New Techniques in Radiation therapy

Moderator: Dr S C Sharma Department of Radiotherapy PGIMER Chandigarh

Trends
Number of Publications in Google Scholar
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1990

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3 DCRT IMRT

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IGRT

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Overview
3 3 DCRT DCRT IMRT IMRT Tomotherap Tomotherap y y

Teletherapy Teletherapy

IGRT IGRT

DART DART

Radiation Radiation Therapy Therapy

Stereotactic Stereotactic radiotherapy radiotherapy

Gamma Gamma Knife Knife LINAC LINAC based based Cyberknife Cyberknife

Brachytherap Brachytherap y y

Image Image Assisted Assisted Brachytherpy Brachytherpy Electronic Electronic Brachytherapy Brachytherapy

Solutions ?

Electron Electron s s Proton Proton s s Use radiation technologies Use alternative alternative Develop radiation modalities modalities Develop technologies to to circumvent circumvent limitations limitations Mesons Mesons Neutron Neutron s s

Heavy Heavy Charged Charged Nuclei Nuclei Antiprotons Antiprotons

Development Timeline
Takahashi discusses conformal RT 1st MLCs invented (1959)

1950 1960 1970 1980

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

Wedge: Uniform Modulation

Coarse spatial and Coarse intensity

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 eldshaping alone Techniques to modulate the intensity of uence across the geometricallyshaped eld (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 elds Dynamic MLC techniques (DMLC) including modulated arc therapy (IMAT) Binary MLCs - NOMOS MIMiC and in tomotherapy Robot delivered IMRT Scanning attenuating bar Swept pencils of radiation (Race Track Microtron - Scanditronix)

Comparision

MLC based IMRT

Step & Shoot IMRT

Since beam is interrupted between movements leakage radiation is less. Easier to deliver and plan. More time consuming

Distance

Dynamic IMRT

Faster than Static IMRT Smooth intensity modulation acheived Beam remains on throughout leakage radiation increased More susceptible to tumor motion related errors. Additional QA required for MLC motion accuracy.

Intesntiy

Distance

Caveats: Conformal Therapy

Significantly increased expenditure:

Machine with treatment capability Imaging equipment: Planning and Verification Software and Computer hardware

Extensive physics manpower and time required. Conformal nature highly susceptible to motion and setup related errors Achilles heel of CFRT Target delineation remains problematic. Treatment and Planning time both significantly increased Radiobiological disadvantage:

Decreased dose-rate to the tumor Increased integral dose (Cyberknife > Tomotherapy > IMRT)

3D Conformal Radiation Planning

How to Plan CFRT

Patient positioning and Immobilization

Volumetric Data acqusition

Image Transfer to the TPS

Treatment QA

Treatment Delivery Forward Planning Inverse Planning Dose distribution Analysis 3D Model generation

Target Volume Delineation

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

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

Flat couch top insert

PET scanner

CT Scanner 60 cm

Allows Allows hardware hardware based based registration registration as as the the patient patient is is scanned scanned in in the the treatment treatment position position CT CT images images can can be be used used to to provide provide attenuation attenuation correction correction factors factors for for the the PET PET scan scan image image reducing reducing scanning scanning time time by by upto upto 40% 40%

Markers for PET Scans

Metabolic marker

2- 18Fluoro 2- Deoxy Glucose Radiolabelled thymidine: 18F Fluorothymidine Radiolabelled amino acids: Methyl methionine, 11C Tyrosine
60Cu-diacetyl-bis(N-411C

Proliferation markers

Hypoxia markers

methylthiosemicarbazone) (60Cu-ATSM)

Apoptosis markers

PET Fiducials

99

Technicium Annexin V

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) Rigid Translations and Rotations Deformable For motion studies

Types of Transformations:

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) Targeted Volume Irradiated Volume Biological Volume

Other volumes:

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

ITV

TV

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.

IV

PTV

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. PET fused images lead to a change in GTV volume in 79%. Can improve parotid sparing in 70% patients.

Head and Neck Cancer:

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 Total Dose Dose Total Total Time Time of of delivery delivery of of dose dose Define Define a a dose dose objective objective Total Total number number of of fractions fractions Organ Organ at at risk risk dose dose levels levels

Choose Choose Number Number of of Beams Beams Choose Choose beam beam angles angles and and couch couch angles angles

Choose Choose Planning Planning Technique Technique

Forward Forward Planning Planning

Inverse Inverse Planning Planning

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

Beams Eye View Display Room's Eye View

Digital Composite Radiograph

Inverse Planning
Inverse Inverse Planning Planning

1. 1. Dose Dose distribution distribution specified specified

Forward Forward Planning Planning 3. 3. Beam Beam Fluence Fluence modulated modulated to to recreate recreate intensity intensity map map

2. 2. Intensity Intensity map map created created

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 Rectum

DVH display

PTV

GTV

Plan Evaluation

Differential DVH

Cumulative DVH Colour Wash Display

Image Guided Radiotherapy and 4D planning

Why 4D Planning?

Organ motion types:

Types of movement:

Interfraction motion Intrafraction motion

Translations:

Craniocaudal Lateral Vertical Roll Pitch Yaw Flattening Balloning Pulsation

Even intracranial structures can move 1.5 mm shift when patient goes from sitting to supine!!

Rotations:

Shape:

Interfraction Motion

Prostate:

Rectum:

Motion max in SI and AP SI 1.7 - 4.5 mm AP 1.5 4.1 mm Lateral 0.7 1.9 mm SV motion > Prostate SI: 7 mm AP : 4 mm

Diameter: 3 46 mm Volumes: 20 40% In many studies decrease in volume found Max transverse diameter mean 15 mm variation SI displacement 15 mm Volume variation 20% 50%

Bladder:

Uterus:

Cervix:

Intrafraction Motion

Liver:

Lung:

Normal Breathing: 10 25 mm Deep breathing: 37 55 mm Normal breathing: 11 -18 mm Deep Breathing: 14 -40 mm Average 10 -30 mm

Quiet breathing

AP 2.4 1.3 mm Lateral 2.4 1.4 mm SI 3.9 2.6 mm

Kidney:

2 to Cardiac motion: 9 lateral motion

6 mm

Tumors located close to the chest wall and in upper lobe show reduced interfraction motion. Maximum motion is in tumors close to mediastinum

Pancreas:

IGRT: Solutions
Imaging Imaging techniques techniques

USG USG based based BAT BAT Sonoarray Sonoarray I-Beam I-Beam Resitu Resitu

Video Planar CT Video based based Planar XXCT ray ray AlignRT AlignRT Photogrammetry Photogrammetry Fan Real Fan Beam Beam Real Time Time Video Video guided guided IMRT IMRT Tomotherapy Video substraction Video substraction In room CT MV MV CT CT Siemens

MRI MRI Cone Cone Beam Beam

KV KV X-ray X-ray OBI OBI Gantry Gantry Mounted Mounted Varian Varian OBI OBI Elekta Elekta Synergy Synergy IRIS IRIS

Room Room Mounted Mounted Cyberknife Cyberknife RTRT RTRT (Mitsubishi) (Mitsubishi) BrainLAB BrainLAB (Exectrac) (Exectrac)

MV MV X-ray X-ray EPI

KV KV CT 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) 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.

Problems with EPI:

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 electrode

High voltage applied

Liquid 2,2,4 trimethylpentane

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

d d with with the the RPM RPM system system to to ascertain ascertain baseline baseline motion motion profile profile

A A periodicity periodicity filter filter algorithm algorithm checks checks the the breathing breathing per per Breathing Breathing comes comes to to a a rythm rythm

Breathing Breathing cycle cycle is is recorded 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) Logistic Constraints: Time requirement for a single contouring can be increased by a factor of ~ 10. Fundamental Constraints:

Why automatic contouring?

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 Options for for 4D 4D delivery delivery

Ignore Ignore motion motion

Freeze Freeze the the motion motion

Follow Follow the the motion motion (Tracking) (Tracking)

Patient Patient breaths breaths normally normally Respiratory Respiratory Gating Gating

Breathing Breathing is is controlled controlled Breath Breath holding holding (DIBH) (DIBH) Jet Jet Ventilation Ventilation Active Active Breathing Breathing control control

Minimizing Organ Motion

Abdominal Compression(Hof et al. 2003 Lung tumors):

Breath Hold technique:

Cranio-caudal movement of tumor 5.12.4 mm. Lateral movement 2.61.4 Anterior-posterior movement 3.11.5 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

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 Implanted radiofrequncy coils (tracked magnetically) Implanted wireless transponders (tracked using wireless signals) 3-D USG based tracking (earlier BAT system)

Non radiographic tracking:

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. 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

4 ways to adapt radiation beam to tracked tumor motion:

ART: Concept
1. 2. 3.

Offline ART Conventional Rx Individual patient based Sample Population based margins Frequent imaging of margins 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

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

Binary MLCs are provided 2 positions open or closed Pneumatically driven 64 leaves Open close time of 20 ms Width 6.25 mm at isocenter 10 cm thick 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.

Y jaw

Fan Beam

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

Newer Techniques in Radiation therapy

Prostate Cancer

Late rectal toxicity (Gr 2 or more) is seen in 20 30%; ED occurs in 50 -60%!!!

Prostate Cancer

Zelefsky et al (2006, J. Urol) 561 patients (1996 - 2000) All localized prostate cancer Risk group according to the NCCN guidelines Treated with IMRT

NAAD 10%

Dose: 81 Gy in 1.8 Gy PTV dose homogenity

Rectal wall constraints:

53% vol = 46 Gy 36% vol = 75.6 Gy

Prostate Cancer

8 yr biochemical relapse free survival rates:

85% - Favourable 76% - Intermediate 72% - Unfavourable 100% - Favourable 96% - Intermediate 84% - Unfavourable

CSS (8 yrs):

NAAT: No significant difference in outcomes

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%. 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%.

Urinary Toxicity:

47% patient developed ED (43% IMRT alone; 57% ADT) No 2nd cancers!

Prostate Cancer

91% 71% 63%

Arcangeli et al (2007) WP-IMRT with Prostate boost N = 55; All had NAADT, Risk of 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%

Head and Neck Cancers

Table showing Results of IMRT in H&N Ca

Head and Neck Cancers

Table showing results of IMRT in H& N Ca

Head and Neck Cancers

Table showing Salivary sparing and QOL improvement with IMRT

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

Breast Cancer

The control arm had 1.7 times (95% CI 1.22.5) 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

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

Table showing results of IMRT in Lung Cancer

Brain Tumors

Table showing results of IMRT in brain tumors

Cervical Cancer

Anal Canal

New Techniques in Stereotactic Radiation therapy

Stereotaxy

Derived from the greek words Stereo = 3 dimensional space and Taxis = to arrange. A method which denes a point in the patients 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, dened 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

d application application of of a a stereotactic stereotactic frame frame to to the the patient patient

Two braod groups:

Radiosurgery: Single treatment fraction Radiotherapy: Multiple fractions

D D Volumetric Volumetric imaging imaging with with the the frame frame attached attached

Target Target delineation delineation and and Treatment Treatment planning planning

Frameless stereotactic radiation is possible in one system cyberknife used: Cranial Extracranial

ioning of tioning of patinet patinet with with the the frame frame after after verification verification Sites

QA QA of of treatment treatment and and delivery delivery of of therapy therapy

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 Robotic arm with 6 degrees of freedon

6 MV LINAC 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

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.

New Techniques in Brachytherapy

Brachytherpy

An inherently conformal method of radiation delivery Relies on the inverse square law for the conformity Unlike traditional EBRT brachytherapy is both :

Rapid dose fall off from the radio-isotope

Physically conformal Biologically conformal

Dose

Distance

Recent advances have focused on better method of target identification and radio-

Brachytherapy: What's New

Image Based Brachytherapy Image Guided Brachytherapy Robotic Brachytherapy Electronic Brachytherapy*

Image Assisted 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

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.

Equipment: Overview

Equipment: Imaging

Table showing Imaging modality of choice in different anatomical areas

Equipment: Applicators

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

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

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

Image based brachytherapy

Dose Distribution at level of ovoids and tandem

3 D view of the applicator geometry

Rectum 3 D Dose distribution

Bladder

Provisional Planning
B Mode USG with stepper Template Pubic arch

Prostate Urethra Rectum Acquired sagittal image demonstrating bladder prostate interface Saggital Image with template overlay

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.

Image Guided Brachytherapy

Radiation Oncologist acquiring sectional USG images

Contouring and dose planning being done on the TPS

The finalized plan with the superimposed grid on the template indicated the point of placement of each needle

Image Guided Brachytherapy

Seed afterloader with the needle containing the in postion. Needles being inserted into the prostate under direct USG guidance

A machine called the seed loader can receive instructions from the TPS directly

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

Real Time dynamic IGBRT

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 (7882% for IGRT vs 8084% for IGBRT) IGRT higher chronic grade2 GI toxicity (22% vs 12% for EBRT+HDR) EBRT+HDR higher chronic grade2 GU toxicity (30% vs 17% for IGRT) 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.

Nandalur et al (IJROBP 2006)

Electronic Brachytherapy
AXXENT Customized Ballon Applicator

X ray Source Assembly

KV Xray Tube

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?

Thank You
Radiotherapy can treat 30% cancers while Chemo/Biotherapy 2% - But considered as the sticking plaster of oncology S. Webb