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 1995 2000 2005

3 DCRT IMRT IGRT

Overview

3 DCRT IMRT

Teletherapy IGRT DART Tomotherapy

Gamma Knife
Radiation
Stereotactic radiotherapy LINAC based
Therapy
Cyberknife

Image Assisted Brachytherpy

Brachytherapy
Electronic Brachytherapy
Solutions ?

Electrons

Protons

Neutrons
Use alternative radiation
Develop technologies to circumvent limitations
modalities
π- Mesons

Heavy Charged Nuclei

Antiprotons
 Development Timeline

Takahashi discusses conformal RT

1950
1st MLCs invented (1959)

1960
Proimos develops gravity oriented
blocking and conformal field shaping

Tracking Cobalt unit invented

1970
at Royal Free Hospital

1st inverse planning algorithm

1980
Brahame conceptualized inverse planning
developed by Webb (1989) & gives prototype algorithm for (1982-88)

Boyer and Webb develop Carol demonstrates NOMOS MiMIC (1992)

principle of static IMRT (1991) Tomotherapy developed in Wisconsin
(1993)
1990

Stein develops optimal dMLC equations

First discussion of Robotic (1994)
IMRT (1999)
 Modulation: Examples

Block: Wedge:
Binary Modulation Uniform Modulation

Coarse spatial and Fine spatial

Coarse intensity 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
Problems in conformation


Nature of the photon beam
is the biggest impediment

Has an entrance
dose.

Has an exit dose.

Follows the inverse
square law.
Types of CFRT


Two broad subtypes :

Techniques aiming to
employ geometric
fieldshaping alone

Techniques to modulate
the intensity of fluence
across the geometrically-
shaped field (IMRT)
Modulation : Intensity or Fluence
?

Intensity Modulation is a misnomer – The actual term is
Fluence

Fluence referes to the number of “particles” incident on an
unit area (m-2)
How to modulate intensity


Cast metal compensator

Jaw defined static fields

Multiple-static MLC-shaped fields

Dynamic MLC techniques (DMLC)
including modulated arc therapy (IMAT)

Binary MLCs - NOMOS MIMiC and in
tomotherapy

Robot delivered IMRT

Scanning attenuating bar

Swept pencils of radiation (Race Track
Microtron - Scanditronix)
Comparision
MLC based IMRT

√
 Step & Shoot IMRT

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

Distance
Dynamic IMRT

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

Distance
Caveats: Conformal Therapy


Significantly increased expenditure:

Machine with treatment capability

Imaging equipment: Planning and Verification

Software and Computer hardware

Extensive physics manpower and time required.

Conformal nature – highly susceptible to motion and setup related
errors – Achilles heel of CFRT

Target delineation remains problematic.

Treatment and Planning time both significantly increased

Radiobiological disadvantage:

Decreased “dose-rate” to the tumor

Increased integral dose (Cyberknife > Tomotherapy > IMRT)
3D Conformal
Radiation Planning
 How to Plan CFRT

Patient positioning Volumetric Data Image Transfer

and Immobilization acqusition to the TPS

Target Volume
Delineation
Treatment Treatment Delivery
QA
Forward
Planning

Inverse
Planning
Dose distribution 3D Model
Analysis generation
Positioning and Immobilization


Two of the most important aspects of conformal radiation
therapy.

Basis for the precision in conformal RT

Needs to be:

Comfortable

Reproducible

Minimal beam attenuating

Affordable

Holds the Target in place while the beam is turned on

Types of Immobilization

Invasive

Frame based
Noninvasive

Immoblization
devices

Frameless


Usually based on a combination of heat deformable
“casts” of the part to be immobilized attached to a
baseplate that can be reproducibly attached with the
treatment couch.

The elegant term is “Indexing”
Cranial Immobilization

BrainLab System

TLC System

Leksell Frame

Gill Thomas Cosman System

Extracranial Immobilization

Body Fix system

Elekta Body Frame

 Accuracy of systems

System Techniqe Setup Accuracy

Noninvasive Non invasive,
0.7– 0.8 mm (± 0.5–0.6 mm)
Stereotactic frame mouthpiece

Non invasive, x = 1.0 mm ± 0.7; y= 0.8 mm ± 0.8; z = 1.7

Latinen Frame
nasion, earplugs mm ± 1.0
Non invasive, X = 0.35 mm ± 0.06; Y = 0.52 mm ± 0.09;
GTC Frame
mouthpiece Z= 0.34 mm ± 0.09
Stereotactic Body Non invasive,
X = 5 – 7 mm ,Y = 1 cm Z = 1.0 cm (mean)
Frame vacccum based
Non invasive,
Heidelberg frame X = 5 mm,Y = 5 mm, Z = 10 mm (mean)
vaccum based
Non invasive, X = 0.4 ± 3.9 mm , Y = 0.1 ± 1.6 mm Z = 0.3
Body Fix Frame Vacccum based ± 3.6 mm. Rotation accuracy of 1.8 ± 1.6
with plastic foil degrees.

With the precision of the body fix frame the

target volume will be underdosed (< 90% of
prescribed dose) 14% of the time!!!
CT simulator


70 – 85 cm bore

Scanning Field of View (SFOV) 48 cm –
60 cm – Allows wider separation to be
imaged.

Multi slice capacity:

Speed up acquistion times

Reduce motion and breathing artifacts

Allow thinner slices to be taken – better
DRR and CT resolution

Allows gating capabilities

Flat couch top – simulate treatment
table
MRI


Superior soft tissue resolution

Ability to assess neural and marrow infiltration

Ability to obtain images in any plane - coronal/saggital/axial

Imaging of metabolic activity through MR Spectroscopy

Imaging of tumor vasculature and blood supply using a new
technique – dynamic contrast enhanced MRI

No radiation exposure to patient or personnel
PET: Principle


Unlike other imaging can
biologically characterize a leison

Relies on detection of photons
liberated by annhilation reaction
of positron with electron

Photons are liberated at 180° angle
and simultaneously – detection of
this pair and subsequent mapping
of the event of origin allows spatial
localization

The detectors are arranged in an
circular array around the patient

PET- CT scanners integrate both
imaging modalities
PET-CT scanner

PET scanner
Flat couch top insert

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


Metabolic marker

2- 18
Fluoro 2- Deoxy Glucose

Proliferation markers

Radiolabelled thymidine: 18
F
Fluorothymidine

Radiolabelled amino acids: 11C Methyl
methionine, 11C Tyrosine

Hypoxia markers

Cu-diacetyl-bis(N-4-
60

methylthiosemicarbazone) (60Cu-
ATSM)

Apoptosis markers
 99
Technicium Annexin V
m

PET Fiducials
Image Registration


Technique by which the coordinates of identical points in
two imaging data sets are determined and a set of
transformations determined to map the coordinates of one
image to another

Uses of Image registration:

Study Organ Motion (4 D CT)

Assess Tumor extent (PET / MRI fusion)

Assess Changes in organ and tumor volumes over time
(Adaptive RT)

Types of Transformations:

Rigid – Translations and Rotations

Deformable – For motion studies
Concept
Process: Image Registration


The algorithm first measures the degree of mismatch between
identical points in two images (metric).

The algorithm then determines a set of transformations that
minimize this metric.

Optimization of this transformations with multiple iterations take
place

After the transformation the images are “fused” - a display which
contains relevant information from both images.
Image Registration
Target Volume delineation


The most important and most error prone step in
radiotherapy.

Also called Image Segmentation

The target volume is of following types:

GTV (Gross Target Volume)

CTV (Clinical Target Volume)

ITV (Internal Target Volume)

PTV (Planning Target Volume)

Other volumes:

Targeted Volume

Irradiated Volume

Biological Volume
Target Volumes


GTV: Macroscopic extent of the tumor as defined by
radiological and clinical investigations.

CTV: The GTV together with the surrounding microscopic
extension of the tumor constitutes the CTV. The CTV also
includes the tumor bed of a R0 resection (no residual).

ITV (ICRU 62): The ITV encompasses the GTV/CTV with an
additional margin to account for physiological movement of
the tumor or organs. It is defined with respect to a internal
reference – most commonly rigid bony skeleton.

PTV: A margin given to above to account for uncertainities
in patient setup and beam adjustment.
Target Volumes
Definitions: ICRU 50/62
GTV
CTV

Treated Volume: Volume of the
tumor and surrounding normal
ITV
tissue that is included in the isodose
surface representing the irradiation
TV
dose proposed for the treatment
(V95)

Irradiated Volume: Volume
included in an isodose surface with
PTV
IV a possible biological impact on the
normal tissue encompassed in this
volume. Choice of isodose depends
on the biological end point in mind.
Example

PTV

CTV

GTV
Organ at Risk (ICRU 62)


Normal critical structures whose
radiation sensitivity may
significantly influence treatment
planning and/or prescribed dose.

A planning organ at risk volume
(PORV) is added to the contoured
organs at risk to account for the
same uncertainities in patient
setup and treatment as well as
organ motion that are used in the
delineation of the PTV.

Each organ is made up of a
functional subunit (FSU)
Biological Target Volume


A target volume that
incorporated data from
molecular imaging techniques

Target volume drawn
incorporates information
regarding:

Cellular burden

Cellular metabolism

Tumor hypoxia

Tumor proliferation

Intrinsic Radioresistance or
sensitivity
Biological Target Volumes


Lung Cancer:

30 -60% of all GTVs and PTVs are changed with PET.

Increase in the volume can be seen in 20 -40%.

Decrease in the volume in 20 – 30%.

Several studies show significant improvement in nodal
delineation.

Head and Neck Cancer:

PET fused images lead to a change in GTV volume in 79%.

Can improve parotid sparing in 70% patients.
3 D TPS


Treatment planning systems are complex computer systems
that help design radiation treatments and facilitate the
calculation of patient doses.

Several vendors with varying characteristics

Provide tools for:

Image registration

Image segmentation: Manual and automated

Virtual Simualtion

Dose calculation

Plan Evaluation

Data Storage and transmission to console

Treatment verification
Planning workflow
Total Dose

Total Time of delivery of dose

Define a dose objective
Total number of fractions

Choose Number of Beams Organ at risk dose levels

Choose beam angles and couch angles

Choose Planning Technique

Forward Planning Inverse Planning

“Forward” Planning


A technique where the planner will try a variety of
combinations of beam angles, couch angles, beam weights
and beam modifying devices (e.g. wedges) to find a
optimum dose distribution.

Iterations are done manually till the optimum solution is
reached.

Choice for some situations:

Small number of fields: 4 or less.

Convex dose distribution required.

Conventional dose distribution desired.

Conformity of high dose region is a less important concern.
Planning Beams

Digital Composite
Beams Eye View Radiograph
Display

Room's Eye
View
“Inverse” Planning

Inverse Planning

1. Dose distribution specified

Forward Planning

3. Beam Fluence
modulated to recreate
2. Intensity map created
intensity map
Optimization


Refers to the technique of finding the best physical and
technically possible treatment plan to fulfill the specified
physical and clinical criteria.

A mathematical technique that aims to maximize (or
minimize) a score under certain constraints.

It is one of the most commonly used techniques for inverse
planning.

Variables that may be optimized:

Intensity maps

Number of beams

Number of intensity levels

Beam angles

Beam energy
Optimization
Optimization Criteria


Refers to the constraints that need to be fulfilled during the
planning process

Types:

Physical Optimization Criteria: Based on physical dose coverage

Biological Optimization Criteria: Based on TCP and NTCP
calculation

A total objective function (score) is then derived from these
criteria.

Priorities are defined to tell the algorithm the relative
importance of the different planning objectives (penalties)

The algorithm attempts to maximize the score based on the
criteria and penalties.
Multicriteria Optimization

Intestine

Sliders for
adjusting EUD

Bladder DVH display

Rectum

PTV GTV
Plan Evaluation

Differential DVH

Cumulative DVH

Colour Wash Display

Image Guided
Radiotherapy and
4D planning
Why 4D Planning?


Organ motion types: 
Types of movement:

Interfraction motion 
Translations:

Intrafraction motion 
Craniocaudal
Lateral
Even intracranial structures



can move – 1.5 mm shift 

Vertical
when patient goes from 
Rotations:
sitting to supine!! 
Roll

Pitch

Yaw

Shape:

Flattening

Balloning

Pulsation
Interfraction Motion

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


Liver: 
Lung:

Normal Breathing: 10 – 25 
Quiet breathing
mm 
AP 2.4 ± 1.3 mm

Deep breathing: 37 – 55 mm 
Lateral 2.4 ± 1.4 mm

Kidney: 
SI 3.9 ± 2.6 mm

2° to Cardiac motion: 9 ± 6

Normal breathing: 11 -18
mm mm lateral motion


Deep Breathing: 14 -40 mm

Tumors located close to the
chest wall and in upper lobe

Pancreas: show reduced interfraction
motion.

Average 10 -30 mm

Maximum motion is in
tumors close to mediastinum
IGRT: Solutions
Imaging techniques

USG based Video based Planar X-ray CT MRI


BAT 
AlignRT

Sonoarray 
Photogrammetry

I-Beam 
Real Time Video guided Fan Beam Cone Beam

Resitu IMRT 
Tomotherapy

Video substraction 
In room CT

MV CT KV CT
Siemens
 
Mobile C arm
KV X-ray OBI 
Varian OBI

Elekta

Siemens Inline
Gantry Mounted Room Mounted MV X-ray

Varian OBI 
Cyberknife 
EPI

Elekta Synergy 
RTRT (Mitsubishi)

IRIS 
BrainLAB
(Exectrac)
IGRT: Solution Comparision

DOF = degrees of freedom – directions in which motion can be

corrected – 3 translations and 3 rotations
EPI


Uses of EPI:

Correction of individual interfraction errors

Estimation of poulation based setup errors

Verification of dose distribution (QA)

Problems with EPI:

Poor image quality (MV xray)

Increased radiation dose to patient

Planar Xray – 3 dimensional body movement is not seen

Tumor is not tracked – surrogates like bony anatomy or
implanted fiducials are tracked.
Types of EPID


Liquid Matrix Ion Chamber*

Camera based devices

Amorphous silicon flat panel detectors

Amorphous selenium flat panel detectors

Electrode High voltage applied

connected to
high voltage

“Output” Output read out

Liquid 2,2,4 - ionized liquid
electrode by the lower
trimethylpentane
electrodes
 On board imaging

Intensifier

Gantry mounted OBI

KV Xray

Room Mounted OBI

 4 D CT acqusition
Axial scans are acquired
with the use of a RPM
camera attached to couch.

The “cine” mode of the scanner is used to

acquire multiple axial scans at
predetermined phases of respiratory cycle
for each couch position
RPM System

Patient imaged with the RPM system

to ascertain baseline motion profile
A periodicity filter algorithm
checks the breathing periodicity
Breathing comes to a rythm

Breathing cycle is recorded

4D CT Data set

Normal
Problems with 4 D CT


The image quality depends on the reproducibility of the
respiratory motion.

The volume of images produced is increased by a factor of
10.

Specialized software needed to sort and visualize the 4D
data.

Dose delivered during the scans can increase 3-4 times.

Image fusion with other modalities remains an unsolved
problem
4D Target delineation


Target delineation can be done on all images acquired.

Methods of contouring:

Manual

Automatic (Deformable Image Registration)

Why automatic contouring?

Logistic Constraints: Time requirement for a single
contouring can be increased by a factor of ~ 10.

Fundamental Constraints:

To calculate the cumulative dose delivered to the tumor during
the treatment.

However the dose for each moving voxel needs to be integrated
together for this to occur.

So an estimate of the individual voxel motion is needed.
4D Manual Contouring


The tumor is manually contoured in end expiration and end
inspiration

The two volumes are fused to generate at MIV – Maximum
Intensity Volume

The projection of this to a DRR is called MIP (Maximum
Intensity Projection)

End Inspiration

MIV

End Expiration
Automated Contouring


Technique by which a single moving voxel is matched on CT
slices that are taken in different phases of respiration

The treatment is planned on a reference CT – usually the
end expiration (for Lung)

Matching the voxels allows the dose to be visualized at each
phase of respiration

Several algorithms under evaluation:

Finite element method

Optical flow technique

Large deformation diffeomorphic image registration

Splines thin plate and b
Automated Contouring

Movement
vectors
Automated Contouring

Individaul
Pixels

+
=

Day 1 Image Day 2 Image

Due to the changes in shape
of the object the same pixel
occupies a different
coordinate in the 2nd image

Deformable Image registration circumvents this problems

4D Treatment Planning


A treatment plan is usually
generated for a single phase of
CT.

The automatic planning
software then changes the field
apertures to match for the PTV
at each respiratory phase.

MLCs used should be aligned
parallel to the long axis of the
largest motion.
Limitations of 4D Planning


Computing resource intensive – Parallel calculations require
computer clusters at present

No commercial TPS allows 4 D dose calculation

Respiratory motion is unpredictable – calculated dose good
for a certain pattern only

Incorporating respiratory motion in dynamic IMRT means
MLC motion parameters become important constraints

Tumor tracking is needed for delivery if true potential is to
be realized

The time delay for dMLC response to a detected motion
means that even with tracking gating is important
4D Treatment delivery

Options for 4D delivery

Ignore motion Freeze the motion Follow the motion (Tracking)

Patient breaths normally Breathing is controlled

Respiratory Gating 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)
Minimizing Organ Motion


Active Breathing Control

Consists of a spirometer to “actively” suspend the patients
breathing at a predetermined postion in the respiratory cycle

A valve holds the respiratory cycle at a particular phase of
respiration

Breath hold duration : 15 -30 sec

Usually immobilized at moderate DIBH (Deep Inspiration Breath
Hold) – 75% of the max inspiratory capacity

Max experience: Breast

Intrafractional lung motion reduced

Mean reproducibility 1.6 mm
Tracking Target motion


Also known as Real-time Postion Management respiratory
tracking system (RPM)

Various systems:

Video camera based tracking (external)

Radiological tracking:

Implanted fiducials

Direct tracking of tumor mass

Non radiographic tracking:

Implanted radiofrequncy coils (tracked magnetically)

Implanted wireless transponders (tracked using wireless signals)

3-D USG based tracking (earlier BAT system)
Results

a = includes setup error

Adaptive
Radiotherapy
Planning
Adaptive Radiotherapy (ART)


Adaptive radiotherapy is a technique by which a conformal
radiation dose plan is modified to conform to a mobile and
deformable target.

Two components:

Adapt to tumor motion (IGRT)

Adapt to tumor / organ deformation and volume change.

4 ways to adapt radiation beam to tracked tumor motion:

Move couch electronically to adapt to the moving tumor

Move a charged particle beam electromagnetically

Move a robotic lightweight linear accelerator

Move aperture shaped by a dynamic MLC
 ART: Concept

1. 2. 3.


Offline ART
 Conventional Rx 
Individual patient based

Online ART

Sample Population based margins 
Individual patient based
margins 
Frequent imaging of margins

Accomadates variations of patients 
Daily imaging of patients
setup for the populations 
Estimated systemic error

Daily error corrected

No or infrequent imaging corrected based on prior to the treatment

Largest margin repeated measurements

Smallest margin required

A small margin kept for

Plans adapted to the
random error changing anatomy daily!

Plans adapted to average
changes
ART: Why ?

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

Binary MLCs are provided – 2
positions – open or closed
Cone Beam 
Pneumatically driven 64 leaves

Y jaw

Open close time of 20 ms
Binary MLC 
Width 6.25 mm at isocenter

10 cm thick

Y jaw

Interleaf transmission – 0.5% in
field and 0.25% out field

Maximum FOV = 40 cm
Fan Beam

However Targets of 60 cm dia
meter can be treated.
Helical Tomotherapy


Flat Couch provided allows
automatic translations during
treatment

Target Length long as 160 cm
can be treated

“Cobra action” of the couch
limits the length treatable

Manual lateral couch translations
possible

Automatic longitudinal and
vertical motions possible
Helical Tomotherapy


Integrated MV CT obtained by an
integrated CT detector array.

MV beam produced with 3.5 MV photons

Allows accurate setup and image guidance

Allows higher image resolution than cone
beam MV CT (3 cm dia with 3% contrast
difference)

Tissue heterogenity calculations can be
done reliably on the CT images as scatter is
less (HU more reliable per pixel)

Not affected by High Z materials (implant)

Dose 0.3 – 3 Gy depending on slice
thickness

Dose verification possible
Breat Cancer


Leonard et al 2007 – APBI

55 patients , Non randomized

All patients stage I

Dose: 34 Gy (n=7) / 38.5 (n = 48) BID over 5 days

Median F/U – 1 yr

Good to excellent cosmesis:

Patient assessed: 98% (54)

Physician assessed: 98% (54)

Considered a reasonable option for patients who have large
target volumes and/or target volumes that are in anatomic
locations that are very difficult to cover.
Lung Cancer

Author Year N CCT Dose Result

Yom et al 2005 37 (I) Yes 63 Gy (median) 7% incidence of Gr III
(R, NR) pneumonitis
Yorke et al 2005 78 No Dose escalation 22% incidence of Gr III
(P, NR) (3D) (50.7 – 90 Gy); pneumonitis above doses of 70
Gy.
Videtec (R, 2006 28 (I) No 50 Gy in 5 fraction 64% T1; 2.6% Gr II pneumonitis,
NR) (SBRT) no Gr III reactions; LC and OS at
1 yr 96.4% and 93% respectively
Scarbrough 2006 17 (I) Yes 71.2 Gy (69–73.5 Mean age 70; 73% IIIB, FU 1 yr,
(R, NR) Gy) No Gr III tox, 2 yr OS 66%
Jensen (P, 2007 17 (I) Yes 66 Gy Patients no suited for CCRT. 1 Gr
NR (citux) III esophagitis; 79% response (6
mo)
Yom et al 2007 68 (I), Yes 63 Gy (median); 60% stage IIIB, FU = 8 mo
(R, NR) 222 Dose > 60 Gy (median); Gr III pneumonitis 8%
(3D) 84% (I), 63% (32% for 3D CRT); V20 35% (I) vs
(3D) 38%(3D) (p = 0.001)

Table showing results of IMRT in Lung Cancer

 Brain Tumors

Author Year N Dose Result

Sultanem 2004 25 60 Gy (GTV); 40 All GBM,Post op volume < 110 cc;
Gy (CTV); 20 # Majority RPA class 4/5; The 1-year
overall survival rate is 40%, Median
survial 9 mo. No late toxicity.
Luchi 2006 25 48 – 68 Gy 2 AA patients; Median KPS 70; 2 yr PFS
(GTV); 40 Gy 53.6%; 2 yr survival 55.6%; Pattern of
(CTV1); 32 Gy death – CSF dissemination most
(CTV2); 8 # common cause of death!
Narayana 2006 58 60 Gy (PTV); 70% GBM; 1 yr OS 30% (2 yr 0%) for
30# GBM; No Gr III late toxicity; Pattern of
failure – local

Table showing results of IMRT in brain tumors

Cervical Cancer

Author Year N CCT Dose Result

Mundt 2003 36 Y 45 Gy (1.8 80% stage I-II; PTV S3 to L4/5
(P,NR) (53%) Gy/#) interspace; Chronic GI toxicity 15% (n=
3; 1 Gr II, 2 Gr I); 50% incidence in
Conventional
Mundt 2002 40 Y 45 Gy (1.8 60% Acute Gr II toxicity (90% Gr II in
(P,NR) Gy/#) Conv.); Less GU toxicity (10% vs 20%);
Patients not requiring antidiarrheal
halved!
Chen 2007 33 Y 50.4 Gy / All Stage I -II; All Post Hysterectomy; 1
(P,NR) 28# yr LRC 93%; Acute GI toxicity 36% (Gr I-
II); Acute Gu toxicity 30% (Gr I-II)
Beriwal 2007 36 Y 45 Gy 2 Yr LC 80%; 2 yr OS 65%; 11 had
(P,NR) (EFRT) + recurrences – 9 distant; Gr III toxicity –
10-15 Gy 10%
boost
Kochanski 2005 62 Y 45 Gy (1.8 29% Post op; 20 Stage IIB-IIIB; 3 yr DFS
(64%) Gy /#) 72.7%; 3 yr pelvic control 87.5%; 5% Gr
II or higher late toxicity
Anal Canal

Author Year N CCT Dose Result

Salama et 2006 40 (I) Yes 45 Gy WP + 9 Gy 12.5% Gr III GI toxicity, 0 Gr III
al (R, NR) boost skin toxicity, 2 year colostomy-
free, disease free, and overall
survival 81%, 73%, and 86%

Milano et al 2005 17 (I) Yes 45 Gy WP + 9 Gy 53% Gr II GI toxicity, No Gr III

(P, NR) boost acute or late complications. 82%
CR rate, the 2-year CFS, PFS,
and overall survial are: 82%,
65%, and 91%
Devisetty 2006 34 (I) Yes 45 Gy WP + 9 Gy 17% Acute GI toxicity; volume of
(P,NR) boost bowel receiving 22 Gy (V22) was
correlated with toxicity (31.8%
acute GI toxicity for V22 > 563 cc
vs. 0% for V22 ≤ 563 cc)

Hwang 2006 12 (I) Yes 30.6 Gy WP + 42% Gr III dermal toxicity, 8% Gr

(P,NR) 14.4 Gy Low III GI toxicity, 83% CR rate
Pelvic + 9 Gy
boost
New Techniques in
Stereotactic
Radiation therapy
Stereotaxy


Derived from the greek words Stereo = 3 dimensional space
and Taxis = to arrange.

A method which defines a point in the patient’s body by
using an external three-dimensional coordinate system
which is rigidly attached to the patient.

Stereotactic radiotherapy uses this technique to position a
target reference point, defined in the tumor, in the isocenter
of the radiation machine (LINAC, gamma knife, etc.).

Units used:

Gamma Knife

LINAC with special collimators or mico MLC

Cyberknife

Neutron beams
Stereotactic Radiation

Rigid application of a
stereotactic frame to the patient
3 D Volumetric imaging with the
frame attached
Target delineation and
Treatment planning

Two braod groups:

Radiosurgery: Single
treatment fraction

Radiotherapy: Multiple
fractions

Frameless stereotactic
radiation is possible in one
system – cyberknife

Postioning of patinet with the


Sites used:
frame after verification 
Cranial

Extracranial
QA of treatment and delivery of
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
6 MV LINAC freedon

Circular Collimator
attached to head

Frameless patient Floor mounted Amorphous

immobilization couch silicon detectors
Advantages of Cyberknife


An image-guided, frameless radiosurgery system.

Non-isocentric treatment allows for simultaneous
irradiation of multiple lesions.

The lack of a requirement for the use of a head-frame allows
for staged treatment.

Real time organ position and movement correction facility

Potentially superior inverse optimization solutions
available.
Cyberknife


185 published articles till date; 5000 patients treated.

73 worldwide installations

Areas where clinically evaluated:

Intracranial tumors

Trigeminal neuralgia and AVMs

Paraspinal tumors – 1° and 2°

Juvenile Nasopharyngeal Angiofibroma

Perioptic tumors

Localized prostate cancer

However till date maximum expirence with Intracranial or
Peri-spinal Stereotactic RT
Results

Tumor Year N Result

Brain mets 2004 333 (164 Survival advantage for patients with single
(Andrews et al) SRT / 164 brain mets (Median survival 6.5 – 4.9 mo);
C) Better functional status at follow up – SRT with
WBRT Rx in single brain mets (RTOG 9508)
Benign brain 2003 285 95% tumor control (media F/U 10 yr); actuarial
tumors tumor control rate at 15 years was 93.7%.
( Kondziolka et al) Normal facial nerve function was maintained in
95% with aucostic neuromas
Malignant Glioma UP 203 SRT + EBRT + BCNU did not result in significant
(Souhami et al) survial advantage – 13.6 vs 13.5 mo (RTOG
9305)
Malignant Glioma 2002 203 SRT + EBRT + BCNU did not result in significant
(Souhami et al) improvement in Quality adjusted survival
(RTOG 9305)

The only randomized trial comparing stereotactic radiation therapy boost

has failed to reveal a significant survival benefit for patients with malignant
gliomas. (RTOG 9305). However 18% of the patients in the stereotactic
radiotherapy arm had significant protocol deviations.