New Techniques in Radiation therapy Moderator: Dr S C Sharma Department of Radiotherapy PGIMER Chandigarh

Trends

Overview 3 DCRT Radiation Therapy Teletherapy Brachytherapy IMRT IGRT DART Electronic Brachytherapy Tomotherapy Image Assisted Brachytherpy Stereotactic radiotherapy Gamma Knife LINAC based Cyberknife

Solutions ? Develop technologies to circumvent limitations Use alternative radiation modalities Electrons Protons Neutrons π - Mesons Heavy Charged Nuclei Antiprotons

Development Timeline 1990 1960 Proimos develops gravity oriented blocking and conformal field shaping 1980 Brahame conceptualized inverse planning & gives prototype algorithm for (1982-88) 1 st inverse planning algorithm developed by Webb (1989) 1970 Tracking Cobalt unit invented at Royal Free Hospital 1950 Takahashi discusses conformal RT 1 st MLCs invented (1959) Boyer and Webb develop principle of static IMRT (1991) Carol demonstrates NOMOS MiMIC (1992) Tomotherapy developed in Wisconsin (1993) Stein develops optimal dMLC equations (1994) First discussion of Robotic IMRT (1999)

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 high-dose irradiation volume - S. Webb in Intensity Modulated Radiotherapy IOP

Conformal radiotherapy (CFRT) is a technique that aims to exploit the potential biological improvements consequent on better spatial localization of the high-dose irradiation volume

- S. Webb

in Intensity Modulated Radiotherapy

IOP

Problems in conformation Nature of the photon beam is the biggest impediment Has an entrance dose. Has an exit dose. Follows the inverse square law.

Nature of the photon beam is the biggest impediment

Has an entrance dose.

Has an exit dose.

Follows the inverse square law.

Types of CFRT Two broad subtypes : Techniques aiming to employ geometric fieldshaping alone Techniques to modulate the intensity of fluence across the geometrically-shaped field (IMRT)

Two broad subtypes :

Techniques aiming to employ geometric fieldshaping alone

Techniques to modulate the intensity of fluence across the geometrically-shaped field (IMRT)

Modulation : Intensity or Fluence ? Intensity Modulation is a misnomer – The actual term is Fluence Fluence referes to the number of “particles” incident on an unit area (m -2 )

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)

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

Since beam is interrupted between movements leakage radiation is less.

Easier to deliver and plan.

More time consuming

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

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)

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 Target Volume Delineation 3D Model generation Forward Planning Inverse Planning Dose distribution Analysis Treatment QA Treatment Delivery

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

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

Types of Immobilization Immoblization devices Frame based Frameless Invasive Noninvasive 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 ”

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 TLC System Gill Thomas Cosman System Leksell Frame BrainLab System

Extracranial Immobilization Elekta Body Frame Body Fix system

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

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

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

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 CT Scanner PET 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%

Allows hardware based registration as the patient is scanned in the treatment position

CT images can be used to provide attenuation correction factors for the PET scan image reducing scanning time by upto 40%

Markers for PET Scans Metabolic marker 2- 18 Fluoro 2- Deoxy Glucose Proliferation markers Radiolabelled thymidine: 18 F Fluorothymidine Radiolabelled amino acids: 11 C Methyl methionine, 11 C Tyrosine Hypoxia markers 60 Cu-diacetyl-bis(N-4-methylthiosemicarbazone) ( 60 Cu-ATSM) Apoptosis markers 99 m Technicium Annexin V PET Fiducials

Metabolic marker

2- 18 Fluoro 2- Deoxy Glucose

Proliferation markers

Radiolabelled thymidine: 18 F Fluorothymidine

Radiolabelled amino acids: 11 C Methyl methionine, 11 C Tyrosine

Hypoxia markers

60 Cu-diacetyl-bis(N-4-methylthiosemicarbazone) ( 60 Cu-ATSM)

Apoptosis markers

99 m 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) Types of Transformations : Rigid – Translations and Rotations Deformable – For motion studies

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.

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

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.

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 PTV TV IV 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 (V 95 ) 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.

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 (V 95 )

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 )

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

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.

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

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 Define a dose objective Total Dose Total Time of delivery of dose Total number of fractions Choose Number of Beams Choose beam angles and couch angles Organ at risk dose levels Choose Planning Technique Forward Planning Inverse 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.

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 1. Dose distribution specified Forward Planning 2. Intensity map created 3. Beam Fluence modulated to recreate intensity map Inverse Planning

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

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.

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 Sliders for adjusting EUD Rectum Bladder Intestine PTV GTV DVH display

Plan Evaluation Colour Wash Display Differential DVH Cumulative DVH

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

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 SI 1.7 - 4.5 mm AP 1.5 – 4.1 mm Lateral 0.7 – 1.9 mm SV motion > Prostate Uterus : SI: 7 mm AP : 4 mm Cervix : SI: 4 mm Rectum : Diameter: 3 – 46 mm Volumes: 20 – 40% In many studies decrease in volume found Bladder : Max transverse diameter mean 15 mm variation SI displacement 15 mm Volume variation 20% - 50%

Prostate :

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

Uterus :

SI: 7 mm

AP : 4 mm

Cervix :

SI: 4 mm

Rectum :

Diameter: 3 – 46 mm

Volumes: 20 – 40%

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

Liver :

Normal Breathing: 10 – 25 mm

Deep breathing: 37 – 55 mm

Kidney :

Normal breathing: 11 -18 mm

Deep Breathing: 14 -40 mm

Pancreas :

Average 10 -30 mm

Lung :

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 Mobile C arm Varian OBI Elekta Siemens Inline Imaging techniques USG based Video based Planar X-ray CT MRI BAT Sonoarray I-Beam Resitu AlignRT Photogrammetry Real Time Video guided IMRT Video substraction KV X-ray OBI MV X-ray Gantry Mounted Room Mounted Varian OBI Elekta Synergy IRIS Cyberknife RTRT (Mitsubishi) BrainLAB (Exectrac) EPI Fan Beam Cone Beam Tomotherapy In room CT MV CT KV CT Siemens

Mobile C arm

Varian OBI

Elekta

Siemens Inline

BAT

Sonoarray

I-Beam

Resitu

AlignRT

Photogrammetry

Real Time Video guided IMRT

Video substraction

Varian OBI

Elekta Synergy

IRIS

Cyberknife

RTRT (Mitsubishi)

BrainLAB (Exectrac)

EPI

Tomotherapy

In room CT

Siemens

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.

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” electrode Liquid 2,2,4 - trimethylpentane ionized liquid High voltage applied Output read out by the lower electrodes

Liquid Matrix Ion Chamber*

Camera based devices

Amorphous silicon flat panel detectors

Amorphous selenium flat panel detectors

On board imaging Room Mounted OBI Gantry mounted OBI KV Xray Intensifier

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

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.

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 Expiration End Inspiration MIV

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)

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

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 Day 1 Image Day 2 Image Individaul Pixels Due to the changes in shape of the object the same pixel occupies a different coordinate in the 2 nd 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.

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

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 Follow the motion (Tracking) Patient breaths normally Breathing is controlled Respiratory Gating Breath holding (DIBH) Jet Ventilation Active Breathing control

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. Lateral movement 2.6±1.4 Anterior-posterior movement 3.1±1.5 mm Breath Hold technique: 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)

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

Cranio-caudal movement of tumor 5.1±2.4 mm.

Lateral movement 2.6±1.4

Anterior-posterior movement 3.1±1.5 mm

Breath Hold technique:

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

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 R eal-time P ostion M anagement 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)

Also known as R eal-time P ostion M anagement 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

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 Conventional R x Sample Population based margins Accomadates variations of setup for the populations No or infrequent imaging Largest margin Offline ART Individual patient based margins Frequent imaging of patients Estimated systemic error corrected based on 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! 1. 2. 3.

Conventional R x

Sample Population based margins

Accomadates variations of setup for the populations

No or infrequent imaging

Largest margin

Offline ART

Individual patient based margins

Frequent imaging of patients

Estimated systemic error corrected based on 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

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 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. LINAC Cone Beam Y jaw Y jaw Fan Beam 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.

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

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

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 Treatment Results (Clinical)

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 Dose: 81 Gy in 1.8 Gy PTV dose homogenity ± 10% Rectal wall constraints: 53% vol = 46 Gy 36% vol = 75.6 Gy

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

Dose: 81 Gy in 1.8 Gy

PTV dose homogenity ± 10%

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 CSS (8 yrs): 100% - Favourable 96% - Intermediate 84% - Unfavourable NAAT : No significant difference in outcomes

8 yr biochemical relapse free survival rates:

85% - Favourable

76% - Intermediate

72% - Unfavourable

CSS (8 yrs):

100% - Favourable

96% - Intermediate

84% - Unfavourable

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%. Urinary Toxicity : Grade 2 chronic urethritis in 50 patients (9%); Urethral stricture requiring dilation (grade 3) developed in 18 patients (3%). The 8-year actuarial likelihood of late grade 2 or greater urinary toxicities was 15%. 47% patient developed ED (43% IMRT alone; 57% ADT) No 2 nd cancers!

Rectal Toxicity :

Grade 2: 7 patients (1.5%); Grade 3: 3 patients (less than 1%)

The 8-year actuarial likelihood of late grade 2 or greater rectal toxicity 1.6%.

Urinary Toxicity :

Grade 2 chronic urethritis in 50 patients (9%); Urethral stricture requiring dilation (grade 3) developed in 18 patients (3%).

The 8-year actuarial likelihood of late grade 2 or greater urinary toxicities was 15%.

47% patient developed ED (43% IMRT alone; 57% ADT)

No 2 nd cancers!

Prostate Cancer 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% 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

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 1.2–2.5) more likely to have had some change than the IMRT arm, p = 0.008. Areas with dose > 105% have 1.9 times higher risk of any change in cosmesis

The control arm had 1.7 times (95% CI 1.2–2.5) more likely to have had some change than the IMRT arm, p = 0.008.

Areas with dose > 105% have 1.9 times higher risk of any change in cosmesis

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.

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 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

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 Two braod groups: Radiosurgery: Single treatment fraction Radiotherapy: Multiple fractions Frameless stereotactic radiation is possible in one system – cyberknife Sites used: Cranial Extracranial 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

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 Co 60 sources (30 Ci) Unit Center Point 40 cm Dose Rate 300 cGy/min

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 Co 60 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

Conventional LINAC aperture modified by a tertiary collimator.

Two commercial machines

Varian Trilogy

Novalis

Cyberknife Floor mounted Amorphous silicon detectors 6 MV LINAC Roof mounted KV X-ray Frameless patient immobilization couch Robotic arm with 6 degrees of freedon Circular Collimator attached to head

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.

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

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 : Physically conformal Biologically conformal Recent advances have focused on better method of target identification and radio-isotope placement. Dose Distance Rapid dose fall off from the radio-isotope

An inherently conformal method of radiation delivery

Relies on the inverse square law for the conformity

Unlike traditional EBRT brachytherapy is both :

Physically conformal

Biologically conformal

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

Brachytherapy: What's New Image Based Brachytherapy Image Guided Brachytherapy Robotic Brachytherapy ‡ Electronic Brachytherapy* Image Based Brachytherapy : Technique where advanced imaging modalites are used to gain information about the volumetric dose delivery by brachytherapy Image Guided Brachytherapy : Technique where imaging is used to guide brachytherapy source placement as well give information regarding the volumetric dose distribution Image Assisted Brachytherapy

Image Based Brachytherapy

Image Guided Brachytherapy

Robotic Brachytherapy ‡

Electronic Brachytherapy*

Image Based Brachytherapy : Technique where advanced imaging modalites are used to gain information about the volumetric dose delivery by brachytherapy

Image Guided Brachytherapy : Technique where imaging is used to guide brachytherapy source placement as well give information regarding the volumetric dose distribution

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.

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

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

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

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 the whole volume

The target volumes as defined by ICRU 58 are similiar to the ICRU 62 recommendations

Modifications specific to brachytherapy:

PTV generally “approximates” CTV as applicators are considered to maintain positional accuracy.

If the patient is treated with EBRT / Sx prior to brachy the CTV is the initial tumor volume (GTV) prior to treatment.

The GTV for brachytherapy should be recorded seperately in such cases.

Due to high dose gradient organ delineation is meaningful if done in the vicinity of the applicator

For luminal structures wall delineation can give a better idea about the dose received as compared to the whole volume

Image based brachytherapy Dose Distribution at level of ovoids and tandem 3 D view of the applicator geometry 3 D Dose distribution Rectum Bladder

Provisional Planning B Mode USG with stepper Template Acquired sagittal image demonstrating bladder prostate interface Saggital Image with template overlay Pubic arch Prostate Urethra Rectum

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 V 100 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.

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 V 100 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 A machine called the seed loader can receive instructions from the TPS directly “Seed afterloader” with the needle containing the in postion. Needles being inserted into the prostate under direct USG guidance

Image Guide Brachytherapy View of the B Mode Stepped USG device with the template for insertion of the needles. Some needles have been placed already Final Seed placement

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 (78–82% for IGRT vs 80–84% for IGBRT) IGRT higher chronic grade≥2 GI toxicity (22% vs 12% for EBRT+HDR) EBRT+HDR higher chronic grade≥2 GU toxicity (30% vs 17% for IGRT) Nandalur et al (IJROBP 2006) 479 Prostate cancer patients IGRT vs IGBT 5 yr biochemical control rates > 90% (GR III toxicity ~ 4-6%!!) C-IGBT patients experienced significantly less chronic grade 2 GI toxicity and sexual dysfunction.

Keasten et al (IJROBP 2006)

564 patients of prostate CA – IGRT or IGBRT (5 yr FU)

5-year BC rates were similar in both groups (78–82% for IGRT vs 80–84% for IGBRT)

IGRT higher chronic grade≥2 GI toxicity (22% vs 12% for EBRT+HDR)

EBRT+HDR higher chronic grade≥2 GU toxicity (30% vs 17% for IGRT)

Nandalur et al (IJROBP 2006)

479 Prostate cancer patients IGRT vs IGBT

5 yr biochemical control rates > 90% (GR III toxicity ~ 4-6%!!)

C-IGBT patients experienced significantly less chronic grade 2 GI toxicity and sexual dysfunction.

Electronic Brachytherapy Customized Ballon Applicator KV Xray Tube AXXENT X ray Source Assembly

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 ?

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

Radiotherapy can treat 30% cancers while Chemo/Biotherapy 2% - But considered as the “sticking plaster” of oncology”

S. Webb