal movement of tumor 5.1±2.4 mm.
Breath Hold technique:
Lateral movement 2.6±1.4 Anterior-posterior movement 3.1±1.5 mm
Patients instructed to hold breath in one phase Usually 10 -13 breath holding sessions tolerated (each 12 -16 sec) 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
a = includes setup error
Adaptive Radiotherapy Planning
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
ART: Concept 1.
2.
Offline ART Conventional Rx Individual patient based Sample Population based margins margins Frequent imaging of Accomadates variations of patients setup for the populations Estimated systemic error No or infrequent imaging corrected based on Largest margin repeated measurements A small margin kept for random error Plans adapted to average changes
3.
Online ART Individual patient based margins Daily imaging of patients Daily error corrected prior to the treatment Smallest margin required Plans adapted to the changing anatomy daily!
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.
ART: Problem
Real time adaptive RT is not possible “today”
ART: Steps..
ART: Steps
Helical Tomotherapy
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
Helical Tomotherapy
LINAC Cone Beam Y jaw Binary MLC
Pneumatically driven 64 leaves
Open close time of 20 ms
Width 6.25 mm at isocenter
10 cm thick
Y jaw
Binary MLCs are provided – 2 positions – open or closed
Fan Beam
Interleaf transmission – 0.5% in field and 0.25% out field Maximum FOV = 40 cm 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 Author
Year
N
CCT
Dose
Result
Yom et al (R, NR)
2005
37 (I)
Yes
63 Gy (median)
7% incidence of Gr III pneumonitis
Yorke et al (P, NR)
2005
78 (3D)
No
Dose escalation (50.7 – 90 Gy);
22% incidence of Gr III pneumonitis above doses of 70 Gy.
Videtec (R, NR)
2006
28 (I)
No
50 Gy in 5 fraction 64% T1; 2.6% Gr II pneumonitis, (SBRT) no Gr III reactions; LC and OS at 1 yr 96.4% and 93% respectively
Scarbrough (R, NR)
2006
17 (I)
Yes
71.2 Gy (69–73.5 Mean age 70; 73% IIIB, FU 1 yr, Gy) No Gr III tox, 2 yr OS 66%
Jensen (P, NR
2007
17 (I)
Yes (citux)
Yom et al (R, NR)
2007 68 (I), 222 (3D)
Yes
66 Gy
Patients no suited for CCRT. 1 Gr III esophagitis; 79% response (6 mo)
63 Gy (median); 60% stage IIIB, FU = 8 mo Dose > 60 Gy (median); Gr III pneumonitis 8% 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
Brain Tumors Author Year N Dose Sultanem 2004 25 60 Gy (GTV); 40 Gy (CTV); 20 #
Luchi
2006 25
Narayana 2006 58
48 – 68 Gy (GTV); 40 Gy (CTV1); 32 Gy (CTV2); 8 # 60 Gy (PTV); 30#
Result All GBM,Post op volume < 110 cc; Majority RPA class 4/5; The 1-year overall survival rate is 40%, Median survial 9 mo. No late toxicity. 2 AA patients; Median KPS 70; 2 yr PFS 53.6%; 2 yr survival 55.6%; Pattern of death – CSF dissemination most common cause of death! 70% GBM; 1 yr OS 30% (2 yr 0%) for GBM; No Gr III late toxicity; Pattern of failure – local
Table showing results of IMRT in brain tumors
Cervical Cancer Author
Year
N
CCT
Dose
Result
Mundt (P,NR)
2003
36
Y 45 Gy (1.8 80% stage I-II; PTV S3 to L4/5 (53%) Gy/#) interspace; Chronic GI toxicity 15% (n= 3; 1 Gr II, 2 Gr I); 50% incidence in Conventional
Mundt (P,NR)
2002
40
Y
Chen (P,NR)
2007
33
Y
Beriwal (P,NR)
2007
36
Y
Kochanski
2005
45 Gy (1.8 60% Acute Gr II toxicity (90% Gr II in Gy/#) Conv.); Less GU toxicity (10% vs 20%); Patients not requiring antidiarrheal halved! 50.4 Gy / 28#
All Stage I -II; All Post Hysterectomy; 1 yr LRC 93%; Acute GI toxicity 36% (Gr III); Acute Gu toxicity 30% (Gr I-II)
45 Gy 2 Yr LC 80%; 2 yr OS 65%; 11 had (EFRT) + recurrences – 9 distant; Gr III toxicity – 10-15 Gy 10% boost 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
Anal Canal Author
Year
N
CCT
Dose
Result
Salama et al (R, NR)
2006
40 (I)
Yes
45 Gy WP + 9 Gy boost
12.5% Gr III GI toxicity, 0 Gr III skin toxicity, 2 year colostomyfree, disease free, and overall survival 81%, 73%, and 86%
Milano et al (P, NR)
2005
17 (I)
Yes
Devisetty (P,NR)
2006
34 (I)
Yes
45 Gy WP + 9 Gy 53% Gr II GI toxicity, No Gr III boost acute or late complications. 82% CR rate, the 2-year CFS, PFS, and overall survial are: 82%, 65%, and 91% 45 Gy WP + 9 Gy 17% Acute GI toxicity; volume of 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 (P,NR)
2006
12 (I)
Yes
30.6 Gy WP + 14.4 Gy Low Pelvic + 9 Gy boost
42% Gr III dermal toxicity, 8% Gr III GI toxicity, 83% CR rate
New Techniques in Stereotactic Radiation therapy
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
Stereotactic Radiation Rigid application of a stereotactic frame to the patient
3 D Volumetric imaging with the frame attached
Target delineation and Treatment planning Postioning of patinet with the frame after verification
QA of treatment and delivery of therapy
Two braod groups:
Radiosurgery: Single treatment fraction Radiotherapy: Multiple fractions
Frameless stereotactic radiation is possible in one system – cyberknife Sites used:
Cranial
Extracranial
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
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
Roof mounted KV X-ray
6 MV LINAC
Robotic arm with 6 degrees of freedon
Circular Collimator attached to head
Frameless patient immobilization couch
Floor mounted Amorphous silicon detectors
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.
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 Tumor
Year
N
Result
Brain mets (Andrews et al)
2004
333 (164 SRT / 164 C)
Survival advantage for patients with single brain mets (Median survival 6.5 – 4.9 mo); Better functional status at follow up – SRT with WBRT Rx in single brain mets (RTOG 9508)
Benign brain tumors ( Kondziolka et al)
2003
285
Malignant Glioma (Souhami et al)
UP
203
95% tumor control (media F/U 10 yr); actuarial tumor control rate at 15 years was 93.7%. Normal facial nerve function was maintained in 95% with aucostic neuromas SRT + EBRT + BCNU did not result in significant survial advantage – 13.6 vs 13.5 mo (RTOG 9305)
Malignant Glioma (Souhami et al)
2002
203
SRT + EBRT + BCNU did not result in significant 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.
Trends Number of Publications in Google Scholar 2000 1750 1500 1250 1000 750 500 250 0
1990
1995 3 DCRT
2000 IMRT
IGRT
2005
Overview 3 DCRT
Teletherapy
IGRT
IMRT
DART
Tomotherapy
Gamma Knife
Radiation Therapy
Stereotactic radiotherapy
LINAC based Cyberknife
Image Assisted Brachytherpy
Brachytherapy Electronic Brachytherapy
Solutions ?
Electrons Protons Neutrons Use alternative radiation Develop technologies to circumvent limitations modalities π- Mesons Heavy Charged Nuclei Antiprotons
Takahashi discusses conformal RT
Tracking Cobalt unit invented at Royal Free Hospital
1970
1st inverse planning algorithm developed by Webb (1989)
1980
1960
1st MLCs invented (1959)
1950
Development Timeline
1990
Boyer and Webb develop principle of static IMRT (1991)
First discussion of Robotic IMRT (1999)
Proimos develops gravity oriented blocking and conformal field shaping
Brahame conceptualized inverse planning & gives prototype algorithm for (1982-88) Carol demonstrates NOMOS MiMIC (1992) Tomotherapy developed in Wisconsin (1993) Stein develops optimal dMLC equations (1994)
Modulation: Examples
Block: Binary Modulation
Coarse spatial and Coarse intensity
Wedge: Uniform Modulation
Fine spatial coarse intensity
Fine Spatial and Fine Intensity modulation
Conformal Radiotherapy Conformal radiotherapy (CFRT) is a technique that aims to exploit the potential biological improvements consequent on better spatial localization of the highdose 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 geometricallyshaped 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
Intesntiy
Distance
Since beam is interrupted between movements leakage radiation is less.
Easier to deliver and plan.
More time consuming
Dynamic IMRT
Intesntiy
Distance
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.
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
Patient positioning and Immobilization
Treatment QA
Volumetric Data acqusition
Image Transfer to the TPS
Target Volume Delineation
Treatment Delivery Forward Planning Inverse Planning Dose distribution Analysis
3D Model 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
Holds the Target in place while the beam is turned on
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”
Cranial Immobilization
BrainLab System
TLC System Leksell Frame
Gill Thomas Cosman System
Extracranial Immobilization
Body Fix system Elekta Body Frame
Accuracy of systems System
Techniqe
Noninvasive Stereotactic frame
Non invasive, mouthpiece
Latinen Frame GTC Frame Stereotactic Body Frame Heidelberg frame Body Fix Frame
Setup Accuracy 0.7– 0.8 mm (± 0.5–0.6 mm)
Non invasive, x = 1.0 mm ± 0.7; y= 0.8 mm ± 0.8; z = 1.7 nasion, earplugs mm ± 1.0 Non invasive, mouthpiece Non invasive, vacccum based Non invasive, vaccum based Non invasive, Vacccum based with plastic foil
X = 0.35 mm ± 0.06; Y = 0.52 mm ± 0.09; Z= 0.34 mm ± 0.09 X = 5 – 7 mm ,Y = 1 cm Z = 1.0 cm (mean) X = 5 mm,Y = 5 mm, Z = 10 mm (mean) X = 0.4 ± 3.9 mm , Y = 0.1 ± 1.6 mm Z = 0.3 ± 3.6 mm. Rotation accuracy of 1.8 ± 1.6 degrees.
With the precision of the body fix frame the target volume will be underdosed (< 90% of prescribed dose) 14% of the time!!!
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
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
Radiolabelled thymidine: Fluorothymidine
18
F
Radiolabelled amino acids: 11C Methyl methionine, 11C Tyrosine
Cu-diacetyl-bis(N-4methylthiosemicarbazone) (60CuATSM) 60
Apoptosis markers
PET Fiducials
Fluoro 2- Deoxy Glucose
Hypoxia markers
18
Proliferation markers
2-
99
Technicium Annexin V
m
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
ITV
TV
IV
PTV
Treated Volume: Volume of the tumor and surrounding normal tissue that is included in the isodose surface representing the irradiation dose proposed for the treatment (V95) Irradiated Volume: Volume included in an isodose surface with 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 Total Time of delivery of dose Define a dose objective
Choose Number of Beams
Choose beam angles and couch angles
Choose Planning Technique
Forward Planning
Inverse Planning
Total number of fractions Organ at risk dose levels
“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.
Planning Beams
Digital Composite Radiograph
Beams Eye View Display Room's Eye View
“Inverse” Planning Inverse Planning
1. Dose distribution specified
Forward Planning
2. Intensity map created
3. Beam Fluence modulated to recreate 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
Bladder
DVH display Rectum
PTV
GTV
Plan Evaluation
Differential DVH
Cumulative DVH Colour Wash Display
Image Guided Radiotherapy and 4D planning
Why 4D Planning?
Organ motion types:
Interfraction motion
Intrafraction motion
Even intracranial structures can move – 1.5 mm shift when patient goes from sitting to supine!!
Types of movement:
Translations:
Craniocaudal
Lateral
Vertical
Rotations:
Roll
Pitch
Yaw
Shape:
Flattening
Balloning
Pulsation
Interfraction Motion
Prostate: 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
Lateral 0.7 – 1.9 mm SV motion > Prostate
Uterus:
Rectum:
SI: 7 mm AP : 4 mm
Cervix:
SI: 4 mm
In many studies decrease in volume found
Bladder:
Max transverse diameter mean 15 mm variation SI displacement 15 mm Volume variation 20% 50%
Intrafraction Motion
Liver:
Lung:
Deep breathing: 37 – 55 mm
Kidney:
Normal Breathing: 10 – 25 mm
Normal breathing: 11 -18 mm
Deep Breathing: 14 -40 mm
Pancreas:
Average 10 -30 mm
Quiet breathing
AP 2.4 ± 1.3 mm
Lateral 2.4 ± 1.4 mm
SI 3.9 ± 2.6 mm
2° to Cardiac motion: 9 ± 6 mm lateral motion Tumors located close to the chest wall and in upper lobe show reduced interfraction motion. Maximum motion is in tumors close to mediastinum
IGRT: Solutions Imaging techniques
USG based
Video based
BAT Sonoarray I-Beam Resitu
Planar X-ray
AlignRT Photogrammetry Real Time Video guided IMRT Video substraction
CT
MRI
Fan Beam
Cone Beam
Tomotherapy In room CT
MV CT Siemens
KV X-ray OBI Gantry Mounted Varian OBI Elekta Synergy IRIS
Room Mounted Cyberknife RTRT (Mitsubishi) BrainLAB (Exectrac)
MV X-ray EPI
KV CT Mobile C arm Varian OBI Elekta Siemens Inline
IGRT: Solution Comparision
DOF = degrees of freedom – directions in which motion can be corrected – 3 translations and 3 rotations
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.
Types of EPID
Liquid Matrix Ion Chamber*
Camera based devices
Amorphous silicon flat panel detectors
Amorphous selenium flat panel detectors
Electrode connected to high voltage “Output” Liquid 2,2,4 electrode trimethylpentane
High voltage applied
ionized liquid
Output read out by the lower electrodes
On board imaging
Intensifier
Gantry mounted OBI
KV Xray Room Mounted OBI
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
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
4D CT Data set
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
+
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
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.
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 Options for 4D delivery
Ignore motion
Freeze the motion
Patient breaths normally
Respiratory Gating
Follow the motion (Tracking)
Breathing is controlled
Breath holding (DIBH) Jet Ventilation Active Breathing control
Minimizing Organ Motion
Abdominal Compression(Hof et al. 2003 – Lung tumors):
Cranio-caudal movement of tumor 5.1±2.4 mm.
Breath Hold technique:
Lateral movement 2.6±1.4 Anterior-posterior movement 3.1±1.5 mm
Patients instructed to hold breath in one phase Usually 10 -13 breath holding sessions tolerated (each 12 -16 sec) 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
a = includes setup error
Adaptive Radiotherapy Planning
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
ART: Concept 1.
2.
Offline ART Conventional Rx Individual patient based Sample Population based margins margins Frequent imaging of Accomadates variations of patients setup for the populations Estimated systemic error No or infrequent imaging corrected based on Largest margin repeated measurements A small margin kept for random error Plans adapted to average changes
3.
Online ART Individual patient based margins Daily imaging of patients Daily error corrected prior to the treatment Smallest margin required Plans adapted to the changing anatomy daily!
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.
ART: Problem
Real time adaptive RT is not possible “today”
ART: Steps..
ART: Steps
Helical Tomotherapy
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
Helical Tomotherapy
LINAC Cone Beam Y jaw Binary MLC
Pneumatically driven 64 leaves
Open close time of 20 ms
Width 6.25 mm at isocenter
10 cm thick
Y jaw
Binary MLCs are provided – 2 positions – open or closed
Fan Beam
Interleaf transmission – 0.5% in field and 0.25% out field Maximum FOV = 40 cm 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 Author
Year
N
CCT
Dose
Result
Yom et al (R, NR)
2005
37 (I)
Yes
63 Gy (median)
7% incidence of Gr III pneumonitis
Yorke et al (P, NR)
2005
78 (3D)
No
Dose escalation (50.7 – 90 Gy);
22% incidence of Gr III pneumonitis above doses of 70 Gy.
Videtec (R, NR)
2006
28 (I)
No
50 Gy in 5 fraction 64% T1; 2.6% Gr II pneumonitis, (SBRT) no Gr III reactions; LC and OS at 1 yr 96.4% and 93% respectively
Scarbrough (R, NR)
2006
17 (I)
Yes
71.2 Gy (69–73.5 Mean age 70; 73% IIIB, FU 1 yr, Gy) No Gr III tox, 2 yr OS 66%
Jensen (P, NR
2007
17 (I)
Yes (citux)
Yom et al (R, NR)
2007 68 (I), 222 (3D)
Yes
66 Gy
Patients no suited for CCRT. 1 Gr III esophagitis; 79% response (6 mo)
63 Gy (median); 60% stage IIIB, FU = 8 mo Dose > 60 Gy (median); Gr III pneumonitis 8% 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
Brain Tumors Author Year N Dose Sultanem 2004 25 60 Gy (GTV); 40 Gy (CTV); 20 #
Luchi
2006 25
Narayana 2006 58
48 – 68 Gy (GTV); 40 Gy (CTV1); 32 Gy (CTV2); 8 # 60 Gy (PTV); 30#
Result All GBM,Post op volume < 110 cc; Majority RPA class 4/5; The 1-year overall survival rate is 40%, Median survial 9 mo. No late toxicity. 2 AA patients; Median KPS 70; 2 yr PFS 53.6%; 2 yr survival 55.6%; Pattern of death – CSF dissemination most common cause of death! 70% GBM; 1 yr OS 30% (2 yr 0%) for GBM; No Gr III late toxicity; Pattern of failure – local
Table showing results of IMRT in brain tumors
Cervical Cancer Author
Year
N
CCT
Dose
Result
Mundt (P,NR)
2003
36
Y 45 Gy (1.8 80% stage I-II; PTV S3 to L4/5 (53%) Gy/#) interspace; Chronic GI toxicity 15% (n= 3; 1 Gr II, 2 Gr I); 50% incidence in Conventional
Mundt (P,NR)
2002
40
Y
Chen (P,NR)
2007
33
Y
Beriwal (P,NR)
2007
36
Y
Kochanski
2005
45 Gy (1.8 60% Acute Gr II toxicity (90% Gr II in Gy/#) Conv.); Less GU toxicity (10% vs 20%); Patients not requiring antidiarrheal halved! 50.4 Gy / 28#
All Stage I -II; All Post Hysterectomy; 1 yr LRC 93%; Acute GI toxicity 36% (Gr III); Acute Gu toxicity 30% (Gr I-II)
45 Gy 2 Yr LC 80%; 2 yr OS 65%; 11 had (EFRT) + recurrences – 9 distant; Gr III toxicity – 10-15 Gy 10% boost 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
Anal Canal Author
Year
N
CCT
Dose
Result
Salama et al (R, NR)
2006
40 (I)
Yes
45 Gy WP + 9 Gy boost
12.5% Gr III GI toxicity, 0 Gr III skin toxicity, 2 year colostomyfree, disease free, and overall survival 81%, 73%, and 86%
Milano et al (P, NR)
2005
17 (I)
Yes
Devisetty (P,NR)
2006
34 (I)
Yes
45 Gy WP + 9 Gy 53% Gr II GI toxicity, No Gr III boost acute or late complications. 82% CR rate, the 2-year CFS, PFS, and overall survial are: 82%, 65%, and 91% 45 Gy WP + 9 Gy 17% Acute GI toxicity; volume of 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 (P,NR)
2006
12 (I)
Yes
30.6 Gy WP + 14.4 Gy Low Pelvic + 9 Gy boost
42% Gr III dermal toxicity, 8% Gr III GI toxicity, 83% CR rate
New Techniques in Stereotactic Radiation therapy
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
Stereotactic Radiation Rigid application of a stereotactic frame to the patient
3 D Volumetric imaging with the frame attached
Target delineation and Treatment planning Postioning of patinet with the frame after verification
QA of treatment and delivery of therapy
Two braod groups:
Radiosurgery: Single treatment fraction Radiotherapy: Multiple fractions
Frameless stereotactic radiation is possible in one system – cyberknife Sites used:
Cranial
Extracranial
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
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
Roof mounted KV X-ray
6 MV LINAC
Robotic arm with 6 degrees of freedon
Circular Collimator attached to head
Frameless patient immobilization couch
Floor mounted Amorphous silicon detectors
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.
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 Tumor
Year
N
Result
Brain mets (Andrews et al)
2004
333 (164 SRT / 164 C)
Survival advantage for patients with single brain mets (Median survival 6.5 – 4.9 mo); Better functional status at follow up – SRT with WBRT Rx in single brain mets (RTOG 9508)
Benign brain tumors ( Kondziolka et al)
2003
285
Malignant Glioma (Souhami et al)
UP
203
95% tumor control (media F/U 10 yr); actuarial tumor control rate at 15 years was 93.7%. Normal facial nerve function was maintained in 95% with aucostic neuromas SRT + EBRT + BCNU did not result in significant survial advantage – 13.6 vs 13.5 mo (RTOG 9305)
Malignant Glioma (Souhami et al)
2002
203
SRT + EBRT + BCNU did not result in significant 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.
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