Technological Advances in Radiotherapy

Samuel ChiuDepartment of Clinical Oncology

Prince of Wales HospitalHong Kong

HA Convention

May 2007

Discovery of X ray1895• German Physics Professor

Wilhem Conrad Roentgen discovered X ray when he noticed that only the bones of his hand was shown on the fluorescent screen placed at the path of a beam produced by the Crooke’s tube

1901• Get the Nobel Prize

The beginning of Radiotherapy

1904• Thomas Edison’s assistant died of

repeated exposure to x rays causing severe burns with several amputations

• Noticed the harmful effects of x rays and marks the beginning of the potential use of x rays in radiotherapy

Development of Radiotherapy Machines

Early half of twentieth century

• Orthovoltage machines • low energy (200-300kv) x-rays

machines for treatment of cancer

• Low penetration• High toxicities

Development of Radiotherapy Machines

1951-The first high energy Cobalt 60 machines

• gamma rays, high energy.

• Deep penetration• Allows more widely

use of x rays in treatment of cancers

Development of Radiotherapy Machines

1970’s• Development of Linear

accelerators • accelerate electrons,

then slow them down through their collision with a metal target, causing high energy x-rays to be released

• Marks the beginning of technological development of teletherapy and widely use of external beam irradiation in treatment of cancers

Two dimensional radiotherapy in 80’s

Two dimensional RTTwo fields Three fields

HIGH DOSE to SURROUNDING NORMAL TISSUE

HIGH TOXICITIES LIMITING RADIATION DOSE

RT late toxicityBrain as an example

• Focal injury Necrosis (related to the high dose region)– Optic neuropathy– Pituitary dysfunction

• Neuropsychologic/cognitive (related to the whole brain dose)– Volume, fraction, size dose, age

dependent

How to decrease late toxicities

• Focal injury (Better Conformity to decrease volume and dose to critical organs)

• Neuropsychologic/cognitive (Increase conformity and number of beams to decrease volume of high dose zone)

Three dimensional Conformal Radiotherapy

(3DCRT)

Computer Planning

CT scan

MultileafCollimator

PWH RTPWH RT

ImmobilisationDevice

3 dimensional conformal RT (3DCRT) – 90’s

•Imaged guided target localisation•Computer 3D planning•Multiple beams•High conformity•Spare surrounding critical organs•Less dose to surrounding brain

2DCRT 3DCRT

High conformity decrease risk of focal injuries

Decrease high dose volume

Decrease cognitive impact

3-DCRTConventional 2-D

3D CRT treatment Dosimetric advantage over 2D

LimitationSuboptimal for irregular Targets (Concave shape)

Brainstem

60Gy Tumour

50Gy Chiasm

54Gy brainstem

3DCRT cannot produce an isodose distribution to exactly to what we want ?

70Gy Highly proliferativetumour

Limitation

The planner starts with a set of beam weights and profiles to obtain a plan by trial-and-error process.

3DCRT - Conventional (Forward) Planning

Based on two new principles:

1. Inverse treatment planning

2. Intensity modulated treatment beams

Intensity Modulated Radiotherapy (IMRT)

•The planner define the required dose & dose distribution

•The computer can calculate and optimized the beam intensity patterns of the individual IMRT beams.

Principle of Inverse Planning

70Gy to tumor

54Gy to Brainstem

90Gy to visible tumour by imaging

81Gy to subclinicaldisease

60Gy to urethra to prevent stenosis

Intensity modulated radiotherapy (IMRT)-the use of optimised multiple non uniform radiation beam intensities with multiple small beamlets

IMRTDynamic Multileaf Collimator

Methods of IMRT Treatment Delivery

3-DCRT IMRTConventional 2-D

IMRT Dosimetric advantage over 2D and 3D CRT treatment

High conformity

IMRT Dosimetric AdvantageNon uniform dose

Higher dose to Tumor

Lower dose to subclinical diseae

Potential Benefits of IMRT

1 Deliver treatments with better dose conformity and coverage to the target,hence reducing the probability of in-field recurrence.

2 Better sparing and protection of normal tissue, hence minimise the degree of morbidity associated with treatment.

3 Facilitating the escalation of dose to improve local control.

Gy

2DRT IMRT

Gy 1. 2D-Ho’s2. 3DCRT3. IMRT

Cumulative Dose Volume HistogramStructure :Rt Parotid

Parotid Gland

Kam et al, Asco 2006

Clinical Oncology, PWH

Parotid Sparing

RTOG/EORTC Xerostomia Grade

Grade ≧2 (%) Chi-Square

2DRT IMRT p-value

6 week 85.7 46.4 0.0019

6 month 92.9 75 0.0689

1 year 82.1 39.3 0.0010

85.7

46.4

92.9

7582.1

39.3

0102030405060708090

100

Xer

osto

mia

Gra

de ≧

2(%

)

6 week 6 month 1yearTime after RT

2DRTIMRT

Dose Escalation For Ca prostate

Decrease in biochemical failure with increase dose

Decrease Grade 2 rectal complications using IMRT

Alan Pollack et al.

World J Urol (2003)

Problems & Challenges - IMRT

1. High precision & sophisticated treatment planning procedures

2. High cost 3. Radiation safety- higher x ray exposure 4. Higher integral dose- Increases the probability

of radiation induced secondary cancer in the irradiated volumes.

5. The effect of geometrical errors on treatment dosimetry is more serious then conventional treatments.

Geometric Errors in RadiotherapyInter-fraction treatment errors1 Set up errors2 Organ positional changes3 Integrity of immobilization cast4 Changes in patient physical conditions 5 Machine errors

Intra-fraction treatment errors 1 Patient movement2 Organ movement caused by e.g. breathing

Conventional setup only relies on laser to line up surface markers on skin/cast disregard the positions of internal organs and the targetInter-fraction treatment errors

Better Immobilization DeviceHelp to decrease setup errors but not the ultimate solution

PWH RTPWH RT

Irradiated VolumeTreated Volume

PTV

ITV

CTV

GTV

ICRU Report 50 & 62

Internal margin

Setup margin

Penumbra

Geometrical Uncertainties

Definition of Target Volumes Definition of Critical Normal Structures

OAR

PRV

Image-Guided Radiation Therapy (IGRT)

What is IGRT?

• Measure and correct target and critical structure positional errors immediately prior to or duringtreatment delivery

• To reduce ITV and / or Setup inaccuracy thus decrease RT related toxicity and allow tumourdose escalation

IGRT

• Positioning of patient based on internal bone landmark or implanted marker using X rays

IGRT – Acquisition of CT scan images

Allow reconstruction of images in different planes

IGRT

1st set of X ray images

2nd set of X ray images

IGRT

•Fusion of x ray images to the digitally reconstructed images from planning CT

•Patient aligned to correct position based on bony landmarks/implanted markers

IGRTPositioning of patient based on internal bone landmark or

implanted marker using X rays

Courtesy of BrainLab

IGRT

Positioning of patient with CT guided

Helical Tomotherapy

LINAC and CT Scan in the same machine

Multileafcollimator with IMRT

No limitation on field size and field matching

On-line treatment verification by matching of the planning CT image (bottom left) with the tomotherapy treatment set up image (top left) immediately before treatment delivery without moving the patient.

TomotherapyCT image guided treatment delivery

Courtesy of Peter Teo, HKS & Hospital

Intra-fraction Errors

Tumour moves with respiration. Range: 0.5 ~3cm

Convention RT: Need extra margin for tumour motion – Internal Target Volume (ITV)

What is IGRT?

• Measure and correct target and critical structure positional errors immediately prior to or duringtreatment delivery

• To reduce ITV and / or Setup inaccuracy thus decrease RT related toxicity and allow tumourdose escalation

Respiratory Gated RT: Less extra margin for tumour motion – Decreased ITV

IGRT Equipments – PWH – Respiratory Gating

• Real-time Positioning Management (RPM) system (Varian)

• 4D-CT

• Respiratory Gated RT

Gating of radiotherapy treatment beams by respiratory motion waveform to compensate for target movement

Beam On

Beam On Window

Beam off

Breathing signal

Liver Volume: 1010 cm3

GTV= 119 cm3

Liver Volume: 1010 cm3

GTV= 119 cm3

PTV = 684 cm3

without Gating Txmargins: SI=2.5cm, circumferential=1.5cm

Liver Volume: 1010 cm3

GTV= 119 cm3

PTV = 684 cm3

without Gating Txmargins: SI=2.5cm, circumferential=1.5cm

PTV = 286 cm3

with Gating Txmargins: 0.75cm for all

Liver Volume: 1010 cm3

GTV= 119 cm3

PTV = 684 cm3

without Gating Txmargins: SI=2.5cm, circumferential=1.5cm

PTV = 286 cm3

with Gating Txmargins: 0.75cm for all

PTV VolumeReduction: 58%

Gating of respiratory motionExternal infrared markers and internal implanted markers

Courtesy of BrainLab

REAL-TIME tumor-tracking - CyberknifeCorrect for respiratory tumor motion

Robot motion is steered by external fiducial motion

Internal tumor motionX-ray images

The Synchrony™ Respiratory Tracking SystemBuilding the correspondence model

Implanted gold seeds

External fiducial motionInfrared LED-camera system

The Synchrony™ Respiratory Tracking System

Building the correspondence model

The Synchrony™ Respiratory Tracking System

Robot follows internal fiducials using a correspondence modelbetweenmeasured internal fiducial motion (implanted gold markers)

andmeasured external fiducial motion (LEDs)Correspondence model is build prior to the start of treatmentCorrespondence model is verified and updated during the treatment

LED position

Inte

rnal

fidu

cial

x,y,

z (m

m)

Correspondencemodel

Surgery

Multidisciplinary Management of Cancers

Radiotherapy

Department of Clinical Oncology, PWH

Chemotherapy Biological Therapy

Pathology

Radiology

Clinical Psychology Palliative Medicine

Conclusion

• The rapid technological advancement brings radiotherapy to a new era

• Development of radiotherapy from two dimensional to three dimensional conformal radiotherapy achieve high conformity of radiation to the target with sparing of surrounding normal tissue and allow dose escalation with improvement in tumor control

Conclusion• Intensity modulated radiotherapy (IMRT)

further improves the conformity of radiation especially for the irregular targets, allows the delivery of differential doses within the target according to the tumor characteristics and dose limitations of critical organs

• The development of these highly conformed radiotherapy further facilitated by the development of imaged guided radiotherapy (IGRT) with or without respiratory gating and assures accurate setup, decrease margins and decrease volume of irradiation

Conclusion

• Treatment of cancers require multidisciplinary management. Good coordination among the different disciplines and careful selection of patient will allow provision of best services to our patients.

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