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Errors and margins in image guided radiation therapy
Marcel van Herk, David Jaffray*, Anja Betgen, Peter Remeijer, Jan-Jakob Sonke, Roel Steenbakkers, Monique Smitsmans, Marnix Witte and Joos Lebesque
Netherlands Cancer Institute, Amsterdam, The Netherlands
*Princess Margaret Hospital, Toronto, Canada
This work was sponsored by the Dutch Cancer Foundation, NIH and Elekta Oncology Systems
Classic radiotherapy procedure
Tattoo, align and scan patient
Draw target and plan treatment on RTP
Align patient on machine on tattoos and treat (many days)
In principle this procedure should be accurate but
Problems in radiotherapy:The patient is nervous, did not sleep the night before and lay
wriggling on the CT scanner
The physician was in a rush when drawing the target volume
The patients belly flopped from day to day, letting the skin marks move all over the place
The patient was breathing
And the tumor shrank away from its original place
Motion counts: prostate trial data (digital image analysis of 660 patients)
Risk+ rectal distention Crevoisier et al, IJROBP 2004Heemsbergen et al, IJROBP 2006
How can we solve this problem ?
1. Use large margins, irradiating too much healthy tissues
2. Use small margins, and risk missing the target
3. Or: use image guided radiotherapy
Image Guided Radiotherapy
The gain of image guidance depends on the magnitude of geometrical uncertainties and variations that are and aren t addressed by the image guidance protocol
Image guidance will introduce its own uncertainties and variations
Let s look at geometrical errors in RTImaging errorsPlanning errorsTreatment errorsImage guidance errors
Increase precision by imaging target and/or healthy tissues just prior to treatment
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NomenclatureGross error: mistakes, transcription errors, software faults:
must be caught by QA, not in this lecture
Error: difference between planned measurand and its true value during treatment, however small
Uncertainty: the fact that unpredictable errors occur quantified by standard deviations
Variation: the fact that predictable or periodic errors occur quantified by amplitude or standard deviations
Nomenclature
Systematic error: average difference between planned and executed treatment
Patient group errorsInter-patient errors
Random error: uncertainty and variation in difference between planned and executed treatment
Inter-fraction errorsIntra-fraction errors
Did you do a good job planning the treatment?
Imaging errors
CT scan is just a random snapshot of a changing patient
Organ motion and setup error are frozen in arbitrary position
Interference between motion and imaging distorts image contents
The beams will be pointed to the target in this image systematic error !
Better imaging in adaptive RT: use multiple scans to get better estimate of prostate position
Day 1 Day 2
Day 3 Composite
Match up to 10 scans
Paint each prostate
Automatic generation:
- composite
- mean
Yan et al; IJROBP 96
Better imaging: respiration correlated CT & PET
Free-breathing What it should be!
Allows determination of correct shape, SUV, mean position and trajectory of tumor
Fused 4DCT and 4DPET: Wolthaus et al, PMB 2005
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Main planning error: GTV/CTV delineation
- 11 observers from 5 institutions, 22 patients- newly developed delineation software (runs from CD)- delineation on CT + (one year later) CT+PET
Steenbakkers et al, IJROBP 2005
CT (T2N2)
SD 7.5 mm
CT + PET (T2N1)
SD 3.5 mm
Delineation variation: CT versus CT + PET
The beams will be pointed to the target the physician draws !
4.210.2Total
8.214.6Lymph nodes
4.819.1Tumor atelectasis
3.74.0Tumor chest wall
4.47.4Tumor mediastinum
3.35.9Tumor lung
CT + PETSD (mm)
CTSD (mm)
Interface / region
Delineation variation in lung cancer
Steenbakkers et al, IJROBP 2005
Main errors in image guided RTImaging (planning CT) and planning errors
Systematic error not solved by image guidance
Observer errors in image guidanceRandom and systematic
Short-term (intra-fraction) motionNegligible for bony anatomyRandom and systematic soft tissue
Inadequacy of surrogate for tumor position
Machine calibrationGroup systematic error
This is what IGRT solves: setup errors -measured with CBCT at NKI
Van Herk et al EPI 2K4, Borst et al, IJROBP 2007
Elekta Synergy system Bony setup error: 3 mm SD
Are you an accurate observer ?
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Reference Localization
IGRT software: automatic bone localization IGRT software: automatic bone localization
Reference Localization
Cone beam CT series matched to planning CT on bone
Estimated match accuracy << 1 mm SD
-10.0
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-10.0 -5.0 0.0 5.0 10.0
Correlation CBCT EPID for lung
-10.0
-8.0
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-10.0 -5.0 0.0 5.0 10.0
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-10.0 -5.0 0.0 5.0 10.0
Left-Right Sup-Inf Ant-Post
Setup error measured with cone beam CT
EPI
D
EPI
D
EPI
D
Observer error in CBCT is negligible large observer error in EPID such as a clear under-estimation of AP shift (lung)
Slope: 0.81 .. 1.06 0.66 .. 0.88 0.30 .. 0.66 (95% CI)
Borst et al, IJROBP 2007
Difference 0.2 3.7 mm
LR
Difference 2.7 3.9 mm
SI
Difference 1.6 3.1 mm
AP
Observer error in US prostate localization
Comparison of marker and US based prostate localization:
Langen et al, IJROBP 2003Van den Heuvel et al, IJROBP 2003
Automatic prostate localization in CBCT (30 s)
Cone beam CT
Planning CT contours placed automatically
10 CBCT scans: automatic bone match
10 CBCT scans: automatic prostate matchhelp line (GTV+3.6 mm)
Smitsmans et al., IJROBP 2004, 2005
LR (mm)
CC (mm)
AP (mm)
Mean 0.2 -0.4 -0.9
SD 1.0 2.4 2.3
Observer error:(calcifications)
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Does the tumor move after imaging ?
Intra-fraction patient motion (bone) negligible example:
6 bladder cancer patients35 x 2 CBCT scans10 minutes between post- and pre-scanmeasured set-up changes:
0.3
SD
anterior-posterior (mm)
cranio-caudal(mm)
left-right (mm)
0.5-0.100.40post-pre
SDmeanmeanSDmean
A. Betgen et al, ESTRO 2005
Short-term prostate motion (1 h)
Data courtesy of Jaffray and Gilhezan, Beaumont
Main problem for any prostate IGRT: moving gas
cone-beam CT scanProjection images
Moving gas reduces image quality and introduces short term motion
Are you using a good surrogate for the tumor
position?
The tumor changes: repeated 4D cone beam CT
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Baseline motion: 4D scans taken within one week and matched on bone, displayed in same phase
Imagine treating this patient with gating and a small margin, without 4D cone-beam CT!
Mean Tumor Position Variability (4DCBCT)
Mean SD
0 0.5 cm (10 Pts)
0.5 1.0 cm (8 Pts)
1.0 1.5 cm (9 Pts)
1.5 2.0 cm (5 Pts)
Amplitude:
Jan-Jakob Sonke et al, IJROBP 2007On average 3 mm SD
What should the margin be ?
Analysis of motion(random and systematic errors)
mean =M
RMS = SD =
Intra-fraction
0.0
0.3
0.4
0.1
0.3
_________
Mean = 0.2
RMS of SD = f
patient 1 patient 2 patient 3 patient 4fraction 1 0.5 0.0 0.2 0.7fraction 2 0.6 -0.5 0.3 0.2fraction 3 0.9 0.2 0.2 -0.4fraction 4 1.3 -1.1 0.3 -0.1
mean 0.8 -0.4 0.3 0.1sd 0.3 0.6 0.1 0.5
van Herk et al, Sem Rad Onc 2004
M = group systematic error (equipment)= standard deviation of the systematic (preparation) error= standard deviation of the random (execution) error
f = standard deviation of the intra-fraction motion{
Definitions (sloppy)
CTV: Clinical Target VolumeThe region that needs to be treated (visible plus suspected tumor)
PTV: Planning Target VolumeThe region that is given a high dose to allow for errors in the position of the CTV
PTV margin: distance between CTV and PTV
Don t even think of using an ITV! (SD adds quadratically)
Demonstration errors in RT
Margin between CTV and PTV: 10 mm
Errors:Setup error:
4 mm SD (x, y)
Organ motion: 3 mm SD (x, y)10 mm respiration
Delineation error: optional
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What is the effect of geometrical errors on the CTV dose ?
Treatment execution (random) errors blur the dose distribution
Preparation (systematic) errors shift the dose distribution
dose
CTV
CTV
Error distributionsCentral limit theorem:
the distribution of the sum of an increasing number of errors with arbitrary distribution will approach a Normal (Gaussian) distribution
Large errors happen sometimes if all or most of the small sub-errors are in the same direction
Normal distribution:
-3 0 30
200
400
600
800
1,000
1,200
1,400
mean = 0s.d. = 1N = 10000
-2..2 = 95%
Analysis of CTV dose probabilityBlur planned dose distribution with all execution (random) errors to estimate the cumulative dose distribution
For a given dose level:
Find region of space where the cumulative dose exceeds the given level
Compute probability that the CTV is in this region
Computation of the dose probability for a small CTV in 1D
x
dose
x
P
..and compute the probability that the average CTV position is in this area
In the cumulative (blurred) dose, find where the dose > 95%
98%
95%
average CTV position
What should the margin be ?
0 100minimum CTV Dose (%)
prob
abili
ty (
%)
0
100
0 mm
6 mm
9 mm
12 mm
How to choose the PTV margin
Express required CTV dose for a specified fraction of patients. For example: 90% of the patients must get a minimum CTV dose of 95% or more
Add first margin so that 90% of the preparation (systematic) errors are covered
Add margin for penumbra and execution (random) variation so that CTV + first margin lies within the 95% isodose
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Simplified PTV margin recipe for dose - probability
To cover the CTV for 90% of the patients with the 95%isodose (analytical solution) :
PTV margin = 2.5 0.7
quadratic sum of SD of all preparation (systematic) errors quadratic sum of SD of all execution (random) errors
van Herk et al, IJROBP 47: 1121-1135, 2000)
*For a big CTV with smooth shape, penumbra 5 mm
What about respiration ?
0 0.5 cm (10 Pts)
0.5 1.0 cm (8 Pts)
1.0 1.5 cm (9 Pts)
1.5 2.0 cm (5 Pts)
Amplitude:
Jan-Jakob Sonke et al, IJROBP 2007SD = 0.35 peak-peak
Computing margins
A=10 mm 3.3 mmTreatment respiration
22 mmMargin M
Lung classicError (SD)
4 mmDelineation
4 mmTreatment setup
3 mmTreatment organ motion
A=10 mm 3.3 mmImaging snapshot respiration
3 mmImaging snapshot organ
4 mmImaging snapshot setup
7.05.2M
van Herk et al IJROBP 2000
2.5 + 0.7 is a gross simplificationDose gradients ( penumbra = p) very shallow in lung small margins for random errors
Number of fractions is small in hypofractionationBUT: beam on time is very long respiration only causes dose blurring
Dose prescription at 80% instead of 95%
Respiration is not gaussian asymmetry
222 64.1)(64.15.2 ppM
222 84.0)(84.05.2 ppM
Margins in lung hypo (3 x 18 Gy)
0 mm7 mm +Margin A=10 mm
7 mm +
3 mm SD
1.5 mm SD
1.5 mm SD
2 mm SD
Systematic
2 mmMargin A=20 mm
2.2 mm SDTotal
1.5 mm SDIntra-fraction motion
1.5 mm SDRegistration/couch shift
-Delineation
Random
222 84.0)(84.05.2 ppM p 7.8 mm
Ensures 80% isodose encompasses GTV 90% of time in lung
Future developments
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Incorporation of remaining geometrical errors in radiotherapy planning
blurred dose
CTV
PTV
planned dose
Correct - blur for random and test all systematic errors
Wrong - compute DVH and TCP for PTV
Uncertainty management: Conventional IMRT planning with margin
CTV PTV
Inverseoptimization
Objective functionsPoisson cell kill, EUD,
DVH points, ...
Dose distribution
90% prob. ofD 95% Dprescribed
in CTV
M = 2.5 +0.7
OAR
Witte et al, IJROBP 2007
Uncertainty management: Probabilistic biological IMRT planning without margin
CTV
Inverseoptimization
Objective functionswith simulated errors
TCP , NTCP
Dose distribution
Maximum TCPfor given
OAR NTCP
OAR
,
no PTV margin!
Witte et al, IJROBP 2007
Best current practice versusProbabilistic planning
74.1 Gy64.6 Gy39.0 Gy
78.0 Gy
SIB Probabilistic (PTVs not used)
CTVCTV CTVCTV
RectumRectumRectumRectum axial
Same control, complications down with 50%Witte et al, IJROBP 2007
ConclusionsThere are many error sources in radiotherapy
Determine what these error sources are and what their impact is in your department
Focus on correcting remaining systematic errorsDo not forget the doctor s error delineation4D CT and portal imaging can half the margin for lung
IGRT does not eliminate all errors; carefully consider the margins to be used
IGRT introduces new errors and makes old errors more important (where is the CTV?)
Margin recipes assume that you know ALL ERRORSUSE AT YOUR OWN RISK
Thank you for your attention!
IGRT+IMRT
US
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