Radiotherapy and Oncology 96 (2010) 277–279
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Radiotherapy and Oncology
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Editorial
Clinical use of PET-CT data for radiotherapy planning: What are we looking for?
Arturo Chiti a,*, Margarita Kirienko a, Vincent Grégoire b
a
Department of Nuclear Medicine, Istituto Clinico Humanitas, Milan, Italy; b Department of Radiation Oncology, St-Luc University Hospital, Brussels, Belgium
Personalized medicine is the new driving force in the modern
era of medicine. In oncology, personalized management of a pa-
tient’s disease means the application of specific therapeutic strate-
gies that are best suited for an individual patient and for the
particular type of tumour, which the therapy is aiming to target.
Molecular diagnostics influences cancer management in several
ways that aid personalisation and this is why research has now fo-
cused on individualizing treatment strategies by incorporating a
combination of physiological variables, genetic characteristics
and environmental factors together with the traditional tumour
characteristics that currently drive clinical decision making.
Imaging is playing a major role in individualizing treatment
strategies and the approach differs depending on whether the tar-
get is a single disease control point or a general disease control
point applicable to a number of treatment paradigms (e.g. prolifer-
ation, angiogenesis, inflammation, etc.). Among the many different
imaging tools that are available nowadays, Positron emission
tomography (PET) can be used to visualize molecular alterations
in the living subject, thus facilitating early diagnosis and treatment
of disease. The state of art of molecular imaging with PET requires
the use of integrated PET and computed tomography (CT) scanners,
which are able to offer combined information on molecular and
morphological characteristics of tumours.
PET-CT using fluoro-deoxy-glucose as a molecular probe of glu-
cose metabolism in cancer cells has been demonstrated to have
high accuracy for detection of many tumour types [1]. Along with
diagnosis, staging, detection of relapse, restaging and follow-up,
one of the main applications of PET-CT is the assessment of therapy
response and treatment planning. In routine practice, structural
and tumour volume changes are used to guide therapeutic strate-
gies and to measure the disease-free and overall survival. However,
tissue metabolism changes more rapidly than morphology, and
changes in tumour FDG uptake may therefore predict alterations
in volume [2].
The use of FDG-PET as a surrogate tool for monitoring therapy
response offers better patient care by individualizing treatment
and avoiding ineffective chemotherapy. The use of PET, not only
with FDG, to identify patients who can benefit from targeted ther-
apies with monoclonal antibodies has also been demonstrated to
be useful, as well as to evaluate the response to therapy in those
patients selected for treatment [3,4].
*
Corresponding author.
E-mail address: arturo.chiti@humanitas.it (A. Chiti).
0167-8140/$ - see front matter Ó 2010 European Society for Therapeutic Radiology and Oncology and European Association of Nuclear Medicine. Published by Elsevier
Ireland Ltd. All rights reserved.
doi:10.1016/j.radonc.2010.07.021
Like other imaging tools PET can be used to inform decision-
making, e.g. whether a surgical approach is advisable, which inter-
vention will be most appropriate and whether advanced therapies
are feasible. It can also further improve tailoring of therapy by
guiding radiation therapy planning and improving definition of tu-
mour target volumes, as is described in the other contributions of
this journal’s issue. Although CT remains the gold standard for
depicting anatomy for the purpose of target volume definition
and dose calculation, PET-CT could help with respect to the dose
constraints for organs at risk, if the hypermetabolic component is
smaller than the morphological appearance of the tumour, reduc-
ing the gross tumour volume. Further, PET could permit the inclu-
sion of FDG-avid, but non-enlarged, lymph nodes within the field
of treatment or could modify the TNM staging, resulting in a shift
in treatment modality from curative to palliative.
Radiation oncologists rely only on the representation through
imaging tools to select and delineate target volumes. The limita-
tion is the fact that none of the imaging modalities has sensitivity
and specificity of 100% because of their spatial resolution, the spe-
cific affinity of the tracer or the contrast medium used to visualize
different characteristics of the neoplastic tissue.
Sensitivity and the specificity of a diagnostic tool depend also
on the criteria used for the image interpretation. CT acquisition
and reconstruction parameters are standardized, Hounsfield unit
(HU) is easily correlated with tissue density and patterns of vascu-
lar enhancement through contrast medium are well-defined. This
accounts for the high reliability of contrast enhanced CT in oncol-
ogy. The high specificity is counterbalanced by suboptimal sensi-
tivity in some neoplasm due to the fact that only morphological
and density parameters are taken into account. Magnetic reso-
nance imaging (MR) adds functional information to high resolution
images particularly in some tissues, like brain. New sequences are
very promising for tissue characterization but the clinical utiliza-
tion is still to be assessed. Different carriers for gadolinium are
available to study different tissues increasing signal specificity
when compared to CT.
PET radiopharmaceuticals have the theoretical advantage of
high specificity due to specific binding to particular targets. Tracers
may be viewed as probes for specific metabolic pathways: i.e.
hexokinase activity, apoptosis, hypoxia, etc. [5]. In the clinical set-
ting this specificity is limited by the fact that the same metabolic
pathways are activated in neoplastic and non-neoplastic tissues.
Diagnostic accuracy might be flawed by inflammatory reaction
and physiological pattern of distribution of the tracer. For instance
278 Editorial / Radiotherapy and Oncology 96 (2010) 277–279

granulomatous lesions might have FDG uptake as high as very
aggressive tumours, or the high background uptake of 11C-choline
in the liver might hinder huge metastatic invasion. Limited spatial
resolution is also an issue: for instance micro-embolic nodal
metastases are missed in PET and this reduces the accuracy of
the method to assess micrometastases [6]. Furthermore, different
radiopharmaceuticals should be used to image different tumour
types. For instance, bladder cancer is known not to be FDG avid
(Fig. 1), while prostate cancer can be detected with high sensitivity
with 11C-choline (Fig. 2).
Image standardization has been recently established for FDG
PET to overcome several differences existing in reported images,
which accounted for a lack of confidence in the technique from
radiation oncologist and oncologist [7]. Nonetheless, since PET is
going to be used even more frequently with radiopharmaceutical
different than FDG, the problem of standardization will still exist
for other radiopharmaceuticals as soon as they enter the clinical
use.
The use of imaging to better delineate the radiation treatment
target is a particular example of personalized treatment [8]. In fact,
instead of using a prior established field, the radiation dose is
shaped on the tumour for each single patient. The advantage of
functional imaging with PET is the possibility of further increasing
the accuracy of target delineation including only metabolic active
tissue.
The clinical setting and the objective of the treatment are essen-
tial in choosing the most appropriate imaging modality. If for a par-
ticular case the objective is to avoid the miss of the localization of
tumour cells, the most sensitive imaging modality or, in case of
PET, the most sensitive tracer and highly sensitive criteria for the

Fig. 1. Primary bladder cancer. Axial slices of 18F-FDG PET (upper left), CT (lower left) and fusion images (right). The primary tumour is clearly depicted on CT images (arrow)
but, due to low glucose consumption, no abnormality can be seen on PET images. Physiological elimination of the radiopharmaceutical in the bladder is easily recognized.

Fig. 2. Metastatic prostate cancer. Axial slices of 11C-choline PET (upper left), CT (lower left) and fusion images (right). Focal uptake of the radiopharmaceutical is clearly seen
in the right proximal femur, without any abnormality on CT images.
 Editorial / Radiotherapy and Oncology 96 (2010) 277–279 279

Table 1 images are considered easier to delineate but it makes poor sense
PET sensitivity and specificity for different tumour types. Results often show large to use an anatomic modality to better delineate functional images.
variations in range due to the patients selection and lesions sizes, particularly for
lymph node staging. Therefore, this table should be used just as a reference. Further
Another approach to reduce the variability of the delineation con-
details are described in the dedicated chapters of this journal’s issue. FDG is sists in relying on automatic or semi-automatic segmentation
considered unless otherwise stated. methods.
Site Sensitivity (%) Specificity (%)
Whichever approach is going to be used, the fine tuning of the
method is going to affect diagnostic accuracy. The operator’s mind
Brain Primarya 78–94 93–100
H&N Primary 93–100 90–100
might want to be set towards a more specific or sensitive reading
Nodesb 76–85 33–67 of images, therefore setting the threshold for the target volume
NSCLC Primaryc 90 79–96 in different ways. In the same way, different parameters of the
Nodes 83 89 automatic segmentation program might affect the final target vol-
Oesophagus Primary 94 92
ume identification.
Nodes 24–82 81–99
Cervical Primary 75 96 In conclusion, in order to get a really personalized approach of
Nodes 38–91 83–100 radiation target volume delineation in each patient, many param-
Endometrial Primary 89–97 50 eters must be taken into account. The inclusion of clinical param-
Nodes 53–100 99 eters pertaining to a single patient is going to heavily affect the
a
Amino acid PET. therapeutic approach, which should be the result of the best use
b
N0 neck. of technical and clinical information. This means the physicians
c
Lung nodules. in charge of choosing the best treatment strategy for the patient
have still to choose whether they prefer to use a sensitive or spe-
cific approach to obtain the patient’s best outcome.
image interpretation have to be chosen. This can determine that
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