4D Radiotherapy1

4D Radiotherapy4D Radiotherapy

Paul KeallPaul KeallVirginia Commonwealth UniversityVirginia Commonwealth University

4D Radiotherapy2

OutlineOutline

Medical rationale Basic science and technology State-of-the-art Future needs, directions and

opportunities Advice …

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Medical rationaleMedical rationale

What is the purpose of your research?

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What do we know?What do we know?

Where the ‘visible’ tumor is To within 1 cm (on day of imaging study)

Where the microscopic tumor extends to To within 1 cm

Where the patient’s skeleton is wrt the radiation beam To within 1 cm

What the shape of the tumor is To within 1 cm

Where the tumor is wrt the skeleton To within 2 cm

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What can we do about it?What can we do about it?

Reduce the uncertainties Improved/functional imaging Ongoing commitment to education Daily 2D/3D imaging Monte Carlo dose calculation/optimization Intrafraction motion

Develop methods to account for residual uncertainties Incorporate uncertainties into planning process Probabilistic planning Online planning

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Chem

o-response

GI motion

Inter-observer

differences

Tumor growth

Tu

mo

r sh

rin

kag

e

Tumor spread

ReoxygenationR

epair

Repopulation

RedistributionVascular growth

Weight loss

Cardiac motion

Hormone response

Diet

Bladder filling

Rectal fillin

g

Intra-observerdifferences

Skeletal motion

Respiratory motion

Weight gain

Respiratory motion

Why 4D?Why 4D?

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Respiratory motion affects:Respiratory motion affects:

All tumor sites in the thorax and abdomen

Lung cancer alone: 173 770 new cases in 2004 (ACS) 160 440 deaths (28% of cancer deaths) 15% five-year survival Evidence of tumor dose response 50%/30

month LPFS at 85 Gy (Martel et al) Strong evidence of lung dose response (many

100+ patient studies)

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Problems of Problems of respiratory motion respiratory motion

in radiotherapyin radiotherapy

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The tumor moves with time The tumor moves with time

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Conventional With gated imaging

Distorted images, incorrect Distorted images, incorrect anatomical positions, volumes or anatomical positions, volumes or

shapesshapes

Tumor

Keall et al Aust Phys Eng Sci Med 2002

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PTV

Treatment Planning: Large margins Treatment Planning: Large margins are added to the clinical target are added to the clinical target

volumevolume Increases normal tissue dose

and limits target dose

CTV

Conventional With gating

PTV

CTV

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IMRT Delivery: Interplay between IMRT Delivery: Interplay between anatomy and MLC leaf motion anatomy and MLC leaf motion

leads to motion artifactsleads to motion artifacts

Dos

e

Position

Planned doseDelivered dose

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Basic science and technologyBasic science and technology

What is the underlying scientific/technological basis of your research?

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“The explicit inclusion of the temporal changes in anatomy during the imaging, planning and delivery of radiotherapy”

4D Radiotherapy PanelASTRO 2003

What is 4D radiotherapy?What is 4D radiotherapy?

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4D Radiotherapy

4D CT Imaging

4D Treatment Planning

4D Treatment Delivery

Acquisition of a sequence of CT image sets over consecutive phases of a breathing cycle

The explicit inclusion of the temporal changes in

anatomy during the imaging, planning and

delivery of radiotherapy

Designing treatment plans on CT image sets obtained for each phase of the breathing cycle

Continuous delivery of the 4D treatment plans throughout the

breathing cycle

The 4D radiotherapy processThe 4D radiotherapy process

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4D Radiotherapy I:4D Radiotherapy I:

4D CT Imaging4D CT Imaging

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4D CT imaging4D CT imaging

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Vedam et al PMB 2003 48:45-62

8 respiratory phases Peak inhale Early inhale Mid inhale End inhale Peak exhale Early exhale Mid exhale Late exhale

4D CT images4D CT images

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4D Radiotherapy II:4D Radiotherapy II:

4D Planning4D Planning

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Acquire 4D CT

Define anatomy

Create/adjust treatment plan

Evaluate dose distribution

1

4

3

2

Proceed to treatment6

…

Plan acceptable?No

Yes

Deformable registration …

Automatedplanning…

Deform

able

regis

tratio

n

5

4D Planning Flow Chart4D Planning Flow Chart

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4D PTVs4D PTVs

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3D BEV 4D BEV

BEVsBEVs

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3D (solid) vs 4D (dashed) DVHs3D (solid) vs 4D (dashed) DVHs

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4D Radiotherapy III:4D Radiotherapy III:

4D Delivery4D Delivery

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4D radiotherapy delivery4D radiotherapy delivery

Linac Controller MLC Workstation

MLC Controller4DC

Tracking Signal

Treatment parameters

Linac Controller MLC Workstation

MLC Controller4DC

Tracking Signal

Treatment parameters

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MLC leaf motion MLC leaf motion

3D 4D Keall et al PMB 2001 46:1-10

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MLC leaf motion MLC leaf motion

3D IMRT 4D IMRT

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Tracking motion perpendicular Tracking motion perpendicular and parallel to the MLC and parallel to the MLC

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Finite response time- Finite response time- need motion predictionneed motion prediction

Linac Controller MLC Workstation

MLC Controller4DC

Tracking Signal

Treatment parameters

Linac Controller MLC Workstation

MLC Controller4DC

Tracking Signal

Treatment parameters

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Respiratory motion causes problems during the imaging, planning and treatment stages of radiotherapy

Several methods have been proposed to address respiratory motion

4D radiotherapy has some advantages over existing methods

There are still many unanswered questions …

4D radiotherapy summary4D radiotherapy summary

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State-of-the-artState-of-the-art

How does your research fit into the overall scheme of

medical research?

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Respiratory motion solutionsRespiratory motion solutions Breath-hold techniques (ABC/DIBH)

Uncomfortable for patients, limited applicability (MSKCC: 7/13 patients)

Increases treatment time (MSKCC: 17 to 33 minutes for conventional RT)

Respiratory gating Residual motion within gating window Increases treatment time Baseline shift

4D Radiotherapy Hardware/Software complexity

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Future needs, directions and Future needs, directions and opportunitiesopportunities

What is currently limiting your research or what change in

direction do you anticipate in the future?

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LimitationsLimitations

Ethics/IRB Length of grant review cycles Industry support

We need them unless resource and time unlimited

Why isn’t my project the highest priority?

Distractions

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DirectionsDirections

Incorporate recent scientific and technical developments

Greater scope More general More scientifically rigorous Integrate with concurrent internal

and external programs

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OpportunitiesOpportunities

Many problems to solve Many different ways to solve

problems

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NCI RoadmapNCI Roadmap

A focus on the following initiatives will move the work of NCI through the process of discovery, development, and delivery toward the goal of eliminating suffering and death from cancer by 2015 …

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AdviceAdvice

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1999 $4500 VCU faculty grant-in-aid 2001 $20 000 ACS Inst. Research Grant 2002 $1.5 million NCI grant 2003 $400 000 industrial grant 2003 Co-I $1 million NCI grant 2004 Consultant $1 million NCI grant 2004 Co-I STTR …

How did you get started?How did you get started?

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Why get a grant?Why get a grant?

Promotion Tenure Independence Invitations Staff Resources Travel Intangibles

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What advice can you give?What advice can you give?

Write early Write often Work hard Work smart Think broadly Good luck

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And get a great team!And get a great team! Ted Chung Rohini George Sarang Joshi Vijay Kini Radhe Mohan Jeffrey Siebers Sastry Vedam Krishni

Wijesooriya Jeffrey Williamson

ACS NIH MDACC MGH Philips Medical

Systems Standard Imaging UNC Varian Medical Systems

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Another great team!Another great team!