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Acta Oncologica

ISSN: 0284-186X (Print) 1651-226X (Online) Journal homepage:

Will IGRT live up to its promise?

Marcel Van Herk

To cite this article: Marcel Van Herk (2008) Will IGRT live up to its promise?, Acta Oncologica,
47:7, 1186-1187, DOI: 10.1080/02841860802279717

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Published online: 08 Jul 2009.

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Acta Oncologica, 2008; 47: 11861187


Will IGRT live up to its promise?


The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

A definition of Image Guided Radiotherapy (IGRT) reflection of this issue is the inter- and intra-observer
is to improve the precision of radiotherapy by variation in target volume definition that we see for
imaging the target and/or normal structures just almost all tumor sites, and even for definition of
before or during treatment, and if indicated using whole organ targets such as the prostate. If a
this information to adapt the treatment. The ratio- physician is not convinced that this is an important
nale for this development is the observation that the issue, a simple exercise of blindly re-delineating a
classical method of preparation and execution of couple of his or her own target volumes after a period
radiotherapy using external markers gives rise to of a few months should clearly make the point: the
large geometrical uncertainties. volumes will probably differ significantly.
These uncertainties, in the physical realm, can When we get to this situation, we should take a
now easily be detected and corrected. What I mean step back and realize that radiation therapy should
by this is that now, in principle, it is possible to target be, and for a large part is, an evidence-based form of
any clearly visible object in the body with such a medicine. We do what we are doing because we are
precision that only a few mm margin is required to convinced that it works - not because we exactly
account for residual uncertainties such as calibration know why or how it works. It is, for instance quite
issues and intrafraction motion. In the past, the net likely that incidental dose around the margins takes
effect of the uncorrected uncertainties often required care of microscopic disease spread that may be
margins of 1 cm or more. This potential reduction of present but that cannot be detected by any form of
margin can lead to an enormous reduction in the non-invasive medical imaging. Similarly, the PTV
amount of normal tissue that is exposed to a high margin will partly take care of the observer variation.
dose, with a large increase in therapeutic ratio. The Changes in therapy that may seem safe in terms of
required IGRT equipment for this improvement has physical data may therefore not be safe at all when
gone through an enormous pace of development  biological factors are taken into account. For exam-
and has become quite usable by now. ple, in prostate cancer extra capsular extension
It is logical therefore that many clinics are tempted (ECE) is a well-recognized factor. However, classical
and willing to act on this large improvement in CT based planning gives rise to such a generous
geometrical accuracy. In some IGRT talks, authors delineation of the organ, that capsule and base of
are indeed proposing to use margins of only a few seminal vesicles are automatically included, covering
mm with, for instance, external beam prostate most ECE. Also, the PTV margin that is needed to
radiotherapy. What these authors seem to be forget- guarantee that the CTV is treated to a high dose in
ting, however, that we are not in the business of the majority of cases, will in many cases eradicate
treating gold markers, but that we are treating cancer ECE that has a small volume and therefore is more
with a complicated and mostly poorly known disease radiosensitive. With a smaller margin that is indi-
spread and biology. In other words, we know exactly cated by an increased precision, this may no longer
what we are doing in the physical realm, but are not be the case, leading to a loss of local control. Indeed,
sure at all in the biological realm. A (meager) there is some evidence that the application of small

Correspondence: Marcel van Herk, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. E-mail:

(Received 10 June 2008; accepted 17 June 2008)

ISSN 0284-186X print/ISSN 1651-226X online # 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/02841860802279717
Will IGRT live up to its promise? 1187

margins in precision image guided prostate radio- based on bony anatomy is used. Such protocols can
therapy leads to a reduction of local control [1]. help optimize image quality, lead to more precise
In the Acta Oncologica meeting, resulting in this and consistent image registration, and to rational
special issue, there have been many talks about the decision criteria for when and how to act on
application of biological imaging for so called dose observed deviations, which often will include
painting or boosting of a selected part of the tumor. changes in the anatomy.
This development is even becoming the major focus Second, with image guidance one should be very
of some medical physics departments. Even though careful in shrinking the margins. One should start
it is an exciting field, several authors have advocated with estimating all uncertainties in the current
caution, and rightly so. clinical settings, with a realistic estimate of the
The main problem of this development, as was biological uncertainties, reflected partly in the ob-
pointed out by Dr. Markus Alber in his talk at the server variation between well-trained physicians.
Acta Oncologica Symposium, is that the sensitivity Then the effect of image guidance on the margin
and specificity of the new imaging modalities is can be estimated. Since image guidance does not
limited for the task of detecting primary tumor reduce the biological uncertainties, I personally
nodes and/or regions of the tumor that require a believe that a PTV margin of 5 mm or less is highly
higher dose. Of course this is not a serious problem if unrealistic for most tumors. Careful training and
all we want to do is raise the dose locally without fine-tuning of delineation protocols must be per-
reducing the dose elsewhere (although a misplaced formed to bring consistency to the target volumes
boost dose may damage normal tissue that is and it is has become critically important to review
interspersed with the tumor without benefit). How- GTV and CTV delineations with a multi-disciplinary
ever, to have an appreciable gain of dose painting in team.
terms of normal tissue sparing it is necessary to Finally, the increased complexity of IMRT and
redistribute the dose and actually lower the dose in IGRT therapy makes it more error-prone, while
some parts of the tumor, while raising it elsewhere. If anatomical guidance fails to validate the complex
the imaging gets it wrong, such a redistribution of beam delivery. I therefore think we should rethink
dose will hurt the patient (the dose is lowered where verification, and build in independent verification of
it is needed), while if the imaging gets it right the the entire chain, otherwise big errors that occur in a
dose redistribution will benefit the patient. Dr Alber small fraction of patients may go unnoticed. For that
showed a simple calculation illustrating that the lack reason, we have implemented a portal dosimetry
of sensitivity poses a lower limit on the dose program that validates the treatment of each curative
redistribution that should be applied to have any patient efficiently (in vivo) [3].
gain at all. Similarly, he illustrated that normal tissue In summary, IGRT requires consistent and precise
constraints limit the amount that the dose can be definition of the target volume, clear protocols and
raised in the boost. Combining these models, a 10% independent delivery verification. It is the responsi-
dose modulation (95%) seem to be a reasonable bility of the individual departments to implement
starting value. IGRT based on these guidelines, while carefully
However, one should still realize that no form of monitoring clinical outcomes to make sure that
biological imaging is capable of showing tumor biological uncertainties are not underestimated.
deposits that are small relative to the resolution of Otherwise, a change in practice towards IGRT that
the scanners (which is, for instance, at best 5 mm for seems logical and exciting may not live to its promise
PET). This means that tumor deposits on a micro- to lead to a better clinical outcome!
scopical level cannot be visualized and may be
missed, and moreover that dose painting based
upon biological images showing radioresistant areas
(i.e hypoxia) at a low resolution may be suboptimal References
[2]. In addition, the complexity of the tumor biology
[1] Engels B, Soete G, Verellen D, Storme G. Conformal arc
makes the interpretation of molecular images far
radiotherapy for prostate cancer: Increased biochemical fail-
from trivial  this is a field of active research. ure in patients with distended rectum on the planning CT in
So that leads to the main question of this editorial: spite of image guidance by implanted markers. Int J Radiat
what should we do in a daily practice with our newly Oncol Biol Phys 2008 (submitted).
acquired IGRT equipment? [2] Busk M, Horsman MR, Overgaard J. PET hypoxia resolution:
Voxel size matters, Acta Oncol 2008;47:120110.
First, from our own experience it is clear that it is
[3] McDermott LN, Wendling M, Sonke JJ, van Herk M,
good to build-in a learning trajectory, where images Mijnheer BJ. Replacing pretreatment verification with in
are collected and optimized to serve for soft-tissue vivo EPID dosimetry for prostate IMRT. Int J Radiat Oncol
guidance, at the same time that a simpler protocol Biol Phys 2007;67:156877.
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