Abstract Margins in Radiation Therapy · • Fiorin o C, Reni M, Bolo gnesi A, et al. Set -up error in supine -posit ioned patients immobili zed with two dif ferent modali ties during

Department of Radiation Oncology • University of Michigan Health Systems

Margins in Radiat ion Th erapyDATE: Tuesday, July 28, 2009 START TIME: 07:30 AM END TIME: 08:25AM LOCATION: 211A

Dan Low Dale LitzenbergWashington University University of Michigan

Abstract

Conformal radiation therapy has historically used margins to account for geometrical uncertainties in the position of a target volume. The margins, in their simplest form, are simply expansions to the shape of a treatment beam, to ensure that dosimetric planning criteria are met in the presence of inter- and intra-fraction setup variations. Historically, the size of the margin in a given treatment site was difficult to determine due to the available technology and the time and effort required to obtaining accurate data. Consequently, margins were estimated to accommodate a population of patients. As new technologies have emerged, target volume position errors have become easier to measure, their accuracy has increased, and the measurements can be made much more frequently. As the quantity and quality of data has increased for patient populations, and even for individual patients, the conceptual basis of employing margins has evolved. Strategies for ensuring dosimetric coverage may now be individualized to a specific patient’s geometric uncertainty characteristics with customized margins, or they may incorporate geometric correction based on predefined action levels. Other strategies may incorporate continuous monitoring to gate or modify the beam. And finally, other strategies seek to eliminate margins by including the estimated geometrical uncertainty into the development of the dose distribution.

Educati onal Objective s

• To motivate the need for margins and review ICRU definitions

• To provide an educational review of the technologies and methods of measuring target volume positioning errors.

• To review methods of determining population margins from measured data.

• To review corrective and intervention strategies for patients with individualized margins.

• To briefly review planning strategies which seek to eliminate margins.

Disclaimer

The content of this presentation is for general educational purposes only.

The mention of trade names, commercial products does not imply an endorsement on the part of AAPM or the presenters.

The views, opinions and comments made in this refresher course are those of the presenters and not necessarily those of AAPM.


Conflict of Interest

DA Low: TomotherapyVarian Medical Systems

DW Litzenberg: Calypso Medical Technologies

Outline

I. The Need for Margins

II. Treatment Site Considerations

III. Simulation Imaging Modalities

IV. Examples of Motion

V. Treatment Planning

VI. In-room Guidance and Correction Strategies

VII. Off-line Adaptive Strategies

VIII. Planning without margins

Outline







VII. Off-line Adaptive Stratagies



A. Systematic and random errors

B. Inter- and intra-fraction motion

C. Dosimetric criteria

D. Population and individualized margins


Systematic and Random Errors

Σ smallσ small

Σ largeσ small

Σ largeσ large

Σ smallσ large

Inter- and Intra-Fraction Positioning Errors

Inter-Fraction:Variations caused by uncertainty in reproducing target volume position at isocenter each time patient is placed on treatment table

Intra-Fraction:Variations in position while patient is on treatment table

Each may have Systematic and Random Errors

Systematic Error Example

Systematic shift due to distention on planning CT

Systematic Error Example


Impo rtance of Image Guid ance

N=127, patients treated to 78 Gy between 1993 and 1998No daily image guidanceOutcomes analyzed by rectal distention at the time of simulation

MDACC: de Crevoisier et al., IJROBP, 62, 965-973, 2004

What was Missing?

• Method for directly measuring prostate position

• On-board CT– CBCT

• Kilovoltage or Megavoltage– Helical Megavoltage CT

• Markers– Imbedded markers– Planar imaging– On-board CT– Radiofrequency

Dosimetric Coverage

“ Tumor”

Prescribed Dose Level(eg. 95%)

Dose

x

Underdos e

mm

1.0

0.5

0.0

Fre

qu

ency

-4 -2 0 2 4Position (cm)

Population-Based Motion


1.0

0.5

0.0

Fre

qu

ency

-4 -2 0 2 4Posit ion (cm)

Patient Specific Motion Patient Specific Margin

Fre

quen

cy

Position (cm)

Σ = 0

PTV margin = Setup + Inter + Intra-fraction

Σ = 0


Estimate ΣAnd correct Estimate ΣAnd correct

Ten Haken Ten Haken


Outline










A. Treatment Position

B. Immobilization & Localization

Accuracy of Localization

MeasurementMeasurement

LocalizationLocalization

Patient PositionPatient Position

ImmobilizationImmobilization

Simulation &Planning

Simulation &Planning

CorrectionCorrection

Motion Management

Motion Management

Treatment Position

Zelefsky, IJROBP, 1997;37:13-19.

1997: No in -room soft tissu e guidance availabl e,Lit tle t o no ev idence of r espir ator y moti on.


Treatment Position Intrafraction Motion: Fluoroscopy

-4

-2

0

2

4

Po

siti

on

(cm

)

Patient #7 8 9 10 Ave

LRAPIS

LRAPIS

Initial PositionInitial Position

Supine Positioning ResultsSupine Positioning Results

Average+/- 1σ

Maximum

Minimum

2

-2

-4

-2

0

2

4

Po

siti

on

(cm

)

Patien t #7 8 9 10 Ave

-4

-2

0

2

4

Po

siti

on

(cm

)

Patien t #7 8 9 10 Ave

LRAPIS

LRAPIS

Initial PositionInitial Position

Final PositionFinal Position

Supine Positioning ResultsSupine Positioning Results


Supine vs Prone Treatment Position

• Respiratory motion reduced when supineDawson, IJROBP, 2000Kitamura, IJROBP, 2002

• Significantly less dose to small bowel, bladder and rectum when supine

Bayley, Radiother & Oncol, 2004

• ~ 95% treated supineASTRO IGRT Symposium, 2006

• Respiratory motion reduced when supineDawson, IJROBP, 2000Kitamura, IJROBP, 2002

• Significantly less dose to small bowel, bladder and rectum when supine

Bayley, Radiother & Oncol, 2004

• ~ 95% treated supineASTRO IGRT Symposium, 2006

Treatment Position • Steenbakkers RJHM, Duppen JC, Betgen A, et al. Impact of knee support and shape of tabletop on

rectum and prostate position. International Journal of Radiation Oncology*Biology*Physics

2004;60:1364-1372.

• Adli M, Mayr NA, Kaiser HS, et al. Does prone positioning reduce small bowel dose in pelvic

radiation with intensity-modulated radiotherapy for gynecologic cancer? International Journal of

Radiation Oncology*Biology*Physics 2003;57:230-238.

• Algan Ö, Fowble B, McNeeley S, et al. Use of the Prone Position in Radiation Treatment for Women

With Early Stage Breast Cancer. International Journal of Radiation Oncology*Biology*Physics

1998;40:1137-1140.

• Liu B, Lerma FA, Patel S, et al. Dosimetric effects of the prone and supine positions on image

guided localized prostate cancer radiotherapy. Radiotherapy and Oncology, 2008; 88(1):67-76.

• Stroom JC, Koper PCM, Korevaaar GA, et al. Internal organ motion in prostate cancer patients

treated in prone and supine treatment position. Radiotherapy and Oncology 1999;51:237-248.

• Verhey LJ. Immobilizing and positioning patients for radiotherapy. Seminars in Radiation Oncology

1995;5:100-114.

• Dawson LA, Litzenberg DW, Brock KK, et al. A comparison of ventilatory prostate movement in four

treatment positions. International Journal of Radiation Oncology*Biology*Physics 2000;48:319-323.

• Zelefsky MJ, Happersett L, Leibel SA, et al. The effect of treatment positioning on normal tissue

dose in patients with prostate cancer treated with three-dimensional conformal radiotherapy.

International Journal of Radiation Oncology*Biology*Physics 1997;37:13-19.

Immobilization • Fiorino C, Reni M, Bolognesi A, et al. Set-up error in supine-positioned patients immobilized with two

different modalities during conformal radiotherapy of prostate cancer. Radiotherapy and Oncology1998;49:133-141.

• Halperin R, Roa W, Field M, et al. Setup reproducibility in radiation therapy for lung cancer: a comparison between T-bar and expanded foam immobilization devices. International Journal of Radiation Oncology*Biology*Physics 1999;43:211-216.

• Hanley J, Debois MM, Mah D, et al. Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation. International Journal of Radiation Oncology*Biology*Physics 1999;45:603-611.

• Wong JW, Sharpe MB, Jaffray DA, et al. The use of active breathing control (ABC) to reduce margin for breathing motion. International Journal of Radiation Oncology*Biology*Physics 1999;44:911-919.

• Barnes EA, Murray BR, Robinson DM, et al. Dosimetric evaluation of lung tumor immobilization using breath hold at deep inspiration. International Journal of Radiation Oncology*Biology*Physics2001;50:1091-1098.

• D'Amico AV, Manola J, Loffredo M, et al. A practical method to achieve prostate gland immobilizationand target verification for daily treatment. International Journal of Radiation Oncology*Biology*Physics2001;51:1431-1436.

• Gilbeau L, Octave-Prignot M, Loncol T, et al. Comparison of setup accuracy of three different thermoplastic masks for the treatment of brain and head and neck tumors. Radiotherapy and Oncology2001;58:155-162.

• Negoro Y, Nagata Y, Aoki T, et al. The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup accuracy. International Journal of Radiation Oncology*Biology*Physics 2001;50:889-898.

• Bayley AJ, Giovinazzo J, Rakaric P, et al. Med-Tek type-S immobilization system: calculating the set-up margin for radiotherapy of head and neck cancer patients. International Journal of Radiation Oncology*Biology*Physics 2002;54:289-289.

• Fuss M, Salter BJ, Cheek D, et al. Repositioning accuracy of a commercially available thermoplasticmask system. Radiotherapy and Oncology 2004;71:339-345.

Outline










Simulation Imaging Modality

A. What you see

1. Computed Tomography

2. Magnetic Resonance

3. Positron-Emission Tomography

B. What you contour

K Langen

Visible Human Project - Male6 radiation oncologists, 120 delineations on KV CTs

Radiotherapy and Oncology, 85(2), 239-246, 2007

PROSTATE DELINEATION: DIAGNOSTIC KV CT vs ABSOLUTE TRUTH


Visible Human Project - Male6 radiation oncologists, 120 delineations on KV CTs

CT volumes on average 30% larger than true volume

CT volumes encompassed, on average, 84% of the true volume.

Extended too anteriorlyMissed posteriorly

PROSTATE DELINEATION: DIAGNOSTIC KV CT vs ABSOLUTE TRU TH

Radiotherapy and Oncology, 85(2), 239-246, 2007


Ten Haken, Radiotherapy and Oncology, 25, 121-133, 1992.

• 15 bra in ca ses

• 1 neuro -rad iologi st

• 1 radi ation onc olog ist

• Contours on CT, MR, regist ered CT-MR


Ten Haken, Radiotherapy and Oncology, 25, 121-133, 1992.

GTV CTV = GTV + 2 cm

“… the degree of inter-observer variation in volume definition is on the order of the magnitude of differences in volume definition seen between the modalities, …”

14% CT only

56% Both

30% MR only

“Given that tumor volumes independently apparent on CT and MRI have equal validity, composite CT-MRI input should be considered for planning …”

Adding mar gin reduc es im pact


Ford, IJROBP, 71, 595-602, 2008.

12 patients

Inflammation used to ID lumpectomy cavity

Cavity volume ratio(PET CT)/CT = 1.68Range = 1.24 – 2.45

PTV volume ratio(PET CT)/CT = 1.16Range = 1.08 – 1.64

PET CT largely encompassed CT


Outline









III. Examples of Motion

A. Head and Neck

B. Lung

C. Liver

D. Pancreas

E. Prostate

Inter-Fraction Motion:Head and Neck: Implanted Markers

Markers

Zeidan, ASTRO 2007

Fraction

Marker Stability

Low, Wash U.

Intrafraction Motion and Deformation: 4D CT


Liver – Inter-Fraction Motion

• Implanted Markers (clips okay)• Localized using OBI (orthogonal X-Rays at Exhale)• 3 mm threshold for adjustment

Balter, UM

Intrafraction Motion and Deformation: MRI

Courtesy Larry Kestin and Michel Ghilezan, WBH

Intrafraction Motion and Deformation: cineMRI Outline










IV. Treatment Planning

A. Margins

1. ICRU-29, 50, 62 – Definitions2. Margin Recipes

B. Margin Compromises

Margins

ICRU 29 (1978)

2 years after wh ole-body CT scanner s introducedTarget volume:• contains those tissues that are to be irradiated to a

specified absorbed dose according to a specified time-dose pattern.

• Includes expected movements, expected variation in shape and size, variations in treatment setup

Treated volu me:• The volume enclosed by the isodose surface

representing the minimal target dose.Irradiated vo lum e:• The volume that receives a dose considered significant

in relation to normal tissue tolerance.Hot spot:• Area that received a dose higher than 100% of the

specified target dose, at least 2cm in a section. J Purdy, 2004

ICRU 50 (1993)

J Purdy, 2004

Gross Target Volu meDemonstrable e xtent o f m align ant growth

Clinical T arget V olumeMicroscopic ex tension , fu ll d ose t o achi eve aim

Planning Target Volum eCTV + uncerta inty marg ins, “dose cloud ”

Organs at Ris kNormal tissues th at may influen ce plan

ICRU Referenc e Point


ICRU 62 Supplement (1999)

ICRU 50

+Setup M argin

Uncertainties in machine -pati ent posi tioni ng

Internal MarginUncertainties in patien t-CTV pos iti oni ng

Internal Target Volum eCTV + in ternal margin

Plannin g Organ at Risk Volum eOAR + unce rtainty margins

J Purdy, 2004

ICRU Definitions Evolve

J Purdy, 2004

Skip over ICRU definitions!

ICRU Definitions

Irradiated vol ume:

• Tissue volume that receives a dose

that is considered significant in relation

to normal tissue tolerance.

ICRU Definitions

Treated volum e:

• Tissue volume that is planned to receive at

least a dose selected and specified by

radiation oncology team as being

appropriate to achieve the purpose of the

treatment.


ICRU Definitions

GTV - Gross Tumor Volume• Complete actual or visible/demonstrable extent and

location of the malignant growth.

CTV - Clinical Target Volume• A tissue volume that contains a GTV and/or subclinical

microscopic malignant disease, which has to be eliminated.

• This volume has to be treated sufficiently in order to achieve the aim of the therapy: cure or palliation.

ICRU Definitions

PTV - Planning Target Volume• Defined by specifying the margins that must be

added around the CTV to compensate for the

variations of organ, tumor and patient movements,

inaccuracies in beam and patient setup, and any

other uncertainties.

• A static geometrical concept, can be considered a 3D

envelope in which the tumor and any microscopic

extensions reside and move (Dose cloud)

ICRU Definitions

Organs at risk :

• Normal tissues (eg, spinal cord) whose

radiation sensitivity may significantly

influence treatment planning and/or

prescribed dose.

ICRU Definitions

ICRU Reference point :• The system for reporting doses is based on the selection of a

point within the PTV, which is referred to as the ICRU Reference

point

– The dose at the point should be clinically relevant.

– The point should be easy to define in clear and unambiguous way.

– The point should be selected so that the dose can be accurately

determined.

– The point should in a region where there is no steep dose gradient.


ICRU Definitions

Setup margin (SM):• Uncertainties in patient-beam positioning in

reference to the treatment machine coordinate system.

• Related to technical factors.

• Can be reduced by

– Accurate setup and immobilization of the patient

– Improved mechanical stability of the machine.

ICRU Definitions

Internal ma rgi n (IM):• Variations in size, shape, and position of the CTV in reference

to the patient’s coordinate system using anatomic reference points.

• Caused by physiologic variations

• Difficult to control from a practical viewpoint.

• The volume formed by the CTV and the IM called Internal

target volume (ITV)

ICRU Definitions

Plann ing organ a t ris k volume (PRV):• A margin is added around the organ at risk to

compensate for that organ’s geometric uncertainties.

• Analogous to the PTV margin around the CTV.

Margins Around Organs at Risk

Conside rations– Systematic errors

• Sensitive to shifts in a particular direction

– Random errors

• Impact of dose blurring

– Serial organs at risk

• Sensitive to hot spots

– Parallel organs at risk

• Some tolerance to limited hot spots


Challenges of Implementing ICRU 50 & 62

A. Delineating Volumes

B. New Technologies

C.Adding Errors

Delineating the GTV

• Based mostly on clinical judgment

• Depends significantly on the imaging modality

(CT, MRI, PET, Registration)

• CT is still the principal source of imaging data

used for defining the GTV for 3DCRT and IMRT

• Window and level settings are critical

J Purdy, 2004

Delineating the CTV

• More of an art than a science because

current imaging techniques are not

capable of detecting subclinical tumor

involvement directly.

J Purdy, 2004

GTV to CTV Margins

• Giraud P, Antoine M, Larrouy A, et al. Evaluation of microscopic tumor extension in non-small-cell lung cancer for three-dimensional conformal radiotherapy planning. International Journal of Radiation Oncology*Biology*Physics 2000;48:1015-1024.

• Choo R, Woo T, Assaad D, et al. What is the microscopic tumor extent beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers? International Journal of Radiation Oncology*Biology*Physics 2005;62:1096-1099.

• Apisarnthanarax S, Elliott DD, El-Naggar AK, et al. Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsularextension of metastatic neck nodes. International Journal of Radiation Oncology*Biology*Physics 2006;64:678-683.

• Chao KK, Goldstein NS, Yan D, et al. Clinicopathologic analysis of extracapsularextension in prostate cancer: Should the clinical target volume be expanded posterolaterally to account for microscopic extension? International Journal of Radiation Oncology*Biology*Physics 2006;65:999-1007.

• Gao X-s, Qiao X, Wu F, et al. Pathological analysis of clinical target volume margin for radiotherapy in patients with esophageal and gastroesophageal junction carcinoma. International Journal of Radiation Oncology*Biology*Physics 2007;67:389-396.

• Grills IS, Fitch DL, Goldstein NS, et al. Clinicopathologic Analysis of Microscopic Extension in Lung Adenocarcinoma: Defining Clinical Target Volume for Radiotherapy. International Journal of Radiation Oncology*Biology*Physics 2007;69:334-341.


Delineating the PTV

The following should be taken into account:

– Data from published literature

– Any uncertainty studies performed in the clinic

– the presence of nearby organs at risk.

– The asymmetrical nature of the GTV/CTV

geometric uncertainties.

J Purdy, 2004

Compromises Between Volumes

• PTV and PRV may overlap

• Conflict in optimization criteria

• Judgment required in resolving volume conflicts

J Purdy, 2004

Challenges with New Technologies

IMRT

– Sharp beam gradients

– More conformal

– More sensitive to geometric uncertainties

– Time-dependant delivery

– Motion interplay may lead to hot/cold spots

J Purdy, 2004

4D CT and Cone Beam CT

– Protocols for defining volumes

– Variations in motion after simulation

– Changes in volumes during therapy

J Purdy, 2004

Challenges with New Technologies


Adding systematic and random errors

Systematic errors, ΣΣΣΣ– treatment preparation errors

– influence all fractions

Random errors, σσσσ– treatment execution errors

– influence each fraction individually

ICRU 62 – Combining Errors

Add systematic and random errors quadratically,

with equal weighting

SDTot = ΣΣΣΣ 2 + σ σ σ σ 2

Combining Errors

Systematic errors are much more important in determining margins t han random errors

PTV Margin Recipe

mPTV = αααα ΣΣΣΣ + γγγγ σσσσ’

αααα ~ 2 – 2.5

γγγγ ~ 0.7Σ - combined standard deviation of

systematic errors (Σ2 = Σ2m + Σ2

s + Σ2d)

σ’ - combined standard deviation of random errors (σ’2 = σ2

m + σ2s)

mPTV = αααα ΣΣΣΣ + γγγγ σσσσ’

αααα ~ 2 – 2.5

γγγγ ~ 0.7Σ - combined standard deviation of

systematic errors (Σ2 = Σ2m + Σ2

s + Σ2d)

σ’ - combined standard deviation of random errors (σ’2 = σ2

m + σ2s)


Margins Around Or gans at Risk

The DVH of the Plann ing Risk V olume should not underestim ate the con tr ibution of the high -dose components to the Or gan at Risk, in 90% of the cases.

Margins Around Organs at Risk

Dan Low takes over!

Outline










Target Volume Loca liza tion

A. Skin marks

B. Anatomical Landmarks and Surrogates

Bones

Implanted markers

Soft tissues

C. MV Portal Imaging

D. kV Imaging

E. Ultrasound

F. CBCT

G. MVCT

H. Electromagnetic

I. Surface mapping

Image Guidance: Positional VariationsEarly days

OLD UM STUFF

Balter , IJROBP, 31, 113, 1995

Chamf er match ing of bony anatomy on d igitized por t films

Balter , IJROBP, 31, 113, 1995

N=10Weekly Images4-8 films per patient


TRANSABDO MINAL ULTRASOUND

First widely used targeting technique

Started era of image guidance for routine clinical use(1998)

Introduced DAILY imaging

US (BAT) vs Markers (EPID)

Difference: Average ± SD (mm)Ant / Post -0.7 ± 5.2Sup / Inf 2.7 ± 4.5Lateral 1.8 ± 3.9

US (Sonarray) vs Markers (Exactrac)

Frequency of misalignments0-5 mm 26%5-10 mm 48%10-15 mm 17%15-20 mm 5%>20 mm 4%

Transabdominal Ultrasound: Comparison with Implanted Markers

Scarborough et al., IJROBP, 2006

Langen et al., IJROBP, 2003

Dong et al. (MDACC), ASTRO 2004: BAT vs In-Room CT

N=15 patients, 3 CTs per week.N=342 CT/US pairs Average 23 scans/patientPhysician contours on each CT Prostate center of volume

BAT vs CT differences (Mean + SD):Lateral 0.5 + 3.6 mmAnt / Post 0.7 + 4.5 mmSup / Inf 0.4 + 3.9 mm

“…the overall performance … seems unsatisfactory.”

Transabdominal US: Comparison with CT

Dong et al., IJROBP, 60S, p. S332, 2004

Diagnostic CT quality images

Full body field of view

Limitations:Room size

Integration

Separate imaging and treatment isocenters

KV CT on RailsPRIMATOM (SIEMENS)

Wong et al, IJROBP 61, 561–569, 2005


Cone Beam KV CT

Same GantryCoupled to delivery deviceVolume acquisition

Elekta Synergy

Varian Trilogy

Sampl e CBCT Images: Good f or H&N

Courtesy of Duke Univ Hosp, DurhamCourtesy Varian

Images Courtesy of Floris Pos – Netherlands Cancer Institute

CT scan acquisition & reconstruction time CT scan acquisition & reconstruction time ≈≈ 2 minutes2 minutesElektaElekta SynergySynergy

Sample CBCT Images: Worse for Pelvis Sample CBCT Images – Mot ion Artifacts

TP CT CBCT - 1

Week 2Week 4

Week 6


Sample CBCT – Breat hing Motio n Arti facts


Sample CBCT – Respir atory Syn chronized CB CT


Liu et al, IJROBP, 2007

-152 cases, 7 anatomic sites-Daily MVCT prior to each treatment; 3788 scans-Offsets determined for each case

Li et al, IJROBP, 68; 58 1-91, 2007


Li et al, IJROBP, 68; 581-91, 2007

LATERAL (mm)15

0

-15

LONGITUDINAL (mm)25

0

-25

VERTICAL (mm)20

0

-20

ROLL (mm)6

0

-6

Data to help PTV margin determination

Li et al, IJROBP, 68; 5 81-91, 2007

Institutional variations in patient position, immobilization, localization technique, inter- and intra-fraction motion measurements should also be taken into account when developing margins.

GEOGRAPHIC MISSES

VERTICAL

Li et al, IJROBP, 68; 581-91, 2007

LATER AL

LONGITUDINAL

Kupelian, IJROBP, 66, 876-82, 2006

Prostate D95

1.7

1.8

1.9

2.0

2.1

2.2

2.3

1 2 3 4 5 6 7 8 9 10

Patient

D95 (G

y)

Legend

PlanMeanSDMaxMin

DOSIMETRIC MISSESVERSUS

Li et al: Dosimetric Consequences of Intrafraction Prostate Motion. IJROBP, 71( 3),801-812, 2008.

Langen et al: Observations on real-time prostate gland motion using electromagnetic tracking, IJROBP, 71, 1084-1090, 2008

Pierburg et al: Dosimetric Consequences of IntrafractionProstate Motion on Patients Enrolled on Multi-Institutional Hypofractionation Study. IJROBP, 69, S23-S24. ASTRO 2007

Rajendran et al: Daily Isocenter correction with electromagnetic based localization improves target coverage and rectal sparing during prostate radiotherapy, IJROBP, In Press, 2009

Impact of real time motion on dosimetry: Prostate (Calypso tracks)


IMAGING DOSE: MVCT vs KV CBCT

WHY NOT IMAGE EVERYDAY?

KV CBCT: 1 - 5 cGy per image**, depending on siteHeterogeneous throughout scan volume40 - 200 cGy per entire courseCannot limit length of scan

** Amer et al., Br J Radiol. 2007;80(954):476-82. ** Wen et al.,Phys Med Biol. 2007;52(8):2267-76. ** Islam et al., Med Phys. 2006;33(6):1573-82.

MVCT:1 - 2 cGy per image*Relatively uniform dose40 - 80 cGy per entire courseCan limit length of scan

* Meeks et al., Med Phys. 2005;32(8):2673-81 * Shah et al., IJROBP, 2007; 69(3), S193-194. ASTRO 07; ABSTRACT 1100

In-Room Guidance:Inter-Fraction

Motion Management Example

Implanted Markers

Advantages of Markers

• Accuracy• Measured in treatment position• Semi- to fully automated• User independent• No contouring• Real-time position possible• Beam gating

Marker Visualization & Extraction

• 3 – 4 markers

• Centroid of visible markersσCM < 1 mm Pouliot, IJROBP, 2003

• 99.6% visualization of 3 markers18 MV (1x3 mm) Herman, IJROBP, 2003

• Automated marker extraction� 93% per marker, 85% for 3 markers

Aubin, MedPhys, 2003

� 90% - 100% based on ROI (MVCT)Chen, AAPM, 2005


Marker Migration & Stability

• 1.3 (0.44 – 3.04) mm (Pouliot, IJROBP, 2003)

• 1.2 +/- 0.2 mm (Kitamura, Radiother Oncol, 2002)

• 0.7 – 1.7 mm (Litzenberg, IJROBP, 2002)

• 1.01 +/- 1.03 mm (Kupelian, IJROBP, 2005)

• 0.8 mm with Beacons (Willoughby, IJROBP, 2006)

� Area of marker triangle proportional to CT volume of prostate (Moseley, AAPM, 2005)

Frequency & Time for Adjustment

• 5 mm action threshold with skin mark setup53% of fractions realigned pre-treatment

1.5 minute mean increase in treatment time

Herman, IJROBP, 2003

• 2 mm action threshold

74% of fractions realigned

< 5 minute increase in treatment time

Beaulieu, Radiother & Oncol, 2004

Need for implanted fiducialswith CT scans

kV cone beam CTMV cone beam CT

Helical MV CT

SagittalMV CT Sagittal

CB CT

Radiation Therapist vs Physician

Alignment methods: MarkerAnatomyContours

3 patients, 112 scans

Prostate alignment studyMVCT scans

Langen et al., IJROBP, 62, 1517, 2005


Therapist vs Physician registration

Marker Anatomy Contour

A/P: 1 %S/I: 2 %Lat: 1 %

A/P: 5 %S/I: 10 %Lat: 0 %

A/P: 17 %S/I: 31 %Lat: 3 %

Difference ≥ 5 mm

Langen et al., IJROBP, 62, 1517, 2005

Cone Beam KV CT Alignment techniquesFiducials vs Soft Tissues

Princess Margaret Hospital: 15 patients, 256 CT sets

Fiducial vs Soft tissues on cone-beam CT

PTV margins: 10 mm except 7 mm posteriorly

Moseley et al., IJROBP, 67(3), 942–953, 2007

kV Cone Beam CT: Soft T issues vs Markers

Less in ter -observer va riab il ity with markers


Inter-obse rver Variability (mm)

Lateral (LR) Vertical (AP) Long (SI)

MarkersSystematic Error (SD) 0.03 0.15 0.01Random Error 0.26 0.95 0.47

Soft ti ssues on CBCTSystematic Error (SD) 0.61 1.61 2.21Random Error 1.50 2.86 2.85

Cone Beam KV CT Alignment techniquesFiducials vs Soft Tissues


Agreement within 3 mm Pearson’s correlations R2

LR 91% LR 0.90AP 64% AP 0.55SI 64% SI 0.41


In-Room Guidance:MOTION

INTRA FRACTION

Courtesy George Chen, Harvard and Mass General Hospital

IRIS Dual Fluoroscopy and Flat Panels

Real-Time Marker Tracking

Real-Time Marker Tracking Real-Time Marker Tracking


Marker Implantation Feasibility AC Wireless Magnetic Tracking

Calypso SystemCalypso System

Measurements at 10 HzSub-mm resolutionReal-time trackingPotential for fast correction

Real Time Motion Data – Patient 1

Pos

ition

(m

m)

ISAPLR

Pos

ition

(m

m)

ISAPLR

Real Time Motion Data – Patient 2


v5

v85v90

v95

v98

Percentile: Regular Breather

vx = Volume at which patient had v or less volume x% of the time

Regular Breather

v5

v85 v90

v95 v98

Percentile Analysis

Irregular Breather

Example V98 (93% of time) vs V85 (80% of time)

Images that cov er 80% of b reathing cycle s how only 72% of themotion at 93% of the b reathin g cycle!

Available 3D Image DatasetsAmount of Moti on We Want to Kno w

Ratio 1. 38 ± 0.19

In-Room Correction Strategies

A. Action Levels

B. Gating


Variation vs Action Level

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

Co

rrec

ted

Un

cert

ain

ty,

σσ σσ (m

m)

0.12 4 6 8

12 4 6 8

102 4 6 8

100Action Level (m m)

1.0

0.8

0.6

0.4

0.2

0.0

Adju

stment Frequency

(σmeas2 + σpos

2)1/2

Lam, AAPM, 2006

Patient Specific Margin

Fre

quen

cy

Position (cm)

Σ = 0


Σ = 0

PTV margin = Setup + Inter + Intra-fraction0 0

+ Measurement+ Correction+ Measurement+ Correction

-0.5

-0.4

-0.3

-0.2

-0.1

0.0

0.1

Po

siti

on

(cm

)

600540480420360300240180120600Time (s)

Initial Setup Variations

Pos

ition

(m

m)

1

0

-1

-2

-3

-4

-5

SystematicσIntra

AP

Assume σs = 1 mm

1.0

0.8

0.6

0.4

0.2

0.0

-0.2

-0.4

Po

siti

on

(cm

)

600540480420360300240180120600Time (s)

Pos

ition

(m

m)

2

0

-2

-4

6

8

10

4

Intra-Fraction Correction


Margins vs Management Strategy Radiofrequency transponders: Prostate rotation

• Apply real rotations from tracked data to assess plan efficacy

• Real-tracking data (sampled at 10Hz) from a research version of the Calypso System

• Rotational and translational corrections were applied to the prostate contours for each patient and the amount of time the prostate was outside the PTV was determined

C. Noel, Washington University

Plan Evaluation

For 3 patients, over 122 total fractions, the percentage of timeany portion of the prostate is outside of a 5mm PTV: ***

25%Patient 1

51%Patient 3

<1%Patient 2

% Time out of 5m m PTV

***C Noel, ASTRO 2008

Plan Evaluation

…for a 3mm PTV margin:

80%Patient 1

93%Patient 3

5%Patient 2

% Time out of 3mm PTV



Plan Evaluation

<1%Patient 1

3.3%Patient 3

0%Patient 2

% Time out of 8m m PTV

…for a 8mm PTV margin:


Visualize Rotations

Cont oured prost ate and PTV f rom plan

Day 1 Prostate Position at Set -up: 9 ˚Day 2 Prostate Posit ion at Set-up: 30 ˚

Visualize RotationsTracked motion data

Visualize RotationsChange PTV fro m 5mm to 3mm


Outline









Offline Adaptive Protocols

• Adaptive Radiation Therapy – ART– N ~ 5 CT scans with contours– Union of volumes to form patient-specific PTV

Yan, et al, IJROBP, 2000.

• No Action Level protocol – NAL– N ~ 5 portal images to estimate Σ

De Boer, et al, IJROBP, 2001

• Shrinking Action Level protocol – SAL– Nmax ~ 5 portal images to estimate ΣN

– If ΣN < αN = α / N1/2, apply offset to all fractions– Else apply and restart at N = 1

Bel, et al, Radiother Oncol, 1993.

Initial CTV + 4 CTVs = ITVITV + Random Setup Error of Bones = cl-PTV

Confidence-Limited PTV (cl-PTV)

transverse coronalsagittal

Kestin, RTOG, 2006

Adaptive Radiation Therapy - ART


• PTV volume reduced by mean of 34% (N=600 patients)– > 30% of conventional PTV unnecessary in 75% of patients

• Equivalent uniform margin: mean = 5.6 mm

• If planning based on single CT scan:– ~ 14 mm margin (AP) required to meet similar dosimetric

criteria

• Average IMRT dose escalation of 7.5% (86.7 Gy)

Margin Reduction (N=600)Margin Reduction (N=600)

Adaptive RT TrialAdaptive RT Trial

MeldolesiMeldolesi et al. et al. IntInt J J RadiatRadiat OncolOncol BiolBiol PhysPhys 63:S9063:S90--S91; 2005S91; 2005

Conventional PTV cl-PTV

•• Margins stringently designed to allow <3% Margins stringently designed to allow <3% dose reduction within CTV with an 80% dose reduction within CTV with an 80% confidenceconfidence

Kestin, RTOG, 2006

Outline









Treatment without Margins

• Multiple Instance Geometry Approximation (MIGA)

• Approximate positional uncertainties by a modeled sequence of positions (e.g. independent CT scans)

• Dose calculation is for weighted sum of different patient geometries

• Assuming that model is correct, dose calculation accounts for geometric uncertainty

MIGA


MIGA

• Fluence is NOT just a blurring of the PTV-based plan!

• No PTV margin

• Simultaneous optimization of multiple instances of geometry• Solutions maybe worse than the static geometry solution,

but are much better than the static geometry solution when compromised by motion

The End!

Thanks for attending!

Up Next:

Treatment Planning of Complex Cases

M Hunt and T Nurushev

Documents

Abstract Margins in Radiation Therapy · • Fiorin o C, Reni M, Bolo gnesi A, et al. Set -up error in supine -posit ioned patients immobili zed with two dif ferent modali ties during