Different Styles of Image-Guided Radiotherapy

Marcel van Herk

To account for geometric uncertainties during radiotherapy, safety margins are applied. In
many cases, these margins overlap organs at risk, thereby limiting dose escalation. The aim
of image-guided radiotherapy is to improve the accuracy by imaging tumors and critical
structures on the machine just before irradiation. The availability of high-quality imaging
systems and automatic image registration on the machine leads to many new clinical
applications, such as high-precision hypofractionated treatments of brain metastases and
solitary long tumors with online tumor position corrections. In this review, the prerequisites
for image guidance in terms of planning, image acquisition, and processing are first
described. Then, the various methods of correction are discussed such as table shifts and
rotation and direct adaptation of machine parameters. Then, online, offline, and intrafrac-
tion correction strategies are discussed. Finally, some imaging dose issues are discussed
showing that kilovoltage cone-beam computed tomography guidance has a net positive
impact on the integral dose; the gain caused by margin reduction is larger than the image
dose. We can conclude that image-guided radiotherapy is very much a clinical reality and
that the development of optimal clinical protocols should currently be the focus of research.
Semin Radiat Oncol 17:258-267 © 2007 Elsevier Inc. All rights reserved.

E xternal-beam radiotherapy (RT) is one of the primary

treatment modalities for cancer. Generally, generous
safety margins are applied around the target and optionally
for organs at risk (OARs) such that under- and overtreatment
caused by geometric uncertainties can be avoided with an
acceptable probability.1 However, the dose delivered to these
margins affects surrounding tissues such that to spare these
tissues the achievable dose for the tumor is often compro-
mised. For instance, in prostate cancer, the dose to the rec-
tum limits dose escalation,2 whereas for the lung it is often the
esophagus or the healthy lungs that are dose limiting.3 The
introduction of novel techniques in RT such as intensity-
modulation RT (IMRT) and image-guidance RT (IGRT) gives
the possibility to apply tighter margins and higher-dose gra-
dients as with conventional RT. These techniques aim at
maximizing the dose to the target while minimizing the dose
to the OARs. To exploit these new technologies, geometric
variations have to be quantified and corrected. This reduces
the required safety margin and allows dose escalation with-
out compromising nearby OARs.
Radiotherapy Department, The Netherlands Cancer Institute/Antoni van
Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Address reprint requests to Marcel van Herk, Department of Radiotherapy,
The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,
Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail:
portal@nki.nl
For this reason, all major RT system vendors are develop-
ing IGRT systems that allow imaging and/or correction of the
target position before each RT session. Even though it may
seem obvious that accuracy in RT is a good thing, there is no
direct and only limited indirect evidence of the impact of
geometric accuracy on outcome. Recently, 2 publications
have retrospectively analyzed prostate trial data and found a
correlation between rectal distention and outcome.4,5 It has
been hypothesized that this relation is because of a geometric
miss; in those patients in whom the rectum is distended in
the planning scan, there is a larger systematic error in the
prostate position during treatment6 than in those patients
without distended rectum. Even though this explanation
sounds likely, this hypothesis still needs to be confirmed.
IGRT can be defined as follows: increasing the precision by
frequently imaging the target and/or healthy tissues just be-
fore treatment and acting on these images to adapt the treat-
ment. There are several image-guidance options available. A
non-integrated option is to use a computed tomography (CT)
scanner outside the treatment room (adaptive RT).7 Options
that are integrated in the treatment room include: kilovoltage
(kV) x-ray imaging, active implanted markers, ultrasound,
megavoltage (MV) single slice CT (Tomotherapy), conven-
tional CT, and kV or MV cone-beam CT.8-14 Key components
of any image-guidance system are an image-acquisition sys-
tem that provides soft-tissue contrast and/or adequate imag-
ing of the used surrogate. The imaging system should be in a
calibrated position and have a high speed of acquisition and

258 1053-4296/07/$-see front matter © 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.semradonc.2007.07.003
Styles of IGRT
reconstruction. Then, a reference dataset should be available,
such as the planning CT with the gross target volume (GTV)
contour. The user should have the ability to define a region of
interest so that the target localization software, which con-
sists of fast automatic image registration, knows which part of
the image to focus on. Finally, there should be a method for
correction (eg, on- or offline). This article inventories the
possible correction strategies that have been developed so far
as a guideline for selecting one for the particular clinical
problem at hand.
Image Guidance
Goals of Image Guidance
The following questions can be asked when developing a
correction strategy: (1) How does the relevant anatomy move
or change? (2) How fast does it move (at different timescales)?
(3) How and when to measure it (use surrogate)? (4) When to
correct it, (5) How to correct it? and (6) How to determine
efficiency of a correction protocol? Table 1 lists typical ana-
tomic motions and the timescale at which they occur. Ana-
tomic motion can cause poor quality of scans; random and
systematic setup errors when the bony anatomy moves rela-
tive to the machine; random and systematic organ motion
when the target moves relative to bony anatomy; and dose
inhomogeneity during IMRT delivery, the so-called interplay
effect.15
Before IGRT
Before your image-guided treatment can start, a (initial) treat-
ment plan has to be made in a correct way. This implies that
good-quality image data are available that are representative
for the patient in treatment position. However, parts of the
lung move appreciably because of breathing,16 whereas re-
spiratory motion induces imaging artifacts during CT scan-
ning,17,18 leading to degradation in the ability to delineate
anatomic structures19 and to erroneous position, shape, and
volume information.20 To improve imaging, a number of cen-
ters have introduced respiratory-correlated CT,21,22 provid-
ing a 4-dimensional CT dataset. Respiratory-correlated CT
reduces motion artifacts such that the mean position, trajec-
tory, and shape of moving anatomy can be determined with
high accuracy. A recent survey about management of respi-
ratory motion is the AAPM Task Group Report 76.23 But how
to use a 4-dimensional scan in clinical practice? Currently,
no clinically released planning system can deal with 4-di-
mensional data. The solution that we chose is to derive a
Table 1 Anatomic “Motions” and the Timescale at Which They
Occur
Day to day Skin motion Nonpredictable
Hour to hour Prostate motion Nonpredictable
Minute to minute Bladder filling Predictable
Neck flex Nonpredictable
Second to second Respiration Predictable
Heartbeat Predictable
Peristalsis Nonpredictable
259
single frame of a 4-dimensional CT movie, in which the mov-
ing tumor is closest to its mean position, a midventilation
scan.24,25 This scan is fused with a midventilation PET. This
midventilation scan is geometrically and dosimetrically rep-
resentative for the breathing patient (ie, by blurring the dose
distribution with the respiratory motion function, a virtually
identical dose distribution is obtained as in 4-dimensional
planning).26,27
Although in the lung, the tumor motion is mostly predict-
able; in prostate cancer, this is not the case. So the best that
we can do when using a single-planning CT is to avoid that
this CT is an outlier. This means that the scan needs to be
redone when the rectum is distended28 and maybe when
there is extreme bladder filling. Other reasons for redoing the
planning CT could be a awkward patient setup that would be
hard to reproduce during treatment or patient or gas motion
during scanning.29,30 For improved target volume delinea-
tion, the scan needs to be fused with magnetic resonance
imaging.31 For many tumor sites, it is beneficial to apply a
moderate amount of contrast to help in distinguishing nor-
mal vessels from tumor even though this might have some
impact on dose computation.32 The bottom line is that ade-
quate image information should be available to accurately
delineate target volumes and normal structures. Even in op-
timal conditions, one should realize that interobserver varia-
tion is not negligible and may exceed by far the uncertainties
in the rest of the treatment chain (ie, the largest part of the
margin will have to deal with this uncertainty).33 Further-
more, clinicians must have population statistics of the uncer-
tainties available and, if required, also data on predictable
patient-specific motion (eg, amplitude in 3 directions of
breathing motion from 4-dimensional CT, for instance deter-
mined by local rigid image registration25). A summary detail-
ing how to derive population data for setup error and organ
motion can be found in van Herk.18 Next to the so-called
“stationary” errors, there may be time trends in the position
and shape of the tumors that should be investigated.34-36
There are no protocols defined yet to deal with time trends in
tumor shape or volume, apart from replanning.
IGRT Systems
Nowadays, all major research groups and vendors have de-
velopments in IGRT using volumetric imaging. Clinical ex-
perience has been reported with megavoltage14 and kilovolt-
age37 CBCT systems and diagnostic CT scanners on rails.12,38
Most of these developments are quite new and focus on the
acquisition of images with sufficient image quality for the
clinical task at hand. In addition, several image-registration
techniques are under development to localize specific organs.
Ultrasound image guidance and electronic portal imaging are
older developments in IGRT. However, the 2-dimensional
nature of these systems limits the information that can be
gathered. Portal imaging is generally limited to bony anat-
omy, and it has been observed that the accuracy of the CBCT
for bone localization by far exceeds that of planar imaging,
specifically for lung treatments.39 Also, ultrasound imaging
has been hampered with large observer errors.40,41 However,
with the implementation of 3-dimensional ultrasound sen-
260 M. van Herk

sors for soft-tissue localization purposes, these errors will
probably decrease.
Measurement of Setup Error and
Organ Motion in an IGRT System
Methods for measurement of setup error and organ motion in
an IGRT system are based on image registration. The simplest
systems are based on rigid registration of the entire scanned
portion of the patient. However, this has a disadvantage be-
cause anatomic deformation will invariably lead to poor reg-
istration. It is better to have a rigid registration method using
a box-shaped or arbitrarily shaped region of interest; this
accelerates registration, provides a stable solution even in the
presence of deformations, and provides a visual aid when
validating the registration results. Many groups are also
working on more advanced solutions such as rigid registra-
tion of multiple regions of interest or deformable registration.
However, such methods are not in clinical use yet. In all
cases, automatic image-registration techniques can fail so
a fallback mechanism must be available based on user inter-
action.
In general, the process of registration has more degrees of
freedom than the applied correction. This is acceptable as
long as one realizes that the registered images do not show a
setup that is clinically achievable (eg, a couch shift after de-
formable registration can only correct a few out of the hun-
dreds parameters determined). This means that there is a
need to convert registration results into a correctable error.
Our group described a method to discard rotations from a
rigid body registration (translation ⫹ rotation) to obtain an
optimal couch shift based on a correction reference point that
acts as a virtual rotation point.42 In all cases, it is extremely
important to define protocols in which algorithm setting,
regions of interest, visual tools to be used, and other settings
are defined. In an optimal image-guidance system, such op-
tions should be preset once and reused for all fractions. How-
ever, one should realize that visual verification (and manual
registration tools as fallback) remains essential because auto-
matic algorithms will fail occasionally. The screen layout and
image fusion methods of the image guidance application
should be such that misregistration can be quickly detected
(Fig 1).
Correction Strategies
Correction Methods: How To
Correct Setup Error or Organ Motion
The first-generation IGRT systems typically only allow cor-
rections through table shifts. For offline protocols, one needs
a relative couch readout, allowing a programmed ad hoc
couch shift after setup to reference marks. Auto shift is now
available from all vendors. Rotations in setup error have gen-
erally been ignored because of the difficulty of estimating

Figure 1 Example of user interface of an image-guidance system. Visual verification of the registration is through a
green-purple image mix. Because green and purple are complimentary colors, correctly registered anatomy shows up
as black and white. In this case, registration was based on a box-shaped (gray) region of interest containing bony
anatomy in close proximity of the gross tumor (contour). Because there is sizeable deformation in the patient due to a
change in swelling, registration based on the whole volume would have been unsuccessful. (Color version of figure is
available online.)
Styles of IGRT
out-of-plane rotations from 2-dimensional images. One way
to overcome this situation is to apply 2-dimensional to 3-di-
mensional registration.43,44 This method was then not imple-
mented clinically, mainly because of the complexity of anal-
ysis and data transfer, which was prohibitive a decade ago.
Recently, however, BrainLAB (Heimstetten, Germany) has
implemented a similar method in their in-room imaging sys-
tem.45 Such a development is now feasible because of the
tighter integration between planning and image-guidance
systems. Several researchers stated that larger margins are
required around the seminal vesicles to account for rotations
of the prostate46,47 and that significant time trends were
present in the rotations.46 To that end, margin recipes have
been developed that explicitly include rotations,48 possibly
based on physical or biological considerations.49,50 Herman
and coworkers51 used markers for prostate setup and re-
planned the beams if systematic prostate rotations larger than
3° were found. With the advent of in-room volumetric sys-
tems, accurate measurement of rotational errors is straight-
forward, and their correction is clearly a next step to improve
the precision.39 Deformations of prostate and seminal vesi-
cles during the course of RT are small relative to organ mo-
tion.52 Therefore, it is a valid approximation in IGRT of pros-
tate cancer, in first order, to correct only for translations and
rotations. Based on these results, methods for automatic lo-
calization of the prostate for online or offline IGRT have been
developed using local automatic or semi-automatic rigid
grey-value registration of CT scans.53-55
Tables that can tilt and roll are now available. For the
patients’ comfort and safety, these tables are limited to rota-
tions of a few degrees. This is generally enough to correct for
rotations of the bony anatomy,39,44 even though it is impor-
tant to have rigid immobilization because the patient will
react to and potentially compensate for the rotation with a
translation.56 Because such systems are limited to a few de-
grees rotation, they cannot deal with prostate rotations that
can easily exceed 10°.28 Tilt-and-roll couches remain inter-
esting for some stereotactic applications, even though the
impact of rotational errors up to 3° (ie, 1° standard deviation
[SD]) are very limited for most tumors.49 Thus, rotating the
patient is generally not a useful option. Therefore, it may be
more suitable to adapt parameters, such as gantry and colli-
mator angle of the treatment machine, which allow correc-
tions of larger and, therefore, more relevant rotations such as
of the prostate.57 However, control of the machine parame-
ters requires tight coupling of the accelerator and IGRT sys-
tem. In the tomotherapy system, the starting point of the
gantry rotation is changed to perform a patient roll correc-
tion.58 In the CyberKnife system (Accuray, Sunnyvale, CA),
the robot has enough degrees of freedom to correct for arbi-
trary rotations.59 Several groups are developing methods to
adapt multi-leaf collimator or other machine parameters.60
Again, these systems require tight coupling between the im-
age-guidance system and the linear accelerator and are not
expected to be available for online corrections soon.
Next to rotations, deformations and changes of the anat-
omy are important. Large deformations in cervix cancer were
found for which rotational corrections would certainly not be
261
enough.61 Also, considerable lung tumor shrinkage occurs,
maybe in up to 40% of the patients.35 Several groups are
developing methods to include knowledge of organ deforma-
tions.62,63 In current systems, a full replan based on the mod-
ified geometry provides the most versatile correction
method. It is feasible to replan using knowledge of the accu-
mulated dose.64 Online planning for single-fraction treat-
ment is also an option.65
Correction Procedures: How To
Correct Setup Error or Organ Motion
There are 3 types of correction strategies: offline correc-
tions—reacting to the image, data are delayed to a sub-
sequent fraction; online corrections—a reaction is made im-
mediately following imaging; intrafraction corrections—
multiple images and corrections are made per fraction. A
mixture of these 3 is also possible.66
Offline Correction Strategies
The rationale for offline correction strategies is that margin
requirements are dominantly determined by systematic er-
rors and much less by random errors. Offline protocols aim
to correct for the mean error of a patient without correcting
daily variation. They allow a large step in margin reduction
with limited workload. Statistical procedures to drive offline
corrections have been addressed extensively from the field of
electronic portal imaging. Early correction strategies were
aimed at correcting systematic errors with minimal work-
load.67,68 More recently, a no-action level protocol has been
proposed that requires less workload but that is, in its base
form, less fail-safe. It has therefore later been expanded with
extra measurements to improve safety69 or to correct time
trends.70 Corrections based on maximum likelihood have
been proposed as further improvement of these proto-
cols.41,71 Based on biological modeling and physical con-
siderations, the optimal number of imaging days in offline
correction protocols was considered to be ⬃10% of all
fractions.72,73
Adaptive RT
Yan and coworkers7 extended the idea of off-line corrections
to include organ motion. By combining the information of
multiple CT scans obtained in the first week of treatment, a
better representation can be made of the average position of
internal anatomy, and margins can be tailored to individual
patients (adaptive RT).7 They found that a single-plan mod-
ification within the second week of treatment improves the
efficacy of dose delivery and dose escalation for RT of prostate
cancer. The construction of the adapted target volume can be
done in different ways. Yan applied patient specific statistics
to determine the margin size; the convex hull of the prostate
on 4 CT scans was used to replan, and this hull will be bigger
when the prostate moves more. In our clinic, we recently imple-
mented adaptive RT based on kilovoltage CBCT images.37,53
Here we use population statistics and do not adapt the mar-
gin for individual patients; we derive the mean prostate po-
sition and use a reduced margin of 7 mm for the 68 Gy part of
the treatment of all patients compared with the original
10-mm margin before the introduction of the adaptive RT
262
Figure 2 Measurement error in the SD. This graph shows the 95%
confidence interval for the SD estimated from n measurements.
After 4 measurements (eg, 4 CT scans or 4 setup images pairs), a
patient with a true ␴ error of motion of 1 would show an observer
SD between 0.27␴ and 1.77␴. (Color version of figure is available
online.)
procedure. Analysis showed that the convex hull approach
with a 4-mm margin (similar to Yan) and the mean prostate
with a 7-mm margin are equally efficient in terms of normal
tissue sparing and coverage.74 This is probably because of the
fact that too few measurements are available to make a defin-
itive statement about an individual patient’s statistic.75 This
means that a patient-specific PTV derived from a few scans
will be a poor estimate of the required margin (Fig 2). Be-
Figure 3 Infrastructure for adaptive radiotherapy. An in-house developed delineation and image-registration software
package is used as input for the clinical planning system. It also acts as an entrance point for the data to adapt the target
volumes. (Color version of figure is available online.)
M. van Herk
cause of the large uncertainty in the estimate of the SD, it is
better to use a Kalman or Bayesian style approach76; here the
data of the SD of individual patient data are combined in a
weighed method with population data. With just a few mea-
surements (scans), this estimate is mostly determined by the
population data. The adaptive RT approach is also feasible for
bladder cancer irradiation, resulting in 40% reduction of the
mean boost treatment volume.77 Because adaptive RT is an
offline correction, it can correct complex errors (eg, rotation/
deformation) by simply replanning.
Our infrastructure for adaptive RT is shown in Figure 3.37
Kilovoltage CBCT acquired on Elekta Synergy machines
(Elekta Oncology Systems Ltd., Crawley, UK) is used to
adapt the GTV after 5 fractions. The advantage of using soft-
tissue imaging for image guidance rather than markers is that
an adapted version of the rectum can also be made.37 How-
ever, this is quite time consuming at present because the
rectums are delineated manually in all CBCT scans. To clin-
ically implement the adaptive RT procedure, we use in-
house– developed image registration and delineation soft-
ware78 that acts as input for our clinical planning system
Pinnacle (Philips Medical Systems, Best, The Netherlands)
and provides a feedback point where image guidance data
may be processed.
Online Correction Strategies
The rationale for online corrections is that the workload of
measurement and correction is reducing; it becomes feasible
Styles of IGRT
to perform corrections directly after imaging. Ghilezan and
coworkers79 analyzed the potential for daily online IGRT for
prostate cancer and found that, on average, a 13% dose es-
calation (ranging from 5%-41%) was possible. However,
such an application requires that efficient correction strate-
gies are available that go beyond a simple couch shift. One
issue that has not received adequate attention is the degree of
correlation between motion of disjoint parts of the anatomy
that influences the choice of optimal margins and correc-
tions. The explicit selection of margins may in the future be
omitted by integrating knowledge of geometric uncertainties
in treatment-plan evaluation49 or optimization.80-82
An obvious advantage of online corrections is that both
systematic and random errors are corrected efficiently. A dis-
advantage is that analysis and corrections must be fast, sim-
ple, and unambiguous, whereas the time pressure could af-
fect the accuracy of the procedure. In addition, because of
remaining uncertainties, the gain of online procedures must
not be overestimated. Careful analysis showed that in pros-
tate cancer online correction based on kilovoltage CBCT im-
aging could allow margins of 5 mm.53 Even though surro-
gates for prostate motion can be localized with a much higher
accuracy, uncertainties such as the initial target volume de-
lineation and later deformations will probably limit the accu-
racy to similar levels.66 One should also realize that more and
more accurate delivery might expose limitations in the accu-
racy of the CTV definition. We, therefore, consider margins
of less than 5 mm unrealistic for most applications.
Online planning using volumetric imaging data are being
explored specifically for application in the context of “simu-
late and treat” cases. The arguments for this development
include more accurate target definition compared with radio-
graphic methods (eg, conventional simulator), reduced time
spent in the department by the patient, and more conformal
treatment volumes for the increasing practice of retreats in
the palliative context. The challenges are numerous. Image
quality, accurate CT numbers, and rapid segmentation, plan-
ning, quality assurance, and delivery all need to be addressed
for this process to be feasible.65 Letourneau and coworkers65
have shown that this process can be completed in ⬍30 min-
utes with appropriate streamlining of existing imaging, plan-
ning, and quality assurance tools.
Correction of Intrafraction Motion
The rationale for intrafraction correction is to correct even
the last bit of motion. The conventional solution to correct for
respiratory motion is to expand the PTV. Consequently, high
dose is also delivered to adjacent structures. If the time-aver-
aged tumor position is accurately known (no systematic er-
rors), however, the required margin for respiration is rela-
tively small.83,84 Methods that lead to a further margin
reduction are gated RT,85 breath-hold techniques,86,87 and
tumor tracking.88,89 For unpredictable motion, such tech-
niques add safety, whereas for predictable motion it removes
the dose blurring effect of the motion. Continuous correc-
tions require an extremely robust motion detection of the
tumor. For this reason, often a surrogate is used (eg, abdom-
inal motion) that has to be calibrated once or many times with
263
the actual tumor motion to keep it reliable. These methods re-
quire extensive quality assurance, and the gain is debatable.
Also, changes in anatomy and respiratory pattern occur that
need to be monitored and corrected. For this reason, CBCT-
guided linear accelerators have been developed that acquire
regular (3-dimensional) or respiratory correlated (4-dimen-
sional) CBCT just before treatment.
Especially for hypofractionation, online verification and
correction of tumor position is extremely important and
CBCT provides soft-tissue localization without implanting
markers. However, 3-dimensional CBCT of lung has a poor
quality when respiratory motion is large. Therefore, we im-
plement daily respiration correlated (4-dimensional) CBCT
acquisition and analysis for online tumor position correction
of lung cancer patients that receive 3x18 Gy. Residual respi-
ratory motion is covered with a (small) margin accounting for
its dose-blurring effect. The system works without external
sensor, analyzing projection images to obtain the respiration
phase used for sorting.90,91 To obtain adequate respiratory
phases, the scan time is 4 minutes over a 220o arc. A newly
developed reconstruction algorithm works simultaneous
with CBCT acquisition and produces a 4-dimensional recon-
struction (10 ⫻ 2563 pixels) within 5 seconds after the end of
scanning.92 A local rigid registration algorithm is next used to
match the tumor region defined in the midventilation frame
of the 4-dimensional planning CT with each of the phases of
the 4-dimensional CBCT. An animation technique provides
rapid visual verification. The mean position of the tumor is
computed and used for correction, whereas the amplitude is
reviewed to validate the margin. Validation scans are made
after correction and treatment. So far, we have treated 50
patients with the 4-dimensional technique without encoun-
tering reconstruction or analysis problems. Typically, mar-
gins in the order of 7 mm are required that account for
delineation uncertainty and some intrafraction motion of the
patient. Respiratory motion has a very limited impact on the
margin requirement because of the shallow penumbra in
lung tissue and because the dose prescription at 70 or 80% of
the nominal dose.93,94
Other Issues
Advanced Correction Strategies
The availability of in-room volumetric imaging gives the pos-
sibility to quantify and correct anatomic variations in great
detail. In principle, it is possible to do a regular full replan to
correct for any geometric error, provided that the previously
delivered dose can be accurate accumulated using knowledge
of motion deformation of all tissues of interest.63,95 In clinical
practice, such a procedure has never been implemented be-
cause of the high workload and the inherent uncertainties in
the dose accumulation that yet need to be characterized.
Therefore, for efficient implementation of daily IGRT, more
simple approaches compared with full replanning have to be
developed. Two recent articles show the interest in such a
development. Mohan and coworkers96 proposed to take an-
atomic changes into account by deforming the intensity dis-
tributions of each beam based on deformations of anatomy as
264
seen in the beam’s eye view. They showed preliminary results
based on a single case that show that this methodology fol-
lowed by resequencing may be a rapid way to produce new
treatment plans online based on daily in-room CT images.
Court and coworkers60 developed a method based on slice-
based registration and leaf-by-leaf correction to take ana-
tomic variations into account. They tested their method on 2
patients with 23 scans each and showed the feasibility of their
approach. These approaches, however, clearly need to be
applied to larger groups of patients to confirm their validity.
Besides geometry-based decision rules, it may be beneficial to
use information about target anatomy and the planned dose
distribution. This allows designing correction strategies that
are better tailored to the individual patient and that comply
effectively with initial treatment plan intent.97
The step that is currently lacking is the development of
efficient techniques to translate the observed variation into
changes into the parameters that drive the treatment machine
(control points in Digital Imaging and Communications in
Medicine [DICOM] terminology) and communicate these
changes to the treatment machine. Jaffray and coworkers98
proposed online selection of one out of a cohort of plans to
account for a single rotational variation. However, such a
method is impractical, in particular in the context of IMRT, if
multiple degrees of freedom need to be addressed. So in
many cases, adaptation of the treatment plan is the only op-
tion, requiring regular time-consuming plan quality assur-
ance. To avoid this step, we are developing a safe method to
perform small modifications of a plan outside the planning
system (eg, to expedite corrections for adaptive RT of prostate
cancer). In this method, DICOM radiotherapy plan (RTPlan)
objects are exported from the planning system to the linear
accelerator, the image guidance (IGRT) system, and a couch
readout system. We maintain a copy of the original RTPlan
and modify it to generate the adapted RTPlan. Such a proce-
dure is potentially unsafe because parameters can be freely
modified. To make the system safe, the unique identifier of
the unmodified plan is added as a “private” element to the
new RTPlan. The IGRT system compares the original and
modified RTPlan to forbid modifications outside predefined
tolerances. We currently use the system for an ad hoc couch
shift resulting from an adaptive RT procedure. Loading the
modified RTPlan object updates the couch shift display and
the isocenter in the IGRT system. In principle, this method
can be used to correct for roll (modifying gantry angles) and
approximately for tilt (modifying collimator angles).57 Fur-
thermore, organ deformations may be corrected by modify-
ing leaf positions. Even though modification of the RTPlan
takes only a few seconds, importing such a modified RTPlan
is currently time consuming; when importing it into the
record and verify system, scheduling data need to be reen-
tered. Still, this time compares favorably with full-plan mod-
ification, which takes several hours in clinical practice. In
future, vendors of record and verify systems should make this
method more efficient.
Imaging Dose Aspects
In external-beam RT, a large portion of the body receives
some dose. A typical integral dose for a prostate IMRT to 78
M. van Herk
Gy is 150 J (Gy ⫻ kg). When considering the additional dose
that is required for image guidance, it is the increased integral
dose that should be used as a guiding factor. Of course, there
are image guidance methods that do not use ionizing radia-
tion, such as ultrasound. If these techniques are just as pre-
cise and efficient as techniques using x-rays, they should be
preferred. However, if the technique is invasive (like electro-
magnetic markers), the additional discomfort and risk of
complications should be considered. In an adaptive RT pro-
cedure for prostate cancer using CBCT soft tissue imaging,
typically 12 fractions are imaged using 3 cGy dose per image
with a scan length of 12 cm.37 The integral dose is about 3 J
(ie, 2% increase compared with the original 150 J of the IMRT
plan). However, the procedure allows us to reduce margins
from 10 to 7 mm, sparing 10 J because of the plan itself (as
the area of all beams is reduced). As a net result, the integral
dose with image guidance reduces by 4% to the whole body,
whereas the rectum dose reduces much more. A less precise
technique (eg, ultrasound) would offer less benefit in terms
of integral dose. For imaging bony anatomy, a typical CBCT
dose of 0.1 cGy is adequate.99 In these cases, the increase in
integral dose is negligible. We believe that the dose required
with different radiograph techniques depends on task and
not so much on the technique (ie, localizing seeds with CBCT
does not require more dose then with orthogonal images). In
conclusion, the imaging dose is not negligible for soft-tissue
protocols, but the additional risk is very small. Maybe one of
the most critical setups in terms of dose delivered outside the
target volume is breast RT; the induction of contra-lateral
breast cancer is a significant risk. The current skin-based
setup is adequate for the margins used in accelerated partial
breast RT treatments. To reduce the image guidance dose as
much as possible, a “multistep process” has been suggested in
which on the first fraction a high-dose (3 cGy) scan is made to
visualize the seroma for quality assurance of targeting. Then,
low-dose imaging (⬃0.15 cGy) is used for daily position-
ing.100 Per case, it is good to make a careful consideration
based on the integral imaging dose relative to integral thera-
peutic dose, taking margins, risk of failure, and risk of com-
plications into account.
Conclusions
In summary, detailed information about translation, defor-
mations, and rotations are currently becoming available for
target and organs at risk. In the literature, correction strate-
gies are based on either table shifts (manual or computer
controlled) or daily full replanning. Although the former
method has been widely implemented in clinical practice, the
latter method has mainly been used in theoretical studies
because of its high clinical workload. Replanning is consid-
ered only feasible in an offline adaptive protocol. There are
almost no methods to act rapidly on this information to cor-
rect the patient setup. Several groups are implementing ad-
vanced correction strategies for high-precision RT that allows
safe dose escalation and margin reduction for (hypofraction-
ated) lung and prostate treatments. Note that the increases in
precision in image guidance are only relevant when other
Styles of IGRT
steps in the RT procedure have a similar accuracy. In partic-
ular, improved target definition and pathology validation are
essential.
Acknowledgments
The author would like to thank Jan-Jakob Sonke, Joos Leb-
esque, and David Jaffray for their valuable input.
References
1. van Herk M, Remeijer P, Rasch C, et al: The probability of correct
target dosage: Dose-population histograms for deriving treatment
margins in radiotherapy. Int J Radiat Oncol Biol Phys 47:1121-35,
2000
2. Boersma LJ, van den Brink M, Bruce AM, et al: Estimation of the
incidence of late bladder and rectum complications after high-dose
(70-78 GY) conformal radiotherapy for prostate cancer, using dose-
volume histograms. Int J Radiat Oncol Biol Phys 41:83-92, 1998
3. Grills IS, Yan D, Martinez AA, et al: Potential for reduced toxicity and
dose escalation in the treatment of inoperable non-small-cell lung
cancer: A comparison of intensity-modulated radiation therapy
(IMRT), 3D conformal radiation, and elective nodal irradiation. Int J
Radiat Oncol Biol Phys 57:875-890, 2003
4. de Crevoisier R, Tucker SL, Dong L, et al: Increased risk of biochem-
ical and local failure in patients with distended rectum on the plan-
ning CT for prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys
62:965-973, 2005
5. Heemsbergen WD, Hoogeman MS, Witte MG, et al: Increased risk of
biochemical and clinical failure for prostate patients with a large rec-
tum at radiotherapy planning: Results from the Dutch trial of 68 GY
versus 78 Gy. Int J Radiat Oncol Biol Phys 67:1418-1424, 2007
6. Hoogeman MS, van Herk M, de Bois J, et al: Strategies to reduce the
systematic error due to tumor and rectum motion in radiotherapy of
prostate cancer. Radiother Oncol 74:177-185, 2005
7. Yan D, Lockman D, Brabbins D, et al: An off-line strategy for con-
structing a patient-specific planning target volume in adaptive treat-
ment process for prostate cancer. Int J Radiat Oncol Biol Phys 48:289-
302, 2000
8. Shimizu S, Shirato H, Kitamura K, et al: Use of an implanted marker
and real-time tracking of the marker for the positioning of prostate
and bladder cancers. Int J Radiat Oncol Biol Phys 48:1591-1597,
2000
9. Balter JM, Wright JN, Newell LJ, et al: Accuracy of a wireless localiza-
tion system for radiotherapy. Int J Radiat Oncol Biol Phys 61:933-937,
2005
10. Mohan DS, Kupelian PA, Willoughby TR: Short-course intensity-
modulated radiotherapy for localized prostate cancer with daily trans-
abdominal ultrasound localization of the prostate gland. Int J Radiat
Oncol Biol Phys 46:575-580, 2000
11. Mackie TR: History of tomotherapy. Phys Med Biol 51:R427-R453,
2006
12. Court L, Rosen I, Mohan R, et al: Evaluation of mechanical precision
and alignment uncertainties for an integrated CT/LINAC system. Med
Phys 30:1198-1210, 2003
13. Jaffray DA, Siewerdsen JH, Wong JW, et al: Flat-panel cone-beam
computed tomography for image-guided radiation therapy. Int J Ra-
diat Oncol Biol Phys 53:1337-1349, 2002
14. Pouliot J, Bani-Hashemi A, Chen J, et al: Low-dose megavoltage cone-
beam CT for radiation therapy. Int J Radiat Oncol Biol Phys 61:552-
560, 2005
15. Bortfeld T, Jiang SB, Rietzel E: Effects of motion on the total dose
distribution. Semin Radiat Oncol 14:41-51, 2004
16. Seppenwoolde Y, Shirato H, Kitamura K, et al: Precise and real-time
measurement of 3D tumor motion in lung due to breathing and heart-
beat, measured during radiotherapy. Int J Radiat Oncol Biol Phys
53:822-834, 2002
17. Ritchie CJ, Hsieh J, Gard MF, et al: Predictive respiratory gating: A
265
new method to reduce motion artifacts on CT scans. Radiology
190:847-852, 1994
18. van Herk M: Errors and margins in radiotherapy. Semin Radiat Oncol
14:52-64, 2004
19. Keall PJ, Kini VR, Vedam SS, et al: Potential radiotherapy improve-
ments with respiratory gating. Australas Phys Eng Sci Med 25:1-6,
2002
20. Shimizu S, Shirato H, Kagei K, et al: Impact of respiratory movement
on the computed tomographic images of small lung tumors in three-
dimensional (3D) radiotherapy. Int J Radiat Oncol Biol Phys 46:1127-
1133, 2000
21. Ford EC, Mageras GS, Yorke E, et al: Respiration-correlated spiral CT:
A method of measuring respiratory-induced anatomic motion for ra-
diation treatment planning. Med Phys 30:88-97, 2003
22. Vedam SS, Keall PJ, Kini VR, et al: Acquiring a four-dimensional
computed tomography dataset using an external respiratory signal.
Phys Med Biol 48:45-62, 2003
23. Keall PJ, Mageras GS, Balter JM, et al: The management of respiratory
motion in radiation oncology report of AAPM Task Group 76. Med
Phys 33:3874-3900, 2006
24. Wolthaus JW, Schneider C, Sonke JJ, et al: Mid-ventilation CT scan
construction from four-dimensional respiration-correlated CT scans
for radiotherapy planning of lung cancer patients. Int J Radiat Oncol
Biol Phys 65:1560-1571, 2006
25. Nijkamp J, Wolthaus J, Sonke J, et al: Mid-ventilation determination
with automatic four-dimensional rigid grey-value registration on res-
piration-correlated computed tomography scans with moving lung
tumours. Proceedings of the XVth ICCR. 2007, Toronto, Canada,
June 4-7, 2007, 258-262
26. Keall PJ, Joshi S, Vedam SS, et al: Four-dimensional radiotherapy
planning for DMLC-based respiratory motion tracking. Med Phys
32:942-951, 2005
27. Mexner V, Wolthaus J, Nijkamp J, et al: Effects of respiration-induced
anatomy variations on dose distributions. Radiother Oncol 84:S75,
2007 (suppl) [abstract]
28. van Herk M, Bruce A, Kroes AP, et al: Quantification of organ motion
during conformal radiotherapy of the prostate by three dimensional
image registration. Int J Radiat Oncol Biol Phys 33:1311-1320, 1995
29. Lebesque JV, Bruce AM, Kroes AP, et al: Variation in volumes, dose-
volume histograms, and estimated normal tissue complication prob-
abilities of rectum and bladder during conformal radiotherapy of T3
prostate cancer. Int J Radiat Oncol Biol Phys 33:1109-1119, 1995
30. Voogt J, de Bois J, van Herk M, et al: Cone beam CT motion artifact
reduction by projection image selection. Proceedings of the XVth
ICCR, 2007, Toronto, Canada, June 4-7, 2007, 13-17
31. Rasch C, Keus R, Pameijer FA, et al: The potential impact of CT-MRI
matching on tumor volume delineation in advanced head and neck
cancer. Int J Radiat Oncol Biol Phys 39:841-848, 1997
32. Burridge NA, Rowbottom CG, Burt PA: Effect of contrast enhanced
CT scans on heterogeneity corrected dose computations in the lung.
J Appl Clin Med Phys 7:1-12, 2006
33. Steenbakkers RJ, Duppen JC, Fitton I, et al: Reduction of observer
variation using matched CT-PET for lung cancer delineation: A three-
dimensional analysis. Int J Radiat Oncol Biol Phys 64:435-448, 2006
34. el-Gayed AA, Bel A, Vijlbrief R, et al: Time trend of patient setup
deviations during pelvic irradiation using electronic portal imaging.
Radiother Oncol 26:162-171, 1993
35. Erridge SC, Seppenwoolde Y, Muller SH, et al: Portal imaging to assess
set-up errors, tumor motion and tumor shrinkage during conformal
radiotherapy of non-small cell lung cancer. Radiother Oncol 66:75-
85, 2003
36. van der Heide UA, Kotte AN, Dehnad H, et al: Analysis of fiducial
marker-based position verification in the external beam radiotherapy
of patients with prostate cancer. Radiother Oncol 82:38-45, 2007
37. Nijkamp J, Pos FJ, Nuver TT, et al: Adaptive radiotherapy for prostate
cancer using kilovoltage cone-beam computed tomography: First
Clinical Results. Int J Radiat Oncol Biol Phys (in press)
38. Uematsu M, Shioda A, Suda A, et al: Intrafractional tumor position
stability during computed tomography (CT)-guided frameless stereo-
266
tactic radiation therapy for lung or liver cancers with a fusion of CT
and linear accelerator (FOCAL) unit. Int J Radiat Oncol Biol Phys
48:443-448, 2000
39. Borst GR, Sonke JJ, Betgen A, et al: Kilo-voltage cone-beam computed
tomography setup measurements for lung cancer patients; First clin-
ical results and comparison with electronic portal-imaging device. Int
J Radiat Oncol Biol Phys 68:555-561, 2007
40. Langen KM, Pouliot J, Anezinos C, et al: Evaluation of ultrasound-
based prostate localization for image-guided radiotherapy. Int J Radiat
Oncol Biol Phys 57:635-644, 2003
41. Keller H, Tome W, Ritter MA, et al: Design of adaptive treatment
margins for non-negligible measurement uncertainty: Application to
ultrasound-guided prostate radiation therapy. Phys Med Biol 49:69
86, 2004
42. van Herk M, Betgen A, Remeijer P, et al: A simple method to correctly
account for rotational errors in radiotherapy. Radiother Oncol 76:S1-
S231, 2005 (suppl 2)
43. Gilhuijs KG, van de Ven PJ, van Herk M: Automatic three-dimensional
inspection of patient setup in radiation therapy using portal images,
simulator images, and computed tomography data. Med Phys 23:389-
399, 1996
44. Remeijer P, Geerlof E, Ploeger L, et al: 3-D portal image analysis in
clinical practice: An evaluation of 2-D and 3-D analysis techniques as
applied to 30 prostate cancer patients. Int J Radiat Oncol Biol Phys
46:1281-1290, 2000
45. Linthout N, Verellen D, Tournel K, et al: Six dimensional analysis with
daily stereoscopic x-ray imaging of intrafraction patient motion in
head and neck treatments using five points fixation masks. Med Phys
33:504-513, 2006
46. de Boer HC, van Os MJ, Jansen PP, et al: Application of the No Action
Level (NAL) protocol to correct for prostate motion based on elec-
tronic portal imaging of implanted markers. Int J Radiat Oncol Biol
Phys 61:969-983, 2005
47. Miralbell R, Ozsoy O, Pugliesi A, et al: Dosimetric implications of
changes in patient repositioning and organ motion in conformal ra-
diotherapy for prostate cancer. Radiother Oncol 66:197-202, 2003
48. Remeijer P, Rasch C, Lebesque JV, et al: Margins for translational and
rotational uncertainties: A probability-based approach. Int J Radiat
Oncol Biol Phys 53:464-474, 2002
49. van Herk M, Remeijer P, Lebesque JV: Inclusion of geometric uncer-
tainties in treatment plan evaluation. Int J Radiat Oncol Biol Phys
52:1407-1422, 2002
50. Song W, Dunscombe P: EUD-based margin selection in the presence
of set-up uncertainties. Med Phys 31:849-859, 2004
51. Herman MG, Pisansky TM, Kruse JJ, et al: Technical aspects of daily
online positioning of the prostate for three-dimensional conformal
radiotherapy using an electronic portal imaging device. Int J Radiat
Oncol Biol Phys 57:1131-1140, 2003
52. Deurloo KE, Steenbakkers RJ, Zijp LJ, et al: Quantification of shape
variation of prostate and seminal vesicles during external beam radio-
therapy. Int J Radiat Oncol Biol Phys 61:228-238, 2005 (erratum in
Int J Radiat Oncol Biol Phys 61:1609, 2005)
53. Smitsmans MH, de Bois J, Sonke JJ, et al: Automatic prostate localiza-
tion on cone-beam CT scans for high precision image-guided radio-
therapy. Int J Radiat Oncol Biol Phys 63:975-984, 2005
54. Court LE, Dong L, Taylor N, et al: Evaluation of a contour-alignment
technique for CT-guided prostate radiotherapy: An intra- and inter-
observer study. Int J Radiat Oncol Biol Phys 59:412-418, 2004
55. Hua C, Lovelock DM, Mageras GS, et al: Development of a semi-
automatic alignment tool for accelerated localization of the prostate.
Int J Radiat Oncol Biol Phys 55:811-824, 2003
56. Guckenberger M, Meyer J, Wilbert J, et al: Precision of image-guided
radiotherapy (IGRT) in six degrees of freedom and limitations in clin-
ical practice. Strahlenther Onkol 183:307-313, 2007
57. Rijkhorst EJ, van Herk M, Lebesque JV, et al: Strategy for online
correction of rotational organ motion for IMRT of prostate cancer. Int
J Radiat Oncol Biol Phys 2007 (in press)
58. Boswell SA, Jeraj R, Ruchala KJ, et al: A novel method to correct for
M. van Herk
pitch and yaw patient setup errors in helical tomotherapy. Med Phys
32:1630-1639, 2005
59. Suzuki O, Shiomi H, Nakamura S, et al: Novel correction methods as
alternatives for the six-dimensional correction in CyberKnife treat-
ment. Radiat Med 25:31-37, 2007
60. Court LE, Dong L, Lee AK, et al: An automatic CT-guided adaptive
radiation therapy technique by online modification of multileaf colli-
mator leaf positions for prostate cancer. Int J Radiat Oncol Biol Phys
62:154-163, 2005
61. Kaatee RS, Olofsen MJ, Verstraate MB, et al: Detection of organ move-
ment in cervix cancer patients using a fluoroscopic electronic portal
imaging device and radiopaque markers. Int J Radiat Oncol Biol Phys
54:576-583, 2002
62. Brock KM, Balter JM, Dawson LA, et al: Automated generation of a
four-dimensional model of the liver using warping and mutual infor-
mation. Med Phys 30:1128-1133, 2003
63. Yan D, Jaffray DA, Wong JW: A model to accumulate fractionated dose
in a deforming organ. Int J Radiat Oncol Biol Phys 44:665-675, 1999
64. Kessler ML: Image registration and data fusion in radiation therapy.
Br J Radiol 79:S99-S108, 2006
65. Letourneau D, Wong R, Moseley D, et al: Online planning and deliv-
ery technique for radiotherapy of spinal metastases using cone-beam
CT: Image quality and system performance. Int J Radiat Oncol Biol
Phys 67:1229-1237, 2007
66. Wu Q, Ivaldi G, Liang J, et al: Geometric and dosimetric evaluations of
an online image-guidance strategy for 3D-CRT of prostate cancer. Int
J Radiat Oncol Biol Phys 64:1596-1609, 2006
67. Bijhold J, Lebesque JV, Hart AA, et al: Maximizing setup accuracy
using portal images as applied to a conformal boost technique for
prostatic cancer. Radiother Oncol 24:261-271, 1992
68. Bel A, Vos PH, Rodrigus PT, et al: High-precision prostate cancer
irradiation by clinical application of an offline patient setup verifica-
tion procedure, using portal imaging. Int J Radiat Oncol Biol Phys
35:321-332, 1996
69. de Boer HC, van Sornsen de Koste JR, Creutzberg CL, et al: Electronic
portal image assisted reduction of systematic set-up errors in head and
neck irradiation. Radiother Oncol 61:299-308, 2001
70. de Boer HC, Heijmen BJ: eNAL: An extension of the NAL setup cor-
rection protocol for effective use of weekly follow-up measurements.
Int J Radiat Oncol Biol Phys 67:1586-1595, 2007
71. Pouliot J, Lirette A: Verification and correction of setup deviations in
tangential breast irradiation using EPID: Gain versus workload. Med
Phys 23:1393-1398, 1996
72. Amer AM, Mackay RI, Roberts SA, et al: The required number of
treatment imaging days for an effective off-line correction of system-
atic errors in conformal radiotherapy of prostate cancer—A radiobio-
logical analysis. Radiother Oncol 61:143-150, 2001
73. Bortfeld T, van Herk M, Jiang SB: When should systematic patient
positioning errors in radiotherapy be corrected? Phys Med Biol 47:
N297-N302, 2002
74. Nuver TT, Hoogeman MS, Remeijer P, et al: An adaptive off-line
procedure for radiotherapy of prostate cancer. Int J Radiat Oncol Biol
Phys 67:1559-1567, 2007
75. van Herk M, Witte M: Patient specific differences in setup error vari-
ability and its effect on treatment margins in fractioned radiotherapy.
Med Phys 33:2187, 2006
76. Lam KL, Ten Haken RK, Litzenberg D, et al: An application of Bayes-
ian statistical methods to adaptive radiotherapy. Phys Med Biol 50:
3849-3858, 2005
77. Pos FJ, Hulshof M, Lebesque J, et al: Adaptive radiotherapy for inva-
sive bladder cancer: A feasibility study. Int J Radiat Oncol Biol Phys
64:862-868, 2006
78. Steenbakkers RJ, Duppen JC, Fitton I, et al: Observer variation in
target volume delineation of lung cancer related to radiation oncolo-
gist-computer interaction: A ‘Big Brother’ evaluation. Radiother Oncol
77:182-190, 2005
79. Ghilezan M, Yan D, Liang J, et al: Online image-guided intensity-
modulated radiotherapy for prostate cancer: How much improve-
ment can we expect? A theoretical assessment of clinical benefits
Styles of IGRT
and potential dose escalation by improving precision and accuracy
of radiation delivery. Int J Radiat Oncol Biol Phys 60:1602-1610,
2004
80. McShan DL, Kessler ML, Vineberg K, et al: Inverse plan optimization
accounting for random geometric uncertainties with a multiple in-
stance geometry approximation (MIGA). Med Phys 33:1510-1521,
2006
81. Witte MG, vd Geer J, Schneider C, et al: IMRT optimization including
random and systematic geometric errors based on the expectation of
TCP and NTCP. Med Phys (in press)
82. Unkelbach J, Oelfke U: Incorporating organ movements in IMRT
treatment planning for prostate cancer: Minimizing uncertainties in
the inverse planning process. Med Phys 32:2471-2483, 2005
83. Ten Haken RK, Balter JM, Marsh LH, et al: Potential benefits of elimi-
nating planning target volume expansions for patient breathing in the
treatment of liver tumors. Int J Radiat Oncol Biol Phys 38:613-617, 1997
84. Engelsman M, Remeijer P, van Herk M, et al: The theoretical benefit of
beam fringe compensation and field size reduction for iso-normal
tissue complication probability dose escalation in radiotherapy of
lung cancer. Med Phys 30:1086-1095, 2003
85. Kubo HD, Hill BC: Respiration gated radiotherapy treatment: a tech-
nical study. Phys Med Biol 41:83-91, 1996
86. Wong JW, Sharpe MB, Jaffray DA, et al: The use of active breathing
control (ABC) to reduce margin for breathing motion. Int J Radiat
Oncol Biol Phys 44:911-919, 1999
87. Mageras GS, Yorke E: Deep inspiration breath hold and respiratory
gating strategies for reducing organ motion in radiation treatment.
Semin Radiat Oncol 14:65-75, 2004
88. Shirato H, Shimizu S, Shimizu T, et al: Real-time tumour-tracking
radiotherapy. Lancet 353:1331-1332, 1999
89. Murphy MJ: Tracking moving organs in real time. Semin Radiat Oncol
14:91-100, 2004
90. Sonke JJ, Zijp L, Remeijer P, et al: Respiratory correlated cone beam
CT. Med Phys 32:1176-1186, 2005
91. Zijp L, Sonke JJ, van Herk M: Extraction of the respiratory signal from
267
sequential thorax cone-beam X-ray images. Proceedings of the XIVth
ICCR. Seoul, Korea, May 10-13, 2004
92. van Herk M, Zijp L, Remeijer P, et al: On-line 4D cone beam CT for
daily correction of lung tumour position during hypofractionated ra-
diotherapy. Proceedings of the XVth ICCR. 2007, Toronto, Canada,
June 4-7, 2007, 33-37
93. van Herk M, Witte M, van der Geer J, et al: Biologic and physical
fractionation effects of random geometric errors. Int J Radiat Oncol
Biol Phys 57:1460-1471, 2003
94. Witte MG, van der Geer J, Schneider C, et al: The effects of target size
and tissue density on the minimum margin required for random er-
rors. Med Phys 31:3068-3079, 2004
95. Lof J, Lind BK, Brahme A: An adaptive control algorithm for optimi-
zation of intensity modulated radiotherapy considering uncertainties
in beam profiles, patient set-up and internal organ motion. Phys Med
Biol 43:1605-1628, 1998
96. Mohan R, Zhang X, Wang H, et al: Use of deformed intensity distri-
butions for on-line modification of image-guided IMRT to account for
interfractional anatomic changes. Int J Radiat Oncol Biol Phys 61:
1258-1266, 2005
97. Keller H, Jaffray DA, Rosewall T, et al: Efficient on-line setup correc-
tion strategies using plan-intent functions. Med Phys 33:1388-1397,
2006
98. Jaffray D, van Herk M, Lebesque JV, et al: Image guided radiotherapy
of the prostate, in Niessen WJ, Viergever MA (eds): Medical Image
Computing and Computer-Assisted Intervention—MICCAI 2001,
4th International Conference, Utrecht, The Netherlands, October 14-
17, 2001, Proceedings. Lecture Notes in Computer Science 2208,
Springer 2001, pp 1075-1080
99. Sykes JR, Amer A, Czajka J, et al: A feasibility study for image guided
radiotherapy using low dose, high speed, cone beam X-ray volumetric
imaging. Radiother Oncol 77:45-52, 2005
100. White EA, Cho J, Vallis KA, et al: Cone beam computed tomography
guidance for setup of patients receiving accelerated partial breast ir-
radiation. Int J Radiat Oncol Biol Phys 68:547-554, 2007